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. 2022 Nov 28:14:966933.
doi: 10.3389/fnagi.2022.966933. eCollection 2022.

Does folic acid supplementation have a positive effect on improving memory? A systematic review and meta-analysis of randomized controlled trials

Camellia Akhgarjand  1 , Sara Ebrahimi Mousavi  1 , Zahra Kalantar  2 , Amir Bagheri  3 , Hossein Imani  1 , Hamid Rezvani  4 , Mahmoud Dehghani Ghorbi  5 , Zahra Vahabi  6   7
Affiliations

Does folic acid supplementation have a positive effect on improving memory? A systematic review and meta-analysis of randomized controlled trials

Camellia Akhgarjand et al. Front Aging Neurosci. .

Abstract

Introduction: The results of randomized controlled trials (RCTs) on the effect of folic acid supplementation on memory status due to various heterogeneity, dosage, duration, and cognitive function assessments were inconclusive. Therefore, we have performed a systematic review and meta-analysis to investigate the effect of folic acid supplementation on memory in RCTs.

Method: Comprehensive computerized systematic searches were conducted throughout Scopus, PubMed/Medline, and Google Scholar from inception until February 2022 to investigate the effect of folic acid supplementation memory levels in RCTs. The standardized mean difference (SMD) and 95% confidence interval (CIs) were used to estimate the overall effect size using random-effects meta-analyses.

Results: The overall results of nine trials with 641 participants, revealed that folic acid supplementation did not significantly change memory score compared to placebo (SMD: 0.12; 95% CI: -0.17, 0.40, p = 0.418; I 2 = 62.6%). However, subgroup analyses showed that supplementation with folic acid had favorable effects on memory levels considering the following conditions: (1) doses lower than 1 mg/day, (2) treatment lasting more than 6 months, (3) conducted in eastern countries, and (4) in participants equal to or older than 70 years old. The dose-response analysis suggested a significant favorable effect on memory status at doses of 6-11 mg/d and a significant decline at doses of 17-20 mg/d.

Discussion: Although we did not find a significant effect of folic acid supplementation on memory, there were some suggestions of beneficial effects in the subgroup analyses.

Keywords: cognition; folic acid; memory; oral supplementation; psychological testing.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Flow diagram of study selection. Adopted from Moher et al. (2009).
FIGURE 2
FIGURE 2
Forest plot for the effect of folic acid supplementation on memory, expressed as standardized mean differences between intervention and control groups. Weights are from random effects analysis.
FIGURE 3
FIGURE 3
Non-linear dose-response relations between folic acid dosage (mg/d) and memory. The 95% CI is revealed in the shaded regions.
FIGURE 4
FIGURE 4
Funnel plot for the effect of folic acid supplementation on memory to identify publication bias.
See this image and copyright information in PMC

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