title: Vitamin D and risk of cause specific death: systematic review and meta-analysis of observational cohort and randomised intervention studies.
abstract: OBJECTIVE
  To evaluate the extent to which circulating biomarker and supplements of vitamin D are associated with mortality from cardiovascular, cancer, or other conditions, under various circumstances.
  
  
  METHODS
  Systematic review and meta-analysis of observational studies and randomised controlled trials.
  
  
  METHODS
  Medline, Embase, Cochrane Library, and reference lists of relevant studies to August 2013; correspondance with investigators.
  
  
  METHODS
  Observational cohort studies and randomised controlled trials in adults, which reported associations between vitamin D (measured as circulating 25-hydroxyvitamin D concentration or vitamin D supplement given singly) and cause specific mortality outcomes.
  
  
  METHODS
  Data were extracted by two independent investigators, and a consensus was reached with involvement of a third. Study specific relative risks from 73 cohort studies (849,412 participants) and 22 randomised controlled trials (vitamin D given alone versus placebo or no treatment; 30,716 participants) were meta-analysed using random effects models and were grouped by study and population characteristics.
  
  
  RESULTS
  In the primary prevention observational studies, comparing bottom versus top thirds of baseline circulating 25-hydroxyvitamin D distribution, pooled relative risks were 1.35 (95% confidence interval 1.13 to 1.61) for death from cardiovascular disease, 1.14 (1.01 to 1.29) for death from cancer, 1.30 (1.07 to 1.59) for non-vascular, non-cancer death, and 1.35 (1.22 to 1.49) for all cause mortality. Subgroup analyses in the observational studies indicated that risk of mortality was significantly higher in studies with lower baseline use of vitamin D supplements. In randomised controlled trials, relative risks for all cause mortality were 0.89 (0.80 to 0.99) for vitamin D3 supplementation and 1.04 (0.97 to 1.11) for vitamin D2 supplementation. The effects observed for vitamin D3 supplementation remained unchanged when grouped by various characteristics. However, for vitamin D2 supplementation, increased risks of mortality were observed in studies with lower intervention doses and shorter average intervention periods.
  
  
  CONCLUSIONS
  Evidence from observational studies indicates inverse associations of circulating 25-hydroxyvitamin D with risks of death due to cardiovascular disease, cancer, and other causes. Supplementation with vitamin D3 significantly reduces overall mortality among older adults; however, before any widespread supplementation, further investigations will be required to establish the optimal dose and duration and whether vitamin D3 and D2 have different effects on mortality risk.
authors.affiliation: Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge CB1 8RN, UK.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Chowdhury
authors.forename: Setor
authors.initials: S
authors.lastname: Kunutsor
authors.forename: Anna
authors.initials: A
authors.lastname: Vitezova
authors.forename: Clare
authors.initials: C
authors.lastname: Oliver-Williams
authors.forename: Susmita
authors.initials: S
authors.lastname: Chowdhury
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Kiefte-de-Jong
authors.forename: Hassan
authors.initials: H
authors.lastname: Khan
authors.forename: Cristina P
authors.initials: CP
authors.lastname: Baena
authors.forename: Dorairaj
authors.initials: D
authors.lastname: Prabhakaran
authors.forename: Moshe B
authors.initials: MB
authors.lastname: Hoshen
authors.forename: Becca S
authors.initials: BS
authors.lastname: Feldman
authors.forename: An
authors.initials: A
authors.lastname: Pan
authors.forename: Laura
authors.initials: L
authors.lastname: Johnson
authors.forename: Francesca
authors.initials: F
authors.lastname: Crowe
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
authors.forename: Oscar H
authors.initials: OH
authors.lastname: Franco
mesh_terms: D002423:Cause of Death; D019587:Dietary Supplements; D006801:Humans; D012307:Risk Factors; D014807:Vitamin D / Q000097:blood / Q000627:therapeutic use; D014808:Vitamin D Deficiency / Q000401:mortality*; D014815:Vitamins / Q000097:blood / Q000627:therapeutic use
chemical_list: D014815:Vitamins; D014807:Vitamin D