title: Folic Acid Supplementation and the Risk of Cardiovascular Diseases: A Meta-Analysis of Randomized Controlled Trials.
abstract: Results from observational and genetic epidemiological studies suggest that lower serum homocysteine levels are associated with lower incidence of cardiovascular disease (CVD). Numerous randomized controlled trials have investigated the efficacy of lowering homocysteine with folic acid supplementation for CVD risk, but conflicting results have been reported.
  
  
  
  Three bibliographic databases (Medline, Embase, and the Cochrane Database of Systematic Reviews) were searched from database inception until December 1, 2015. Of the 1933 references reviewed for eligibility, 30 randomized controlled trials involving 82 334 participants were included in the final analysis. The pooled relative risks of folic acid supplementation compared with controls were 0.90 (95% CI 0.84-0.96; P=0.002) for stroke, 1.04 (95% CI 0.99-1.09; P=0.16) for coronary heart disease, and 0.96 (95% CI 0.92-0.99; P=0.02) for overall CVD. The intervention effects for both stroke and combined CVD were more pronounced among participants with lower plasma folate levels at baseline (both P<0.02 for interaction). In stratified analyses, a greater beneficial effect for overall CVD was seen in trials among participants without preexisting CVD (P=0.006 for interaction) or in trials with larger reduction in homocysteine levels (P=0.009 for interaction).
  
  
  
  Our meta-analysis indicated a 10% lower risk of stroke and a 4% lower risk of overall CVD with folic acid supplementation. A greater benefit for CVD was observed among participants with lower plasma folate levels and without preexisting CVD and in studies with larger decreases in homocysteine levels. Folic acid supplementation had no significant effect on risk of coronary heart disease.
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Tianyi
authors.initials: T
authors.lastname: Huang
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Tauland
authors.initials: T
authors.lastname: Muka
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Jenna
authors.initials: J
authors.lastname: Troup
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA nhbfh@channing.harvard.edu.
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D003327:Coronary Disease / Q000517:prevention & control; D019587:Dietary Supplements; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D020521:Stroke / Q000517:prevention & control
chemical_list: D005492:Folic Acid
keywords: cardiovascular disease prevention; folate; stroke prevention