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Review
. 2021 May 28;10(6):871.
doi: 10.3390/antiox10060871.

Effects of Folic Acid Supplementation on Oxidative Stress Markers: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Omid Asbaghi  1 , Matin Ghanavati  2 , Damoon Ashtary-Larky  3 , Reza Bagheri  4 , Mahnaz Rezaei Kelishadi  5 , Behzad Nazarian  6 , Michael Nordvall  7 , Alexei Wong  7 , Frédéric Dutheil  8 , Katsuhiko Suzuki  9 , Amirmansour Alavi Naeini  5
Affiliations
Review

Effects of Folic Acid Supplementation on Oxidative Stress Markers: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Omid Asbaghi et al. Antioxidants (Basel). .

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.

Keywords: folate; folic acid; meta-analysis; oxidative stress; supplementation; systematic review.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flowchart of study selection for inclusion studies.
Figure 2
Figure 2
Forest plot detailing weighted mean difference and 95% confidence intervals (CIs) for the effect of folic acid supplementation on (A) NO, (B) MDA, (C) TAC, and (D) GSH.
Figure 2
Figure 2
Forest plot detailing weighted mean difference and 95% confidence intervals (CIs) for the effect of folic acid supplementation on (A) NO, (B) MDA, (C) TAC, and (D) GSH.
Figure 3
Figure 3
Funnel plot representing publication bias in the studies reporting the effect of folic acid on (A) NO (nitric oxide), (B) MDA (malondialdehyde), (C) TAC (total antioxidant capacity), and (D) GSH (reduced glutathione).
Figure 4
Figure 4
Linear meta-regression plots of the association between dose of folic acid supplementation and weighted mean difference of (A) NO (nitric oxide), (B) MDA (malondialdehyde), (C) TAC (total antioxidant capacity), and (D) GSH (reduced glutathione).
Figure 5
Figure 5
Linear meta-regression plots of the association between duration of folic acid supplementation and weighted mean difference of A) NO (nitric oxide), (B) MDA (malondialdehyde), (C) TAC (total antioxidant capacity), and (D) GSH (reduced glutathione).
Figure 6
Figure 6
Non-linear dose-response of the association between dose of folic acid supplementation and weighted mean difference of A) NO (nitric oxide), (B) MDA (malondialdehyde), (C) TAC (total antioxidant capacity), and (D) GSH (reduced glutathione).
See this image and copyright information in PMC

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