title: Vitamin D with or without calcium supplementation for prevention of cancer and fractures: an updated meta-analysis for the U.S. Preventive Services Task Force.
abstract: BACKGROUND
  Studies suggest that vitamin D supplementation may reduce cancer and fracture risks.
  
  
  OBJECTIVE
  To examine the benefits and harms of vitamin D with or without calcium supplementation on clinical outcomes of cancer and fractures in adults.
  
  
  METHODS
  English-language studies identified from MEDLINE and the Cochrane Central Register of Controlled Trials through July 2011.
  
  
  METHODS
  Randomized, controlled trials (RCTs), prospective cohort studies, and nested case-control studies reporting incidence of or death from cancer and fracture outcomes.
  
  
  METHODS
  Multiple reviewers extracted details about participant characteristics, including baseline vitamin D status and use of supplements; details of statistical analyses, including adjustments for confounding; and methodological quality. Differences were resolved by consensus.
  
  
  RESULTS
  19 RCTs (3 for cancer and 16 for fracture outcomes) and 28 observational studies (for cancer outcomes) were analyzed. Limited data from RCTs suggested that high-dose (1000 IU/d) vitamin D supplementation can reduce the risk for total cancer, and data from observational studies suggested that higher blood 25-hydroxyvitamin D (25-[OH]D) concentrations might be associated with increased risk for cancer. Mixed-effects dose-response meta-analyses showed that each 10-nmol/L increase in blood 25-(OH)D concentration was associated with a 6% (95% CI, 3% to 9%) reduced risk for colorectal cancer but no statistically significant dose-response relationships for prostate and breast cancer. Random-effects model meta-analysis showed that combined vitamin D and calcium supplementation reduced fracture risk (pooled relative risk, 0.88 [CI, 0.78 to 0.99]) in older adults, but the effects differed according to study setting: institution (relative risk, 0.71 [CI, 0.57 to 0.89]) versus community-dwelling (relative risk, 0.89 [CI, 0.76 to 1.04]). One RCT showed adverse outcomes associated with supplementation, including increased risk for renal and urinary tract stones.
  
  
  CONCLUSIONS
  Most trial participants were older (aged≥65 years) postmenopausal women. Observational studies were heterogeneous and were limited by potential confounders.
  
  
  CONCLUSIONS
  Combined vitamin D and calcium supplementation can reduce fracture risk, but the effects may be smaller among community-dwelling older adults than among institutionalized elderly persons. Appropriate dose and dosing regimens, however, require further study. Evidence is not sufficiently robust to draw conclusions regarding the benefits or harms of vitamin D supplementation for the prevention of cancer.
  
  
  BACKGROUND
  Agency for Healthcare Research and Quality.
authors.affiliation: Tufts Evidence-based Practice Center, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, Massachusetts 02111, USA. mchung1@tuftsmedicalcenter.org
authors.forename: Mei
authors.initials: M
authors.lastname: Chung
authors.forename: Jounghee
authors.initials: J
authors.lastname: Lee
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Terasawa
authors.forename: Joseph
authors.initials: J
authors.lastname: Lau
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Trikalinos
mesh_terms: D015652:25-Hydroxyvitamin D 2 / Q000097:blood; D026683:Advisory Committees; D000367:Age Factors; D002118:Calcium / Q000008:administration & dosage* / Q000009:adverse effects; D019587:Dietary Supplements / Q000009:adverse effects; D050723:Fractures, Bone / Q000517:prevention & control*; D006801:Humans; D009369:Neoplasms / Q000517:prevention & control*; D012737:Sex Factors; D014481:United States; D014545:Urinary Calculi / Q000209:etiology; D014807:Vitamin D / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D014807:Vitamin D; D015652:25-Hydroxyvitamin D 2; D002118:Calcium