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

Mohammad Zamani, Fatemeh Rezaiian, Saeede Saadati, Kaveh Naseri, Damoon Ashtary-Larky, Mohsen Yousefi, Elnaz Golalipour, Cain C.T. Clark, Samira Rastgoo, Omid Asbaghi

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    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.

    Original languageEnglish
    Article number12
    Number of pages14
    JournalNutrition Journal
    Volume22
    Issue number1
    DOIs
    Publication statusPublished - 24 Feb 2023

    Bibliographical note

    © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

    Keywords

    • Endothelial function
    • Flow mediated dilation
    • FMD
    • Folic acid supplementation
    • Meta-analysis

    ASJC Scopus subject areas

    • Medicine (miscellaneous)
    • Nutrition and Dietetics

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