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All About: Auto-Immunity

What is 'autoimmunity'? And what does the evidence tell us about treating autoimmune conditions with diet and lifestyle?

Key Points

  • Auto-immune conditions result from the body attacking ‘self’ tissue with the immune responses
  • The shift to a modern diet high in refined foods may have increased rates of autoimmune disorders
  • Dietary and lifestyle triggers might be related to negative changes to the gut biome, metabolic syndrome, obesity and diabetes
  • Stress and poor sleep also trigger relapse and worsen symptoms in autoimmune conditions
  • Dietary interventions: gluten-free diet, vitamin D, fasting, dairy reduction, and a low-allergen diet might offer clinical benefits

Autoimmunity refers to the situation in which the immune system launches a response against its healthy cells instead of against a foreign ‘invader’ like a bacteria, virus, fungi, protozoa or helminth (worm).

The diseases that can result from this type of response are collectively known as autoimmune diseases. Autoimmune conditions include diseases such as myocarditis, systemic lupus, autoimmune hepatitis, dermatitis herpetiformis, psoriasis, vitiligo, Addison’s disease, autoimmune pancreatitis, type 1 diabetes, Hashimoto’s thyroiditis, multiple sclerosis, and many more.

Autoimmune conditions usually result from a mixture of ‘nature and nurture’ with a strong genetic basis, amplified by environmental and lifestyle factors. For example, in some individuals, infectious parasites might help to protect people against autoimmune conditions (hygiene theory) whereas in others, different parasites can trigger autoimmune reactions, likely as a result of molecular mimicry (in which the pathogen carries markers similar to self-tissue) or because the pathogen becomes inextricably linked to tissue in the body.

Diet and lifestyle could also play a role in the development of autoimmune conditions. A healthy diet can help the immune system to better recognise self vs non-self but the exact effects of specific nutrients on autoimmune conditions are at this time, not clear.1 

The shift to a western-style diet high in processed and refined foods could be a risk factor for the development of autoimmune conditions

It has been suspected that the shift to a western-style diet high in processed and refined foods could be a risk factor for the development of autoimmune conditions.2

The modern diet and its effect on the gut microbiome have also been suggested as one of the myriad reasons why people might develop AI diseases, and one of the reasons that fasting is beginning to show efficacy for the treatment of AI conditions.3 The modern diet also predisposes people to fat gain and obesity. Fat tissue (adipose tissue) produces pro-inflammatory adipokines that have been linked to autoimmune diseases and obesity is considered a risk factor for conditions like multiple sclerosis,4 while insulin resistance (metabolic syndrome) is considered a risk factor for AI conditions including autoimmune hepatitis.5

Fat tissue produces adipokines that have been linked to autoimmune diseases

What do we know about diet and lifestyle, and AI conditions?

Stress

The onset of around 50% of autoimmune conditions has been attributed to ‘unknown triggers’, and stress (psychosocial, emotional, and physical) is thought to play a primary role in the development of autoimmunity.6-9 It is presumed that the stress-triggered hormones lead to altered regulation of the immune system which can ultimately result in autoimmune disease,6 stressful life events are associated with increased risk of developing an autoimmune disease.10

~50% of autoimmune conditions have been attributed to ‘unknown triggers’, and stress

However, ‘stressors’ can be positive or negative.11 For example, exercise can be ‘stressful’ to the body but results in positive adaptations. Similarly, fasting can promote stress reactions in the body that are beneficial. In both cases though, a positive stressor can easily become a negative one if carried out to the extreme.

Sleep

One of the effects of stress (and a cause of it) is poor sleep. Poor sleep has been associated with increased inflammation,12 and increases the symptoms or risk of developing autoimmune diseases such as multiple sclerosis,13 rheumatoid arthritis, scleroderma, and lupus.14 Sleep apnoea has also been suggested as a risk factor for autoimmune diseases,15 and Chrono insomnia (with sleeping pill prescription) has been linked to a 70% increased risk of autoimmune disease.16

Poor sleep increases the symptoms, or risk of developing autoimmune diseases

Sleep is thought to have a ‘bidirectional’ relationship with the immune system (poor sleep can affect our immune control and poor immune function can affect sleep). In a study of a mouse model of lupus, the results indicated that mice submitted to sleep deprivation exhibited an earlier onset of the disease, as reflected by the increased number of antinuclear antibodies. However, no statistical difference was found in the other parameters analysed. According to these results, sleep deprivation could be considered as a risk factor for the onset but not for the evolution of the disease.17

Gluten-free diet

The gluten-free diet is an obvious intervention for the autoimmune disease of gluten intolerance, Coeliac disease, but it is also potentially linked to other non-Coeliac autoimmune diseases too and may increase the risk of other diseases due to a range of factors including; shared genes (with Coeliac disease), increased intestinal permeability, and increased intestinal and systemic inflammation.18

It is known that a gluten-free diet reduces zonulin (which is responsible for modulating intestinal permeability) and reduces ‘leaky gut’ and auto-antibodies, further suggesting a role for a gluten-free diet for autoimmune conditions.19 There is, for example, a higher incidence of autoimmune thyroid disease amongst those with Coeliac disease,20 and the risk for someone with Coeliac disease developing another autoimmune disease is more than double if they have not been compliant with a gluten-free diet.21 Several cases have noted reductions in systemic symptoms or comorbidities in people with autoimmune conditions, suggesting a wider benefit in autoimmunity from a gluten-free diet.22-24 In another series of case studies, improvements were seen in a range of autoimmune conditions (including Crohn’s disease and type 1 diabetes) from the implementation of a wheat-free Paleo-style diet.25

Improvements were seen in a range of autoimmune conditions from a Paleo-style diet

Dairy?

While diary is typically anti-inflammatory dairy is a relatively common allergen and the incidence of dairy allergies appears to be rising.26 

A review of 52 clinical trials evaluated the inflammatory score of diets containing dairy. The overall evidence suggested an anti-inflammatory effect of dairy whether low-fat, high-fat, or fermented. However, when the subjects in the studies were analysed according to health status, dairy was found to be inflammatory for those with underlying allergies to dairy proteins,27 and elimination diets that include the reduction or complete elimination of dairy have shown efficacy for autoimmune conditions such as Crohn’s disease,28 ulcerative colitis,29 and asthma,30 and clinical experience suggests that dairy elimination should be trialled in those with autoimmune conditions. 

The reduction or complete elimination of dairy has shown some efficacy for autoimmune conditions

Improved gut health

Changes to the gut microbiota and the production of bacterial metabolites (like short-chain fatty acids) have been suggested as a possible reason for the rising incidence of autoimmune conditions.3, 31 In one of the broadest autoimmune conditions, systemic lupus erythematosus, which can affect many organs and tissue throughout the body, there is a high rate of dysbiosis, and the microbiota is being considered as a promising therapeutic target.32

Vitamin D

Industrialised countries further from the equator (New Zealand, Australia, the UK) have some of the highest prevalence of autoimmune conditions and this has been linked to vitamin D levels from sun exposure.33

Fasting

Dietary energy restriction helps to modulate inflammatory and immune responses and offers promise as part of the adjunctive treatment for autoimmune conditions.34, 35

Cocoa and other flavonoids?

While feeding cocoa did not reduce swelling in a mice model of autoimmune arthritis, it did reduce reactive oxygen species production, and the inflammatory marker tumour necrosis factor-α (a common marker of inflammation in autoimmune conditions).36

References

1.         Arabi S, Molazadeh M, Rezaei N. Nutrition, Immunity, and Autoimmune Diseases. In: Mahmoudi M, Rezaei N, editors. Nutrition and Immunity. Cham: Springer International Publishing; 2019. p. 415-36.

2.         Manzel A, Muller DN, Hafler DA, Erdman SE, Linker RA, Kleinewietfeld M. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Current Allergy and Asthma Reports. 2013;14(1):404.

3.         Vieira S, Pagovich O, Kriegel M. Diet, microbiota and autoimmune diseases. Lupus. 2014;23(6):518-26.

4.         Ahn JJ, Revelo X, Winer DA, Dunn SE. Diet-induced obesity enhances the severity of experimental autoimmune encephalomyelitis. Journal of Neuroimmunology. 2014;275(1):133.

5.         Natasha A V, McAnenny C.

6.         Stojanovich L, Marisavljevich D. Stress as a trigger of autoimmune disease. Autoimmunity Reviews. 2008;7(3):209-13.

7.         WALLACE R. SYSTEMIC LUPUS ERYTHEMATOSUS IN AFRICAN-AMERICAN WOMEN: COGNITIVE PHYSIOLOGICAL MODULES, AUTOIMMUNE DISEASE, AND STRUCTURED PSYCHOSOCIAL STRESS. Advances in Complex Systems. 2003;06(04):599-629.

8.         Rabin BS. Can stress participate in the pathogenesis of autoimmune disease? Journal of Adolescent Health. 2002;30(4):71-5.

9.         Allison M. Correlations in Stress Disorders and Autoimmune Disease: A Review. Microreviews in Cell and Molecular Biology. 2019;5(1).

10.       Song H, Fang F, Tomasson G, Arnberg FK, Mataix-Cols D, Fernández de la Cruz L, et al. Association of Stress-Related Disorders With Subsequent Autoimmune Disease. JAMA. 2018;319(23):2388-400.

11.       Jessop DS, Richards LJ, Harbuz MS. Brief ReviewEffects of Stress on Inflammatory Autoimmune Disease: Destructive or Protective? Stress (Amsterdam, Netherlands). 2004;7(4):261-6.

12.       Irwin MR, Olmstead R, Carroll JE. Sleep Disturbance, Sleep Duration, and Inflammation: A Systematic Review and Meta-Analysis of Cohort Studies and Experimental Sleep Deprivation. Biological Psychiatry. 2016;80(1):40-52.

13.       Hughes AJ, Dunn KM, Chaffee T. Sleep Disturbance and Cognitive Dysfunction in Multiple Sclerosis: a Systematic Review. Current Neurology and Neuroscience Reports. 2018;18(1):2.

14.       Sangle SR, Tench CM, D’Cruz DP. Autoimmune rheumatic disease and sleep: a review. Current Opinion in Pulmonary Medicine. 2015;21(6):553-6.

15.       Abrams B. Long-term sleep apnea as a pathogenic factor for cell-mediated autoimmune disease. Medical Hypotheses. 2005;65(6):1024-7.

16.       Kok VC, Horng J-T, Hung G-D, Xu J-L, Hung T-W, Chen Y-C, et al. Risk of Autoimmune Disease in Adults with Chronic Insomnia Requiring Sleep-Inducing Pills: A Population-Based Longitudinal Study. Journal of general internal medicine. 2016;31(9):1019-26.

17.       Palma BD, Alexandre Gabriel J, Colugnati FAB, Tufik S. Effects of sleep deprivation on the development of autoimmune disease in an experimental model of systemic lupus erythematosus. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 2006;291(5):R1527-R32.

18.       Lerner A, Ramesh A, Matthias T. Are non-celiac autoimmune diseases responsive to gluten-free diet. Int J Celiac Dis. 2017;5:164-7.

19.       Kryszak D, Neri E, Palese T, Sapone A, Counts DR, Not T, et al. Effect Of the Gluten Free Diet on Serum Zonulin Levels and Autoimmune Biomarkers in Both Treated and Untreated Celiac Disease Patients2005 2005.

20.       Metso S, Hyytiä-Ilmonen H, Kaukinen K, Huhtala H, Jaatinen P, Salmi J, et al. Gluten-free diet and autoimmune thyroiditis in patients with celiac disease. A prospective controlled study. Scandinavian Journal of Gastroenterology. 2012;47(1):43-8.

21.       Cosnes J, Cellier C, Viola S, Colombel JF, Michaud L, Sarles J, et al. Incidence of Autoimmune Diseases in Celiac Disease: Protective Effect of the Gluten-Free Diet. Clinical Gastroenterology and Hepatology. 2008;6(7):753-8.

22.       William W. Eaton, Ph.D., Lian-Yu Chen, M.D., F. Curtis Dohan J, , M.D., Deanna L. Kelly, Pharm.D., Nicola Cascella, M.D. Improvement in Psychotic Symptoms After a Gluten-Free Diet in a Boy With Complex Autoimmune Illness. American Journal of Psychiatry. 2015;172(3):219-21.

23.       Iorio R, Sepe A, Giannattasio A, Spagnuolo MI, Vecchione R, Vegnente A. Lack of Benefit of Gluten-Free Diet on Autoimmune Hepatitis in a Boy With Celiac Disease. Journal of Pediatric Gastroenterology and Nutrition. 2004;39(2):207-10.

24.       Iqbal U, Chaudhary A, Karim MA, Siddiqui MA, Anwar H, Merrell N. Association of Autoimmune Hepatitis and Celiac Disease: Role of Gluten-Free Diet in Reversing Liver Dysfunction. Journal of Investigative Medicine High Impact Case Reports. 2017;5(2):2324709617705679.

25.       Connor T. Case study of a wheat-free diet on autoimmune disease progression, A: Colorado State University. Libraries; 2014.

26.       Rona RJ, Keil T, Summers C, Gislason D, Zuidmeer L, Sodergren E, et al. The prevalence of food allergy: A meta-analysis. Journal of Allergy and Clinical Immunology. 2007;120(3):638-46.

27.       Bordoni A, Danesi F, Dardevet D, Dupont D, Fernandez AS, Gille D, et al. Dairy products and inflammation: A review of the clinical evidence. Crit Rev Food Sci Nutr. 2017;57(12):2497-525.

28.       Slonim AE, Grovit M, Bulone L. Effect of Exclusion Diet with Nutraceutical Therapy in Juvenile Crohn’s Disease. Journal of the American College of Nutrition. 2009;28(3):277-85.

29.       Wright R, Truelove SC, Draper GJ. A Controlled Therapeutic Trial Of Various Diets In Ulcerative Colitis. The British Medical Journal. 1965;2(5454):138-41.

30.       Liu AH, Jaramillo R, Sicherer SH, Wood RA, Bock SA, Burks AW, et al. National prevalence and risk factors for food allergy and relationship to asthma: Results from the National Health and Nutrition Examination Survey 2005-2006. Journal of Allergy and Clinical Immunology. 2010;126(4):798-806.e14.

31.       Mackay CR. Chapter 19 – Diet, the Gut Microbiome, and Autoimmune Diseases. In: Rose NR, Mackay IR, editors. The Autoimmune Diseases (Sixth Edition): Academic Press; 2020. p. 331-42.

32.       Mu Q, Zhang H, Luo XM. SLE: Another Autoimmune Disorder Influenced by Microbes and Diet? Frontiers in Immunology. 2015;6(608).

33.       Weiss ST, Litonjua AA. Maternal diet vs lack of exposure to sunlight as the cause of the epidemic of asthma, allergies and other autoimmune diseases. Thorax. 2007;62(9):746.

34.       Jolly CA. Diet manipulation and prevention of aging, cancer and autoimmune disease. Current Opinion in Clinical Nutrition & Metabolic Care. 2005;8(4):382-7.

35.       Choi IY, Lee C, Longo VD. Nutrition and fasting mimicking diets in the prevention and treatment of autoimmune diseases and immunosenescence. Molecular and Cellular Endocrinology. 2017;455:4-12.

36.       Ramos-Romero S, Pérez-Cano FJ, Pérez-Berezo T, Castellote C, Franch A, Castell M. Effect of a cocoa flavonoid-enriched diet on experimental autoimmune arthritis. British Journal of Nutrition. 2012;107(4):523-32.

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