testing the effect of nutrition and lifestyle ...• mori k, obara y, hirota m, azumi y, kinugasa s,...

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Testing the Effect of Nutrition and Lifestyle Interventions to Treat MS and Other Progressive Health Problems Terry Wahls, MD, IFMCP Clinical Professor of Medicine University of Iowa

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Page 1: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

Testing the Effect of Nutrition and Lifestyle Interventions to

Treat MS and Other Progressive Health Problems

Terry Wahls MD IFMCP

Clinical Professor of Medicine

University of Iowa

Disclosuresbull Grant Funding ndash

ndash National MS Society

bull Trademarks ndash Wahlstrade Diet Plans Wahls Protocolreg

bull Financial relationships with Penguin Random House Inc Integrative Medicine for Mental Health Institute for Health and Healing Suttler Pacific BioCeuticals NCURA MCG Health Inc Genova Diagnostics

bull Minding My Mitochondria

bull Wahls Protocol Wahls Protocol Cooking for Life

bull Equity interest ndash Dr Terry Wahls LLC

ndash The Wahls Institute PLC

ndash wwwterrywahlscom

Objectives- Review

bull The published research on dietary interventions for MS

bull The mechanisms by which dietary factors may contribute to potential worsening of MS related symptoms

bull The rationale for the structure of the dietary intervention in the Dietary Approaches to Treating MS Related Fatigue Trial NCT02914964

bull At present there are no dietary recommendations in the Evidence Analysis Library for treatment of neuroinflammation or neurodegeneration by the Academy of Nutrition and Dietetics

How many cups of vegetables did you eat in last 24 hours

In 2000 I Became A Patient

bull Left leg weakness

bull Prior history visual dimming

bull Lesions in spinal chord

bull Abnormal CSF

bull Diagnosis relapsing-remitting MS

2003

copyright 2010 Terry Wahls all rights reserved

2007

Institute For Functional Medicine

11

copyright 2010 Terry Wahls all rights reserved

2008

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

The Swank Diet

bull N=144 followed 50 years

bull lt 15 grams saturated fat vs gt 20 grams

bull Greatest benefit earlier in the disease course

bull More likely to remain ambulatory

Review of MS patient survival on a Swank low saturated fat dietNutrition 2003 Feb19(2)161-2 ReviewEffect of low saturated fat diet in early and late cases of multiple sclerosisLancet 1990 Jul 7336(8706)37-9Multiple sclerosis twenty years on low fat dietArch Neurol 1970 Nov23(5)460-74

Low-fat plant-based diet in multiple sclerosis A randomized controlled trial

bull This was a randomized-controlled assessor-blinded one-year long study

bull N=61

bull No change in EDSS MRI

bull Trend towards reduced FSS (fatigue)

Low-fat plant-based diet in multiple sclerosis A randomized controlled trial Mult Scler Relat Disord 2016 Sep980-90

Mediterranean diet adherence and risk of multiple sclerosis ndash Case control study

bull N=70 RRMS 140 controls Interviews re diet

bull Reduced risk of MS

ndash Fruits (OR=028 95 CI 012-063 p-value 0002)

ndash Vegetables (OR=023 95 CI 010-053 p-value 0001)

Mediterranean diet adherence and risk of multiple sclerosis a case-control study Asia Pac J Clin Nutr 201625(2)377-84

Mediterranean Diet bull High olive oil

bull High vegetable polyphenol

bull Whole grains

bull Low red meat

Potential for diet to prevent and remediate cognitive deficits in neurological disordersNutr Rev 2018 Mar 176(3)204-217The Role of Diet in Multiple Sclerosis Mechanistic Connections and Current EvidenceCurr Nutr Rep 2018 Aug 16Anti-inflammatory Activity of Extra Virgin Olive Oil Polyphenols Which Role in the Prevention and Treatment of Immune-Mediated Inflammatory DiseasesEndocr Metab Immune Disord Drug Targets 201818(1)36-50

bull The following slides represent the rationale for the dietary intervention we are studying in the Dietary Approaches to Treating MS Related Fatigue

bull This protocol is not validated nor does it currently meet the current evidence based guideline criteria as set forth by the American Academy of Neurology or the Academy of Nutrition and Dietetics

Dairy amp MSCasein Gluten amp Schizophrenia

bull Liquid cow milk (not cheese) and MS prevalence was highly correlated (rho = 0836) across 27 countries and 29 populations

bull IgG to Casein and gluten were significantly uarrin recent onset and non-recent onset schizophrenia compared to controls (ple000001-0004)

1 Correlation between milk and dairy product consumption and multiple sclerosis prevalence a worldwide

study Neuroepidemiology 199211(4-6)304-12

2 Severance EG Alaedini A Yang S Halling M Gressitt KL Stallings CR Origoni AE Vaughan C

Khushalani S Leweke FM Dickerson FB Yolken RH Gastrointestinal inflammation and associated

immune activation in schizophrenia Schizophr Res2012 Jun138(1)48-53

Gluten and Casein and Opioids

bull Gluten can be degraded into several morphine-like substances named gluten exorphins

bull Milk proteins are particularly strong allergens and are additional source of bioactive peptides including β-casomorphin-7 and exerts its influence on nervous digestive and immune functions via the opioid receptor

1 The opioid effects of gluten exorphins asymptomatic celiac disease J Health PopulNutr 2015 Nov 243324

2 Opioid receptor ligands derived from food proteins Curr Pharm Des 20039(16)1331-44

3 β-casomorphin-7 alters μ-opioid receptor and dipeptidyl peptidase IV genes expression in children with atopic dermatitis Peptides 2014 Dec62144-9

Nutrition in Parkinsons Disease

Seidl SE Santiago JA Bilyk H Potashkin JA The emerging role of nutrition in Parkinsons disease Front Aging Neurosci 2014 Mar 7636 doi 103389fnagi201400036 eCollection 2014

Gluten sensitivity is an abnormal immune response to gluten in genetically susceptible individuals and may manifest solely with neurological dysfunction 90 of gluten sensitive individuals have no GI symptoms

Lancet Neurol 2010 Mar9(3)318-30 Hadjivassiliou M

Figure 2 MRI in four patients with gluten encephalopathy The extent and variability of white matter abnormalities caused by gluten sensitivity can be seen in these four patients (AndashD) A and C show diffuse white matter changes whereas B and D show more f

Marios Hadjivassiliou David S Sanders Richard A Gruumlnewald Nicola Woodroofe Sabrina Boscolo Daniel Aeschl

Gluten sensitivity from gut to brain

The Lancet Neurology Volume 9 Issue 3 2010 318 - 330

httpdxdoiorg101016S1474-4422(09)70290-X

MS and Gluten References 1 Gluten antibodies in patients with multiple sclerosis Hum Nutr Appl

Nutr 1984 Apr38(2)142-32 Multiple sclerosis and gluten sensitivity Clin Neurol Neurosurg 2007

Oct109(8)651-33 Prevalence of celiac disease in multiple sclerosis BMC Neurol 2011 Mar

711314 Celiac disease with neurologic manifestations in children Rev Med Chir

Soc Med Nat Iasi 2013 Jan-Mar117(1)88-945 Celiac disease with cerebral and peripheral nerve involvement

mimicking multiple sclerosis J Med Life 2014 Sep 157(3)440-4 Epub2014 Sep 25

6 A case of multiple sclerosis and celiac disease Case Rep NeurolMed 20132013576921

7 Gluten-related disorders gluten ataxia Dig Dis 201533(2)264-88 Transglutaminase-6 is an autoantigen in progressive multiple sclerosis and

is upregulated in reactive astrocytes Mult Scler 2016 Dec 11352458516684022

9 The progression of coeliac disease its neurological and psychiatric implications Nutr Res Rev 2017 Jun30(1)25-35

Risks of Eggs

bull Prosndash Grass fed - DHA choline biotin lutein Vitamins A D K2 and

B3 B6 B9 B12

bull Cons ndash Eggs are most common food allergen in IBD gt70ndash 60 allergy patients have IgG Ab to eggsndash 13 seasonal allergies have IgG Ab to eggs ndash Wheat milk eggs are common food triggers to Eosinophilic

Esophagitis

References next slide

References Risks of Eggs bull Wang G Ren J Li G et al The utility of food antigen test in the diagnosis of Crohnrsquos disease

and remission maintenance after exclusive enteral nutrition Clin Res Hepatol Gastroenterol 201842(2)145-152 doi101016jclinre201709002

bull Shakoor Z AlFaifi A AlAmro B AlTawil LN AlOhaly RY Prevalence of IgG-mediated food intolerance among patients with allergic symptoms Ann Saudi Med 2016 Nov-Dec36(6)386-390

bull Dhanapala P De Silva C Doran T Suphioglu C Cracking the egg An insight into egg hypersensitivity Mol Immunol 2015 Aug66(2)375-83 doi 101016jmolimm201504016

bull Pang KA Pang KP Pang EB Tan YN Chan YH Siow JK Food allergy and allergic rhinitis in 435 asian patients - A descriptive review Med J Malaysia 2017 Aug72(4)215-220

bull Philpott H Nandurkar S Royce SG Thien F Gibson PR Allergy tests do not predict food triggers in adult patients with eosinophilic oesophagitis A comprehensive prospective study using five modalities Aliment Pharmacol Ther 2016 Aug44(3)223-33 doi 101111apt13676

bull Cai C Shen J Zhao D et al Serological Investigation of Food Specific Immunoglobulin G Antibodies in Patients with Inflammatory Bowel Diseases Boone DL ed PLoS ONE 20149(11)e112154 doi101371journalpone0112154

Lectins

bull ldquoBy eliminating dietary elements particularly lectins which adversely influence both enterocyte and lymphocyte structure and function it is proposed that the peripheral antigenic stimulus (both pathogenic and dietary) will be reduced and thereby result in a diminution of disease symptoms in certain patients with RArdquo

Cordain L Toohey L Smith MJ Hickey MS Modulation of immune function by dietary lectins in rheumatoid arthritis British Journal of Nutrition 200083(03)207-217

bull Lectins are proteins found in plants and animals that bind sugars (hemagglutinins)

bull They can bind the glycoproteins on the intestinal lining leading to barrier damage

bull Lectins are found in most foods but are especially high in grains (esp wheat) dairy legumes and nightshade vegetables

bull Most traditional methods cooking these foods such as soaking ferment-ing amp cooking will decrease the lectin content

Nutrient Triage

bull Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage

ndash Zn Mg biotin Vitamin K D A

ndash Lipoic Acid Acetyl carnitine

Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triageProc Natl Acad Sci U S A 2006 Nov 21103(47)17589-94

What to Eat

Fruit and vegetable consumption and mortality from all causes cardiovascular disease and cancer systematic review and dose-response meta-analysis of prospective cohort studies

16 studies - 833234 participants

BMJ 2014 349 g4490

BMJ 2014 349 g4490

Risk of all cause mortality associated with servingsday of fruit and vegetables

Dose-response relation between fruit and vegetable consumption and risk of all cause mortality

BMJ 2014 349 g4490

Myelin

ndash Omega 3 Fatty Acids

ndash Thiamine (B1)

ndash Folate (B9)

ndash Cobolamin (B12)

ndash Minerals

Key Micronutrients

Bourre JM Effects of nutrients (in food) on the structure and function of the nervous

system update on dietary requirements for brain Part 1 micronutrients

Part 2 Macronutriients

J Nutr Health Aging 200610(5)377-85

Bowman Nutrient biomarker patterns cognitive function and MRI measures of

brain aging Neurology 2012 Jan 2478(4)241-9 Bowman

Sulfur Rich Foods

Why Brassica and Allium

bull Improve detoxification

bull Increase glutathione production

bull Increase GABA production

bull Enhance Neuroprotection

bull Improve endothelial function

Brassica and Allium References

1 Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimers Disease Med Cell Longev20152015781938

2 Learning and memory promoting effects of crude garlic extract Indian J Exp Biol2013 Dec51(12)1094-100

3 Enhancement of the neuroprotective activity of Hericiumerinaceus mycelium co-cultivated with Allium sativum extract Arch Physiol Biochem2015 Feb121(1)19-25

Why Emphasize Mushrooms

bull Increase nerve growth factors (NGF)

bull Hericium erinaceus (Yamabushitake or Lionrsquos Mane) stimulate the production of NGF (in vitro)

bull Activate natural killer cells

bull Prime innate and adaptive immunity

bull Mori K Obara Y Hirota M Azumi Y Kinugasa S Inatomi S Nakahata N Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human

astrocytoma cells Biol Pharm Bull 2008 Sep31(9)1727-32

bull Lee DH Kim HW Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway Int J Med Mushrooms 201416(1)1-16

bull Akramiene D Kondrotas A Didziapetriene J Kevelaitis E Effects of beta-glucans on the immune system Medicina (Kaunas)200743(8)597-606

bull Lai PL Naidu MSabaratnam VWong K DaviP Kuppusamy UR Abdullah N Malek SN Neurotrophic properties of the Lions mane medicinal mushroom

Hericium erinaceus (Higher Basidiomycetes) from Malaysia Int J Med Mushrooms201315(6)539-54

bull Phan CW David P Naidu M Wong KH Sabaratnam V Therapeutic potential of culinary-medicinal mushrooms for the management of

neurodegenerative diseases diversity metabolite and mechanism Crit Rev Biotechnol201535(3)355-68

Why Greens

bull Vitamin K1 metabolized to K2-mk7 in gut

bull K2 important in hellip

ndash Myelin production

ndash Calcium influx into bones and teeth

bull Carotenoids magnesium

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 2: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

Disclosuresbull Grant Funding ndash

ndash National MS Society

bull Trademarks ndash Wahlstrade Diet Plans Wahls Protocolreg

bull Financial relationships with Penguin Random House Inc Integrative Medicine for Mental Health Institute for Health and Healing Suttler Pacific BioCeuticals NCURA MCG Health Inc Genova Diagnostics

bull Minding My Mitochondria

bull Wahls Protocol Wahls Protocol Cooking for Life

bull Equity interest ndash Dr Terry Wahls LLC

ndash The Wahls Institute PLC

ndash wwwterrywahlscom

Objectives- Review

bull The published research on dietary interventions for MS

bull The mechanisms by which dietary factors may contribute to potential worsening of MS related symptoms

bull The rationale for the structure of the dietary intervention in the Dietary Approaches to Treating MS Related Fatigue Trial NCT02914964

bull At present there are no dietary recommendations in the Evidence Analysis Library for treatment of neuroinflammation or neurodegeneration by the Academy of Nutrition and Dietetics

How many cups of vegetables did you eat in last 24 hours

In 2000 I Became A Patient

bull Left leg weakness

bull Prior history visual dimming

bull Lesions in spinal chord

bull Abnormal CSF

bull Diagnosis relapsing-remitting MS

2003

copyright 2010 Terry Wahls all rights reserved

2007

Institute For Functional Medicine

11

copyright 2010 Terry Wahls all rights reserved

2008

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

The Swank Diet

bull N=144 followed 50 years

bull lt 15 grams saturated fat vs gt 20 grams

bull Greatest benefit earlier in the disease course

bull More likely to remain ambulatory

Review of MS patient survival on a Swank low saturated fat dietNutrition 2003 Feb19(2)161-2 ReviewEffect of low saturated fat diet in early and late cases of multiple sclerosisLancet 1990 Jul 7336(8706)37-9Multiple sclerosis twenty years on low fat dietArch Neurol 1970 Nov23(5)460-74

Low-fat plant-based diet in multiple sclerosis A randomized controlled trial

bull This was a randomized-controlled assessor-blinded one-year long study

bull N=61

bull No change in EDSS MRI

bull Trend towards reduced FSS (fatigue)

Low-fat plant-based diet in multiple sclerosis A randomized controlled trial Mult Scler Relat Disord 2016 Sep980-90

Mediterranean diet adherence and risk of multiple sclerosis ndash Case control study

bull N=70 RRMS 140 controls Interviews re diet

bull Reduced risk of MS

ndash Fruits (OR=028 95 CI 012-063 p-value 0002)

ndash Vegetables (OR=023 95 CI 010-053 p-value 0001)

Mediterranean diet adherence and risk of multiple sclerosis a case-control study Asia Pac J Clin Nutr 201625(2)377-84

Mediterranean Diet bull High olive oil

bull High vegetable polyphenol

bull Whole grains

bull Low red meat

Potential for diet to prevent and remediate cognitive deficits in neurological disordersNutr Rev 2018 Mar 176(3)204-217The Role of Diet in Multiple Sclerosis Mechanistic Connections and Current EvidenceCurr Nutr Rep 2018 Aug 16Anti-inflammatory Activity of Extra Virgin Olive Oil Polyphenols Which Role in the Prevention and Treatment of Immune-Mediated Inflammatory DiseasesEndocr Metab Immune Disord Drug Targets 201818(1)36-50

bull The following slides represent the rationale for the dietary intervention we are studying in the Dietary Approaches to Treating MS Related Fatigue

bull This protocol is not validated nor does it currently meet the current evidence based guideline criteria as set forth by the American Academy of Neurology or the Academy of Nutrition and Dietetics

Dairy amp MSCasein Gluten amp Schizophrenia

bull Liquid cow milk (not cheese) and MS prevalence was highly correlated (rho = 0836) across 27 countries and 29 populations

bull IgG to Casein and gluten were significantly uarrin recent onset and non-recent onset schizophrenia compared to controls (ple000001-0004)

1 Correlation between milk and dairy product consumption and multiple sclerosis prevalence a worldwide

study Neuroepidemiology 199211(4-6)304-12

2 Severance EG Alaedini A Yang S Halling M Gressitt KL Stallings CR Origoni AE Vaughan C

Khushalani S Leweke FM Dickerson FB Yolken RH Gastrointestinal inflammation and associated

immune activation in schizophrenia Schizophr Res2012 Jun138(1)48-53

Gluten and Casein and Opioids

bull Gluten can be degraded into several morphine-like substances named gluten exorphins

bull Milk proteins are particularly strong allergens and are additional source of bioactive peptides including β-casomorphin-7 and exerts its influence on nervous digestive and immune functions via the opioid receptor

1 The opioid effects of gluten exorphins asymptomatic celiac disease J Health PopulNutr 2015 Nov 243324

2 Opioid receptor ligands derived from food proteins Curr Pharm Des 20039(16)1331-44

3 β-casomorphin-7 alters μ-opioid receptor and dipeptidyl peptidase IV genes expression in children with atopic dermatitis Peptides 2014 Dec62144-9

Nutrition in Parkinsons Disease

Seidl SE Santiago JA Bilyk H Potashkin JA The emerging role of nutrition in Parkinsons disease Front Aging Neurosci 2014 Mar 7636 doi 103389fnagi201400036 eCollection 2014

Gluten sensitivity is an abnormal immune response to gluten in genetically susceptible individuals and may manifest solely with neurological dysfunction 90 of gluten sensitive individuals have no GI symptoms

Lancet Neurol 2010 Mar9(3)318-30 Hadjivassiliou M

Figure 2 MRI in four patients with gluten encephalopathy The extent and variability of white matter abnormalities caused by gluten sensitivity can be seen in these four patients (AndashD) A and C show diffuse white matter changes whereas B and D show more f

Marios Hadjivassiliou David S Sanders Richard A Gruumlnewald Nicola Woodroofe Sabrina Boscolo Daniel Aeschl

Gluten sensitivity from gut to brain

The Lancet Neurology Volume 9 Issue 3 2010 318 - 330

httpdxdoiorg101016S1474-4422(09)70290-X

MS and Gluten References 1 Gluten antibodies in patients with multiple sclerosis Hum Nutr Appl

Nutr 1984 Apr38(2)142-32 Multiple sclerosis and gluten sensitivity Clin Neurol Neurosurg 2007

Oct109(8)651-33 Prevalence of celiac disease in multiple sclerosis BMC Neurol 2011 Mar

711314 Celiac disease with neurologic manifestations in children Rev Med Chir

Soc Med Nat Iasi 2013 Jan-Mar117(1)88-945 Celiac disease with cerebral and peripheral nerve involvement

mimicking multiple sclerosis J Med Life 2014 Sep 157(3)440-4 Epub2014 Sep 25

6 A case of multiple sclerosis and celiac disease Case Rep NeurolMed 20132013576921

7 Gluten-related disorders gluten ataxia Dig Dis 201533(2)264-88 Transglutaminase-6 is an autoantigen in progressive multiple sclerosis and

is upregulated in reactive astrocytes Mult Scler 2016 Dec 11352458516684022

9 The progression of coeliac disease its neurological and psychiatric implications Nutr Res Rev 2017 Jun30(1)25-35

Risks of Eggs

bull Prosndash Grass fed - DHA choline biotin lutein Vitamins A D K2 and

B3 B6 B9 B12

bull Cons ndash Eggs are most common food allergen in IBD gt70ndash 60 allergy patients have IgG Ab to eggsndash 13 seasonal allergies have IgG Ab to eggs ndash Wheat milk eggs are common food triggers to Eosinophilic

Esophagitis

References next slide

References Risks of Eggs bull Wang G Ren J Li G et al The utility of food antigen test in the diagnosis of Crohnrsquos disease

and remission maintenance after exclusive enteral nutrition Clin Res Hepatol Gastroenterol 201842(2)145-152 doi101016jclinre201709002

bull Shakoor Z AlFaifi A AlAmro B AlTawil LN AlOhaly RY Prevalence of IgG-mediated food intolerance among patients with allergic symptoms Ann Saudi Med 2016 Nov-Dec36(6)386-390

bull Dhanapala P De Silva C Doran T Suphioglu C Cracking the egg An insight into egg hypersensitivity Mol Immunol 2015 Aug66(2)375-83 doi 101016jmolimm201504016

bull Pang KA Pang KP Pang EB Tan YN Chan YH Siow JK Food allergy and allergic rhinitis in 435 asian patients - A descriptive review Med J Malaysia 2017 Aug72(4)215-220

bull Philpott H Nandurkar S Royce SG Thien F Gibson PR Allergy tests do not predict food triggers in adult patients with eosinophilic oesophagitis A comprehensive prospective study using five modalities Aliment Pharmacol Ther 2016 Aug44(3)223-33 doi 101111apt13676

bull Cai C Shen J Zhao D et al Serological Investigation of Food Specific Immunoglobulin G Antibodies in Patients with Inflammatory Bowel Diseases Boone DL ed PLoS ONE 20149(11)e112154 doi101371journalpone0112154

Lectins

bull ldquoBy eliminating dietary elements particularly lectins which adversely influence both enterocyte and lymphocyte structure and function it is proposed that the peripheral antigenic stimulus (both pathogenic and dietary) will be reduced and thereby result in a diminution of disease symptoms in certain patients with RArdquo

Cordain L Toohey L Smith MJ Hickey MS Modulation of immune function by dietary lectins in rheumatoid arthritis British Journal of Nutrition 200083(03)207-217

bull Lectins are proteins found in plants and animals that bind sugars (hemagglutinins)

bull They can bind the glycoproteins on the intestinal lining leading to barrier damage

bull Lectins are found in most foods but are especially high in grains (esp wheat) dairy legumes and nightshade vegetables

bull Most traditional methods cooking these foods such as soaking ferment-ing amp cooking will decrease the lectin content

Nutrient Triage

bull Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage

ndash Zn Mg biotin Vitamin K D A

ndash Lipoic Acid Acetyl carnitine

Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triageProc Natl Acad Sci U S A 2006 Nov 21103(47)17589-94

What to Eat

Fruit and vegetable consumption and mortality from all causes cardiovascular disease and cancer systematic review and dose-response meta-analysis of prospective cohort studies

16 studies - 833234 participants

BMJ 2014 349 g4490

BMJ 2014 349 g4490

Risk of all cause mortality associated with servingsday of fruit and vegetables

Dose-response relation between fruit and vegetable consumption and risk of all cause mortality

BMJ 2014 349 g4490

Myelin

ndash Omega 3 Fatty Acids

ndash Thiamine (B1)

ndash Folate (B9)

ndash Cobolamin (B12)

ndash Minerals

Key Micronutrients

Bourre JM Effects of nutrients (in food) on the structure and function of the nervous

system update on dietary requirements for brain Part 1 micronutrients

Part 2 Macronutriients

J Nutr Health Aging 200610(5)377-85

Bowman Nutrient biomarker patterns cognitive function and MRI measures of

brain aging Neurology 2012 Jan 2478(4)241-9 Bowman

Sulfur Rich Foods

Why Brassica and Allium

bull Improve detoxification

bull Increase glutathione production

bull Increase GABA production

bull Enhance Neuroprotection

bull Improve endothelial function

Brassica and Allium References

1 Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimers Disease Med Cell Longev20152015781938

2 Learning and memory promoting effects of crude garlic extract Indian J Exp Biol2013 Dec51(12)1094-100

3 Enhancement of the neuroprotective activity of Hericiumerinaceus mycelium co-cultivated with Allium sativum extract Arch Physiol Biochem2015 Feb121(1)19-25

Why Emphasize Mushrooms

bull Increase nerve growth factors (NGF)

bull Hericium erinaceus (Yamabushitake or Lionrsquos Mane) stimulate the production of NGF (in vitro)

bull Activate natural killer cells

bull Prime innate and adaptive immunity

bull Mori K Obara Y Hirota M Azumi Y Kinugasa S Inatomi S Nakahata N Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human

astrocytoma cells Biol Pharm Bull 2008 Sep31(9)1727-32

bull Lee DH Kim HW Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway Int J Med Mushrooms 201416(1)1-16

bull Akramiene D Kondrotas A Didziapetriene J Kevelaitis E Effects of beta-glucans on the immune system Medicina (Kaunas)200743(8)597-606

bull Lai PL Naidu MSabaratnam VWong K DaviP Kuppusamy UR Abdullah N Malek SN Neurotrophic properties of the Lions mane medicinal mushroom

Hericium erinaceus (Higher Basidiomycetes) from Malaysia Int J Med Mushrooms201315(6)539-54

bull Phan CW David P Naidu M Wong KH Sabaratnam V Therapeutic potential of culinary-medicinal mushrooms for the management of

neurodegenerative diseases diversity metabolite and mechanism Crit Rev Biotechnol201535(3)355-68

Why Greens

bull Vitamin K1 metabolized to K2-mk7 in gut

bull K2 important in hellip

ndash Myelin production

ndash Calcium influx into bones and teeth

bull Carotenoids magnesium

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 3: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

Objectives- Review

bull The published research on dietary interventions for MS

bull The mechanisms by which dietary factors may contribute to potential worsening of MS related symptoms

bull The rationale for the structure of the dietary intervention in the Dietary Approaches to Treating MS Related Fatigue Trial NCT02914964

bull At present there are no dietary recommendations in the Evidence Analysis Library for treatment of neuroinflammation or neurodegeneration by the Academy of Nutrition and Dietetics

How many cups of vegetables did you eat in last 24 hours

In 2000 I Became A Patient

bull Left leg weakness

bull Prior history visual dimming

bull Lesions in spinal chord

bull Abnormal CSF

bull Diagnosis relapsing-remitting MS

2003

copyright 2010 Terry Wahls all rights reserved

2007

Institute For Functional Medicine

11

copyright 2010 Terry Wahls all rights reserved

2008

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

The Swank Diet

bull N=144 followed 50 years

bull lt 15 grams saturated fat vs gt 20 grams

bull Greatest benefit earlier in the disease course

bull More likely to remain ambulatory

Review of MS patient survival on a Swank low saturated fat dietNutrition 2003 Feb19(2)161-2 ReviewEffect of low saturated fat diet in early and late cases of multiple sclerosisLancet 1990 Jul 7336(8706)37-9Multiple sclerosis twenty years on low fat dietArch Neurol 1970 Nov23(5)460-74

Low-fat plant-based diet in multiple sclerosis A randomized controlled trial

bull This was a randomized-controlled assessor-blinded one-year long study

bull N=61

bull No change in EDSS MRI

bull Trend towards reduced FSS (fatigue)

Low-fat plant-based diet in multiple sclerosis A randomized controlled trial Mult Scler Relat Disord 2016 Sep980-90

Mediterranean diet adherence and risk of multiple sclerosis ndash Case control study

bull N=70 RRMS 140 controls Interviews re diet

bull Reduced risk of MS

ndash Fruits (OR=028 95 CI 012-063 p-value 0002)

ndash Vegetables (OR=023 95 CI 010-053 p-value 0001)

Mediterranean diet adherence and risk of multiple sclerosis a case-control study Asia Pac J Clin Nutr 201625(2)377-84

Mediterranean Diet bull High olive oil

bull High vegetable polyphenol

bull Whole grains

bull Low red meat

Potential for diet to prevent and remediate cognitive deficits in neurological disordersNutr Rev 2018 Mar 176(3)204-217The Role of Diet in Multiple Sclerosis Mechanistic Connections and Current EvidenceCurr Nutr Rep 2018 Aug 16Anti-inflammatory Activity of Extra Virgin Olive Oil Polyphenols Which Role in the Prevention and Treatment of Immune-Mediated Inflammatory DiseasesEndocr Metab Immune Disord Drug Targets 201818(1)36-50

bull The following slides represent the rationale for the dietary intervention we are studying in the Dietary Approaches to Treating MS Related Fatigue

bull This protocol is not validated nor does it currently meet the current evidence based guideline criteria as set forth by the American Academy of Neurology or the Academy of Nutrition and Dietetics

Dairy amp MSCasein Gluten amp Schizophrenia

bull Liquid cow milk (not cheese) and MS prevalence was highly correlated (rho = 0836) across 27 countries and 29 populations

bull IgG to Casein and gluten were significantly uarrin recent onset and non-recent onset schizophrenia compared to controls (ple000001-0004)

1 Correlation between milk and dairy product consumption and multiple sclerosis prevalence a worldwide

study Neuroepidemiology 199211(4-6)304-12

2 Severance EG Alaedini A Yang S Halling M Gressitt KL Stallings CR Origoni AE Vaughan C

Khushalani S Leweke FM Dickerson FB Yolken RH Gastrointestinal inflammation and associated

immune activation in schizophrenia Schizophr Res2012 Jun138(1)48-53

Gluten and Casein and Opioids

bull Gluten can be degraded into several morphine-like substances named gluten exorphins

bull Milk proteins are particularly strong allergens and are additional source of bioactive peptides including β-casomorphin-7 and exerts its influence on nervous digestive and immune functions via the opioid receptor

1 The opioid effects of gluten exorphins asymptomatic celiac disease J Health PopulNutr 2015 Nov 243324

2 Opioid receptor ligands derived from food proteins Curr Pharm Des 20039(16)1331-44

3 β-casomorphin-7 alters μ-opioid receptor and dipeptidyl peptidase IV genes expression in children with atopic dermatitis Peptides 2014 Dec62144-9

Nutrition in Parkinsons Disease

Seidl SE Santiago JA Bilyk H Potashkin JA The emerging role of nutrition in Parkinsons disease Front Aging Neurosci 2014 Mar 7636 doi 103389fnagi201400036 eCollection 2014

Gluten sensitivity is an abnormal immune response to gluten in genetically susceptible individuals and may manifest solely with neurological dysfunction 90 of gluten sensitive individuals have no GI symptoms

Lancet Neurol 2010 Mar9(3)318-30 Hadjivassiliou M

Figure 2 MRI in four patients with gluten encephalopathy The extent and variability of white matter abnormalities caused by gluten sensitivity can be seen in these four patients (AndashD) A and C show diffuse white matter changes whereas B and D show more f

Marios Hadjivassiliou David S Sanders Richard A Gruumlnewald Nicola Woodroofe Sabrina Boscolo Daniel Aeschl

Gluten sensitivity from gut to brain

The Lancet Neurology Volume 9 Issue 3 2010 318 - 330

httpdxdoiorg101016S1474-4422(09)70290-X

MS and Gluten References 1 Gluten antibodies in patients with multiple sclerosis Hum Nutr Appl

Nutr 1984 Apr38(2)142-32 Multiple sclerosis and gluten sensitivity Clin Neurol Neurosurg 2007

Oct109(8)651-33 Prevalence of celiac disease in multiple sclerosis BMC Neurol 2011 Mar

711314 Celiac disease with neurologic manifestations in children Rev Med Chir

Soc Med Nat Iasi 2013 Jan-Mar117(1)88-945 Celiac disease with cerebral and peripheral nerve involvement

mimicking multiple sclerosis J Med Life 2014 Sep 157(3)440-4 Epub2014 Sep 25

6 A case of multiple sclerosis and celiac disease Case Rep NeurolMed 20132013576921

7 Gluten-related disorders gluten ataxia Dig Dis 201533(2)264-88 Transglutaminase-6 is an autoantigen in progressive multiple sclerosis and

is upregulated in reactive astrocytes Mult Scler 2016 Dec 11352458516684022

9 The progression of coeliac disease its neurological and psychiatric implications Nutr Res Rev 2017 Jun30(1)25-35

Risks of Eggs

bull Prosndash Grass fed - DHA choline biotin lutein Vitamins A D K2 and

B3 B6 B9 B12

bull Cons ndash Eggs are most common food allergen in IBD gt70ndash 60 allergy patients have IgG Ab to eggsndash 13 seasonal allergies have IgG Ab to eggs ndash Wheat milk eggs are common food triggers to Eosinophilic

Esophagitis

References next slide

References Risks of Eggs bull Wang G Ren J Li G et al The utility of food antigen test in the diagnosis of Crohnrsquos disease

and remission maintenance after exclusive enteral nutrition Clin Res Hepatol Gastroenterol 201842(2)145-152 doi101016jclinre201709002

bull Shakoor Z AlFaifi A AlAmro B AlTawil LN AlOhaly RY Prevalence of IgG-mediated food intolerance among patients with allergic symptoms Ann Saudi Med 2016 Nov-Dec36(6)386-390

bull Dhanapala P De Silva C Doran T Suphioglu C Cracking the egg An insight into egg hypersensitivity Mol Immunol 2015 Aug66(2)375-83 doi 101016jmolimm201504016

bull Pang KA Pang KP Pang EB Tan YN Chan YH Siow JK Food allergy and allergic rhinitis in 435 asian patients - A descriptive review Med J Malaysia 2017 Aug72(4)215-220

bull Philpott H Nandurkar S Royce SG Thien F Gibson PR Allergy tests do not predict food triggers in adult patients with eosinophilic oesophagitis A comprehensive prospective study using five modalities Aliment Pharmacol Ther 2016 Aug44(3)223-33 doi 101111apt13676

bull Cai C Shen J Zhao D et al Serological Investigation of Food Specific Immunoglobulin G Antibodies in Patients with Inflammatory Bowel Diseases Boone DL ed PLoS ONE 20149(11)e112154 doi101371journalpone0112154

Lectins

bull ldquoBy eliminating dietary elements particularly lectins which adversely influence both enterocyte and lymphocyte structure and function it is proposed that the peripheral antigenic stimulus (both pathogenic and dietary) will be reduced and thereby result in a diminution of disease symptoms in certain patients with RArdquo

Cordain L Toohey L Smith MJ Hickey MS Modulation of immune function by dietary lectins in rheumatoid arthritis British Journal of Nutrition 200083(03)207-217

bull Lectins are proteins found in plants and animals that bind sugars (hemagglutinins)

bull They can bind the glycoproteins on the intestinal lining leading to barrier damage

bull Lectins are found in most foods but are especially high in grains (esp wheat) dairy legumes and nightshade vegetables

bull Most traditional methods cooking these foods such as soaking ferment-ing amp cooking will decrease the lectin content

Nutrient Triage

bull Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage

ndash Zn Mg biotin Vitamin K D A

ndash Lipoic Acid Acetyl carnitine

Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triageProc Natl Acad Sci U S A 2006 Nov 21103(47)17589-94

What to Eat

Fruit and vegetable consumption and mortality from all causes cardiovascular disease and cancer systematic review and dose-response meta-analysis of prospective cohort studies

16 studies - 833234 participants

BMJ 2014 349 g4490

BMJ 2014 349 g4490

Risk of all cause mortality associated with servingsday of fruit and vegetables

Dose-response relation between fruit and vegetable consumption and risk of all cause mortality

BMJ 2014 349 g4490

Myelin

ndash Omega 3 Fatty Acids

ndash Thiamine (B1)

ndash Folate (B9)

ndash Cobolamin (B12)

ndash Minerals

Key Micronutrients

Bourre JM Effects of nutrients (in food) on the structure and function of the nervous

system update on dietary requirements for brain Part 1 micronutrients

Part 2 Macronutriients

J Nutr Health Aging 200610(5)377-85

Bowman Nutrient biomarker patterns cognitive function and MRI measures of

brain aging Neurology 2012 Jan 2478(4)241-9 Bowman

Sulfur Rich Foods

Why Brassica and Allium

bull Improve detoxification

bull Increase glutathione production

bull Increase GABA production

bull Enhance Neuroprotection

bull Improve endothelial function

Brassica and Allium References

1 Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimers Disease Med Cell Longev20152015781938

2 Learning and memory promoting effects of crude garlic extract Indian J Exp Biol2013 Dec51(12)1094-100

3 Enhancement of the neuroprotective activity of Hericiumerinaceus mycelium co-cultivated with Allium sativum extract Arch Physiol Biochem2015 Feb121(1)19-25

Why Emphasize Mushrooms

bull Increase nerve growth factors (NGF)

bull Hericium erinaceus (Yamabushitake or Lionrsquos Mane) stimulate the production of NGF (in vitro)

bull Activate natural killer cells

bull Prime innate and adaptive immunity

bull Mori K Obara Y Hirota M Azumi Y Kinugasa S Inatomi S Nakahata N Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human

astrocytoma cells Biol Pharm Bull 2008 Sep31(9)1727-32

bull Lee DH Kim HW Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway Int J Med Mushrooms 201416(1)1-16

bull Akramiene D Kondrotas A Didziapetriene J Kevelaitis E Effects of beta-glucans on the immune system Medicina (Kaunas)200743(8)597-606

bull Lai PL Naidu MSabaratnam VWong K DaviP Kuppusamy UR Abdullah N Malek SN Neurotrophic properties of the Lions mane medicinal mushroom

Hericium erinaceus (Higher Basidiomycetes) from Malaysia Int J Med Mushrooms201315(6)539-54

bull Phan CW David P Naidu M Wong KH Sabaratnam V Therapeutic potential of culinary-medicinal mushrooms for the management of

neurodegenerative diseases diversity metabolite and mechanism Crit Rev Biotechnol201535(3)355-68

Why Greens

bull Vitamin K1 metabolized to K2-mk7 in gut

bull K2 important in hellip

ndash Myelin production

ndash Calcium influx into bones and teeth

bull Carotenoids magnesium

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 4: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

bull At present there are no dietary recommendations in the Evidence Analysis Library for treatment of neuroinflammation or neurodegeneration by the Academy of Nutrition and Dietetics

How many cups of vegetables did you eat in last 24 hours

In 2000 I Became A Patient

bull Left leg weakness

bull Prior history visual dimming

bull Lesions in spinal chord

bull Abnormal CSF

bull Diagnosis relapsing-remitting MS

2003

copyright 2010 Terry Wahls all rights reserved

2007

Institute For Functional Medicine

11

copyright 2010 Terry Wahls all rights reserved

2008

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

The Swank Diet

bull N=144 followed 50 years

bull lt 15 grams saturated fat vs gt 20 grams

bull Greatest benefit earlier in the disease course

bull More likely to remain ambulatory

Review of MS patient survival on a Swank low saturated fat dietNutrition 2003 Feb19(2)161-2 ReviewEffect of low saturated fat diet in early and late cases of multiple sclerosisLancet 1990 Jul 7336(8706)37-9Multiple sclerosis twenty years on low fat dietArch Neurol 1970 Nov23(5)460-74

Low-fat plant-based diet in multiple sclerosis A randomized controlled trial

bull This was a randomized-controlled assessor-blinded one-year long study

bull N=61

bull No change in EDSS MRI

bull Trend towards reduced FSS (fatigue)

Low-fat plant-based diet in multiple sclerosis A randomized controlled trial Mult Scler Relat Disord 2016 Sep980-90

Mediterranean diet adherence and risk of multiple sclerosis ndash Case control study

bull N=70 RRMS 140 controls Interviews re diet

bull Reduced risk of MS

ndash Fruits (OR=028 95 CI 012-063 p-value 0002)

ndash Vegetables (OR=023 95 CI 010-053 p-value 0001)

Mediterranean diet adherence and risk of multiple sclerosis a case-control study Asia Pac J Clin Nutr 201625(2)377-84

Mediterranean Diet bull High olive oil

bull High vegetable polyphenol

bull Whole grains

bull Low red meat

Potential for diet to prevent and remediate cognitive deficits in neurological disordersNutr Rev 2018 Mar 176(3)204-217The Role of Diet in Multiple Sclerosis Mechanistic Connections and Current EvidenceCurr Nutr Rep 2018 Aug 16Anti-inflammatory Activity of Extra Virgin Olive Oil Polyphenols Which Role in the Prevention and Treatment of Immune-Mediated Inflammatory DiseasesEndocr Metab Immune Disord Drug Targets 201818(1)36-50

bull The following slides represent the rationale for the dietary intervention we are studying in the Dietary Approaches to Treating MS Related Fatigue

bull This protocol is not validated nor does it currently meet the current evidence based guideline criteria as set forth by the American Academy of Neurology or the Academy of Nutrition and Dietetics

Dairy amp MSCasein Gluten amp Schizophrenia

bull Liquid cow milk (not cheese) and MS prevalence was highly correlated (rho = 0836) across 27 countries and 29 populations

bull IgG to Casein and gluten were significantly uarrin recent onset and non-recent onset schizophrenia compared to controls (ple000001-0004)

1 Correlation between milk and dairy product consumption and multiple sclerosis prevalence a worldwide

study Neuroepidemiology 199211(4-6)304-12

2 Severance EG Alaedini A Yang S Halling M Gressitt KL Stallings CR Origoni AE Vaughan C

Khushalani S Leweke FM Dickerson FB Yolken RH Gastrointestinal inflammation and associated

immune activation in schizophrenia Schizophr Res2012 Jun138(1)48-53

Gluten and Casein and Opioids

bull Gluten can be degraded into several morphine-like substances named gluten exorphins

bull Milk proteins are particularly strong allergens and are additional source of bioactive peptides including β-casomorphin-7 and exerts its influence on nervous digestive and immune functions via the opioid receptor

1 The opioid effects of gluten exorphins asymptomatic celiac disease J Health PopulNutr 2015 Nov 243324

2 Opioid receptor ligands derived from food proteins Curr Pharm Des 20039(16)1331-44

3 β-casomorphin-7 alters μ-opioid receptor and dipeptidyl peptidase IV genes expression in children with atopic dermatitis Peptides 2014 Dec62144-9

Nutrition in Parkinsons Disease

Seidl SE Santiago JA Bilyk H Potashkin JA The emerging role of nutrition in Parkinsons disease Front Aging Neurosci 2014 Mar 7636 doi 103389fnagi201400036 eCollection 2014

Gluten sensitivity is an abnormal immune response to gluten in genetically susceptible individuals and may manifest solely with neurological dysfunction 90 of gluten sensitive individuals have no GI symptoms

Lancet Neurol 2010 Mar9(3)318-30 Hadjivassiliou M

Figure 2 MRI in four patients with gluten encephalopathy The extent and variability of white matter abnormalities caused by gluten sensitivity can be seen in these four patients (AndashD) A and C show diffuse white matter changes whereas B and D show more f

Marios Hadjivassiliou David S Sanders Richard A Gruumlnewald Nicola Woodroofe Sabrina Boscolo Daniel Aeschl

Gluten sensitivity from gut to brain

The Lancet Neurology Volume 9 Issue 3 2010 318 - 330

httpdxdoiorg101016S1474-4422(09)70290-X

MS and Gluten References 1 Gluten antibodies in patients with multiple sclerosis Hum Nutr Appl

Nutr 1984 Apr38(2)142-32 Multiple sclerosis and gluten sensitivity Clin Neurol Neurosurg 2007

Oct109(8)651-33 Prevalence of celiac disease in multiple sclerosis BMC Neurol 2011 Mar

711314 Celiac disease with neurologic manifestations in children Rev Med Chir

Soc Med Nat Iasi 2013 Jan-Mar117(1)88-945 Celiac disease with cerebral and peripheral nerve involvement

mimicking multiple sclerosis J Med Life 2014 Sep 157(3)440-4 Epub2014 Sep 25

6 A case of multiple sclerosis and celiac disease Case Rep NeurolMed 20132013576921

7 Gluten-related disorders gluten ataxia Dig Dis 201533(2)264-88 Transglutaminase-6 is an autoantigen in progressive multiple sclerosis and

is upregulated in reactive astrocytes Mult Scler 2016 Dec 11352458516684022

9 The progression of coeliac disease its neurological and psychiatric implications Nutr Res Rev 2017 Jun30(1)25-35

Risks of Eggs

bull Prosndash Grass fed - DHA choline biotin lutein Vitamins A D K2 and

B3 B6 B9 B12

bull Cons ndash Eggs are most common food allergen in IBD gt70ndash 60 allergy patients have IgG Ab to eggsndash 13 seasonal allergies have IgG Ab to eggs ndash Wheat milk eggs are common food triggers to Eosinophilic

Esophagitis

References next slide

References Risks of Eggs bull Wang G Ren J Li G et al The utility of food antigen test in the diagnosis of Crohnrsquos disease

and remission maintenance after exclusive enteral nutrition Clin Res Hepatol Gastroenterol 201842(2)145-152 doi101016jclinre201709002

bull Shakoor Z AlFaifi A AlAmro B AlTawil LN AlOhaly RY Prevalence of IgG-mediated food intolerance among patients with allergic symptoms Ann Saudi Med 2016 Nov-Dec36(6)386-390

bull Dhanapala P De Silva C Doran T Suphioglu C Cracking the egg An insight into egg hypersensitivity Mol Immunol 2015 Aug66(2)375-83 doi 101016jmolimm201504016

bull Pang KA Pang KP Pang EB Tan YN Chan YH Siow JK Food allergy and allergic rhinitis in 435 asian patients - A descriptive review Med J Malaysia 2017 Aug72(4)215-220

bull Philpott H Nandurkar S Royce SG Thien F Gibson PR Allergy tests do not predict food triggers in adult patients with eosinophilic oesophagitis A comprehensive prospective study using five modalities Aliment Pharmacol Ther 2016 Aug44(3)223-33 doi 101111apt13676

bull Cai C Shen J Zhao D et al Serological Investigation of Food Specific Immunoglobulin G Antibodies in Patients with Inflammatory Bowel Diseases Boone DL ed PLoS ONE 20149(11)e112154 doi101371journalpone0112154

Lectins

bull ldquoBy eliminating dietary elements particularly lectins which adversely influence both enterocyte and lymphocyte structure and function it is proposed that the peripheral antigenic stimulus (both pathogenic and dietary) will be reduced and thereby result in a diminution of disease symptoms in certain patients with RArdquo

Cordain L Toohey L Smith MJ Hickey MS Modulation of immune function by dietary lectins in rheumatoid arthritis British Journal of Nutrition 200083(03)207-217

bull Lectins are proteins found in plants and animals that bind sugars (hemagglutinins)

bull They can bind the glycoproteins on the intestinal lining leading to barrier damage

bull Lectins are found in most foods but are especially high in grains (esp wheat) dairy legumes and nightshade vegetables

bull Most traditional methods cooking these foods such as soaking ferment-ing amp cooking will decrease the lectin content

Nutrient Triage

bull Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage

ndash Zn Mg biotin Vitamin K D A

ndash Lipoic Acid Acetyl carnitine

Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triageProc Natl Acad Sci U S A 2006 Nov 21103(47)17589-94

What to Eat

Fruit and vegetable consumption and mortality from all causes cardiovascular disease and cancer systematic review and dose-response meta-analysis of prospective cohort studies

16 studies - 833234 participants

BMJ 2014 349 g4490

BMJ 2014 349 g4490

Risk of all cause mortality associated with servingsday of fruit and vegetables

Dose-response relation between fruit and vegetable consumption and risk of all cause mortality

BMJ 2014 349 g4490

Myelin

ndash Omega 3 Fatty Acids

ndash Thiamine (B1)

ndash Folate (B9)

ndash Cobolamin (B12)

ndash Minerals

Key Micronutrients

Bourre JM Effects of nutrients (in food) on the structure and function of the nervous

system update on dietary requirements for brain Part 1 micronutrients

Part 2 Macronutriients

J Nutr Health Aging 200610(5)377-85

Bowman Nutrient biomarker patterns cognitive function and MRI measures of

brain aging Neurology 2012 Jan 2478(4)241-9 Bowman

Sulfur Rich Foods

Why Brassica and Allium

bull Improve detoxification

bull Increase glutathione production

bull Increase GABA production

bull Enhance Neuroprotection

bull Improve endothelial function

Brassica and Allium References

1 Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimers Disease Med Cell Longev20152015781938

2 Learning and memory promoting effects of crude garlic extract Indian J Exp Biol2013 Dec51(12)1094-100

3 Enhancement of the neuroprotective activity of Hericiumerinaceus mycelium co-cultivated with Allium sativum extract Arch Physiol Biochem2015 Feb121(1)19-25

Why Emphasize Mushrooms

bull Increase nerve growth factors (NGF)

bull Hericium erinaceus (Yamabushitake or Lionrsquos Mane) stimulate the production of NGF (in vitro)

bull Activate natural killer cells

bull Prime innate and adaptive immunity

bull Mori K Obara Y Hirota M Azumi Y Kinugasa S Inatomi S Nakahata N Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human

astrocytoma cells Biol Pharm Bull 2008 Sep31(9)1727-32

bull Lee DH Kim HW Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway Int J Med Mushrooms 201416(1)1-16

bull Akramiene D Kondrotas A Didziapetriene J Kevelaitis E Effects of beta-glucans on the immune system Medicina (Kaunas)200743(8)597-606

bull Lai PL Naidu MSabaratnam VWong K DaviP Kuppusamy UR Abdullah N Malek SN Neurotrophic properties of the Lions mane medicinal mushroom

Hericium erinaceus (Higher Basidiomycetes) from Malaysia Int J Med Mushrooms201315(6)539-54

bull Phan CW David P Naidu M Wong KH Sabaratnam V Therapeutic potential of culinary-medicinal mushrooms for the management of

neurodegenerative diseases diversity metabolite and mechanism Crit Rev Biotechnol201535(3)355-68

Why Greens

bull Vitamin K1 metabolized to K2-mk7 in gut

bull K2 important in hellip

ndash Myelin production

ndash Calcium influx into bones and teeth

bull Carotenoids magnesium

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 5: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

How many cups of vegetables did you eat in last 24 hours

In 2000 I Became A Patient

bull Left leg weakness

bull Prior history visual dimming

bull Lesions in spinal chord

bull Abnormal CSF

bull Diagnosis relapsing-remitting MS

2003

copyright 2010 Terry Wahls all rights reserved

2007

Institute For Functional Medicine

11

copyright 2010 Terry Wahls all rights reserved

2008

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

The Swank Diet

bull N=144 followed 50 years

bull lt 15 grams saturated fat vs gt 20 grams

bull Greatest benefit earlier in the disease course

bull More likely to remain ambulatory

Review of MS patient survival on a Swank low saturated fat dietNutrition 2003 Feb19(2)161-2 ReviewEffect of low saturated fat diet in early and late cases of multiple sclerosisLancet 1990 Jul 7336(8706)37-9Multiple sclerosis twenty years on low fat dietArch Neurol 1970 Nov23(5)460-74

Low-fat plant-based diet in multiple sclerosis A randomized controlled trial

bull This was a randomized-controlled assessor-blinded one-year long study

bull N=61

bull No change in EDSS MRI

bull Trend towards reduced FSS (fatigue)

Low-fat plant-based diet in multiple sclerosis A randomized controlled trial Mult Scler Relat Disord 2016 Sep980-90

Mediterranean diet adherence and risk of multiple sclerosis ndash Case control study

bull N=70 RRMS 140 controls Interviews re diet

bull Reduced risk of MS

ndash Fruits (OR=028 95 CI 012-063 p-value 0002)

ndash Vegetables (OR=023 95 CI 010-053 p-value 0001)

Mediterranean diet adherence and risk of multiple sclerosis a case-control study Asia Pac J Clin Nutr 201625(2)377-84

Mediterranean Diet bull High olive oil

bull High vegetable polyphenol

bull Whole grains

bull Low red meat

Potential for diet to prevent and remediate cognitive deficits in neurological disordersNutr Rev 2018 Mar 176(3)204-217The Role of Diet in Multiple Sclerosis Mechanistic Connections and Current EvidenceCurr Nutr Rep 2018 Aug 16Anti-inflammatory Activity of Extra Virgin Olive Oil Polyphenols Which Role in the Prevention and Treatment of Immune-Mediated Inflammatory DiseasesEndocr Metab Immune Disord Drug Targets 201818(1)36-50

bull The following slides represent the rationale for the dietary intervention we are studying in the Dietary Approaches to Treating MS Related Fatigue

bull This protocol is not validated nor does it currently meet the current evidence based guideline criteria as set forth by the American Academy of Neurology or the Academy of Nutrition and Dietetics

Dairy amp MSCasein Gluten amp Schizophrenia

bull Liquid cow milk (not cheese) and MS prevalence was highly correlated (rho = 0836) across 27 countries and 29 populations

bull IgG to Casein and gluten were significantly uarrin recent onset and non-recent onset schizophrenia compared to controls (ple000001-0004)

1 Correlation between milk and dairy product consumption and multiple sclerosis prevalence a worldwide

study Neuroepidemiology 199211(4-6)304-12

2 Severance EG Alaedini A Yang S Halling M Gressitt KL Stallings CR Origoni AE Vaughan C

Khushalani S Leweke FM Dickerson FB Yolken RH Gastrointestinal inflammation and associated

immune activation in schizophrenia Schizophr Res2012 Jun138(1)48-53

Gluten and Casein and Opioids

bull Gluten can be degraded into several morphine-like substances named gluten exorphins

bull Milk proteins are particularly strong allergens and are additional source of bioactive peptides including β-casomorphin-7 and exerts its influence on nervous digestive and immune functions via the opioid receptor

1 The opioid effects of gluten exorphins asymptomatic celiac disease J Health PopulNutr 2015 Nov 243324

2 Opioid receptor ligands derived from food proteins Curr Pharm Des 20039(16)1331-44

3 β-casomorphin-7 alters μ-opioid receptor and dipeptidyl peptidase IV genes expression in children with atopic dermatitis Peptides 2014 Dec62144-9

Nutrition in Parkinsons Disease

Seidl SE Santiago JA Bilyk H Potashkin JA The emerging role of nutrition in Parkinsons disease Front Aging Neurosci 2014 Mar 7636 doi 103389fnagi201400036 eCollection 2014

Gluten sensitivity is an abnormal immune response to gluten in genetically susceptible individuals and may manifest solely with neurological dysfunction 90 of gluten sensitive individuals have no GI symptoms

Lancet Neurol 2010 Mar9(3)318-30 Hadjivassiliou M

Figure 2 MRI in four patients with gluten encephalopathy The extent and variability of white matter abnormalities caused by gluten sensitivity can be seen in these four patients (AndashD) A and C show diffuse white matter changes whereas B and D show more f

Marios Hadjivassiliou David S Sanders Richard A Gruumlnewald Nicola Woodroofe Sabrina Boscolo Daniel Aeschl

Gluten sensitivity from gut to brain

The Lancet Neurology Volume 9 Issue 3 2010 318 - 330

httpdxdoiorg101016S1474-4422(09)70290-X

MS and Gluten References 1 Gluten antibodies in patients with multiple sclerosis Hum Nutr Appl

Nutr 1984 Apr38(2)142-32 Multiple sclerosis and gluten sensitivity Clin Neurol Neurosurg 2007

Oct109(8)651-33 Prevalence of celiac disease in multiple sclerosis BMC Neurol 2011 Mar

711314 Celiac disease with neurologic manifestations in children Rev Med Chir

Soc Med Nat Iasi 2013 Jan-Mar117(1)88-945 Celiac disease with cerebral and peripheral nerve involvement

mimicking multiple sclerosis J Med Life 2014 Sep 157(3)440-4 Epub2014 Sep 25

6 A case of multiple sclerosis and celiac disease Case Rep NeurolMed 20132013576921

7 Gluten-related disorders gluten ataxia Dig Dis 201533(2)264-88 Transglutaminase-6 is an autoantigen in progressive multiple sclerosis and

is upregulated in reactive astrocytes Mult Scler 2016 Dec 11352458516684022

9 The progression of coeliac disease its neurological and psychiatric implications Nutr Res Rev 2017 Jun30(1)25-35

Risks of Eggs

bull Prosndash Grass fed - DHA choline biotin lutein Vitamins A D K2 and

B3 B6 B9 B12

bull Cons ndash Eggs are most common food allergen in IBD gt70ndash 60 allergy patients have IgG Ab to eggsndash 13 seasonal allergies have IgG Ab to eggs ndash Wheat milk eggs are common food triggers to Eosinophilic

Esophagitis

References next slide

References Risks of Eggs bull Wang G Ren J Li G et al The utility of food antigen test in the diagnosis of Crohnrsquos disease

and remission maintenance after exclusive enteral nutrition Clin Res Hepatol Gastroenterol 201842(2)145-152 doi101016jclinre201709002

bull Shakoor Z AlFaifi A AlAmro B AlTawil LN AlOhaly RY Prevalence of IgG-mediated food intolerance among patients with allergic symptoms Ann Saudi Med 2016 Nov-Dec36(6)386-390

bull Dhanapala P De Silva C Doran T Suphioglu C Cracking the egg An insight into egg hypersensitivity Mol Immunol 2015 Aug66(2)375-83 doi 101016jmolimm201504016

bull Pang KA Pang KP Pang EB Tan YN Chan YH Siow JK Food allergy and allergic rhinitis in 435 asian patients - A descriptive review Med J Malaysia 2017 Aug72(4)215-220

bull Philpott H Nandurkar S Royce SG Thien F Gibson PR Allergy tests do not predict food triggers in adult patients with eosinophilic oesophagitis A comprehensive prospective study using five modalities Aliment Pharmacol Ther 2016 Aug44(3)223-33 doi 101111apt13676

bull Cai C Shen J Zhao D et al Serological Investigation of Food Specific Immunoglobulin G Antibodies in Patients with Inflammatory Bowel Diseases Boone DL ed PLoS ONE 20149(11)e112154 doi101371journalpone0112154

Lectins

bull ldquoBy eliminating dietary elements particularly lectins which adversely influence both enterocyte and lymphocyte structure and function it is proposed that the peripheral antigenic stimulus (both pathogenic and dietary) will be reduced and thereby result in a diminution of disease symptoms in certain patients with RArdquo

Cordain L Toohey L Smith MJ Hickey MS Modulation of immune function by dietary lectins in rheumatoid arthritis British Journal of Nutrition 200083(03)207-217

bull Lectins are proteins found in plants and animals that bind sugars (hemagglutinins)

bull They can bind the glycoproteins on the intestinal lining leading to barrier damage

bull Lectins are found in most foods but are especially high in grains (esp wheat) dairy legumes and nightshade vegetables

bull Most traditional methods cooking these foods such as soaking ferment-ing amp cooking will decrease the lectin content

Nutrient Triage

bull Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage

ndash Zn Mg biotin Vitamin K D A

ndash Lipoic Acid Acetyl carnitine

Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triageProc Natl Acad Sci U S A 2006 Nov 21103(47)17589-94

What to Eat

Fruit and vegetable consumption and mortality from all causes cardiovascular disease and cancer systematic review and dose-response meta-analysis of prospective cohort studies

16 studies - 833234 participants

BMJ 2014 349 g4490

BMJ 2014 349 g4490

Risk of all cause mortality associated with servingsday of fruit and vegetables

Dose-response relation between fruit and vegetable consumption and risk of all cause mortality

BMJ 2014 349 g4490

Myelin

ndash Omega 3 Fatty Acids

ndash Thiamine (B1)

ndash Folate (B9)

ndash Cobolamin (B12)

ndash Minerals

Key Micronutrients

Bourre JM Effects of nutrients (in food) on the structure and function of the nervous

system update on dietary requirements for brain Part 1 micronutrients

Part 2 Macronutriients

J Nutr Health Aging 200610(5)377-85

Bowman Nutrient biomarker patterns cognitive function and MRI measures of

brain aging Neurology 2012 Jan 2478(4)241-9 Bowman

Sulfur Rich Foods

Why Brassica and Allium

bull Improve detoxification

bull Increase glutathione production

bull Increase GABA production

bull Enhance Neuroprotection

bull Improve endothelial function

Brassica and Allium References

1 Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimers Disease Med Cell Longev20152015781938

2 Learning and memory promoting effects of crude garlic extract Indian J Exp Biol2013 Dec51(12)1094-100

3 Enhancement of the neuroprotective activity of Hericiumerinaceus mycelium co-cultivated with Allium sativum extract Arch Physiol Biochem2015 Feb121(1)19-25

Why Emphasize Mushrooms

bull Increase nerve growth factors (NGF)

bull Hericium erinaceus (Yamabushitake or Lionrsquos Mane) stimulate the production of NGF (in vitro)

bull Activate natural killer cells

bull Prime innate and adaptive immunity

bull Mori K Obara Y Hirota M Azumi Y Kinugasa S Inatomi S Nakahata N Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human

astrocytoma cells Biol Pharm Bull 2008 Sep31(9)1727-32

bull Lee DH Kim HW Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway Int J Med Mushrooms 201416(1)1-16

bull Akramiene D Kondrotas A Didziapetriene J Kevelaitis E Effects of beta-glucans on the immune system Medicina (Kaunas)200743(8)597-606

bull Lai PL Naidu MSabaratnam VWong K DaviP Kuppusamy UR Abdullah N Malek SN Neurotrophic properties of the Lions mane medicinal mushroom

Hericium erinaceus (Higher Basidiomycetes) from Malaysia Int J Med Mushrooms201315(6)539-54

bull Phan CW David P Naidu M Wong KH Sabaratnam V Therapeutic potential of culinary-medicinal mushrooms for the management of

neurodegenerative diseases diversity metabolite and mechanism Crit Rev Biotechnol201535(3)355-68

Why Greens

bull Vitamin K1 metabolized to K2-mk7 in gut

bull K2 important in hellip

ndash Myelin production

ndash Calcium influx into bones and teeth

bull Carotenoids magnesium

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 6: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

In 2000 I Became A Patient

bull Left leg weakness

bull Prior history visual dimming

bull Lesions in spinal chord

bull Abnormal CSF

bull Diagnosis relapsing-remitting MS

2003

copyright 2010 Terry Wahls all rights reserved

2007

Institute For Functional Medicine

11

copyright 2010 Terry Wahls all rights reserved

2008

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

The Swank Diet

bull N=144 followed 50 years

bull lt 15 grams saturated fat vs gt 20 grams

bull Greatest benefit earlier in the disease course

bull More likely to remain ambulatory

Review of MS patient survival on a Swank low saturated fat dietNutrition 2003 Feb19(2)161-2 ReviewEffect of low saturated fat diet in early and late cases of multiple sclerosisLancet 1990 Jul 7336(8706)37-9Multiple sclerosis twenty years on low fat dietArch Neurol 1970 Nov23(5)460-74

Low-fat plant-based diet in multiple sclerosis A randomized controlled trial

bull This was a randomized-controlled assessor-blinded one-year long study

bull N=61

bull No change in EDSS MRI

bull Trend towards reduced FSS (fatigue)

Low-fat plant-based diet in multiple sclerosis A randomized controlled trial Mult Scler Relat Disord 2016 Sep980-90

Mediterranean diet adherence and risk of multiple sclerosis ndash Case control study

bull N=70 RRMS 140 controls Interviews re diet

bull Reduced risk of MS

ndash Fruits (OR=028 95 CI 012-063 p-value 0002)

ndash Vegetables (OR=023 95 CI 010-053 p-value 0001)

Mediterranean diet adherence and risk of multiple sclerosis a case-control study Asia Pac J Clin Nutr 201625(2)377-84

Mediterranean Diet bull High olive oil

bull High vegetable polyphenol

bull Whole grains

bull Low red meat

Potential for diet to prevent and remediate cognitive deficits in neurological disordersNutr Rev 2018 Mar 176(3)204-217The Role of Diet in Multiple Sclerosis Mechanistic Connections and Current EvidenceCurr Nutr Rep 2018 Aug 16Anti-inflammatory Activity of Extra Virgin Olive Oil Polyphenols Which Role in the Prevention and Treatment of Immune-Mediated Inflammatory DiseasesEndocr Metab Immune Disord Drug Targets 201818(1)36-50

bull The following slides represent the rationale for the dietary intervention we are studying in the Dietary Approaches to Treating MS Related Fatigue

bull This protocol is not validated nor does it currently meet the current evidence based guideline criteria as set forth by the American Academy of Neurology or the Academy of Nutrition and Dietetics

Dairy amp MSCasein Gluten amp Schizophrenia

bull Liquid cow milk (not cheese) and MS prevalence was highly correlated (rho = 0836) across 27 countries and 29 populations

bull IgG to Casein and gluten were significantly uarrin recent onset and non-recent onset schizophrenia compared to controls (ple000001-0004)

1 Correlation between milk and dairy product consumption and multiple sclerosis prevalence a worldwide

study Neuroepidemiology 199211(4-6)304-12

2 Severance EG Alaedini A Yang S Halling M Gressitt KL Stallings CR Origoni AE Vaughan C

Khushalani S Leweke FM Dickerson FB Yolken RH Gastrointestinal inflammation and associated

immune activation in schizophrenia Schizophr Res2012 Jun138(1)48-53

Gluten and Casein and Opioids

bull Gluten can be degraded into several morphine-like substances named gluten exorphins

bull Milk proteins are particularly strong allergens and are additional source of bioactive peptides including β-casomorphin-7 and exerts its influence on nervous digestive and immune functions via the opioid receptor

1 The opioid effects of gluten exorphins asymptomatic celiac disease J Health PopulNutr 2015 Nov 243324

2 Opioid receptor ligands derived from food proteins Curr Pharm Des 20039(16)1331-44

3 β-casomorphin-7 alters μ-opioid receptor and dipeptidyl peptidase IV genes expression in children with atopic dermatitis Peptides 2014 Dec62144-9

Nutrition in Parkinsons Disease

Seidl SE Santiago JA Bilyk H Potashkin JA The emerging role of nutrition in Parkinsons disease Front Aging Neurosci 2014 Mar 7636 doi 103389fnagi201400036 eCollection 2014

Gluten sensitivity is an abnormal immune response to gluten in genetically susceptible individuals and may manifest solely with neurological dysfunction 90 of gluten sensitive individuals have no GI symptoms

Lancet Neurol 2010 Mar9(3)318-30 Hadjivassiliou M

Figure 2 MRI in four patients with gluten encephalopathy The extent and variability of white matter abnormalities caused by gluten sensitivity can be seen in these four patients (AndashD) A and C show diffuse white matter changes whereas B and D show more f

Marios Hadjivassiliou David S Sanders Richard A Gruumlnewald Nicola Woodroofe Sabrina Boscolo Daniel Aeschl

Gluten sensitivity from gut to brain

The Lancet Neurology Volume 9 Issue 3 2010 318 - 330

httpdxdoiorg101016S1474-4422(09)70290-X

MS and Gluten References 1 Gluten antibodies in patients with multiple sclerosis Hum Nutr Appl

Nutr 1984 Apr38(2)142-32 Multiple sclerosis and gluten sensitivity Clin Neurol Neurosurg 2007

Oct109(8)651-33 Prevalence of celiac disease in multiple sclerosis BMC Neurol 2011 Mar

711314 Celiac disease with neurologic manifestations in children Rev Med Chir

Soc Med Nat Iasi 2013 Jan-Mar117(1)88-945 Celiac disease with cerebral and peripheral nerve involvement

mimicking multiple sclerosis J Med Life 2014 Sep 157(3)440-4 Epub2014 Sep 25

6 A case of multiple sclerosis and celiac disease Case Rep NeurolMed 20132013576921

7 Gluten-related disorders gluten ataxia Dig Dis 201533(2)264-88 Transglutaminase-6 is an autoantigen in progressive multiple sclerosis and

is upregulated in reactive astrocytes Mult Scler 2016 Dec 11352458516684022

9 The progression of coeliac disease its neurological and psychiatric implications Nutr Res Rev 2017 Jun30(1)25-35

Risks of Eggs

bull Prosndash Grass fed - DHA choline biotin lutein Vitamins A D K2 and

B3 B6 B9 B12

bull Cons ndash Eggs are most common food allergen in IBD gt70ndash 60 allergy patients have IgG Ab to eggsndash 13 seasonal allergies have IgG Ab to eggs ndash Wheat milk eggs are common food triggers to Eosinophilic

Esophagitis

References next slide

References Risks of Eggs bull Wang G Ren J Li G et al The utility of food antigen test in the diagnosis of Crohnrsquos disease

and remission maintenance after exclusive enteral nutrition Clin Res Hepatol Gastroenterol 201842(2)145-152 doi101016jclinre201709002

bull Shakoor Z AlFaifi A AlAmro B AlTawil LN AlOhaly RY Prevalence of IgG-mediated food intolerance among patients with allergic symptoms Ann Saudi Med 2016 Nov-Dec36(6)386-390

bull Dhanapala P De Silva C Doran T Suphioglu C Cracking the egg An insight into egg hypersensitivity Mol Immunol 2015 Aug66(2)375-83 doi 101016jmolimm201504016

bull Pang KA Pang KP Pang EB Tan YN Chan YH Siow JK Food allergy and allergic rhinitis in 435 asian patients - A descriptive review Med J Malaysia 2017 Aug72(4)215-220

bull Philpott H Nandurkar S Royce SG Thien F Gibson PR Allergy tests do not predict food triggers in adult patients with eosinophilic oesophagitis A comprehensive prospective study using five modalities Aliment Pharmacol Ther 2016 Aug44(3)223-33 doi 101111apt13676

bull Cai C Shen J Zhao D et al Serological Investigation of Food Specific Immunoglobulin G Antibodies in Patients with Inflammatory Bowel Diseases Boone DL ed PLoS ONE 20149(11)e112154 doi101371journalpone0112154

Lectins

bull ldquoBy eliminating dietary elements particularly lectins which adversely influence both enterocyte and lymphocyte structure and function it is proposed that the peripheral antigenic stimulus (both pathogenic and dietary) will be reduced and thereby result in a diminution of disease symptoms in certain patients with RArdquo

Cordain L Toohey L Smith MJ Hickey MS Modulation of immune function by dietary lectins in rheumatoid arthritis British Journal of Nutrition 200083(03)207-217

bull Lectins are proteins found in plants and animals that bind sugars (hemagglutinins)

bull They can bind the glycoproteins on the intestinal lining leading to barrier damage

bull Lectins are found in most foods but are especially high in grains (esp wheat) dairy legumes and nightshade vegetables

bull Most traditional methods cooking these foods such as soaking ferment-ing amp cooking will decrease the lectin content

Nutrient Triage

bull Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage

ndash Zn Mg biotin Vitamin K D A

ndash Lipoic Acid Acetyl carnitine

Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triageProc Natl Acad Sci U S A 2006 Nov 21103(47)17589-94

What to Eat

Fruit and vegetable consumption and mortality from all causes cardiovascular disease and cancer systematic review and dose-response meta-analysis of prospective cohort studies

16 studies - 833234 participants

BMJ 2014 349 g4490

BMJ 2014 349 g4490

Risk of all cause mortality associated with servingsday of fruit and vegetables

Dose-response relation between fruit and vegetable consumption and risk of all cause mortality

BMJ 2014 349 g4490

Myelin

ndash Omega 3 Fatty Acids

ndash Thiamine (B1)

ndash Folate (B9)

ndash Cobolamin (B12)

ndash Minerals

Key Micronutrients

Bourre JM Effects of nutrients (in food) on the structure and function of the nervous

system update on dietary requirements for brain Part 1 micronutrients

Part 2 Macronutriients

J Nutr Health Aging 200610(5)377-85

Bowman Nutrient biomarker patterns cognitive function and MRI measures of

brain aging Neurology 2012 Jan 2478(4)241-9 Bowman

Sulfur Rich Foods

Why Brassica and Allium

bull Improve detoxification

bull Increase glutathione production

bull Increase GABA production

bull Enhance Neuroprotection

bull Improve endothelial function

Brassica and Allium References

1 Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimers Disease Med Cell Longev20152015781938

2 Learning and memory promoting effects of crude garlic extract Indian J Exp Biol2013 Dec51(12)1094-100

3 Enhancement of the neuroprotective activity of Hericiumerinaceus mycelium co-cultivated with Allium sativum extract Arch Physiol Biochem2015 Feb121(1)19-25

Why Emphasize Mushrooms

bull Increase nerve growth factors (NGF)

bull Hericium erinaceus (Yamabushitake or Lionrsquos Mane) stimulate the production of NGF (in vitro)

bull Activate natural killer cells

bull Prime innate and adaptive immunity

bull Mori K Obara Y Hirota M Azumi Y Kinugasa S Inatomi S Nakahata N Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human

astrocytoma cells Biol Pharm Bull 2008 Sep31(9)1727-32

bull Lee DH Kim HW Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway Int J Med Mushrooms 201416(1)1-16

bull Akramiene D Kondrotas A Didziapetriene J Kevelaitis E Effects of beta-glucans on the immune system Medicina (Kaunas)200743(8)597-606

bull Lai PL Naidu MSabaratnam VWong K DaviP Kuppusamy UR Abdullah N Malek SN Neurotrophic properties of the Lions mane medicinal mushroom

Hericium erinaceus (Higher Basidiomycetes) from Malaysia Int J Med Mushrooms201315(6)539-54

bull Phan CW David P Naidu M Wong KH Sabaratnam V Therapeutic potential of culinary-medicinal mushrooms for the management of

neurodegenerative diseases diversity metabolite and mechanism Crit Rev Biotechnol201535(3)355-68

Why Greens

bull Vitamin K1 metabolized to K2-mk7 in gut

bull K2 important in hellip

ndash Myelin production

ndash Calcium influx into bones and teeth

bull Carotenoids magnesium

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 7: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

2003

copyright 2010 Terry Wahls all rights reserved

2007

Institute For Functional Medicine

11

copyright 2010 Terry Wahls all rights reserved

2008

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

The Swank Diet

bull N=144 followed 50 years

bull lt 15 grams saturated fat vs gt 20 grams

bull Greatest benefit earlier in the disease course

bull More likely to remain ambulatory

Review of MS patient survival on a Swank low saturated fat dietNutrition 2003 Feb19(2)161-2 ReviewEffect of low saturated fat diet in early and late cases of multiple sclerosisLancet 1990 Jul 7336(8706)37-9Multiple sclerosis twenty years on low fat dietArch Neurol 1970 Nov23(5)460-74

Low-fat plant-based diet in multiple sclerosis A randomized controlled trial

bull This was a randomized-controlled assessor-blinded one-year long study

bull N=61

bull No change in EDSS MRI

bull Trend towards reduced FSS (fatigue)

Low-fat plant-based diet in multiple sclerosis A randomized controlled trial Mult Scler Relat Disord 2016 Sep980-90

Mediterranean diet adherence and risk of multiple sclerosis ndash Case control study

bull N=70 RRMS 140 controls Interviews re diet

bull Reduced risk of MS

ndash Fruits (OR=028 95 CI 012-063 p-value 0002)

ndash Vegetables (OR=023 95 CI 010-053 p-value 0001)

Mediterranean diet adherence and risk of multiple sclerosis a case-control study Asia Pac J Clin Nutr 201625(2)377-84

Mediterranean Diet bull High olive oil

bull High vegetable polyphenol

bull Whole grains

bull Low red meat

Potential for diet to prevent and remediate cognitive deficits in neurological disordersNutr Rev 2018 Mar 176(3)204-217The Role of Diet in Multiple Sclerosis Mechanistic Connections and Current EvidenceCurr Nutr Rep 2018 Aug 16Anti-inflammatory Activity of Extra Virgin Olive Oil Polyphenols Which Role in the Prevention and Treatment of Immune-Mediated Inflammatory DiseasesEndocr Metab Immune Disord Drug Targets 201818(1)36-50

bull The following slides represent the rationale for the dietary intervention we are studying in the Dietary Approaches to Treating MS Related Fatigue

bull This protocol is not validated nor does it currently meet the current evidence based guideline criteria as set forth by the American Academy of Neurology or the Academy of Nutrition and Dietetics

Dairy amp MSCasein Gluten amp Schizophrenia

bull Liquid cow milk (not cheese) and MS prevalence was highly correlated (rho = 0836) across 27 countries and 29 populations

bull IgG to Casein and gluten were significantly uarrin recent onset and non-recent onset schizophrenia compared to controls (ple000001-0004)

1 Correlation between milk and dairy product consumption and multiple sclerosis prevalence a worldwide

study Neuroepidemiology 199211(4-6)304-12

2 Severance EG Alaedini A Yang S Halling M Gressitt KL Stallings CR Origoni AE Vaughan C

Khushalani S Leweke FM Dickerson FB Yolken RH Gastrointestinal inflammation and associated

immune activation in schizophrenia Schizophr Res2012 Jun138(1)48-53

Gluten and Casein and Opioids

bull Gluten can be degraded into several morphine-like substances named gluten exorphins

bull Milk proteins are particularly strong allergens and are additional source of bioactive peptides including β-casomorphin-7 and exerts its influence on nervous digestive and immune functions via the opioid receptor

1 The opioid effects of gluten exorphins asymptomatic celiac disease J Health PopulNutr 2015 Nov 243324

2 Opioid receptor ligands derived from food proteins Curr Pharm Des 20039(16)1331-44

3 β-casomorphin-7 alters μ-opioid receptor and dipeptidyl peptidase IV genes expression in children with atopic dermatitis Peptides 2014 Dec62144-9

Nutrition in Parkinsons Disease

Seidl SE Santiago JA Bilyk H Potashkin JA The emerging role of nutrition in Parkinsons disease Front Aging Neurosci 2014 Mar 7636 doi 103389fnagi201400036 eCollection 2014

Gluten sensitivity is an abnormal immune response to gluten in genetically susceptible individuals and may manifest solely with neurological dysfunction 90 of gluten sensitive individuals have no GI symptoms

Lancet Neurol 2010 Mar9(3)318-30 Hadjivassiliou M

Figure 2 MRI in four patients with gluten encephalopathy The extent and variability of white matter abnormalities caused by gluten sensitivity can be seen in these four patients (AndashD) A and C show diffuse white matter changes whereas B and D show more f

Marios Hadjivassiliou David S Sanders Richard A Gruumlnewald Nicola Woodroofe Sabrina Boscolo Daniel Aeschl

Gluten sensitivity from gut to brain

The Lancet Neurology Volume 9 Issue 3 2010 318 - 330

httpdxdoiorg101016S1474-4422(09)70290-X

MS and Gluten References 1 Gluten antibodies in patients with multiple sclerosis Hum Nutr Appl

Nutr 1984 Apr38(2)142-32 Multiple sclerosis and gluten sensitivity Clin Neurol Neurosurg 2007

Oct109(8)651-33 Prevalence of celiac disease in multiple sclerosis BMC Neurol 2011 Mar

711314 Celiac disease with neurologic manifestations in children Rev Med Chir

Soc Med Nat Iasi 2013 Jan-Mar117(1)88-945 Celiac disease with cerebral and peripheral nerve involvement

mimicking multiple sclerosis J Med Life 2014 Sep 157(3)440-4 Epub2014 Sep 25

6 A case of multiple sclerosis and celiac disease Case Rep NeurolMed 20132013576921

7 Gluten-related disorders gluten ataxia Dig Dis 201533(2)264-88 Transglutaminase-6 is an autoantigen in progressive multiple sclerosis and

is upregulated in reactive astrocytes Mult Scler 2016 Dec 11352458516684022

9 The progression of coeliac disease its neurological and psychiatric implications Nutr Res Rev 2017 Jun30(1)25-35

Risks of Eggs

bull Prosndash Grass fed - DHA choline biotin lutein Vitamins A D K2 and

B3 B6 B9 B12

bull Cons ndash Eggs are most common food allergen in IBD gt70ndash 60 allergy patients have IgG Ab to eggsndash 13 seasonal allergies have IgG Ab to eggs ndash Wheat milk eggs are common food triggers to Eosinophilic

Esophagitis

References next slide

References Risks of Eggs bull Wang G Ren J Li G et al The utility of food antigen test in the diagnosis of Crohnrsquos disease

and remission maintenance after exclusive enteral nutrition Clin Res Hepatol Gastroenterol 201842(2)145-152 doi101016jclinre201709002

bull Shakoor Z AlFaifi A AlAmro B AlTawil LN AlOhaly RY Prevalence of IgG-mediated food intolerance among patients with allergic symptoms Ann Saudi Med 2016 Nov-Dec36(6)386-390

bull Dhanapala P De Silva C Doran T Suphioglu C Cracking the egg An insight into egg hypersensitivity Mol Immunol 2015 Aug66(2)375-83 doi 101016jmolimm201504016

bull Pang KA Pang KP Pang EB Tan YN Chan YH Siow JK Food allergy and allergic rhinitis in 435 asian patients - A descriptive review Med J Malaysia 2017 Aug72(4)215-220

bull Philpott H Nandurkar S Royce SG Thien F Gibson PR Allergy tests do not predict food triggers in adult patients with eosinophilic oesophagitis A comprehensive prospective study using five modalities Aliment Pharmacol Ther 2016 Aug44(3)223-33 doi 101111apt13676

bull Cai C Shen J Zhao D et al Serological Investigation of Food Specific Immunoglobulin G Antibodies in Patients with Inflammatory Bowel Diseases Boone DL ed PLoS ONE 20149(11)e112154 doi101371journalpone0112154

Lectins

bull ldquoBy eliminating dietary elements particularly lectins which adversely influence both enterocyte and lymphocyte structure and function it is proposed that the peripheral antigenic stimulus (both pathogenic and dietary) will be reduced and thereby result in a diminution of disease symptoms in certain patients with RArdquo

Cordain L Toohey L Smith MJ Hickey MS Modulation of immune function by dietary lectins in rheumatoid arthritis British Journal of Nutrition 200083(03)207-217

bull Lectins are proteins found in plants and animals that bind sugars (hemagglutinins)

bull They can bind the glycoproteins on the intestinal lining leading to barrier damage

bull Lectins are found in most foods but are especially high in grains (esp wheat) dairy legumes and nightshade vegetables

bull Most traditional methods cooking these foods such as soaking ferment-ing amp cooking will decrease the lectin content

Nutrient Triage

bull Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage

ndash Zn Mg biotin Vitamin K D A

ndash Lipoic Acid Acetyl carnitine

Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triageProc Natl Acad Sci U S A 2006 Nov 21103(47)17589-94

What to Eat

Fruit and vegetable consumption and mortality from all causes cardiovascular disease and cancer systematic review and dose-response meta-analysis of prospective cohort studies

16 studies - 833234 participants

BMJ 2014 349 g4490

BMJ 2014 349 g4490

Risk of all cause mortality associated with servingsday of fruit and vegetables

Dose-response relation between fruit and vegetable consumption and risk of all cause mortality

BMJ 2014 349 g4490

Myelin

ndash Omega 3 Fatty Acids

ndash Thiamine (B1)

ndash Folate (B9)

ndash Cobolamin (B12)

ndash Minerals

Key Micronutrients

Bourre JM Effects of nutrients (in food) on the structure and function of the nervous

system update on dietary requirements for brain Part 1 micronutrients

Part 2 Macronutriients

J Nutr Health Aging 200610(5)377-85

Bowman Nutrient biomarker patterns cognitive function and MRI measures of

brain aging Neurology 2012 Jan 2478(4)241-9 Bowman

Sulfur Rich Foods

Why Brassica and Allium

bull Improve detoxification

bull Increase glutathione production

bull Increase GABA production

bull Enhance Neuroprotection

bull Improve endothelial function

Brassica and Allium References

1 Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimers Disease Med Cell Longev20152015781938

2 Learning and memory promoting effects of crude garlic extract Indian J Exp Biol2013 Dec51(12)1094-100

3 Enhancement of the neuroprotective activity of Hericiumerinaceus mycelium co-cultivated with Allium sativum extract Arch Physiol Biochem2015 Feb121(1)19-25

Why Emphasize Mushrooms

bull Increase nerve growth factors (NGF)

bull Hericium erinaceus (Yamabushitake or Lionrsquos Mane) stimulate the production of NGF (in vitro)

bull Activate natural killer cells

bull Prime innate and adaptive immunity

bull Mori K Obara Y Hirota M Azumi Y Kinugasa S Inatomi S Nakahata N Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human

astrocytoma cells Biol Pharm Bull 2008 Sep31(9)1727-32

bull Lee DH Kim HW Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway Int J Med Mushrooms 201416(1)1-16

bull Akramiene D Kondrotas A Didziapetriene J Kevelaitis E Effects of beta-glucans on the immune system Medicina (Kaunas)200743(8)597-606

bull Lai PL Naidu MSabaratnam VWong K DaviP Kuppusamy UR Abdullah N Malek SN Neurotrophic properties of the Lions mane medicinal mushroom

Hericium erinaceus (Higher Basidiomycetes) from Malaysia Int J Med Mushrooms201315(6)539-54

bull Phan CW David P Naidu M Wong KH Sabaratnam V Therapeutic potential of culinary-medicinal mushrooms for the management of

neurodegenerative diseases diversity metabolite and mechanism Crit Rev Biotechnol201535(3)355-68

Why Greens

bull Vitamin K1 metabolized to K2-mk7 in gut

bull K2 important in hellip

ndash Myelin production

ndash Calcium influx into bones and teeth

bull Carotenoids magnesium

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 8: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

copyright 2010 Terry Wahls all rights reserved

2007

Institute For Functional Medicine

11

copyright 2010 Terry Wahls all rights reserved

2008

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

The Swank Diet

bull N=144 followed 50 years

bull lt 15 grams saturated fat vs gt 20 grams

bull Greatest benefit earlier in the disease course

bull More likely to remain ambulatory

Review of MS patient survival on a Swank low saturated fat dietNutrition 2003 Feb19(2)161-2 ReviewEffect of low saturated fat diet in early and late cases of multiple sclerosisLancet 1990 Jul 7336(8706)37-9Multiple sclerosis twenty years on low fat dietArch Neurol 1970 Nov23(5)460-74

Low-fat plant-based diet in multiple sclerosis A randomized controlled trial

bull This was a randomized-controlled assessor-blinded one-year long study

bull N=61

bull No change in EDSS MRI

bull Trend towards reduced FSS (fatigue)

Low-fat plant-based diet in multiple sclerosis A randomized controlled trial Mult Scler Relat Disord 2016 Sep980-90

Mediterranean diet adherence and risk of multiple sclerosis ndash Case control study

bull N=70 RRMS 140 controls Interviews re diet

bull Reduced risk of MS

ndash Fruits (OR=028 95 CI 012-063 p-value 0002)

ndash Vegetables (OR=023 95 CI 010-053 p-value 0001)

Mediterranean diet adherence and risk of multiple sclerosis a case-control study Asia Pac J Clin Nutr 201625(2)377-84

Mediterranean Diet bull High olive oil

bull High vegetable polyphenol

bull Whole grains

bull Low red meat

Potential for diet to prevent and remediate cognitive deficits in neurological disordersNutr Rev 2018 Mar 176(3)204-217The Role of Diet in Multiple Sclerosis Mechanistic Connections and Current EvidenceCurr Nutr Rep 2018 Aug 16Anti-inflammatory Activity of Extra Virgin Olive Oil Polyphenols Which Role in the Prevention and Treatment of Immune-Mediated Inflammatory DiseasesEndocr Metab Immune Disord Drug Targets 201818(1)36-50

bull The following slides represent the rationale for the dietary intervention we are studying in the Dietary Approaches to Treating MS Related Fatigue

bull This protocol is not validated nor does it currently meet the current evidence based guideline criteria as set forth by the American Academy of Neurology or the Academy of Nutrition and Dietetics

Dairy amp MSCasein Gluten amp Schizophrenia

bull Liquid cow milk (not cheese) and MS prevalence was highly correlated (rho = 0836) across 27 countries and 29 populations

bull IgG to Casein and gluten were significantly uarrin recent onset and non-recent onset schizophrenia compared to controls (ple000001-0004)

1 Correlation between milk and dairy product consumption and multiple sclerosis prevalence a worldwide

study Neuroepidemiology 199211(4-6)304-12

2 Severance EG Alaedini A Yang S Halling M Gressitt KL Stallings CR Origoni AE Vaughan C

Khushalani S Leweke FM Dickerson FB Yolken RH Gastrointestinal inflammation and associated

immune activation in schizophrenia Schizophr Res2012 Jun138(1)48-53

Gluten and Casein and Opioids

bull Gluten can be degraded into several morphine-like substances named gluten exorphins

bull Milk proteins are particularly strong allergens and are additional source of bioactive peptides including β-casomorphin-7 and exerts its influence on nervous digestive and immune functions via the opioid receptor

1 The opioid effects of gluten exorphins asymptomatic celiac disease J Health PopulNutr 2015 Nov 243324

2 Opioid receptor ligands derived from food proteins Curr Pharm Des 20039(16)1331-44

3 β-casomorphin-7 alters μ-opioid receptor and dipeptidyl peptidase IV genes expression in children with atopic dermatitis Peptides 2014 Dec62144-9

Nutrition in Parkinsons Disease

Seidl SE Santiago JA Bilyk H Potashkin JA The emerging role of nutrition in Parkinsons disease Front Aging Neurosci 2014 Mar 7636 doi 103389fnagi201400036 eCollection 2014

Gluten sensitivity is an abnormal immune response to gluten in genetically susceptible individuals and may manifest solely with neurological dysfunction 90 of gluten sensitive individuals have no GI symptoms

Lancet Neurol 2010 Mar9(3)318-30 Hadjivassiliou M

Figure 2 MRI in four patients with gluten encephalopathy The extent and variability of white matter abnormalities caused by gluten sensitivity can be seen in these four patients (AndashD) A and C show diffuse white matter changes whereas B and D show more f

Marios Hadjivassiliou David S Sanders Richard A Gruumlnewald Nicola Woodroofe Sabrina Boscolo Daniel Aeschl

Gluten sensitivity from gut to brain

The Lancet Neurology Volume 9 Issue 3 2010 318 - 330

httpdxdoiorg101016S1474-4422(09)70290-X

MS and Gluten References 1 Gluten antibodies in patients with multiple sclerosis Hum Nutr Appl

Nutr 1984 Apr38(2)142-32 Multiple sclerosis and gluten sensitivity Clin Neurol Neurosurg 2007

Oct109(8)651-33 Prevalence of celiac disease in multiple sclerosis BMC Neurol 2011 Mar

711314 Celiac disease with neurologic manifestations in children Rev Med Chir

Soc Med Nat Iasi 2013 Jan-Mar117(1)88-945 Celiac disease with cerebral and peripheral nerve involvement

mimicking multiple sclerosis J Med Life 2014 Sep 157(3)440-4 Epub2014 Sep 25

6 A case of multiple sclerosis and celiac disease Case Rep NeurolMed 20132013576921

7 Gluten-related disorders gluten ataxia Dig Dis 201533(2)264-88 Transglutaminase-6 is an autoantigen in progressive multiple sclerosis and

is upregulated in reactive astrocytes Mult Scler 2016 Dec 11352458516684022

9 The progression of coeliac disease its neurological and psychiatric implications Nutr Res Rev 2017 Jun30(1)25-35

Risks of Eggs

bull Prosndash Grass fed - DHA choline biotin lutein Vitamins A D K2 and

B3 B6 B9 B12

bull Cons ndash Eggs are most common food allergen in IBD gt70ndash 60 allergy patients have IgG Ab to eggsndash 13 seasonal allergies have IgG Ab to eggs ndash Wheat milk eggs are common food triggers to Eosinophilic

Esophagitis

References next slide

References Risks of Eggs bull Wang G Ren J Li G et al The utility of food antigen test in the diagnosis of Crohnrsquos disease

and remission maintenance after exclusive enteral nutrition Clin Res Hepatol Gastroenterol 201842(2)145-152 doi101016jclinre201709002

bull Shakoor Z AlFaifi A AlAmro B AlTawil LN AlOhaly RY Prevalence of IgG-mediated food intolerance among patients with allergic symptoms Ann Saudi Med 2016 Nov-Dec36(6)386-390

bull Dhanapala P De Silva C Doran T Suphioglu C Cracking the egg An insight into egg hypersensitivity Mol Immunol 2015 Aug66(2)375-83 doi 101016jmolimm201504016

bull Pang KA Pang KP Pang EB Tan YN Chan YH Siow JK Food allergy and allergic rhinitis in 435 asian patients - A descriptive review Med J Malaysia 2017 Aug72(4)215-220

bull Philpott H Nandurkar S Royce SG Thien F Gibson PR Allergy tests do not predict food triggers in adult patients with eosinophilic oesophagitis A comprehensive prospective study using five modalities Aliment Pharmacol Ther 2016 Aug44(3)223-33 doi 101111apt13676

bull Cai C Shen J Zhao D et al Serological Investigation of Food Specific Immunoglobulin G Antibodies in Patients with Inflammatory Bowel Diseases Boone DL ed PLoS ONE 20149(11)e112154 doi101371journalpone0112154

Lectins

bull ldquoBy eliminating dietary elements particularly lectins which adversely influence both enterocyte and lymphocyte structure and function it is proposed that the peripheral antigenic stimulus (both pathogenic and dietary) will be reduced and thereby result in a diminution of disease symptoms in certain patients with RArdquo

Cordain L Toohey L Smith MJ Hickey MS Modulation of immune function by dietary lectins in rheumatoid arthritis British Journal of Nutrition 200083(03)207-217

bull Lectins are proteins found in plants and animals that bind sugars (hemagglutinins)

bull They can bind the glycoproteins on the intestinal lining leading to barrier damage

bull Lectins are found in most foods but are especially high in grains (esp wheat) dairy legumes and nightshade vegetables

bull Most traditional methods cooking these foods such as soaking ferment-ing amp cooking will decrease the lectin content

Nutrient Triage

bull Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage

ndash Zn Mg biotin Vitamin K D A

ndash Lipoic Acid Acetyl carnitine

Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triageProc Natl Acad Sci U S A 2006 Nov 21103(47)17589-94

What to Eat

Fruit and vegetable consumption and mortality from all causes cardiovascular disease and cancer systematic review and dose-response meta-analysis of prospective cohort studies

16 studies - 833234 participants

BMJ 2014 349 g4490

BMJ 2014 349 g4490

Risk of all cause mortality associated with servingsday of fruit and vegetables

Dose-response relation between fruit and vegetable consumption and risk of all cause mortality

BMJ 2014 349 g4490

Myelin

ndash Omega 3 Fatty Acids

ndash Thiamine (B1)

ndash Folate (B9)

ndash Cobolamin (B12)

ndash Minerals

Key Micronutrients

Bourre JM Effects of nutrients (in food) on the structure and function of the nervous

system update on dietary requirements for brain Part 1 micronutrients

Part 2 Macronutriients

J Nutr Health Aging 200610(5)377-85

Bowman Nutrient biomarker patterns cognitive function and MRI measures of

brain aging Neurology 2012 Jan 2478(4)241-9 Bowman

Sulfur Rich Foods

Why Brassica and Allium

bull Improve detoxification

bull Increase glutathione production

bull Increase GABA production

bull Enhance Neuroprotection

bull Improve endothelial function

Brassica and Allium References

1 Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimers Disease Med Cell Longev20152015781938

2 Learning and memory promoting effects of crude garlic extract Indian J Exp Biol2013 Dec51(12)1094-100

3 Enhancement of the neuroprotective activity of Hericiumerinaceus mycelium co-cultivated with Allium sativum extract Arch Physiol Biochem2015 Feb121(1)19-25

Why Emphasize Mushrooms

bull Increase nerve growth factors (NGF)

bull Hericium erinaceus (Yamabushitake or Lionrsquos Mane) stimulate the production of NGF (in vitro)

bull Activate natural killer cells

bull Prime innate and adaptive immunity

bull Mori K Obara Y Hirota M Azumi Y Kinugasa S Inatomi S Nakahata N Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human

astrocytoma cells Biol Pharm Bull 2008 Sep31(9)1727-32

bull Lee DH Kim HW Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway Int J Med Mushrooms 201416(1)1-16

bull Akramiene D Kondrotas A Didziapetriene J Kevelaitis E Effects of beta-glucans on the immune system Medicina (Kaunas)200743(8)597-606

bull Lai PL Naidu MSabaratnam VWong K DaviP Kuppusamy UR Abdullah N Malek SN Neurotrophic properties of the Lions mane medicinal mushroom

Hericium erinaceus (Higher Basidiomycetes) from Malaysia Int J Med Mushrooms201315(6)539-54

bull Phan CW David P Naidu M Wong KH Sabaratnam V Therapeutic potential of culinary-medicinal mushrooms for the management of

neurodegenerative diseases diversity metabolite and mechanism Crit Rev Biotechnol201535(3)355-68

Why Greens

bull Vitamin K1 metabolized to K2-mk7 in gut

bull K2 important in hellip

ndash Myelin production

ndash Calcium influx into bones and teeth

bull Carotenoids magnesium

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 9: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

Institute For Functional Medicine

11

copyright 2010 Terry Wahls all rights reserved

2008

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

The Swank Diet

bull N=144 followed 50 years

bull lt 15 grams saturated fat vs gt 20 grams

bull Greatest benefit earlier in the disease course

bull More likely to remain ambulatory

Review of MS patient survival on a Swank low saturated fat dietNutrition 2003 Feb19(2)161-2 ReviewEffect of low saturated fat diet in early and late cases of multiple sclerosisLancet 1990 Jul 7336(8706)37-9Multiple sclerosis twenty years on low fat dietArch Neurol 1970 Nov23(5)460-74

Low-fat plant-based diet in multiple sclerosis A randomized controlled trial

bull This was a randomized-controlled assessor-blinded one-year long study

bull N=61

bull No change in EDSS MRI

bull Trend towards reduced FSS (fatigue)

Low-fat plant-based diet in multiple sclerosis A randomized controlled trial Mult Scler Relat Disord 2016 Sep980-90

Mediterranean diet adherence and risk of multiple sclerosis ndash Case control study

bull N=70 RRMS 140 controls Interviews re diet

bull Reduced risk of MS

ndash Fruits (OR=028 95 CI 012-063 p-value 0002)

ndash Vegetables (OR=023 95 CI 010-053 p-value 0001)

Mediterranean diet adherence and risk of multiple sclerosis a case-control study Asia Pac J Clin Nutr 201625(2)377-84

Mediterranean Diet bull High olive oil

bull High vegetable polyphenol

bull Whole grains

bull Low red meat

Potential for diet to prevent and remediate cognitive deficits in neurological disordersNutr Rev 2018 Mar 176(3)204-217The Role of Diet in Multiple Sclerosis Mechanistic Connections and Current EvidenceCurr Nutr Rep 2018 Aug 16Anti-inflammatory Activity of Extra Virgin Olive Oil Polyphenols Which Role in the Prevention and Treatment of Immune-Mediated Inflammatory DiseasesEndocr Metab Immune Disord Drug Targets 201818(1)36-50

bull The following slides represent the rationale for the dietary intervention we are studying in the Dietary Approaches to Treating MS Related Fatigue

bull This protocol is not validated nor does it currently meet the current evidence based guideline criteria as set forth by the American Academy of Neurology or the Academy of Nutrition and Dietetics

Dairy amp MSCasein Gluten amp Schizophrenia

bull Liquid cow milk (not cheese) and MS prevalence was highly correlated (rho = 0836) across 27 countries and 29 populations

bull IgG to Casein and gluten were significantly uarrin recent onset and non-recent onset schizophrenia compared to controls (ple000001-0004)

1 Correlation between milk and dairy product consumption and multiple sclerosis prevalence a worldwide

study Neuroepidemiology 199211(4-6)304-12

2 Severance EG Alaedini A Yang S Halling M Gressitt KL Stallings CR Origoni AE Vaughan C

Khushalani S Leweke FM Dickerson FB Yolken RH Gastrointestinal inflammation and associated

immune activation in schizophrenia Schizophr Res2012 Jun138(1)48-53

Gluten and Casein and Opioids

bull Gluten can be degraded into several morphine-like substances named gluten exorphins

bull Milk proteins are particularly strong allergens and are additional source of bioactive peptides including β-casomorphin-7 and exerts its influence on nervous digestive and immune functions via the opioid receptor

1 The opioid effects of gluten exorphins asymptomatic celiac disease J Health PopulNutr 2015 Nov 243324

2 Opioid receptor ligands derived from food proteins Curr Pharm Des 20039(16)1331-44

3 β-casomorphin-7 alters μ-opioid receptor and dipeptidyl peptidase IV genes expression in children with atopic dermatitis Peptides 2014 Dec62144-9

Nutrition in Parkinsons Disease

Seidl SE Santiago JA Bilyk H Potashkin JA The emerging role of nutrition in Parkinsons disease Front Aging Neurosci 2014 Mar 7636 doi 103389fnagi201400036 eCollection 2014

Gluten sensitivity is an abnormal immune response to gluten in genetically susceptible individuals and may manifest solely with neurological dysfunction 90 of gluten sensitive individuals have no GI symptoms

Lancet Neurol 2010 Mar9(3)318-30 Hadjivassiliou M

Figure 2 MRI in four patients with gluten encephalopathy The extent and variability of white matter abnormalities caused by gluten sensitivity can be seen in these four patients (AndashD) A and C show diffuse white matter changes whereas B and D show more f

Marios Hadjivassiliou David S Sanders Richard A Gruumlnewald Nicola Woodroofe Sabrina Boscolo Daniel Aeschl

Gluten sensitivity from gut to brain

The Lancet Neurology Volume 9 Issue 3 2010 318 - 330

httpdxdoiorg101016S1474-4422(09)70290-X

MS and Gluten References 1 Gluten antibodies in patients with multiple sclerosis Hum Nutr Appl

Nutr 1984 Apr38(2)142-32 Multiple sclerosis and gluten sensitivity Clin Neurol Neurosurg 2007

Oct109(8)651-33 Prevalence of celiac disease in multiple sclerosis BMC Neurol 2011 Mar

711314 Celiac disease with neurologic manifestations in children Rev Med Chir

Soc Med Nat Iasi 2013 Jan-Mar117(1)88-945 Celiac disease with cerebral and peripheral nerve involvement

mimicking multiple sclerosis J Med Life 2014 Sep 157(3)440-4 Epub2014 Sep 25

6 A case of multiple sclerosis and celiac disease Case Rep NeurolMed 20132013576921

7 Gluten-related disorders gluten ataxia Dig Dis 201533(2)264-88 Transglutaminase-6 is an autoantigen in progressive multiple sclerosis and

is upregulated in reactive astrocytes Mult Scler 2016 Dec 11352458516684022

9 The progression of coeliac disease its neurological and psychiatric implications Nutr Res Rev 2017 Jun30(1)25-35

Risks of Eggs

bull Prosndash Grass fed - DHA choline biotin lutein Vitamins A D K2 and

B3 B6 B9 B12

bull Cons ndash Eggs are most common food allergen in IBD gt70ndash 60 allergy patients have IgG Ab to eggsndash 13 seasonal allergies have IgG Ab to eggs ndash Wheat milk eggs are common food triggers to Eosinophilic

Esophagitis

References next slide

References Risks of Eggs bull Wang G Ren J Li G et al The utility of food antigen test in the diagnosis of Crohnrsquos disease

and remission maintenance after exclusive enteral nutrition Clin Res Hepatol Gastroenterol 201842(2)145-152 doi101016jclinre201709002

bull Shakoor Z AlFaifi A AlAmro B AlTawil LN AlOhaly RY Prevalence of IgG-mediated food intolerance among patients with allergic symptoms Ann Saudi Med 2016 Nov-Dec36(6)386-390

bull Dhanapala P De Silva C Doran T Suphioglu C Cracking the egg An insight into egg hypersensitivity Mol Immunol 2015 Aug66(2)375-83 doi 101016jmolimm201504016

bull Pang KA Pang KP Pang EB Tan YN Chan YH Siow JK Food allergy and allergic rhinitis in 435 asian patients - A descriptive review Med J Malaysia 2017 Aug72(4)215-220

bull Philpott H Nandurkar S Royce SG Thien F Gibson PR Allergy tests do not predict food triggers in adult patients with eosinophilic oesophagitis A comprehensive prospective study using five modalities Aliment Pharmacol Ther 2016 Aug44(3)223-33 doi 101111apt13676

bull Cai C Shen J Zhao D et al Serological Investigation of Food Specific Immunoglobulin G Antibodies in Patients with Inflammatory Bowel Diseases Boone DL ed PLoS ONE 20149(11)e112154 doi101371journalpone0112154

Lectins

bull ldquoBy eliminating dietary elements particularly lectins which adversely influence both enterocyte and lymphocyte structure and function it is proposed that the peripheral antigenic stimulus (both pathogenic and dietary) will be reduced and thereby result in a diminution of disease symptoms in certain patients with RArdquo

Cordain L Toohey L Smith MJ Hickey MS Modulation of immune function by dietary lectins in rheumatoid arthritis British Journal of Nutrition 200083(03)207-217

bull Lectins are proteins found in plants and animals that bind sugars (hemagglutinins)

bull They can bind the glycoproteins on the intestinal lining leading to barrier damage

bull Lectins are found in most foods but are especially high in grains (esp wheat) dairy legumes and nightshade vegetables

bull Most traditional methods cooking these foods such as soaking ferment-ing amp cooking will decrease the lectin content

Nutrient Triage

bull Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage

ndash Zn Mg biotin Vitamin K D A

ndash Lipoic Acid Acetyl carnitine

Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triageProc Natl Acad Sci U S A 2006 Nov 21103(47)17589-94

What to Eat

Fruit and vegetable consumption and mortality from all causes cardiovascular disease and cancer systematic review and dose-response meta-analysis of prospective cohort studies

16 studies - 833234 participants

BMJ 2014 349 g4490

BMJ 2014 349 g4490

Risk of all cause mortality associated with servingsday of fruit and vegetables

Dose-response relation between fruit and vegetable consumption and risk of all cause mortality

BMJ 2014 349 g4490

Myelin

ndash Omega 3 Fatty Acids

ndash Thiamine (B1)

ndash Folate (B9)

ndash Cobolamin (B12)

ndash Minerals

Key Micronutrients

Bourre JM Effects of nutrients (in food) on the structure and function of the nervous

system update on dietary requirements for brain Part 1 micronutrients

Part 2 Macronutriients

J Nutr Health Aging 200610(5)377-85

Bowman Nutrient biomarker patterns cognitive function and MRI measures of

brain aging Neurology 2012 Jan 2478(4)241-9 Bowman

Sulfur Rich Foods

Why Brassica and Allium

bull Improve detoxification

bull Increase glutathione production

bull Increase GABA production

bull Enhance Neuroprotection

bull Improve endothelial function

Brassica and Allium References

1 Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimers Disease Med Cell Longev20152015781938

2 Learning and memory promoting effects of crude garlic extract Indian J Exp Biol2013 Dec51(12)1094-100

3 Enhancement of the neuroprotective activity of Hericiumerinaceus mycelium co-cultivated with Allium sativum extract Arch Physiol Biochem2015 Feb121(1)19-25

Why Emphasize Mushrooms

bull Increase nerve growth factors (NGF)

bull Hericium erinaceus (Yamabushitake or Lionrsquos Mane) stimulate the production of NGF (in vitro)

bull Activate natural killer cells

bull Prime innate and adaptive immunity

bull Mori K Obara Y Hirota M Azumi Y Kinugasa S Inatomi S Nakahata N Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human

astrocytoma cells Biol Pharm Bull 2008 Sep31(9)1727-32

bull Lee DH Kim HW Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway Int J Med Mushrooms 201416(1)1-16

bull Akramiene D Kondrotas A Didziapetriene J Kevelaitis E Effects of beta-glucans on the immune system Medicina (Kaunas)200743(8)597-606

bull Lai PL Naidu MSabaratnam VWong K DaviP Kuppusamy UR Abdullah N Malek SN Neurotrophic properties of the Lions mane medicinal mushroom

Hericium erinaceus (Higher Basidiomycetes) from Malaysia Int J Med Mushrooms201315(6)539-54

bull Phan CW David P Naidu M Wong KH Sabaratnam V Therapeutic potential of culinary-medicinal mushrooms for the management of

neurodegenerative diseases diversity metabolite and mechanism Crit Rev Biotechnol201535(3)355-68

Why Greens

bull Vitamin K1 metabolized to K2-mk7 in gut

bull K2 important in hellip

ndash Myelin production

ndash Calcium influx into bones and teeth

bull Carotenoids magnesium

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 10: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

11

copyright 2010 Terry Wahls all rights reserved

2008

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

The Swank Diet

bull N=144 followed 50 years

bull lt 15 grams saturated fat vs gt 20 grams

bull Greatest benefit earlier in the disease course

bull More likely to remain ambulatory

Review of MS patient survival on a Swank low saturated fat dietNutrition 2003 Feb19(2)161-2 ReviewEffect of low saturated fat diet in early and late cases of multiple sclerosisLancet 1990 Jul 7336(8706)37-9Multiple sclerosis twenty years on low fat dietArch Neurol 1970 Nov23(5)460-74

Low-fat plant-based diet in multiple sclerosis A randomized controlled trial

bull This was a randomized-controlled assessor-blinded one-year long study

bull N=61

bull No change in EDSS MRI

bull Trend towards reduced FSS (fatigue)

Low-fat plant-based diet in multiple sclerosis A randomized controlled trial Mult Scler Relat Disord 2016 Sep980-90

Mediterranean diet adherence and risk of multiple sclerosis ndash Case control study

bull N=70 RRMS 140 controls Interviews re diet

bull Reduced risk of MS

ndash Fruits (OR=028 95 CI 012-063 p-value 0002)

ndash Vegetables (OR=023 95 CI 010-053 p-value 0001)

Mediterranean diet adherence and risk of multiple sclerosis a case-control study Asia Pac J Clin Nutr 201625(2)377-84

Mediterranean Diet bull High olive oil

bull High vegetable polyphenol

bull Whole grains

bull Low red meat

Potential for diet to prevent and remediate cognitive deficits in neurological disordersNutr Rev 2018 Mar 176(3)204-217The Role of Diet in Multiple Sclerosis Mechanistic Connections and Current EvidenceCurr Nutr Rep 2018 Aug 16Anti-inflammatory Activity of Extra Virgin Olive Oil Polyphenols Which Role in the Prevention and Treatment of Immune-Mediated Inflammatory DiseasesEndocr Metab Immune Disord Drug Targets 201818(1)36-50

bull The following slides represent the rationale for the dietary intervention we are studying in the Dietary Approaches to Treating MS Related Fatigue

bull This protocol is not validated nor does it currently meet the current evidence based guideline criteria as set forth by the American Academy of Neurology or the Academy of Nutrition and Dietetics

Dairy amp MSCasein Gluten amp Schizophrenia

bull Liquid cow milk (not cheese) and MS prevalence was highly correlated (rho = 0836) across 27 countries and 29 populations

bull IgG to Casein and gluten were significantly uarrin recent onset and non-recent onset schizophrenia compared to controls (ple000001-0004)

1 Correlation between milk and dairy product consumption and multiple sclerosis prevalence a worldwide

study Neuroepidemiology 199211(4-6)304-12

2 Severance EG Alaedini A Yang S Halling M Gressitt KL Stallings CR Origoni AE Vaughan C

Khushalani S Leweke FM Dickerson FB Yolken RH Gastrointestinal inflammation and associated

immune activation in schizophrenia Schizophr Res2012 Jun138(1)48-53

Gluten and Casein and Opioids

bull Gluten can be degraded into several morphine-like substances named gluten exorphins

bull Milk proteins are particularly strong allergens and are additional source of bioactive peptides including β-casomorphin-7 and exerts its influence on nervous digestive and immune functions via the opioid receptor

1 The opioid effects of gluten exorphins asymptomatic celiac disease J Health PopulNutr 2015 Nov 243324

2 Opioid receptor ligands derived from food proteins Curr Pharm Des 20039(16)1331-44

3 β-casomorphin-7 alters μ-opioid receptor and dipeptidyl peptidase IV genes expression in children with atopic dermatitis Peptides 2014 Dec62144-9

Nutrition in Parkinsons Disease

Seidl SE Santiago JA Bilyk H Potashkin JA The emerging role of nutrition in Parkinsons disease Front Aging Neurosci 2014 Mar 7636 doi 103389fnagi201400036 eCollection 2014

Gluten sensitivity is an abnormal immune response to gluten in genetically susceptible individuals and may manifest solely with neurological dysfunction 90 of gluten sensitive individuals have no GI symptoms

Lancet Neurol 2010 Mar9(3)318-30 Hadjivassiliou M

Figure 2 MRI in four patients with gluten encephalopathy The extent and variability of white matter abnormalities caused by gluten sensitivity can be seen in these four patients (AndashD) A and C show diffuse white matter changes whereas B and D show more f

Marios Hadjivassiliou David S Sanders Richard A Gruumlnewald Nicola Woodroofe Sabrina Boscolo Daniel Aeschl

Gluten sensitivity from gut to brain

The Lancet Neurology Volume 9 Issue 3 2010 318 - 330

httpdxdoiorg101016S1474-4422(09)70290-X

MS and Gluten References 1 Gluten antibodies in patients with multiple sclerosis Hum Nutr Appl

Nutr 1984 Apr38(2)142-32 Multiple sclerosis and gluten sensitivity Clin Neurol Neurosurg 2007

Oct109(8)651-33 Prevalence of celiac disease in multiple sclerosis BMC Neurol 2011 Mar

711314 Celiac disease with neurologic manifestations in children Rev Med Chir

Soc Med Nat Iasi 2013 Jan-Mar117(1)88-945 Celiac disease with cerebral and peripheral nerve involvement

mimicking multiple sclerosis J Med Life 2014 Sep 157(3)440-4 Epub2014 Sep 25

6 A case of multiple sclerosis and celiac disease Case Rep NeurolMed 20132013576921

7 Gluten-related disorders gluten ataxia Dig Dis 201533(2)264-88 Transglutaminase-6 is an autoantigen in progressive multiple sclerosis and

is upregulated in reactive astrocytes Mult Scler 2016 Dec 11352458516684022

9 The progression of coeliac disease its neurological and psychiatric implications Nutr Res Rev 2017 Jun30(1)25-35

Risks of Eggs

bull Prosndash Grass fed - DHA choline biotin lutein Vitamins A D K2 and

B3 B6 B9 B12

bull Cons ndash Eggs are most common food allergen in IBD gt70ndash 60 allergy patients have IgG Ab to eggsndash 13 seasonal allergies have IgG Ab to eggs ndash Wheat milk eggs are common food triggers to Eosinophilic

Esophagitis

References next slide

References Risks of Eggs bull Wang G Ren J Li G et al The utility of food antigen test in the diagnosis of Crohnrsquos disease

and remission maintenance after exclusive enteral nutrition Clin Res Hepatol Gastroenterol 201842(2)145-152 doi101016jclinre201709002

bull Shakoor Z AlFaifi A AlAmro B AlTawil LN AlOhaly RY Prevalence of IgG-mediated food intolerance among patients with allergic symptoms Ann Saudi Med 2016 Nov-Dec36(6)386-390

bull Dhanapala P De Silva C Doran T Suphioglu C Cracking the egg An insight into egg hypersensitivity Mol Immunol 2015 Aug66(2)375-83 doi 101016jmolimm201504016

bull Pang KA Pang KP Pang EB Tan YN Chan YH Siow JK Food allergy and allergic rhinitis in 435 asian patients - A descriptive review Med J Malaysia 2017 Aug72(4)215-220

bull Philpott H Nandurkar S Royce SG Thien F Gibson PR Allergy tests do not predict food triggers in adult patients with eosinophilic oesophagitis A comprehensive prospective study using five modalities Aliment Pharmacol Ther 2016 Aug44(3)223-33 doi 101111apt13676

bull Cai C Shen J Zhao D et al Serological Investigation of Food Specific Immunoglobulin G Antibodies in Patients with Inflammatory Bowel Diseases Boone DL ed PLoS ONE 20149(11)e112154 doi101371journalpone0112154

Lectins

bull ldquoBy eliminating dietary elements particularly lectins which adversely influence both enterocyte and lymphocyte structure and function it is proposed that the peripheral antigenic stimulus (both pathogenic and dietary) will be reduced and thereby result in a diminution of disease symptoms in certain patients with RArdquo

Cordain L Toohey L Smith MJ Hickey MS Modulation of immune function by dietary lectins in rheumatoid arthritis British Journal of Nutrition 200083(03)207-217

bull Lectins are proteins found in plants and animals that bind sugars (hemagglutinins)

bull They can bind the glycoproteins on the intestinal lining leading to barrier damage

bull Lectins are found in most foods but are especially high in grains (esp wheat) dairy legumes and nightshade vegetables

bull Most traditional methods cooking these foods such as soaking ferment-ing amp cooking will decrease the lectin content

Nutrient Triage

bull Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage

ndash Zn Mg biotin Vitamin K D A

ndash Lipoic Acid Acetyl carnitine

Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triageProc Natl Acad Sci U S A 2006 Nov 21103(47)17589-94

What to Eat

Fruit and vegetable consumption and mortality from all causes cardiovascular disease and cancer systematic review and dose-response meta-analysis of prospective cohort studies

16 studies - 833234 participants

BMJ 2014 349 g4490

BMJ 2014 349 g4490

Risk of all cause mortality associated with servingsday of fruit and vegetables

Dose-response relation between fruit and vegetable consumption and risk of all cause mortality

BMJ 2014 349 g4490

Myelin

ndash Omega 3 Fatty Acids

ndash Thiamine (B1)

ndash Folate (B9)

ndash Cobolamin (B12)

ndash Minerals

Key Micronutrients

Bourre JM Effects of nutrients (in food) on the structure and function of the nervous

system update on dietary requirements for brain Part 1 micronutrients

Part 2 Macronutriients

J Nutr Health Aging 200610(5)377-85

Bowman Nutrient biomarker patterns cognitive function and MRI measures of

brain aging Neurology 2012 Jan 2478(4)241-9 Bowman

Sulfur Rich Foods

Why Brassica and Allium

bull Improve detoxification

bull Increase glutathione production

bull Increase GABA production

bull Enhance Neuroprotection

bull Improve endothelial function

Brassica and Allium References

1 Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimers Disease Med Cell Longev20152015781938

2 Learning and memory promoting effects of crude garlic extract Indian J Exp Biol2013 Dec51(12)1094-100

3 Enhancement of the neuroprotective activity of Hericiumerinaceus mycelium co-cultivated with Allium sativum extract Arch Physiol Biochem2015 Feb121(1)19-25

Why Emphasize Mushrooms

bull Increase nerve growth factors (NGF)

bull Hericium erinaceus (Yamabushitake or Lionrsquos Mane) stimulate the production of NGF (in vitro)

bull Activate natural killer cells

bull Prime innate and adaptive immunity

bull Mori K Obara Y Hirota M Azumi Y Kinugasa S Inatomi S Nakahata N Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human

astrocytoma cells Biol Pharm Bull 2008 Sep31(9)1727-32

bull Lee DH Kim HW Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway Int J Med Mushrooms 201416(1)1-16

bull Akramiene D Kondrotas A Didziapetriene J Kevelaitis E Effects of beta-glucans on the immune system Medicina (Kaunas)200743(8)597-606

bull Lai PL Naidu MSabaratnam VWong K DaviP Kuppusamy UR Abdullah N Malek SN Neurotrophic properties of the Lions mane medicinal mushroom

Hericium erinaceus (Higher Basidiomycetes) from Malaysia Int J Med Mushrooms201315(6)539-54

bull Phan CW David P Naidu M Wong KH Sabaratnam V Therapeutic potential of culinary-medicinal mushrooms for the management of

neurodegenerative diseases diversity metabolite and mechanism Crit Rev Biotechnol201535(3)355-68

Why Greens

bull Vitamin K1 metabolized to K2-mk7 in gut

bull K2 important in hellip

ndash Myelin production

ndash Calcium influx into bones and teeth

bull Carotenoids magnesium

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 11: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

copyright 2010 Terry Wahls all rights reserved

2008

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

The Swank Diet

bull N=144 followed 50 years

bull lt 15 grams saturated fat vs gt 20 grams

bull Greatest benefit earlier in the disease course

bull More likely to remain ambulatory

Review of MS patient survival on a Swank low saturated fat dietNutrition 2003 Feb19(2)161-2 ReviewEffect of low saturated fat diet in early and late cases of multiple sclerosisLancet 1990 Jul 7336(8706)37-9Multiple sclerosis twenty years on low fat dietArch Neurol 1970 Nov23(5)460-74

Low-fat plant-based diet in multiple sclerosis A randomized controlled trial

bull This was a randomized-controlled assessor-blinded one-year long study

bull N=61

bull No change in EDSS MRI

bull Trend towards reduced FSS (fatigue)

Low-fat plant-based diet in multiple sclerosis A randomized controlled trial Mult Scler Relat Disord 2016 Sep980-90

Mediterranean diet adherence and risk of multiple sclerosis ndash Case control study

bull N=70 RRMS 140 controls Interviews re diet

bull Reduced risk of MS

ndash Fruits (OR=028 95 CI 012-063 p-value 0002)

ndash Vegetables (OR=023 95 CI 010-053 p-value 0001)

Mediterranean diet adherence and risk of multiple sclerosis a case-control study Asia Pac J Clin Nutr 201625(2)377-84

Mediterranean Diet bull High olive oil

bull High vegetable polyphenol

bull Whole grains

bull Low red meat

Potential for diet to prevent and remediate cognitive deficits in neurological disordersNutr Rev 2018 Mar 176(3)204-217The Role of Diet in Multiple Sclerosis Mechanistic Connections and Current EvidenceCurr Nutr Rep 2018 Aug 16Anti-inflammatory Activity of Extra Virgin Olive Oil Polyphenols Which Role in the Prevention and Treatment of Immune-Mediated Inflammatory DiseasesEndocr Metab Immune Disord Drug Targets 201818(1)36-50

bull The following slides represent the rationale for the dietary intervention we are studying in the Dietary Approaches to Treating MS Related Fatigue

bull This protocol is not validated nor does it currently meet the current evidence based guideline criteria as set forth by the American Academy of Neurology or the Academy of Nutrition and Dietetics

Dairy amp MSCasein Gluten amp Schizophrenia

bull Liquid cow milk (not cheese) and MS prevalence was highly correlated (rho = 0836) across 27 countries and 29 populations

bull IgG to Casein and gluten were significantly uarrin recent onset and non-recent onset schizophrenia compared to controls (ple000001-0004)

1 Correlation between milk and dairy product consumption and multiple sclerosis prevalence a worldwide

study Neuroepidemiology 199211(4-6)304-12

2 Severance EG Alaedini A Yang S Halling M Gressitt KL Stallings CR Origoni AE Vaughan C

Khushalani S Leweke FM Dickerson FB Yolken RH Gastrointestinal inflammation and associated

immune activation in schizophrenia Schizophr Res2012 Jun138(1)48-53

Gluten and Casein and Opioids

bull Gluten can be degraded into several morphine-like substances named gluten exorphins

bull Milk proteins are particularly strong allergens and are additional source of bioactive peptides including β-casomorphin-7 and exerts its influence on nervous digestive and immune functions via the opioid receptor

1 The opioid effects of gluten exorphins asymptomatic celiac disease J Health PopulNutr 2015 Nov 243324

2 Opioid receptor ligands derived from food proteins Curr Pharm Des 20039(16)1331-44

3 β-casomorphin-7 alters μ-opioid receptor and dipeptidyl peptidase IV genes expression in children with atopic dermatitis Peptides 2014 Dec62144-9

Nutrition in Parkinsons Disease

Seidl SE Santiago JA Bilyk H Potashkin JA The emerging role of nutrition in Parkinsons disease Front Aging Neurosci 2014 Mar 7636 doi 103389fnagi201400036 eCollection 2014

Gluten sensitivity is an abnormal immune response to gluten in genetically susceptible individuals and may manifest solely with neurological dysfunction 90 of gluten sensitive individuals have no GI symptoms

Lancet Neurol 2010 Mar9(3)318-30 Hadjivassiliou M

Figure 2 MRI in four patients with gluten encephalopathy The extent and variability of white matter abnormalities caused by gluten sensitivity can be seen in these four patients (AndashD) A and C show diffuse white matter changes whereas B and D show more f

Marios Hadjivassiliou David S Sanders Richard A Gruumlnewald Nicola Woodroofe Sabrina Boscolo Daniel Aeschl

Gluten sensitivity from gut to brain

The Lancet Neurology Volume 9 Issue 3 2010 318 - 330

httpdxdoiorg101016S1474-4422(09)70290-X

MS and Gluten References 1 Gluten antibodies in patients with multiple sclerosis Hum Nutr Appl

Nutr 1984 Apr38(2)142-32 Multiple sclerosis and gluten sensitivity Clin Neurol Neurosurg 2007

Oct109(8)651-33 Prevalence of celiac disease in multiple sclerosis BMC Neurol 2011 Mar

711314 Celiac disease with neurologic manifestations in children Rev Med Chir

Soc Med Nat Iasi 2013 Jan-Mar117(1)88-945 Celiac disease with cerebral and peripheral nerve involvement

mimicking multiple sclerosis J Med Life 2014 Sep 157(3)440-4 Epub2014 Sep 25

6 A case of multiple sclerosis and celiac disease Case Rep NeurolMed 20132013576921

7 Gluten-related disorders gluten ataxia Dig Dis 201533(2)264-88 Transglutaminase-6 is an autoantigen in progressive multiple sclerosis and

is upregulated in reactive astrocytes Mult Scler 2016 Dec 11352458516684022

9 The progression of coeliac disease its neurological and psychiatric implications Nutr Res Rev 2017 Jun30(1)25-35

Risks of Eggs

bull Prosndash Grass fed - DHA choline biotin lutein Vitamins A D K2 and

B3 B6 B9 B12

bull Cons ndash Eggs are most common food allergen in IBD gt70ndash 60 allergy patients have IgG Ab to eggsndash 13 seasonal allergies have IgG Ab to eggs ndash Wheat milk eggs are common food triggers to Eosinophilic

Esophagitis

References next slide

References Risks of Eggs bull Wang G Ren J Li G et al The utility of food antigen test in the diagnosis of Crohnrsquos disease

and remission maintenance after exclusive enteral nutrition Clin Res Hepatol Gastroenterol 201842(2)145-152 doi101016jclinre201709002

bull Shakoor Z AlFaifi A AlAmro B AlTawil LN AlOhaly RY Prevalence of IgG-mediated food intolerance among patients with allergic symptoms Ann Saudi Med 2016 Nov-Dec36(6)386-390

bull Dhanapala P De Silva C Doran T Suphioglu C Cracking the egg An insight into egg hypersensitivity Mol Immunol 2015 Aug66(2)375-83 doi 101016jmolimm201504016

bull Pang KA Pang KP Pang EB Tan YN Chan YH Siow JK Food allergy and allergic rhinitis in 435 asian patients - A descriptive review Med J Malaysia 2017 Aug72(4)215-220

bull Philpott H Nandurkar S Royce SG Thien F Gibson PR Allergy tests do not predict food triggers in adult patients with eosinophilic oesophagitis A comprehensive prospective study using five modalities Aliment Pharmacol Ther 2016 Aug44(3)223-33 doi 101111apt13676

bull Cai C Shen J Zhao D et al Serological Investigation of Food Specific Immunoglobulin G Antibodies in Patients with Inflammatory Bowel Diseases Boone DL ed PLoS ONE 20149(11)e112154 doi101371journalpone0112154

Lectins

bull ldquoBy eliminating dietary elements particularly lectins which adversely influence both enterocyte and lymphocyte structure and function it is proposed that the peripheral antigenic stimulus (both pathogenic and dietary) will be reduced and thereby result in a diminution of disease symptoms in certain patients with RArdquo

Cordain L Toohey L Smith MJ Hickey MS Modulation of immune function by dietary lectins in rheumatoid arthritis British Journal of Nutrition 200083(03)207-217

bull Lectins are proteins found in plants and animals that bind sugars (hemagglutinins)

bull They can bind the glycoproteins on the intestinal lining leading to barrier damage

bull Lectins are found in most foods but are especially high in grains (esp wheat) dairy legumes and nightshade vegetables

bull Most traditional methods cooking these foods such as soaking ferment-ing amp cooking will decrease the lectin content

Nutrient Triage

bull Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage

ndash Zn Mg biotin Vitamin K D A

ndash Lipoic Acid Acetyl carnitine

Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triageProc Natl Acad Sci U S A 2006 Nov 21103(47)17589-94

What to Eat

Fruit and vegetable consumption and mortality from all causes cardiovascular disease and cancer systematic review and dose-response meta-analysis of prospective cohort studies

16 studies - 833234 participants

BMJ 2014 349 g4490

BMJ 2014 349 g4490

Risk of all cause mortality associated with servingsday of fruit and vegetables

Dose-response relation between fruit and vegetable consumption and risk of all cause mortality

BMJ 2014 349 g4490

Myelin

ndash Omega 3 Fatty Acids

ndash Thiamine (B1)

ndash Folate (B9)

ndash Cobolamin (B12)

ndash Minerals

Key Micronutrients

Bourre JM Effects of nutrients (in food) on the structure and function of the nervous

system update on dietary requirements for brain Part 1 micronutrients

Part 2 Macronutriients

J Nutr Health Aging 200610(5)377-85

Bowman Nutrient biomarker patterns cognitive function and MRI measures of

brain aging Neurology 2012 Jan 2478(4)241-9 Bowman

Sulfur Rich Foods

Why Brassica and Allium

bull Improve detoxification

bull Increase glutathione production

bull Increase GABA production

bull Enhance Neuroprotection

bull Improve endothelial function

Brassica and Allium References

1 Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimers Disease Med Cell Longev20152015781938

2 Learning and memory promoting effects of crude garlic extract Indian J Exp Biol2013 Dec51(12)1094-100

3 Enhancement of the neuroprotective activity of Hericiumerinaceus mycelium co-cultivated with Allium sativum extract Arch Physiol Biochem2015 Feb121(1)19-25

Why Emphasize Mushrooms

bull Increase nerve growth factors (NGF)

bull Hericium erinaceus (Yamabushitake or Lionrsquos Mane) stimulate the production of NGF (in vitro)

bull Activate natural killer cells

bull Prime innate and adaptive immunity

bull Mori K Obara Y Hirota M Azumi Y Kinugasa S Inatomi S Nakahata N Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human

astrocytoma cells Biol Pharm Bull 2008 Sep31(9)1727-32

bull Lee DH Kim HW Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway Int J Med Mushrooms 201416(1)1-16

bull Akramiene D Kondrotas A Didziapetriene J Kevelaitis E Effects of beta-glucans on the immune system Medicina (Kaunas)200743(8)597-606

bull Lai PL Naidu MSabaratnam VWong K DaviP Kuppusamy UR Abdullah N Malek SN Neurotrophic properties of the Lions mane medicinal mushroom

Hericium erinaceus (Higher Basidiomycetes) from Malaysia Int J Med Mushrooms201315(6)539-54

bull Phan CW David P Naidu M Wong KH Sabaratnam V Therapeutic potential of culinary-medicinal mushrooms for the management of

neurodegenerative diseases diversity metabolite and mechanism Crit Rev Biotechnol201535(3)355-68

Why Greens

bull Vitamin K1 metabolized to K2-mk7 in gut

bull K2 important in hellip

ndash Myelin production

ndash Calcium influx into bones and teeth

bull Carotenoids magnesium

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 12: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

The Swank Diet

bull N=144 followed 50 years

bull lt 15 grams saturated fat vs gt 20 grams

bull Greatest benefit earlier in the disease course

bull More likely to remain ambulatory

Review of MS patient survival on a Swank low saturated fat dietNutrition 2003 Feb19(2)161-2 ReviewEffect of low saturated fat diet in early and late cases of multiple sclerosisLancet 1990 Jul 7336(8706)37-9Multiple sclerosis twenty years on low fat dietArch Neurol 1970 Nov23(5)460-74

Low-fat plant-based diet in multiple sclerosis A randomized controlled trial

bull This was a randomized-controlled assessor-blinded one-year long study

bull N=61

bull No change in EDSS MRI

bull Trend towards reduced FSS (fatigue)

Low-fat plant-based diet in multiple sclerosis A randomized controlled trial Mult Scler Relat Disord 2016 Sep980-90

Mediterranean diet adherence and risk of multiple sclerosis ndash Case control study

bull N=70 RRMS 140 controls Interviews re diet

bull Reduced risk of MS

ndash Fruits (OR=028 95 CI 012-063 p-value 0002)

ndash Vegetables (OR=023 95 CI 010-053 p-value 0001)

Mediterranean diet adherence and risk of multiple sclerosis a case-control study Asia Pac J Clin Nutr 201625(2)377-84

Mediterranean Diet bull High olive oil

bull High vegetable polyphenol

bull Whole grains

bull Low red meat

Potential for diet to prevent and remediate cognitive deficits in neurological disordersNutr Rev 2018 Mar 176(3)204-217The Role of Diet in Multiple Sclerosis Mechanistic Connections and Current EvidenceCurr Nutr Rep 2018 Aug 16Anti-inflammatory Activity of Extra Virgin Olive Oil Polyphenols Which Role in the Prevention and Treatment of Immune-Mediated Inflammatory DiseasesEndocr Metab Immune Disord Drug Targets 201818(1)36-50

bull The following slides represent the rationale for the dietary intervention we are studying in the Dietary Approaches to Treating MS Related Fatigue

bull This protocol is not validated nor does it currently meet the current evidence based guideline criteria as set forth by the American Academy of Neurology or the Academy of Nutrition and Dietetics

Dairy amp MSCasein Gluten amp Schizophrenia

bull Liquid cow milk (not cheese) and MS prevalence was highly correlated (rho = 0836) across 27 countries and 29 populations

bull IgG to Casein and gluten were significantly uarrin recent onset and non-recent onset schizophrenia compared to controls (ple000001-0004)

1 Correlation between milk and dairy product consumption and multiple sclerosis prevalence a worldwide

study Neuroepidemiology 199211(4-6)304-12

2 Severance EG Alaedini A Yang S Halling M Gressitt KL Stallings CR Origoni AE Vaughan C

Khushalani S Leweke FM Dickerson FB Yolken RH Gastrointestinal inflammation and associated

immune activation in schizophrenia Schizophr Res2012 Jun138(1)48-53

Gluten and Casein and Opioids

bull Gluten can be degraded into several morphine-like substances named gluten exorphins

bull Milk proteins are particularly strong allergens and are additional source of bioactive peptides including β-casomorphin-7 and exerts its influence on nervous digestive and immune functions via the opioid receptor

1 The opioid effects of gluten exorphins asymptomatic celiac disease J Health PopulNutr 2015 Nov 243324

2 Opioid receptor ligands derived from food proteins Curr Pharm Des 20039(16)1331-44

3 β-casomorphin-7 alters μ-opioid receptor and dipeptidyl peptidase IV genes expression in children with atopic dermatitis Peptides 2014 Dec62144-9

Nutrition in Parkinsons Disease

Seidl SE Santiago JA Bilyk H Potashkin JA The emerging role of nutrition in Parkinsons disease Front Aging Neurosci 2014 Mar 7636 doi 103389fnagi201400036 eCollection 2014

Gluten sensitivity is an abnormal immune response to gluten in genetically susceptible individuals and may manifest solely with neurological dysfunction 90 of gluten sensitive individuals have no GI symptoms

Lancet Neurol 2010 Mar9(3)318-30 Hadjivassiliou M

Figure 2 MRI in four patients with gluten encephalopathy The extent and variability of white matter abnormalities caused by gluten sensitivity can be seen in these four patients (AndashD) A and C show diffuse white matter changes whereas B and D show more f

Marios Hadjivassiliou David S Sanders Richard A Gruumlnewald Nicola Woodroofe Sabrina Boscolo Daniel Aeschl

Gluten sensitivity from gut to brain

The Lancet Neurology Volume 9 Issue 3 2010 318 - 330

httpdxdoiorg101016S1474-4422(09)70290-X

MS and Gluten References 1 Gluten antibodies in patients with multiple sclerosis Hum Nutr Appl

Nutr 1984 Apr38(2)142-32 Multiple sclerosis and gluten sensitivity Clin Neurol Neurosurg 2007

Oct109(8)651-33 Prevalence of celiac disease in multiple sclerosis BMC Neurol 2011 Mar

711314 Celiac disease with neurologic manifestations in children Rev Med Chir

Soc Med Nat Iasi 2013 Jan-Mar117(1)88-945 Celiac disease with cerebral and peripheral nerve involvement

mimicking multiple sclerosis J Med Life 2014 Sep 157(3)440-4 Epub2014 Sep 25

6 A case of multiple sclerosis and celiac disease Case Rep NeurolMed 20132013576921

7 Gluten-related disorders gluten ataxia Dig Dis 201533(2)264-88 Transglutaminase-6 is an autoantigen in progressive multiple sclerosis and

is upregulated in reactive astrocytes Mult Scler 2016 Dec 11352458516684022

9 The progression of coeliac disease its neurological and psychiatric implications Nutr Res Rev 2017 Jun30(1)25-35

Risks of Eggs

bull Prosndash Grass fed - DHA choline biotin lutein Vitamins A D K2 and

B3 B6 B9 B12

bull Cons ndash Eggs are most common food allergen in IBD gt70ndash 60 allergy patients have IgG Ab to eggsndash 13 seasonal allergies have IgG Ab to eggs ndash Wheat milk eggs are common food triggers to Eosinophilic

Esophagitis

References next slide

References Risks of Eggs bull Wang G Ren J Li G et al The utility of food antigen test in the diagnosis of Crohnrsquos disease

and remission maintenance after exclusive enteral nutrition Clin Res Hepatol Gastroenterol 201842(2)145-152 doi101016jclinre201709002

bull Shakoor Z AlFaifi A AlAmro B AlTawil LN AlOhaly RY Prevalence of IgG-mediated food intolerance among patients with allergic symptoms Ann Saudi Med 2016 Nov-Dec36(6)386-390

bull Dhanapala P De Silva C Doran T Suphioglu C Cracking the egg An insight into egg hypersensitivity Mol Immunol 2015 Aug66(2)375-83 doi 101016jmolimm201504016

bull Pang KA Pang KP Pang EB Tan YN Chan YH Siow JK Food allergy and allergic rhinitis in 435 asian patients - A descriptive review Med J Malaysia 2017 Aug72(4)215-220

bull Philpott H Nandurkar S Royce SG Thien F Gibson PR Allergy tests do not predict food triggers in adult patients with eosinophilic oesophagitis A comprehensive prospective study using five modalities Aliment Pharmacol Ther 2016 Aug44(3)223-33 doi 101111apt13676

bull Cai C Shen J Zhao D et al Serological Investigation of Food Specific Immunoglobulin G Antibodies in Patients with Inflammatory Bowel Diseases Boone DL ed PLoS ONE 20149(11)e112154 doi101371journalpone0112154

Lectins

bull ldquoBy eliminating dietary elements particularly lectins which adversely influence both enterocyte and lymphocyte structure and function it is proposed that the peripheral antigenic stimulus (both pathogenic and dietary) will be reduced and thereby result in a diminution of disease symptoms in certain patients with RArdquo

Cordain L Toohey L Smith MJ Hickey MS Modulation of immune function by dietary lectins in rheumatoid arthritis British Journal of Nutrition 200083(03)207-217

bull Lectins are proteins found in plants and animals that bind sugars (hemagglutinins)

bull They can bind the glycoproteins on the intestinal lining leading to barrier damage

bull Lectins are found in most foods but are especially high in grains (esp wheat) dairy legumes and nightshade vegetables

bull Most traditional methods cooking these foods such as soaking ferment-ing amp cooking will decrease the lectin content

Nutrient Triage

bull Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage

ndash Zn Mg biotin Vitamin K D A

ndash Lipoic Acid Acetyl carnitine

Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triageProc Natl Acad Sci U S A 2006 Nov 21103(47)17589-94

What to Eat

Fruit and vegetable consumption and mortality from all causes cardiovascular disease and cancer systematic review and dose-response meta-analysis of prospective cohort studies

16 studies - 833234 participants

BMJ 2014 349 g4490

BMJ 2014 349 g4490

Risk of all cause mortality associated with servingsday of fruit and vegetables

Dose-response relation between fruit and vegetable consumption and risk of all cause mortality

BMJ 2014 349 g4490

Myelin

ndash Omega 3 Fatty Acids

ndash Thiamine (B1)

ndash Folate (B9)

ndash Cobolamin (B12)

ndash Minerals

Key Micronutrients

Bourre JM Effects of nutrients (in food) on the structure and function of the nervous

system update on dietary requirements for brain Part 1 micronutrients

Part 2 Macronutriients

J Nutr Health Aging 200610(5)377-85

Bowman Nutrient biomarker patterns cognitive function and MRI measures of

brain aging Neurology 2012 Jan 2478(4)241-9 Bowman

Sulfur Rich Foods

Why Brassica and Allium

bull Improve detoxification

bull Increase glutathione production

bull Increase GABA production

bull Enhance Neuroprotection

bull Improve endothelial function

Brassica and Allium References

1 Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimers Disease Med Cell Longev20152015781938

2 Learning and memory promoting effects of crude garlic extract Indian J Exp Biol2013 Dec51(12)1094-100

3 Enhancement of the neuroprotective activity of Hericiumerinaceus mycelium co-cultivated with Allium sativum extract Arch Physiol Biochem2015 Feb121(1)19-25

Why Emphasize Mushrooms

bull Increase nerve growth factors (NGF)

bull Hericium erinaceus (Yamabushitake or Lionrsquos Mane) stimulate the production of NGF (in vitro)

bull Activate natural killer cells

bull Prime innate and adaptive immunity

bull Mori K Obara Y Hirota M Azumi Y Kinugasa S Inatomi S Nakahata N Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human

astrocytoma cells Biol Pharm Bull 2008 Sep31(9)1727-32

bull Lee DH Kim HW Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway Int J Med Mushrooms 201416(1)1-16

bull Akramiene D Kondrotas A Didziapetriene J Kevelaitis E Effects of beta-glucans on the immune system Medicina (Kaunas)200743(8)597-606

bull Lai PL Naidu MSabaratnam VWong K DaviP Kuppusamy UR Abdullah N Malek SN Neurotrophic properties of the Lions mane medicinal mushroom

Hericium erinaceus (Higher Basidiomycetes) from Malaysia Int J Med Mushrooms201315(6)539-54

bull Phan CW David P Naidu M Wong KH Sabaratnam V Therapeutic potential of culinary-medicinal mushrooms for the management of

neurodegenerative diseases diversity metabolite and mechanism Crit Rev Biotechnol201535(3)355-68

Why Greens

bull Vitamin K1 metabolized to K2-mk7 in gut

bull K2 important in hellip

ndash Myelin production

ndash Calcium influx into bones and teeth

bull Carotenoids magnesium

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 13: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

The Swank Diet

bull N=144 followed 50 years

bull lt 15 grams saturated fat vs gt 20 grams

bull Greatest benefit earlier in the disease course

bull More likely to remain ambulatory

Review of MS patient survival on a Swank low saturated fat dietNutrition 2003 Feb19(2)161-2 ReviewEffect of low saturated fat diet in early and late cases of multiple sclerosisLancet 1990 Jul 7336(8706)37-9Multiple sclerosis twenty years on low fat dietArch Neurol 1970 Nov23(5)460-74

Low-fat plant-based diet in multiple sclerosis A randomized controlled trial

bull This was a randomized-controlled assessor-blinded one-year long study

bull N=61

bull No change in EDSS MRI

bull Trend towards reduced FSS (fatigue)

Low-fat plant-based diet in multiple sclerosis A randomized controlled trial Mult Scler Relat Disord 2016 Sep980-90

Mediterranean diet adherence and risk of multiple sclerosis ndash Case control study

bull N=70 RRMS 140 controls Interviews re diet

bull Reduced risk of MS

ndash Fruits (OR=028 95 CI 012-063 p-value 0002)

ndash Vegetables (OR=023 95 CI 010-053 p-value 0001)

Mediterranean diet adherence and risk of multiple sclerosis a case-control study Asia Pac J Clin Nutr 201625(2)377-84

Mediterranean Diet bull High olive oil

bull High vegetable polyphenol

bull Whole grains

bull Low red meat

Potential for diet to prevent and remediate cognitive deficits in neurological disordersNutr Rev 2018 Mar 176(3)204-217The Role of Diet in Multiple Sclerosis Mechanistic Connections and Current EvidenceCurr Nutr Rep 2018 Aug 16Anti-inflammatory Activity of Extra Virgin Olive Oil Polyphenols Which Role in the Prevention and Treatment of Immune-Mediated Inflammatory DiseasesEndocr Metab Immune Disord Drug Targets 201818(1)36-50

bull The following slides represent the rationale for the dietary intervention we are studying in the Dietary Approaches to Treating MS Related Fatigue

bull This protocol is not validated nor does it currently meet the current evidence based guideline criteria as set forth by the American Academy of Neurology or the Academy of Nutrition and Dietetics

Dairy amp MSCasein Gluten amp Schizophrenia

bull Liquid cow milk (not cheese) and MS prevalence was highly correlated (rho = 0836) across 27 countries and 29 populations

bull IgG to Casein and gluten were significantly uarrin recent onset and non-recent onset schizophrenia compared to controls (ple000001-0004)

1 Correlation between milk and dairy product consumption and multiple sclerosis prevalence a worldwide

study Neuroepidemiology 199211(4-6)304-12

2 Severance EG Alaedini A Yang S Halling M Gressitt KL Stallings CR Origoni AE Vaughan C

Khushalani S Leweke FM Dickerson FB Yolken RH Gastrointestinal inflammation and associated

immune activation in schizophrenia Schizophr Res2012 Jun138(1)48-53

Gluten and Casein and Opioids

bull Gluten can be degraded into several morphine-like substances named gluten exorphins

bull Milk proteins are particularly strong allergens and are additional source of bioactive peptides including β-casomorphin-7 and exerts its influence on nervous digestive and immune functions via the opioid receptor

1 The opioid effects of gluten exorphins asymptomatic celiac disease J Health PopulNutr 2015 Nov 243324

2 Opioid receptor ligands derived from food proteins Curr Pharm Des 20039(16)1331-44

3 β-casomorphin-7 alters μ-opioid receptor and dipeptidyl peptidase IV genes expression in children with atopic dermatitis Peptides 2014 Dec62144-9

Nutrition in Parkinsons Disease

Seidl SE Santiago JA Bilyk H Potashkin JA The emerging role of nutrition in Parkinsons disease Front Aging Neurosci 2014 Mar 7636 doi 103389fnagi201400036 eCollection 2014

Gluten sensitivity is an abnormal immune response to gluten in genetically susceptible individuals and may manifest solely with neurological dysfunction 90 of gluten sensitive individuals have no GI symptoms

Lancet Neurol 2010 Mar9(3)318-30 Hadjivassiliou M

Figure 2 MRI in four patients with gluten encephalopathy The extent and variability of white matter abnormalities caused by gluten sensitivity can be seen in these four patients (AndashD) A and C show diffuse white matter changes whereas B and D show more f

Marios Hadjivassiliou David S Sanders Richard A Gruumlnewald Nicola Woodroofe Sabrina Boscolo Daniel Aeschl

Gluten sensitivity from gut to brain

The Lancet Neurology Volume 9 Issue 3 2010 318 - 330

httpdxdoiorg101016S1474-4422(09)70290-X

MS and Gluten References 1 Gluten antibodies in patients with multiple sclerosis Hum Nutr Appl

Nutr 1984 Apr38(2)142-32 Multiple sclerosis and gluten sensitivity Clin Neurol Neurosurg 2007

Oct109(8)651-33 Prevalence of celiac disease in multiple sclerosis BMC Neurol 2011 Mar

711314 Celiac disease with neurologic manifestations in children Rev Med Chir

Soc Med Nat Iasi 2013 Jan-Mar117(1)88-945 Celiac disease with cerebral and peripheral nerve involvement

mimicking multiple sclerosis J Med Life 2014 Sep 157(3)440-4 Epub2014 Sep 25

6 A case of multiple sclerosis and celiac disease Case Rep NeurolMed 20132013576921

7 Gluten-related disorders gluten ataxia Dig Dis 201533(2)264-88 Transglutaminase-6 is an autoantigen in progressive multiple sclerosis and

is upregulated in reactive astrocytes Mult Scler 2016 Dec 11352458516684022

9 The progression of coeliac disease its neurological and psychiatric implications Nutr Res Rev 2017 Jun30(1)25-35

Risks of Eggs

bull Prosndash Grass fed - DHA choline biotin lutein Vitamins A D K2 and

B3 B6 B9 B12

bull Cons ndash Eggs are most common food allergen in IBD gt70ndash 60 allergy patients have IgG Ab to eggsndash 13 seasonal allergies have IgG Ab to eggs ndash Wheat milk eggs are common food triggers to Eosinophilic

Esophagitis

References next slide

References Risks of Eggs bull Wang G Ren J Li G et al The utility of food antigen test in the diagnosis of Crohnrsquos disease

and remission maintenance after exclusive enteral nutrition Clin Res Hepatol Gastroenterol 201842(2)145-152 doi101016jclinre201709002

bull Shakoor Z AlFaifi A AlAmro B AlTawil LN AlOhaly RY Prevalence of IgG-mediated food intolerance among patients with allergic symptoms Ann Saudi Med 2016 Nov-Dec36(6)386-390

bull Dhanapala P De Silva C Doran T Suphioglu C Cracking the egg An insight into egg hypersensitivity Mol Immunol 2015 Aug66(2)375-83 doi 101016jmolimm201504016

bull Pang KA Pang KP Pang EB Tan YN Chan YH Siow JK Food allergy and allergic rhinitis in 435 asian patients - A descriptive review Med J Malaysia 2017 Aug72(4)215-220

bull Philpott H Nandurkar S Royce SG Thien F Gibson PR Allergy tests do not predict food triggers in adult patients with eosinophilic oesophagitis A comprehensive prospective study using five modalities Aliment Pharmacol Ther 2016 Aug44(3)223-33 doi 101111apt13676

bull Cai C Shen J Zhao D et al Serological Investigation of Food Specific Immunoglobulin G Antibodies in Patients with Inflammatory Bowel Diseases Boone DL ed PLoS ONE 20149(11)e112154 doi101371journalpone0112154

Lectins

bull ldquoBy eliminating dietary elements particularly lectins which adversely influence both enterocyte and lymphocyte structure and function it is proposed that the peripheral antigenic stimulus (both pathogenic and dietary) will be reduced and thereby result in a diminution of disease symptoms in certain patients with RArdquo

Cordain L Toohey L Smith MJ Hickey MS Modulation of immune function by dietary lectins in rheumatoid arthritis British Journal of Nutrition 200083(03)207-217

bull Lectins are proteins found in plants and animals that bind sugars (hemagglutinins)

bull They can bind the glycoproteins on the intestinal lining leading to barrier damage

bull Lectins are found in most foods but are especially high in grains (esp wheat) dairy legumes and nightshade vegetables

bull Most traditional methods cooking these foods such as soaking ferment-ing amp cooking will decrease the lectin content

Nutrient Triage

bull Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage

ndash Zn Mg biotin Vitamin K D A

ndash Lipoic Acid Acetyl carnitine

Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triageProc Natl Acad Sci U S A 2006 Nov 21103(47)17589-94

What to Eat

Fruit and vegetable consumption and mortality from all causes cardiovascular disease and cancer systematic review and dose-response meta-analysis of prospective cohort studies

16 studies - 833234 participants

BMJ 2014 349 g4490

BMJ 2014 349 g4490

Risk of all cause mortality associated with servingsday of fruit and vegetables

Dose-response relation between fruit and vegetable consumption and risk of all cause mortality

BMJ 2014 349 g4490

Myelin

ndash Omega 3 Fatty Acids

ndash Thiamine (B1)

ndash Folate (B9)

ndash Cobolamin (B12)

ndash Minerals

Key Micronutrients

Bourre JM Effects of nutrients (in food) on the structure and function of the nervous

system update on dietary requirements for brain Part 1 micronutrients

Part 2 Macronutriients

J Nutr Health Aging 200610(5)377-85

Bowman Nutrient biomarker patterns cognitive function and MRI measures of

brain aging Neurology 2012 Jan 2478(4)241-9 Bowman

Sulfur Rich Foods

Why Brassica and Allium

bull Improve detoxification

bull Increase glutathione production

bull Increase GABA production

bull Enhance Neuroprotection

bull Improve endothelial function

Brassica and Allium References

1 Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimers Disease Med Cell Longev20152015781938

2 Learning and memory promoting effects of crude garlic extract Indian J Exp Biol2013 Dec51(12)1094-100

3 Enhancement of the neuroprotective activity of Hericiumerinaceus mycelium co-cultivated with Allium sativum extract Arch Physiol Biochem2015 Feb121(1)19-25

Why Emphasize Mushrooms

bull Increase nerve growth factors (NGF)

bull Hericium erinaceus (Yamabushitake or Lionrsquos Mane) stimulate the production of NGF (in vitro)

bull Activate natural killer cells

bull Prime innate and adaptive immunity

bull Mori K Obara Y Hirota M Azumi Y Kinugasa S Inatomi S Nakahata N Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human

astrocytoma cells Biol Pharm Bull 2008 Sep31(9)1727-32

bull Lee DH Kim HW Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway Int J Med Mushrooms 201416(1)1-16

bull Akramiene D Kondrotas A Didziapetriene J Kevelaitis E Effects of beta-glucans on the immune system Medicina (Kaunas)200743(8)597-606

bull Lai PL Naidu MSabaratnam VWong K DaviP Kuppusamy UR Abdullah N Malek SN Neurotrophic properties of the Lions mane medicinal mushroom

Hericium erinaceus (Higher Basidiomycetes) from Malaysia Int J Med Mushrooms201315(6)539-54

bull Phan CW David P Naidu M Wong KH Sabaratnam V Therapeutic potential of culinary-medicinal mushrooms for the management of

neurodegenerative diseases diversity metabolite and mechanism Crit Rev Biotechnol201535(3)355-68

Why Greens

bull Vitamin K1 metabolized to K2-mk7 in gut

bull K2 important in hellip

ndash Myelin production

ndash Calcium influx into bones and teeth

bull Carotenoids magnesium

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 14: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

Low-fat plant-based diet in multiple sclerosis A randomized controlled trial

bull This was a randomized-controlled assessor-blinded one-year long study

bull N=61

bull No change in EDSS MRI

bull Trend towards reduced FSS (fatigue)

Low-fat plant-based diet in multiple sclerosis A randomized controlled trial Mult Scler Relat Disord 2016 Sep980-90

Mediterranean diet adherence and risk of multiple sclerosis ndash Case control study

bull N=70 RRMS 140 controls Interviews re diet

bull Reduced risk of MS

ndash Fruits (OR=028 95 CI 012-063 p-value 0002)

ndash Vegetables (OR=023 95 CI 010-053 p-value 0001)

Mediterranean diet adherence and risk of multiple sclerosis a case-control study Asia Pac J Clin Nutr 201625(2)377-84

Mediterranean Diet bull High olive oil

bull High vegetable polyphenol

bull Whole grains

bull Low red meat

Potential for diet to prevent and remediate cognitive deficits in neurological disordersNutr Rev 2018 Mar 176(3)204-217The Role of Diet in Multiple Sclerosis Mechanistic Connections and Current EvidenceCurr Nutr Rep 2018 Aug 16Anti-inflammatory Activity of Extra Virgin Olive Oil Polyphenols Which Role in the Prevention and Treatment of Immune-Mediated Inflammatory DiseasesEndocr Metab Immune Disord Drug Targets 201818(1)36-50

bull The following slides represent the rationale for the dietary intervention we are studying in the Dietary Approaches to Treating MS Related Fatigue

bull This protocol is not validated nor does it currently meet the current evidence based guideline criteria as set forth by the American Academy of Neurology or the Academy of Nutrition and Dietetics

Dairy amp MSCasein Gluten amp Schizophrenia

bull Liquid cow milk (not cheese) and MS prevalence was highly correlated (rho = 0836) across 27 countries and 29 populations

bull IgG to Casein and gluten were significantly uarrin recent onset and non-recent onset schizophrenia compared to controls (ple000001-0004)

1 Correlation between milk and dairy product consumption and multiple sclerosis prevalence a worldwide

study Neuroepidemiology 199211(4-6)304-12

2 Severance EG Alaedini A Yang S Halling M Gressitt KL Stallings CR Origoni AE Vaughan C

Khushalani S Leweke FM Dickerson FB Yolken RH Gastrointestinal inflammation and associated

immune activation in schizophrenia Schizophr Res2012 Jun138(1)48-53

Gluten and Casein and Opioids

bull Gluten can be degraded into several morphine-like substances named gluten exorphins

bull Milk proteins are particularly strong allergens and are additional source of bioactive peptides including β-casomorphin-7 and exerts its influence on nervous digestive and immune functions via the opioid receptor

1 The opioid effects of gluten exorphins asymptomatic celiac disease J Health PopulNutr 2015 Nov 243324

2 Opioid receptor ligands derived from food proteins Curr Pharm Des 20039(16)1331-44

3 β-casomorphin-7 alters μ-opioid receptor and dipeptidyl peptidase IV genes expression in children with atopic dermatitis Peptides 2014 Dec62144-9

Nutrition in Parkinsons Disease

Seidl SE Santiago JA Bilyk H Potashkin JA The emerging role of nutrition in Parkinsons disease Front Aging Neurosci 2014 Mar 7636 doi 103389fnagi201400036 eCollection 2014

Gluten sensitivity is an abnormal immune response to gluten in genetically susceptible individuals and may manifest solely with neurological dysfunction 90 of gluten sensitive individuals have no GI symptoms

Lancet Neurol 2010 Mar9(3)318-30 Hadjivassiliou M

Figure 2 MRI in four patients with gluten encephalopathy The extent and variability of white matter abnormalities caused by gluten sensitivity can be seen in these four patients (AndashD) A and C show diffuse white matter changes whereas B and D show more f

Marios Hadjivassiliou David S Sanders Richard A Gruumlnewald Nicola Woodroofe Sabrina Boscolo Daniel Aeschl

Gluten sensitivity from gut to brain

The Lancet Neurology Volume 9 Issue 3 2010 318 - 330

httpdxdoiorg101016S1474-4422(09)70290-X

MS and Gluten References 1 Gluten antibodies in patients with multiple sclerosis Hum Nutr Appl

Nutr 1984 Apr38(2)142-32 Multiple sclerosis and gluten sensitivity Clin Neurol Neurosurg 2007

Oct109(8)651-33 Prevalence of celiac disease in multiple sclerosis BMC Neurol 2011 Mar

711314 Celiac disease with neurologic manifestations in children Rev Med Chir

Soc Med Nat Iasi 2013 Jan-Mar117(1)88-945 Celiac disease with cerebral and peripheral nerve involvement

mimicking multiple sclerosis J Med Life 2014 Sep 157(3)440-4 Epub2014 Sep 25

6 A case of multiple sclerosis and celiac disease Case Rep NeurolMed 20132013576921

7 Gluten-related disorders gluten ataxia Dig Dis 201533(2)264-88 Transglutaminase-6 is an autoantigen in progressive multiple sclerosis and

is upregulated in reactive astrocytes Mult Scler 2016 Dec 11352458516684022

9 The progression of coeliac disease its neurological and psychiatric implications Nutr Res Rev 2017 Jun30(1)25-35

Risks of Eggs

bull Prosndash Grass fed - DHA choline biotin lutein Vitamins A D K2 and

B3 B6 B9 B12

bull Cons ndash Eggs are most common food allergen in IBD gt70ndash 60 allergy patients have IgG Ab to eggsndash 13 seasonal allergies have IgG Ab to eggs ndash Wheat milk eggs are common food triggers to Eosinophilic

Esophagitis

References next slide

References Risks of Eggs bull Wang G Ren J Li G et al The utility of food antigen test in the diagnosis of Crohnrsquos disease

and remission maintenance after exclusive enteral nutrition Clin Res Hepatol Gastroenterol 201842(2)145-152 doi101016jclinre201709002

bull Shakoor Z AlFaifi A AlAmro B AlTawil LN AlOhaly RY Prevalence of IgG-mediated food intolerance among patients with allergic symptoms Ann Saudi Med 2016 Nov-Dec36(6)386-390

bull Dhanapala P De Silva C Doran T Suphioglu C Cracking the egg An insight into egg hypersensitivity Mol Immunol 2015 Aug66(2)375-83 doi 101016jmolimm201504016

bull Pang KA Pang KP Pang EB Tan YN Chan YH Siow JK Food allergy and allergic rhinitis in 435 asian patients - A descriptive review Med J Malaysia 2017 Aug72(4)215-220

bull Philpott H Nandurkar S Royce SG Thien F Gibson PR Allergy tests do not predict food triggers in adult patients with eosinophilic oesophagitis A comprehensive prospective study using five modalities Aliment Pharmacol Ther 2016 Aug44(3)223-33 doi 101111apt13676

bull Cai C Shen J Zhao D et al Serological Investigation of Food Specific Immunoglobulin G Antibodies in Patients with Inflammatory Bowel Diseases Boone DL ed PLoS ONE 20149(11)e112154 doi101371journalpone0112154

Lectins

bull ldquoBy eliminating dietary elements particularly lectins which adversely influence both enterocyte and lymphocyte structure and function it is proposed that the peripheral antigenic stimulus (both pathogenic and dietary) will be reduced and thereby result in a diminution of disease symptoms in certain patients with RArdquo

Cordain L Toohey L Smith MJ Hickey MS Modulation of immune function by dietary lectins in rheumatoid arthritis British Journal of Nutrition 200083(03)207-217

bull Lectins are proteins found in plants and animals that bind sugars (hemagglutinins)

bull They can bind the glycoproteins on the intestinal lining leading to barrier damage

bull Lectins are found in most foods but are especially high in grains (esp wheat) dairy legumes and nightshade vegetables

bull Most traditional methods cooking these foods such as soaking ferment-ing amp cooking will decrease the lectin content

Nutrient Triage

bull Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage

ndash Zn Mg biotin Vitamin K D A

ndash Lipoic Acid Acetyl carnitine

Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triageProc Natl Acad Sci U S A 2006 Nov 21103(47)17589-94

What to Eat

Fruit and vegetable consumption and mortality from all causes cardiovascular disease and cancer systematic review and dose-response meta-analysis of prospective cohort studies

16 studies - 833234 participants

BMJ 2014 349 g4490

BMJ 2014 349 g4490

Risk of all cause mortality associated with servingsday of fruit and vegetables

Dose-response relation between fruit and vegetable consumption and risk of all cause mortality

BMJ 2014 349 g4490

Myelin

ndash Omega 3 Fatty Acids

ndash Thiamine (B1)

ndash Folate (B9)

ndash Cobolamin (B12)

ndash Minerals

Key Micronutrients

Bourre JM Effects of nutrients (in food) on the structure and function of the nervous

system update on dietary requirements for brain Part 1 micronutrients

Part 2 Macronutriients

J Nutr Health Aging 200610(5)377-85

Bowman Nutrient biomarker patterns cognitive function and MRI measures of

brain aging Neurology 2012 Jan 2478(4)241-9 Bowman

Sulfur Rich Foods

Why Brassica and Allium

bull Improve detoxification

bull Increase glutathione production

bull Increase GABA production

bull Enhance Neuroprotection

bull Improve endothelial function

Brassica and Allium References

1 Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimers Disease Med Cell Longev20152015781938

2 Learning and memory promoting effects of crude garlic extract Indian J Exp Biol2013 Dec51(12)1094-100

3 Enhancement of the neuroprotective activity of Hericiumerinaceus mycelium co-cultivated with Allium sativum extract Arch Physiol Biochem2015 Feb121(1)19-25

Why Emphasize Mushrooms

bull Increase nerve growth factors (NGF)

bull Hericium erinaceus (Yamabushitake or Lionrsquos Mane) stimulate the production of NGF (in vitro)

bull Activate natural killer cells

bull Prime innate and adaptive immunity

bull Mori K Obara Y Hirota M Azumi Y Kinugasa S Inatomi S Nakahata N Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human

astrocytoma cells Biol Pharm Bull 2008 Sep31(9)1727-32

bull Lee DH Kim HW Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway Int J Med Mushrooms 201416(1)1-16

bull Akramiene D Kondrotas A Didziapetriene J Kevelaitis E Effects of beta-glucans on the immune system Medicina (Kaunas)200743(8)597-606

bull Lai PL Naidu MSabaratnam VWong K DaviP Kuppusamy UR Abdullah N Malek SN Neurotrophic properties of the Lions mane medicinal mushroom

Hericium erinaceus (Higher Basidiomycetes) from Malaysia Int J Med Mushrooms201315(6)539-54

bull Phan CW David P Naidu M Wong KH Sabaratnam V Therapeutic potential of culinary-medicinal mushrooms for the management of

neurodegenerative diseases diversity metabolite and mechanism Crit Rev Biotechnol201535(3)355-68

Why Greens

bull Vitamin K1 metabolized to K2-mk7 in gut

bull K2 important in hellip

ndash Myelin production

ndash Calcium influx into bones and teeth

bull Carotenoids magnesium

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 15: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

Mediterranean diet adherence and risk of multiple sclerosis ndash Case control study

bull N=70 RRMS 140 controls Interviews re diet

bull Reduced risk of MS

ndash Fruits (OR=028 95 CI 012-063 p-value 0002)

ndash Vegetables (OR=023 95 CI 010-053 p-value 0001)

Mediterranean diet adherence and risk of multiple sclerosis a case-control study Asia Pac J Clin Nutr 201625(2)377-84

Mediterranean Diet bull High olive oil

bull High vegetable polyphenol

bull Whole grains

bull Low red meat

Potential for diet to prevent and remediate cognitive deficits in neurological disordersNutr Rev 2018 Mar 176(3)204-217The Role of Diet in Multiple Sclerosis Mechanistic Connections and Current EvidenceCurr Nutr Rep 2018 Aug 16Anti-inflammatory Activity of Extra Virgin Olive Oil Polyphenols Which Role in the Prevention and Treatment of Immune-Mediated Inflammatory DiseasesEndocr Metab Immune Disord Drug Targets 201818(1)36-50

bull The following slides represent the rationale for the dietary intervention we are studying in the Dietary Approaches to Treating MS Related Fatigue

bull This protocol is not validated nor does it currently meet the current evidence based guideline criteria as set forth by the American Academy of Neurology or the Academy of Nutrition and Dietetics

Dairy amp MSCasein Gluten amp Schizophrenia

bull Liquid cow milk (not cheese) and MS prevalence was highly correlated (rho = 0836) across 27 countries and 29 populations

bull IgG to Casein and gluten were significantly uarrin recent onset and non-recent onset schizophrenia compared to controls (ple000001-0004)

1 Correlation between milk and dairy product consumption and multiple sclerosis prevalence a worldwide

study Neuroepidemiology 199211(4-6)304-12

2 Severance EG Alaedini A Yang S Halling M Gressitt KL Stallings CR Origoni AE Vaughan C

Khushalani S Leweke FM Dickerson FB Yolken RH Gastrointestinal inflammation and associated

immune activation in schizophrenia Schizophr Res2012 Jun138(1)48-53

Gluten and Casein and Opioids

bull Gluten can be degraded into several morphine-like substances named gluten exorphins

bull Milk proteins are particularly strong allergens and are additional source of bioactive peptides including β-casomorphin-7 and exerts its influence on nervous digestive and immune functions via the opioid receptor

1 The opioid effects of gluten exorphins asymptomatic celiac disease J Health PopulNutr 2015 Nov 243324

2 Opioid receptor ligands derived from food proteins Curr Pharm Des 20039(16)1331-44

3 β-casomorphin-7 alters μ-opioid receptor and dipeptidyl peptidase IV genes expression in children with atopic dermatitis Peptides 2014 Dec62144-9

Nutrition in Parkinsons Disease

Seidl SE Santiago JA Bilyk H Potashkin JA The emerging role of nutrition in Parkinsons disease Front Aging Neurosci 2014 Mar 7636 doi 103389fnagi201400036 eCollection 2014

Gluten sensitivity is an abnormal immune response to gluten in genetically susceptible individuals and may manifest solely with neurological dysfunction 90 of gluten sensitive individuals have no GI symptoms

Lancet Neurol 2010 Mar9(3)318-30 Hadjivassiliou M

Figure 2 MRI in four patients with gluten encephalopathy The extent and variability of white matter abnormalities caused by gluten sensitivity can be seen in these four patients (AndashD) A and C show diffuse white matter changes whereas B and D show more f

Marios Hadjivassiliou David S Sanders Richard A Gruumlnewald Nicola Woodroofe Sabrina Boscolo Daniel Aeschl

Gluten sensitivity from gut to brain

The Lancet Neurology Volume 9 Issue 3 2010 318 - 330

httpdxdoiorg101016S1474-4422(09)70290-X

MS and Gluten References 1 Gluten antibodies in patients with multiple sclerosis Hum Nutr Appl

Nutr 1984 Apr38(2)142-32 Multiple sclerosis and gluten sensitivity Clin Neurol Neurosurg 2007

Oct109(8)651-33 Prevalence of celiac disease in multiple sclerosis BMC Neurol 2011 Mar

711314 Celiac disease with neurologic manifestations in children Rev Med Chir

Soc Med Nat Iasi 2013 Jan-Mar117(1)88-945 Celiac disease with cerebral and peripheral nerve involvement

mimicking multiple sclerosis J Med Life 2014 Sep 157(3)440-4 Epub2014 Sep 25

6 A case of multiple sclerosis and celiac disease Case Rep NeurolMed 20132013576921

7 Gluten-related disorders gluten ataxia Dig Dis 201533(2)264-88 Transglutaminase-6 is an autoantigen in progressive multiple sclerosis and

is upregulated in reactive astrocytes Mult Scler 2016 Dec 11352458516684022

9 The progression of coeliac disease its neurological and psychiatric implications Nutr Res Rev 2017 Jun30(1)25-35

Risks of Eggs

bull Prosndash Grass fed - DHA choline biotin lutein Vitamins A D K2 and

B3 B6 B9 B12

bull Cons ndash Eggs are most common food allergen in IBD gt70ndash 60 allergy patients have IgG Ab to eggsndash 13 seasonal allergies have IgG Ab to eggs ndash Wheat milk eggs are common food triggers to Eosinophilic

Esophagitis

References next slide

References Risks of Eggs bull Wang G Ren J Li G et al The utility of food antigen test in the diagnosis of Crohnrsquos disease

and remission maintenance after exclusive enteral nutrition Clin Res Hepatol Gastroenterol 201842(2)145-152 doi101016jclinre201709002

bull Shakoor Z AlFaifi A AlAmro B AlTawil LN AlOhaly RY Prevalence of IgG-mediated food intolerance among patients with allergic symptoms Ann Saudi Med 2016 Nov-Dec36(6)386-390

bull Dhanapala P De Silva C Doran T Suphioglu C Cracking the egg An insight into egg hypersensitivity Mol Immunol 2015 Aug66(2)375-83 doi 101016jmolimm201504016

bull Pang KA Pang KP Pang EB Tan YN Chan YH Siow JK Food allergy and allergic rhinitis in 435 asian patients - A descriptive review Med J Malaysia 2017 Aug72(4)215-220

bull Philpott H Nandurkar S Royce SG Thien F Gibson PR Allergy tests do not predict food triggers in adult patients with eosinophilic oesophagitis A comprehensive prospective study using five modalities Aliment Pharmacol Ther 2016 Aug44(3)223-33 doi 101111apt13676

bull Cai C Shen J Zhao D et al Serological Investigation of Food Specific Immunoglobulin G Antibodies in Patients with Inflammatory Bowel Diseases Boone DL ed PLoS ONE 20149(11)e112154 doi101371journalpone0112154

Lectins

bull ldquoBy eliminating dietary elements particularly lectins which adversely influence both enterocyte and lymphocyte structure and function it is proposed that the peripheral antigenic stimulus (both pathogenic and dietary) will be reduced and thereby result in a diminution of disease symptoms in certain patients with RArdquo

Cordain L Toohey L Smith MJ Hickey MS Modulation of immune function by dietary lectins in rheumatoid arthritis British Journal of Nutrition 200083(03)207-217

bull Lectins are proteins found in plants and animals that bind sugars (hemagglutinins)

bull They can bind the glycoproteins on the intestinal lining leading to barrier damage

bull Lectins are found in most foods but are especially high in grains (esp wheat) dairy legumes and nightshade vegetables

bull Most traditional methods cooking these foods such as soaking ferment-ing amp cooking will decrease the lectin content

Nutrient Triage

bull Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage

ndash Zn Mg biotin Vitamin K D A

ndash Lipoic Acid Acetyl carnitine

Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triageProc Natl Acad Sci U S A 2006 Nov 21103(47)17589-94

What to Eat

Fruit and vegetable consumption and mortality from all causes cardiovascular disease and cancer systematic review and dose-response meta-analysis of prospective cohort studies

16 studies - 833234 participants

BMJ 2014 349 g4490

BMJ 2014 349 g4490

Risk of all cause mortality associated with servingsday of fruit and vegetables

Dose-response relation between fruit and vegetable consumption and risk of all cause mortality

BMJ 2014 349 g4490

Myelin

ndash Omega 3 Fatty Acids

ndash Thiamine (B1)

ndash Folate (B9)

ndash Cobolamin (B12)

ndash Minerals

Key Micronutrients

Bourre JM Effects of nutrients (in food) on the structure and function of the nervous

system update on dietary requirements for brain Part 1 micronutrients

Part 2 Macronutriients

J Nutr Health Aging 200610(5)377-85

Bowman Nutrient biomarker patterns cognitive function and MRI measures of

brain aging Neurology 2012 Jan 2478(4)241-9 Bowman

Sulfur Rich Foods

Why Brassica and Allium

bull Improve detoxification

bull Increase glutathione production

bull Increase GABA production

bull Enhance Neuroprotection

bull Improve endothelial function

Brassica and Allium References

1 Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimers Disease Med Cell Longev20152015781938

2 Learning and memory promoting effects of crude garlic extract Indian J Exp Biol2013 Dec51(12)1094-100

3 Enhancement of the neuroprotective activity of Hericiumerinaceus mycelium co-cultivated with Allium sativum extract Arch Physiol Biochem2015 Feb121(1)19-25

Why Emphasize Mushrooms

bull Increase nerve growth factors (NGF)

bull Hericium erinaceus (Yamabushitake or Lionrsquos Mane) stimulate the production of NGF (in vitro)

bull Activate natural killer cells

bull Prime innate and adaptive immunity

bull Mori K Obara Y Hirota M Azumi Y Kinugasa S Inatomi S Nakahata N Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human

astrocytoma cells Biol Pharm Bull 2008 Sep31(9)1727-32

bull Lee DH Kim HW Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway Int J Med Mushrooms 201416(1)1-16

bull Akramiene D Kondrotas A Didziapetriene J Kevelaitis E Effects of beta-glucans on the immune system Medicina (Kaunas)200743(8)597-606

bull Lai PL Naidu MSabaratnam VWong K DaviP Kuppusamy UR Abdullah N Malek SN Neurotrophic properties of the Lions mane medicinal mushroom

Hericium erinaceus (Higher Basidiomycetes) from Malaysia Int J Med Mushrooms201315(6)539-54

bull Phan CW David P Naidu M Wong KH Sabaratnam V Therapeutic potential of culinary-medicinal mushrooms for the management of

neurodegenerative diseases diversity metabolite and mechanism Crit Rev Biotechnol201535(3)355-68

Why Greens

bull Vitamin K1 metabolized to K2-mk7 in gut

bull K2 important in hellip

ndash Myelin production

ndash Calcium influx into bones and teeth

bull Carotenoids magnesium

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 16: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

Mediterranean Diet bull High olive oil

bull High vegetable polyphenol

bull Whole grains

bull Low red meat

Potential for diet to prevent and remediate cognitive deficits in neurological disordersNutr Rev 2018 Mar 176(3)204-217The Role of Diet in Multiple Sclerosis Mechanistic Connections and Current EvidenceCurr Nutr Rep 2018 Aug 16Anti-inflammatory Activity of Extra Virgin Olive Oil Polyphenols Which Role in the Prevention and Treatment of Immune-Mediated Inflammatory DiseasesEndocr Metab Immune Disord Drug Targets 201818(1)36-50

bull The following slides represent the rationale for the dietary intervention we are studying in the Dietary Approaches to Treating MS Related Fatigue

bull This protocol is not validated nor does it currently meet the current evidence based guideline criteria as set forth by the American Academy of Neurology or the Academy of Nutrition and Dietetics

Dairy amp MSCasein Gluten amp Schizophrenia

bull Liquid cow milk (not cheese) and MS prevalence was highly correlated (rho = 0836) across 27 countries and 29 populations

bull IgG to Casein and gluten were significantly uarrin recent onset and non-recent onset schizophrenia compared to controls (ple000001-0004)

1 Correlation between milk and dairy product consumption and multiple sclerosis prevalence a worldwide

study Neuroepidemiology 199211(4-6)304-12

2 Severance EG Alaedini A Yang S Halling M Gressitt KL Stallings CR Origoni AE Vaughan C

Khushalani S Leweke FM Dickerson FB Yolken RH Gastrointestinal inflammation and associated

immune activation in schizophrenia Schizophr Res2012 Jun138(1)48-53

Gluten and Casein and Opioids

bull Gluten can be degraded into several morphine-like substances named gluten exorphins

bull Milk proteins are particularly strong allergens and are additional source of bioactive peptides including β-casomorphin-7 and exerts its influence on nervous digestive and immune functions via the opioid receptor

1 The opioid effects of gluten exorphins asymptomatic celiac disease J Health PopulNutr 2015 Nov 243324

2 Opioid receptor ligands derived from food proteins Curr Pharm Des 20039(16)1331-44

3 β-casomorphin-7 alters μ-opioid receptor and dipeptidyl peptidase IV genes expression in children with atopic dermatitis Peptides 2014 Dec62144-9

Nutrition in Parkinsons Disease

Seidl SE Santiago JA Bilyk H Potashkin JA The emerging role of nutrition in Parkinsons disease Front Aging Neurosci 2014 Mar 7636 doi 103389fnagi201400036 eCollection 2014

Gluten sensitivity is an abnormal immune response to gluten in genetically susceptible individuals and may manifest solely with neurological dysfunction 90 of gluten sensitive individuals have no GI symptoms

Lancet Neurol 2010 Mar9(3)318-30 Hadjivassiliou M

Figure 2 MRI in four patients with gluten encephalopathy The extent and variability of white matter abnormalities caused by gluten sensitivity can be seen in these four patients (AndashD) A and C show diffuse white matter changes whereas B and D show more f

Marios Hadjivassiliou David S Sanders Richard A Gruumlnewald Nicola Woodroofe Sabrina Boscolo Daniel Aeschl

Gluten sensitivity from gut to brain

The Lancet Neurology Volume 9 Issue 3 2010 318 - 330

httpdxdoiorg101016S1474-4422(09)70290-X

MS and Gluten References 1 Gluten antibodies in patients with multiple sclerosis Hum Nutr Appl

Nutr 1984 Apr38(2)142-32 Multiple sclerosis and gluten sensitivity Clin Neurol Neurosurg 2007

Oct109(8)651-33 Prevalence of celiac disease in multiple sclerosis BMC Neurol 2011 Mar

711314 Celiac disease with neurologic manifestations in children Rev Med Chir

Soc Med Nat Iasi 2013 Jan-Mar117(1)88-945 Celiac disease with cerebral and peripheral nerve involvement

mimicking multiple sclerosis J Med Life 2014 Sep 157(3)440-4 Epub2014 Sep 25

6 A case of multiple sclerosis and celiac disease Case Rep NeurolMed 20132013576921

7 Gluten-related disorders gluten ataxia Dig Dis 201533(2)264-88 Transglutaminase-6 is an autoantigen in progressive multiple sclerosis and

is upregulated in reactive astrocytes Mult Scler 2016 Dec 11352458516684022

9 The progression of coeliac disease its neurological and psychiatric implications Nutr Res Rev 2017 Jun30(1)25-35

Risks of Eggs

bull Prosndash Grass fed - DHA choline biotin lutein Vitamins A D K2 and

B3 B6 B9 B12

bull Cons ndash Eggs are most common food allergen in IBD gt70ndash 60 allergy patients have IgG Ab to eggsndash 13 seasonal allergies have IgG Ab to eggs ndash Wheat milk eggs are common food triggers to Eosinophilic

Esophagitis

References next slide

References Risks of Eggs bull Wang G Ren J Li G et al The utility of food antigen test in the diagnosis of Crohnrsquos disease

and remission maintenance after exclusive enteral nutrition Clin Res Hepatol Gastroenterol 201842(2)145-152 doi101016jclinre201709002

bull Shakoor Z AlFaifi A AlAmro B AlTawil LN AlOhaly RY Prevalence of IgG-mediated food intolerance among patients with allergic symptoms Ann Saudi Med 2016 Nov-Dec36(6)386-390

bull Dhanapala P De Silva C Doran T Suphioglu C Cracking the egg An insight into egg hypersensitivity Mol Immunol 2015 Aug66(2)375-83 doi 101016jmolimm201504016

bull Pang KA Pang KP Pang EB Tan YN Chan YH Siow JK Food allergy and allergic rhinitis in 435 asian patients - A descriptive review Med J Malaysia 2017 Aug72(4)215-220

bull Philpott H Nandurkar S Royce SG Thien F Gibson PR Allergy tests do not predict food triggers in adult patients with eosinophilic oesophagitis A comprehensive prospective study using five modalities Aliment Pharmacol Ther 2016 Aug44(3)223-33 doi 101111apt13676

bull Cai C Shen J Zhao D et al Serological Investigation of Food Specific Immunoglobulin G Antibodies in Patients with Inflammatory Bowel Diseases Boone DL ed PLoS ONE 20149(11)e112154 doi101371journalpone0112154

Lectins

bull ldquoBy eliminating dietary elements particularly lectins which adversely influence both enterocyte and lymphocyte structure and function it is proposed that the peripheral antigenic stimulus (both pathogenic and dietary) will be reduced and thereby result in a diminution of disease symptoms in certain patients with RArdquo

Cordain L Toohey L Smith MJ Hickey MS Modulation of immune function by dietary lectins in rheumatoid arthritis British Journal of Nutrition 200083(03)207-217

bull Lectins are proteins found in plants and animals that bind sugars (hemagglutinins)

bull They can bind the glycoproteins on the intestinal lining leading to barrier damage

bull Lectins are found in most foods but are especially high in grains (esp wheat) dairy legumes and nightshade vegetables

bull Most traditional methods cooking these foods such as soaking ferment-ing amp cooking will decrease the lectin content

Nutrient Triage

bull Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage

ndash Zn Mg biotin Vitamin K D A

ndash Lipoic Acid Acetyl carnitine

Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triageProc Natl Acad Sci U S A 2006 Nov 21103(47)17589-94

What to Eat

Fruit and vegetable consumption and mortality from all causes cardiovascular disease and cancer systematic review and dose-response meta-analysis of prospective cohort studies

16 studies - 833234 participants

BMJ 2014 349 g4490

BMJ 2014 349 g4490

Risk of all cause mortality associated with servingsday of fruit and vegetables

Dose-response relation between fruit and vegetable consumption and risk of all cause mortality

BMJ 2014 349 g4490

Myelin

ndash Omega 3 Fatty Acids

ndash Thiamine (B1)

ndash Folate (B9)

ndash Cobolamin (B12)

ndash Minerals

Key Micronutrients

Bourre JM Effects of nutrients (in food) on the structure and function of the nervous

system update on dietary requirements for brain Part 1 micronutrients

Part 2 Macronutriients

J Nutr Health Aging 200610(5)377-85

Bowman Nutrient biomarker patterns cognitive function and MRI measures of

brain aging Neurology 2012 Jan 2478(4)241-9 Bowman

Sulfur Rich Foods

Why Brassica and Allium

bull Improve detoxification

bull Increase glutathione production

bull Increase GABA production

bull Enhance Neuroprotection

bull Improve endothelial function

Brassica and Allium References

1 Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimers Disease Med Cell Longev20152015781938

2 Learning and memory promoting effects of crude garlic extract Indian J Exp Biol2013 Dec51(12)1094-100

3 Enhancement of the neuroprotective activity of Hericiumerinaceus mycelium co-cultivated with Allium sativum extract Arch Physiol Biochem2015 Feb121(1)19-25

Why Emphasize Mushrooms

bull Increase nerve growth factors (NGF)

bull Hericium erinaceus (Yamabushitake or Lionrsquos Mane) stimulate the production of NGF (in vitro)

bull Activate natural killer cells

bull Prime innate and adaptive immunity

bull Mori K Obara Y Hirota M Azumi Y Kinugasa S Inatomi S Nakahata N Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human

astrocytoma cells Biol Pharm Bull 2008 Sep31(9)1727-32

bull Lee DH Kim HW Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway Int J Med Mushrooms 201416(1)1-16

bull Akramiene D Kondrotas A Didziapetriene J Kevelaitis E Effects of beta-glucans on the immune system Medicina (Kaunas)200743(8)597-606

bull Lai PL Naidu MSabaratnam VWong K DaviP Kuppusamy UR Abdullah N Malek SN Neurotrophic properties of the Lions mane medicinal mushroom

Hericium erinaceus (Higher Basidiomycetes) from Malaysia Int J Med Mushrooms201315(6)539-54

bull Phan CW David P Naidu M Wong KH Sabaratnam V Therapeutic potential of culinary-medicinal mushrooms for the management of

neurodegenerative diseases diversity metabolite and mechanism Crit Rev Biotechnol201535(3)355-68

Why Greens

bull Vitamin K1 metabolized to K2-mk7 in gut

bull K2 important in hellip

ndash Myelin production

ndash Calcium influx into bones and teeth

bull Carotenoids magnesium

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 17: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

bull The following slides represent the rationale for the dietary intervention we are studying in the Dietary Approaches to Treating MS Related Fatigue

bull This protocol is not validated nor does it currently meet the current evidence based guideline criteria as set forth by the American Academy of Neurology or the Academy of Nutrition and Dietetics

Dairy amp MSCasein Gluten amp Schizophrenia

bull Liquid cow milk (not cheese) and MS prevalence was highly correlated (rho = 0836) across 27 countries and 29 populations

bull IgG to Casein and gluten were significantly uarrin recent onset and non-recent onset schizophrenia compared to controls (ple000001-0004)

1 Correlation between milk and dairy product consumption and multiple sclerosis prevalence a worldwide

study Neuroepidemiology 199211(4-6)304-12

2 Severance EG Alaedini A Yang S Halling M Gressitt KL Stallings CR Origoni AE Vaughan C

Khushalani S Leweke FM Dickerson FB Yolken RH Gastrointestinal inflammation and associated

immune activation in schizophrenia Schizophr Res2012 Jun138(1)48-53

Gluten and Casein and Opioids

bull Gluten can be degraded into several morphine-like substances named gluten exorphins

bull Milk proteins are particularly strong allergens and are additional source of bioactive peptides including β-casomorphin-7 and exerts its influence on nervous digestive and immune functions via the opioid receptor

1 The opioid effects of gluten exorphins asymptomatic celiac disease J Health PopulNutr 2015 Nov 243324

2 Opioid receptor ligands derived from food proteins Curr Pharm Des 20039(16)1331-44

3 β-casomorphin-7 alters μ-opioid receptor and dipeptidyl peptidase IV genes expression in children with atopic dermatitis Peptides 2014 Dec62144-9

Nutrition in Parkinsons Disease

Seidl SE Santiago JA Bilyk H Potashkin JA The emerging role of nutrition in Parkinsons disease Front Aging Neurosci 2014 Mar 7636 doi 103389fnagi201400036 eCollection 2014

Gluten sensitivity is an abnormal immune response to gluten in genetically susceptible individuals and may manifest solely with neurological dysfunction 90 of gluten sensitive individuals have no GI symptoms

Lancet Neurol 2010 Mar9(3)318-30 Hadjivassiliou M

Figure 2 MRI in four patients with gluten encephalopathy The extent and variability of white matter abnormalities caused by gluten sensitivity can be seen in these four patients (AndashD) A and C show diffuse white matter changes whereas B and D show more f

Marios Hadjivassiliou David S Sanders Richard A Gruumlnewald Nicola Woodroofe Sabrina Boscolo Daniel Aeschl

Gluten sensitivity from gut to brain

The Lancet Neurology Volume 9 Issue 3 2010 318 - 330

httpdxdoiorg101016S1474-4422(09)70290-X

MS and Gluten References 1 Gluten antibodies in patients with multiple sclerosis Hum Nutr Appl

Nutr 1984 Apr38(2)142-32 Multiple sclerosis and gluten sensitivity Clin Neurol Neurosurg 2007

Oct109(8)651-33 Prevalence of celiac disease in multiple sclerosis BMC Neurol 2011 Mar

711314 Celiac disease with neurologic manifestations in children Rev Med Chir

Soc Med Nat Iasi 2013 Jan-Mar117(1)88-945 Celiac disease with cerebral and peripheral nerve involvement

mimicking multiple sclerosis J Med Life 2014 Sep 157(3)440-4 Epub2014 Sep 25

6 A case of multiple sclerosis and celiac disease Case Rep NeurolMed 20132013576921

7 Gluten-related disorders gluten ataxia Dig Dis 201533(2)264-88 Transglutaminase-6 is an autoantigen in progressive multiple sclerosis and

is upregulated in reactive astrocytes Mult Scler 2016 Dec 11352458516684022

9 The progression of coeliac disease its neurological and psychiatric implications Nutr Res Rev 2017 Jun30(1)25-35

Risks of Eggs

bull Prosndash Grass fed - DHA choline biotin lutein Vitamins A D K2 and

B3 B6 B9 B12

bull Cons ndash Eggs are most common food allergen in IBD gt70ndash 60 allergy patients have IgG Ab to eggsndash 13 seasonal allergies have IgG Ab to eggs ndash Wheat milk eggs are common food triggers to Eosinophilic

Esophagitis

References next slide

References Risks of Eggs bull Wang G Ren J Li G et al The utility of food antigen test in the diagnosis of Crohnrsquos disease

and remission maintenance after exclusive enteral nutrition Clin Res Hepatol Gastroenterol 201842(2)145-152 doi101016jclinre201709002

bull Shakoor Z AlFaifi A AlAmro B AlTawil LN AlOhaly RY Prevalence of IgG-mediated food intolerance among patients with allergic symptoms Ann Saudi Med 2016 Nov-Dec36(6)386-390

bull Dhanapala P De Silva C Doran T Suphioglu C Cracking the egg An insight into egg hypersensitivity Mol Immunol 2015 Aug66(2)375-83 doi 101016jmolimm201504016

bull Pang KA Pang KP Pang EB Tan YN Chan YH Siow JK Food allergy and allergic rhinitis in 435 asian patients - A descriptive review Med J Malaysia 2017 Aug72(4)215-220

bull Philpott H Nandurkar S Royce SG Thien F Gibson PR Allergy tests do not predict food triggers in adult patients with eosinophilic oesophagitis A comprehensive prospective study using five modalities Aliment Pharmacol Ther 2016 Aug44(3)223-33 doi 101111apt13676

bull Cai C Shen J Zhao D et al Serological Investigation of Food Specific Immunoglobulin G Antibodies in Patients with Inflammatory Bowel Diseases Boone DL ed PLoS ONE 20149(11)e112154 doi101371journalpone0112154

Lectins

bull ldquoBy eliminating dietary elements particularly lectins which adversely influence both enterocyte and lymphocyte structure and function it is proposed that the peripheral antigenic stimulus (both pathogenic and dietary) will be reduced and thereby result in a diminution of disease symptoms in certain patients with RArdquo

Cordain L Toohey L Smith MJ Hickey MS Modulation of immune function by dietary lectins in rheumatoid arthritis British Journal of Nutrition 200083(03)207-217

bull Lectins are proteins found in plants and animals that bind sugars (hemagglutinins)

bull They can bind the glycoproteins on the intestinal lining leading to barrier damage

bull Lectins are found in most foods but are especially high in grains (esp wheat) dairy legumes and nightshade vegetables

bull Most traditional methods cooking these foods such as soaking ferment-ing amp cooking will decrease the lectin content

Nutrient Triage

bull Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage

ndash Zn Mg biotin Vitamin K D A

ndash Lipoic Acid Acetyl carnitine

Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triageProc Natl Acad Sci U S A 2006 Nov 21103(47)17589-94

What to Eat

Fruit and vegetable consumption and mortality from all causes cardiovascular disease and cancer systematic review and dose-response meta-analysis of prospective cohort studies

16 studies - 833234 participants

BMJ 2014 349 g4490

BMJ 2014 349 g4490

Risk of all cause mortality associated with servingsday of fruit and vegetables

Dose-response relation between fruit and vegetable consumption and risk of all cause mortality

BMJ 2014 349 g4490

Myelin

ndash Omega 3 Fatty Acids

ndash Thiamine (B1)

ndash Folate (B9)

ndash Cobolamin (B12)

ndash Minerals

Key Micronutrients

Bourre JM Effects of nutrients (in food) on the structure and function of the nervous

system update on dietary requirements for brain Part 1 micronutrients

Part 2 Macronutriients

J Nutr Health Aging 200610(5)377-85

Bowman Nutrient biomarker patterns cognitive function and MRI measures of

brain aging Neurology 2012 Jan 2478(4)241-9 Bowman

Sulfur Rich Foods

Why Brassica and Allium

bull Improve detoxification

bull Increase glutathione production

bull Increase GABA production

bull Enhance Neuroprotection

bull Improve endothelial function

Brassica and Allium References

1 Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimers Disease Med Cell Longev20152015781938

2 Learning and memory promoting effects of crude garlic extract Indian J Exp Biol2013 Dec51(12)1094-100

3 Enhancement of the neuroprotective activity of Hericiumerinaceus mycelium co-cultivated with Allium sativum extract Arch Physiol Biochem2015 Feb121(1)19-25

Why Emphasize Mushrooms

bull Increase nerve growth factors (NGF)

bull Hericium erinaceus (Yamabushitake or Lionrsquos Mane) stimulate the production of NGF (in vitro)

bull Activate natural killer cells

bull Prime innate and adaptive immunity

bull Mori K Obara Y Hirota M Azumi Y Kinugasa S Inatomi S Nakahata N Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human

astrocytoma cells Biol Pharm Bull 2008 Sep31(9)1727-32

bull Lee DH Kim HW Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway Int J Med Mushrooms 201416(1)1-16

bull Akramiene D Kondrotas A Didziapetriene J Kevelaitis E Effects of beta-glucans on the immune system Medicina (Kaunas)200743(8)597-606

bull Lai PL Naidu MSabaratnam VWong K DaviP Kuppusamy UR Abdullah N Malek SN Neurotrophic properties of the Lions mane medicinal mushroom

Hericium erinaceus (Higher Basidiomycetes) from Malaysia Int J Med Mushrooms201315(6)539-54

bull Phan CW David P Naidu M Wong KH Sabaratnam V Therapeutic potential of culinary-medicinal mushrooms for the management of

neurodegenerative diseases diversity metabolite and mechanism Crit Rev Biotechnol201535(3)355-68

Why Greens

bull Vitamin K1 metabolized to K2-mk7 in gut

bull K2 important in hellip

ndash Myelin production

ndash Calcium influx into bones and teeth

bull Carotenoids magnesium

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 18: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

bull This protocol is not validated nor does it currently meet the current evidence based guideline criteria as set forth by the American Academy of Neurology or the Academy of Nutrition and Dietetics

Dairy amp MSCasein Gluten amp Schizophrenia

bull Liquid cow milk (not cheese) and MS prevalence was highly correlated (rho = 0836) across 27 countries and 29 populations

bull IgG to Casein and gluten were significantly uarrin recent onset and non-recent onset schizophrenia compared to controls (ple000001-0004)

1 Correlation between milk and dairy product consumption and multiple sclerosis prevalence a worldwide

study Neuroepidemiology 199211(4-6)304-12

2 Severance EG Alaedini A Yang S Halling M Gressitt KL Stallings CR Origoni AE Vaughan C

Khushalani S Leweke FM Dickerson FB Yolken RH Gastrointestinal inflammation and associated

immune activation in schizophrenia Schizophr Res2012 Jun138(1)48-53

Gluten and Casein and Opioids

bull Gluten can be degraded into several morphine-like substances named gluten exorphins

bull Milk proteins are particularly strong allergens and are additional source of bioactive peptides including β-casomorphin-7 and exerts its influence on nervous digestive and immune functions via the opioid receptor

1 The opioid effects of gluten exorphins asymptomatic celiac disease J Health PopulNutr 2015 Nov 243324

2 Opioid receptor ligands derived from food proteins Curr Pharm Des 20039(16)1331-44

3 β-casomorphin-7 alters μ-opioid receptor and dipeptidyl peptidase IV genes expression in children with atopic dermatitis Peptides 2014 Dec62144-9

Nutrition in Parkinsons Disease

Seidl SE Santiago JA Bilyk H Potashkin JA The emerging role of nutrition in Parkinsons disease Front Aging Neurosci 2014 Mar 7636 doi 103389fnagi201400036 eCollection 2014

Gluten sensitivity is an abnormal immune response to gluten in genetically susceptible individuals and may manifest solely with neurological dysfunction 90 of gluten sensitive individuals have no GI symptoms

Lancet Neurol 2010 Mar9(3)318-30 Hadjivassiliou M

Figure 2 MRI in four patients with gluten encephalopathy The extent and variability of white matter abnormalities caused by gluten sensitivity can be seen in these four patients (AndashD) A and C show diffuse white matter changes whereas B and D show more f

Marios Hadjivassiliou David S Sanders Richard A Gruumlnewald Nicola Woodroofe Sabrina Boscolo Daniel Aeschl

Gluten sensitivity from gut to brain

The Lancet Neurology Volume 9 Issue 3 2010 318 - 330

httpdxdoiorg101016S1474-4422(09)70290-X

MS and Gluten References 1 Gluten antibodies in patients with multiple sclerosis Hum Nutr Appl

Nutr 1984 Apr38(2)142-32 Multiple sclerosis and gluten sensitivity Clin Neurol Neurosurg 2007

Oct109(8)651-33 Prevalence of celiac disease in multiple sclerosis BMC Neurol 2011 Mar

711314 Celiac disease with neurologic manifestations in children Rev Med Chir

Soc Med Nat Iasi 2013 Jan-Mar117(1)88-945 Celiac disease with cerebral and peripheral nerve involvement

mimicking multiple sclerosis J Med Life 2014 Sep 157(3)440-4 Epub2014 Sep 25

6 A case of multiple sclerosis and celiac disease Case Rep NeurolMed 20132013576921

7 Gluten-related disorders gluten ataxia Dig Dis 201533(2)264-88 Transglutaminase-6 is an autoantigen in progressive multiple sclerosis and

is upregulated in reactive astrocytes Mult Scler 2016 Dec 11352458516684022

9 The progression of coeliac disease its neurological and psychiatric implications Nutr Res Rev 2017 Jun30(1)25-35

Risks of Eggs

bull Prosndash Grass fed - DHA choline biotin lutein Vitamins A D K2 and

B3 B6 B9 B12

bull Cons ndash Eggs are most common food allergen in IBD gt70ndash 60 allergy patients have IgG Ab to eggsndash 13 seasonal allergies have IgG Ab to eggs ndash Wheat milk eggs are common food triggers to Eosinophilic

Esophagitis

References next slide

References Risks of Eggs bull Wang G Ren J Li G et al The utility of food antigen test in the diagnosis of Crohnrsquos disease

and remission maintenance after exclusive enteral nutrition Clin Res Hepatol Gastroenterol 201842(2)145-152 doi101016jclinre201709002

bull Shakoor Z AlFaifi A AlAmro B AlTawil LN AlOhaly RY Prevalence of IgG-mediated food intolerance among patients with allergic symptoms Ann Saudi Med 2016 Nov-Dec36(6)386-390

bull Dhanapala P De Silva C Doran T Suphioglu C Cracking the egg An insight into egg hypersensitivity Mol Immunol 2015 Aug66(2)375-83 doi 101016jmolimm201504016

bull Pang KA Pang KP Pang EB Tan YN Chan YH Siow JK Food allergy and allergic rhinitis in 435 asian patients - A descriptive review Med J Malaysia 2017 Aug72(4)215-220

bull Philpott H Nandurkar S Royce SG Thien F Gibson PR Allergy tests do not predict food triggers in adult patients with eosinophilic oesophagitis A comprehensive prospective study using five modalities Aliment Pharmacol Ther 2016 Aug44(3)223-33 doi 101111apt13676

bull Cai C Shen J Zhao D et al Serological Investigation of Food Specific Immunoglobulin G Antibodies in Patients with Inflammatory Bowel Diseases Boone DL ed PLoS ONE 20149(11)e112154 doi101371journalpone0112154

Lectins

bull ldquoBy eliminating dietary elements particularly lectins which adversely influence both enterocyte and lymphocyte structure and function it is proposed that the peripheral antigenic stimulus (both pathogenic and dietary) will be reduced and thereby result in a diminution of disease symptoms in certain patients with RArdquo

Cordain L Toohey L Smith MJ Hickey MS Modulation of immune function by dietary lectins in rheumatoid arthritis British Journal of Nutrition 200083(03)207-217

bull Lectins are proteins found in plants and animals that bind sugars (hemagglutinins)

bull They can bind the glycoproteins on the intestinal lining leading to barrier damage

bull Lectins are found in most foods but are especially high in grains (esp wheat) dairy legumes and nightshade vegetables

bull Most traditional methods cooking these foods such as soaking ferment-ing amp cooking will decrease the lectin content

Nutrient Triage

bull Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage

ndash Zn Mg biotin Vitamin K D A

ndash Lipoic Acid Acetyl carnitine

Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triageProc Natl Acad Sci U S A 2006 Nov 21103(47)17589-94

What to Eat

Fruit and vegetable consumption and mortality from all causes cardiovascular disease and cancer systematic review and dose-response meta-analysis of prospective cohort studies

16 studies - 833234 participants

BMJ 2014 349 g4490

BMJ 2014 349 g4490

Risk of all cause mortality associated with servingsday of fruit and vegetables

Dose-response relation between fruit and vegetable consumption and risk of all cause mortality

BMJ 2014 349 g4490

Myelin

ndash Omega 3 Fatty Acids

ndash Thiamine (B1)

ndash Folate (B9)

ndash Cobolamin (B12)

ndash Minerals

Key Micronutrients

Bourre JM Effects of nutrients (in food) on the structure and function of the nervous

system update on dietary requirements for brain Part 1 micronutrients

Part 2 Macronutriients

J Nutr Health Aging 200610(5)377-85

Bowman Nutrient biomarker patterns cognitive function and MRI measures of

brain aging Neurology 2012 Jan 2478(4)241-9 Bowman

Sulfur Rich Foods

Why Brassica and Allium

bull Improve detoxification

bull Increase glutathione production

bull Increase GABA production

bull Enhance Neuroprotection

bull Improve endothelial function

Brassica and Allium References

1 Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimers Disease Med Cell Longev20152015781938

2 Learning and memory promoting effects of crude garlic extract Indian J Exp Biol2013 Dec51(12)1094-100

3 Enhancement of the neuroprotective activity of Hericiumerinaceus mycelium co-cultivated with Allium sativum extract Arch Physiol Biochem2015 Feb121(1)19-25

Why Emphasize Mushrooms

bull Increase nerve growth factors (NGF)

bull Hericium erinaceus (Yamabushitake or Lionrsquos Mane) stimulate the production of NGF (in vitro)

bull Activate natural killer cells

bull Prime innate and adaptive immunity

bull Mori K Obara Y Hirota M Azumi Y Kinugasa S Inatomi S Nakahata N Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human

astrocytoma cells Biol Pharm Bull 2008 Sep31(9)1727-32

bull Lee DH Kim HW Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway Int J Med Mushrooms 201416(1)1-16

bull Akramiene D Kondrotas A Didziapetriene J Kevelaitis E Effects of beta-glucans on the immune system Medicina (Kaunas)200743(8)597-606

bull Lai PL Naidu MSabaratnam VWong K DaviP Kuppusamy UR Abdullah N Malek SN Neurotrophic properties of the Lions mane medicinal mushroom

Hericium erinaceus (Higher Basidiomycetes) from Malaysia Int J Med Mushrooms201315(6)539-54

bull Phan CW David P Naidu M Wong KH Sabaratnam V Therapeutic potential of culinary-medicinal mushrooms for the management of

neurodegenerative diseases diversity metabolite and mechanism Crit Rev Biotechnol201535(3)355-68

Why Greens

bull Vitamin K1 metabolized to K2-mk7 in gut

bull K2 important in hellip

ndash Myelin production

ndash Calcium influx into bones and teeth

bull Carotenoids magnesium

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 19: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

Dairy amp MSCasein Gluten amp Schizophrenia

bull Liquid cow milk (not cheese) and MS prevalence was highly correlated (rho = 0836) across 27 countries and 29 populations

bull IgG to Casein and gluten were significantly uarrin recent onset and non-recent onset schizophrenia compared to controls (ple000001-0004)

1 Correlation between milk and dairy product consumption and multiple sclerosis prevalence a worldwide

study Neuroepidemiology 199211(4-6)304-12

2 Severance EG Alaedini A Yang S Halling M Gressitt KL Stallings CR Origoni AE Vaughan C

Khushalani S Leweke FM Dickerson FB Yolken RH Gastrointestinal inflammation and associated

immune activation in schizophrenia Schizophr Res2012 Jun138(1)48-53

Gluten and Casein and Opioids

bull Gluten can be degraded into several morphine-like substances named gluten exorphins

bull Milk proteins are particularly strong allergens and are additional source of bioactive peptides including β-casomorphin-7 and exerts its influence on nervous digestive and immune functions via the opioid receptor

1 The opioid effects of gluten exorphins asymptomatic celiac disease J Health PopulNutr 2015 Nov 243324

2 Opioid receptor ligands derived from food proteins Curr Pharm Des 20039(16)1331-44

3 β-casomorphin-7 alters μ-opioid receptor and dipeptidyl peptidase IV genes expression in children with atopic dermatitis Peptides 2014 Dec62144-9

Nutrition in Parkinsons Disease

Seidl SE Santiago JA Bilyk H Potashkin JA The emerging role of nutrition in Parkinsons disease Front Aging Neurosci 2014 Mar 7636 doi 103389fnagi201400036 eCollection 2014

Gluten sensitivity is an abnormal immune response to gluten in genetically susceptible individuals and may manifest solely with neurological dysfunction 90 of gluten sensitive individuals have no GI symptoms

Lancet Neurol 2010 Mar9(3)318-30 Hadjivassiliou M

Figure 2 MRI in four patients with gluten encephalopathy The extent and variability of white matter abnormalities caused by gluten sensitivity can be seen in these four patients (AndashD) A and C show diffuse white matter changes whereas B and D show more f

Marios Hadjivassiliou David S Sanders Richard A Gruumlnewald Nicola Woodroofe Sabrina Boscolo Daniel Aeschl

Gluten sensitivity from gut to brain

The Lancet Neurology Volume 9 Issue 3 2010 318 - 330

httpdxdoiorg101016S1474-4422(09)70290-X

MS and Gluten References 1 Gluten antibodies in patients with multiple sclerosis Hum Nutr Appl

Nutr 1984 Apr38(2)142-32 Multiple sclerosis and gluten sensitivity Clin Neurol Neurosurg 2007

Oct109(8)651-33 Prevalence of celiac disease in multiple sclerosis BMC Neurol 2011 Mar

711314 Celiac disease with neurologic manifestations in children Rev Med Chir

Soc Med Nat Iasi 2013 Jan-Mar117(1)88-945 Celiac disease with cerebral and peripheral nerve involvement

mimicking multiple sclerosis J Med Life 2014 Sep 157(3)440-4 Epub2014 Sep 25

6 A case of multiple sclerosis and celiac disease Case Rep NeurolMed 20132013576921

7 Gluten-related disorders gluten ataxia Dig Dis 201533(2)264-88 Transglutaminase-6 is an autoantigen in progressive multiple sclerosis and

is upregulated in reactive astrocytes Mult Scler 2016 Dec 11352458516684022

9 The progression of coeliac disease its neurological and psychiatric implications Nutr Res Rev 2017 Jun30(1)25-35

Risks of Eggs

bull Prosndash Grass fed - DHA choline biotin lutein Vitamins A D K2 and

B3 B6 B9 B12

bull Cons ndash Eggs are most common food allergen in IBD gt70ndash 60 allergy patients have IgG Ab to eggsndash 13 seasonal allergies have IgG Ab to eggs ndash Wheat milk eggs are common food triggers to Eosinophilic

Esophagitis

References next slide

References Risks of Eggs bull Wang G Ren J Li G et al The utility of food antigen test in the diagnosis of Crohnrsquos disease

and remission maintenance after exclusive enteral nutrition Clin Res Hepatol Gastroenterol 201842(2)145-152 doi101016jclinre201709002

bull Shakoor Z AlFaifi A AlAmro B AlTawil LN AlOhaly RY Prevalence of IgG-mediated food intolerance among patients with allergic symptoms Ann Saudi Med 2016 Nov-Dec36(6)386-390

bull Dhanapala P De Silva C Doran T Suphioglu C Cracking the egg An insight into egg hypersensitivity Mol Immunol 2015 Aug66(2)375-83 doi 101016jmolimm201504016

bull Pang KA Pang KP Pang EB Tan YN Chan YH Siow JK Food allergy and allergic rhinitis in 435 asian patients - A descriptive review Med J Malaysia 2017 Aug72(4)215-220

bull Philpott H Nandurkar S Royce SG Thien F Gibson PR Allergy tests do not predict food triggers in adult patients with eosinophilic oesophagitis A comprehensive prospective study using five modalities Aliment Pharmacol Ther 2016 Aug44(3)223-33 doi 101111apt13676

bull Cai C Shen J Zhao D et al Serological Investigation of Food Specific Immunoglobulin G Antibodies in Patients with Inflammatory Bowel Diseases Boone DL ed PLoS ONE 20149(11)e112154 doi101371journalpone0112154

Lectins

bull ldquoBy eliminating dietary elements particularly lectins which adversely influence both enterocyte and lymphocyte structure and function it is proposed that the peripheral antigenic stimulus (both pathogenic and dietary) will be reduced and thereby result in a diminution of disease symptoms in certain patients with RArdquo

Cordain L Toohey L Smith MJ Hickey MS Modulation of immune function by dietary lectins in rheumatoid arthritis British Journal of Nutrition 200083(03)207-217

bull Lectins are proteins found in plants and animals that bind sugars (hemagglutinins)

bull They can bind the glycoproteins on the intestinal lining leading to barrier damage

bull Lectins are found in most foods but are especially high in grains (esp wheat) dairy legumes and nightshade vegetables

bull Most traditional methods cooking these foods such as soaking ferment-ing amp cooking will decrease the lectin content

Nutrient Triage

bull Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage

ndash Zn Mg biotin Vitamin K D A

ndash Lipoic Acid Acetyl carnitine

Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triageProc Natl Acad Sci U S A 2006 Nov 21103(47)17589-94

What to Eat

Fruit and vegetable consumption and mortality from all causes cardiovascular disease and cancer systematic review and dose-response meta-analysis of prospective cohort studies

16 studies - 833234 participants

BMJ 2014 349 g4490

BMJ 2014 349 g4490

Risk of all cause mortality associated with servingsday of fruit and vegetables

Dose-response relation between fruit and vegetable consumption and risk of all cause mortality

BMJ 2014 349 g4490

Myelin

ndash Omega 3 Fatty Acids

ndash Thiamine (B1)

ndash Folate (B9)

ndash Cobolamin (B12)

ndash Minerals

Key Micronutrients

Bourre JM Effects of nutrients (in food) on the structure and function of the nervous

system update on dietary requirements for brain Part 1 micronutrients

Part 2 Macronutriients

J Nutr Health Aging 200610(5)377-85

Bowman Nutrient biomarker patterns cognitive function and MRI measures of

brain aging Neurology 2012 Jan 2478(4)241-9 Bowman

Sulfur Rich Foods

Why Brassica and Allium

bull Improve detoxification

bull Increase glutathione production

bull Increase GABA production

bull Enhance Neuroprotection

bull Improve endothelial function

Brassica and Allium References

1 Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimers Disease Med Cell Longev20152015781938

2 Learning and memory promoting effects of crude garlic extract Indian J Exp Biol2013 Dec51(12)1094-100

3 Enhancement of the neuroprotective activity of Hericiumerinaceus mycelium co-cultivated with Allium sativum extract Arch Physiol Biochem2015 Feb121(1)19-25

Why Emphasize Mushrooms

bull Increase nerve growth factors (NGF)

bull Hericium erinaceus (Yamabushitake or Lionrsquos Mane) stimulate the production of NGF (in vitro)

bull Activate natural killer cells

bull Prime innate and adaptive immunity

bull Mori K Obara Y Hirota M Azumi Y Kinugasa S Inatomi S Nakahata N Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human

astrocytoma cells Biol Pharm Bull 2008 Sep31(9)1727-32

bull Lee DH Kim HW Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway Int J Med Mushrooms 201416(1)1-16

bull Akramiene D Kondrotas A Didziapetriene J Kevelaitis E Effects of beta-glucans on the immune system Medicina (Kaunas)200743(8)597-606

bull Lai PL Naidu MSabaratnam VWong K DaviP Kuppusamy UR Abdullah N Malek SN Neurotrophic properties of the Lions mane medicinal mushroom

Hericium erinaceus (Higher Basidiomycetes) from Malaysia Int J Med Mushrooms201315(6)539-54

bull Phan CW David P Naidu M Wong KH Sabaratnam V Therapeutic potential of culinary-medicinal mushrooms for the management of

neurodegenerative diseases diversity metabolite and mechanism Crit Rev Biotechnol201535(3)355-68

Why Greens

bull Vitamin K1 metabolized to K2-mk7 in gut

bull K2 important in hellip

ndash Myelin production

ndash Calcium influx into bones and teeth

bull Carotenoids magnesium

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 20: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

Gluten and Casein and Opioids

bull Gluten can be degraded into several morphine-like substances named gluten exorphins

bull Milk proteins are particularly strong allergens and are additional source of bioactive peptides including β-casomorphin-7 and exerts its influence on nervous digestive and immune functions via the opioid receptor

1 The opioid effects of gluten exorphins asymptomatic celiac disease J Health PopulNutr 2015 Nov 243324

2 Opioid receptor ligands derived from food proteins Curr Pharm Des 20039(16)1331-44

3 β-casomorphin-7 alters μ-opioid receptor and dipeptidyl peptidase IV genes expression in children with atopic dermatitis Peptides 2014 Dec62144-9

Nutrition in Parkinsons Disease

Seidl SE Santiago JA Bilyk H Potashkin JA The emerging role of nutrition in Parkinsons disease Front Aging Neurosci 2014 Mar 7636 doi 103389fnagi201400036 eCollection 2014

Gluten sensitivity is an abnormal immune response to gluten in genetically susceptible individuals and may manifest solely with neurological dysfunction 90 of gluten sensitive individuals have no GI symptoms

Lancet Neurol 2010 Mar9(3)318-30 Hadjivassiliou M

Figure 2 MRI in four patients with gluten encephalopathy The extent and variability of white matter abnormalities caused by gluten sensitivity can be seen in these four patients (AndashD) A and C show diffuse white matter changes whereas B and D show more f

Marios Hadjivassiliou David S Sanders Richard A Gruumlnewald Nicola Woodroofe Sabrina Boscolo Daniel Aeschl

Gluten sensitivity from gut to brain

The Lancet Neurology Volume 9 Issue 3 2010 318 - 330

httpdxdoiorg101016S1474-4422(09)70290-X

MS and Gluten References 1 Gluten antibodies in patients with multiple sclerosis Hum Nutr Appl

Nutr 1984 Apr38(2)142-32 Multiple sclerosis and gluten sensitivity Clin Neurol Neurosurg 2007

Oct109(8)651-33 Prevalence of celiac disease in multiple sclerosis BMC Neurol 2011 Mar

711314 Celiac disease with neurologic manifestations in children Rev Med Chir

Soc Med Nat Iasi 2013 Jan-Mar117(1)88-945 Celiac disease with cerebral and peripheral nerve involvement

mimicking multiple sclerosis J Med Life 2014 Sep 157(3)440-4 Epub2014 Sep 25

6 A case of multiple sclerosis and celiac disease Case Rep NeurolMed 20132013576921

7 Gluten-related disorders gluten ataxia Dig Dis 201533(2)264-88 Transglutaminase-6 is an autoantigen in progressive multiple sclerosis and

is upregulated in reactive astrocytes Mult Scler 2016 Dec 11352458516684022

9 The progression of coeliac disease its neurological and psychiatric implications Nutr Res Rev 2017 Jun30(1)25-35

Risks of Eggs

bull Prosndash Grass fed - DHA choline biotin lutein Vitamins A D K2 and

B3 B6 B9 B12

bull Cons ndash Eggs are most common food allergen in IBD gt70ndash 60 allergy patients have IgG Ab to eggsndash 13 seasonal allergies have IgG Ab to eggs ndash Wheat milk eggs are common food triggers to Eosinophilic

Esophagitis

References next slide

References Risks of Eggs bull Wang G Ren J Li G et al The utility of food antigen test in the diagnosis of Crohnrsquos disease

and remission maintenance after exclusive enteral nutrition Clin Res Hepatol Gastroenterol 201842(2)145-152 doi101016jclinre201709002

bull Shakoor Z AlFaifi A AlAmro B AlTawil LN AlOhaly RY Prevalence of IgG-mediated food intolerance among patients with allergic symptoms Ann Saudi Med 2016 Nov-Dec36(6)386-390

bull Dhanapala P De Silva C Doran T Suphioglu C Cracking the egg An insight into egg hypersensitivity Mol Immunol 2015 Aug66(2)375-83 doi 101016jmolimm201504016

bull Pang KA Pang KP Pang EB Tan YN Chan YH Siow JK Food allergy and allergic rhinitis in 435 asian patients - A descriptive review Med J Malaysia 2017 Aug72(4)215-220

bull Philpott H Nandurkar S Royce SG Thien F Gibson PR Allergy tests do not predict food triggers in adult patients with eosinophilic oesophagitis A comprehensive prospective study using five modalities Aliment Pharmacol Ther 2016 Aug44(3)223-33 doi 101111apt13676

bull Cai C Shen J Zhao D et al Serological Investigation of Food Specific Immunoglobulin G Antibodies in Patients with Inflammatory Bowel Diseases Boone DL ed PLoS ONE 20149(11)e112154 doi101371journalpone0112154

Lectins

bull ldquoBy eliminating dietary elements particularly lectins which adversely influence both enterocyte and lymphocyte structure and function it is proposed that the peripheral antigenic stimulus (both pathogenic and dietary) will be reduced and thereby result in a diminution of disease symptoms in certain patients with RArdquo

Cordain L Toohey L Smith MJ Hickey MS Modulation of immune function by dietary lectins in rheumatoid arthritis British Journal of Nutrition 200083(03)207-217

bull Lectins are proteins found in plants and animals that bind sugars (hemagglutinins)

bull They can bind the glycoproteins on the intestinal lining leading to barrier damage

bull Lectins are found in most foods but are especially high in grains (esp wheat) dairy legumes and nightshade vegetables

bull Most traditional methods cooking these foods such as soaking ferment-ing amp cooking will decrease the lectin content

Nutrient Triage

bull Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage

ndash Zn Mg biotin Vitamin K D A

ndash Lipoic Acid Acetyl carnitine

Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triageProc Natl Acad Sci U S A 2006 Nov 21103(47)17589-94

What to Eat

Fruit and vegetable consumption and mortality from all causes cardiovascular disease and cancer systematic review and dose-response meta-analysis of prospective cohort studies

16 studies - 833234 participants

BMJ 2014 349 g4490

BMJ 2014 349 g4490

Risk of all cause mortality associated with servingsday of fruit and vegetables

Dose-response relation between fruit and vegetable consumption and risk of all cause mortality

BMJ 2014 349 g4490

Myelin

ndash Omega 3 Fatty Acids

ndash Thiamine (B1)

ndash Folate (B9)

ndash Cobolamin (B12)

ndash Minerals

Key Micronutrients

Bourre JM Effects of nutrients (in food) on the structure and function of the nervous

system update on dietary requirements for brain Part 1 micronutrients

Part 2 Macronutriients

J Nutr Health Aging 200610(5)377-85

Bowman Nutrient biomarker patterns cognitive function and MRI measures of

brain aging Neurology 2012 Jan 2478(4)241-9 Bowman

Sulfur Rich Foods

Why Brassica and Allium

bull Improve detoxification

bull Increase glutathione production

bull Increase GABA production

bull Enhance Neuroprotection

bull Improve endothelial function

Brassica and Allium References

1 Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimers Disease Med Cell Longev20152015781938

2 Learning and memory promoting effects of crude garlic extract Indian J Exp Biol2013 Dec51(12)1094-100

3 Enhancement of the neuroprotective activity of Hericiumerinaceus mycelium co-cultivated with Allium sativum extract Arch Physiol Biochem2015 Feb121(1)19-25

Why Emphasize Mushrooms

bull Increase nerve growth factors (NGF)

bull Hericium erinaceus (Yamabushitake or Lionrsquos Mane) stimulate the production of NGF (in vitro)

bull Activate natural killer cells

bull Prime innate and adaptive immunity

bull Mori K Obara Y Hirota M Azumi Y Kinugasa S Inatomi S Nakahata N Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human

astrocytoma cells Biol Pharm Bull 2008 Sep31(9)1727-32

bull Lee DH Kim HW Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway Int J Med Mushrooms 201416(1)1-16

bull Akramiene D Kondrotas A Didziapetriene J Kevelaitis E Effects of beta-glucans on the immune system Medicina (Kaunas)200743(8)597-606

bull Lai PL Naidu MSabaratnam VWong K DaviP Kuppusamy UR Abdullah N Malek SN Neurotrophic properties of the Lions mane medicinal mushroom

Hericium erinaceus (Higher Basidiomycetes) from Malaysia Int J Med Mushrooms201315(6)539-54

bull Phan CW David P Naidu M Wong KH Sabaratnam V Therapeutic potential of culinary-medicinal mushrooms for the management of

neurodegenerative diseases diversity metabolite and mechanism Crit Rev Biotechnol201535(3)355-68

Why Greens

bull Vitamin K1 metabolized to K2-mk7 in gut

bull K2 important in hellip

ndash Myelin production

ndash Calcium influx into bones and teeth

bull Carotenoids magnesium

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 21: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

Nutrition in Parkinsons Disease

Seidl SE Santiago JA Bilyk H Potashkin JA The emerging role of nutrition in Parkinsons disease Front Aging Neurosci 2014 Mar 7636 doi 103389fnagi201400036 eCollection 2014

Gluten sensitivity is an abnormal immune response to gluten in genetically susceptible individuals and may manifest solely with neurological dysfunction 90 of gluten sensitive individuals have no GI symptoms

Lancet Neurol 2010 Mar9(3)318-30 Hadjivassiliou M

Figure 2 MRI in four patients with gluten encephalopathy The extent and variability of white matter abnormalities caused by gluten sensitivity can be seen in these four patients (AndashD) A and C show diffuse white matter changes whereas B and D show more f

Marios Hadjivassiliou David S Sanders Richard A Gruumlnewald Nicola Woodroofe Sabrina Boscolo Daniel Aeschl

Gluten sensitivity from gut to brain

The Lancet Neurology Volume 9 Issue 3 2010 318 - 330

httpdxdoiorg101016S1474-4422(09)70290-X

MS and Gluten References 1 Gluten antibodies in patients with multiple sclerosis Hum Nutr Appl

Nutr 1984 Apr38(2)142-32 Multiple sclerosis and gluten sensitivity Clin Neurol Neurosurg 2007

Oct109(8)651-33 Prevalence of celiac disease in multiple sclerosis BMC Neurol 2011 Mar

711314 Celiac disease with neurologic manifestations in children Rev Med Chir

Soc Med Nat Iasi 2013 Jan-Mar117(1)88-945 Celiac disease with cerebral and peripheral nerve involvement

mimicking multiple sclerosis J Med Life 2014 Sep 157(3)440-4 Epub2014 Sep 25

6 A case of multiple sclerosis and celiac disease Case Rep NeurolMed 20132013576921

7 Gluten-related disorders gluten ataxia Dig Dis 201533(2)264-88 Transglutaminase-6 is an autoantigen in progressive multiple sclerosis and

is upregulated in reactive astrocytes Mult Scler 2016 Dec 11352458516684022

9 The progression of coeliac disease its neurological and psychiatric implications Nutr Res Rev 2017 Jun30(1)25-35

Risks of Eggs

bull Prosndash Grass fed - DHA choline biotin lutein Vitamins A D K2 and

B3 B6 B9 B12

bull Cons ndash Eggs are most common food allergen in IBD gt70ndash 60 allergy patients have IgG Ab to eggsndash 13 seasonal allergies have IgG Ab to eggs ndash Wheat milk eggs are common food triggers to Eosinophilic

Esophagitis

References next slide

References Risks of Eggs bull Wang G Ren J Li G et al The utility of food antigen test in the diagnosis of Crohnrsquos disease

and remission maintenance after exclusive enteral nutrition Clin Res Hepatol Gastroenterol 201842(2)145-152 doi101016jclinre201709002

bull Shakoor Z AlFaifi A AlAmro B AlTawil LN AlOhaly RY Prevalence of IgG-mediated food intolerance among patients with allergic symptoms Ann Saudi Med 2016 Nov-Dec36(6)386-390

bull Dhanapala P De Silva C Doran T Suphioglu C Cracking the egg An insight into egg hypersensitivity Mol Immunol 2015 Aug66(2)375-83 doi 101016jmolimm201504016

bull Pang KA Pang KP Pang EB Tan YN Chan YH Siow JK Food allergy and allergic rhinitis in 435 asian patients - A descriptive review Med J Malaysia 2017 Aug72(4)215-220

bull Philpott H Nandurkar S Royce SG Thien F Gibson PR Allergy tests do not predict food triggers in adult patients with eosinophilic oesophagitis A comprehensive prospective study using five modalities Aliment Pharmacol Ther 2016 Aug44(3)223-33 doi 101111apt13676

bull Cai C Shen J Zhao D et al Serological Investigation of Food Specific Immunoglobulin G Antibodies in Patients with Inflammatory Bowel Diseases Boone DL ed PLoS ONE 20149(11)e112154 doi101371journalpone0112154

Lectins

bull ldquoBy eliminating dietary elements particularly lectins which adversely influence both enterocyte and lymphocyte structure and function it is proposed that the peripheral antigenic stimulus (both pathogenic and dietary) will be reduced and thereby result in a diminution of disease symptoms in certain patients with RArdquo

Cordain L Toohey L Smith MJ Hickey MS Modulation of immune function by dietary lectins in rheumatoid arthritis British Journal of Nutrition 200083(03)207-217

bull Lectins are proteins found in plants and animals that bind sugars (hemagglutinins)

bull They can bind the glycoproteins on the intestinal lining leading to barrier damage

bull Lectins are found in most foods but are especially high in grains (esp wheat) dairy legumes and nightshade vegetables

bull Most traditional methods cooking these foods such as soaking ferment-ing amp cooking will decrease the lectin content

Nutrient Triage

bull Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage

ndash Zn Mg biotin Vitamin K D A

ndash Lipoic Acid Acetyl carnitine

Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triageProc Natl Acad Sci U S A 2006 Nov 21103(47)17589-94

What to Eat

Fruit and vegetable consumption and mortality from all causes cardiovascular disease and cancer systematic review and dose-response meta-analysis of prospective cohort studies

16 studies - 833234 participants

BMJ 2014 349 g4490

BMJ 2014 349 g4490

Risk of all cause mortality associated with servingsday of fruit and vegetables

Dose-response relation between fruit and vegetable consumption and risk of all cause mortality

BMJ 2014 349 g4490

Myelin

ndash Omega 3 Fatty Acids

ndash Thiamine (B1)

ndash Folate (B9)

ndash Cobolamin (B12)

ndash Minerals

Key Micronutrients

Bourre JM Effects of nutrients (in food) on the structure and function of the nervous

system update on dietary requirements for brain Part 1 micronutrients

Part 2 Macronutriients

J Nutr Health Aging 200610(5)377-85

Bowman Nutrient biomarker patterns cognitive function and MRI measures of

brain aging Neurology 2012 Jan 2478(4)241-9 Bowman

Sulfur Rich Foods

Why Brassica and Allium

bull Improve detoxification

bull Increase glutathione production

bull Increase GABA production

bull Enhance Neuroprotection

bull Improve endothelial function

Brassica and Allium References

1 Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimers Disease Med Cell Longev20152015781938

2 Learning and memory promoting effects of crude garlic extract Indian J Exp Biol2013 Dec51(12)1094-100

3 Enhancement of the neuroprotective activity of Hericiumerinaceus mycelium co-cultivated with Allium sativum extract Arch Physiol Biochem2015 Feb121(1)19-25

Why Emphasize Mushrooms

bull Increase nerve growth factors (NGF)

bull Hericium erinaceus (Yamabushitake or Lionrsquos Mane) stimulate the production of NGF (in vitro)

bull Activate natural killer cells

bull Prime innate and adaptive immunity

bull Mori K Obara Y Hirota M Azumi Y Kinugasa S Inatomi S Nakahata N Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human

astrocytoma cells Biol Pharm Bull 2008 Sep31(9)1727-32

bull Lee DH Kim HW Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway Int J Med Mushrooms 201416(1)1-16

bull Akramiene D Kondrotas A Didziapetriene J Kevelaitis E Effects of beta-glucans on the immune system Medicina (Kaunas)200743(8)597-606

bull Lai PL Naidu MSabaratnam VWong K DaviP Kuppusamy UR Abdullah N Malek SN Neurotrophic properties of the Lions mane medicinal mushroom

Hericium erinaceus (Higher Basidiomycetes) from Malaysia Int J Med Mushrooms201315(6)539-54

bull Phan CW David P Naidu M Wong KH Sabaratnam V Therapeutic potential of culinary-medicinal mushrooms for the management of

neurodegenerative diseases diversity metabolite and mechanism Crit Rev Biotechnol201535(3)355-68

Why Greens

bull Vitamin K1 metabolized to K2-mk7 in gut

bull K2 important in hellip

ndash Myelin production

ndash Calcium influx into bones and teeth

bull Carotenoids magnesium

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 22: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

Gluten sensitivity is an abnormal immune response to gluten in genetically susceptible individuals and may manifest solely with neurological dysfunction 90 of gluten sensitive individuals have no GI symptoms

Lancet Neurol 2010 Mar9(3)318-30 Hadjivassiliou M

Figure 2 MRI in four patients with gluten encephalopathy The extent and variability of white matter abnormalities caused by gluten sensitivity can be seen in these four patients (AndashD) A and C show diffuse white matter changes whereas B and D show more f

Marios Hadjivassiliou David S Sanders Richard A Gruumlnewald Nicola Woodroofe Sabrina Boscolo Daniel Aeschl

Gluten sensitivity from gut to brain

The Lancet Neurology Volume 9 Issue 3 2010 318 - 330

httpdxdoiorg101016S1474-4422(09)70290-X

MS and Gluten References 1 Gluten antibodies in patients with multiple sclerosis Hum Nutr Appl

Nutr 1984 Apr38(2)142-32 Multiple sclerosis and gluten sensitivity Clin Neurol Neurosurg 2007

Oct109(8)651-33 Prevalence of celiac disease in multiple sclerosis BMC Neurol 2011 Mar

711314 Celiac disease with neurologic manifestations in children Rev Med Chir

Soc Med Nat Iasi 2013 Jan-Mar117(1)88-945 Celiac disease with cerebral and peripheral nerve involvement

mimicking multiple sclerosis J Med Life 2014 Sep 157(3)440-4 Epub2014 Sep 25

6 A case of multiple sclerosis and celiac disease Case Rep NeurolMed 20132013576921

7 Gluten-related disorders gluten ataxia Dig Dis 201533(2)264-88 Transglutaminase-6 is an autoantigen in progressive multiple sclerosis and

is upregulated in reactive astrocytes Mult Scler 2016 Dec 11352458516684022

9 The progression of coeliac disease its neurological and psychiatric implications Nutr Res Rev 2017 Jun30(1)25-35

Risks of Eggs

bull Prosndash Grass fed - DHA choline biotin lutein Vitamins A D K2 and

B3 B6 B9 B12

bull Cons ndash Eggs are most common food allergen in IBD gt70ndash 60 allergy patients have IgG Ab to eggsndash 13 seasonal allergies have IgG Ab to eggs ndash Wheat milk eggs are common food triggers to Eosinophilic

Esophagitis

References next slide

References Risks of Eggs bull Wang G Ren J Li G et al The utility of food antigen test in the diagnosis of Crohnrsquos disease

and remission maintenance after exclusive enteral nutrition Clin Res Hepatol Gastroenterol 201842(2)145-152 doi101016jclinre201709002

bull Shakoor Z AlFaifi A AlAmro B AlTawil LN AlOhaly RY Prevalence of IgG-mediated food intolerance among patients with allergic symptoms Ann Saudi Med 2016 Nov-Dec36(6)386-390

bull Dhanapala P De Silva C Doran T Suphioglu C Cracking the egg An insight into egg hypersensitivity Mol Immunol 2015 Aug66(2)375-83 doi 101016jmolimm201504016

bull Pang KA Pang KP Pang EB Tan YN Chan YH Siow JK Food allergy and allergic rhinitis in 435 asian patients - A descriptive review Med J Malaysia 2017 Aug72(4)215-220

bull Philpott H Nandurkar S Royce SG Thien F Gibson PR Allergy tests do not predict food triggers in adult patients with eosinophilic oesophagitis A comprehensive prospective study using five modalities Aliment Pharmacol Ther 2016 Aug44(3)223-33 doi 101111apt13676

bull Cai C Shen J Zhao D et al Serological Investigation of Food Specific Immunoglobulin G Antibodies in Patients with Inflammatory Bowel Diseases Boone DL ed PLoS ONE 20149(11)e112154 doi101371journalpone0112154

Lectins

bull ldquoBy eliminating dietary elements particularly lectins which adversely influence both enterocyte and lymphocyte structure and function it is proposed that the peripheral antigenic stimulus (both pathogenic and dietary) will be reduced and thereby result in a diminution of disease symptoms in certain patients with RArdquo

Cordain L Toohey L Smith MJ Hickey MS Modulation of immune function by dietary lectins in rheumatoid arthritis British Journal of Nutrition 200083(03)207-217

bull Lectins are proteins found in plants and animals that bind sugars (hemagglutinins)

bull They can bind the glycoproteins on the intestinal lining leading to barrier damage

bull Lectins are found in most foods but are especially high in grains (esp wheat) dairy legumes and nightshade vegetables

bull Most traditional methods cooking these foods such as soaking ferment-ing amp cooking will decrease the lectin content

Nutrient Triage

bull Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage

ndash Zn Mg biotin Vitamin K D A

ndash Lipoic Acid Acetyl carnitine

Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triageProc Natl Acad Sci U S A 2006 Nov 21103(47)17589-94

What to Eat

Fruit and vegetable consumption and mortality from all causes cardiovascular disease and cancer systematic review and dose-response meta-analysis of prospective cohort studies

16 studies - 833234 participants

BMJ 2014 349 g4490

BMJ 2014 349 g4490

Risk of all cause mortality associated with servingsday of fruit and vegetables

Dose-response relation between fruit and vegetable consumption and risk of all cause mortality

BMJ 2014 349 g4490

Myelin

ndash Omega 3 Fatty Acids

ndash Thiamine (B1)

ndash Folate (B9)

ndash Cobolamin (B12)

ndash Minerals

Key Micronutrients

Bourre JM Effects of nutrients (in food) on the structure and function of the nervous

system update on dietary requirements for brain Part 1 micronutrients

Part 2 Macronutriients

J Nutr Health Aging 200610(5)377-85

Bowman Nutrient biomarker patterns cognitive function and MRI measures of

brain aging Neurology 2012 Jan 2478(4)241-9 Bowman

Sulfur Rich Foods

Why Brassica and Allium

bull Improve detoxification

bull Increase glutathione production

bull Increase GABA production

bull Enhance Neuroprotection

bull Improve endothelial function

Brassica and Allium References

1 Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimers Disease Med Cell Longev20152015781938

2 Learning and memory promoting effects of crude garlic extract Indian J Exp Biol2013 Dec51(12)1094-100

3 Enhancement of the neuroprotective activity of Hericiumerinaceus mycelium co-cultivated with Allium sativum extract Arch Physiol Biochem2015 Feb121(1)19-25

Why Emphasize Mushrooms

bull Increase nerve growth factors (NGF)

bull Hericium erinaceus (Yamabushitake or Lionrsquos Mane) stimulate the production of NGF (in vitro)

bull Activate natural killer cells

bull Prime innate and adaptive immunity

bull Mori K Obara Y Hirota M Azumi Y Kinugasa S Inatomi S Nakahata N Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human

astrocytoma cells Biol Pharm Bull 2008 Sep31(9)1727-32

bull Lee DH Kim HW Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway Int J Med Mushrooms 201416(1)1-16

bull Akramiene D Kondrotas A Didziapetriene J Kevelaitis E Effects of beta-glucans on the immune system Medicina (Kaunas)200743(8)597-606

bull Lai PL Naidu MSabaratnam VWong K DaviP Kuppusamy UR Abdullah N Malek SN Neurotrophic properties of the Lions mane medicinal mushroom

Hericium erinaceus (Higher Basidiomycetes) from Malaysia Int J Med Mushrooms201315(6)539-54

bull Phan CW David P Naidu M Wong KH Sabaratnam V Therapeutic potential of culinary-medicinal mushrooms for the management of

neurodegenerative diseases diversity metabolite and mechanism Crit Rev Biotechnol201535(3)355-68

Why Greens

bull Vitamin K1 metabolized to K2-mk7 in gut

bull K2 important in hellip

ndash Myelin production

ndash Calcium influx into bones and teeth

bull Carotenoids magnesium

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 23: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

Figure 2 MRI in four patients with gluten encephalopathy The extent and variability of white matter abnormalities caused by gluten sensitivity can be seen in these four patients (AndashD) A and C show diffuse white matter changes whereas B and D show more f

Marios Hadjivassiliou David S Sanders Richard A Gruumlnewald Nicola Woodroofe Sabrina Boscolo Daniel Aeschl

Gluten sensitivity from gut to brain

The Lancet Neurology Volume 9 Issue 3 2010 318 - 330

httpdxdoiorg101016S1474-4422(09)70290-X

MS and Gluten References 1 Gluten antibodies in patients with multiple sclerosis Hum Nutr Appl

Nutr 1984 Apr38(2)142-32 Multiple sclerosis and gluten sensitivity Clin Neurol Neurosurg 2007

Oct109(8)651-33 Prevalence of celiac disease in multiple sclerosis BMC Neurol 2011 Mar

711314 Celiac disease with neurologic manifestations in children Rev Med Chir

Soc Med Nat Iasi 2013 Jan-Mar117(1)88-945 Celiac disease with cerebral and peripheral nerve involvement

mimicking multiple sclerosis J Med Life 2014 Sep 157(3)440-4 Epub2014 Sep 25

6 A case of multiple sclerosis and celiac disease Case Rep NeurolMed 20132013576921

7 Gluten-related disorders gluten ataxia Dig Dis 201533(2)264-88 Transglutaminase-6 is an autoantigen in progressive multiple sclerosis and

is upregulated in reactive astrocytes Mult Scler 2016 Dec 11352458516684022

9 The progression of coeliac disease its neurological and psychiatric implications Nutr Res Rev 2017 Jun30(1)25-35

Risks of Eggs

bull Prosndash Grass fed - DHA choline biotin lutein Vitamins A D K2 and

B3 B6 B9 B12

bull Cons ndash Eggs are most common food allergen in IBD gt70ndash 60 allergy patients have IgG Ab to eggsndash 13 seasonal allergies have IgG Ab to eggs ndash Wheat milk eggs are common food triggers to Eosinophilic

Esophagitis

References next slide

References Risks of Eggs bull Wang G Ren J Li G et al The utility of food antigen test in the diagnosis of Crohnrsquos disease

and remission maintenance after exclusive enteral nutrition Clin Res Hepatol Gastroenterol 201842(2)145-152 doi101016jclinre201709002

bull Shakoor Z AlFaifi A AlAmro B AlTawil LN AlOhaly RY Prevalence of IgG-mediated food intolerance among patients with allergic symptoms Ann Saudi Med 2016 Nov-Dec36(6)386-390

bull Dhanapala P De Silva C Doran T Suphioglu C Cracking the egg An insight into egg hypersensitivity Mol Immunol 2015 Aug66(2)375-83 doi 101016jmolimm201504016

bull Pang KA Pang KP Pang EB Tan YN Chan YH Siow JK Food allergy and allergic rhinitis in 435 asian patients - A descriptive review Med J Malaysia 2017 Aug72(4)215-220

bull Philpott H Nandurkar S Royce SG Thien F Gibson PR Allergy tests do not predict food triggers in adult patients with eosinophilic oesophagitis A comprehensive prospective study using five modalities Aliment Pharmacol Ther 2016 Aug44(3)223-33 doi 101111apt13676

bull Cai C Shen J Zhao D et al Serological Investigation of Food Specific Immunoglobulin G Antibodies in Patients with Inflammatory Bowel Diseases Boone DL ed PLoS ONE 20149(11)e112154 doi101371journalpone0112154

Lectins

bull ldquoBy eliminating dietary elements particularly lectins which adversely influence both enterocyte and lymphocyte structure and function it is proposed that the peripheral antigenic stimulus (both pathogenic and dietary) will be reduced and thereby result in a diminution of disease symptoms in certain patients with RArdquo

Cordain L Toohey L Smith MJ Hickey MS Modulation of immune function by dietary lectins in rheumatoid arthritis British Journal of Nutrition 200083(03)207-217

bull Lectins are proteins found in plants and animals that bind sugars (hemagglutinins)

bull They can bind the glycoproteins on the intestinal lining leading to barrier damage

bull Lectins are found in most foods but are especially high in grains (esp wheat) dairy legumes and nightshade vegetables

bull Most traditional methods cooking these foods such as soaking ferment-ing amp cooking will decrease the lectin content

Nutrient Triage

bull Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage

ndash Zn Mg biotin Vitamin K D A

ndash Lipoic Acid Acetyl carnitine

Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triageProc Natl Acad Sci U S A 2006 Nov 21103(47)17589-94

What to Eat

Fruit and vegetable consumption and mortality from all causes cardiovascular disease and cancer systematic review and dose-response meta-analysis of prospective cohort studies

16 studies - 833234 participants

BMJ 2014 349 g4490

BMJ 2014 349 g4490

Risk of all cause mortality associated with servingsday of fruit and vegetables

Dose-response relation between fruit and vegetable consumption and risk of all cause mortality

BMJ 2014 349 g4490

Myelin

ndash Omega 3 Fatty Acids

ndash Thiamine (B1)

ndash Folate (B9)

ndash Cobolamin (B12)

ndash Minerals

Key Micronutrients

Bourre JM Effects of nutrients (in food) on the structure and function of the nervous

system update on dietary requirements for brain Part 1 micronutrients

Part 2 Macronutriients

J Nutr Health Aging 200610(5)377-85

Bowman Nutrient biomarker patterns cognitive function and MRI measures of

brain aging Neurology 2012 Jan 2478(4)241-9 Bowman

Sulfur Rich Foods

Why Brassica and Allium

bull Improve detoxification

bull Increase glutathione production

bull Increase GABA production

bull Enhance Neuroprotection

bull Improve endothelial function

Brassica and Allium References

1 Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimers Disease Med Cell Longev20152015781938

2 Learning and memory promoting effects of crude garlic extract Indian J Exp Biol2013 Dec51(12)1094-100

3 Enhancement of the neuroprotective activity of Hericiumerinaceus mycelium co-cultivated with Allium sativum extract Arch Physiol Biochem2015 Feb121(1)19-25

Why Emphasize Mushrooms

bull Increase nerve growth factors (NGF)

bull Hericium erinaceus (Yamabushitake or Lionrsquos Mane) stimulate the production of NGF (in vitro)

bull Activate natural killer cells

bull Prime innate and adaptive immunity

bull Mori K Obara Y Hirota M Azumi Y Kinugasa S Inatomi S Nakahata N Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human

astrocytoma cells Biol Pharm Bull 2008 Sep31(9)1727-32

bull Lee DH Kim HW Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway Int J Med Mushrooms 201416(1)1-16

bull Akramiene D Kondrotas A Didziapetriene J Kevelaitis E Effects of beta-glucans on the immune system Medicina (Kaunas)200743(8)597-606

bull Lai PL Naidu MSabaratnam VWong K DaviP Kuppusamy UR Abdullah N Malek SN Neurotrophic properties of the Lions mane medicinal mushroom

Hericium erinaceus (Higher Basidiomycetes) from Malaysia Int J Med Mushrooms201315(6)539-54

bull Phan CW David P Naidu M Wong KH Sabaratnam V Therapeutic potential of culinary-medicinal mushrooms for the management of

neurodegenerative diseases diversity metabolite and mechanism Crit Rev Biotechnol201535(3)355-68

Why Greens

bull Vitamin K1 metabolized to K2-mk7 in gut

bull K2 important in hellip

ndash Myelin production

ndash Calcium influx into bones and teeth

bull Carotenoids magnesium

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 24: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

MS and Gluten References 1 Gluten antibodies in patients with multiple sclerosis Hum Nutr Appl

Nutr 1984 Apr38(2)142-32 Multiple sclerosis and gluten sensitivity Clin Neurol Neurosurg 2007

Oct109(8)651-33 Prevalence of celiac disease in multiple sclerosis BMC Neurol 2011 Mar

711314 Celiac disease with neurologic manifestations in children Rev Med Chir

Soc Med Nat Iasi 2013 Jan-Mar117(1)88-945 Celiac disease with cerebral and peripheral nerve involvement

mimicking multiple sclerosis J Med Life 2014 Sep 157(3)440-4 Epub2014 Sep 25

6 A case of multiple sclerosis and celiac disease Case Rep NeurolMed 20132013576921

7 Gluten-related disorders gluten ataxia Dig Dis 201533(2)264-88 Transglutaminase-6 is an autoantigen in progressive multiple sclerosis and

is upregulated in reactive astrocytes Mult Scler 2016 Dec 11352458516684022

9 The progression of coeliac disease its neurological and psychiatric implications Nutr Res Rev 2017 Jun30(1)25-35

Risks of Eggs

bull Prosndash Grass fed - DHA choline biotin lutein Vitamins A D K2 and

B3 B6 B9 B12

bull Cons ndash Eggs are most common food allergen in IBD gt70ndash 60 allergy patients have IgG Ab to eggsndash 13 seasonal allergies have IgG Ab to eggs ndash Wheat milk eggs are common food triggers to Eosinophilic

Esophagitis

References next slide

References Risks of Eggs bull Wang G Ren J Li G et al The utility of food antigen test in the diagnosis of Crohnrsquos disease

and remission maintenance after exclusive enteral nutrition Clin Res Hepatol Gastroenterol 201842(2)145-152 doi101016jclinre201709002

bull Shakoor Z AlFaifi A AlAmro B AlTawil LN AlOhaly RY Prevalence of IgG-mediated food intolerance among patients with allergic symptoms Ann Saudi Med 2016 Nov-Dec36(6)386-390

bull Dhanapala P De Silva C Doran T Suphioglu C Cracking the egg An insight into egg hypersensitivity Mol Immunol 2015 Aug66(2)375-83 doi 101016jmolimm201504016

bull Pang KA Pang KP Pang EB Tan YN Chan YH Siow JK Food allergy and allergic rhinitis in 435 asian patients - A descriptive review Med J Malaysia 2017 Aug72(4)215-220

bull Philpott H Nandurkar S Royce SG Thien F Gibson PR Allergy tests do not predict food triggers in adult patients with eosinophilic oesophagitis A comprehensive prospective study using five modalities Aliment Pharmacol Ther 2016 Aug44(3)223-33 doi 101111apt13676

bull Cai C Shen J Zhao D et al Serological Investigation of Food Specific Immunoglobulin G Antibodies in Patients with Inflammatory Bowel Diseases Boone DL ed PLoS ONE 20149(11)e112154 doi101371journalpone0112154

Lectins

bull ldquoBy eliminating dietary elements particularly lectins which adversely influence both enterocyte and lymphocyte structure and function it is proposed that the peripheral antigenic stimulus (both pathogenic and dietary) will be reduced and thereby result in a diminution of disease symptoms in certain patients with RArdquo

Cordain L Toohey L Smith MJ Hickey MS Modulation of immune function by dietary lectins in rheumatoid arthritis British Journal of Nutrition 200083(03)207-217

bull Lectins are proteins found in plants and animals that bind sugars (hemagglutinins)

bull They can bind the glycoproteins on the intestinal lining leading to barrier damage

bull Lectins are found in most foods but are especially high in grains (esp wheat) dairy legumes and nightshade vegetables

bull Most traditional methods cooking these foods such as soaking ferment-ing amp cooking will decrease the lectin content

Nutrient Triage

bull Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage

ndash Zn Mg biotin Vitamin K D A

ndash Lipoic Acid Acetyl carnitine

Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triageProc Natl Acad Sci U S A 2006 Nov 21103(47)17589-94

What to Eat

Fruit and vegetable consumption and mortality from all causes cardiovascular disease and cancer systematic review and dose-response meta-analysis of prospective cohort studies

16 studies - 833234 participants

BMJ 2014 349 g4490

BMJ 2014 349 g4490

Risk of all cause mortality associated with servingsday of fruit and vegetables

Dose-response relation between fruit and vegetable consumption and risk of all cause mortality

BMJ 2014 349 g4490

Myelin

ndash Omega 3 Fatty Acids

ndash Thiamine (B1)

ndash Folate (B9)

ndash Cobolamin (B12)

ndash Minerals

Key Micronutrients

Bourre JM Effects of nutrients (in food) on the structure and function of the nervous

system update on dietary requirements for brain Part 1 micronutrients

Part 2 Macronutriients

J Nutr Health Aging 200610(5)377-85

Bowman Nutrient biomarker patterns cognitive function and MRI measures of

brain aging Neurology 2012 Jan 2478(4)241-9 Bowman

Sulfur Rich Foods

Why Brassica and Allium

bull Improve detoxification

bull Increase glutathione production

bull Increase GABA production

bull Enhance Neuroprotection

bull Improve endothelial function

Brassica and Allium References

1 Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimers Disease Med Cell Longev20152015781938

2 Learning and memory promoting effects of crude garlic extract Indian J Exp Biol2013 Dec51(12)1094-100

3 Enhancement of the neuroprotective activity of Hericiumerinaceus mycelium co-cultivated with Allium sativum extract Arch Physiol Biochem2015 Feb121(1)19-25

Why Emphasize Mushrooms

bull Increase nerve growth factors (NGF)

bull Hericium erinaceus (Yamabushitake or Lionrsquos Mane) stimulate the production of NGF (in vitro)

bull Activate natural killer cells

bull Prime innate and adaptive immunity

bull Mori K Obara Y Hirota M Azumi Y Kinugasa S Inatomi S Nakahata N Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human

astrocytoma cells Biol Pharm Bull 2008 Sep31(9)1727-32

bull Lee DH Kim HW Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway Int J Med Mushrooms 201416(1)1-16

bull Akramiene D Kondrotas A Didziapetriene J Kevelaitis E Effects of beta-glucans on the immune system Medicina (Kaunas)200743(8)597-606

bull Lai PL Naidu MSabaratnam VWong K DaviP Kuppusamy UR Abdullah N Malek SN Neurotrophic properties of the Lions mane medicinal mushroom

Hericium erinaceus (Higher Basidiomycetes) from Malaysia Int J Med Mushrooms201315(6)539-54

bull Phan CW David P Naidu M Wong KH Sabaratnam V Therapeutic potential of culinary-medicinal mushrooms for the management of

neurodegenerative diseases diversity metabolite and mechanism Crit Rev Biotechnol201535(3)355-68

Why Greens

bull Vitamin K1 metabolized to K2-mk7 in gut

bull K2 important in hellip

ndash Myelin production

ndash Calcium influx into bones and teeth

bull Carotenoids magnesium

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 25: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

Risks of Eggs

bull Prosndash Grass fed - DHA choline biotin lutein Vitamins A D K2 and

B3 B6 B9 B12

bull Cons ndash Eggs are most common food allergen in IBD gt70ndash 60 allergy patients have IgG Ab to eggsndash 13 seasonal allergies have IgG Ab to eggs ndash Wheat milk eggs are common food triggers to Eosinophilic

Esophagitis

References next slide

References Risks of Eggs bull Wang G Ren J Li G et al The utility of food antigen test in the diagnosis of Crohnrsquos disease

and remission maintenance after exclusive enteral nutrition Clin Res Hepatol Gastroenterol 201842(2)145-152 doi101016jclinre201709002

bull Shakoor Z AlFaifi A AlAmro B AlTawil LN AlOhaly RY Prevalence of IgG-mediated food intolerance among patients with allergic symptoms Ann Saudi Med 2016 Nov-Dec36(6)386-390

bull Dhanapala P De Silva C Doran T Suphioglu C Cracking the egg An insight into egg hypersensitivity Mol Immunol 2015 Aug66(2)375-83 doi 101016jmolimm201504016

bull Pang KA Pang KP Pang EB Tan YN Chan YH Siow JK Food allergy and allergic rhinitis in 435 asian patients - A descriptive review Med J Malaysia 2017 Aug72(4)215-220

bull Philpott H Nandurkar S Royce SG Thien F Gibson PR Allergy tests do not predict food triggers in adult patients with eosinophilic oesophagitis A comprehensive prospective study using five modalities Aliment Pharmacol Ther 2016 Aug44(3)223-33 doi 101111apt13676

bull Cai C Shen J Zhao D et al Serological Investigation of Food Specific Immunoglobulin G Antibodies in Patients with Inflammatory Bowel Diseases Boone DL ed PLoS ONE 20149(11)e112154 doi101371journalpone0112154

Lectins

bull ldquoBy eliminating dietary elements particularly lectins which adversely influence both enterocyte and lymphocyte structure and function it is proposed that the peripheral antigenic stimulus (both pathogenic and dietary) will be reduced and thereby result in a diminution of disease symptoms in certain patients with RArdquo

Cordain L Toohey L Smith MJ Hickey MS Modulation of immune function by dietary lectins in rheumatoid arthritis British Journal of Nutrition 200083(03)207-217

bull Lectins are proteins found in plants and animals that bind sugars (hemagglutinins)

bull They can bind the glycoproteins on the intestinal lining leading to barrier damage

bull Lectins are found in most foods but are especially high in grains (esp wheat) dairy legumes and nightshade vegetables

bull Most traditional methods cooking these foods such as soaking ferment-ing amp cooking will decrease the lectin content

Nutrient Triage

bull Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage

ndash Zn Mg biotin Vitamin K D A

ndash Lipoic Acid Acetyl carnitine

Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triageProc Natl Acad Sci U S A 2006 Nov 21103(47)17589-94

What to Eat

Fruit and vegetable consumption and mortality from all causes cardiovascular disease and cancer systematic review and dose-response meta-analysis of prospective cohort studies

16 studies - 833234 participants

BMJ 2014 349 g4490

BMJ 2014 349 g4490

Risk of all cause mortality associated with servingsday of fruit and vegetables

Dose-response relation between fruit and vegetable consumption and risk of all cause mortality

BMJ 2014 349 g4490

Myelin

ndash Omega 3 Fatty Acids

ndash Thiamine (B1)

ndash Folate (B9)

ndash Cobolamin (B12)

ndash Minerals

Key Micronutrients

Bourre JM Effects of nutrients (in food) on the structure and function of the nervous

system update on dietary requirements for brain Part 1 micronutrients

Part 2 Macronutriients

J Nutr Health Aging 200610(5)377-85

Bowman Nutrient biomarker patterns cognitive function and MRI measures of

brain aging Neurology 2012 Jan 2478(4)241-9 Bowman

Sulfur Rich Foods

Why Brassica and Allium

bull Improve detoxification

bull Increase glutathione production

bull Increase GABA production

bull Enhance Neuroprotection

bull Improve endothelial function

Brassica and Allium References

1 Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimers Disease Med Cell Longev20152015781938

2 Learning and memory promoting effects of crude garlic extract Indian J Exp Biol2013 Dec51(12)1094-100

3 Enhancement of the neuroprotective activity of Hericiumerinaceus mycelium co-cultivated with Allium sativum extract Arch Physiol Biochem2015 Feb121(1)19-25

Why Emphasize Mushrooms

bull Increase nerve growth factors (NGF)

bull Hericium erinaceus (Yamabushitake or Lionrsquos Mane) stimulate the production of NGF (in vitro)

bull Activate natural killer cells

bull Prime innate and adaptive immunity

bull Mori K Obara Y Hirota M Azumi Y Kinugasa S Inatomi S Nakahata N Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human

astrocytoma cells Biol Pharm Bull 2008 Sep31(9)1727-32

bull Lee DH Kim HW Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway Int J Med Mushrooms 201416(1)1-16

bull Akramiene D Kondrotas A Didziapetriene J Kevelaitis E Effects of beta-glucans on the immune system Medicina (Kaunas)200743(8)597-606

bull Lai PL Naidu MSabaratnam VWong K DaviP Kuppusamy UR Abdullah N Malek SN Neurotrophic properties of the Lions mane medicinal mushroom

Hericium erinaceus (Higher Basidiomycetes) from Malaysia Int J Med Mushrooms201315(6)539-54

bull Phan CW David P Naidu M Wong KH Sabaratnam V Therapeutic potential of culinary-medicinal mushrooms for the management of

neurodegenerative diseases diversity metabolite and mechanism Crit Rev Biotechnol201535(3)355-68

Why Greens

bull Vitamin K1 metabolized to K2-mk7 in gut

bull K2 important in hellip

ndash Myelin production

ndash Calcium influx into bones and teeth

bull Carotenoids magnesium

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 26: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

References Risks of Eggs bull Wang G Ren J Li G et al The utility of food antigen test in the diagnosis of Crohnrsquos disease

and remission maintenance after exclusive enteral nutrition Clin Res Hepatol Gastroenterol 201842(2)145-152 doi101016jclinre201709002

bull Shakoor Z AlFaifi A AlAmro B AlTawil LN AlOhaly RY Prevalence of IgG-mediated food intolerance among patients with allergic symptoms Ann Saudi Med 2016 Nov-Dec36(6)386-390

bull Dhanapala P De Silva C Doran T Suphioglu C Cracking the egg An insight into egg hypersensitivity Mol Immunol 2015 Aug66(2)375-83 doi 101016jmolimm201504016

bull Pang KA Pang KP Pang EB Tan YN Chan YH Siow JK Food allergy and allergic rhinitis in 435 asian patients - A descriptive review Med J Malaysia 2017 Aug72(4)215-220

bull Philpott H Nandurkar S Royce SG Thien F Gibson PR Allergy tests do not predict food triggers in adult patients with eosinophilic oesophagitis A comprehensive prospective study using five modalities Aliment Pharmacol Ther 2016 Aug44(3)223-33 doi 101111apt13676

bull Cai C Shen J Zhao D et al Serological Investigation of Food Specific Immunoglobulin G Antibodies in Patients with Inflammatory Bowel Diseases Boone DL ed PLoS ONE 20149(11)e112154 doi101371journalpone0112154

Lectins

bull ldquoBy eliminating dietary elements particularly lectins which adversely influence both enterocyte and lymphocyte structure and function it is proposed that the peripheral antigenic stimulus (both pathogenic and dietary) will be reduced and thereby result in a diminution of disease symptoms in certain patients with RArdquo

Cordain L Toohey L Smith MJ Hickey MS Modulation of immune function by dietary lectins in rheumatoid arthritis British Journal of Nutrition 200083(03)207-217

bull Lectins are proteins found in plants and animals that bind sugars (hemagglutinins)

bull They can bind the glycoproteins on the intestinal lining leading to barrier damage

bull Lectins are found in most foods but are especially high in grains (esp wheat) dairy legumes and nightshade vegetables

bull Most traditional methods cooking these foods such as soaking ferment-ing amp cooking will decrease the lectin content

Nutrient Triage

bull Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage

ndash Zn Mg biotin Vitamin K D A

ndash Lipoic Acid Acetyl carnitine

Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triageProc Natl Acad Sci U S A 2006 Nov 21103(47)17589-94

What to Eat

Fruit and vegetable consumption and mortality from all causes cardiovascular disease and cancer systematic review and dose-response meta-analysis of prospective cohort studies

16 studies - 833234 participants

BMJ 2014 349 g4490

BMJ 2014 349 g4490

Risk of all cause mortality associated with servingsday of fruit and vegetables

Dose-response relation between fruit and vegetable consumption and risk of all cause mortality

BMJ 2014 349 g4490

Myelin

ndash Omega 3 Fatty Acids

ndash Thiamine (B1)

ndash Folate (B9)

ndash Cobolamin (B12)

ndash Minerals

Key Micronutrients

Bourre JM Effects of nutrients (in food) on the structure and function of the nervous

system update on dietary requirements for brain Part 1 micronutrients

Part 2 Macronutriients

J Nutr Health Aging 200610(5)377-85

Bowman Nutrient biomarker patterns cognitive function and MRI measures of

brain aging Neurology 2012 Jan 2478(4)241-9 Bowman

Sulfur Rich Foods

Why Brassica and Allium

bull Improve detoxification

bull Increase glutathione production

bull Increase GABA production

bull Enhance Neuroprotection

bull Improve endothelial function

Brassica and Allium References

1 Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimers Disease Med Cell Longev20152015781938

2 Learning and memory promoting effects of crude garlic extract Indian J Exp Biol2013 Dec51(12)1094-100

3 Enhancement of the neuroprotective activity of Hericiumerinaceus mycelium co-cultivated with Allium sativum extract Arch Physiol Biochem2015 Feb121(1)19-25

Why Emphasize Mushrooms

bull Increase nerve growth factors (NGF)

bull Hericium erinaceus (Yamabushitake or Lionrsquos Mane) stimulate the production of NGF (in vitro)

bull Activate natural killer cells

bull Prime innate and adaptive immunity

bull Mori K Obara Y Hirota M Azumi Y Kinugasa S Inatomi S Nakahata N Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human

astrocytoma cells Biol Pharm Bull 2008 Sep31(9)1727-32

bull Lee DH Kim HW Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway Int J Med Mushrooms 201416(1)1-16

bull Akramiene D Kondrotas A Didziapetriene J Kevelaitis E Effects of beta-glucans on the immune system Medicina (Kaunas)200743(8)597-606

bull Lai PL Naidu MSabaratnam VWong K DaviP Kuppusamy UR Abdullah N Malek SN Neurotrophic properties of the Lions mane medicinal mushroom

Hericium erinaceus (Higher Basidiomycetes) from Malaysia Int J Med Mushrooms201315(6)539-54

bull Phan CW David P Naidu M Wong KH Sabaratnam V Therapeutic potential of culinary-medicinal mushrooms for the management of

neurodegenerative diseases diversity metabolite and mechanism Crit Rev Biotechnol201535(3)355-68

Why Greens

bull Vitamin K1 metabolized to K2-mk7 in gut

bull K2 important in hellip

ndash Myelin production

ndash Calcium influx into bones and teeth

bull Carotenoids magnesium

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 27: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

Lectins

bull ldquoBy eliminating dietary elements particularly lectins which adversely influence both enterocyte and lymphocyte structure and function it is proposed that the peripheral antigenic stimulus (both pathogenic and dietary) will be reduced and thereby result in a diminution of disease symptoms in certain patients with RArdquo

Cordain L Toohey L Smith MJ Hickey MS Modulation of immune function by dietary lectins in rheumatoid arthritis British Journal of Nutrition 200083(03)207-217

bull Lectins are proteins found in plants and animals that bind sugars (hemagglutinins)

bull They can bind the glycoproteins on the intestinal lining leading to barrier damage

bull Lectins are found in most foods but are especially high in grains (esp wheat) dairy legumes and nightshade vegetables

bull Most traditional methods cooking these foods such as soaking ferment-ing amp cooking will decrease the lectin content

Nutrient Triage

bull Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage

ndash Zn Mg biotin Vitamin K D A

ndash Lipoic Acid Acetyl carnitine

Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triageProc Natl Acad Sci U S A 2006 Nov 21103(47)17589-94

What to Eat

Fruit and vegetable consumption and mortality from all causes cardiovascular disease and cancer systematic review and dose-response meta-analysis of prospective cohort studies

16 studies - 833234 participants

BMJ 2014 349 g4490

BMJ 2014 349 g4490

Risk of all cause mortality associated with servingsday of fruit and vegetables

Dose-response relation between fruit and vegetable consumption and risk of all cause mortality

BMJ 2014 349 g4490

Myelin

ndash Omega 3 Fatty Acids

ndash Thiamine (B1)

ndash Folate (B9)

ndash Cobolamin (B12)

ndash Minerals

Key Micronutrients

Bourre JM Effects of nutrients (in food) on the structure and function of the nervous

system update on dietary requirements for brain Part 1 micronutrients

Part 2 Macronutriients

J Nutr Health Aging 200610(5)377-85

Bowman Nutrient biomarker patterns cognitive function and MRI measures of

brain aging Neurology 2012 Jan 2478(4)241-9 Bowman

Sulfur Rich Foods

Why Brassica and Allium

bull Improve detoxification

bull Increase glutathione production

bull Increase GABA production

bull Enhance Neuroprotection

bull Improve endothelial function

Brassica and Allium References

1 Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimers Disease Med Cell Longev20152015781938

2 Learning and memory promoting effects of crude garlic extract Indian J Exp Biol2013 Dec51(12)1094-100

3 Enhancement of the neuroprotective activity of Hericiumerinaceus mycelium co-cultivated with Allium sativum extract Arch Physiol Biochem2015 Feb121(1)19-25

Why Emphasize Mushrooms

bull Increase nerve growth factors (NGF)

bull Hericium erinaceus (Yamabushitake or Lionrsquos Mane) stimulate the production of NGF (in vitro)

bull Activate natural killer cells

bull Prime innate and adaptive immunity

bull Mori K Obara Y Hirota M Azumi Y Kinugasa S Inatomi S Nakahata N Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human

astrocytoma cells Biol Pharm Bull 2008 Sep31(9)1727-32

bull Lee DH Kim HW Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway Int J Med Mushrooms 201416(1)1-16

bull Akramiene D Kondrotas A Didziapetriene J Kevelaitis E Effects of beta-glucans on the immune system Medicina (Kaunas)200743(8)597-606

bull Lai PL Naidu MSabaratnam VWong K DaviP Kuppusamy UR Abdullah N Malek SN Neurotrophic properties of the Lions mane medicinal mushroom

Hericium erinaceus (Higher Basidiomycetes) from Malaysia Int J Med Mushrooms201315(6)539-54

bull Phan CW David P Naidu M Wong KH Sabaratnam V Therapeutic potential of culinary-medicinal mushrooms for the management of

neurodegenerative diseases diversity metabolite and mechanism Crit Rev Biotechnol201535(3)355-68

Why Greens

bull Vitamin K1 metabolized to K2-mk7 in gut

bull K2 important in hellip

ndash Myelin production

ndash Calcium influx into bones and teeth

bull Carotenoids magnesium

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 28: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

bull Lectins are proteins found in plants and animals that bind sugars (hemagglutinins)

bull They can bind the glycoproteins on the intestinal lining leading to barrier damage

bull Lectins are found in most foods but are especially high in grains (esp wheat) dairy legumes and nightshade vegetables

bull Most traditional methods cooking these foods such as soaking ferment-ing amp cooking will decrease the lectin content

Nutrient Triage

bull Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage

ndash Zn Mg biotin Vitamin K D A

ndash Lipoic Acid Acetyl carnitine

Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triageProc Natl Acad Sci U S A 2006 Nov 21103(47)17589-94

What to Eat

Fruit and vegetable consumption and mortality from all causes cardiovascular disease and cancer systematic review and dose-response meta-analysis of prospective cohort studies

16 studies - 833234 participants

BMJ 2014 349 g4490

BMJ 2014 349 g4490

Risk of all cause mortality associated with servingsday of fruit and vegetables

Dose-response relation between fruit and vegetable consumption and risk of all cause mortality

BMJ 2014 349 g4490

Myelin

ndash Omega 3 Fatty Acids

ndash Thiamine (B1)

ndash Folate (B9)

ndash Cobolamin (B12)

ndash Minerals

Key Micronutrients

Bourre JM Effects of nutrients (in food) on the structure and function of the nervous

system update on dietary requirements for brain Part 1 micronutrients

Part 2 Macronutriients

J Nutr Health Aging 200610(5)377-85

Bowman Nutrient biomarker patterns cognitive function and MRI measures of

brain aging Neurology 2012 Jan 2478(4)241-9 Bowman

Sulfur Rich Foods

Why Brassica and Allium

bull Improve detoxification

bull Increase glutathione production

bull Increase GABA production

bull Enhance Neuroprotection

bull Improve endothelial function

Brassica and Allium References

1 Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimers Disease Med Cell Longev20152015781938

2 Learning and memory promoting effects of crude garlic extract Indian J Exp Biol2013 Dec51(12)1094-100

3 Enhancement of the neuroprotective activity of Hericiumerinaceus mycelium co-cultivated with Allium sativum extract Arch Physiol Biochem2015 Feb121(1)19-25

Why Emphasize Mushrooms

bull Increase nerve growth factors (NGF)

bull Hericium erinaceus (Yamabushitake or Lionrsquos Mane) stimulate the production of NGF (in vitro)

bull Activate natural killer cells

bull Prime innate and adaptive immunity

bull Mori K Obara Y Hirota M Azumi Y Kinugasa S Inatomi S Nakahata N Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human

astrocytoma cells Biol Pharm Bull 2008 Sep31(9)1727-32

bull Lee DH Kim HW Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway Int J Med Mushrooms 201416(1)1-16

bull Akramiene D Kondrotas A Didziapetriene J Kevelaitis E Effects of beta-glucans on the immune system Medicina (Kaunas)200743(8)597-606

bull Lai PL Naidu MSabaratnam VWong K DaviP Kuppusamy UR Abdullah N Malek SN Neurotrophic properties of the Lions mane medicinal mushroom

Hericium erinaceus (Higher Basidiomycetes) from Malaysia Int J Med Mushrooms201315(6)539-54

bull Phan CW David P Naidu M Wong KH Sabaratnam V Therapeutic potential of culinary-medicinal mushrooms for the management of

neurodegenerative diseases diversity metabolite and mechanism Crit Rev Biotechnol201535(3)355-68

Why Greens

bull Vitamin K1 metabolized to K2-mk7 in gut

bull K2 important in hellip

ndash Myelin production

ndash Calcium influx into bones and teeth

bull Carotenoids magnesium

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 29: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

Nutrient Triage

bull Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage

ndash Zn Mg biotin Vitamin K D A

ndash Lipoic Acid Acetyl carnitine

Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triageProc Natl Acad Sci U S A 2006 Nov 21103(47)17589-94

What to Eat

Fruit and vegetable consumption and mortality from all causes cardiovascular disease and cancer systematic review and dose-response meta-analysis of prospective cohort studies

16 studies - 833234 participants

BMJ 2014 349 g4490

BMJ 2014 349 g4490

Risk of all cause mortality associated with servingsday of fruit and vegetables

Dose-response relation between fruit and vegetable consumption and risk of all cause mortality

BMJ 2014 349 g4490

Myelin

ndash Omega 3 Fatty Acids

ndash Thiamine (B1)

ndash Folate (B9)

ndash Cobolamin (B12)

ndash Minerals

Key Micronutrients

Bourre JM Effects of nutrients (in food) on the structure and function of the nervous

system update on dietary requirements for brain Part 1 micronutrients

Part 2 Macronutriients

J Nutr Health Aging 200610(5)377-85

Bowman Nutrient biomarker patterns cognitive function and MRI measures of

brain aging Neurology 2012 Jan 2478(4)241-9 Bowman

Sulfur Rich Foods

Why Brassica and Allium

bull Improve detoxification

bull Increase glutathione production

bull Increase GABA production

bull Enhance Neuroprotection

bull Improve endothelial function

Brassica and Allium References

1 Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimers Disease Med Cell Longev20152015781938

2 Learning and memory promoting effects of crude garlic extract Indian J Exp Biol2013 Dec51(12)1094-100

3 Enhancement of the neuroprotective activity of Hericiumerinaceus mycelium co-cultivated with Allium sativum extract Arch Physiol Biochem2015 Feb121(1)19-25

Why Emphasize Mushrooms

bull Increase nerve growth factors (NGF)

bull Hericium erinaceus (Yamabushitake or Lionrsquos Mane) stimulate the production of NGF (in vitro)

bull Activate natural killer cells

bull Prime innate and adaptive immunity

bull Mori K Obara Y Hirota M Azumi Y Kinugasa S Inatomi S Nakahata N Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human

astrocytoma cells Biol Pharm Bull 2008 Sep31(9)1727-32

bull Lee DH Kim HW Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway Int J Med Mushrooms 201416(1)1-16

bull Akramiene D Kondrotas A Didziapetriene J Kevelaitis E Effects of beta-glucans on the immune system Medicina (Kaunas)200743(8)597-606

bull Lai PL Naidu MSabaratnam VWong K DaviP Kuppusamy UR Abdullah N Malek SN Neurotrophic properties of the Lions mane medicinal mushroom

Hericium erinaceus (Higher Basidiomycetes) from Malaysia Int J Med Mushrooms201315(6)539-54

bull Phan CW David P Naidu M Wong KH Sabaratnam V Therapeutic potential of culinary-medicinal mushrooms for the management of

neurodegenerative diseases diversity metabolite and mechanism Crit Rev Biotechnol201535(3)355-68

Why Greens

bull Vitamin K1 metabolized to K2-mk7 in gut

bull K2 important in hellip

ndash Myelin production

ndash Calcium influx into bones and teeth

bull Carotenoids magnesium

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 30: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

What to Eat

Fruit and vegetable consumption and mortality from all causes cardiovascular disease and cancer systematic review and dose-response meta-analysis of prospective cohort studies

16 studies - 833234 participants

BMJ 2014 349 g4490

BMJ 2014 349 g4490

Risk of all cause mortality associated with servingsday of fruit and vegetables

Dose-response relation between fruit and vegetable consumption and risk of all cause mortality

BMJ 2014 349 g4490

Myelin

ndash Omega 3 Fatty Acids

ndash Thiamine (B1)

ndash Folate (B9)

ndash Cobolamin (B12)

ndash Minerals

Key Micronutrients

Bourre JM Effects of nutrients (in food) on the structure and function of the nervous

system update on dietary requirements for brain Part 1 micronutrients

Part 2 Macronutriients

J Nutr Health Aging 200610(5)377-85

Bowman Nutrient biomarker patterns cognitive function and MRI measures of

brain aging Neurology 2012 Jan 2478(4)241-9 Bowman

Sulfur Rich Foods

Why Brassica and Allium

bull Improve detoxification

bull Increase glutathione production

bull Increase GABA production

bull Enhance Neuroprotection

bull Improve endothelial function

Brassica and Allium References

1 Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimers Disease Med Cell Longev20152015781938

2 Learning and memory promoting effects of crude garlic extract Indian J Exp Biol2013 Dec51(12)1094-100

3 Enhancement of the neuroprotective activity of Hericiumerinaceus mycelium co-cultivated with Allium sativum extract Arch Physiol Biochem2015 Feb121(1)19-25

Why Emphasize Mushrooms

bull Increase nerve growth factors (NGF)

bull Hericium erinaceus (Yamabushitake or Lionrsquos Mane) stimulate the production of NGF (in vitro)

bull Activate natural killer cells

bull Prime innate and adaptive immunity

bull Mori K Obara Y Hirota M Azumi Y Kinugasa S Inatomi S Nakahata N Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human

astrocytoma cells Biol Pharm Bull 2008 Sep31(9)1727-32

bull Lee DH Kim HW Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway Int J Med Mushrooms 201416(1)1-16

bull Akramiene D Kondrotas A Didziapetriene J Kevelaitis E Effects of beta-glucans on the immune system Medicina (Kaunas)200743(8)597-606

bull Lai PL Naidu MSabaratnam VWong K DaviP Kuppusamy UR Abdullah N Malek SN Neurotrophic properties of the Lions mane medicinal mushroom

Hericium erinaceus (Higher Basidiomycetes) from Malaysia Int J Med Mushrooms201315(6)539-54

bull Phan CW David P Naidu M Wong KH Sabaratnam V Therapeutic potential of culinary-medicinal mushrooms for the management of

neurodegenerative diseases diversity metabolite and mechanism Crit Rev Biotechnol201535(3)355-68

Why Greens

bull Vitamin K1 metabolized to K2-mk7 in gut

bull K2 important in hellip

ndash Myelin production

ndash Calcium influx into bones and teeth

bull Carotenoids magnesium

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 31: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

BMJ 2014 349 g4490

Risk of all cause mortality associated with servingsday of fruit and vegetables

Dose-response relation between fruit and vegetable consumption and risk of all cause mortality

BMJ 2014 349 g4490

Myelin

ndash Omega 3 Fatty Acids

ndash Thiamine (B1)

ndash Folate (B9)

ndash Cobolamin (B12)

ndash Minerals

Key Micronutrients

Bourre JM Effects of nutrients (in food) on the structure and function of the nervous

system update on dietary requirements for brain Part 1 micronutrients

Part 2 Macronutriients

J Nutr Health Aging 200610(5)377-85

Bowman Nutrient biomarker patterns cognitive function and MRI measures of

brain aging Neurology 2012 Jan 2478(4)241-9 Bowman

Sulfur Rich Foods

Why Brassica and Allium

bull Improve detoxification

bull Increase glutathione production

bull Increase GABA production

bull Enhance Neuroprotection

bull Improve endothelial function

Brassica and Allium References

1 Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimers Disease Med Cell Longev20152015781938

2 Learning and memory promoting effects of crude garlic extract Indian J Exp Biol2013 Dec51(12)1094-100

3 Enhancement of the neuroprotective activity of Hericiumerinaceus mycelium co-cultivated with Allium sativum extract Arch Physiol Biochem2015 Feb121(1)19-25

Why Emphasize Mushrooms

bull Increase nerve growth factors (NGF)

bull Hericium erinaceus (Yamabushitake or Lionrsquos Mane) stimulate the production of NGF (in vitro)

bull Activate natural killer cells

bull Prime innate and adaptive immunity

bull Mori K Obara Y Hirota M Azumi Y Kinugasa S Inatomi S Nakahata N Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human

astrocytoma cells Biol Pharm Bull 2008 Sep31(9)1727-32

bull Lee DH Kim HW Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway Int J Med Mushrooms 201416(1)1-16

bull Akramiene D Kondrotas A Didziapetriene J Kevelaitis E Effects of beta-glucans on the immune system Medicina (Kaunas)200743(8)597-606

bull Lai PL Naidu MSabaratnam VWong K DaviP Kuppusamy UR Abdullah N Malek SN Neurotrophic properties of the Lions mane medicinal mushroom

Hericium erinaceus (Higher Basidiomycetes) from Malaysia Int J Med Mushrooms201315(6)539-54

bull Phan CW David P Naidu M Wong KH Sabaratnam V Therapeutic potential of culinary-medicinal mushrooms for the management of

neurodegenerative diseases diversity metabolite and mechanism Crit Rev Biotechnol201535(3)355-68

Why Greens

bull Vitamin K1 metabolized to K2-mk7 in gut

bull K2 important in hellip

ndash Myelin production

ndash Calcium influx into bones and teeth

bull Carotenoids magnesium

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 32: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

Dose-response relation between fruit and vegetable consumption and risk of all cause mortality

BMJ 2014 349 g4490

Myelin

ndash Omega 3 Fatty Acids

ndash Thiamine (B1)

ndash Folate (B9)

ndash Cobolamin (B12)

ndash Minerals

Key Micronutrients

Bourre JM Effects of nutrients (in food) on the structure and function of the nervous

system update on dietary requirements for brain Part 1 micronutrients

Part 2 Macronutriients

J Nutr Health Aging 200610(5)377-85

Bowman Nutrient biomarker patterns cognitive function and MRI measures of

brain aging Neurology 2012 Jan 2478(4)241-9 Bowman

Sulfur Rich Foods

Why Brassica and Allium

bull Improve detoxification

bull Increase glutathione production

bull Increase GABA production

bull Enhance Neuroprotection

bull Improve endothelial function

Brassica and Allium References

1 Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimers Disease Med Cell Longev20152015781938

2 Learning and memory promoting effects of crude garlic extract Indian J Exp Biol2013 Dec51(12)1094-100

3 Enhancement of the neuroprotective activity of Hericiumerinaceus mycelium co-cultivated with Allium sativum extract Arch Physiol Biochem2015 Feb121(1)19-25

Why Emphasize Mushrooms

bull Increase nerve growth factors (NGF)

bull Hericium erinaceus (Yamabushitake or Lionrsquos Mane) stimulate the production of NGF (in vitro)

bull Activate natural killer cells

bull Prime innate and adaptive immunity

bull Mori K Obara Y Hirota M Azumi Y Kinugasa S Inatomi S Nakahata N Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human

astrocytoma cells Biol Pharm Bull 2008 Sep31(9)1727-32

bull Lee DH Kim HW Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway Int J Med Mushrooms 201416(1)1-16

bull Akramiene D Kondrotas A Didziapetriene J Kevelaitis E Effects of beta-glucans on the immune system Medicina (Kaunas)200743(8)597-606

bull Lai PL Naidu MSabaratnam VWong K DaviP Kuppusamy UR Abdullah N Malek SN Neurotrophic properties of the Lions mane medicinal mushroom

Hericium erinaceus (Higher Basidiomycetes) from Malaysia Int J Med Mushrooms201315(6)539-54

bull Phan CW David P Naidu M Wong KH Sabaratnam V Therapeutic potential of culinary-medicinal mushrooms for the management of

neurodegenerative diseases diversity metabolite and mechanism Crit Rev Biotechnol201535(3)355-68

Why Greens

bull Vitamin K1 metabolized to K2-mk7 in gut

bull K2 important in hellip

ndash Myelin production

ndash Calcium influx into bones and teeth

bull Carotenoids magnesium

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 33: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

Myelin

ndash Omega 3 Fatty Acids

ndash Thiamine (B1)

ndash Folate (B9)

ndash Cobolamin (B12)

ndash Minerals

Key Micronutrients

Bourre JM Effects of nutrients (in food) on the structure and function of the nervous

system update on dietary requirements for brain Part 1 micronutrients

Part 2 Macronutriients

J Nutr Health Aging 200610(5)377-85

Bowman Nutrient biomarker patterns cognitive function and MRI measures of

brain aging Neurology 2012 Jan 2478(4)241-9 Bowman

Sulfur Rich Foods

Why Brassica and Allium

bull Improve detoxification

bull Increase glutathione production

bull Increase GABA production

bull Enhance Neuroprotection

bull Improve endothelial function

Brassica and Allium References

1 Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimers Disease Med Cell Longev20152015781938

2 Learning and memory promoting effects of crude garlic extract Indian J Exp Biol2013 Dec51(12)1094-100

3 Enhancement of the neuroprotective activity of Hericiumerinaceus mycelium co-cultivated with Allium sativum extract Arch Physiol Biochem2015 Feb121(1)19-25

Why Emphasize Mushrooms

bull Increase nerve growth factors (NGF)

bull Hericium erinaceus (Yamabushitake or Lionrsquos Mane) stimulate the production of NGF (in vitro)

bull Activate natural killer cells

bull Prime innate and adaptive immunity

bull Mori K Obara Y Hirota M Azumi Y Kinugasa S Inatomi S Nakahata N Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human

astrocytoma cells Biol Pharm Bull 2008 Sep31(9)1727-32

bull Lee DH Kim HW Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway Int J Med Mushrooms 201416(1)1-16

bull Akramiene D Kondrotas A Didziapetriene J Kevelaitis E Effects of beta-glucans on the immune system Medicina (Kaunas)200743(8)597-606

bull Lai PL Naidu MSabaratnam VWong K DaviP Kuppusamy UR Abdullah N Malek SN Neurotrophic properties of the Lions mane medicinal mushroom

Hericium erinaceus (Higher Basidiomycetes) from Malaysia Int J Med Mushrooms201315(6)539-54

bull Phan CW David P Naidu M Wong KH Sabaratnam V Therapeutic potential of culinary-medicinal mushrooms for the management of

neurodegenerative diseases diversity metabolite and mechanism Crit Rev Biotechnol201535(3)355-68

Why Greens

bull Vitamin K1 metabolized to K2-mk7 in gut

bull K2 important in hellip

ndash Myelin production

ndash Calcium influx into bones and teeth

bull Carotenoids magnesium

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 34: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

Sulfur Rich Foods

Why Brassica and Allium

bull Improve detoxification

bull Increase glutathione production

bull Increase GABA production

bull Enhance Neuroprotection

bull Improve endothelial function

Brassica and Allium References

1 Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimers Disease Med Cell Longev20152015781938

2 Learning and memory promoting effects of crude garlic extract Indian J Exp Biol2013 Dec51(12)1094-100

3 Enhancement of the neuroprotective activity of Hericiumerinaceus mycelium co-cultivated with Allium sativum extract Arch Physiol Biochem2015 Feb121(1)19-25

Why Emphasize Mushrooms

bull Increase nerve growth factors (NGF)

bull Hericium erinaceus (Yamabushitake or Lionrsquos Mane) stimulate the production of NGF (in vitro)

bull Activate natural killer cells

bull Prime innate and adaptive immunity

bull Mori K Obara Y Hirota M Azumi Y Kinugasa S Inatomi S Nakahata N Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human

astrocytoma cells Biol Pharm Bull 2008 Sep31(9)1727-32

bull Lee DH Kim HW Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway Int J Med Mushrooms 201416(1)1-16

bull Akramiene D Kondrotas A Didziapetriene J Kevelaitis E Effects of beta-glucans on the immune system Medicina (Kaunas)200743(8)597-606

bull Lai PL Naidu MSabaratnam VWong K DaviP Kuppusamy UR Abdullah N Malek SN Neurotrophic properties of the Lions mane medicinal mushroom

Hericium erinaceus (Higher Basidiomycetes) from Malaysia Int J Med Mushrooms201315(6)539-54

bull Phan CW David P Naidu M Wong KH Sabaratnam V Therapeutic potential of culinary-medicinal mushrooms for the management of

neurodegenerative diseases diversity metabolite and mechanism Crit Rev Biotechnol201535(3)355-68

Why Greens

bull Vitamin K1 metabolized to K2-mk7 in gut

bull K2 important in hellip

ndash Myelin production

ndash Calcium influx into bones and teeth

bull Carotenoids magnesium

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 35: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

Why Brassica and Allium

bull Improve detoxification

bull Increase glutathione production

bull Increase GABA production

bull Enhance Neuroprotection

bull Improve endothelial function

Brassica and Allium References

1 Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimers Disease Med Cell Longev20152015781938

2 Learning and memory promoting effects of crude garlic extract Indian J Exp Biol2013 Dec51(12)1094-100

3 Enhancement of the neuroprotective activity of Hericiumerinaceus mycelium co-cultivated with Allium sativum extract Arch Physiol Biochem2015 Feb121(1)19-25

Why Emphasize Mushrooms

bull Increase nerve growth factors (NGF)

bull Hericium erinaceus (Yamabushitake or Lionrsquos Mane) stimulate the production of NGF (in vitro)

bull Activate natural killer cells

bull Prime innate and adaptive immunity

bull Mori K Obara Y Hirota M Azumi Y Kinugasa S Inatomi S Nakahata N Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human

astrocytoma cells Biol Pharm Bull 2008 Sep31(9)1727-32

bull Lee DH Kim HW Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway Int J Med Mushrooms 201416(1)1-16

bull Akramiene D Kondrotas A Didziapetriene J Kevelaitis E Effects of beta-glucans on the immune system Medicina (Kaunas)200743(8)597-606

bull Lai PL Naidu MSabaratnam VWong K DaviP Kuppusamy UR Abdullah N Malek SN Neurotrophic properties of the Lions mane medicinal mushroom

Hericium erinaceus (Higher Basidiomycetes) from Malaysia Int J Med Mushrooms201315(6)539-54

bull Phan CW David P Naidu M Wong KH Sabaratnam V Therapeutic potential of culinary-medicinal mushrooms for the management of

neurodegenerative diseases diversity metabolite and mechanism Crit Rev Biotechnol201535(3)355-68

Why Greens

bull Vitamin K1 metabolized to K2-mk7 in gut

bull K2 important in hellip

ndash Myelin production

ndash Calcium influx into bones and teeth

bull Carotenoids magnesium

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 36: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

Brassica and Allium References

1 Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimers Disease Med Cell Longev20152015781938

2 Learning and memory promoting effects of crude garlic extract Indian J Exp Biol2013 Dec51(12)1094-100

3 Enhancement of the neuroprotective activity of Hericiumerinaceus mycelium co-cultivated with Allium sativum extract Arch Physiol Biochem2015 Feb121(1)19-25

Why Emphasize Mushrooms

bull Increase nerve growth factors (NGF)

bull Hericium erinaceus (Yamabushitake or Lionrsquos Mane) stimulate the production of NGF (in vitro)

bull Activate natural killer cells

bull Prime innate and adaptive immunity

bull Mori K Obara Y Hirota M Azumi Y Kinugasa S Inatomi S Nakahata N Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human

astrocytoma cells Biol Pharm Bull 2008 Sep31(9)1727-32

bull Lee DH Kim HW Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway Int J Med Mushrooms 201416(1)1-16

bull Akramiene D Kondrotas A Didziapetriene J Kevelaitis E Effects of beta-glucans on the immune system Medicina (Kaunas)200743(8)597-606

bull Lai PL Naidu MSabaratnam VWong K DaviP Kuppusamy UR Abdullah N Malek SN Neurotrophic properties of the Lions mane medicinal mushroom

Hericium erinaceus (Higher Basidiomycetes) from Malaysia Int J Med Mushrooms201315(6)539-54

bull Phan CW David P Naidu M Wong KH Sabaratnam V Therapeutic potential of culinary-medicinal mushrooms for the management of

neurodegenerative diseases diversity metabolite and mechanism Crit Rev Biotechnol201535(3)355-68

Why Greens

bull Vitamin K1 metabolized to K2-mk7 in gut

bull K2 important in hellip

ndash Myelin production

ndash Calcium influx into bones and teeth

bull Carotenoids magnesium

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 37: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

Why Emphasize Mushrooms

bull Increase nerve growth factors (NGF)

bull Hericium erinaceus (Yamabushitake or Lionrsquos Mane) stimulate the production of NGF (in vitro)

bull Activate natural killer cells

bull Prime innate and adaptive immunity

bull Mori K Obara Y Hirota M Azumi Y Kinugasa S Inatomi S Nakahata N Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human

astrocytoma cells Biol Pharm Bull 2008 Sep31(9)1727-32

bull Lee DH Kim HW Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway Int J Med Mushrooms 201416(1)1-16

bull Akramiene D Kondrotas A Didziapetriene J Kevelaitis E Effects of beta-glucans on the immune system Medicina (Kaunas)200743(8)597-606

bull Lai PL Naidu MSabaratnam VWong K DaviP Kuppusamy UR Abdullah N Malek SN Neurotrophic properties of the Lions mane medicinal mushroom

Hericium erinaceus (Higher Basidiomycetes) from Malaysia Int J Med Mushrooms201315(6)539-54

bull Phan CW David P Naidu M Wong KH Sabaratnam V Therapeutic potential of culinary-medicinal mushrooms for the management of

neurodegenerative diseases diversity metabolite and mechanism Crit Rev Biotechnol201535(3)355-68

Why Greens

bull Vitamin K1 metabolized to K2-mk7 in gut

bull K2 important in hellip

ndash Myelin production

ndash Calcium influx into bones and teeth

bull Carotenoids magnesium

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 38: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

Why Greens

bull Vitamin K1 metabolized to K2-mk7 in gut

bull K2 important in hellip

ndash Myelin production

ndash Calcium influx into bones and teeth

bull Carotenoids magnesium

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 39: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

Greens References

1 Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides Nutr Biochem2010 Nov21(11)1083-8

2 Vitamin K and sphingolipid metabolism evidence to date Nutr Rev2005 Apr63(4)111-21

3 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 1 micronutrients J Nutr Health Aging 2006 Sep-Oct10(5)377-85

4 Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system update on dietary requirements for brain Part 2 macronutrients J Nutr Health Aging 2006 Sep-Oct10(5)386-99

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antioxidants small fruits providing large benefits J Sci Food Agric2014 Mar 3094(5)825-33

3 Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia Recent Pat Food Nutr Ag 2013 Aug5(2)128-43

4 The impact of fruit flavonoids on memory and cognition Br J Nutr2010 Oct104 Suppl 3S40-7 d

5 Grape juice berries and walnuts affect brain aging and behavior J Nutr 2009 Sep139(9)1813S-7S

6 Fruit polyphenolics and brain aging nutritional interventions targeting age-related neuronal and behavioral deficits Ann N Y Acad Sci2002 Apr959128-32

7 Reversing the deleterious effects of aging on neuronal communication and behavior beneficial properties of fruit polyphenolic compounds Am J ClinNutr2005 Jan81(1 Suppl)313S-316S

Why Organ Meat

bull Pre-industrial - 30 of all meat consumed was organ meat

bull Excellent source of ubiquinone minerals essential fatty acids fat and water soluble vitamins

ndash Retinol Vitamin A

ndash Vitamin K2-mk4

β-carotene Is Not Retinol (Vitamin A)

bull β-Carotene is converted to vitamin A in the intestine by the enzyme β-carotene-1515-monoxygenase (BCMO1) to support vision reproduction immune function and cell differentiation

bull Considerable variability in BCMO1 exists and can effect individual vitamin A status

Lobo GP Amengual J Baus D Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX J Biol

Chem2013 Mar 29288(13)9017-27

Leung WC Hessel S Meacuteplan C Flint J Oberhauser V Tourniaire F Hesketh JE von Lintig J Lietz G Two common

single nucleotide polymorphisms in the gene encoding beta-carotene 1515-monoxygenase alter beta-carotene

metabolism in female volunteers FASEB J 2009 Apr23(4)1041-53 doi 101096fj08-121962 Epub 2008 Dec 22

Figure 1 The two routes by which diet can influence our health (A)

the metabolism of our cells and (B) the population of our gut

microbiota

Paolo Riccio and Rocco Rossano ASN Neuro

201571759091414568185

Copyright copy by SAGE Publications Inc or the American Society for Neurochemistry unless

otherwise noted Manuscript content on this site is licensed under Creative Commons Licenses

Total number of microbiome-related publications in PubMed by year

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

year 199719981999200020012002200320042005200620072008200920102011201220132014201520162017

Articles

Articles

Gut Brain Immune Axis

bull Gut microbiota influence the brain and immune system balance

bull Diet influences the microbiome strongly

bull Exercise sleep stress level also important

bull Changes in the colon mucosa every early in the disease process

1 Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology J Immunol Res 20172017790482

2 The multiple sclerosis microbiome Ann Transl Med 2017 Feb5(3)533 Microbiota-gut-brain axis and the central nervous system Exp Mol Med 2017 May 2649(5)e3394 Microbiota-gut-brain axis and the central nervous system Oncotarget 2017 May 105 Microbiota in T-cell homeostasis and inflammatory diseases Exp Mol Med 2017 May 49(5) e3406 Mucosal biopsy shows immunologic changes of the colon in patients with early MS Neurol Neuroimmunol

Neuroinflamm 2017 Jun 144(4)e362

Life Begins in the Ocean

54

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

Life Timeline Billions of Years

Going back in time Billions of years bull 45 Water bull 40 Simple life bull 30 Photosynthesis bull 25 Oxygen crisis bull 15 Mitochondria Multi-cellularbull 05 (500 Million) Land plants animals bull 02 (200 Million) Mammals bull 000025 (250 Thousand) Humansbull 000001 (10 Thousand) grains and legumes

55

Our Human Ecosystem Began In The Ocean

copy Dr Terry Wahls LLC All Rights Reserved 56

By Tiago Fioreze -httpscommonswikimediaorgwindexphpcurid=6111892

bull We have co-evolved with the organisms that were in the ocean

bull Microbes divide every 20 minutes (1 billion years)

ndash Billions of generations

bull Humans every 25 years (250000 years)

ndash 10000 generations

57

Guts Populated by Ocean Microbiome

bull Co-operative mutualistic relationship

bull We are all supra-organisms ndash as dependent on the microbes as our cells are upon our mitochondria to function

copy Dr Terry Wahls LLC All Rights Reserved 58

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager- Hunter 500000 BC Main Cause of death -Infection trauma Mean age 30s

45 mortality before age 15

Copyright copy 2016 Dr Terry Wahls All rights reserved

Population and Development Review33(2007)321-65 Kaplan

Forager-Hunter 2007Traditional diet no medical careMain cause of deathInfection trauma

Often live into 60s and 80s

Copyright copy 2016 Dr Terry Wahls All rights reserved

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Forager-Hunter to Farmer -10000 BC uarr fertility infection darrheight

Copyright copy 2016 Dr Terry Wahls All rights reserved

Industrial Revolution 1800suarr sugar white flour darr breast feeding

uarr obesity heart disease diabetes

Investig Genet 4 (2013)10 Sajantila Am J Prev Med 37

Copyright copy 2016 Dr Terry Wahls All rights reserved

Sugar intake per capita in the United Kingdom from 1700 to 1978 (30 31 ) and in the United

States from 1975 to 2000 (32 diams) is compared with obesity rates in the United States in non-

Hispanic white men aged 60ndash69 y (17 bull)

Johnson R J et al Am J Clin Nutr 200786899-906

copy2007 by American Society for Nutrition

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Copyright copy 2016 Dr Terry Wahls All rights reserved

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation

Clin Ther 2015 May 137(5)984-95

8 Studies 250 Patient Fecal Samples

van den Hoogen WJ1 Laman JD2 t Hart BA23Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota Front Immunol 2017 8 1081

Fiber Grams Day bull Westernized society 15 grams

bull Target - 30 grams

bull Study Diet 50 grams

bull Hunter Gatherer 100 to 150 grams

bull Feed your bacterial friends more fiber

Kombucha Mature by Mgarten at the English language Wikipedia Licensed under CC BY-SA 30 via Commons

More Vegetables

Favorable Nutrient Profiles

bull Fermented food

ndash Microbiome

bull Seaweed

ndash Iodine alginates

bull Nutritional yeast

ndash B vitamins minerals

bull Algae

ndash Carotenoids detoxification

BristolStoolChart by Cabot Health Bristol Stool Chart - httpcdnintechopencompdfs-wm46082pdf Licensed under CC BY-SA 30 via Commons -httpscommonswikimediaorgwikiFileBristolStoolChartpngmediaFileBristolStoolChartpng

Human Feces by User Cacetudo on enwikipedia - Own work Licensed under CC BY-SA 25 via Commons -httpscommonswikimediaorgwikiFileHuman_FecesjpgmediaFileHuman_Fecesjpg

Modified Paleolithic Diet

Home Exercise Program

+

Neuromuscular Electrical Stimulation

Vitamins amp Nutritional supplements

Stress Management

Multimodal Intervention

Study Diet

Food Instruction Servings

Green leafy vegetables Recommended3 cups cooked6 cups

raw=3srvg

Sulfur-rich vegetables Recommended3 cups raw or cooked=

3srvg

Intensely colored fruits or

vegetablesRecommended

3 cups raw or cooked =3

srvg

Omega-3 oils Encouraged 2 tablespoons

Animal protein Encouraged 4 ounces or more

Gluten-containing grain Excluded

Dairy Excluded

Eggs Excluded

Stop processed foods gluten dairy eggs

Nutritional Adequacy (RDA) US Diet Vs Study Diet

0 100 200 300 400 500 600 700 800 900

Riboflavin

Thiamin

Vitamin B12

Vitamin B6

Niacin

Vitamin C

Vitamin A

Iron

Folate

Zinc

Magnesium

Vitamin E

Calcium

Vitamin D

US Diet

Wahls

Methyl B12 Methyl Folate Vitamin D Fish Oil

httpvitaminreviewsitecomwp-contentuploads201304natural-Vitaminsjpg

Stretching Exercises

Gastro-soleus

Hamstring

Quadriceps

Erector spinae

Electrical Stimulation of Muscles

Builds Muscle Mass

20 individuals (18 SPMS 2 PPMS)

Age 517 (+ 64) years

Baseline EDSS 62 (+1)

Fatigue Severity Scale Score 55 (+ 12)

Subject Demographics

Average daily servings of the study diet recommended (vegetablesfruits) and excluded (glutendairyeggs) foods

p lt 001 difference from baseline to 12 months

Side effect ndash Overweight and obese subjects lost weight and got to a healthy weight

-200 0 200 400 600 800 1000 1200

Retinol

Vitamin B9 (folic acid)

Vitamin K

Alpha Carotene

Iodine

Docosahexaenoic Fatty Acid (DHA)

Percent Change in Intake

Significant Changes in Micronutrient Intake

plt00005

plt 005

Multimodal intervention improves quality of life

Mood and Cognition

90

In the setting of progressive MSImproved thinking ability and

reduced anxiety and reduced depression

Average scores on the mood measuresat each study visit

Average scores on the DKEFS and WAIS subscales at each study visit

Associations Between Adherence and Outcomes P values

Variables 0 to 12 months

Mood BDA BDI

Cognition Verbalreasoning

Fatigue

Vegetables fruits 00001 lt00001 lt00001

Gluten dairy egg free

0001 0005 lt00001

Relapsing Remitting MS

94

In the setting of relapsing-remitting MS Reduction of fatigue and improved motor function

Herorsquos Journey

bull Struggle adversary facing individual society

bull Hero leaves to learn some key point to overcoming the struggle adversary

bull Returns to engage in the struggle

bull Religious mythical stories across time and space

Alzheimerrsquos Disease

99

Reversal of early and moderate dementia usingfunctional medicine approach

Bredesen et al J Alzheimers Dis Parkinsonism 2018 85 DOI 1041722161-04601000450

Subject 3- Baseline and 12 Month Walk

SPMS TUG-127 secFSS-56

SPMS TUG-418 secFSS-44

Subject 17- Baseline and 3 Month Walk

PPMSTUG-21 secFSS-67

PPMSTUG- 153 sec with one cane

176 sec without cane FSS-49

Subject 11- Baseline and 3 Month Walk

SPMS TUG-149 secFSS-53

SPMS TUG- 86 secFSS-14

Subject 11- 6 months

How many cups of vegetables did you eat in last 24 hours

Copies of papers

wwwterrywahlscompapers

One page summary

wwwterrywahlscomdiet

bull Instagram

ndash drterrywahls

bull Facebook

ndash Terry Wahls MD

bull Twitter

ndash TerryWahls

Page 40: Testing the Effect of Nutrition and Lifestyle ...• Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus

Why deeply pigmented

bull Pigments (especially bluepurpleblack) are associated with improved cognitive performance and neuroprotection

Blueberries and Mild Cognitive Impairment (MCI)

bull N = 47 with MCI 68 yo + Blueberry powder vs placebo 16 weeks equivalent of 1 cup berries

bull There was improvement in cognitive performance and brain function compared with placebo

bull N=94 62 to 80 yo with memory complaints bull Fish oil + blueberries vs fish oil + placebo 24 weeksbull The blueberry-supplemented participants had a better sense of

well-being fewer memory mistakes and were less inefficient

Krikorian R Shidler MD Nash TA Kalt W Vinqvist-Tymchuk MR Shukitt-Hale B Joseph JA Blueberry supplementation

improves memory in older adults J Agric Food Chem2010 Apr 1458(7)3996-4000

Funding for the studies was provided by the US Highbush Blueberry Council the National Institute on Aging

and Wild Blueberries of North America Dr Krikorian has disclosed no relevant financial relationships

Pigment amp Blueberry References1 Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

Scientifica (Cairo)201620163109254

2 Berry antio