Does Vitamin D Affect Risk of Developing Autoimmune Disease?: A Systematic Review

Objectives: We evaluated the epidemiologic evidence that vitamin D may be related to human autoimmune disease risk. Methods: PubMed, limited to English from inception through April 2010, was searched using keywords: "vitamin D," "autoimmune," and autoimmune disease names. We summarized in vitro, animal, and genetic association studies of vitamin D in autoimmune disease pathogenesis. We sorted epidemiologic studies by design and disease and performed a systematic review of (a) cross-sectional data concerning vitamin D level and autoimmune disease; (b) interventional data on vitamin D supplementation in autoimmune diseases; and (c) prospective data linking vitamin D level or intake to autoimmune disease risk. Results: Vitamin D has effects on innate and acquired immune systems, and vitamin D receptor polymorphisms have been associated with various autoimmune diseases. In experimental animal models, vitamin D supplementation can prevent or forestall autoimmune disease. Of 1446 studies identified and screened, 76 studies examined vitamin D levels in autoimmune disease patients, particularly with active disease, and compared with controls. Nineteen observational or interventional studies assessed the effect of vitamin D supplementation as therapy for various autoimmune diseases (excluding psoriasis and vitiligo) with a range of study approaches and results. The few prospective human studies performed conflict as to whether vitamin D level or intake is associated with autoimmune disease risk. No interventional trials have investigated whether vitamin D affects human autoimmune disease risk. Conclusions: Cross-sectional data point to a potential role of vitamin D in autoimmune disease prevention, but prospective interventional evidence in humans is still lacking. (C) 2011 Elsevier Inc. All rights reserved. Semin Arthritis Rheum 40:512-531