Abstract

(1) Background: This systematic review and meta-analysis aimed to assess the effects of folic acid supplementation on oxidative stress markers. (2) Methods: Online database including PubMed, Scopus, Web of Science, and Cochrane were searched up to January 2021, to retrieve randomized controlled trials (RCTs) which examined the effect of folic acid supplementation on markers of oxidative stress. Meta-analyses were carried out using a random-effects model. I2 index was used to evaluate the heterogeneity of RCTs. (3) Results: Among the initial 2322 studies that were identified from electronic databases search, 13 studies involving 1013 participants were eligible. Pooled effect size from 13 studies indicated that folic acid supplementation elicits a significant rise in serum concentrations of glutathione (GSH) (WMD: 219.01 umol/L, 95% CI 59.30 to 378.71, p = 0.007) and total antioxidant capacity (TAC) (WMD: 91.70 umol/L, 95% CI 40.52 to 142.88, p < 0.001) but has no effect on serum concentrations of nitric oxide (NO) (WMD: 2.61 umol/L, 95% CI −3.48 to 8.72, p = 0.400). In addition, folic acid supplementation significantly reduced serum concentrations of malondialdehyde (MDA) (WMD: −0.13 umol/L, 95% CI −0.24 to −0.02, p = 0.020). (4) Conclusions: This meta-analysis study suggests that folic acid supplementation may significantly improve markers within the antioxidative defense system by increasing serum concentrations of GSH and TAC and decreasing serum concentrations of MDA.

Highlights

  • The results showed that folic acid supplementation had a significant effect on serum concentrations of nitric oxide (NO) only when the analysis was performed on both sexes (WMD: 10.20 umol/L, 95% CI 5.24 to 15.15, p < 0.001)

  • The findings from 13 randomized controlled trials (RCTs) included in this meta-analysis indicated that an average folic acid supplementation of 5.1 mg/d (0.4–10 mg/d) with an intervention period lasting between eight to 25 weeks causes a significant rise in serum concentrations of GSH and total antioxidant capacity (TAC) but has no effect on NO

  • Subgroup analyses showed that folic acid supplementation among females utilizing an intervention duration of eight weeks or less was associated with significantly increased serum concentrations of GSH; an effect not observed in their male counterparts

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Summary

Introduction

Antioxidants 2021, 10, 871 and immune function [1]. ROS are neutralized by a complex antioxidant defense system consisting of enzymatic groups such as catalase, superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), and non-enzymatic groups, including reduced glutathione (GSH), carotenoids, ascorbic acid, α-tocopherol, and uric acid [2,3]. Oxidative stress is outlined as an alteration in the prooxidant–antioxidant balance in favor of ROS overload that leads to cellular damage [4]. Oxidative stress is established as having a pivotal role in the onset and/or progression of a wide variety of diseases, including cardiovascular disease [5], inflammatory joint disease [6], cancer [7], and diabetes [8]. In particular, have received considerable interest in this context and provides the focus of this study [12]

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