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

doi:10.1186/s12937-023-00843-y

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 language	English
Article number	12
Number of pages	14
Journal	Nutrition Journal
Volume	22
Issue number	1
DOIs	https://doi.org/10.1186/s12937-023-00843-y
Publication status	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1186/s12937-023-00843-yLicence: CC BY

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Zamani, M., Rezaiian, F., Saadati, S., Naseri, K., Ashtary-Larky, D., Yousefi, M., Golalipour, E., Clark, C. C. T., Rastgoo, S., & Asbaghi, O. (2023). The effects of folic acid supplementation on endothelial function in adults: a systematic review and dose-response meta-analysis of randomized controlled trials. Nutrition Journal, 22(1), [12]. https://doi.org/10.1186/s12937-023-00843-y

Zamani, M, Rezaiian, F, Saadati, S, Naseri, K, Ashtary-Larky, D, Yousefi, M, Golalipour, E, Clark, CCT, Rastgoo, S & Asbaghi, O 2023, 'The effects of folic acid supplementation on endothelial function in adults: a systematic review and dose-response meta-analysis of randomized controlled trials', Nutrition Journal, vol. 22, no. 1, 12. https://doi.org/10.1186/s12937-023-00843-y

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

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AU - Rezaiian, Fatemeh

AU - Saadati, Saeede

AU - Naseri, Kaveh

AU - Ashtary-Larky, Damoon

AU - Yousefi, Mohsen

AU - Golalipour, Elnaz

AU - Clark, Cain C.T.

AU - Rastgoo, Samira

AU - Asbaghi, Omid

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N2 - 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.

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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