title: Association between B vitamins supplementation and risk of cardiovascular outcomes: a cumulative meta-analysis of randomized controlled trials.
abstract: BACKGROUND
  Observational studies suggest that B vitamin supplementation reduces cardiovascular risk in adults, but this association remains controversial. This study aimed to summarize the evidence from randomized controlled trials (RCTs) investigating B vitamin supplementation for the primary or secondary prevention of major adverse cardiovascular outcomes and to perform a cumulative meta-analysis to determine the evidence base.
  
  
  RESULTS
  In April 2013, we searched PubMed, Embase, and the Cochrane Library to identify relevant RCTs. We included RCTs investigating the effect of B vitamin supplementation on cardiovascular outcome. Relative risk (RR) was used to measure the effect using a random-effect model. Statistical heterogeneity scores were assessed using the Q statistic. We included data on 57,952 individuals from 24 RCTs: 12 primary prevention trials and 12 secondary prevention trials. In 23 of these trials, 10,917 major adverse cardiovascular events (MACE) occurred; in 20 trials, 7,203 deaths occurred; in 15 trials, 3,422 cardiac deaths occurred; in 19 trials, 3,623 myocardial infarctions (MI) occurred; and in 18 trials, 2,465 strokes occurred. B vitamin supplementation had little or no effect on the incidence of MACE (RR, 0.98; 95% confidence interval [CI]: 0.93-1.03; P = 0.37), total mortality (RR, 1.01; 95% CI: 0.97-1.05; P = 0.77), cardiac death (RR, 0.96; 95% CI: 0.90-1.02; P = 0.21), MI (RR, 0.99; 95% CI: 0.93-1.06; P = 0.82), or stroke (RR, 0.94; 95% CI: 0.85-1.03; P = 0.18).
  
  
  CONCLUSIONS
  B vitamin supplementation, when used for primary or secondary prevention, is not associated with a reduction in MACE, total mortality, cardiac death, MI, or stroke.
authors.affiliation: Department of Neurosurgery, Shanghai Seventh People's Hospital, Shanghai, China.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Information, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Wang
authors.affiliation: Department of Health Statistics, Second Military Medical University, Shanghai, China.
authors.forename: Ying-Yi
authors.initials: YY
authors.lastname: Qin
authors.affiliation: Department of Health Statistics, Second Military Medical University, Shanghai, China.
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Yu
authors.affiliation: Department of Rehabilitation Institute, Shanghai Seventh People's Hospital, Shanghai, China.
authors.forename: Yu-Hao
authors.initials: YH
authors.lastname: Zhou
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000517:prevention & control*; D019587:Dietary Supplements / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020011:Protective Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D014803:Vitamin B Complex / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D020011:Protective Agents; D014803:Vitamin B Complex