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

Seminars in Arthritis and Rheumatism
doi:10.1016/j.semarthrit.2010.07.009
Copyright © 2010 Elsevier Inc. All rights reserved.
Martin A. Kriegel MDlow asterisk, JoAnn E. Manson MD, DrPH† and Karen H. Costenbader MD, MPH Kcostenbader at Partners.org
† Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA

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
cross-sectional data concerning vitamin D level and autoimmune disease;
interventional data on vitamin D supplementation in autoimmune diseases; and
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 that 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.

Results

Basic Science: In Vitro and In Vivo Studies
Evidence in Humans: Associations of Vitamin D with Circulating Biomarkers of Systemic Inflammation
Ecologic Associations Implicating Vitamin D in Autoimmune Disease
Genetic Polymorphisms in Vitamin D Pathway Genes Associated with Autoimmune Diseases
Cross-Sectional Studies of Vitamin D in Existing Autoimmune Diseases (Table 1)
Vitamin D Supplementation and Effects on Existing Disease Activity (Table 2)
Epidemiologic Studies of Vitamin D Level and Risk of Developing Autoimmune Disease (Table 3)
Epidemiologic Studies of Vitamin D Intake and Risk of Developing Autoimmune Disease (Table 4)
Potential Causes of Conflicting Results