title: Can supplementation with vitamin D reduce the risk or modify the course of autoimmune diseases? A systematic review of the literature.
abstract: OBJECTIVE
  To evaluate whether vitamin D levels are related to the risk of developing autoimmune diseases and whether supplementation with vitamin D can modify the course of the diseases.
  
  
  METHODS
  We reviewed the most relevant papers published from January 1973 to October 2011, using Medline and EMBASE and the search terms "vitamin D"; "autoimmune disease"; "autoimmunity"; "rheumatoid arthritis"; "systemic lupus erythematosus"; "scleroderma"; "systemic sclerosis"; "type 1 diabetes"; "multiple sclerosis"; and "undifferentiated connective tissue disease". We selected studies on the environmental, genetic and epidemiologic association of vitamin D with autoimmune diseases. Using the strategy described, we identified 1268 articles. 331 articles were eliminated on the basis of the title and another 703 on the basis of the abstract, since they were considered irrelevant for the purposes of the study. Full-text examination was performed on the remaining 234 studies, and a further 15 studies were excluded from the review, since the results had been confirmed or superseded by more recent research. Finally, a systematic review was conducted on 219 articles concerning cross-sectional data on: vitamin D levels and autoimmune diseases; interventional data on vitamin D supplementation in autoimmune diseases; prospective data linking vitamin D level or intake to autoimmune disease risk.
  
  
  RESULTS
  Physiopathology studies confirm that hypovitaminosis D, in genetically predisposed subjects, can impair self tolerance by compromising the regulation of dendritic cells, of regulatory T-lymphocytes and of Th1 cells. Cross-sectional studies show that levels of vitamin D <30 ng/mL are present in a significant percentage, not only in patients with autoimmune disease, but also in healthy subjects (30-77%), and link profound deficiency (<10 ng/mL) with aggravation of symptomatology, while genetic studies associate polymorphism of vitamin D receptors to various autoimmune diseases. Among experimental studies on humans, only those on type-1 diabetes prove that the risks are significantly reduced in infants treated with vitamin D after the 7th month (OR 0.71, 95% CI, 0.60 to 0.84) and that a dose-response effect exists.
  
  
  CONCLUSIONS
  Basic, genetic, and epidemiological studies indicate a potential role of vitamin D in the prevention of autoimmune diseases, but randomized and controlled trials are necessary to establish the clinical efficacy of vitamin D supplementation in ill or at-risk subjects.
authors: Laboratorio di Patologia Clinica, Ospedale Civile, Cittadella, Italy. antonioantico@virgilio.it
authors: Antonio
authors: A
authors: Antico
authors: Marilina
authors: M
authors: Tampoia
authors: Renato
authors: R
authors: Tozzoli
authors: Nicola
authors: N
authors: Bizzaro
mesh_terms: D001327:Autoimmune Diseases / Q000178:diet therapy* / Q000453:epidemiology / Q000276:immunology*; D019587:Dietary Supplements; D004777:Environment; D059647:Gene-Environment Interaction; D056726:Genetic Association Studies; D006801:Humans; D015995:Prevalence; D014807:Vitamin D / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D014807:Vitamin D