Effects of folic acid supplementation on cognitive function and inflammation in elderly patients with mild cognitive impairment: A systematic review and meta-analysis of randomized controlled trials

The aim was to assess the effect of folic acid supplementation on cognitive function and inflammatory cytokines in elderly patients with mild cognitive impairment. From its inception until February 2024, four databases including Web of Science were searched. Two researchers independently screened the literature, assessed the quality, extracted data, and conducted a meta-analysis using RevMan. The systematic review included seven studies (with a total of 1102 participants, mean age 65–80 years), seven of which were appropriate for meta-analysis. Although a small number of studies found relatively large heterogeneity, the majority of studies showed significant benefit from folic acid supplementation, including the FSIQ (823 individuals, standardized mean difference [SMD] = 8.36, 95 % confidence interval [CI] = 0.79 - 1.08), Arithmetic (823 individuals, SMD = 0.17, 95 % CI = -0.03–0.31), Information, SMD = 1.73, 95 % CI 0.41–3.05), Digit Span (823 individuals, SMD = 0.17, 95 % CI = -0.03 - 0.31), Block Design (823 individuals, SMD = 0.26, 95 % CI 0.03–0.49), Picture Completion (823 individuals, SMD = 0.27, 95 % CI = -0.15 - 0.69) and Picture Arrangement (823 individuals, SMD = -0.12, 95 % CI = -0.26 - 0.01). Finally, folic acid supplementation had a significant effect on the reduction of most inflammatory cytokines, blood biomarkers of Alzheimer's disease, and Hcy. Folic acid supplementation seems to have a positive impact on cognitive function in older adults with mild cognitive impairment, but further evidence of its effectiveness in improving inflammatory cytokines is needed from high-quality studies.