title: Folic acid improves vascular reactivity in humans: a meta-analysis of randomized controlled trials.
abstract: BACKGROUND
  The effect of folic acid on endothelial function, a prognostic factor for cardiovascular diseases, is not well established. We calculated this effect in a meta-analysis of randomized, double-blind, placebo-controlled trials in humans.
  
  
  OBJECTIVE
  The objective of the study was to quantify the effect of folic acid on endothelial function, as measured with the use of flow-mediated dilatation (FMD).
  
  
  METHODS
  We conducted a meta-analysis of randomized, double-blind, placebo-controlled folic acid trials evaluating endothelial function. Trials were identified through MEDLINE (1966-15 Sept 2005), by hand-searching of references, and by contact with investigators for unpublished results. Two of us (AdB and RD) independently extracted trial data. A pooled estimate was calculated by using random-effects meta-analysis. Previously defined stratified analyses were conducted to explore the influence of study characteristics.
  
  
  RESULTS
  Of 163 identified studies, 14 met inclusion criteria and provided data on 732 persons. Evidence for publication bias was not obvious. In the overall pooled estimate, folic acid improved FMD by 1.08 (95% CI: 0.57,1.59; P = 0.0005) percentage points over placebo. Of the study characteristics, only folic acid dose significantly influenced the outcome. Post hoc analysis, which should be interpreted with caution, seemed to indicate a dose-response effect: the change in FMD was -0.07 (95% CI: -0.37, 0.22) percentage points at doses between 400 and 800 microg/d, 1.37 (95% CI: 1.12, 1.54) percentage points at doses of 5000 microg/d, and 2.04 (95% CI: 1.43, 2.65) percentage points at doses of 10,000 microg/d.
  
  
  CONCLUSIONS
  This study indicates that high doses of folic acid improve endothelial function, which could potentially reduce the risk of cardiovascular disease.
authors.affiliation: Unilever Research and Development, Unilever Food and Health Research Institute, Vlaardingen, Netherlands. angelika-de.bree@unilever.com
authors.forename: Angelika
authors.initials: A
authors.lastname: de Bree
authors.forename: Linda A
authors.initials: LA
authors.lastname: van Mierlo
authors.forename: Richard
authors.initials: R
authors.lastname: Draijer
mesh_terms: D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005492:Folic Acid / Q000494:pharmacology*; D006710:Homocysteine / Q000097:blood / Q000378:metabolism; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D014803:Vitamin B Complex / Q000494:pharmacology*