healing the aging metabolism: breakthroughs in anti-aging ... · diabetes and obesity •particular...

Healing the Aging Metabolism: Breakthroughs in Anti-Aging Nutrition

Dr. Robert G. Silverman DC, DACBN, MS, CNS, CCN, CSCS, CIISN, CKTP, CES, DCBCN, HKC, SASTM

www.DrRobertSilverman.cominfo@drrobertsilverman.com

“Take care of your body, it’s the

only place you have to live”.

Jim Rohn

Objective

What’s the Problem?

THE THINKER, Auguste Rodin in 1902

Obesogenic Overview

• Obesity epidemic

• 50% of US adults will be obese by 2030

• Obesity prevalence in adults in their 40’s and 50’s would be 60%

Additionally:

• 6 mil to 8.5 mil more people with diabetes

• 5.7 mil to 7.3 mil more cases of heart disease and stroke

• 490,000 to 670,000 additional cancers

• 26 to 55 mil quality–adjusted life years left

• Increase medical expenditures: 48 bil – 66 bil by 2030 (not including lost productivity estimated at 390 bil – 580 bil per year)

The Lancet 2011. 378: p.815-25

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1971-1974 1976-1980 1988-1994 1999-2000 2000-2012

Protein

Obesity & Diabetes

Carbohydrates

Fat

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Change in Dietary Composition in Relation to Obesity Prevalence (1971-2010)

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Adapted from: Flegal KM, Int J Obes 1998; Hedley AA et al JAMA 2004;291(23):2847-50; Flegal KM et al, JAMA. 2012 307(5):491-7

1971-1974 1976-1980 1988-1994 1999-2000 2009-2010

No Nation Has Lowered Obesity Rate in 33 Years• The Lancet, June 2014: Study combining 3 decades of data from 188

countries

• Nearly 30% of world’s population is overweight or obese – not one country has reduced its obesity rate in 33 years

New York Times, June 3, 2014

Obesity-Related Ills May Shave Up to 8 Years Off Your Life: Study

Excess weight also shortens the time you live free of chronic diseases that lower quality of life

Published online Dec. 5, The Lancet Diabetes & Endocrinology

Obesity = Postural Compensation

Obesity as an Inflammatory Disorder

One of the more interesting discoveries of the past decade has been the recognition that the adipocyte produces inflammatory cytokines

Obesity, therefore, may be viewed as a low grade systemic inflammatory disease

A.M.A. Recognizes Obesity as a Disease

• The American Medical Association officially recognized obesity as a disease, a move that could induce physicians to pay more attention to the condition

The New York Times, June 18, 2013

Lipotoxicity: the result of unhealthy lifestyle choices

Lipotoxicity• ectopic fat accumulation in various

tissues and organs leading to pathologic changes and impaired function.

Ectopic• occurring in an abnormal position or

place; displaced.

What really determines aging for most of us?

Genetics

Physiology/

Biochemistry

Environment

Lifestyle

Shift focus from calorie counting to nutritional value for heart health• It’s time to stop counting calories

• Start promoting nutritional value of foods:• Rapidly cut illness

• Death from cardiovascular disease

• Curb rising tide of obesity

BMJ Aug 26, 2015

There are too many people counting calories and

not enough people counting chemicals

“obesity and diabetes have joined the list of

adverse effects that have been associated with

developmental exposure to environmental

estrogens and other endocrine-disrupting

chemicals.”

Am J Clin Nutr. 2011 Dec;94(6 Suppl):1939S-1942S

Chemical exposure may be linked to rising rates in diabetes and obesity

• Particular concern to unborn children exposed to EDCs

• Studies demonstrated that exposure to even very small amounts of EDCs during pregnancy can trigger obesity in the child later in life

• EDCs directly target beta and alpha cells in the pancreas, fat cells, and liver cells, which can lead to insulin resistance and type-2 diabetes

Chemical exposure may be linked to rising rates in diabetesand obesity

• The Journal of Clinical Endocrinology and Metabolism, March 2015: EDC exposure will likely cost the EU $209 billion a year in actual health care expenses and lost earning potential

Is your belly turning you into a pregnant woman?

The Obesity Epidemic: It’s a Guy Thing

• The other gender gap

• 72% of men are overweight or obese; 64% for women

• Life expectancy is less for men

• CHD mortality starts at younger ages for men

• 3 main factors:• Declining testosterone

• Increasing visceral fat

• Chronic inflammation

An Estrogen Factory

• Overweight men 9x more likely to have low testosterone

• Insulin sensitivity has a strong inverse relationship with visceral fat (VF)

• VF is an estrogen factory

• VF converts testosterone to estrogen to further fat deposition

Testosterone

Insulin resistanceWeight gain

Visceral fat

Low Testosterone Linked to Obesity and Muscle Loss

Lower levels of testosterone and free testosterone linked to increased body fat, body mass index

(proportion of weight to height) and waist-to-hip ratio

Journal Clinical Endocrinology Metabolism. 98:p.2442-50, 2013

Additional Causes of Low T

• Estrogen and estrogen-like compounds in our water:• Government researchers found natural estrogens and estrogen mimickers in 80% of

the streams they tested in 30 states

• Excess estrogen in body: new consideration – beta-glucuronidase:• Protocol: Indole-3-carbinol, Probiotic

• High levels of aromatase enzymes (estrogen synthase):• Transforms androstenedione to estrone• Transforms testosterone to estradiol

• Takeaway: it converts steroid hormones to bad estrogens• Protocol: Indole-3-carbinol

Pharmaceuticals, Hormones, and Other Organic Wastewater Contaminants in U.S. Streams, Environmental Science & Technology

Low “T”

• Links exposure to phthalates – to a 13% lower testosterone level in men ages 40-60

J of Clin Endocrinology & Metab, 2014 report

Declining Testosterone

• Current measure indicate that testosterone levels are declining at a rate greater than would have been expected purely from aging

Travison, T. et al. Clin Endocrinol Metab. 2007: 92(1) p.196-202

Low-T

• U.S. prescription testosterone sales – 2.4 in 2013

• Expected growth to 3.8 by 2018

• Happening without FDA approval

• Testosterone therapy approved for males who suffer from medical conditions associated with a deficient or absence of endogenous test

• U.S. prescriptions grew ten-fold from 2000 to 2011

Time Magazine, Aug. 18, 2014

Testosterone gel has modest benefits for men

NESM, Feb. 17, 2016

“Time the healer also time the destroyer”

Tips for Men: Nutritional Support for Low T

• CYCYP test – great motivation

• Detox/heavy metal/estrogen detox/avoid plastics

• Improve body composition/cut simple carbs

• Eat more monounsaturated fats – increase manufacture of testosterone

• Squat, don’t run – squats, pushups and burpees burn more fat than running

• Add vitamin D, zinc, omega-3 fatty acids, DHEA, Indole-3-carbinol, resveratrol

• Tribulus, cowage seed, flax lignans, ashwagandha root

The Endocrine Society, news release, June 25, 2012

Best Time of Day for a Testosterone Test

Before 2 PM

The Journal of Urology, July 2014

Case Study

• Patient is a 40 year-old male who is unable to lose weight. Has to take Viagra to “perform”. Has tried various diets, including Androgell

Jan. 2014 Aug. 2014

Weight 284 215

% Body Fat 33.1 15.8

Total Testosterone 176 622 QuestLab250-1100ng/dl

Free Testosterone 38 168 QuestLab46-224 pg/nl

HPQ 62 12

Inflammaging

Optimal ResolutionLow proinflammatory statusHigh efficiency of stress response

Inadequate Resolution High proinflammatory statusLow efficiency of stress response

Young Aged

Chronic Disease

Unresolved Immune Function leads to Chronic Disease

Poor DietInjuries Infection

Chronic Inflammation Leads to Many Chronic Diseases

Chronic Systemic Inflammation

Inactivity Obesity Aging

Adipocytes Immune Cells Brain CellsSystemic and local increase in cytokine concentrations

Immune Cells

Insulin ResistanceType 2 Diabetes

Atherosclerosis Alzheimer’s DiseaseHuntington’s DiseaseParkinson’s Disease

CancerArthritis

Handschin & Spiegelman. Nature. 2008;454:463-9

Health Trajectory’s Have Age Thresholds

36Time Magazine 2015

Aging is a Young Person’s Disease!

Prevalence of two or more of nine selected chronic conditions among adults aged 45 and over, by age and sex: United States, 1999–2000 and 2009–2010

Chronic Disease on the rise

CDC/NCHS, National Health Interview Survey

The primary driver of chronic disease is the interaction among genes, activities of daily living (lifestyle), and the environment

Willett WC. Balancing lifestyle and genomics research for disease prevention. Science, 2002;296:695-97Thorpe KE, Florence CS, et al. The rising prevalence of treated disease: effects on private health insurance spending. Health Affairs, web exclusive, June 27, 2005Henry RP. Long-latency deficiency disease: insights from calcium and vitamin D. Am J Clin Nutr2003;78:912-9

Why doesn’t the old healthcare model work?

Because chronic disease is a food- and lifestyle-driven, environment- and genetics-influenced phenomenon

Major influences contributing to the epidemic of chronic disease

Chronic disease

epidemic

Nutrition(food supply, dietary habits)

Sedentary lifestyles(young and old)

Chronic stress

Poverty/Uninsured Aging population

Outdoor living ( vit D)

Fragmented families, communities

Environmental toxicity

The Institute for Functional Medicine

Core clinical imbalances – Multiple influencesOne Condition – Many Imbalances

One Imbalance – Many Conditions

Inflammation Hormones Genetics and Epigenetics Diet and Exercise Mood Disorders

Obesity

Heart Disease Depression Arthritis Cancer Diabetes

Inflammation

Study shows 70 percent of Americans take prescription drugs• CBS Atlanta: Nearly 70% of Americans on at least 1 prescription drug

• 55% take 2 prescription drugs

• 20% take 5 or more prescriptions

• Mayo Clinic: Antibiotics, antidepressants and pain killer opioids are most common

The U.S. accounts for 4.4% of the world’s population and consumes 52% of the world’s pharmaceuticals (medications)

Anti Inflammatory drugs (NSAIDS) cause leaky gut.Leaky Gut causes inflammation

Inflammation

NSAIDS cause

FDA Strengthens Stroke and Heart Attack Warnings on NSAIDs• Lancet analysis of more than

600 studies and 350,000 people: showed significant doses of these medications daily can increase risk of cardiovascular event by up to a third

NY Times, July 10, 2015

“Over 99% of us are born healthy and suffer premature death or disability only as a result of personal misbehavior and

environmental conditions”.

John Knowles 1977

The Anti-Aging Promise

Lighting

Botox

Make-up

Why your DNA isn’t your Destiny

“For decades, we have stumbled around massive Darwinian roadblocks. DNA, we thought, was an ironclad code that we and our children and their children had to live by. Now we can imagine a world in which we can tinker with DNA, bend it to our will.”

www.time.com Wednesday, Jan. 06, 2010

7. Brain health

4. Healthy blood-sugar regulation /Whole body alkalization

3. Increase telomere length

2. Body composition/protein synthesis (muscle mass)

1. Functional movement – move well, joint health

Dr. Rob’s 7 Steps to Anti-Aging Through Epigenetic Science

5. Environment/microbiome

6. Lifestyle/exercise

Epigenetics

• Food is a powerful epigenetic modulator

• It can change our DNA for better or worse

• Epigenetics refers loosely to heritable changes of gene expression (methylation, histone modification)

Methylation

Addition of (CH3) to either cytosine or guanine nucleotides

Expression of genes

Epigenetics (cont’d)

• Discoveries in epigenetics are rewriting the roles of disease, heredity, identity and aging

• Epigenetics is the phenomena whereby genetically identical cells express their genes differently, resulting in different physical traits

Adams, J. (2008) Obesity, epigenetics, and gene regulation. Nature Education 1(1):128

Transforming Youth: Turn Back the Epigenetic Aging Clock

Functional movement

Functional Medicine

=

Optimal Health

+

The NMS Detonation SequencePain DynamicTight muscle

Inhibited muscle

Strain point

PAIN

Complaint

Sherrington’s law of reciprocal

inhibition

Head = 10 lbs 1” = 2x weight

Tight muscle Inhibited muscles1. Pecs 1. Mid-lower trap2. Suboccipitals 2. Deep neck flexors3. Erector spinae 3. Abdominals4. Psoas 4. Gluteus maximus

Suboccipitals

Medial scapula stabilizers

C7 – T1TMJ

Deep neck flexorsGH jtPec major

Abs

Psoas

Hip

T/L jct

Erector spinaeL/S jct

Gluteus maximus

Strain points Symptoms1. TMJ neck & shoulder2. C7-T1 jct stiffness & pain3. GH joint4. T/L junction SI, L/S & hip5. L/S junction stiffness & pain6. Hip

1 2 34

Posture follows movement like a shadow

Sherrington - 1906

Pathogenesis of the cumulative trauma disorder

RecoveryCycle

Injury Cycle

Frequency of Insult

Am

ou

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of

Tiss

ue

Insu

lt

SymptomaticInjury Threshold

Pathogenesis of the cumulative trauma disorder

Injury Cycle

Frequency of Insult

Am

ou

nt

of

Tiss

ue

Insu

lt

Insufficient Tissue Recovery Between Injury Cycles

Tissue Damage Accumulates

Copyright Jerome M. True, DC

Hypertonicity

Weakness

Does posture change with age?

Dr. Rob’s Magnificent 7

• Posture/pain

Functional Movement Assessment

• Push-up

• Overhead squat

• 1-legged squat

• Trunk stability push-up

• Valgus jump test

• Upper/lower muscle firing patterns

Functional Movement Assessment

“Our response to injury is like hearing the smoke detector go off and running to pull out the battery.”

UltraPrevention by Hyman & Liponis

Kinetic Chain = Functional Anatomy

Muscles act in synergy not in

isolation” Movement, not muscles

Movement becomes habit, which becomes posture, which becomes

structure

FORM = FUNCTION =

PERFORMANCE

Correct Altered Motor Control

Age Risk-Factors:Genetic AlterationInflammationMechanical StressObesity

Transcription Factors Epigenetics Changes

Catabolism Anabolism

Dysregulation of Target Gene Expression in Various Joint-Cells

Disrupted Cellular Function

OsteoarthritisSports Health. Vol.6(1), Jan/Feb 2014

Age-Related Factors in the Maturing Adult

The Mature Adult: Aging Tendons and Ligaments

• Several published reports shown increased levels of matrix metalloproteinases (MMPS) lead to degenerative tendon disease

• MMP inhibitors associated with a decrease in tendon dysfunction

Sports Health, Jan/Feb. 2014, p.41-48

Disc Injuries

Flexion movement

Flexing the spine

Strains layers of collagen in spinal discs

MMPS, cytokines

Inflammation

Flexion moment

Flexing moment or torque

Ab muscle stiffening

No movement

Stuart McGill website

vs.

Interleukin-1β in intervertebral disk degeneration

• Interleukin-1 (IL-1) β has strong pro-inflammatory activity by stimulating the secretion of multiple pro-inflammatory mediators

• IL-1β is highly expressed in degenerative intervertebral disk (IVD) tissues and cells

• Inhibition of IL-1β found to promote extracellular matrix (ECM) repair and protect against disk degeneration

Yang W, et al. Clin Chim Acta 2015

New approach to diagnosing low back pain

• Findings determined serum levels of IL-6 significantly higher in subjects with low back pain compared with control participants

• Participants with low back pain due to spinal stenosis or degenerative disc disease also had higher levels than those with intervertebral disc herniation and controls

• Findings suggest that patients with low back pain have low-grade systemic inflammation

• Biochemical profiling or circulating cytokines can assist in diagnosing those with low back pain

North Shore-Long Island Jweish (LIJ) Health System-Jan-7-2016

Key Takeaway

• Inflammation/MMPs cause cartilage loss, not “wear-and-tear”

• This is the same process that causes disc nuclear degradation and herniation

Failed healing of rotator cuff repair

• Found that gene expression related to tissue remodeling, particularly MMP-1 and MMP-9, differs between rotator cuffs that healed and those that failed to heal after orthoscopic repair

• MMP-1 and MMP-9 are highly effective in degrading type-1 and 3 collagen

• Their expression contributes to poor cuff healing

• MMP-1 and MMP-9 expression reflect a highly degenerated tendon or diminished ability to heal

American Journal of Sports Medicine, 2012, vol. 40 (9):1993-2000

Your connective tissues are your extracellular matrix

TendonsLigaments

CartilageFascia

What is Extracellular Matrix (ECM)?

The Extracellular Matrix: the network that binds us together

“The ECM is a conglomerate of substances in which biochemicals and biophysical properties allow for the construction of a flexible network that integrates information from loading and converts it into mechanical capacities…It serves as a scaffold for adhesion of cells mediated by integrins, dystroglycan, and proteoglycans at the cell surface and of tyrosine kinase receptors. The interaction between the ECM and the adhesion molecules leads to activation of intracellular signaling pathways and cytoskeletal rearrangement.”

Kjaer, M. Physiol. Rev. 84:649-698, 2004

The extracellular matrix is composed of tissues that serve multiple purposes

A complex web that of connective tissues that

• Provide adhesion to cells

• Act as a structural scaffold

• Actively participate in intracellular signaling

• Translates mechanical loading into cellular response

EFFECTFASCIA

Key

Extracellular matrix — the fascial system is

the largest system in the body and is the only system that touches every other system

An unhealthy ECM:Torn, weak or relaxed

tendonsSoft tissue injuryRepetitive injury

Structural imbalances

A healthy ECM:healthy,

well-functioning tendons, ligaments

and cartilage

The extracellular matrix

IT’S ALL CONNECTED

• MMPs are collagen-digesting enzymes naturally produced by the chondrocyte during time of injury

• Poor diet, lifestyle, injury, tissue damage can trigger cell signals which can lead to the over-activated release of MMPs

• Excessive release of MMPs can damage healthy tendon and cartilage tissue

Litherland et al., JBC, Papers in press, March 10, 2008

Matrix metalloproteinase (MMPs) enzymes damage collagen and connective tissue

Matrix metalloproteinases digest collagen and connective tissue

Collagen Triple Helix

Chondrocyte

MMPs are released from the chondrocyte in response to injury or inflammation

MMP-9

MMP- 2

MMP-1

MMP-13

MMP-13

MMP-13

MMPs further degrade collagen tissue during injury or inflammation

Modulate expression of MMPs to support healthy remodeling of connective tissue

A comprehensive strategy to support the health and integrity of extracellular matrix tissues

• THIAA & Berberine synergistically modulate MMP-13

• Selenium to address MMP-1 & MMP-2

• Folic acid to impact MMP-9

• Niacinamide to address tissue-damaging PARS

• Zinc – to reduce cytokine release

• Biotin – to reduce NF-Kappa production

Nutrients that impact matrix metalloproteinases:

Nutrients that affect the lifespan and health of connective tissues:

Additional nutrients:

Quote

As a rule of thumb, the earlier a musculoskeletal injury is treated, the

sooner healing can begin. An untreated injury can easily slide from “acute” into

“sub-acute”, and even into “chronic”

Nutrients to Address Swelling (within the First 72 Hours)

Tricket P. Proteolytic enzymes in treatment of athletic injury. Appl Ther 1964;30:647-652

Fortschr Med. 1995;113(19):303-306

Trypsin, Chymotrypsin, Bromelain

• Proteolytic enzymes –work on protein –containing chemicals

• Enzymes showed reduction in swelling, pain and inflammation

Proteolytic Enzymes

• Proteolytic enzymes – various enzymes that digest proteins and fibrin

• Work systemically when taken orally away from food

• Without food, they are absorbed with enzymes intact in the small intestines

• Turmeric:

1) Inhibit inflammation by blocking cyclooxygenase and lipoxygenase

2) Stimulates tissue repair, mainly the regeneration of muscle tissue

3) NF-KB inhibitor

• Ginger:

• Anti-inflammatory, antioxidant

• Boswelia serrata: inhibits 5-lipoxygenase

• Quercetin, cayenne: anti-inflammatory properties

Nutrients to Address Pain and Inflammation (within the first 72 hours)

Prostagladins Leukotr Med 1986;24:195-98Int J Clin Pharmacol Ther Toxicol 1986;24(12):651-54Journal of Biological Chemistry – August 2011. “Curcumin modulates nuclear factor-KB”

Iseri LT, French JH. Magnesium: nature’s physiologic calcium blocker. Am Heart J 1984;108(1):188-194.

Calcium & magnesium

• Calcium may work to relieve spasms by acting via pre-synaptic inhibition at neuromuscular junction

• Magnesium promotes muscle relaxation

• A balance of these minerals reduces spasm and cramping

Passion flower & valerian root

These herbs have been traditionally used to promote relaxation and are considered to be safe and effective

Nutrients to Address Muscle Tissue

Therapeutic Strategiesfor the UnavoidableAspects of Aging

• Osteoporosis affects over 20 million people in the United States alone

• Osteoporosis accounts for approximately 250,000 hip fractures per year

• Annual toll of 1.5 million fractures in total

Dempster DW, Lindsay R. Pathogenesis of osteoporosis. Lancet; 1993;341:797-805

Nutrition Masters Course™1988, Advanced Nutrition

Publications, Inc.. rev 1999