title: Meta-analysis of folic acid efficacy trials in stroke prevention: Insight into effect modifiers.
abstract: OBJECTIVE
  To examine the efficacy and effect modifiers of folic acid supplementation in the prevention of stroke in regions without folic acid fortification based on relevant, up-to-date published randomized trials.
  
  
  METHODS
  Relative risk (RR) was used to measure the effect of folic acid supplementation on risk of stroke using a fixed effects model.
  
  
  RESULTS
  Overall, folic acid supplementation significantly reduced the stroke risk by 11% (22 trials, n = 82,723; RR 0.89, 95% confidence interval [CI] 0.84-0.96). The effect was greater in low folate regions (2 trials, n = 24,020; Asia, 0.78, 0.67-0.90) compared to high folate regions (7 trials, n = 14,655; America, 1.05, 0.90-1.23), and among patients without folic acid fortification (11 trials, n = 49,957; 0.85; 0.77-0.94) compared with those with folic acid fortification (7 trials, n = 14,655; 1.05, 0.90-1.23). In further stratified analyses among trials without folic acid fortification, a larger beneficial effect was found in those trials that used a low dosage of folic acid (≤0.8 mg: 0.78, 0.69-0.88) or low baseline vitamin B12levels (<384 pg/mL: 0.78, 0.68-0.89). In the corresponding comparison groups, the effect sizes were attenuated and insignificant (pfor interaction <0.05 for both). Although the interaction tests were not significant, there might be a higher benefit in trials with a low dosage of vitamin B12, a low prevalence of statin use, but a high prevalence of hypertension.
  
  
  CONCLUSIONS
  Folic acid supplementation could reduce the stroke risk in regions without folic acid fortification, particularly in trials using a relatively low dosage of folic acid and with low vitamin B12levels.
authors.affiliation: From the National Clinical Research Study Center for Kidney Disease (M.Z., Y.L., F.F.H., X.X., X.Q.), State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University; Second Clinical Medical College of Guangzhou University of Chinese Medicine (G.W.), Guangdong, China; Department of Population, Family, and Reproductive Health (X.W.), Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD; and Department of Neurology (M.Z., Y.C.), Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.affiliation: From the National Clinical Research Study Center for Kidney Disease (M.Z., Y.L., F.F.H., X.X., X.Q.), State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University; Second Clinical Medical College of Guangzhou University of Chinese Medicine (G.W.), Guangdong, China; Department of Population, Family, and Reproductive Health (X.W.), Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD; and Department of Neurology (M.Z., Y.C.), Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.
authors.forename: Guangliang
authors.initials: G
authors.lastname: Wu
authors.affiliation: From the National Clinical Research Study Center for Kidney Disease (M.Z., Y.L., F.F.H., X.X., X.Q.), State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University; Second Clinical Medical College of Guangzhou University of Chinese Medicine (G.W.), Guangdong, China; Department of Population, Family, and Reproductive Health (X.W.), Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD; and Department of Neurology (M.Z., Y.C.), Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.
authors.forename: Youbao
authors.initials: Y
authors.lastname: Li
authors.affiliation: From the National Clinical Research Study Center for Kidney Disease (M.Z., Y.L., F.F.H., X.X., X.Q.), State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University; Second Clinical Medical College of Guangzhou University of Chinese Medicine (G.W.), Guangdong, China; Department of Population, Family, and Reproductive Health (X.W.), Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD; and Department of Neurology (M.Z., Y.C.), Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Wang
authors.affiliation: From the National Clinical Research Study Center for Kidney Disease (M.Z., Y.L., F.F.H., X.X., X.Q.), State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University; Second Clinical Medical College of Guangzhou University of Chinese Medicine (G.W.), Guangdong, China; Department of Population, Family, and Reproductive Health (X.W.), Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD; and Department of Neurology (M.Z., Y.C.), Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.
authors.forename: Fan Fan
authors.initials: FF
authors.lastname: Hou
authors.affiliation: From the National Clinical Research Study Center for Kidney Disease (M.Z., Y.L., F.F.H., X.X., X.Q.), State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University; Second Clinical Medical College of Guangzhou University of Chinese Medicine (G.W.), Guangdong, China; Department of Population, Family, and Reproductive Health (X.W.), Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD; and Department of Neurology (M.Z., Y.C.), Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.
authors.forename: Xiping
authors.initials: X
authors.lastname: Xu
authors.affiliation: From the National Clinical Research Study Center for Kidney Disease (M.Z., Y.L., F.F.H., X.X., X.Q.), State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University; Second Clinical Medical College of Guangzhou University of Chinese Medicine (G.W.), Guangdong, China; Department of Population, Family, and Reproductive Health (X.W.), Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD; and Department of Neurology (M.Z., Y.C.), Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China. pharmaqin@126.com caiyefeng@126.com.
authors.forename: Xianhui
authors.initials: X
authors.lastname: Qin
authors.affiliation: From the National Clinical Research Study Center for Kidney Disease (M.Z., Y.L., F.F.H., X.X., X.Q.), State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University; Second Clinical Medical College of Guangzhou University of Chinese Medicine (G.W.), Guangdong, China; Department of Population, Family, and Reproductive Health (X.W.), Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD; and Department of Neurology (M.Z., Y.C.), Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China. pharmaqin@126.com caiyefeng@126.com.
authors.forename: Yefeng
authors.initials: Y
authors.lastname: Cai
mesh_terms: D005492:Folic Acid / Q000627:therapeutic use*; D006801:Humans; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D020521:Stroke / Q000517:prevention & control*
chemical_list: D018696:Neuroprotective Agents; D005492:Folic Acid