Folic Acid Supplementation for Stroke Prevention in Patients With Cardiovascular Disease

Am J Med Sci. 2017 Oct;354(4):379-387. doi: 10.1016/j.amjms.2017.05.020.


Background: Controversy remains regarding the efficacy of folic acid supplementation in reducing the risk of stroke. This study aimed to evaluate the effect of folic acid supplementation on stroke prevention in patients with cardiovascular disease (CVD).

Materials and methods: We searched the PubMed, EMBASE and Cochrane Library databases through October 2016 to identify randomized clinical trials of folic acid supplementation to prevent stroke in patients with CVD. Relative risks (RRs) with 95% CIs were used to examine the association between folic acid supplementation and the risk of stroke with a fixed-effect model. Stratified analyses were performed according to modifiers that may affect the efficacy of folic acid supplementation.

Results: Eleven studies with a total of 65,790 participants were included. Folic acid supplementation was associated with a significant benefit in reducing the risk of stroke in patients with CVD (RR = 0.90; 95% CI: 0.84-0.97; P = 0.005). In the stratified analysis, greater beneficial effects were observed in participants with a decrease in homocysteine concentrations of 25% or greater (RR = 0.85; 95% CI: 0.74-0.97; P = 0.03), those with a daily folate dose of less than 2mg (RR = 0.78; 95% CI: 0.68-0.89; P = 0.01), and populations in regions with no or partly fortified grain (RR = 0.87; 95% CI: 0.81-0.94; P = 0.04).

Conclusions: Our meta-analysis demonstrated that folic acid supplementation is effective in stroke prevention in patients with CVD.

Keywords: Cardiovascular disease; Folic acid; Homocysteine; Meta-analysis; Stroke.

Publication types

  • Meta-Analysis
  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Dietary Supplements*
  • Female
  • Folic Acid / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Models, Biological*
  • Randomized Controlled Trials as Topic
  • Risk Factors
  • Stroke / prevention & control*


  • Folic Acid