Abstract
This study aimed to evaluate whether folic acid supplementation would improve cognitive performance by reducing serum inflammatory cytokine concentrations. This RCT was performed in Tianjin, China. Participants with mild cognitive impairment (MCI) were randomly assigned to the folic acid (400 μg/day) or conventional treatment groups. Neuropsychological tests were administered, and folate, homocysteine, vitamin B12, IL-6, TNF-α, Aβ-42, and Aβ-40 were measured at baseline and at 6- and 12-month time points.152 participants (folic acid: 77, conventional: 75) completed the trial. Significant improvements in folate (ηp2 = 0.703, P = 0.011), homocysteine (ηp2 = 0.644, P = 0.009), Aβ-42 (ηp2 = 0.687, P = 0.013), peripheral IL-6 (ηp2 = 0.477, P = 0.025), TNF-α (ηp2 = 0.709, P = 0.009) levels were observed in folic acid group compared with conventional group. Folic acid supplementation improved the Full Scale Intelligence Quotient (P = 0.028; effect size d = 0.153), Information (P = 0.031; d = 0.157) and Digit Span (P = 0.009; d = 0.172) scores at 12 months compared with conventional treatment. Based on these findings, daily oral administration of a 400-μg folic acid supplement to MCI subjects for 12 months can significantly improve cognitive performance and reduce peripheral inflammatory cytokine levels.