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 Table of Contents  
REVIEW ARTICLE
Year : 2017  |  Volume : 12  |  Issue : 4  |  Page : 219-222

Vitamin D and autoimmune diseases


1 Sheba Medical Center, The Zabludowicz Center for Autoimmune Diseases, Tel-Hashomer, Ramat-Gan; Sackler Faculty of Medicine, Tel-Aviv University, Israel
2 Sheba Medical Center, The Zabludowicz Center for Autoimmune Diseases, Tel-Hashomer, Ramat-Gan; Sackler Faculty of Medicine, Tel-Aviv University; Tel-Aviv University, Incumbent of the Laura Schwarz-Kip Chair for Research of Autoimmune Diseases, Ramat-Aviv, Tel-Aviv, Israel

Date of Web Publication16-Nov-2017

Correspondence Address:
Yehuda Shoenfeld
Sheba Medical Center, Zabludowicz Center for Autoimmune Diseases, Tel-Hashomer 5265601
Israel
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/injr.injr_99_17

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  Abstract 


Vitamin D and its deficiency are becoming a subject of great interest in recent years. In addition to the well-known role of vitamin D in maintaining bone health, evidence from recent years are accumulating in favor of its importance in the functioning of the immune system. The association between vitamin D deficiency and autoimmune diseases has been supported by epidemiological studies, demonstrating higher prevalence of vitamin D deficiency among autoimmune patients, in comparison to the general population. Vitamin D was also associated to various autoimmune diseases in both molecular and interventional studies; among the associated diseases are: systemic lupus erythematosus, type 1 diabetes mellitus, multiple sclerosis and others. In this review, relevant literature on the association between autoimmunity and vitamin D deficiency will be reviewed and discussed, as well as a summary of important recommendations for vitamin D supplementations in autoimmune patients.

Keywords: Autoimmunity, multiple sclerosis, systemic lupus erythematosus, type 1 diabetes mellitus, Vitamin D


How to cite this article:
Azrielant S, Shoenfeld Y. Vitamin D and autoimmune diseases. Indian J Rheumatol 2017;12:219-22

How to cite this URL:
Azrielant S, Shoenfeld Y. Vitamin D and autoimmune diseases. Indian J Rheumatol [serial online] 2017 [cited 2019 Sep 15];12:219-22. Available from: http://www.indianjrheumatol.com/text.asp?2017/12/4/219/214161




  Introduction Top


Genetic, immunological, hormonal, and environmental factors are assumed to contribute to the development of autoimmune diseases. One of the environmental factors studied has been Vitamin D.[1],[2] Vitamin D has a significant role in various processes of the immune system,[1],[3] and its receptors (Vitamin D receptor) were found in immune cells, including macrophages, dendritic cells, B-cells, and T-cells.[1],[4],[5],[6]In vitro studies showed an attenuating effect of Vitamin D on various immune cells of the immune system: neutrophils,[7] dendritic cells,[8] and T regulatory cells (Treg).[9],[10],[11] In terms of its activity on immune cells, Vitamin D was shown to have an inhibitory effect on Th1 cells,[12] leading to a decrease in Th1 cytokine production,[12],[13],[14] and possibly by increasing Th2 cytokines, and leading to an immunologic shift toward Th2.[12],[15] There is some evidence that Vitamin D modulates the activity of Th17 cells, which are known for their role in autoimmunity,[16] and increases the population of Treg cells, thereby promoting tolerance.[14],[17],[18] In an in vitro study, Vitamin D was shown to inhibit autoantibody production and secretion.[19]

Vitamin D deficiency is becoming more common. Epidemiological studies suggest Vitamin D deficiency is prevalent in the general population even in sunny countries like Israel,[20] but even more so among autoimmune patients.[3],[13],[21],[22],[23] Vitamin D deficiency's definition is still under controversy; one accepted definition is a serum level of 25-hydroxy-vitamin D (25[OH]D) under 30–40 ng/ml, which is the necessary level for maintaining bone health.[24] Within the normal range of serum Vitamin D concentration, an optimal level for the functioning of the immune system is yet to be determined.[25]


  Systemic Lupus Erythematosus Top


Much of the evidence for the association between Vitamin D and autoimmunity comes from research of systemic lupus erythematosus (SLE). Vitamin D deficiency is more common in SLE patients than in healthy controls,[22],[23] as in many other autoimmune diseases;[21] however, SLE patients are even more prone to develop Vitamin D deficiency, as they are advised to avoid sun exposure, due to photosensitivity.[26]

Low levels of Vitamin D were associated with higher SLE activity.[27],[28],[29],[30] Vitamin D levels were also associated with other manifestations of the disease and its comorbidities, such as cognitive impairment,[31] insulin resistance,[23] and sleep disturbances.[32]

Analysis of the intervening variables for the association between Vitamin D levels and SLE found that the most significant were medications (hydroxychloroquine, steroids, and Vitamin D supplements), body mass index, renal function, and proteinuria.[33]

To further investigate this association, interventional studies were done, using Vitamin D supplementation. The conventional doses described in the literature are 800, 2000, and 4000 IU/day.[4],[25] In a large-scale cohort study, Vitamin D supplementation was given to lupus patients who had Vitamin D levels lower than 40 ng/ml. Improvement in proteinuria was shown in patients with higher 25(OH)D levels; also, a correlation was observed between disease activity and the change in 25(OH)D values, but only in patients who were Vitamin D-deficient at the beginning of the study. No effect on disease activity was found after increasing Vitamin D levels above 40 ng/mL.[34]


  Multiple Sclerosis Top


Proof for the association between Vitamin D and multiple sclerosis (MS) arose from epidemiological studies. A review from 2008 suggests that distance from the equator is the strongest risk factor for MS, seemingly due to ultraviolet (UV) radiation exposure, and that emigration from cold countries to sunny ones decreased the risk for the disease.[35]

Analysis of dietary and supplementary Vitamin D intake in two large cohorts of nurses, with over 90,000 participants each, demonstrated lower risk for MS in women with high Vitamin D intake, compared to women with low intake, and Vitamin D supplementation was inversely associated with MS risk. Notably, high dietary intake of Vitamin D alone did not generate similar association.[36]

Vitamin D was reported to be an early predictor of MS activity and progression, with slower progression and low disease activity in patients with high serum Vitamin D levels at the time of MS diagnosis.[37],[38] A seasonal pattern was described for manifestations MS, a pattern that could be attributed to changing levels of Vitamin D in different seasons.[39]


  Type 1 Diabetes Mellitus Top


The prevalence of diabetes mellitus type 1 (DM1) is highly dependent on geographic location. In a research on this matter, researchers demonstrated a correlation between the disease's rates and distance from the equator and assumed this correlation to be, at least in part, explained by distribution of UV-B irradiance, the main source of Vitamin D in humans.[40] Supplementation studies also support this conclusion. Studies have shown that Vitamin D supplementation in early life reduced the risk for developing DM1 later on,[41] improved glycemic control in pediatric patients who suffered from Vitamin D deficiency,[42] and correlated with lower prevalence of diabetic nephropathy.[43]


  Miscellaneous Top


Vitamin D deficiency was found to be more common among patients with inflammatory bowel disease (IBD),[44] rheumatoid arthritis (RA),[45] and psoriasis [46] compared to controls; low levels of Vitamin D were associated with higher disease activity in IBD and RA.[44],[47]


  Conclusion Top


Vitamin D has a crucial role in the functioning of the immune system. Vitamin D was shown to be an immunomodulator in various molecular studies. Therefore, maintaining normal levels of Vitamin D is important.

Vitamin D deficiency is common in patients with autoimmune diseases, as was seen in patients with MS, type 1 diabetes, IBD, and RA, and seems to affect the activity and outcomes of these autoimmune diseases.

Vitamin D is very safe to use, and adverse effects and toxicity are rarely reached, even at doses as high as 10,000 IU;[48] therefore, although further studies are needed to determine the exact mechanism of the effect of Vitamin D in autoimmune diseases, we recommend considering Vitamin D supplementation in all autoimmune patients based on existing evidence. Currently, there is no across-the-board recommendation for vitamin D supplementation dosage in autoimmune patients. However, based on previous interventional studies, supplementation dosage of 800–1000 units per day seems to be appropriate.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Introduction
Systemic Lupus E...
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