Article Text


  1. Yong Huo1,
  2. Xianhui Qin2,
  3. Jiguang Wang3,
  4. Ningling Sun4,
  5. Qiang Zeng5,
  6. Xin Xu6,
  7. Lisheng Liu7,
  8. Xiping Xu8,
  9. Xiaobin Wang9,
  10. Yong Huo1
  1. 1Department of Cardiology, Peking University First Hospital, Beijing, China
  2. 2Institute of Biomedicine, Anhui Medical University, Hefei, China
  3. 3Centre for Epidemiological Studies and Clinical Trials, Ruijin Hospital, The Shanghai Institute of Hypertension, Shanghai Jiaotong University School of Medicine, Shanghai, China
  4. 4Department of Cardiology, Beijing University Peoples Hospital, Beijing, China
  5. 5Health Examination Center, Chinese People's Liberation Army General Hospital, Beijing, China
  6. 6Guangdong Institute of Nephrology, Southern Medical University, Guangzhou, China
  7. 7Division of Hypertension, Fu-Wai Hospital, and Cardiovascular Institute, Chinese Academy of Medical Sciences, Beijing, China
  8. 8Institute of Biomedicine, Anhui Medical University, Hefei, China
  9. 9Center on the Childhood Origins of Disease Johns Hopkins University Bloomberg School of Public Health Department of Population, Family and Reproductive Health, Baltimore, USA


    Objectives There are growing data and a continuing controversy over the efficacy of folic acid supplementation in stroke prevention. We conducted a meta-analysis based on relevant, up-to-date published randomised trials to further examine this issue.

    Methods Relative risk (RR) was used to measure the effect of folic acid supplementation on risk of stroke with a fixed-effects model.

    Results Overall, folic acid supplementation reduced the risk of stroke by 8% (n=55, 764, RR: 0.92, 95% CI 0.86 to 1.00, p=0.038). In the 10 trials with no or partial folic acid fortification (n=43 426), the risk of stroke was reduced by 11% (0.89, 0.82–0.97, p=0.010). Within these trials, a greater beneficial effect was observer among trials with a lower percent use of statins (<80% (median), 0.77, 0.64–0.92, p=0.005), and a meta-regression analysis also suggested a positive dose-response relationship between percent use of statins and log-RR for stroke associated with folic acid supplementation (p=0.013). A daily dose of 0.4–0.8 mg folic acid appeared to be adequate for stroke prevention in comparison with larger doses. In the remaining 5 trials conducted in populations with folic acid fortification (n=12 338), folic acid supplementation had no effect on stroke risk (1.03, 0.88–1.21, p=0.69).

    Conclusions Our analysis indicated that folic acid supplementation is effective in stroke prevention in populations with no or partial folic acid fortification. Additionally, a greater beneficial effect was observed among trials with a lower percent use of statins. Our findings underscore the importance of identifying target populations that can particularly benefit from folic acid therapy.

    Statistics from

    Request permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.