The effects of folic acid supplementation on endothelial function in adults: a systematic review and dose-response meta-analysis of randomized controlled trials

source extracted confidence: high 2026-04-09
#adult #humans #cardiovascular-diseases #dietary-supplements #endothelium-vascular

The effects of folic acid supplementation on endothelial function in adults: a systematic review and dose-response meta-analysis of randomized controlled trials

Zamani et al., 2023 | Nutr J | Meta Analysis

Citation

Zamani Mohammad, Rezaiian Fatemeh, ... Asbaghi Omid. The effects of folic acid supplementation on endothelial function in adults: a systematic review and dose-response meta-analysis of randomized controlled trials. Nutr J. 2023-Feb-24;22(1):12. doi:10.1186/s12937-023-00843-y

Abstract

BACKGROUND: Endothelial dysfunction serves as an early marker for the risk of cardiovascular disease (CVD); therefore, it is an attractive site of therapeutic interventions to reduce the risk of CVD. This study was conducted to investigate the effect of folic acid supplementation on endothelial function markers in randomized controlled trials (RCTs). METHODS: PubMed, ISI web of science, and Scopus databases were searched up to July 2022 for detecting eligible studies. A random-effects model was used for meta-analysis, and linear Meta-regression and non-linear dose-response analysis were performed to assess whether the effect of folic acid supplementation was affected by the dose and duration of intervention. Cochrane tools were also used to assess the risk of bias in the included studies. RESULTS: Twenty-one studies, including 2025 participants (1010 cases and 1015 controls), were included in the present meta-analysis. Folic acid supplementation significantly affected the percentage of flow-mediated dilation (FMD%) (WMD: 2.59%; 95% CI: 1.51, 3.67; P < 0.001) and flow-mediated dilation (FMD) (WMD: 24.38 μm; 95% CI: 3.08, 45.68; P = 0.025), but not end-diastolic diameter (EDD) (WMD: 0.21 mm; 95% CI: - 0.09, 0.52; P = 0.176), and intercellular adhesion molecule (ICAM) (WMD: 0.18 ng/ml; 95% CI: - 10.02, 13.81; P = 0.755). CONCLUSIONS: These findings suggest that folic acid supplementation may improve endothelial function by increasing FMD and FMD% levels. TRIAL REGISTRATION: PROSPERO registration cod: CRD42021289744.

Key Findings

Twenty-one studies, including 2025 participants (1010 cases and 1015 controls), were included in the present meta-analysis. Folic acid supplementation significantly affected the percentage of flow-mediated dilation (FMD%) (WMD: 2.59%; 95% CI: 1.51, 3.67; P < 0.001) and flow-mediated dilation (FMD) (WMD: 24.38 μm; 95% CI: 3.08, 45.68; P = 0.025), but not end-diastolic diameter (EDD) (WMD: 0.21 mm; 95% CI: - 0.09, 0.52; P = 0.176), and intercellular adhesion molecule (ICAM) (WMD: 0.18 ng/ml; 95% C

Outcomes Measured

  • diastolic blood pressure

Population

Field Value
Population See abstract
Sample Size 2025
Age Range See abstract
Condition See abstract

MeSH Terms

  • Adult
  • Humans
  • Cardiovascular Diseases
  • Dietary Supplements
  • Endothelium, Vascular
  • Folic Acid
  • Randomized Controlled Trials as Topic
  • Vasodilation

Evidence Classification

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

Provenance

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