title: The effect of folate fortification on folic acid-based homocysteine-lowering intervention and stroke risk: a meta-analysis.
abstract: OBJECTIVE
  Folate and vitamin B12 are two vital regulators in the metabolic process of homocysteine, which is a risk factor of atherothrombotic events. Low folate intake or low plasma folate concentration is associated with increased stroke risk. Previous randomized controlled trials presented discordant findings in the effect of folic acid supplementation-based homocysteine lowering on stroke risk. The aim of the present review was to perform a meta-analysis of relevant randomized controlled trials to check the how different folate fortification status might affect the effects of folic acid supplementation in lowering homocysteine and reducing stroke risk.
  
  
  METHODS
  Relevant randomized controlled trials were identified through formal literature search. Homocysteine reduction was compared in subgroups stratified by folate fortification status. Relative risks with 95 % confidence intervals were used as a measure to assess the association between folic acid supplementation and stroke risk.
  
  
  METHODS
  The meta-analysis included fourteen randomized controlled trials,
  
  
  METHODS
  A total of 39 420 patients.
  
  
  RESULTS
  Homocysteine reductions were 26·99 (sd 1·91) %, 18·38 (sd 3·82) % and 21·30 (sd 1·98) %, respectively, in the subgroups without folate fortification, with folate fortification and with partial folate fortification. Significant difference was observed between the subgroups with folate fortification and without folate fortification (P=0·05). The relative risk of stroke was 0·88 (95 % CI 0·77, 1·00, P=0·05) in the subgroup without folate fortification, 0·94 (95 % CI 0·58, 1·54, P=0·82) in the subgroup with folate fortification and 0·91 (95 % CI 0·82, 1·01, P=0·09) in the subgroup with partial folate fortification.
  
  
  CONCLUSIONS
  Folic acid supplementation might have a modest benefit on stroke prevention in regions without folate fortification.
authors.affiliation: 1Department of Cardiovascular Diseases,West China Hospital,School of Clinical Medicine,Sichuan University,Chengdu 610041,People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zeng
authors.affiliation: 2Department of Cardiovascular Diseases,The Second People's Hospital of Neijiang,Neijiang,People's Republic of China.
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Xu
authors.affiliation: 1Department of Cardiovascular Diseases,West China Hospital,School of Clinical Medicine,Sichuan University,Chengdu 610041,People's Republic of China.
authors.forename: Yuan-Ning
authors.initials: YN
authors.lastname: Xu
authors.affiliation: 1Department of Cardiovascular Diseases,West China Hospital,School of Clinical Medicine,Sichuan University,Chengdu 610041,People's Republic of China.
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Wang
authors.affiliation: 1Department of Cardiovascular Diseases,West China Hospital,School of Clinical Medicine,Sichuan University,Chengdu 610041,People's Republic of China.
authors.forename: Mian
authors.initials: M
authors.lastname: Wang
mesh_terms: D016208:Databases, Factual; D005492:Folic Acid / Q000008:administration & dosage / Q000097:blood*; D005527:Food, Fortified; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D020521:Stroke / Q000097:blood / Q000453:epidemiology* / Q000517:prevention & control; D014805:Vitamin B 12 / Q000008:administration & dosage / Q000097:blood
chemical_list: D006710:Homocysteine; D005492:Folic Acid; D014805:Vitamin B 12
keywords: Folate fortification