Does vitamin D affect risk of developing autoimmune disease?: a systematic review

Abstract

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.

Figure 1

Flow diagram of literature search strategy and review.

Figure 2. Funnel plot of the risk estimates (odds ratios or relative risks) of developing autoimmune disease associated with vitamin D intake (none vs. supplementation or highest vs. lowest level of intake)

Sample size of the study refers to the number of autoimmune disease cases in each study. The appearance of an inverted funnel, where small studies of positive and negative studies have been published argues against a potential publication bias.