The effect of folic acid in patients with cardiovascular disease: A systematic review and meta-analysis

Medicine (Baltimore). 2019 Sep;98(37):e17095. doi: 10.1097/MD.0000000000017095.


Background: The effectiveness of folic acid supplementation in stroke risk has been investigated, however, the available results are inconclusive and conflicting. The purpose of this systemic review and meta-analysis was to assess the effect of folic acid in patients with cardiovascular disease (CVD).

Methods: By searching the PubMed, EMBASE, and Cochrane library databases, we conducted a meta-analysis to evaluate effect of folic acid supplementation in patients with CVD. All-cause mortality, cardiovascular mortality, the risk of coronary heart disease (CHD) and stroke were summarized; hazard ratios (HR), the relative risk (RR) and its 95% confidence interval (CI) were also calculated. Fixed effects models were used to combine the data. A total of 12 randomized controlled trials, which involved 47,523 participants, met the inclusion criteria in this systematic review and meta-analysis.

Results: Our meta-analysis showed that cardiovascular patients who received folic acid therapy had significantly decreased risk of stroke (RR = 0.85, 95% CI = 0.77-0.94, Pheterogeneity = .347, I = 10.6%) compared with patients who received control treatment. However, no significant difference in all-cause mortality (HR, 0.97, 95% CI, 0.86-1.10, Pheterogeneity = .315, I = 15.4%), cardiovascular mortality (HR, 0.87, 95% CI, 0.66-1.15, Pheterogeneity = .567, I = 0) and risk of CHD (RR, 1.04, 95% CI, 0.99-1.10, Pheterogeneity = .725, I = 0) were found between the 2 groups.

Conclusion: This meta-analysis suggested that folic acid supplementation significantly reduced the risk of stroke in patients with CVD.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Cardiovascular Diseases / drug therapy*
  • Cardiovascular Diseases / mortality
  • Dietary Supplements
  • Folic Acid / pharmacology*
  • Folic Acid / therapeutic use
  • Humans
  • Vitamin B Complex / pharmacology
  • Vitamin B Complex / therapeutic use


  • Vitamin B Complex
  • Folic Acid