Effects of Folic Acid and Vitamin B12, Alone and in Combination on Cognitive Function and Inflammatory Factors in the Elderly with Mild Cognitive Impairment: A Single-blind Experimental Design

Background: Folate and vitamin B-12 are well-known as essential nutrients that play key roles in the normal functions of the brain. Inflammatory processes play at least some role in the pathology of AD. Effective nutritional intervention approaches for improving cognitive deficits that reduce the peripheral inflammatory cytokine levels have garnered special attention. Objective: The present study aimed to determine whether supplementation with folic acid and vitamin B-12, alone and in combination improves cognitive performance via reducing levels of peripheral inflammatory cytokines. Methods: 240 participants with MCI were randomly assigned in equal proportion to four treatment groups: folic acid alone, vitamin B-12 alone, folic acid plus vitamin B-12 or control without treatment daily for 6 months. Cognition was measured with WAIS-RC. The levels of inflammatory cytolcines were measured using ELISA. Changes in cognitive function or blood biomarkers were analyzed by repeated-measure analysis of variance or mixed-effects models. This trial has been registered with trial number ChiCTR-ROC-16008305. Results: Compared with control group, the folic acid plus vitamin B-12 group had significantly greater improvements in serum folate, homocysteine, vitamin B(1)(2 )and IL-6, TNF-alpha, MCP-1. The folic acid plus vitamin B-12 supplementation significantly changed the Full Scale IQ (effect size d = 0.169; P = 0.024), verbal IQ (effect size d= 0.146; P= 0.033). Information (d= 0.172; P= 0.019) and Digit Span (d= 0.187; P = 0.009) scores. Post hoc Turkey tests found that folic acid and vitamin B-12 supplementation was significantly more effective than folic acid alone for all endpoints. Conclusions: The combination of oral folic acid plus vitamin B-12 in MCI elderly for six months can significantly improve cognitive performance and reduce the levels of inflammatory cytokines in human peripheral blood. The combination of folic acid and vitamin B-12 was significantly superior to either folic acid or vitamin B-12 alone.