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Salt and Spices in Rheumatic Autoimmune Diseases

 
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This article was co-written by: Prof Yehuda Schoenfeld, Shani Dahan and Yahel Segal 


The concept of the mosaic of autoimmunity was initially coined in 1989 by Shoenfeld et al[1], referring to the complex interaction of genetic, hormonal, immunological and environmental factors in the pathogenesis of autoimmune diseases. 

During the past decades, the incidence of autoimmune diseases has increased,[2,3] whereas human genetics have not experienced much turmoil. In an attempt to elucidate this epidemiology, many environmental factors have been explored in relation to their correlation with autoimmune diseases. A prominent example is vitamin D deficiency, which has long been studied as one of the environmental factors in the development of autoimmune diseases such as multiple sclerosis (MS), type 1 diabetes and systemic lupus erythematosus (SLE).[4-9

Dietary habits have long been known to have a crucial influence on human health, affecting the risk for hypertension, heart diseases and stroke, as well as influencing the development of cancer.[10-13] Therefore, when considering the complex web of factors compiling the mosaic of autoimmunity, it is not surprising that various novel dietary elements were recently found to play a role in disease development and prevention.

In fact, there is no question that ‘we are what we eat’, and it is probably safe to assume every ingredient we consume has some effect on our health and specifically on our immune system.

There are several components of our diet for which there are relevant evidence as to their effect on rheumatic autoimmune diseases; 
  
First, salt was demonstrated to influence Th17 cells, which are known to play an integral part in several autoimmune diseases such as Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE), MS and psoriasis.[14-18] When examining the effect of high-salt diet on mice with Experimental Autoimmune Encephalitis (EAE), a murine model for MS, studies found the disease to be aggravated by high salt intake,[15] through different molecular mechanisms.

A recent observational study performed in Sweden, evaluating 1285 subjects from the Epidemiological Investigation of Rheumatoid Arthritis (EIRA), showed an increased risk of Anti Citrullinated Peptide Antibodies (ACPA) positivity among high sodium intake heavy smokers.[16] This eludes to a synergistic detrimental effect of sodium consumption and smoking in RA.[16

The next nutritional factor comprising the mosaic is spicy food. Spices have been a cardinal part of culinary cultures around the world, with chilli peppers being the most widely used seasoning, especially in China, Mexico and Italy.[17

The beneficial effects of spices are related to their bioactive ingredients such as capsaicin. Capsaicin, the main active ingredient of chilli peppers, is a phytochemical  which is responsible for the characteristic hot taste of these plants.[18] Recent studies have focused on investigating the influence of capsaicin in the pathogenesis of some autoimmune rheumatic diseases, with the most extensive data available in RA. Capsaicin was demonstrated to exert a beneficial effect in a clinical randomised controlled trial involving 31 RA patients.[19]

Topical capsaicin administration (0.025%), applied on painful knees four times a day, for a period of four weeks, was demonstrated to induce a 57% reduction in pain assessment as compared to the placebo group.[19] Topical capsaicin has been also evaluated in severely affected fibromyalgia patients, demonstrating short-term efficacy.

In a randomized trial of 130 fibromyalgia patients, topical administration on 0.075% topical capsaicin three times daily for six weeks, resulted in a significant improvement of several pain outcomes, such as myalgic score and the pressure pain threshold, compared to controls.[20]

Last but not least in the nutritional factors of the mosaic is Curcumin is a principal active component of the common spice Curcuma longa (turmeric), and its use dates back nearly 4000 years to India, where it has been used as a culinary spice and had religious significance.

Recently, the scientific community began exploring this substance for its effects on the human immune system and immune pathologies. The descibed mechanisms for the effect induced by curcumin included elevated expression of antioxidative stress and anti-inflammatory related genes; increased regulatory T cells (Treg) expression along with decreased Th1 expression; and a shift toward regulatory B cells, with a rise in protective anti-inflammatory antibody production.[21]

A clinical trial that assessed the effect of turmeric supplementation (standardised to 66mg curcumin daily) on lupus nephritis patients, showed a significant decrease in proteinuria, systolic blood pressure and haematuria in the turmeric group, while the control group presented no significant effect.[22]  

To summarise, the mosaic of autoimmunity has been a well-established concept for more than two decades; however various pieces of the mosaic continue to unravel as research progresses. Autoimmune rheumatic diseases are chronic diseases, greatly influenced by the life style of their carrier. In light of this, nutritional agents represent an attractive alternative to conventional therapeutics and require further investigation.

Current data suggests dietary factors hold significant effects on both the innate and the adaptive immune system. While salt appears to promote inflammation in various mechanisms, it seems that consumption of curcumin and spicy food may attenuate immune hyperactivity. These factors compile a novel, unexplored mosaic of autoimmunity, leaving some piquant taste for more!

 

References

  1. Shoenfeld Y, Isenberg DA. The mosaic of autoimmunity. Immunology today 1989; 10(4)123-126. [Abstract]
     
  2. Versini M, Jeandel P-Y, Bashi T, et al. Unraveling the Hygiene Hypothesis of helminthes and autoimmunity: origins, pathophysiology, and clinical applications. BMC medicine 2015;13:81. [Abstract]
     
  3. Lerner A, Matthias T. Changes in intestinal tight junction permeability associated with industrial food additives explain the rising incidence of autoimmune disease. Autoimmunity reviews 2015;14(6)479-489. [Abstract]
     
  4. Agmon-Levin N, Theodor E, Segal RM, et al. Vitamin D in systemic and organ-specific autoimmune diseases. Clinical reviews in allergy & immunology 2013;45(2):256-266. [Abstract]
     
  5. Azrielant S, Shoenfeld Y. Eppur Si Muove: vitamin D is essential in preventing and modulating SLE. Lupus 2016;25(6):563-572.[Abstract]
     
  6. Amital H, Szekanecz Z, Szucs G, et al. Serum concentrations of 25-OH vitamin D in patients with systemic lupus erythematosus (SLE) are inversely related to disease activity: is it time to routinely supplement patients with SLE with vitamin D? Ann Rheum Dis 2010;69(6):1155-1157.[Abstract]
     
  7. Carvalho JF, Blank M, Kiss E, et al. Anti-vitamin D, vitamin D in SLE: preliminary results. Ann N Y Acad Sci 2007;1109:550-557.[Abstract]
  8. Orbach H, Zandman-Goddard G, Amital H, et al. Novel biomarkers in autoimmune diseases: prolactin, ferritin, vitamin D, and TPA levels in autoimmune diseases. Ann N Y Acad Sci 2007;1109385-400.[Abstract]
  9. Oren Y, Shapira Y, Schoenfeld Y, et al. Vitamin D insufficiency in a sunny environment: a demographic and seasonal analysis. Israel Medical Association J (IMAJ) 2010;12(12):751-756.[Abstract]
     
  10. Abnet CC, Corley DA, Freedman ND, et al. Diet and upper gastrointestinal malignancies. Gastroenterol 201;148(6):1234-1243.e4.[Abstract]
     
  11. Del Gobbo LC, Falk MC, Feldman R, et al. Effects of tree nuts on blood lipids, apolipoproteins, and blood pressure: systematic review, meta-analysis, and dose-response of 61 controlled intervention trials. Am J clin nut 2015;102(6):1347-1356.[Abstract]
     
  12. Jayalath VH, de Souza RJ, Ha V, et al. Sugar-sweetened beverage consumption and incident hypertension: a systematic review and meta-analysis of prospective cohorts. Am J clin nutr 2015;102(4):914-921.[Abstract]
     
  13. Widmer RJ, Flammer AJ, Lerman LO, et al. The Mediterranean diet, its components, and cardiovascular disease. American J med 2015;128(3):229-238.[Abstract]
     
  14. Zhu S, Qian Y. IL-17/IL-17 receptor system in autoimmune disease: mechanisms and therapeutic potential. Clinical science (London, England :1979) 2012;122(11):487-511.[Abstract]
     
  15. Farez MF, Fiol MP, Gaitan MI, et al. Sodium intake is associated with increased disease activity in multiple sclerosis. J neurology, neurosurgery, and psychiatry 2015; 86(1):26-31.[Abstract]
     
  16. Jiang X, Sundstrom B, Alfredsson L, et al. High sodium chloride consumption enhances the effects of smoking but does not interact with SGK1 polymorphisms in the development of ACPA-positive status in patients with RA. Annals of the rheumatic diseases 2016;75(5):943-946.[Abstract]
     
  17. Cichewicz RH, Thorpe PA. The antimicrobial properties of chile peppers (Capsicum species) and their uses in Mayan medicine. J ethnopharmacol 1996;52(2):61-70.[Abstract]
     
  18. Deng Y, Huang X, Wu Haijing, et al Some like it hot: The emerging role of spicy food (capsaicin) in autoimmune diseases. Autoimmun Rev 2016;15(5):451-456.[Abstract]
     
  19. Deal CL, Schnitzer TJ, Lipstein E, et al. Treatment of arthritis with topical capsaicin: a double-blind trial. Clin Ther 1991;13(3):383-395.[Abstract]
     
  20. Casanueva B, Rodero B, Quintial C, et al. Short-term efficacy of topical capsaicin therapy in severely affected fibromyalgia patients. Rheumatol Int 2013;33(10):2665-2670.[Abstract]
     
  21. Dahan S, Segal Y, Shoenfeld Y. Dietary factors in rheumatic autoimmune diseases: a recipe for therapy? Nature Reviews Rheumatology 2017;13(6):348.[Abstract]
     
  22. Khajehdehi P, Zanjaninejad B, Aflaki E, et al. Oral supplementation of turmeric decreases proteinuria, hematuria, and systolic blood pressure in patients suffering from relapsing or refractory lupus nephritis: a randomized and placebo-controlled study. J renal nutrition 2012;22(1):50-57.[Abstract]

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