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Autoimmune Disorders and Lifestyle Medicine AMANDA MCKINNEY, MD, FACLM, FACOG, CPE

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Page 1: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

Autoimmune Disordersand Lifestyle MedicineAMANDA MCKINNEY MD FACLM FACOG CPE

Western Lifestyle and AutoimmunityGenetic Predisposition

Low Concordance rates in Monozygotic Twins

Environmental Factors (modulation of gut bacteria) Hygiene hypothesis

Psychosocial Stress

SmokingAlcohol

Lack of Physical Activity

Excess caloric intakeobesity

Lifestyle Related Autoimmune DisordersInflammatory Bowel Disease

Rheumatoid Arthritis

Multiple Sclerosis

Type 1 Diabetes

Inflammatory Bowel Disease

IBD16 million Americans

70000 new cases annually

80000 children

500100000 persons

Similar Trend in Westernized nations

SulfurEpigenetic modulation via Microbiome

Sulfur containing amino acids (methioninecysteine) and sulfur additives (food preservation)

Fermentative sulfidogenesis produces hydrogen sulfide gas

Linear relationship

Hydrogen SulfideDNA hypomethylation Apoptosis

Crypt architectural distortion

Mucosal Ulceration (cancer pre-cursor)

27mmolday vs 166 mmolday

H2S and UCH2S main factor responsible for UC relapse

Elimination of cowrsquos milk can improve symptomsreduce relapses

Meat consumption = 3 fold risk

Processed meat consumption = 5 fold risk

Alcohol consumption = 27 fold risk

Crohnrsquos DiseaseDramatic increases in Japan over the last century

Strong positive correlation with increases in dietary fat (total animal PUFA) and protein (animal and milk)

Inverse association with vegetable protein

IBD and SucraloseAspartame methanol formaldehyde

Sucralose reduces rsquos of beneficial bacteria

Sucralose mutagenic at high temperatures chloropropanols

Butyrate and IBD Butyrate SCFA produced via carbohydrate metabolism by

beneficial gut microbes Plays an important protective role in intestinal homeostasis

acting in both adaptive immunity and innate immunity

PBD high in fiber promote butyrate producing bacteria

PBD play a role in both prevention and treatment

Fiber Butyrate and UC Topical butyrate (enemas) is effective in UC

treatment

60 grams oat bran daily for 3 months increases butyrate by 36

Effect seen after 4 weeks

No relapse and improved symptoms in intervention group

Diet and Crohnrsquos2 year clinical trial 22 Crohnrsquos patients sp inpatient remission- SVD Remission rates on SVD 100 at 1 year 92 at 2

years

46 omnivores relapsed by end of year 2

Compared to drugs Higher remission rates (614136)

Less expense

No side effects

Additional Therapies2000 IU Vitamin D3

75 nmL = 44 reduced risk of Crohnrsquos related surgery

40 ngml = improved QOL scores and reduced disease activity

Additional TherapiesCurcumin alone 45 with UC remission

1 gram curcumin BID plus sulfasalazine or mesalamine 243 with relapse (5)

839 with relapse for those with no curcumin (20)

Endoscopic improvement in curcumin group

Rheumatoid Arthritis

(Epi)genetics of RAHLA-DR4 70 of RA patients

30 of general population

Subtypes = 90

Monozygotic concordance rate 15

Smoking triggers HLA production and seroconversion to HLA positive RA

Microbes and RARole of microbial infections in rheumatic disease GAS in rheumatic fever

Spirochetal infections in Lyme disease

Campylobacter Salmonella Shigella Yersinia and Chlamydia in reactive arthritis

Nowhellipoccult Proteus UTI and RA

Microbes and RAP mirabilis amino acid sequence resembles type XI collagen

Isolation rates of P mirabilis in RA patients is double that of E coli

Proteus isolated in 6350 of RA patients compared to 3211 controls

Urine from RA patients have elevated levels of Proteus antibodies

RA TreatmentProteus is a member of the Bacteroidesenterotype (associated with animal food diets)

Prevotella enterotype (associated with plant based diets)

Shifting from animalfoods to PBD reduces risk of occult Proteus UTI

AND reduces anti-Proteus antibodies

PBD also increases urine lignans which are anti-microbial

PBD for RA Treatment1999 randomized trial

13 months 27 intervention

26 controls

1227 intervention patients with 50 reduction in symptoms (responders)

226 control ldquorespondersrdquo

Intervention group 13 pound weight loss

Improved sed rate CRP and WBC count

After the intervention period patients were allowed to change diet however all rdquorespondersrdquo stayed with the diet and half of all ldquonon-respondersrdquo as well

Turmeric and RA2012- 8 week randomized pilot 45 patients2 groups

Group 1 500mg curcumin BID

Group 2 500 mg curcumin and 50mg diclofenac BID

Group 3 50mg diclofenac BID

Primary endpoint reduction in disease activity and joint swellingtenderness

Results Group 1 445 improvement

Group 2 444 improvement

Group 3 421 improvement

Adverse events only in diclofenac groups

Multiple Sclerosis

MS DistributionMost diagnosed ages 20-40

400000 in US and 25 million globally

Prevalence increases with distance from equator

57-78100000 below 37th parallel

110-140100000 above it

Higher incidence in colder climates and people of Northern European descent regardless of where they live

Women men 21

(Epi)genetics of MS

1-3 chance of MS if you have a sibling or parent with MS

Monozygotic concordance rate of 30 Roy Swank at OHSU hypothesized that the

distribution might be because people in northern latitudes tend to eat more animal foods

1952 study Frequency of MS in Norway directly related to amount of saturated animal fat consumed

Vitamin D and MSThose in northern latitudes also get less sun exposure

MS patients have lower 125(OH)2D levels at time of relapse

In Norway inland MS is higher than in fishing villages

Oily fish may compensate for relative lack of UV expsoure

Vitamin D and MS125(OH)2D moderates demyelination remyelination and stops oligodendrocyte apoptosis

Upreglates genomic activity on the strongest susceptiblility allele

Homozygosity of the CYP27B1 gene causes a form of rickets

3 individuals in Norway with this genetic rickets also developed MS

Heterozygosity increases risk of MS by 47 times

Dairy and MSMolecular mimicry between butyrophilin and myelin oligodendrocyte glycoprotein

Anti-BTN antibodies attack myelinated structures in the CNS and have been isolated in those with MS

MS TreatmentSafe and effective treatments are elusive

Interferon Side effects

$30000 per year

No evidence of a reduction in diabilityprogression

Mitoxantrone NNH 8 for irreversible systolic dysfunction and

123 for therapy-related acute leukemia

Dr Swank1951- 100 patients limited to 10-15 grams of saturated animal fat per day

3 frac12 year 5 frac12 year 7 year 20 year 34 year and 50 year follow up reports

After 34 years (1990) 95 of the patients were without progression of their disease

Increase in fat to 25-42gday was accompanied by increased disability and 3-fold increased risk of death to 79

In 2000 15 patients identified (50 year follow up) All could care for themselves independently

15 could ambulate as needed 13 truly ambulatory

MS TreatmentStudy on Vitamin D treatment in MS did not look at clinical outcomes

High dose Vitamin D supplementation did reduce helper T cells believed to be major contributors in immunopathogenesis of MS

Dose was 10400 IU daily and 21 of had to stop because of adverse effects

Type 1 Diabetes

Molecular Mimicry

Genetic Factors -alone cannot explain etiology

Environmental Factors- Cowrsquos milk antigens-Viruses

bull Enterovirusbull Coxackievirus Bbull Rotavirusbull Mumpsbull CMVbull Congenital Rubella

MYCOBACTERIUM PARATUBERCULOSISHSP 65

PBD in T1DType 1rsquos can develop insulin resistance with a high fat diet

PBD can reduce insulin requirements by 30-50

PBD can reduce risk of diabetic comorbidities

Latent autoimmune diabetes Adult onset non-obese Present without ketoacidosis and weight loss Anti-body positive Gradual insulin-dependence

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 2: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

Western Lifestyle and AutoimmunityGenetic Predisposition

Low Concordance rates in Monozygotic Twins

Environmental Factors (modulation of gut bacteria) Hygiene hypothesis

Psychosocial Stress

SmokingAlcohol

Lack of Physical Activity

Excess caloric intakeobesity

Lifestyle Related Autoimmune DisordersInflammatory Bowel Disease

Rheumatoid Arthritis

Multiple Sclerosis

Type 1 Diabetes

Inflammatory Bowel Disease

IBD16 million Americans

70000 new cases annually

80000 children

500100000 persons

Similar Trend in Westernized nations

SulfurEpigenetic modulation via Microbiome

Sulfur containing amino acids (methioninecysteine) and sulfur additives (food preservation)

Fermentative sulfidogenesis produces hydrogen sulfide gas

Linear relationship

Hydrogen SulfideDNA hypomethylation Apoptosis

Crypt architectural distortion

Mucosal Ulceration (cancer pre-cursor)

27mmolday vs 166 mmolday

H2S and UCH2S main factor responsible for UC relapse

Elimination of cowrsquos milk can improve symptomsreduce relapses

Meat consumption = 3 fold risk

Processed meat consumption = 5 fold risk

Alcohol consumption = 27 fold risk

Crohnrsquos DiseaseDramatic increases in Japan over the last century

Strong positive correlation with increases in dietary fat (total animal PUFA) and protein (animal and milk)

Inverse association with vegetable protein

IBD and SucraloseAspartame methanol formaldehyde

Sucralose reduces rsquos of beneficial bacteria

Sucralose mutagenic at high temperatures chloropropanols

Butyrate and IBD Butyrate SCFA produced via carbohydrate metabolism by

beneficial gut microbes Plays an important protective role in intestinal homeostasis

acting in both adaptive immunity and innate immunity

PBD high in fiber promote butyrate producing bacteria

PBD play a role in both prevention and treatment

Fiber Butyrate and UC Topical butyrate (enemas) is effective in UC

treatment

60 grams oat bran daily for 3 months increases butyrate by 36

Effect seen after 4 weeks

No relapse and improved symptoms in intervention group

Diet and Crohnrsquos2 year clinical trial 22 Crohnrsquos patients sp inpatient remission- SVD Remission rates on SVD 100 at 1 year 92 at 2

years

46 omnivores relapsed by end of year 2

Compared to drugs Higher remission rates (614136)

Less expense

No side effects

Additional Therapies2000 IU Vitamin D3

75 nmL = 44 reduced risk of Crohnrsquos related surgery

40 ngml = improved QOL scores and reduced disease activity

Additional TherapiesCurcumin alone 45 with UC remission

1 gram curcumin BID plus sulfasalazine or mesalamine 243 with relapse (5)

839 with relapse for those with no curcumin (20)

Endoscopic improvement in curcumin group

Rheumatoid Arthritis

(Epi)genetics of RAHLA-DR4 70 of RA patients

30 of general population

Subtypes = 90

Monozygotic concordance rate 15

Smoking triggers HLA production and seroconversion to HLA positive RA

Microbes and RARole of microbial infections in rheumatic disease GAS in rheumatic fever

Spirochetal infections in Lyme disease

Campylobacter Salmonella Shigella Yersinia and Chlamydia in reactive arthritis

Nowhellipoccult Proteus UTI and RA

Microbes and RAP mirabilis amino acid sequence resembles type XI collagen

Isolation rates of P mirabilis in RA patients is double that of E coli

Proteus isolated in 6350 of RA patients compared to 3211 controls

Urine from RA patients have elevated levels of Proteus antibodies

RA TreatmentProteus is a member of the Bacteroidesenterotype (associated with animal food diets)

Prevotella enterotype (associated with plant based diets)

Shifting from animalfoods to PBD reduces risk of occult Proteus UTI

AND reduces anti-Proteus antibodies

PBD also increases urine lignans which are anti-microbial

PBD for RA Treatment1999 randomized trial

13 months 27 intervention

26 controls

1227 intervention patients with 50 reduction in symptoms (responders)

226 control ldquorespondersrdquo

Intervention group 13 pound weight loss

Improved sed rate CRP and WBC count

After the intervention period patients were allowed to change diet however all rdquorespondersrdquo stayed with the diet and half of all ldquonon-respondersrdquo as well

Turmeric and RA2012- 8 week randomized pilot 45 patients2 groups

Group 1 500mg curcumin BID

Group 2 500 mg curcumin and 50mg diclofenac BID

Group 3 50mg diclofenac BID

Primary endpoint reduction in disease activity and joint swellingtenderness

Results Group 1 445 improvement

Group 2 444 improvement

Group 3 421 improvement

Adverse events only in diclofenac groups

Multiple Sclerosis

MS DistributionMost diagnosed ages 20-40

400000 in US and 25 million globally

Prevalence increases with distance from equator

57-78100000 below 37th parallel

110-140100000 above it

Higher incidence in colder climates and people of Northern European descent regardless of where they live

Women men 21

(Epi)genetics of MS

1-3 chance of MS if you have a sibling or parent with MS

Monozygotic concordance rate of 30 Roy Swank at OHSU hypothesized that the

distribution might be because people in northern latitudes tend to eat more animal foods

1952 study Frequency of MS in Norway directly related to amount of saturated animal fat consumed

Vitamin D and MSThose in northern latitudes also get less sun exposure

MS patients have lower 125(OH)2D levels at time of relapse

In Norway inland MS is higher than in fishing villages

Oily fish may compensate for relative lack of UV expsoure

Vitamin D and MS125(OH)2D moderates demyelination remyelination and stops oligodendrocyte apoptosis

Upreglates genomic activity on the strongest susceptiblility allele

Homozygosity of the CYP27B1 gene causes a form of rickets

3 individuals in Norway with this genetic rickets also developed MS

Heterozygosity increases risk of MS by 47 times

Dairy and MSMolecular mimicry between butyrophilin and myelin oligodendrocyte glycoprotein

Anti-BTN antibodies attack myelinated structures in the CNS and have been isolated in those with MS

MS TreatmentSafe and effective treatments are elusive

Interferon Side effects

$30000 per year

No evidence of a reduction in diabilityprogression

Mitoxantrone NNH 8 for irreversible systolic dysfunction and

123 for therapy-related acute leukemia

Dr Swank1951- 100 patients limited to 10-15 grams of saturated animal fat per day

3 frac12 year 5 frac12 year 7 year 20 year 34 year and 50 year follow up reports

After 34 years (1990) 95 of the patients were without progression of their disease

Increase in fat to 25-42gday was accompanied by increased disability and 3-fold increased risk of death to 79

In 2000 15 patients identified (50 year follow up) All could care for themselves independently

15 could ambulate as needed 13 truly ambulatory

MS TreatmentStudy on Vitamin D treatment in MS did not look at clinical outcomes

High dose Vitamin D supplementation did reduce helper T cells believed to be major contributors in immunopathogenesis of MS

Dose was 10400 IU daily and 21 of had to stop because of adverse effects

Type 1 Diabetes

Molecular Mimicry

Genetic Factors -alone cannot explain etiology

Environmental Factors- Cowrsquos milk antigens-Viruses

bull Enterovirusbull Coxackievirus Bbull Rotavirusbull Mumpsbull CMVbull Congenital Rubella

MYCOBACTERIUM PARATUBERCULOSISHSP 65

PBD in T1DType 1rsquos can develop insulin resistance with a high fat diet

PBD can reduce insulin requirements by 30-50

PBD can reduce risk of diabetic comorbidities

Latent autoimmune diabetes Adult onset non-obese Present without ketoacidosis and weight loss Anti-body positive Gradual insulin-dependence

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 3: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

Lifestyle Related Autoimmune DisordersInflammatory Bowel Disease

Rheumatoid Arthritis

Multiple Sclerosis

Type 1 Diabetes

Inflammatory Bowel Disease

IBD16 million Americans

70000 new cases annually

80000 children

500100000 persons

Similar Trend in Westernized nations

SulfurEpigenetic modulation via Microbiome

Sulfur containing amino acids (methioninecysteine) and sulfur additives (food preservation)

Fermentative sulfidogenesis produces hydrogen sulfide gas

Linear relationship

Hydrogen SulfideDNA hypomethylation Apoptosis

Crypt architectural distortion

Mucosal Ulceration (cancer pre-cursor)

27mmolday vs 166 mmolday

H2S and UCH2S main factor responsible for UC relapse

Elimination of cowrsquos milk can improve symptomsreduce relapses

Meat consumption = 3 fold risk

Processed meat consumption = 5 fold risk

Alcohol consumption = 27 fold risk

Crohnrsquos DiseaseDramatic increases in Japan over the last century

Strong positive correlation with increases in dietary fat (total animal PUFA) and protein (animal and milk)

Inverse association with vegetable protein

IBD and SucraloseAspartame methanol formaldehyde

Sucralose reduces rsquos of beneficial bacteria

Sucralose mutagenic at high temperatures chloropropanols

Butyrate and IBD Butyrate SCFA produced via carbohydrate metabolism by

beneficial gut microbes Plays an important protective role in intestinal homeostasis

acting in both adaptive immunity and innate immunity

PBD high in fiber promote butyrate producing bacteria

PBD play a role in both prevention and treatment

Fiber Butyrate and UC Topical butyrate (enemas) is effective in UC

treatment

60 grams oat bran daily for 3 months increases butyrate by 36

Effect seen after 4 weeks

No relapse and improved symptoms in intervention group

Diet and Crohnrsquos2 year clinical trial 22 Crohnrsquos patients sp inpatient remission- SVD Remission rates on SVD 100 at 1 year 92 at 2

years

46 omnivores relapsed by end of year 2

Compared to drugs Higher remission rates (614136)

Less expense

No side effects

Additional Therapies2000 IU Vitamin D3

75 nmL = 44 reduced risk of Crohnrsquos related surgery

40 ngml = improved QOL scores and reduced disease activity

Additional TherapiesCurcumin alone 45 with UC remission

1 gram curcumin BID plus sulfasalazine or mesalamine 243 with relapse (5)

839 with relapse for those with no curcumin (20)

Endoscopic improvement in curcumin group

Rheumatoid Arthritis

(Epi)genetics of RAHLA-DR4 70 of RA patients

30 of general population

Subtypes = 90

Monozygotic concordance rate 15

Smoking triggers HLA production and seroconversion to HLA positive RA

Microbes and RARole of microbial infections in rheumatic disease GAS in rheumatic fever

Spirochetal infections in Lyme disease

Campylobacter Salmonella Shigella Yersinia and Chlamydia in reactive arthritis

Nowhellipoccult Proteus UTI and RA

Microbes and RAP mirabilis amino acid sequence resembles type XI collagen

Isolation rates of P mirabilis in RA patients is double that of E coli

Proteus isolated in 6350 of RA patients compared to 3211 controls

Urine from RA patients have elevated levels of Proteus antibodies

RA TreatmentProteus is a member of the Bacteroidesenterotype (associated with animal food diets)

Prevotella enterotype (associated with plant based diets)

Shifting from animalfoods to PBD reduces risk of occult Proteus UTI

AND reduces anti-Proteus antibodies

PBD also increases urine lignans which are anti-microbial

PBD for RA Treatment1999 randomized trial

13 months 27 intervention

26 controls

1227 intervention patients with 50 reduction in symptoms (responders)

226 control ldquorespondersrdquo

Intervention group 13 pound weight loss

Improved sed rate CRP and WBC count

After the intervention period patients were allowed to change diet however all rdquorespondersrdquo stayed with the diet and half of all ldquonon-respondersrdquo as well

Turmeric and RA2012- 8 week randomized pilot 45 patients2 groups

Group 1 500mg curcumin BID

Group 2 500 mg curcumin and 50mg diclofenac BID

Group 3 50mg diclofenac BID

Primary endpoint reduction in disease activity and joint swellingtenderness

Results Group 1 445 improvement

Group 2 444 improvement

Group 3 421 improvement

Adverse events only in diclofenac groups

Multiple Sclerosis

MS DistributionMost diagnosed ages 20-40

400000 in US and 25 million globally

Prevalence increases with distance from equator

57-78100000 below 37th parallel

110-140100000 above it

Higher incidence in colder climates and people of Northern European descent regardless of where they live

Women men 21

(Epi)genetics of MS

1-3 chance of MS if you have a sibling or parent with MS

Monozygotic concordance rate of 30 Roy Swank at OHSU hypothesized that the

distribution might be because people in northern latitudes tend to eat more animal foods

1952 study Frequency of MS in Norway directly related to amount of saturated animal fat consumed

Vitamin D and MSThose in northern latitudes also get less sun exposure

MS patients have lower 125(OH)2D levels at time of relapse

In Norway inland MS is higher than in fishing villages

Oily fish may compensate for relative lack of UV expsoure

Vitamin D and MS125(OH)2D moderates demyelination remyelination and stops oligodendrocyte apoptosis

Upreglates genomic activity on the strongest susceptiblility allele

Homozygosity of the CYP27B1 gene causes a form of rickets

3 individuals in Norway with this genetic rickets also developed MS

Heterozygosity increases risk of MS by 47 times

Dairy and MSMolecular mimicry between butyrophilin and myelin oligodendrocyte glycoprotein

Anti-BTN antibodies attack myelinated structures in the CNS and have been isolated in those with MS

MS TreatmentSafe and effective treatments are elusive

Interferon Side effects

$30000 per year

No evidence of a reduction in diabilityprogression

Mitoxantrone NNH 8 for irreversible systolic dysfunction and

123 for therapy-related acute leukemia

Dr Swank1951- 100 patients limited to 10-15 grams of saturated animal fat per day

3 frac12 year 5 frac12 year 7 year 20 year 34 year and 50 year follow up reports

After 34 years (1990) 95 of the patients were without progression of their disease

Increase in fat to 25-42gday was accompanied by increased disability and 3-fold increased risk of death to 79

In 2000 15 patients identified (50 year follow up) All could care for themselves independently

15 could ambulate as needed 13 truly ambulatory

MS TreatmentStudy on Vitamin D treatment in MS did not look at clinical outcomes

High dose Vitamin D supplementation did reduce helper T cells believed to be major contributors in immunopathogenesis of MS

Dose was 10400 IU daily and 21 of had to stop because of adverse effects

Type 1 Diabetes

Molecular Mimicry

Genetic Factors -alone cannot explain etiology

Environmental Factors- Cowrsquos milk antigens-Viruses

bull Enterovirusbull Coxackievirus Bbull Rotavirusbull Mumpsbull CMVbull Congenital Rubella

MYCOBACTERIUM PARATUBERCULOSISHSP 65

PBD in T1DType 1rsquos can develop insulin resistance with a high fat diet

PBD can reduce insulin requirements by 30-50

PBD can reduce risk of diabetic comorbidities

Latent autoimmune diabetes Adult onset non-obese Present without ketoacidosis and weight loss Anti-body positive Gradual insulin-dependence

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 4: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

Inflammatory Bowel Disease

IBD16 million Americans

70000 new cases annually

80000 children

500100000 persons

Similar Trend in Westernized nations

SulfurEpigenetic modulation via Microbiome

Sulfur containing amino acids (methioninecysteine) and sulfur additives (food preservation)

Fermentative sulfidogenesis produces hydrogen sulfide gas

Linear relationship

Hydrogen SulfideDNA hypomethylation Apoptosis

Crypt architectural distortion

Mucosal Ulceration (cancer pre-cursor)

27mmolday vs 166 mmolday

H2S and UCH2S main factor responsible for UC relapse

Elimination of cowrsquos milk can improve symptomsreduce relapses

Meat consumption = 3 fold risk

Processed meat consumption = 5 fold risk

Alcohol consumption = 27 fold risk

Crohnrsquos DiseaseDramatic increases in Japan over the last century

Strong positive correlation with increases in dietary fat (total animal PUFA) and protein (animal and milk)

Inverse association with vegetable protein

IBD and SucraloseAspartame methanol formaldehyde

Sucralose reduces rsquos of beneficial bacteria

Sucralose mutagenic at high temperatures chloropropanols

Butyrate and IBD Butyrate SCFA produced via carbohydrate metabolism by

beneficial gut microbes Plays an important protective role in intestinal homeostasis

acting in both adaptive immunity and innate immunity

PBD high in fiber promote butyrate producing bacteria

PBD play a role in both prevention and treatment

Fiber Butyrate and UC Topical butyrate (enemas) is effective in UC

treatment

60 grams oat bran daily for 3 months increases butyrate by 36

Effect seen after 4 weeks

No relapse and improved symptoms in intervention group

Diet and Crohnrsquos2 year clinical trial 22 Crohnrsquos patients sp inpatient remission- SVD Remission rates on SVD 100 at 1 year 92 at 2

years

46 omnivores relapsed by end of year 2

Compared to drugs Higher remission rates (614136)

Less expense

No side effects

Additional Therapies2000 IU Vitamin D3

75 nmL = 44 reduced risk of Crohnrsquos related surgery

40 ngml = improved QOL scores and reduced disease activity

Additional TherapiesCurcumin alone 45 with UC remission

1 gram curcumin BID plus sulfasalazine or mesalamine 243 with relapse (5)

839 with relapse for those with no curcumin (20)

Endoscopic improvement in curcumin group

Rheumatoid Arthritis

(Epi)genetics of RAHLA-DR4 70 of RA patients

30 of general population

Subtypes = 90

Monozygotic concordance rate 15

Smoking triggers HLA production and seroconversion to HLA positive RA

Microbes and RARole of microbial infections in rheumatic disease GAS in rheumatic fever

Spirochetal infections in Lyme disease

Campylobacter Salmonella Shigella Yersinia and Chlamydia in reactive arthritis

Nowhellipoccult Proteus UTI and RA

Microbes and RAP mirabilis amino acid sequence resembles type XI collagen

Isolation rates of P mirabilis in RA patients is double that of E coli

Proteus isolated in 6350 of RA patients compared to 3211 controls

Urine from RA patients have elevated levels of Proteus antibodies

RA TreatmentProteus is a member of the Bacteroidesenterotype (associated with animal food diets)

Prevotella enterotype (associated with plant based diets)

Shifting from animalfoods to PBD reduces risk of occult Proteus UTI

AND reduces anti-Proteus antibodies

PBD also increases urine lignans which are anti-microbial

PBD for RA Treatment1999 randomized trial

13 months 27 intervention

26 controls

1227 intervention patients with 50 reduction in symptoms (responders)

226 control ldquorespondersrdquo

Intervention group 13 pound weight loss

Improved sed rate CRP and WBC count

After the intervention period patients were allowed to change diet however all rdquorespondersrdquo stayed with the diet and half of all ldquonon-respondersrdquo as well

Turmeric and RA2012- 8 week randomized pilot 45 patients2 groups

Group 1 500mg curcumin BID

Group 2 500 mg curcumin and 50mg diclofenac BID

Group 3 50mg diclofenac BID

Primary endpoint reduction in disease activity and joint swellingtenderness

Results Group 1 445 improvement

Group 2 444 improvement

Group 3 421 improvement

Adverse events only in diclofenac groups

Multiple Sclerosis

MS DistributionMost diagnosed ages 20-40

400000 in US and 25 million globally

Prevalence increases with distance from equator

57-78100000 below 37th parallel

110-140100000 above it

Higher incidence in colder climates and people of Northern European descent regardless of where they live

Women men 21

(Epi)genetics of MS

1-3 chance of MS if you have a sibling or parent with MS

Monozygotic concordance rate of 30 Roy Swank at OHSU hypothesized that the

distribution might be because people in northern latitudes tend to eat more animal foods

1952 study Frequency of MS in Norway directly related to amount of saturated animal fat consumed

Vitamin D and MSThose in northern latitudes also get less sun exposure

MS patients have lower 125(OH)2D levels at time of relapse

In Norway inland MS is higher than in fishing villages

Oily fish may compensate for relative lack of UV expsoure

Vitamin D and MS125(OH)2D moderates demyelination remyelination and stops oligodendrocyte apoptosis

Upreglates genomic activity on the strongest susceptiblility allele

Homozygosity of the CYP27B1 gene causes a form of rickets

3 individuals in Norway with this genetic rickets also developed MS

Heterozygosity increases risk of MS by 47 times

Dairy and MSMolecular mimicry between butyrophilin and myelin oligodendrocyte glycoprotein

Anti-BTN antibodies attack myelinated structures in the CNS and have been isolated in those with MS

MS TreatmentSafe and effective treatments are elusive

Interferon Side effects

$30000 per year

No evidence of a reduction in diabilityprogression

Mitoxantrone NNH 8 for irreversible systolic dysfunction and

123 for therapy-related acute leukemia

Dr Swank1951- 100 patients limited to 10-15 grams of saturated animal fat per day

3 frac12 year 5 frac12 year 7 year 20 year 34 year and 50 year follow up reports

After 34 years (1990) 95 of the patients were without progression of their disease

Increase in fat to 25-42gday was accompanied by increased disability and 3-fold increased risk of death to 79

In 2000 15 patients identified (50 year follow up) All could care for themselves independently

15 could ambulate as needed 13 truly ambulatory

MS TreatmentStudy on Vitamin D treatment in MS did not look at clinical outcomes

High dose Vitamin D supplementation did reduce helper T cells believed to be major contributors in immunopathogenesis of MS

Dose was 10400 IU daily and 21 of had to stop because of adverse effects

Type 1 Diabetes

Molecular Mimicry

Genetic Factors -alone cannot explain etiology

Environmental Factors- Cowrsquos milk antigens-Viruses

bull Enterovirusbull Coxackievirus Bbull Rotavirusbull Mumpsbull CMVbull Congenital Rubella

MYCOBACTERIUM PARATUBERCULOSISHSP 65

PBD in T1DType 1rsquos can develop insulin resistance with a high fat diet

PBD can reduce insulin requirements by 30-50

PBD can reduce risk of diabetic comorbidities

Latent autoimmune diabetes Adult onset non-obese Present without ketoacidosis and weight loss Anti-body positive Gradual insulin-dependence

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 5: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

IBD16 million Americans

70000 new cases annually

80000 children

500100000 persons

Similar Trend in Westernized nations

SulfurEpigenetic modulation via Microbiome

Sulfur containing amino acids (methioninecysteine) and sulfur additives (food preservation)

Fermentative sulfidogenesis produces hydrogen sulfide gas

Linear relationship

Hydrogen SulfideDNA hypomethylation Apoptosis

Crypt architectural distortion

Mucosal Ulceration (cancer pre-cursor)

27mmolday vs 166 mmolday

H2S and UCH2S main factor responsible for UC relapse

Elimination of cowrsquos milk can improve symptomsreduce relapses

Meat consumption = 3 fold risk

Processed meat consumption = 5 fold risk

Alcohol consumption = 27 fold risk

Crohnrsquos DiseaseDramatic increases in Japan over the last century

Strong positive correlation with increases in dietary fat (total animal PUFA) and protein (animal and milk)

Inverse association with vegetable protein

IBD and SucraloseAspartame methanol formaldehyde

Sucralose reduces rsquos of beneficial bacteria

Sucralose mutagenic at high temperatures chloropropanols

Butyrate and IBD Butyrate SCFA produced via carbohydrate metabolism by

beneficial gut microbes Plays an important protective role in intestinal homeostasis

acting in both adaptive immunity and innate immunity

PBD high in fiber promote butyrate producing bacteria

PBD play a role in both prevention and treatment

Fiber Butyrate and UC Topical butyrate (enemas) is effective in UC

treatment

60 grams oat bran daily for 3 months increases butyrate by 36

Effect seen after 4 weeks

No relapse and improved symptoms in intervention group

Diet and Crohnrsquos2 year clinical trial 22 Crohnrsquos patients sp inpatient remission- SVD Remission rates on SVD 100 at 1 year 92 at 2

years

46 omnivores relapsed by end of year 2

Compared to drugs Higher remission rates (614136)

Less expense

No side effects

Additional Therapies2000 IU Vitamin D3

75 nmL = 44 reduced risk of Crohnrsquos related surgery

40 ngml = improved QOL scores and reduced disease activity

Additional TherapiesCurcumin alone 45 with UC remission

1 gram curcumin BID plus sulfasalazine or mesalamine 243 with relapse (5)

839 with relapse for those with no curcumin (20)

Endoscopic improvement in curcumin group

Rheumatoid Arthritis

(Epi)genetics of RAHLA-DR4 70 of RA patients

30 of general population

Subtypes = 90

Monozygotic concordance rate 15

Smoking triggers HLA production and seroconversion to HLA positive RA

Microbes and RARole of microbial infections in rheumatic disease GAS in rheumatic fever

Spirochetal infections in Lyme disease

Campylobacter Salmonella Shigella Yersinia and Chlamydia in reactive arthritis

Nowhellipoccult Proteus UTI and RA

Microbes and RAP mirabilis amino acid sequence resembles type XI collagen

Isolation rates of P mirabilis in RA patients is double that of E coli

Proteus isolated in 6350 of RA patients compared to 3211 controls

Urine from RA patients have elevated levels of Proteus antibodies

RA TreatmentProteus is a member of the Bacteroidesenterotype (associated with animal food diets)

Prevotella enterotype (associated with plant based diets)

Shifting from animalfoods to PBD reduces risk of occult Proteus UTI

AND reduces anti-Proteus antibodies

PBD also increases urine lignans which are anti-microbial

PBD for RA Treatment1999 randomized trial

13 months 27 intervention

26 controls

1227 intervention patients with 50 reduction in symptoms (responders)

226 control ldquorespondersrdquo

Intervention group 13 pound weight loss

Improved sed rate CRP and WBC count

After the intervention period patients were allowed to change diet however all rdquorespondersrdquo stayed with the diet and half of all ldquonon-respondersrdquo as well

Turmeric and RA2012- 8 week randomized pilot 45 patients2 groups

Group 1 500mg curcumin BID

Group 2 500 mg curcumin and 50mg diclofenac BID

Group 3 50mg diclofenac BID

Primary endpoint reduction in disease activity and joint swellingtenderness

Results Group 1 445 improvement

Group 2 444 improvement

Group 3 421 improvement

Adverse events only in diclofenac groups

Multiple Sclerosis

MS DistributionMost diagnosed ages 20-40

400000 in US and 25 million globally

Prevalence increases with distance from equator

57-78100000 below 37th parallel

110-140100000 above it

Higher incidence in colder climates and people of Northern European descent regardless of where they live

Women men 21

(Epi)genetics of MS

1-3 chance of MS if you have a sibling or parent with MS

Monozygotic concordance rate of 30 Roy Swank at OHSU hypothesized that the

distribution might be because people in northern latitudes tend to eat more animal foods

1952 study Frequency of MS in Norway directly related to amount of saturated animal fat consumed

Vitamin D and MSThose in northern latitudes also get less sun exposure

MS patients have lower 125(OH)2D levels at time of relapse

In Norway inland MS is higher than in fishing villages

Oily fish may compensate for relative lack of UV expsoure

Vitamin D and MS125(OH)2D moderates demyelination remyelination and stops oligodendrocyte apoptosis

Upreglates genomic activity on the strongest susceptiblility allele

Homozygosity of the CYP27B1 gene causes a form of rickets

3 individuals in Norway with this genetic rickets also developed MS

Heterozygosity increases risk of MS by 47 times

Dairy and MSMolecular mimicry between butyrophilin and myelin oligodendrocyte glycoprotein

Anti-BTN antibodies attack myelinated structures in the CNS and have been isolated in those with MS

MS TreatmentSafe and effective treatments are elusive

Interferon Side effects

$30000 per year

No evidence of a reduction in diabilityprogression

Mitoxantrone NNH 8 for irreversible systolic dysfunction and

123 for therapy-related acute leukemia

Dr Swank1951- 100 patients limited to 10-15 grams of saturated animal fat per day

3 frac12 year 5 frac12 year 7 year 20 year 34 year and 50 year follow up reports

After 34 years (1990) 95 of the patients were without progression of their disease

Increase in fat to 25-42gday was accompanied by increased disability and 3-fold increased risk of death to 79

In 2000 15 patients identified (50 year follow up) All could care for themselves independently

15 could ambulate as needed 13 truly ambulatory

MS TreatmentStudy on Vitamin D treatment in MS did not look at clinical outcomes

High dose Vitamin D supplementation did reduce helper T cells believed to be major contributors in immunopathogenesis of MS

Dose was 10400 IU daily and 21 of had to stop because of adverse effects

Type 1 Diabetes

Molecular Mimicry

Genetic Factors -alone cannot explain etiology

Environmental Factors- Cowrsquos milk antigens-Viruses

bull Enterovirusbull Coxackievirus Bbull Rotavirusbull Mumpsbull CMVbull Congenital Rubella

MYCOBACTERIUM PARATUBERCULOSISHSP 65

PBD in T1DType 1rsquos can develop insulin resistance with a high fat diet

PBD can reduce insulin requirements by 30-50

PBD can reduce risk of diabetic comorbidities

Latent autoimmune diabetes Adult onset non-obese Present without ketoacidosis and weight loss Anti-body positive Gradual insulin-dependence

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 6: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

SulfurEpigenetic modulation via Microbiome

Sulfur containing amino acids (methioninecysteine) and sulfur additives (food preservation)

Fermentative sulfidogenesis produces hydrogen sulfide gas

Linear relationship

Hydrogen SulfideDNA hypomethylation Apoptosis

Crypt architectural distortion

Mucosal Ulceration (cancer pre-cursor)

27mmolday vs 166 mmolday

H2S and UCH2S main factor responsible for UC relapse

Elimination of cowrsquos milk can improve symptomsreduce relapses

Meat consumption = 3 fold risk

Processed meat consumption = 5 fold risk

Alcohol consumption = 27 fold risk

Crohnrsquos DiseaseDramatic increases in Japan over the last century

Strong positive correlation with increases in dietary fat (total animal PUFA) and protein (animal and milk)

Inverse association with vegetable protein

IBD and SucraloseAspartame methanol formaldehyde

Sucralose reduces rsquos of beneficial bacteria

Sucralose mutagenic at high temperatures chloropropanols

Butyrate and IBD Butyrate SCFA produced via carbohydrate metabolism by

beneficial gut microbes Plays an important protective role in intestinal homeostasis

acting in both adaptive immunity and innate immunity

PBD high in fiber promote butyrate producing bacteria

PBD play a role in both prevention and treatment

Fiber Butyrate and UC Topical butyrate (enemas) is effective in UC

treatment

60 grams oat bran daily for 3 months increases butyrate by 36

Effect seen after 4 weeks

No relapse and improved symptoms in intervention group

Diet and Crohnrsquos2 year clinical trial 22 Crohnrsquos patients sp inpatient remission- SVD Remission rates on SVD 100 at 1 year 92 at 2

years

46 omnivores relapsed by end of year 2

Compared to drugs Higher remission rates (614136)

Less expense

No side effects

Additional Therapies2000 IU Vitamin D3

75 nmL = 44 reduced risk of Crohnrsquos related surgery

40 ngml = improved QOL scores and reduced disease activity

Additional TherapiesCurcumin alone 45 with UC remission

1 gram curcumin BID plus sulfasalazine or mesalamine 243 with relapse (5)

839 with relapse for those with no curcumin (20)

Endoscopic improvement in curcumin group

Rheumatoid Arthritis

(Epi)genetics of RAHLA-DR4 70 of RA patients

30 of general population

Subtypes = 90

Monozygotic concordance rate 15

Smoking triggers HLA production and seroconversion to HLA positive RA

Microbes and RARole of microbial infections in rheumatic disease GAS in rheumatic fever

Spirochetal infections in Lyme disease

Campylobacter Salmonella Shigella Yersinia and Chlamydia in reactive arthritis

Nowhellipoccult Proteus UTI and RA

Microbes and RAP mirabilis amino acid sequence resembles type XI collagen

Isolation rates of P mirabilis in RA patients is double that of E coli

Proteus isolated in 6350 of RA patients compared to 3211 controls

Urine from RA patients have elevated levels of Proteus antibodies

RA TreatmentProteus is a member of the Bacteroidesenterotype (associated with animal food diets)

Prevotella enterotype (associated with plant based diets)

Shifting from animalfoods to PBD reduces risk of occult Proteus UTI

AND reduces anti-Proteus antibodies

PBD also increases urine lignans which are anti-microbial

PBD for RA Treatment1999 randomized trial

13 months 27 intervention

26 controls

1227 intervention patients with 50 reduction in symptoms (responders)

226 control ldquorespondersrdquo

Intervention group 13 pound weight loss

Improved sed rate CRP and WBC count

After the intervention period patients were allowed to change diet however all rdquorespondersrdquo stayed with the diet and half of all ldquonon-respondersrdquo as well

Turmeric and RA2012- 8 week randomized pilot 45 patients2 groups

Group 1 500mg curcumin BID

Group 2 500 mg curcumin and 50mg diclofenac BID

Group 3 50mg diclofenac BID

Primary endpoint reduction in disease activity and joint swellingtenderness

Results Group 1 445 improvement

Group 2 444 improvement

Group 3 421 improvement

Adverse events only in diclofenac groups

Multiple Sclerosis

MS DistributionMost diagnosed ages 20-40

400000 in US and 25 million globally

Prevalence increases with distance from equator

57-78100000 below 37th parallel

110-140100000 above it

Higher incidence in colder climates and people of Northern European descent regardless of where they live

Women men 21

(Epi)genetics of MS

1-3 chance of MS if you have a sibling or parent with MS

Monozygotic concordance rate of 30 Roy Swank at OHSU hypothesized that the

distribution might be because people in northern latitudes tend to eat more animal foods

1952 study Frequency of MS in Norway directly related to amount of saturated animal fat consumed

Vitamin D and MSThose in northern latitudes also get less sun exposure

MS patients have lower 125(OH)2D levels at time of relapse

In Norway inland MS is higher than in fishing villages

Oily fish may compensate for relative lack of UV expsoure

Vitamin D and MS125(OH)2D moderates demyelination remyelination and stops oligodendrocyte apoptosis

Upreglates genomic activity on the strongest susceptiblility allele

Homozygosity of the CYP27B1 gene causes a form of rickets

3 individuals in Norway with this genetic rickets also developed MS

Heterozygosity increases risk of MS by 47 times

Dairy and MSMolecular mimicry between butyrophilin and myelin oligodendrocyte glycoprotein

Anti-BTN antibodies attack myelinated structures in the CNS and have been isolated in those with MS

MS TreatmentSafe and effective treatments are elusive

Interferon Side effects

$30000 per year

No evidence of a reduction in diabilityprogression

Mitoxantrone NNH 8 for irreversible systolic dysfunction and

123 for therapy-related acute leukemia

Dr Swank1951- 100 patients limited to 10-15 grams of saturated animal fat per day

3 frac12 year 5 frac12 year 7 year 20 year 34 year and 50 year follow up reports

After 34 years (1990) 95 of the patients were without progression of their disease

Increase in fat to 25-42gday was accompanied by increased disability and 3-fold increased risk of death to 79

In 2000 15 patients identified (50 year follow up) All could care for themselves independently

15 could ambulate as needed 13 truly ambulatory

MS TreatmentStudy on Vitamin D treatment in MS did not look at clinical outcomes

High dose Vitamin D supplementation did reduce helper T cells believed to be major contributors in immunopathogenesis of MS

Dose was 10400 IU daily and 21 of had to stop because of adverse effects

Type 1 Diabetes

Molecular Mimicry

Genetic Factors -alone cannot explain etiology

Environmental Factors- Cowrsquos milk antigens-Viruses

bull Enterovirusbull Coxackievirus Bbull Rotavirusbull Mumpsbull CMVbull Congenital Rubella

MYCOBACTERIUM PARATUBERCULOSISHSP 65

PBD in T1DType 1rsquos can develop insulin resistance with a high fat diet

PBD can reduce insulin requirements by 30-50

PBD can reduce risk of diabetic comorbidities

Latent autoimmune diabetes Adult onset non-obese Present without ketoacidosis and weight loss Anti-body positive Gradual insulin-dependence

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 7: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

Hydrogen SulfideDNA hypomethylation Apoptosis

Crypt architectural distortion

Mucosal Ulceration (cancer pre-cursor)

27mmolday vs 166 mmolday

H2S and UCH2S main factor responsible for UC relapse

Elimination of cowrsquos milk can improve symptomsreduce relapses

Meat consumption = 3 fold risk

Processed meat consumption = 5 fold risk

Alcohol consumption = 27 fold risk

Crohnrsquos DiseaseDramatic increases in Japan over the last century

Strong positive correlation with increases in dietary fat (total animal PUFA) and protein (animal and milk)

Inverse association with vegetable protein

IBD and SucraloseAspartame methanol formaldehyde

Sucralose reduces rsquos of beneficial bacteria

Sucralose mutagenic at high temperatures chloropropanols

Butyrate and IBD Butyrate SCFA produced via carbohydrate metabolism by

beneficial gut microbes Plays an important protective role in intestinal homeostasis

acting in both adaptive immunity and innate immunity

PBD high in fiber promote butyrate producing bacteria

PBD play a role in both prevention and treatment

Fiber Butyrate and UC Topical butyrate (enemas) is effective in UC

treatment

60 grams oat bran daily for 3 months increases butyrate by 36

Effect seen after 4 weeks

No relapse and improved symptoms in intervention group

Diet and Crohnrsquos2 year clinical trial 22 Crohnrsquos patients sp inpatient remission- SVD Remission rates on SVD 100 at 1 year 92 at 2

years

46 omnivores relapsed by end of year 2

Compared to drugs Higher remission rates (614136)

Less expense

No side effects

Additional Therapies2000 IU Vitamin D3

75 nmL = 44 reduced risk of Crohnrsquos related surgery

40 ngml = improved QOL scores and reduced disease activity

Additional TherapiesCurcumin alone 45 with UC remission

1 gram curcumin BID plus sulfasalazine or mesalamine 243 with relapse (5)

839 with relapse for those with no curcumin (20)

Endoscopic improvement in curcumin group

Rheumatoid Arthritis

(Epi)genetics of RAHLA-DR4 70 of RA patients

30 of general population

Subtypes = 90

Monozygotic concordance rate 15

Smoking triggers HLA production and seroconversion to HLA positive RA

Microbes and RARole of microbial infections in rheumatic disease GAS in rheumatic fever

Spirochetal infections in Lyme disease

Campylobacter Salmonella Shigella Yersinia and Chlamydia in reactive arthritis

Nowhellipoccult Proteus UTI and RA

Microbes and RAP mirabilis amino acid sequence resembles type XI collagen

Isolation rates of P mirabilis in RA patients is double that of E coli

Proteus isolated in 6350 of RA patients compared to 3211 controls

Urine from RA patients have elevated levels of Proteus antibodies

RA TreatmentProteus is a member of the Bacteroidesenterotype (associated with animal food diets)

Prevotella enterotype (associated with plant based diets)

Shifting from animalfoods to PBD reduces risk of occult Proteus UTI

AND reduces anti-Proteus antibodies

PBD also increases urine lignans which are anti-microbial

PBD for RA Treatment1999 randomized trial

13 months 27 intervention

26 controls

1227 intervention patients with 50 reduction in symptoms (responders)

226 control ldquorespondersrdquo

Intervention group 13 pound weight loss

Improved sed rate CRP and WBC count

After the intervention period patients were allowed to change diet however all rdquorespondersrdquo stayed with the diet and half of all ldquonon-respondersrdquo as well

Turmeric and RA2012- 8 week randomized pilot 45 patients2 groups

Group 1 500mg curcumin BID

Group 2 500 mg curcumin and 50mg diclofenac BID

Group 3 50mg diclofenac BID

Primary endpoint reduction in disease activity and joint swellingtenderness

Results Group 1 445 improvement

Group 2 444 improvement

Group 3 421 improvement

Adverse events only in diclofenac groups

Multiple Sclerosis

MS DistributionMost diagnosed ages 20-40

400000 in US and 25 million globally

Prevalence increases with distance from equator

57-78100000 below 37th parallel

110-140100000 above it

Higher incidence in colder climates and people of Northern European descent regardless of where they live

Women men 21

(Epi)genetics of MS

1-3 chance of MS if you have a sibling or parent with MS

Monozygotic concordance rate of 30 Roy Swank at OHSU hypothesized that the

distribution might be because people in northern latitudes tend to eat more animal foods

1952 study Frequency of MS in Norway directly related to amount of saturated animal fat consumed

Vitamin D and MSThose in northern latitudes also get less sun exposure

MS patients have lower 125(OH)2D levels at time of relapse

In Norway inland MS is higher than in fishing villages

Oily fish may compensate for relative lack of UV expsoure

Vitamin D and MS125(OH)2D moderates demyelination remyelination and stops oligodendrocyte apoptosis

Upreglates genomic activity on the strongest susceptiblility allele

Homozygosity of the CYP27B1 gene causes a form of rickets

3 individuals in Norway with this genetic rickets also developed MS

Heterozygosity increases risk of MS by 47 times

Dairy and MSMolecular mimicry between butyrophilin and myelin oligodendrocyte glycoprotein

Anti-BTN antibodies attack myelinated structures in the CNS and have been isolated in those with MS

MS TreatmentSafe and effective treatments are elusive

Interferon Side effects

$30000 per year

No evidence of a reduction in diabilityprogression

Mitoxantrone NNH 8 for irreversible systolic dysfunction and

123 for therapy-related acute leukemia

Dr Swank1951- 100 patients limited to 10-15 grams of saturated animal fat per day

3 frac12 year 5 frac12 year 7 year 20 year 34 year and 50 year follow up reports

After 34 years (1990) 95 of the patients were without progression of their disease

Increase in fat to 25-42gday was accompanied by increased disability and 3-fold increased risk of death to 79

In 2000 15 patients identified (50 year follow up) All could care for themselves independently

15 could ambulate as needed 13 truly ambulatory

MS TreatmentStudy on Vitamin D treatment in MS did not look at clinical outcomes

High dose Vitamin D supplementation did reduce helper T cells believed to be major contributors in immunopathogenesis of MS

Dose was 10400 IU daily and 21 of had to stop because of adverse effects

Type 1 Diabetes

Molecular Mimicry

Genetic Factors -alone cannot explain etiology

Environmental Factors- Cowrsquos milk antigens-Viruses

bull Enterovirusbull Coxackievirus Bbull Rotavirusbull Mumpsbull CMVbull Congenital Rubella

MYCOBACTERIUM PARATUBERCULOSISHSP 65

PBD in T1DType 1rsquos can develop insulin resistance with a high fat diet

PBD can reduce insulin requirements by 30-50

PBD can reduce risk of diabetic comorbidities

Latent autoimmune diabetes Adult onset non-obese Present without ketoacidosis and weight loss Anti-body positive Gradual insulin-dependence

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 8: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

H2S and UCH2S main factor responsible for UC relapse

Elimination of cowrsquos milk can improve symptomsreduce relapses

Meat consumption = 3 fold risk

Processed meat consumption = 5 fold risk

Alcohol consumption = 27 fold risk

Crohnrsquos DiseaseDramatic increases in Japan over the last century

Strong positive correlation with increases in dietary fat (total animal PUFA) and protein (animal and milk)

Inverse association with vegetable protein

IBD and SucraloseAspartame methanol formaldehyde

Sucralose reduces rsquos of beneficial bacteria

Sucralose mutagenic at high temperatures chloropropanols

Butyrate and IBD Butyrate SCFA produced via carbohydrate metabolism by

beneficial gut microbes Plays an important protective role in intestinal homeostasis

acting in both adaptive immunity and innate immunity

PBD high in fiber promote butyrate producing bacteria

PBD play a role in both prevention and treatment

Fiber Butyrate and UC Topical butyrate (enemas) is effective in UC

treatment

60 grams oat bran daily for 3 months increases butyrate by 36

Effect seen after 4 weeks

No relapse and improved symptoms in intervention group

Diet and Crohnrsquos2 year clinical trial 22 Crohnrsquos patients sp inpatient remission- SVD Remission rates on SVD 100 at 1 year 92 at 2

years

46 omnivores relapsed by end of year 2

Compared to drugs Higher remission rates (614136)

Less expense

No side effects

Additional Therapies2000 IU Vitamin D3

75 nmL = 44 reduced risk of Crohnrsquos related surgery

40 ngml = improved QOL scores and reduced disease activity

Additional TherapiesCurcumin alone 45 with UC remission

1 gram curcumin BID plus sulfasalazine or mesalamine 243 with relapse (5)

839 with relapse for those with no curcumin (20)

Endoscopic improvement in curcumin group

Rheumatoid Arthritis

(Epi)genetics of RAHLA-DR4 70 of RA patients

30 of general population

Subtypes = 90

Monozygotic concordance rate 15

Smoking triggers HLA production and seroconversion to HLA positive RA

Microbes and RARole of microbial infections in rheumatic disease GAS in rheumatic fever

Spirochetal infections in Lyme disease

Campylobacter Salmonella Shigella Yersinia and Chlamydia in reactive arthritis

Nowhellipoccult Proteus UTI and RA

Microbes and RAP mirabilis amino acid sequence resembles type XI collagen

Isolation rates of P mirabilis in RA patients is double that of E coli

Proteus isolated in 6350 of RA patients compared to 3211 controls

Urine from RA patients have elevated levels of Proteus antibodies

RA TreatmentProteus is a member of the Bacteroidesenterotype (associated with animal food diets)

Prevotella enterotype (associated with plant based diets)

Shifting from animalfoods to PBD reduces risk of occult Proteus UTI

AND reduces anti-Proteus antibodies

PBD also increases urine lignans which are anti-microbial

PBD for RA Treatment1999 randomized trial

13 months 27 intervention

26 controls

1227 intervention patients with 50 reduction in symptoms (responders)

226 control ldquorespondersrdquo

Intervention group 13 pound weight loss

Improved sed rate CRP and WBC count

After the intervention period patients were allowed to change diet however all rdquorespondersrdquo stayed with the diet and half of all ldquonon-respondersrdquo as well

Turmeric and RA2012- 8 week randomized pilot 45 patients2 groups

Group 1 500mg curcumin BID

Group 2 500 mg curcumin and 50mg diclofenac BID

Group 3 50mg diclofenac BID

Primary endpoint reduction in disease activity and joint swellingtenderness

Results Group 1 445 improvement

Group 2 444 improvement

Group 3 421 improvement

Adverse events only in diclofenac groups

Multiple Sclerosis

MS DistributionMost diagnosed ages 20-40

400000 in US and 25 million globally

Prevalence increases with distance from equator

57-78100000 below 37th parallel

110-140100000 above it

Higher incidence in colder climates and people of Northern European descent regardless of where they live

Women men 21

(Epi)genetics of MS

1-3 chance of MS if you have a sibling or parent with MS

Monozygotic concordance rate of 30 Roy Swank at OHSU hypothesized that the

distribution might be because people in northern latitudes tend to eat more animal foods

1952 study Frequency of MS in Norway directly related to amount of saturated animal fat consumed

Vitamin D and MSThose in northern latitudes also get less sun exposure

MS patients have lower 125(OH)2D levels at time of relapse

In Norway inland MS is higher than in fishing villages

Oily fish may compensate for relative lack of UV expsoure

Vitamin D and MS125(OH)2D moderates demyelination remyelination and stops oligodendrocyte apoptosis

Upreglates genomic activity on the strongest susceptiblility allele

Homozygosity of the CYP27B1 gene causes a form of rickets

3 individuals in Norway with this genetic rickets also developed MS

Heterozygosity increases risk of MS by 47 times

Dairy and MSMolecular mimicry between butyrophilin and myelin oligodendrocyte glycoprotein

Anti-BTN antibodies attack myelinated structures in the CNS and have been isolated in those with MS

MS TreatmentSafe and effective treatments are elusive

Interferon Side effects

$30000 per year

No evidence of a reduction in diabilityprogression

Mitoxantrone NNH 8 for irreversible systolic dysfunction and

123 for therapy-related acute leukemia

Dr Swank1951- 100 patients limited to 10-15 grams of saturated animal fat per day

3 frac12 year 5 frac12 year 7 year 20 year 34 year and 50 year follow up reports

After 34 years (1990) 95 of the patients were without progression of their disease

Increase in fat to 25-42gday was accompanied by increased disability and 3-fold increased risk of death to 79

In 2000 15 patients identified (50 year follow up) All could care for themselves independently

15 could ambulate as needed 13 truly ambulatory

MS TreatmentStudy on Vitamin D treatment in MS did not look at clinical outcomes

High dose Vitamin D supplementation did reduce helper T cells believed to be major contributors in immunopathogenesis of MS

Dose was 10400 IU daily and 21 of had to stop because of adverse effects

Type 1 Diabetes

Molecular Mimicry

Genetic Factors -alone cannot explain etiology

Environmental Factors- Cowrsquos milk antigens-Viruses

bull Enterovirusbull Coxackievirus Bbull Rotavirusbull Mumpsbull CMVbull Congenital Rubella

MYCOBACTERIUM PARATUBERCULOSISHSP 65

PBD in T1DType 1rsquos can develop insulin resistance with a high fat diet

PBD can reduce insulin requirements by 30-50

PBD can reduce risk of diabetic comorbidities

Latent autoimmune diabetes Adult onset non-obese Present without ketoacidosis and weight loss Anti-body positive Gradual insulin-dependence

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 9: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

Crohnrsquos DiseaseDramatic increases in Japan over the last century

Strong positive correlation with increases in dietary fat (total animal PUFA) and protein (animal and milk)

Inverse association with vegetable protein

IBD and SucraloseAspartame methanol formaldehyde

Sucralose reduces rsquos of beneficial bacteria

Sucralose mutagenic at high temperatures chloropropanols

Butyrate and IBD Butyrate SCFA produced via carbohydrate metabolism by

beneficial gut microbes Plays an important protective role in intestinal homeostasis

acting in both adaptive immunity and innate immunity

PBD high in fiber promote butyrate producing bacteria

PBD play a role in both prevention and treatment

Fiber Butyrate and UC Topical butyrate (enemas) is effective in UC

treatment

60 grams oat bran daily for 3 months increases butyrate by 36

Effect seen after 4 weeks

No relapse and improved symptoms in intervention group

Diet and Crohnrsquos2 year clinical trial 22 Crohnrsquos patients sp inpatient remission- SVD Remission rates on SVD 100 at 1 year 92 at 2

years

46 omnivores relapsed by end of year 2

Compared to drugs Higher remission rates (614136)

Less expense

No side effects

Additional Therapies2000 IU Vitamin D3

75 nmL = 44 reduced risk of Crohnrsquos related surgery

40 ngml = improved QOL scores and reduced disease activity

Additional TherapiesCurcumin alone 45 with UC remission

1 gram curcumin BID plus sulfasalazine or mesalamine 243 with relapse (5)

839 with relapse for those with no curcumin (20)

Endoscopic improvement in curcumin group

Rheumatoid Arthritis

(Epi)genetics of RAHLA-DR4 70 of RA patients

30 of general population

Subtypes = 90

Monozygotic concordance rate 15

Smoking triggers HLA production and seroconversion to HLA positive RA

Microbes and RARole of microbial infections in rheumatic disease GAS in rheumatic fever

Spirochetal infections in Lyme disease

Campylobacter Salmonella Shigella Yersinia and Chlamydia in reactive arthritis

Nowhellipoccult Proteus UTI and RA

Microbes and RAP mirabilis amino acid sequence resembles type XI collagen

Isolation rates of P mirabilis in RA patients is double that of E coli

Proteus isolated in 6350 of RA patients compared to 3211 controls

Urine from RA patients have elevated levels of Proteus antibodies

RA TreatmentProteus is a member of the Bacteroidesenterotype (associated with animal food diets)

Prevotella enterotype (associated with plant based diets)

Shifting from animalfoods to PBD reduces risk of occult Proteus UTI

AND reduces anti-Proteus antibodies

PBD also increases urine lignans which are anti-microbial

PBD for RA Treatment1999 randomized trial

13 months 27 intervention

26 controls

1227 intervention patients with 50 reduction in symptoms (responders)

226 control ldquorespondersrdquo

Intervention group 13 pound weight loss

Improved sed rate CRP and WBC count

After the intervention period patients were allowed to change diet however all rdquorespondersrdquo stayed with the diet and half of all ldquonon-respondersrdquo as well

Turmeric and RA2012- 8 week randomized pilot 45 patients2 groups

Group 1 500mg curcumin BID

Group 2 500 mg curcumin and 50mg diclofenac BID

Group 3 50mg diclofenac BID

Primary endpoint reduction in disease activity and joint swellingtenderness

Results Group 1 445 improvement

Group 2 444 improvement

Group 3 421 improvement

Adverse events only in diclofenac groups

Multiple Sclerosis

MS DistributionMost diagnosed ages 20-40

400000 in US and 25 million globally

Prevalence increases with distance from equator

57-78100000 below 37th parallel

110-140100000 above it

Higher incidence in colder climates and people of Northern European descent regardless of where they live

Women men 21

(Epi)genetics of MS

1-3 chance of MS if you have a sibling or parent with MS

Monozygotic concordance rate of 30 Roy Swank at OHSU hypothesized that the

distribution might be because people in northern latitudes tend to eat more animal foods

1952 study Frequency of MS in Norway directly related to amount of saturated animal fat consumed

Vitamin D and MSThose in northern latitudes also get less sun exposure

MS patients have lower 125(OH)2D levels at time of relapse

In Norway inland MS is higher than in fishing villages

Oily fish may compensate for relative lack of UV expsoure

Vitamin D and MS125(OH)2D moderates demyelination remyelination and stops oligodendrocyte apoptosis

Upreglates genomic activity on the strongest susceptiblility allele

Homozygosity of the CYP27B1 gene causes a form of rickets

3 individuals in Norway with this genetic rickets also developed MS

Heterozygosity increases risk of MS by 47 times

Dairy and MSMolecular mimicry between butyrophilin and myelin oligodendrocyte glycoprotein

Anti-BTN antibodies attack myelinated structures in the CNS and have been isolated in those with MS

MS TreatmentSafe and effective treatments are elusive

Interferon Side effects

$30000 per year

No evidence of a reduction in diabilityprogression

Mitoxantrone NNH 8 for irreversible systolic dysfunction and

123 for therapy-related acute leukemia

Dr Swank1951- 100 patients limited to 10-15 grams of saturated animal fat per day

3 frac12 year 5 frac12 year 7 year 20 year 34 year and 50 year follow up reports

After 34 years (1990) 95 of the patients were without progression of their disease

Increase in fat to 25-42gday was accompanied by increased disability and 3-fold increased risk of death to 79

In 2000 15 patients identified (50 year follow up) All could care for themselves independently

15 could ambulate as needed 13 truly ambulatory

MS TreatmentStudy on Vitamin D treatment in MS did not look at clinical outcomes

High dose Vitamin D supplementation did reduce helper T cells believed to be major contributors in immunopathogenesis of MS

Dose was 10400 IU daily and 21 of had to stop because of adverse effects

Type 1 Diabetes

Molecular Mimicry

Genetic Factors -alone cannot explain etiology

Environmental Factors- Cowrsquos milk antigens-Viruses

bull Enterovirusbull Coxackievirus Bbull Rotavirusbull Mumpsbull CMVbull Congenital Rubella

MYCOBACTERIUM PARATUBERCULOSISHSP 65

PBD in T1DType 1rsquos can develop insulin resistance with a high fat diet

PBD can reduce insulin requirements by 30-50

PBD can reduce risk of diabetic comorbidities

Latent autoimmune diabetes Adult onset non-obese Present without ketoacidosis and weight loss Anti-body positive Gradual insulin-dependence

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 10: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

IBD and SucraloseAspartame methanol formaldehyde

Sucralose reduces rsquos of beneficial bacteria

Sucralose mutagenic at high temperatures chloropropanols

Butyrate and IBD Butyrate SCFA produced via carbohydrate metabolism by

beneficial gut microbes Plays an important protective role in intestinal homeostasis

acting in both adaptive immunity and innate immunity

PBD high in fiber promote butyrate producing bacteria

PBD play a role in both prevention and treatment

Fiber Butyrate and UC Topical butyrate (enemas) is effective in UC

treatment

60 grams oat bran daily for 3 months increases butyrate by 36

Effect seen after 4 weeks

No relapse and improved symptoms in intervention group

Diet and Crohnrsquos2 year clinical trial 22 Crohnrsquos patients sp inpatient remission- SVD Remission rates on SVD 100 at 1 year 92 at 2

years

46 omnivores relapsed by end of year 2

Compared to drugs Higher remission rates (614136)

Less expense

No side effects

Additional Therapies2000 IU Vitamin D3

75 nmL = 44 reduced risk of Crohnrsquos related surgery

40 ngml = improved QOL scores and reduced disease activity

Additional TherapiesCurcumin alone 45 with UC remission

1 gram curcumin BID plus sulfasalazine or mesalamine 243 with relapse (5)

839 with relapse for those with no curcumin (20)

Endoscopic improvement in curcumin group

Rheumatoid Arthritis

(Epi)genetics of RAHLA-DR4 70 of RA patients

30 of general population

Subtypes = 90

Monozygotic concordance rate 15

Smoking triggers HLA production and seroconversion to HLA positive RA

Microbes and RARole of microbial infections in rheumatic disease GAS in rheumatic fever

Spirochetal infections in Lyme disease

Campylobacter Salmonella Shigella Yersinia and Chlamydia in reactive arthritis

Nowhellipoccult Proteus UTI and RA

Microbes and RAP mirabilis amino acid sequence resembles type XI collagen

Isolation rates of P mirabilis in RA patients is double that of E coli

Proteus isolated in 6350 of RA patients compared to 3211 controls

Urine from RA patients have elevated levels of Proteus antibodies

RA TreatmentProteus is a member of the Bacteroidesenterotype (associated with animal food diets)

Prevotella enterotype (associated with plant based diets)

Shifting from animalfoods to PBD reduces risk of occult Proteus UTI

AND reduces anti-Proteus antibodies

PBD also increases urine lignans which are anti-microbial

PBD for RA Treatment1999 randomized trial

13 months 27 intervention

26 controls

1227 intervention patients with 50 reduction in symptoms (responders)

226 control ldquorespondersrdquo

Intervention group 13 pound weight loss

Improved sed rate CRP and WBC count

After the intervention period patients were allowed to change diet however all rdquorespondersrdquo stayed with the diet and half of all ldquonon-respondersrdquo as well

Turmeric and RA2012- 8 week randomized pilot 45 patients2 groups

Group 1 500mg curcumin BID

Group 2 500 mg curcumin and 50mg diclofenac BID

Group 3 50mg diclofenac BID

Primary endpoint reduction in disease activity and joint swellingtenderness

Results Group 1 445 improvement

Group 2 444 improvement

Group 3 421 improvement

Adverse events only in diclofenac groups

Multiple Sclerosis

MS DistributionMost diagnosed ages 20-40

400000 in US and 25 million globally

Prevalence increases with distance from equator

57-78100000 below 37th parallel

110-140100000 above it

Higher incidence in colder climates and people of Northern European descent regardless of where they live

Women men 21

(Epi)genetics of MS

1-3 chance of MS if you have a sibling or parent with MS

Monozygotic concordance rate of 30 Roy Swank at OHSU hypothesized that the

distribution might be because people in northern latitudes tend to eat more animal foods

1952 study Frequency of MS in Norway directly related to amount of saturated animal fat consumed

Vitamin D and MSThose in northern latitudes also get less sun exposure

MS patients have lower 125(OH)2D levels at time of relapse

In Norway inland MS is higher than in fishing villages

Oily fish may compensate for relative lack of UV expsoure

Vitamin D and MS125(OH)2D moderates demyelination remyelination and stops oligodendrocyte apoptosis

Upreglates genomic activity on the strongest susceptiblility allele

Homozygosity of the CYP27B1 gene causes a form of rickets

3 individuals in Norway with this genetic rickets also developed MS

Heterozygosity increases risk of MS by 47 times

Dairy and MSMolecular mimicry between butyrophilin and myelin oligodendrocyte glycoprotein

Anti-BTN antibodies attack myelinated structures in the CNS and have been isolated in those with MS

MS TreatmentSafe and effective treatments are elusive

Interferon Side effects

$30000 per year

No evidence of a reduction in diabilityprogression

Mitoxantrone NNH 8 for irreversible systolic dysfunction and

123 for therapy-related acute leukemia

Dr Swank1951- 100 patients limited to 10-15 grams of saturated animal fat per day

3 frac12 year 5 frac12 year 7 year 20 year 34 year and 50 year follow up reports

After 34 years (1990) 95 of the patients were without progression of their disease

Increase in fat to 25-42gday was accompanied by increased disability and 3-fold increased risk of death to 79

In 2000 15 patients identified (50 year follow up) All could care for themselves independently

15 could ambulate as needed 13 truly ambulatory

MS TreatmentStudy on Vitamin D treatment in MS did not look at clinical outcomes

High dose Vitamin D supplementation did reduce helper T cells believed to be major contributors in immunopathogenesis of MS

Dose was 10400 IU daily and 21 of had to stop because of adverse effects

Type 1 Diabetes

Molecular Mimicry

Genetic Factors -alone cannot explain etiology

Environmental Factors- Cowrsquos milk antigens-Viruses

bull Enterovirusbull Coxackievirus Bbull Rotavirusbull Mumpsbull CMVbull Congenital Rubella

MYCOBACTERIUM PARATUBERCULOSISHSP 65

PBD in T1DType 1rsquos can develop insulin resistance with a high fat diet

PBD can reduce insulin requirements by 30-50

PBD can reduce risk of diabetic comorbidities

Latent autoimmune diabetes Adult onset non-obese Present without ketoacidosis and weight loss Anti-body positive Gradual insulin-dependence

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 11: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

Butyrate and IBD Butyrate SCFA produced via carbohydrate metabolism by

beneficial gut microbes Plays an important protective role in intestinal homeostasis

acting in both adaptive immunity and innate immunity

PBD high in fiber promote butyrate producing bacteria

PBD play a role in both prevention and treatment

Fiber Butyrate and UC Topical butyrate (enemas) is effective in UC

treatment

60 grams oat bran daily for 3 months increases butyrate by 36

Effect seen after 4 weeks

No relapse and improved symptoms in intervention group

Diet and Crohnrsquos2 year clinical trial 22 Crohnrsquos patients sp inpatient remission- SVD Remission rates on SVD 100 at 1 year 92 at 2

years

46 omnivores relapsed by end of year 2

Compared to drugs Higher remission rates (614136)

Less expense

No side effects

Additional Therapies2000 IU Vitamin D3

75 nmL = 44 reduced risk of Crohnrsquos related surgery

40 ngml = improved QOL scores and reduced disease activity

Additional TherapiesCurcumin alone 45 with UC remission

1 gram curcumin BID plus sulfasalazine or mesalamine 243 with relapse (5)

839 with relapse for those with no curcumin (20)

Endoscopic improvement in curcumin group

Rheumatoid Arthritis

(Epi)genetics of RAHLA-DR4 70 of RA patients

30 of general population

Subtypes = 90

Monozygotic concordance rate 15

Smoking triggers HLA production and seroconversion to HLA positive RA

Microbes and RARole of microbial infections in rheumatic disease GAS in rheumatic fever

Spirochetal infections in Lyme disease

Campylobacter Salmonella Shigella Yersinia and Chlamydia in reactive arthritis

Nowhellipoccult Proteus UTI and RA

Microbes and RAP mirabilis amino acid sequence resembles type XI collagen

Isolation rates of P mirabilis in RA patients is double that of E coli

Proteus isolated in 6350 of RA patients compared to 3211 controls

Urine from RA patients have elevated levels of Proteus antibodies

RA TreatmentProteus is a member of the Bacteroidesenterotype (associated with animal food diets)

Prevotella enterotype (associated with plant based diets)

Shifting from animalfoods to PBD reduces risk of occult Proteus UTI

AND reduces anti-Proteus antibodies

PBD also increases urine lignans which are anti-microbial

PBD for RA Treatment1999 randomized trial

13 months 27 intervention

26 controls

1227 intervention patients with 50 reduction in symptoms (responders)

226 control ldquorespondersrdquo

Intervention group 13 pound weight loss

Improved sed rate CRP and WBC count

After the intervention period patients were allowed to change diet however all rdquorespondersrdquo stayed with the diet and half of all ldquonon-respondersrdquo as well

Turmeric and RA2012- 8 week randomized pilot 45 patients2 groups

Group 1 500mg curcumin BID

Group 2 500 mg curcumin and 50mg diclofenac BID

Group 3 50mg diclofenac BID

Primary endpoint reduction in disease activity and joint swellingtenderness

Results Group 1 445 improvement

Group 2 444 improvement

Group 3 421 improvement

Adverse events only in diclofenac groups

Multiple Sclerosis

MS DistributionMost diagnosed ages 20-40

400000 in US and 25 million globally

Prevalence increases with distance from equator

57-78100000 below 37th parallel

110-140100000 above it

Higher incidence in colder climates and people of Northern European descent regardless of where they live

Women men 21

(Epi)genetics of MS

1-3 chance of MS if you have a sibling or parent with MS

Monozygotic concordance rate of 30 Roy Swank at OHSU hypothesized that the

distribution might be because people in northern latitudes tend to eat more animal foods

1952 study Frequency of MS in Norway directly related to amount of saturated animal fat consumed

Vitamin D and MSThose in northern latitudes also get less sun exposure

MS patients have lower 125(OH)2D levels at time of relapse

In Norway inland MS is higher than in fishing villages

Oily fish may compensate for relative lack of UV expsoure

Vitamin D and MS125(OH)2D moderates demyelination remyelination and stops oligodendrocyte apoptosis

Upreglates genomic activity on the strongest susceptiblility allele

Homozygosity of the CYP27B1 gene causes a form of rickets

3 individuals in Norway with this genetic rickets also developed MS

Heterozygosity increases risk of MS by 47 times

Dairy and MSMolecular mimicry between butyrophilin and myelin oligodendrocyte glycoprotein

Anti-BTN antibodies attack myelinated structures in the CNS and have been isolated in those with MS

MS TreatmentSafe and effective treatments are elusive

Interferon Side effects

$30000 per year

No evidence of a reduction in diabilityprogression

Mitoxantrone NNH 8 for irreversible systolic dysfunction and

123 for therapy-related acute leukemia

Dr Swank1951- 100 patients limited to 10-15 grams of saturated animal fat per day

3 frac12 year 5 frac12 year 7 year 20 year 34 year and 50 year follow up reports

After 34 years (1990) 95 of the patients were without progression of their disease

Increase in fat to 25-42gday was accompanied by increased disability and 3-fold increased risk of death to 79

In 2000 15 patients identified (50 year follow up) All could care for themselves independently

15 could ambulate as needed 13 truly ambulatory

MS TreatmentStudy on Vitamin D treatment in MS did not look at clinical outcomes

High dose Vitamin D supplementation did reduce helper T cells believed to be major contributors in immunopathogenesis of MS

Dose was 10400 IU daily and 21 of had to stop because of adverse effects

Type 1 Diabetes

Molecular Mimicry

Genetic Factors -alone cannot explain etiology

Environmental Factors- Cowrsquos milk antigens-Viruses

bull Enterovirusbull Coxackievirus Bbull Rotavirusbull Mumpsbull CMVbull Congenital Rubella

MYCOBACTERIUM PARATUBERCULOSISHSP 65

PBD in T1DType 1rsquos can develop insulin resistance with a high fat diet

PBD can reduce insulin requirements by 30-50

PBD can reduce risk of diabetic comorbidities

Latent autoimmune diabetes Adult onset non-obese Present without ketoacidosis and weight loss Anti-body positive Gradual insulin-dependence

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 12: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

Fiber Butyrate and UC Topical butyrate (enemas) is effective in UC

treatment

60 grams oat bran daily for 3 months increases butyrate by 36

Effect seen after 4 weeks

No relapse and improved symptoms in intervention group

Diet and Crohnrsquos2 year clinical trial 22 Crohnrsquos patients sp inpatient remission- SVD Remission rates on SVD 100 at 1 year 92 at 2

years

46 omnivores relapsed by end of year 2

Compared to drugs Higher remission rates (614136)

Less expense

No side effects

Additional Therapies2000 IU Vitamin D3

75 nmL = 44 reduced risk of Crohnrsquos related surgery

40 ngml = improved QOL scores and reduced disease activity

Additional TherapiesCurcumin alone 45 with UC remission

1 gram curcumin BID plus sulfasalazine or mesalamine 243 with relapse (5)

839 with relapse for those with no curcumin (20)

Endoscopic improvement in curcumin group

Rheumatoid Arthritis

(Epi)genetics of RAHLA-DR4 70 of RA patients

30 of general population

Subtypes = 90

Monozygotic concordance rate 15

Smoking triggers HLA production and seroconversion to HLA positive RA

Microbes and RARole of microbial infections in rheumatic disease GAS in rheumatic fever

Spirochetal infections in Lyme disease

Campylobacter Salmonella Shigella Yersinia and Chlamydia in reactive arthritis

Nowhellipoccult Proteus UTI and RA

Microbes and RAP mirabilis amino acid sequence resembles type XI collagen

Isolation rates of P mirabilis in RA patients is double that of E coli

Proteus isolated in 6350 of RA patients compared to 3211 controls

Urine from RA patients have elevated levels of Proteus antibodies

RA TreatmentProteus is a member of the Bacteroidesenterotype (associated with animal food diets)

Prevotella enterotype (associated with plant based diets)

Shifting from animalfoods to PBD reduces risk of occult Proteus UTI

AND reduces anti-Proteus antibodies

PBD also increases urine lignans which are anti-microbial

PBD for RA Treatment1999 randomized trial

13 months 27 intervention

26 controls

1227 intervention patients with 50 reduction in symptoms (responders)

226 control ldquorespondersrdquo

Intervention group 13 pound weight loss

Improved sed rate CRP and WBC count

After the intervention period patients were allowed to change diet however all rdquorespondersrdquo stayed with the diet and half of all ldquonon-respondersrdquo as well

Turmeric and RA2012- 8 week randomized pilot 45 patients2 groups

Group 1 500mg curcumin BID

Group 2 500 mg curcumin and 50mg diclofenac BID

Group 3 50mg diclofenac BID

Primary endpoint reduction in disease activity and joint swellingtenderness

Results Group 1 445 improvement

Group 2 444 improvement

Group 3 421 improvement

Adverse events only in diclofenac groups

Multiple Sclerosis

MS DistributionMost diagnosed ages 20-40

400000 in US and 25 million globally

Prevalence increases with distance from equator

57-78100000 below 37th parallel

110-140100000 above it

Higher incidence in colder climates and people of Northern European descent regardless of where they live

Women men 21

(Epi)genetics of MS

1-3 chance of MS if you have a sibling or parent with MS

Monozygotic concordance rate of 30 Roy Swank at OHSU hypothesized that the

distribution might be because people in northern latitudes tend to eat more animal foods

1952 study Frequency of MS in Norway directly related to amount of saturated animal fat consumed

Vitamin D and MSThose in northern latitudes also get less sun exposure

MS patients have lower 125(OH)2D levels at time of relapse

In Norway inland MS is higher than in fishing villages

Oily fish may compensate for relative lack of UV expsoure

Vitamin D and MS125(OH)2D moderates demyelination remyelination and stops oligodendrocyte apoptosis

Upreglates genomic activity on the strongest susceptiblility allele

Homozygosity of the CYP27B1 gene causes a form of rickets

3 individuals in Norway with this genetic rickets also developed MS

Heterozygosity increases risk of MS by 47 times

Dairy and MSMolecular mimicry between butyrophilin and myelin oligodendrocyte glycoprotein

Anti-BTN antibodies attack myelinated structures in the CNS and have been isolated in those with MS

MS TreatmentSafe and effective treatments are elusive

Interferon Side effects

$30000 per year

No evidence of a reduction in diabilityprogression

Mitoxantrone NNH 8 for irreversible systolic dysfunction and

123 for therapy-related acute leukemia

Dr Swank1951- 100 patients limited to 10-15 grams of saturated animal fat per day

3 frac12 year 5 frac12 year 7 year 20 year 34 year and 50 year follow up reports

After 34 years (1990) 95 of the patients were without progression of their disease

Increase in fat to 25-42gday was accompanied by increased disability and 3-fold increased risk of death to 79

In 2000 15 patients identified (50 year follow up) All could care for themselves independently

15 could ambulate as needed 13 truly ambulatory

MS TreatmentStudy on Vitamin D treatment in MS did not look at clinical outcomes

High dose Vitamin D supplementation did reduce helper T cells believed to be major contributors in immunopathogenesis of MS

Dose was 10400 IU daily and 21 of had to stop because of adverse effects

Type 1 Diabetes

Molecular Mimicry

Genetic Factors -alone cannot explain etiology

Environmental Factors- Cowrsquos milk antigens-Viruses

bull Enterovirusbull Coxackievirus Bbull Rotavirusbull Mumpsbull CMVbull Congenital Rubella

MYCOBACTERIUM PARATUBERCULOSISHSP 65

PBD in T1DType 1rsquos can develop insulin resistance with a high fat diet

PBD can reduce insulin requirements by 30-50

PBD can reduce risk of diabetic comorbidities

Latent autoimmune diabetes Adult onset non-obese Present without ketoacidosis and weight loss Anti-body positive Gradual insulin-dependence

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 13: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

Diet and Crohnrsquos2 year clinical trial 22 Crohnrsquos patients sp inpatient remission- SVD Remission rates on SVD 100 at 1 year 92 at 2

years

46 omnivores relapsed by end of year 2

Compared to drugs Higher remission rates (614136)

Less expense

No side effects

Additional Therapies2000 IU Vitamin D3

75 nmL = 44 reduced risk of Crohnrsquos related surgery

40 ngml = improved QOL scores and reduced disease activity

Additional TherapiesCurcumin alone 45 with UC remission

1 gram curcumin BID plus sulfasalazine or mesalamine 243 with relapse (5)

839 with relapse for those with no curcumin (20)

Endoscopic improvement in curcumin group

Rheumatoid Arthritis

(Epi)genetics of RAHLA-DR4 70 of RA patients

30 of general population

Subtypes = 90

Monozygotic concordance rate 15

Smoking triggers HLA production and seroconversion to HLA positive RA

Microbes and RARole of microbial infections in rheumatic disease GAS in rheumatic fever

Spirochetal infections in Lyme disease

Campylobacter Salmonella Shigella Yersinia and Chlamydia in reactive arthritis

Nowhellipoccult Proteus UTI and RA

Microbes and RAP mirabilis amino acid sequence resembles type XI collagen

Isolation rates of P mirabilis in RA patients is double that of E coli

Proteus isolated in 6350 of RA patients compared to 3211 controls

Urine from RA patients have elevated levels of Proteus antibodies

RA TreatmentProteus is a member of the Bacteroidesenterotype (associated with animal food diets)

Prevotella enterotype (associated with plant based diets)

Shifting from animalfoods to PBD reduces risk of occult Proteus UTI

AND reduces anti-Proteus antibodies

PBD also increases urine lignans which are anti-microbial

PBD for RA Treatment1999 randomized trial

13 months 27 intervention

26 controls

1227 intervention patients with 50 reduction in symptoms (responders)

226 control ldquorespondersrdquo

Intervention group 13 pound weight loss

Improved sed rate CRP and WBC count

After the intervention period patients were allowed to change diet however all rdquorespondersrdquo stayed with the diet and half of all ldquonon-respondersrdquo as well

Turmeric and RA2012- 8 week randomized pilot 45 patients2 groups

Group 1 500mg curcumin BID

Group 2 500 mg curcumin and 50mg diclofenac BID

Group 3 50mg diclofenac BID

Primary endpoint reduction in disease activity and joint swellingtenderness

Results Group 1 445 improvement

Group 2 444 improvement

Group 3 421 improvement

Adverse events only in diclofenac groups

Multiple Sclerosis

MS DistributionMost diagnosed ages 20-40

400000 in US and 25 million globally

Prevalence increases with distance from equator

57-78100000 below 37th parallel

110-140100000 above it

Higher incidence in colder climates and people of Northern European descent regardless of where they live

Women men 21

(Epi)genetics of MS

1-3 chance of MS if you have a sibling or parent with MS

Monozygotic concordance rate of 30 Roy Swank at OHSU hypothesized that the

distribution might be because people in northern latitudes tend to eat more animal foods

1952 study Frequency of MS in Norway directly related to amount of saturated animal fat consumed

Vitamin D and MSThose in northern latitudes also get less sun exposure

MS patients have lower 125(OH)2D levels at time of relapse

In Norway inland MS is higher than in fishing villages

Oily fish may compensate for relative lack of UV expsoure

Vitamin D and MS125(OH)2D moderates demyelination remyelination and stops oligodendrocyte apoptosis

Upreglates genomic activity on the strongest susceptiblility allele

Homozygosity of the CYP27B1 gene causes a form of rickets

3 individuals in Norway with this genetic rickets also developed MS

Heterozygosity increases risk of MS by 47 times

Dairy and MSMolecular mimicry between butyrophilin and myelin oligodendrocyte glycoprotein

Anti-BTN antibodies attack myelinated structures in the CNS and have been isolated in those with MS

MS TreatmentSafe and effective treatments are elusive

Interferon Side effects

$30000 per year

No evidence of a reduction in diabilityprogression

Mitoxantrone NNH 8 for irreversible systolic dysfunction and

123 for therapy-related acute leukemia

Dr Swank1951- 100 patients limited to 10-15 grams of saturated animal fat per day

3 frac12 year 5 frac12 year 7 year 20 year 34 year and 50 year follow up reports

After 34 years (1990) 95 of the patients were without progression of their disease

Increase in fat to 25-42gday was accompanied by increased disability and 3-fold increased risk of death to 79

In 2000 15 patients identified (50 year follow up) All could care for themselves independently

15 could ambulate as needed 13 truly ambulatory

MS TreatmentStudy on Vitamin D treatment in MS did not look at clinical outcomes

High dose Vitamin D supplementation did reduce helper T cells believed to be major contributors in immunopathogenesis of MS

Dose was 10400 IU daily and 21 of had to stop because of adverse effects

Type 1 Diabetes

Molecular Mimicry

Genetic Factors -alone cannot explain etiology

Environmental Factors- Cowrsquos milk antigens-Viruses

bull Enterovirusbull Coxackievirus Bbull Rotavirusbull Mumpsbull CMVbull Congenital Rubella

MYCOBACTERIUM PARATUBERCULOSISHSP 65

PBD in T1DType 1rsquos can develop insulin resistance with a high fat diet

PBD can reduce insulin requirements by 30-50

PBD can reduce risk of diabetic comorbidities

Latent autoimmune diabetes Adult onset non-obese Present without ketoacidosis and weight loss Anti-body positive Gradual insulin-dependence

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 14: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

Additional Therapies2000 IU Vitamin D3

75 nmL = 44 reduced risk of Crohnrsquos related surgery

40 ngml = improved QOL scores and reduced disease activity

Additional TherapiesCurcumin alone 45 with UC remission

1 gram curcumin BID plus sulfasalazine or mesalamine 243 with relapse (5)

839 with relapse for those with no curcumin (20)

Endoscopic improvement in curcumin group

Rheumatoid Arthritis

(Epi)genetics of RAHLA-DR4 70 of RA patients

30 of general population

Subtypes = 90

Monozygotic concordance rate 15

Smoking triggers HLA production and seroconversion to HLA positive RA

Microbes and RARole of microbial infections in rheumatic disease GAS in rheumatic fever

Spirochetal infections in Lyme disease

Campylobacter Salmonella Shigella Yersinia and Chlamydia in reactive arthritis

Nowhellipoccult Proteus UTI and RA

Microbes and RAP mirabilis amino acid sequence resembles type XI collagen

Isolation rates of P mirabilis in RA patients is double that of E coli

Proteus isolated in 6350 of RA patients compared to 3211 controls

Urine from RA patients have elevated levels of Proteus antibodies

RA TreatmentProteus is a member of the Bacteroidesenterotype (associated with animal food diets)

Prevotella enterotype (associated with plant based diets)

Shifting from animalfoods to PBD reduces risk of occult Proteus UTI

AND reduces anti-Proteus antibodies

PBD also increases urine lignans which are anti-microbial

PBD for RA Treatment1999 randomized trial

13 months 27 intervention

26 controls

1227 intervention patients with 50 reduction in symptoms (responders)

226 control ldquorespondersrdquo

Intervention group 13 pound weight loss

Improved sed rate CRP and WBC count

After the intervention period patients were allowed to change diet however all rdquorespondersrdquo stayed with the diet and half of all ldquonon-respondersrdquo as well

Turmeric and RA2012- 8 week randomized pilot 45 patients2 groups

Group 1 500mg curcumin BID

Group 2 500 mg curcumin and 50mg diclofenac BID

Group 3 50mg diclofenac BID

Primary endpoint reduction in disease activity and joint swellingtenderness

Results Group 1 445 improvement

Group 2 444 improvement

Group 3 421 improvement

Adverse events only in diclofenac groups

Multiple Sclerosis

MS DistributionMost diagnosed ages 20-40

400000 in US and 25 million globally

Prevalence increases with distance from equator

57-78100000 below 37th parallel

110-140100000 above it

Higher incidence in colder climates and people of Northern European descent regardless of where they live

Women men 21

(Epi)genetics of MS

1-3 chance of MS if you have a sibling or parent with MS

Monozygotic concordance rate of 30 Roy Swank at OHSU hypothesized that the

distribution might be because people in northern latitudes tend to eat more animal foods

1952 study Frequency of MS in Norway directly related to amount of saturated animal fat consumed

Vitamin D and MSThose in northern latitudes also get less sun exposure

MS patients have lower 125(OH)2D levels at time of relapse

In Norway inland MS is higher than in fishing villages

Oily fish may compensate for relative lack of UV expsoure

Vitamin D and MS125(OH)2D moderates demyelination remyelination and stops oligodendrocyte apoptosis

Upreglates genomic activity on the strongest susceptiblility allele

Homozygosity of the CYP27B1 gene causes a form of rickets

3 individuals in Norway with this genetic rickets also developed MS

Heterozygosity increases risk of MS by 47 times

Dairy and MSMolecular mimicry between butyrophilin and myelin oligodendrocyte glycoprotein

Anti-BTN antibodies attack myelinated structures in the CNS and have been isolated in those with MS

MS TreatmentSafe and effective treatments are elusive

Interferon Side effects

$30000 per year

No evidence of a reduction in diabilityprogression

Mitoxantrone NNH 8 for irreversible systolic dysfunction and

123 for therapy-related acute leukemia

Dr Swank1951- 100 patients limited to 10-15 grams of saturated animal fat per day

3 frac12 year 5 frac12 year 7 year 20 year 34 year and 50 year follow up reports

After 34 years (1990) 95 of the patients were without progression of their disease

Increase in fat to 25-42gday was accompanied by increased disability and 3-fold increased risk of death to 79

In 2000 15 patients identified (50 year follow up) All could care for themselves independently

15 could ambulate as needed 13 truly ambulatory

MS TreatmentStudy on Vitamin D treatment in MS did not look at clinical outcomes

High dose Vitamin D supplementation did reduce helper T cells believed to be major contributors in immunopathogenesis of MS

Dose was 10400 IU daily and 21 of had to stop because of adverse effects

Type 1 Diabetes

Molecular Mimicry

Genetic Factors -alone cannot explain etiology

Environmental Factors- Cowrsquos milk antigens-Viruses

bull Enterovirusbull Coxackievirus Bbull Rotavirusbull Mumpsbull CMVbull Congenital Rubella

MYCOBACTERIUM PARATUBERCULOSISHSP 65

PBD in T1DType 1rsquos can develop insulin resistance with a high fat diet

PBD can reduce insulin requirements by 30-50

PBD can reduce risk of diabetic comorbidities

Latent autoimmune diabetes Adult onset non-obese Present without ketoacidosis and weight loss Anti-body positive Gradual insulin-dependence

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 15: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

Additional TherapiesCurcumin alone 45 with UC remission

1 gram curcumin BID plus sulfasalazine or mesalamine 243 with relapse (5)

839 with relapse for those with no curcumin (20)

Endoscopic improvement in curcumin group

Rheumatoid Arthritis

(Epi)genetics of RAHLA-DR4 70 of RA patients

30 of general population

Subtypes = 90

Monozygotic concordance rate 15

Smoking triggers HLA production and seroconversion to HLA positive RA

Microbes and RARole of microbial infections in rheumatic disease GAS in rheumatic fever

Spirochetal infections in Lyme disease

Campylobacter Salmonella Shigella Yersinia and Chlamydia in reactive arthritis

Nowhellipoccult Proteus UTI and RA

Microbes and RAP mirabilis amino acid sequence resembles type XI collagen

Isolation rates of P mirabilis in RA patients is double that of E coli

Proteus isolated in 6350 of RA patients compared to 3211 controls

Urine from RA patients have elevated levels of Proteus antibodies

RA TreatmentProteus is a member of the Bacteroidesenterotype (associated with animal food diets)

Prevotella enterotype (associated with plant based diets)

Shifting from animalfoods to PBD reduces risk of occult Proteus UTI

AND reduces anti-Proteus antibodies

PBD also increases urine lignans which are anti-microbial

PBD for RA Treatment1999 randomized trial

13 months 27 intervention

26 controls

1227 intervention patients with 50 reduction in symptoms (responders)

226 control ldquorespondersrdquo

Intervention group 13 pound weight loss

Improved sed rate CRP and WBC count

After the intervention period patients were allowed to change diet however all rdquorespondersrdquo stayed with the diet and half of all ldquonon-respondersrdquo as well

Turmeric and RA2012- 8 week randomized pilot 45 patients2 groups

Group 1 500mg curcumin BID

Group 2 500 mg curcumin and 50mg diclofenac BID

Group 3 50mg diclofenac BID

Primary endpoint reduction in disease activity and joint swellingtenderness

Results Group 1 445 improvement

Group 2 444 improvement

Group 3 421 improvement

Adverse events only in diclofenac groups

Multiple Sclerosis

MS DistributionMost diagnosed ages 20-40

400000 in US and 25 million globally

Prevalence increases with distance from equator

57-78100000 below 37th parallel

110-140100000 above it

Higher incidence in colder climates and people of Northern European descent regardless of where they live

Women men 21

(Epi)genetics of MS

1-3 chance of MS if you have a sibling or parent with MS

Monozygotic concordance rate of 30 Roy Swank at OHSU hypothesized that the

distribution might be because people in northern latitudes tend to eat more animal foods

1952 study Frequency of MS in Norway directly related to amount of saturated animal fat consumed

Vitamin D and MSThose in northern latitudes also get less sun exposure

MS patients have lower 125(OH)2D levels at time of relapse

In Norway inland MS is higher than in fishing villages

Oily fish may compensate for relative lack of UV expsoure

Vitamin D and MS125(OH)2D moderates demyelination remyelination and stops oligodendrocyte apoptosis

Upreglates genomic activity on the strongest susceptiblility allele

Homozygosity of the CYP27B1 gene causes a form of rickets

3 individuals in Norway with this genetic rickets also developed MS

Heterozygosity increases risk of MS by 47 times

Dairy and MSMolecular mimicry between butyrophilin and myelin oligodendrocyte glycoprotein

Anti-BTN antibodies attack myelinated structures in the CNS and have been isolated in those with MS

MS TreatmentSafe and effective treatments are elusive

Interferon Side effects

$30000 per year

No evidence of a reduction in diabilityprogression

Mitoxantrone NNH 8 for irreversible systolic dysfunction and

123 for therapy-related acute leukemia

Dr Swank1951- 100 patients limited to 10-15 grams of saturated animal fat per day

3 frac12 year 5 frac12 year 7 year 20 year 34 year and 50 year follow up reports

After 34 years (1990) 95 of the patients were without progression of their disease

Increase in fat to 25-42gday was accompanied by increased disability and 3-fold increased risk of death to 79

In 2000 15 patients identified (50 year follow up) All could care for themselves independently

15 could ambulate as needed 13 truly ambulatory

MS TreatmentStudy on Vitamin D treatment in MS did not look at clinical outcomes

High dose Vitamin D supplementation did reduce helper T cells believed to be major contributors in immunopathogenesis of MS

Dose was 10400 IU daily and 21 of had to stop because of adverse effects

Type 1 Diabetes

Molecular Mimicry

Genetic Factors -alone cannot explain etiology

Environmental Factors- Cowrsquos milk antigens-Viruses

bull Enterovirusbull Coxackievirus Bbull Rotavirusbull Mumpsbull CMVbull Congenital Rubella

MYCOBACTERIUM PARATUBERCULOSISHSP 65

PBD in T1DType 1rsquos can develop insulin resistance with a high fat diet

PBD can reduce insulin requirements by 30-50

PBD can reduce risk of diabetic comorbidities

Latent autoimmune diabetes Adult onset non-obese Present without ketoacidosis and weight loss Anti-body positive Gradual insulin-dependence

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 16: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

Rheumatoid Arthritis

(Epi)genetics of RAHLA-DR4 70 of RA patients

30 of general population

Subtypes = 90

Monozygotic concordance rate 15

Smoking triggers HLA production and seroconversion to HLA positive RA

Microbes and RARole of microbial infections in rheumatic disease GAS in rheumatic fever

Spirochetal infections in Lyme disease

Campylobacter Salmonella Shigella Yersinia and Chlamydia in reactive arthritis

Nowhellipoccult Proteus UTI and RA

Microbes and RAP mirabilis amino acid sequence resembles type XI collagen

Isolation rates of P mirabilis in RA patients is double that of E coli

Proteus isolated in 6350 of RA patients compared to 3211 controls

Urine from RA patients have elevated levels of Proteus antibodies

RA TreatmentProteus is a member of the Bacteroidesenterotype (associated with animal food diets)

Prevotella enterotype (associated with plant based diets)

Shifting from animalfoods to PBD reduces risk of occult Proteus UTI

AND reduces anti-Proteus antibodies

PBD also increases urine lignans which are anti-microbial

PBD for RA Treatment1999 randomized trial

13 months 27 intervention

26 controls

1227 intervention patients with 50 reduction in symptoms (responders)

226 control ldquorespondersrdquo

Intervention group 13 pound weight loss

Improved sed rate CRP and WBC count

After the intervention period patients were allowed to change diet however all rdquorespondersrdquo stayed with the diet and half of all ldquonon-respondersrdquo as well

Turmeric and RA2012- 8 week randomized pilot 45 patients2 groups

Group 1 500mg curcumin BID

Group 2 500 mg curcumin and 50mg diclofenac BID

Group 3 50mg diclofenac BID

Primary endpoint reduction in disease activity and joint swellingtenderness

Results Group 1 445 improvement

Group 2 444 improvement

Group 3 421 improvement

Adverse events only in diclofenac groups

Multiple Sclerosis

MS DistributionMost diagnosed ages 20-40

400000 in US and 25 million globally

Prevalence increases with distance from equator

57-78100000 below 37th parallel

110-140100000 above it

Higher incidence in colder climates and people of Northern European descent regardless of where they live

Women men 21

(Epi)genetics of MS

1-3 chance of MS if you have a sibling or parent with MS

Monozygotic concordance rate of 30 Roy Swank at OHSU hypothesized that the

distribution might be because people in northern latitudes tend to eat more animal foods

1952 study Frequency of MS in Norway directly related to amount of saturated animal fat consumed

Vitamin D and MSThose in northern latitudes also get less sun exposure

MS patients have lower 125(OH)2D levels at time of relapse

In Norway inland MS is higher than in fishing villages

Oily fish may compensate for relative lack of UV expsoure

Vitamin D and MS125(OH)2D moderates demyelination remyelination and stops oligodendrocyte apoptosis

Upreglates genomic activity on the strongest susceptiblility allele

Homozygosity of the CYP27B1 gene causes a form of rickets

3 individuals in Norway with this genetic rickets also developed MS

Heterozygosity increases risk of MS by 47 times

Dairy and MSMolecular mimicry between butyrophilin and myelin oligodendrocyte glycoprotein

Anti-BTN antibodies attack myelinated structures in the CNS and have been isolated in those with MS

MS TreatmentSafe and effective treatments are elusive

Interferon Side effects

$30000 per year

No evidence of a reduction in diabilityprogression

Mitoxantrone NNH 8 for irreversible systolic dysfunction and

123 for therapy-related acute leukemia

Dr Swank1951- 100 patients limited to 10-15 grams of saturated animal fat per day

3 frac12 year 5 frac12 year 7 year 20 year 34 year and 50 year follow up reports

After 34 years (1990) 95 of the patients were without progression of their disease

Increase in fat to 25-42gday was accompanied by increased disability and 3-fold increased risk of death to 79

In 2000 15 patients identified (50 year follow up) All could care for themselves independently

15 could ambulate as needed 13 truly ambulatory

MS TreatmentStudy on Vitamin D treatment in MS did not look at clinical outcomes

High dose Vitamin D supplementation did reduce helper T cells believed to be major contributors in immunopathogenesis of MS

Dose was 10400 IU daily and 21 of had to stop because of adverse effects

Type 1 Diabetes

Molecular Mimicry

Genetic Factors -alone cannot explain etiology

Environmental Factors- Cowrsquos milk antigens-Viruses

bull Enterovirusbull Coxackievirus Bbull Rotavirusbull Mumpsbull CMVbull Congenital Rubella

MYCOBACTERIUM PARATUBERCULOSISHSP 65

PBD in T1DType 1rsquos can develop insulin resistance with a high fat diet

PBD can reduce insulin requirements by 30-50

PBD can reduce risk of diabetic comorbidities

Latent autoimmune diabetes Adult onset non-obese Present without ketoacidosis and weight loss Anti-body positive Gradual insulin-dependence

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 17: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

(Epi)genetics of RAHLA-DR4 70 of RA patients

30 of general population

Subtypes = 90

Monozygotic concordance rate 15

Smoking triggers HLA production and seroconversion to HLA positive RA

Microbes and RARole of microbial infections in rheumatic disease GAS in rheumatic fever

Spirochetal infections in Lyme disease

Campylobacter Salmonella Shigella Yersinia and Chlamydia in reactive arthritis

Nowhellipoccult Proteus UTI and RA

Microbes and RAP mirabilis amino acid sequence resembles type XI collagen

Isolation rates of P mirabilis in RA patients is double that of E coli

Proteus isolated in 6350 of RA patients compared to 3211 controls

Urine from RA patients have elevated levels of Proteus antibodies

RA TreatmentProteus is a member of the Bacteroidesenterotype (associated with animal food diets)

Prevotella enterotype (associated with plant based diets)

Shifting from animalfoods to PBD reduces risk of occult Proteus UTI

AND reduces anti-Proteus antibodies

PBD also increases urine lignans which are anti-microbial

PBD for RA Treatment1999 randomized trial

13 months 27 intervention

26 controls

1227 intervention patients with 50 reduction in symptoms (responders)

226 control ldquorespondersrdquo

Intervention group 13 pound weight loss

Improved sed rate CRP and WBC count

After the intervention period patients were allowed to change diet however all rdquorespondersrdquo stayed with the diet and half of all ldquonon-respondersrdquo as well

Turmeric and RA2012- 8 week randomized pilot 45 patients2 groups

Group 1 500mg curcumin BID

Group 2 500 mg curcumin and 50mg diclofenac BID

Group 3 50mg diclofenac BID

Primary endpoint reduction in disease activity and joint swellingtenderness

Results Group 1 445 improvement

Group 2 444 improvement

Group 3 421 improvement

Adverse events only in diclofenac groups

Multiple Sclerosis

MS DistributionMost diagnosed ages 20-40

400000 in US and 25 million globally

Prevalence increases with distance from equator

57-78100000 below 37th parallel

110-140100000 above it

Higher incidence in colder climates and people of Northern European descent regardless of where they live

Women men 21

(Epi)genetics of MS

1-3 chance of MS if you have a sibling or parent with MS

Monozygotic concordance rate of 30 Roy Swank at OHSU hypothesized that the

distribution might be because people in northern latitudes tend to eat more animal foods

1952 study Frequency of MS in Norway directly related to amount of saturated animal fat consumed

Vitamin D and MSThose in northern latitudes also get less sun exposure

MS patients have lower 125(OH)2D levels at time of relapse

In Norway inland MS is higher than in fishing villages

Oily fish may compensate for relative lack of UV expsoure

Vitamin D and MS125(OH)2D moderates demyelination remyelination and stops oligodendrocyte apoptosis

Upreglates genomic activity on the strongest susceptiblility allele

Homozygosity of the CYP27B1 gene causes a form of rickets

3 individuals in Norway with this genetic rickets also developed MS

Heterozygosity increases risk of MS by 47 times

Dairy and MSMolecular mimicry between butyrophilin and myelin oligodendrocyte glycoprotein

Anti-BTN antibodies attack myelinated structures in the CNS and have been isolated in those with MS

MS TreatmentSafe and effective treatments are elusive

Interferon Side effects

$30000 per year

No evidence of a reduction in diabilityprogression

Mitoxantrone NNH 8 for irreversible systolic dysfunction and

123 for therapy-related acute leukemia

Dr Swank1951- 100 patients limited to 10-15 grams of saturated animal fat per day

3 frac12 year 5 frac12 year 7 year 20 year 34 year and 50 year follow up reports

After 34 years (1990) 95 of the patients were without progression of their disease

Increase in fat to 25-42gday was accompanied by increased disability and 3-fold increased risk of death to 79

In 2000 15 patients identified (50 year follow up) All could care for themselves independently

15 could ambulate as needed 13 truly ambulatory

MS TreatmentStudy on Vitamin D treatment in MS did not look at clinical outcomes

High dose Vitamin D supplementation did reduce helper T cells believed to be major contributors in immunopathogenesis of MS

Dose was 10400 IU daily and 21 of had to stop because of adverse effects

Type 1 Diabetes

Molecular Mimicry

Genetic Factors -alone cannot explain etiology

Environmental Factors- Cowrsquos milk antigens-Viruses

bull Enterovirusbull Coxackievirus Bbull Rotavirusbull Mumpsbull CMVbull Congenital Rubella

MYCOBACTERIUM PARATUBERCULOSISHSP 65

PBD in T1DType 1rsquos can develop insulin resistance with a high fat diet

PBD can reduce insulin requirements by 30-50

PBD can reduce risk of diabetic comorbidities

Latent autoimmune diabetes Adult onset non-obese Present without ketoacidosis and weight loss Anti-body positive Gradual insulin-dependence

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 18: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

Microbes and RARole of microbial infections in rheumatic disease GAS in rheumatic fever

Spirochetal infections in Lyme disease

Campylobacter Salmonella Shigella Yersinia and Chlamydia in reactive arthritis

Nowhellipoccult Proteus UTI and RA

Microbes and RAP mirabilis amino acid sequence resembles type XI collagen

Isolation rates of P mirabilis in RA patients is double that of E coli

Proteus isolated in 6350 of RA patients compared to 3211 controls

Urine from RA patients have elevated levels of Proteus antibodies

RA TreatmentProteus is a member of the Bacteroidesenterotype (associated with animal food diets)

Prevotella enterotype (associated with plant based diets)

Shifting from animalfoods to PBD reduces risk of occult Proteus UTI

AND reduces anti-Proteus antibodies

PBD also increases urine lignans which are anti-microbial

PBD for RA Treatment1999 randomized trial

13 months 27 intervention

26 controls

1227 intervention patients with 50 reduction in symptoms (responders)

226 control ldquorespondersrdquo

Intervention group 13 pound weight loss

Improved sed rate CRP and WBC count

After the intervention period patients were allowed to change diet however all rdquorespondersrdquo stayed with the diet and half of all ldquonon-respondersrdquo as well

Turmeric and RA2012- 8 week randomized pilot 45 patients2 groups

Group 1 500mg curcumin BID

Group 2 500 mg curcumin and 50mg diclofenac BID

Group 3 50mg diclofenac BID

Primary endpoint reduction in disease activity and joint swellingtenderness

Results Group 1 445 improvement

Group 2 444 improvement

Group 3 421 improvement

Adverse events only in diclofenac groups

Multiple Sclerosis

MS DistributionMost diagnosed ages 20-40

400000 in US and 25 million globally

Prevalence increases with distance from equator

57-78100000 below 37th parallel

110-140100000 above it

Higher incidence in colder climates and people of Northern European descent regardless of where they live

Women men 21

(Epi)genetics of MS

1-3 chance of MS if you have a sibling or parent with MS

Monozygotic concordance rate of 30 Roy Swank at OHSU hypothesized that the

distribution might be because people in northern latitudes tend to eat more animal foods

1952 study Frequency of MS in Norway directly related to amount of saturated animal fat consumed

Vitamin D and MSThose in northern latitudes also get less sun exposure

MS patients have lower 125(OH)2D levels at time of relapse

In Norway inland MS is higher than in fishing villages

Oily fish may compensate for relative lack of UV expsoure

Vitamin D and MS125(OH)2D moderates demyelination remyelination and stops oligodendrocyte apoptosis

Upreglates genomic activity on the strongest susceptiblility allele

Homozygosity of the CYP27B1 gene causes a form of rickets

3 individuals in Norway with this genetic rickets also developed MS

Heterozygosity increases risk of MS by 47 times

Dairy and MSMolecular mimicry between butyrophilin and myelin oligodendrocyte glycoprotein

Anti-BTN antibodies attack myelinated structures in the CNS and have been isolated in those with MS

MS TreatmentSafe and effective treatments are elusive

Interferon Side effects

$30000 per year

No evidence of a reduction in diabilityprogression

Mitoxantrone NNH 8 for irreversible systolic dysfunction and

123 for therapy-related acute leukemia

Dr Swank1951- 100 patients limited to 10-15 grams of saturated animal fat per day

3 frac12 year 5 frac12 year 7 year 20 year 34 year and 50 year follow up reports

After 34 years (1990) 95 of the patients were without progression of their disease

Increase in fat to 25-42gday was accompanied by increased disability and 3-fold increased risk of death to 79

In 2000 15 patients identified (50 year follow up) All could care for themselves independently

15 could ambulate as needed 13 truly ambulatory

MS TreatmentStudy on Vitamin D treatment in MS did not look at clinical outcomes

High dose Vitamin D supplementation did reduce helper T cells believed to be major contributors in immunopathogenesis of MS

Dose was 10400 IU daily and 21 of had to stop because of adverse effects

Type 1 Diabetes

Molecular Mimicry

Genetic Factors -alone cannot explain etiology

Environmental Factors- Cowrsquos milk antigens-Viruses

bull Enterovirusbull Coxackievirus Bbull Rotavirusbull Mumpsbull CMVbull Congenital Rubella

MYCOBACTERIUM PARATUBERCULOSISHSP 65

PBD in T1DType 1rsquos can develop insulin resistance with a high fat diet

PBD can reduce insulin requirements by 30-50

PBD can reduce risk of diabetic comorbidities

Latent autoimmune diabetes Adult onset non-obese Present without ketoacidosis and weight loss Anti-body positive Gradual insulin-dependence

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 19: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

Microbes and RAP mirabilis amino acid sequence resembles type XI collagen

Isolation rates of P mirabilis in RA patients is double that of E coli

Proteus isolated in 6350 of RA patients compared to 3211 controls

Urine from RA patients have elevated levels of Proteus antibodies

RA TreatmentProteus is a member of the Bacteroidesenterotype (associated with animal food diets)

Prevotella enterotype (associated with plant based diets)

Shifting from animalfoods to PBD reduces risk of occult Proteus UTI

AND reduces anti-Proteus antibodies

PBD also increases urine lignans which are anti-microbial

PBD for RA Treatment1999 randomized trial

13 months 27 intervention

26 controls

1227 intervention patients with 50 reduction in symptoms (responders)

226 control ldquorespondersrdquo

Intervention group 13 pound weight loss

Improved sed rate CRP and WBC count

After the intervention period patients were allowed to change diet however all rdquorespondersrdquo stayed with the diet and half of all ldquonon-respondersrdquo as well

Turmeric and RA2012- 8 week randomized pilot 45 patients2 groups

Group 1 500mg curcumin BID

Group 2 500 mg curcumin and 50mg diclofenac BID

Group 3 50mg diclofenac BID

Primary endpoint reduction in disease activity and joint swellingtenderness

Results Group 1 445 improvement

Group 2 444 improvement

Group 3 421 improvement

Adverse events only in diclofenac groups

Multiple Sclerosis

MS DistributionMost diagnosed ages 20-40

400000 in US and 25 million globally

Prevalence increases with distance from equator

57-78100000 below 37th parallel

110-140100000 above it

Higher incidence in colder climates and people of Northern European descent regardless of where they live

Women men 21

(Epi)genetics of MS

1-3 chance of MS if you have a sibling or parent with MS

Monozygotic concordance rate of 30 Roy Swank at OHSU hypothesized that the

distribution might be because people in northern latitudes tend to eat more animal foods

1952 study Frequency of MS in Norway directly related to amount of saturated animal fat consumed

Vitamin D and MSThose in northern latitudes also get less sun exposure

MS patients have lower 125(OH)2D levels at time of relapse

In Norway inland MS is higher than in fishing villages

Oily fish may compensate for relative lack of UV expsoure

Vitamin D and MS125(OH)2D moderates demyelination remyelination and stops oligodendrocyte apoptosis

Upreglates genomic activity on the strongest susceptiblility allele

Homozygosity of the CYP27B1 gene causes a form of rickets

3 individuals in Norway with this genetic rickets also developed MS

Heterozygosity increases risk of MS by 47 times

Dairy and MSMolecular mimicry between butyrophilin and myelin oligodendrocyte glycoprotein

Anti-BTN antibodies attack myelinated structures in the CNS and have been isolated in those with MS

MS TreatmentSafe and effective treatments are elusive

Interferon Side effects

$30000 per year

No evidence of a reduction in diabilityprogression

Mitoxantrone NNH 8 for irreversible systolic dysfunction and

123 for therapy-related acute leukemia

Dr Swank1951- 100 patients limited to 10-15 grams of saturated animal fat per day

3 frac12 year 5 frac12 year 7 year 20 year 34 year and 50 year follow up reports

After 34 years (1990) 95 of the patients were without progression of their disease

Increase in fat to 25-42gday was accompanied by increased disability and 3-fold increased risk of death to 79

In 2000 15 patients identified (50 year follow up) All could care for themselves independently

15 could ambulate as needed 13 truly ambulatory

MS TreatmentStudy on Vitamin D treatment in MS did not look at clinical outcomes

High dose Vitamin D supplementation did reduce helper T cells believed to be major contributors in immunopathogenesis of MS

Dose was 10400 IU daily and 21 of had to stop because of adverse effects

Type 1 Diabetes

Molecular Mimicry

Genetic Factors -alone cannot explain etiology

Environmental Factors- Cowrsquos milk antigens-Viruses

bull Enterovirusbull Coxackievirus Bbull Rotavirusbull Mumpsbull CMVbull Congenital Rubella

MYCOBACTERIUM PARATUBERCULOSISHSP 65

PBD in T1DType 1rsquos can develop insulin resistance with a high fat diet

PBD can reduce insulin requirements by 30-50

PBD can reduce risk of diabetic comorbidities

Latent autoimmune diabetes Adult onset non-obese Present without ketoacidosis and weight loss Anti-body positive Gradual insulin-dependence

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 20: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

RA TreatmentProteus is a member of the Bacteroidesenterotype (associated with animal food diets)

Prevotella enterotype (associated with plant based diets)

Shifting from animalfoods to PBD reduces risk of occult Proteus UTI

AND reduces anti-Proteus antibodies

PBD also increases urine lignans which are anti-microbial

PBD for RA Treatment1999 randomized trial

13 months 27 intervention

26 controls

1227 intervention patients with 50 reduction in symptoms (responders)

226 control ldquorespondersrdquo

Intervention group 13 pound weight loss

Improved sed rate CRP and WBC count

After the intervention period patients were allowed to change diet however all rdquorespondersrdquo stayed with the diet and half of all ldquonon-respondersrdquo as well

Turmeric and RA2012- 8 week randomized pilot 45 patients2 groups

Group 1 500mg curcumin BID

Group 2 500 mg curcumin and 50mg diclofenac BID

Group 3 50mg diclofenac BID

Primary endpoint reduction in disease activity and joint swellingtenderness

Results Group 1 445 improvement

Group 2 444 improvement

Group 3 421 improvement

Adverse events only in diclofenac groups

Multiple Sclerosis

MS DistributionMost diagnosed ages 20-40

400000 in US and 25 million globally

Prevalence increases with distance from equator

57-78100000 below 37th parallel

110-140100000 above it

Higher incidence in colder climates and people of Northern European descent regardless of where they live

Women men 21

(Epi)genetics of MS

1-3 chance of MS if you have a sibling or parent with MS

Monozygotic concordance rate of 30 Roy Swank at OHSU hypothesized that the

distribution might be because people in northern latitudes tend to eat more animal foods

1952 study Frequency of MS in Norway directly related to amount of saturated animal fat consumed

Vitamin D and MSThose in northern latitudes also get less sun exposure

MS patients have lower 125(OH)2D levels at time of relapse

In Norway inland MS is higher than in fishing villages

Oily fish may compensate for relative lack of UV expsoure

Vitamin D and MS125(OH)2D moderates demyelination remyelination and stops oligodendrocyte apoptosis

Upreglates genomic activity on the strongest susceptiblility allele

Homozygosity of the CYP27B1 gene causes a form of rickets

3 individuals in Norway with this genetic rickets also developed MS

Heterozygosity increases risk of MS by 47 times

Dairy and MSMolecular mimicry between butyrophilin and myelin oligodendrocyte glycoprotein

Anti-BTN antibodies attack myelinated structures in the CNS and have been isolated in those with MS

MS TreatmentSafe and effective treatments are elusive

Interferon Side effects

$30000 per year

No evidence of a reduction in diabilityprogression

Mitoxantrone NNH 8 for irreversible systolic dysfunction and

123 for therapy-related acute leukemia

Dr Swank1951- 100 patients limited to 10-15 grams of saturated animal fat per day

3 frac12 year 5 frac12 year 7 year 20 year 34 year and 50 year follow up reports

After 34 years (1990) 95 of the patients were without progression of their disease

Increase in fat to 25-42gday was accompanied by increased disability and 3-fold increased risk of death to 79

In 2000 15 patients identified (50 year follow up) All could care for themselves independently

15 could ambulate as needed 13 truly ambulatory

MS TreatmentStudy on Vitamin D treatment in MS did not look at clinical outcomes

High dose Vitamin D supplementation did reduce helper T cells believed to be major contributors in immunopathogenesis of MS

Dose was 10400 IU daily and 21 of had to stop because of adverse effects

Type 1 Diabetes

Molecular Mimicry

Genetic Factors -alone cannot explain etiology

Environmental Factors- Cowrsquos milk antigens-Viruses

bull Enterovirusbull Coxackievirus Bbull Rotavirusbull Mumpsbull CMVbull Congenital Rubella

MYCOBACTERIUM PARATUBERCULOSISHSP 65

PBD in T1DType 1rsquos can develop insulin resistance with a high fat diet

PBD can reduce insulin requirements by 30-50

PBD can reduce risk of diabetic comorbidities

Latent autoimmune diabetes Adult onset non-obese Present without ketoacidosis and weight loss Anti-body positive Gradual insulin-dependence

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 21: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

PBD for RA Treatment1999 randomized trial

13 months 27 intervention

26 controls

1227 intervention patients with 50 reduction in symptoms (responders)

226 control ldquorespondersrdquo

Intervention group 13 pound weight loss

Improved sed rate CRP and WBC count

After the intervention period patients were allowed to change diet however all rdquorespondersrdquo stayed with the diet and half of all ldquonon-respondersrdquo as well

Turmeric and RA2012- 8 week randomized pilot 45 patients2 groups

Group 1 500mg curcumin BID

Group 2 500 mg curcumin and 50mg diclofenac BID

Group 3 50mg diclofenac BID

Primary endpoint reduction in disease activity and joint swellingtenderness

Results Group 1 445 improvement

Group 2 444 improvement

Group 3 421 improvement

Adverse events only in diclofenac groups

Multiple Sclerosis

MS DistributionMost diagnosed ages 20-40

400000 in US and 25 million globally

Prevalence increases with distance from equator

57-78100000 below 37th parallel

110-140100000 above it

Higher incidence in colder climates and people of Northern European descent regardless of where they live

Women men 21

(Epi)genetics of MS

1-3 chance of MS if you have a sibling or parent with MS

Monozygotic concordance rate of 30 Roy Swank at OHSU hypothesized that the

distribution might be because people in northern latitudes tend to eat more animal foods

1952 study Frequency of MS in Norway directly related to amount of saturated animal fat consumed

Vitamin D and MSThose in northern latitudes also get less sun exposure

MS patients have lower 125(OH)2D levels at time of relapse

In Norway inland MS is higher than in fishing villages

Oily fish may compensate for relative lack of UV expsoure

Vitamin D and MS125(OH)2D moderates demyelination remyelination and stops oligodendrocyte apoptosis

Upreglates genomic activity on the strongest susceptiblility allele

Homozygosity of the CYP27B1 gene causes a form of rickets

3 individuals in Norway with this genetic rickets also developed MS

Heterozygosity increases risk of MS by 47 times

Dairy and MSMolecular mimicry between butyrophilin and myelin oligodendrocyte glycoprotein

Anti-BTN antibodies attack myelinated structures in the CNS and have been isolated in those with MS

MS TreatmentSafe and effective treatments are elusive

Interferon Side effects

$30000 per year

No evidence of a reduction in diabilityprogression

Mitoxantrone NNH 8 for irreversible systolic dysfunction and

123 for therapy-related acute leukemia

Dr Swank1951- 100 patients limited to 10-15 grams of saturated animal fat per day

3 frac12 year 5 frac12 year 7 year 20 year 34 year and 50 year follow up reports

After 34 years (1990) 95 of the patients were without progression of their disease

Increase in fat to 25-42gday was accompanied by increased disability and 3-fold increased risk of death to 79

In 2000 15 patients identified (50 year follow up) All could care for themselves independently

15 could ambulate as needed 13 truly ambulatory

MS TreatmentStudy on Vitamin D treatment in MS did not look at clinical outcomes

High dose Vitamin D supplementation did reduce helper T cells believed to be major contributors in immunopathogenesis of MS

Dose was 10400 IU daily and 21 of had to stop because of adverse effects

Type 1 Diabetes

Molecular Mimicry

Genetic Factors -alone cannot explain etiology

Environmental Factors- Cowrsquos milk antigens-Viruses

bull Enterovirusbull Coxackievirus Bbull Rotavirusbull Mumpsbull CMVbull Congenital Rubella

MYCOBACTERIUM PARATUBERCULOSISHSP 65

PBD in T1DType 1rsquos can develop insulin resistance with a high fat diet

PBD can reduce insulin requirements by 30-50

PBD can reduce risk of diabetic comorbidities

Latent autoimmune diabetes Adult onset non-obese Present without ketoacidosis and weight loss Anti-body positive Gradual insulin-dependence

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 22: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

Turmeric and RA2012- 8 week randomized pilot 45 patients2 groups

Group 1 500mg curcumin BID

Group 2 500 mg curcumin and 50mg diclofenac BID

Group 3 50mg diclofenac BID

Primary endpoint reduction in disease activity and joint swellingtenderness

Results Group 1 445 improvement

Group 2 444 improvement

Group 3 421 improvement

Adverse events only in diclofenac groups

Multiple Sclerosis

MS DistributionMost diagnosed ages 20-40

400000 in US and 25 million globally

Prevalence increases with distance from equator

57-78100000 below 37th parallel

110-140100000 above it

Higher incidence in colder climates and people of Northern European descent regardless of where they live

Women men 21

(Epi)genetics of MS

1-3 chance of MS if you have a sibling or parent with MS

Monozygotic concordance rate of 30 Roy Swank at OHSU hypothesized that the

distribution might be because people in northern latitudes tend to eat more animal foods

1952 study Frequency of MS in Norway directly related to amount of saturated animal fat consumed

Vitamin D and MSThose in northern latitudes also get less sun exposure

MS patients have lower 125(OH)2D levels at time of relapse

In Norway inland MS is higher than in fishing villages

Oily fish may compensate for relative lack of UV expsoure

Vitamin D and MS125(OH)2D moderates demyelination remyelination and stops oligodendrocyte apoptosis

Upreglates genomic activity on the strongest susceptiblility allele

Homozygosity of the CYP27B1 gene causes a form of rickets

3 individuals in Norway with this genetic rickets also developed MS

Heterozygosity increases risk of MS by 47 times

Dairy and MSMolecular mimicry between butyrophilin and myelin oligodendrocyte glycoprotein

Anti-BTN antibodies attack myelinated structures in the CNS and have been isolated in those with MS

MS TreatmentSafe and effective treatments are elusive

Interferon Side effects

$30000 per year

No evidence of a reduction in diabilityprogression

Mitoxantrone NNH 8 for irreversible systolic dysfunction and

123 for therapy-related acute leukemia

Dr Swank1951- 100 patients limited to 10-15 grams of saturated animal fat per day

3 frac12 year 5 frac12 year 7 year 20 year 34 year and 50 year follow up reports

After 34 years (1990) 95 of the patients were without progression of their disease

Increase in fat to 25-42gday was accompanied by increased disability and 3-fold increased risk of death to 79

In 2000 15 patients identified (50 year follow up) All could care for themselves independently

15 could ambulate as needed 13 truly ambulatory

MS TreatmentStudy on Vitamin D treatment in MS did not look at clinical outcomes

High dose Vitamin D supplementation did reduce helper T cells believed to be major contributors in immunopathogenesis of MS

Dose was 10400 IU daily and 21 of had to stop because of adverse effects

Type 1 Diabetes

Molecular Mimicry

Genetic Factors -alone cannot explain etiology

Environmental Factors- Cowrsquos milk antigens-Viruses

bull Enterovirusbull Coxackievirus Bbull Rotavirusbull Mumpsbull CMVbull Congenital Rubella

MYCOBACTERIUM PARATUBERCULOSISHSP 65

PBD in T1DType 1rsquos can develop insulin resistance with a high fat diet

PBD can reduce insulin requirements by 30-50

PBD can reduce risk of diabetic comorbidities

Latent autoimmune diabetes Adult onset non-obese Present without ketoacidosis and weight loss Anti-body positive Gradual insulin-dependence

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 23: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

Multiple Sclerosis

MS DistributionMost diagnosed ages 20-40

400000 in US and 25 million globally

Prevalence increases with distance from equator

57-78100000 below 37th parallel

110-140100000 above it

Higher incidence in colder climates and people of Northern European descent regardless of where they live

Women men 21

(Epi)genetics of MS

1-3 chance of MS if you have a sibling or parent with MS

Monozygotic concordance rate of 30 Roy Swank at OHSU hypothesized that the

distribution might be because people in northern latitudes tend to eat more animal foods

1952 study Frequency of MS in Norway directly related to amount of saturated animal fat consumed

Vitamin D and MSThose in northern latitudes also get less sun exposure

MS patients have lower 125(OH)2D levels at time of relapse

In Norway inland MS is higher than in fishing villages

Oily fish may compensate for relative lack of UV expsoure

Vitamin D and MS125(OH)2D moderates demyelination remyelination and stops oligodendrocyte apoptosis

Upreglates genomic activity on the strongest susceptiblility allele

Homozygosity of the CYP27B1 gene causes a form of rickets

3 individuals in Norway with this genetic rickets also developed MS

Heterozygosity increases risk of MS by 47 times

Dairy and MSMolecular mimicry between butyrophilin and myelin oligodendrocyte glycoprotein

Anti-BTN antibodies attack myelinated structures in the CNS and have been isolated in those with MS

MS TreatmentSafe and effective treatments are elusive

Interferon Side effects

$30000 per year

No evidence of a reduction in diabilityprogression

Mitoxantrone NNH 8 for irreversible systolic dysfunction and

123 for therapy-related acute leukemia

Dr Swank1951- 100 patients limited to 10-15 grams of saturated animal fat per day

3 frac12 year 5 frac12 year 7 year 20 year 34 year and 50 year follow up reports

After 34 years (1990) 95 of the patients were without progression of their disease

Increase in fat to 25-42gday was accompanied by increased disability and 3-fold increased risk of death to 79

In 2000 15 patients identified (50 year follow up) All could care for themselves independently

15 could ambulate as needed 13 truly ambulatory

MS TreatmentStudy on Vitamin D treatment in MS did not look at clinical outcomes

High dose Vitamin D supplementation did reduce helper T cells believed to be major contributors in immunopathogenesis of MS

Dose was 10400 IU daily and 21 of had to stop because of adverse effects

Type 1 Diabetes

Molecular Mimicry

Genetic Factors -alone cannot explain etiology

Environmental Factors- Cowrsquos milk antigens-Viruses

bull Enterovirusbull Coxackievirus Bbull Rotavirusbull Mumpsbull CMVbull Congenital Rubella

MYCOBACTERIUM PARATUBERCULOSISHSP 65

PBD in T1DType 1rsquos can develop insulin resistance with a high fat diet

PBD can reduce insulin requirements by 30-50

PBD can reduce risk of diabetic comorbidities

Latent autoimmune diabetes Adult onset non-obese Present without ketoacidosis and weight loss Anti-body positive Gradual insulin-dependence

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 24: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

MS DistributionMost diagnosed ages 20-40

400000 in US and 25 million globally

Prevalence increases with distance from equator

57-78100000 below 37th parallel

110-140100000 above it

Higher incidence in colder climates and people of Northern European descent regardless of where they live

Women men 21

(Epi)genetics of MS

1-3 chance of MS if you have a sibling or parent with MS

Monozygotic concordance rate of 30 Roy Swank at OHSU hypothesized that the

distribution might be because people in northern latitudes tend to eat more animal foods

1952 study Frequency of MS in Norway directly related to amount of saturated animal fat consumed

Vitamin D and MSThose in northern latitudes also get less sun exposure

MS patients have lower 125(OH)2D levels at time of relapse

In Norway inland MS is higher than in fishing villages

Oily fish may compensate for relative lack of UV expsoure

Vitamin D and MS125(OH)2D moderates demyelination remyelination and stops oligodendrocyte apoptosis

Upreglates genomic activity on the strongest susceptiblility allele

Homozygosity of the CYP27B1 gene causes a form of rickets

3 individuals in Norway with this genetic rickets also developed MS

Heterozygosity increases risk of MS by 47 times

Dairy and MSMolecular mimicry between butyrophilin and myelin oligodendrocyte glycoprotein

Anti-BTN antibodies attack myelinated structures in the CNS and have been isolated in those with MS

MS TreatmentSafe and effective treatments are elusive

Interferon Side effects

$30000 per year

No evidence of a reduction in diabilityprogression

Mitoxantrone NNH 8 for irreversible systolic dysfunction and

123 for therapy-related acute leukemia

Dr Swank1951- 100 patients limited to 10-15 grams of saturated animal fat per day

3 frac12 year 5 frac12 year 7 year 20 year 34 year and 50 year follow up reports

After 34 years (1990) 95 of the patients were without progression of their disease

Increase in fat to 25-42gday was accompanied by increased disability and 3-fold increased risk of death to 79

In 2000 15 patients identified (50 year follow up) All could care for themselves independently

15 could ambulate as needed 13 truly ambulatory

MS TreatmentStudy on Vitamin D treatment in MS did not look at clinical outcomes

High dose Vitamin D supplementation did reduce helper T cells believed to be major contributors in immunopathogenesis of MS

Dose was 10400 IU daily and 21 of had to stop because of adverse effects

Type 1 Diabetes

Molecular Mimicry

Genetic Factors -alone cannot explain etiology

Environmental Factors- Cowrsquos milk antigens-Viruses

bull Enterovirusbull Coxackievirus Bbull Rotavirusbull Mumpsbull CMVbull Congenital Rubella

MYCOBACTERIUM PARATUBERCULOSISHSP 65

PBD in T1DType 1rsquos can develop insulin resistance with a high fat diet

PBD can reduce insulin requirements by 30-50

PBD can reduce risk of diabetic comorbidities

Latent autoimmune diabetes Adult onset non-obese Present without ketoacidosis and weight loss Anti-body positive Gradual insulin-dependence

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 25: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

(Epi)genetics of MS

1-3 chance of MS if you have a sibling or parent with MS

Monozygotic concordance rate of 30 Roy Swank at OHSU hypothesized that the

distribution might be because people in northern latitudes tend to eat more animal foods

1952 study Frequency of MS in Norway directly related to amount of saturated animal fat consumed

Vitamin D and MSThose in northern latitudes also get less sun exposure

MS patients have lower 125(OH)2D levels at time of relapse

In Norway inland MS is higher than in fishing villages

Oily fish may compensate for relative lack of UV expsoure

Vitamin D and MS125(OH)2D moderates demyelination remyelination and stops oligodendrocyte apoptosis

Upreglates genomic activity on the strongest susceptiblility allele

Homozygosity of the CYP27B1 gene causes a form of rickets

3 individuals in Norway with this genetic rickets also developed MS

Heterozygosity increases risk of MS by 47 times

Dairy and MSMolecular mimicry between butyrophilin and myelin oligodendrocyte glycoprotein

Anti-BTN antibodies attack myelinated structures in the CNS and have been isolated in those with MS

MS TreatmentSafe and effective treatments are elusive

Interferon Side effects

$30000 per year

No evidence of a reduction in diabilityprogression

Mitoxantrone NNH 8 for irreversible systolic dysfunction and

123 for therapy-related acute leukemia

Dr Swank1951- 100 patients limited to 10-15 grams of saturated animal fat per day

3 frac12 year 5 frac12 year 7 year 20 year 34 year and 50 year follow up reports

After 34 years (1990) 95 of the patients were without progression of their disease

Increase in fat to 25-42gday was accompanied by increased disability and 3-fold increased risk of death to 79

In 2000 15 patients identified (50 year follow up) All could care for themselves independently

15 could ambulate as needed 13 truly ambulatory

MS TreatmentStudy on Vitamin D treatment in MS did not look at clinical outcomes

High dose Vitamin D supplementation did reduce helper T cells believed to be major contributors in immunopathogenesis of MS

Dose was 10400 IU daily and 21 of had to stop because of adverse effects

Type 1 Diabetes

Molecular Mimicry

Genetic Factors -alone cannot explain etiology

Environmental Factors- Cowrsquos milk antigens-Viruses

bull Enterovirusbull Coxackievirus Bbull Rotavirusbull Mumpsbull CMVbull Congenital Rubella

MYCOBACTERIUM PARATUBERCULOSISHSP 65

PBD in T1DType 1rsquos can develop insulin resistance with a high fat diet

PBD can reduce insulin requirements by 30-50

PBD can reduce risk of diabetic comorbidities

Latent autoimmune diabetes Adult onset non-obese Present without ketoacidosis and weight loss Anti-body positive Gradual insulin-dependence

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 26: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

Vitamin D and MSThose in northern latitudes also get less sun exposure

MS patients have lower 125(OH)2D levels at time of relapse

In Norway inland MS is higher than in fishing villages

Oily fish may compensate for relative lack of UV expsoure

Vitamin D and MS125(OH)2D moderates demyelination remyelination and stops oligodendrocyte apoptosis

Upreglates genomic activity on the strongest susceptiblility allele

Homozygosity of the CYP27B1 gene causes a form of rickets

3 individuals in Norway with this genetic rickets also developed MS

Heterozygosity increases risk of MS by 47 times

Dairy and MSMolecular mimicry between butyrophilin and myelin oligodendrocyte glycoprotein

Anti-BTN antibodies attack myelinated structures in the CNS and have been isolated in those with MS

MS TreatmentSafe and effective treatments are elusive

Interferon Side effects

$30000 per year

No evidence of a reduction in diabilityprogression

Mitoxantrone NNH 8 for irreversible systolic dysfunction and

123 for therapy-related acute leukemia

Dr Swank1951- 100 patients limited to 10-15 grams of saturated animal fat per day

3 frac12 year 5 frac12 year 7 year 20 year 34 year and 50 year follow up reports

After 34 years (1990) 95 of the patients were without progression of their disease

Increase in fat to 25-42gday was accompanied by increased disability and 3-fold increased risk of death to 79

In 2000 15 patients identified (50 year follow up) All could care for themselves independently

15 could ambulate as needed 13 truly ambulatory

MS TreatmentStudy on Vitamin D treatment in MS did not look at clinical outcomes

High dose Vitamin D supplementation did reduce helper T cells believed to be major contributors in immunopathogenesis of MS

Dose was 10400 IU daily and 21 of had to stop because of adverse effects

Type 1 Diabetes

Molecular Mimicry

Genetic Factors -alone cannot explain etiology

Environmental Factors- Cowrsquos milk antigens-Viruses

bull Enterovirusbull Coxackievirus Bbull Rotavirusbull Mumpsbull CMVbull Congenital Rubella

MYCOBACTERIUM PARATUBERCULOSISHSP 65

PBD in T1DType 1rsquos can develop insulin resistance with a high fat diet

PBD can reduce insulin requirements by 30-50

PBD can reduce risk of diabetic comorbidities

Latent autoimmune diabetes Adult onset non-obese Present without ketoacidosis and weight loss Anti-body positive Gradual insulin-dependence

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 27: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

Vitamin D and MS125(OH)2D moderates demyelination remyelination and stops oligodendrocyte apoptosis

Upreglates genomic activity on the strongest susceptiblility allele

Homozygosity of the CYP27B1 gene causes a form of rickets

3 individuals in Norway with this genetic rickets also developed MS

Heterozygosity increases risk of MS by 47 times

Dairy and MSMolecular mimicry between butyrophilin and myelin oligodendrocyte glycoprotein

Anti-BTN antibodies attack myelinated structures in the CNS and have been isolated in those with MS

MS TreatmentSafe and effective treatments are elusive

Interferon Side effects

$30000 per year

No evidence of a reduction in diabilityprogression

Mitoxantrone NNH 8 for irreversible systolic dysfunction and

123 for therapy-related acute leukemia

Dr Swank1951- 100 patients limited to 10-15 grams of saturated animal fat per day

3 frac12 year 5 frac12 year 7 year 20 year 34 year and 50 year follow up reports

After 34 years (1990) 95 of the patients were without progression of their disease

Increase in fat to 25-42gday was accompanied by increased disability and 3-fold increased risk of death to 79

In 2000 15 patients identified (50 year follow up) All could care for themselves independently

15 could ambulate as needed 13 truly ambulatory

MS TreatmentStudy on Vitamin D treatment in MS did not look at clinical outcomes

High dose Vitamin D supplementation did reduce helper T cells believed to be major contributors in immunopathogenesis of MS

Dose was 10400 IU daily and 21 of had to stop because of adverse effects

Type 1 Diabetes

Molecular Mimicry

Genetic Factors -alone cannot explain etiology

Environmental Factors- Cowrsquos milk antigens-Viruses

bull Enterovirusbull Coxackievirus Bbull Rotavirusbull Mumpsbull CMVbull Congenital Rubella

MYCOBACTERIUM PARATUBERCULOSISHSP 65

PBD in T1DType 1rsquos can develop insulin resistance with a high fat diet

PBD can reduce insulin requirements by 30-50

PBD can reduce risk of diabetic comorbidities

Latent autoimmune diabetes Adult onset non-obese Present without ketoacidosis and weight loss Anti-body positive Gradual insulin-dependence

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 28: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

Dairy and MSMolecular mimicry between butyrophilin and myelin oligodendrocyte glycoprotein

Anti-BTN antibodies attack myelinated structures in the CNS and have been isolated in those with MS

MS TreatmentSafe and effective treatments are elusive

Interferon Side effects

$30000 per year

No evidence of a reduction in diabilityprogression

Mitoxantrone NNH 8 for irreversible systolic dysfunction and

123 for therapy-related acute leukemia

Dr Swank1951- 100 patients limited to 10-15 grams of saturated animal fat per day

3 frac12 year 5 frac12 year 7 year 20 year 34 year and 50 year follow up reports

After 34 years (1990) 95 of the patients were without progression of their disease

Increase in fat to 25-42gday was accompanied by increased disability and 3-fold increased risk of death to 79

In 2000 15 patients identified (50 year follow up) All could care for themselves independently

15 could ambulate as needed 13 truly ambulatory

MS TreatmentStudy on Vitamin D treatment in MS did not look at clinical outcomes

High dose Vitamin D supplementation did reduce helper T cells believed to be major contributors in immunopathogenesis of MS

Dose was 10400 IU daily and 21 of had to stop because of adverse effects

Type 1 Diabetes

Molecular Mimicry

Genetic Factors -alone cannot explain etiology

Environmental Factors- Cowrsquos milk antigens-Viruses

bull Enterovirusbull Coxackievirus Bbull Rotavirusbull Mumpsbull CMVbull Congenital Rubella

MYCOBACTERIUM PARATUBERCULOSISHSP 65

PBD in T1DType 1rsquos can develop insulin resistance with a high fat diet

PBD can reduce insulin requirements by 30-50

PBD can reduce risk of diabetic comorbidities

Latent autoimmune diabetes Adult onset non-obese Present without ketoacidosis and weight loss Anti-body positive Gradual insulin-dependence

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 29: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

MS TreatmentSafe and effective treatments are elusive

Interferon Side effects

$30000 per year

No evidence of a reduction in diabilityprogression

Mitoxantrone NNH 8 for irreversible systolic dysfunction and

123 for therapy-related acute leukemia

Dr Swank1951- 100 patients limited to 10-15 grams of saturated animal fat per day

3 frac12 year 5 frac12 year 7 year 20 year 34 year and 50 year follow up reports

After 34 years (1990) 95 of the patients were without progression of their disease

Increase in fat to 25-42gday was accompanied by increased disability and 3-fold increased risk of death to 79

In 2000 15 patients identified (50 year follow up) All could care for themselves independently

15 could ambulate as needed 13 truly ambulatory

MS TreatmentStudy on Vitamin D treatment in MS did not look at clinical outcomes

High dose Vitamin D supplementation did reduce helper T cells believed to be major contributors in immunopathogenesis of MS

Dose was 10400 IU daily and 21 of had to stop because of adverse effects

Type 1 Diabetes

Molecular Mimicry

Genetic Factors -alone cannot explain etiology

Environmental Factors- Cowrsquos milk antigens-Viruses

bull Enterovirusbull Coxackievirus Bbull Rotavirusbull Mumpsbull CMVbull Congenital Rubella

MYCOBACTERIUM PARATUBERCULOSISHSP 65

PBD in T1DType 1rsquos can develop insulin resistance with a high fat diet

PBD can reduce insulin requirements by 30-50

PBD can reduce risk of diabetic comorbidities

Latent autoimmune diabetes Adult onset non-obese Present without ketoacidosis and weight loss Anti-body positive Gradual insulin-dependence

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 30: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

Dr Swank1951- 100 patients limited to 10-15 grams of saturated animal fat per day

3 frac12 year 5 frac12 year 7 year 20 year 34 year and 50 year follow up reports

After 34 years (1990) 95 of the patients were without progression of their disease

Increase in fat to 25-42gday was accompanied by increased disability and 3-fold increased risk of death to 79

In 2000 15 patients identified (50 year follow up) All could care for themselves independently

15 could ambulate as needed 13 truly ambulatory

MS TreatmentStudy on Vitamin D treatment in MS did not look at clinical outcomes

High dose Vitamin D supplementation did reduce helper T cells believed to be major contributors in immunopathogenesis of MS

Dose was 10400 IU daily and 21 of had to stop because of adverse effects

Type 1 Diabetes

Molecular Mimicry

Genetic Factors -alone cannot explain etiology

Environmental Factors- Cowrsquos milk antigens-Viruses

bull Enterovirusbull Coxackievirus Bbull Rotavirusbull Mumpsbull CMVbull Congenital Rubella

MYCOBACTERIUM PARATUBERCULOSISHSP 65

PBD in T1DType 1rsquos can develop insulin resistance with a high fat diet

PBD can reduce insulin requirements by 30-50

PBD can reduce risk of diabetic comorbidities

Latent autoimmune diabetes Adult onset non-obese Present without ketoacidosis and weight loss Anti-body positive Gradual insulin-dependence

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 31: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

MS TreatmentStudy on Vitamin D treatment in MS did not look at clinical outcomes

High dose Vitamin D supplementation did reduce helper T cells believed to be major contributors in immunopathogenesis of MS

Dose was 10400 IU daily and 21 of had to stop because of adverse effects

Type 1 Diabetes

Molecular Mimicry

Genetic Factors -alone cannot explain etiology

Environmental Factors- Cowrsquos milk antigens-Viruses

bull Enterovirusbull Coxackievirus Bbull Rotavirusbull Mumpsbull CMVbull Congenital Rubella

MYCOBACTERIUM PARATUBERCULOSISHSP 65

PBD in T1DType 1rsquos can develop insulin resistance with a high fat diet

PBD can reduce insulin requirements by 30-50

PBD can reduce risk of diabetic comorbidities

Latent autoimmune diabetes Adult onset non-obese Present without ketoacidosis and weight loss Anti-body positive Gradual insulin-dependence

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 32: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

Type 1 Diabetes

Molecular Mimicry

Genetic Factors -alone cannot explain etiology

Environmental Factors- Cowrsquos milk antigens-Viruses

bull Enterovirusbull Coxackievirus Bbull Rotavirusbull Mumpsbull CMVbull Congenital Rubella

MYCOBACTERIUM PARATUBERCULOSISHSP 65

PBD in T1DType 1rsquos can develop insulin resistance with a high fat diet

PBD can reduce insulin requirements by 30-50

PBD can reduce risk of diabetic comorbidities

Latent autoimmune diabetes Adult onset non-obese Present without ketoacidosis and weight loss Anti-body positive Gradual insulin-dependence

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 33: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

Molecular Mimicry

Genetic Factors -alone cannot explain etiology

Environmental Factors- Cowrsquos milk antigens-Viruses

bull Enterovirusbull Coxackievirus Bbull Rotavirusbull Mumpsbull CMVbull Congenital Rubella

MYCOBACTERIUM PARATUBERCULOSISHSP 65

PBD in T1DType 1rsquos can develop insulin resistance with a high fat diet

PBD can reduce insulin requirements by 30-50

PBD can reduce risk of diabetic comorbidities

Latent autoimmune diabetes Adult onset non-obese Present without ketoacidosis and weight loss Anti-body positive Gradual insulin-dependence

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 34: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

Genetic Factors -alone cannot explain etiology

Environmental Factors- Cowrsquos milk antigens-Viruses

bull Enterovirusbull Coxackievirus Bbull Rotavirusbull Mumpsbull CMVbull Congenital Rubella

MYCOBACTERIUM PARATUBERCULOSISHSP 65

PBD in T1DType 1rsquos can develop insulin resistance with a high fat diet

PBD can reduce insulin requirements by 30-50

PBD can reduce risk of diabetic comorbidities

Latent autoimmune diabetes Adult onset non-obese Present without ketoacidosis and weight loss Anti-body positive Gradual insulin-dependence

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 35: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

bull Enterovirusbull Coxackievirus Bbull Rotavirusbull Mumpsbull CMVbull Congenital Rubella

MYCOBACTERIUM PARATUBERCULOSISHSP 65

PBD in T1DType 1rsquos can develop insulin resistance with a high fat diet

PBD can reduce insulin requirements by 30-50

PBD can reduce risk of diabetic comorbidities

Latent autoimmune diabetes Adult onset non-obese Present without ketoacidosis and weight loss Anti-body positive Gradual insulin-dependence

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 36: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

MYCOBACTERIUM PARATUBERCULOSISHSP 65

PBD in T1DType 1rsquos can develop insulin resistance with a high fat diet

PBD can reduce insulin requirements by 30-50

PBD can reduce risk of diabetic comorbidities

Latent autoimmune diabetes Adult onset non-obese Present without ketoacidosis and weight loss Anti-body positive Gradual insulin-dependence

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 37: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

PBD in T1DType 1rsquos can develop insulin resistance with a high fat diet

PBD can reduce insulin requirements by 30-50

PBD can reduce risk of diabetic comorbidities

Latent autoimmune diabetes Adult onset non-obese Present without ketoacidosis and weight loss Anti-body positive Gradual insulin-dependence

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 38: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

Latent autoimmune diabetes Adult onset non-obese Present without ketoacidosis and weight loss Anti-body positive Gradual insulin-dependence

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 39: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

Thank you

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 40: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

ReferencesArndt M et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma Rep 2014 Jan 14(1) 404 doi 101007s11882-013-0404-6

Thorburn AN Macia L Mackay CR Diet metabolites and western-lifestyle inflammatory diseases Immunity 2014 Jun 1940(6)833-42 doi 101016jimmuni201405014

Loftus EV Update on the incidence and prevalence of inflammatory bowel disease in the United States Gastroenterol Hepatol 2016 Nov 12(11)704-707

Devkota S Chang EB Interactions between diet bile acid metabolism gut microbiota and inflammatory bowel diseases Digestive Diseases 2015 33(3)

Ijssennagger N et al Sullfide as a mucus barrier-breaker in inflammatory bowel disease Trends in Molecular Medicine 2016 22(3)190-99

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 41: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

ReferencesR Wright S C Truelove A Controlled Therapeutic Trial of Various Diets in Ulcerative Colitis Br Med J 1965 Jul 17 2(5454) 138ndash141 S C Trulove Ulcerative Colitis Provoked by Milk Br Med J 1961 Jan 21 1(5220) 154ndash160 A H Rowe A Rowe Jr Chronic ulcerative colitis--atopic allergy in its etiology Am J Gastroenterol 1960 Jul3449-66

Silva JPB et al Protective Mechanisms of butyrate on inflammatory bowel disease Curr Pharm Des 201824(35)415mdash66 doi 1021741381612824666181001153605

Patel H Lissoos T Rubin DT Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohns disease in the United States PLoS One 201712(4)e0175099 Published 2017 Apr 20 doi101371journalpone0175099

Raftery T Martineau AR Greiller CL Ghosh S McNamara D Bennett K Meddings J OSullivan M Effects of vitamin D supplementation on intestinal permeability cathelicidin and disease markers in Crohns disease Results from a randomised double-blind placebo-controlled study United European Gastroenterol J 2015 Jun3(3)294-302

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 42: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

ReferencesS K Garg not listed) S Kumar V Ahuja M J Sankar A Kumar A C Moss Curcumin for maintenance of remission in ulcerative colitis Cochrane Database Syst Rev 2012 Oct 1710CD008424

Diaz-Pena R Castro-Santos P Genetics of rheumatoid arthritis a new boost is needed in Latin American populations Rev Bras Reumatol 201656(2) httpdxdoiorg101016jrbre201510004

Rashid T Ebringer A Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry Autoimmune Dis 2012 2012 539282

Gorvitovskaia A Holmes SP Huse SM Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle Microbiome 2016 415

B Chandran A Goel A randomized pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis Phytother Res 2012 26(11)1719 - 1725

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 43: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

ReferencesJ Kjeldsen-Kragh Rheumatoid arthritis treated with vegetarian diets Am J Clin Nutr 1999 Sep70(3 Suppl)594S-600S

Swank RL et al Multiple Sclerosis in rural Norway Its geographic and occupational incidence in relation to nutrition NEJM 1952 246(19)

Shirani A et al Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis JAMA 2012 Jul 18 308(3)

J J Marriott J M Miyasaki G Gronseth P W OConnor Evidence Report The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2010 74(18)1463 - 1470

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 44: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

ReferencesR L Swank B B Dugan Effect of low saturated fat diet in early and late cases of multiple sclerosis Lancet 1990 336(8706)37 - 39

Swank MS Foundation 2009 Dr Roy Laver Swank

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Multiple sclerosis Twenty years on low fat diet Arch Neurol 1970 23(5)460 - 474

R L Swank Treatment of multiple sclerosis with low-fat diet AMA Arch Neurol Psychiatry 1953 69(1)91-103

R L Swank Multiple sclerosis a correlation of its incidence with dietary fat Am J Med Sci 1950 Oct 220(4)421-430

M A Kadoch Is the treatment of multiple sclerosis headed in the wrong direction Can J Neurol Sci 2012 39(3)405

R L Swank J Goodwin Review of MS patient survival on a Swank low saturated fat diet Nutrition 2003 19(2)161 - 162

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)

Page 45: Autoimmune Disorders and Lifestyle MedicineArndt M, et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep. 2014 Jan; 14(1): 404. doi: 10.1007/s11882-013-0404-6

ReferencesLempainen J et al Interaction of enterovirus infection and cowrsquos milk based formula nutrition in type 1 diabetes-associated autoimmunity Diabetes Metab Res Rev 201228(2)177-85

Vaarala O Is the origin of type 1 diabetes in the gut Immunology and Cell Biology (2012) 90 271ndash276

Atreya R et al Facts myths and hypotheses on the zoonotic nature of Myobacterium avium subspecies Paratuberculosis Int J Med Microbiol 2014 304(7)858-67

Hesam Shariati S Alaei A Keshavarz R Mosavari N Rabbani A Niegowska M Sechi LA Feizabadi MM (2016) Detection of Mycobacterium avium subsp paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA J Infect Dev Ctries 10857-862 doi 103855jidc7473

Niegowska M et al Type 1 Diabetes at-risk children highly recognize Mycobacterium aviumsubspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin Scientific Reports 20166(22266)