Folic acid improves vascular reactivity in humans: a meta-analysis of randomized controlled trials

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#cardiovascular-diseases #dose-response-relationship-drug #double-blind-method #endothelium-vascular #folic-acid

Folic acid improves vascular reactivity in humans: a meta-analysis of randomized controlled trials

de et al., 2007 | Am J Clin Nutr | Meta Analysis

Citation

de Bree Angelika, van Mierlo Linda A, Draijer Richard. Folic acid improves vascular reactivity in humans: a meta-analysis of randomized controlled trials. Am J Clin Nutr. 2007-Sep;86(3):610-7

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). DESIGN: 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identified through MEDLINE (1966-15 Sept 2005), by hand-searching of references, and by contact with investigators for unpublished results.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. CONCLUSION: This study indicates that high doses of folic acid improve endothelial function, which could potentially reduce the risk of cardiovascular disease.

Key Findings

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

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population See abstract
Sample Size See abstract
Age Range See abstract
Condition See abstract

MeSH Terms

  • Cardiovascular Diseases
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Endothelium, Vascular
  • Folic Acid
  • Homocysteine
  • Humans
  • Randomized Controlled Trials as Topic
  • Risk Factors
  • Vitamin B Complex

Evidence Classification

  • Level: Meta Analysis
  • Publication Types: Journal Article, Meta-Analysis
  • Vertical: folate

Provenance

  • PMID: 17823424
  • DOI: (not available)
  • PMCID: Not in PMC
  • Verified: 2026-04-09 via PubMed E-utilities API

Source extracted via PubMed E-utilities API on 2026-04-09