Background: Folate and vitamin B12 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
B12, alone and in combination improves cognitive performance via reducing levels of peripheral inflammatory
Methods: 240 participants with MCI were randomly assigned in equal proportion to four treatment
groups: folic acid alone, vitamin B12 alone, folic acid plus vitamin B12 or control without treatment daily
for 6 months. Cognition was measured with WAIS-RC. The levels of inflammatory cytokines were
measured using ELISA. Changes in cognitive function or blood biomarkers were analyzed by repeatedmeasure
analysis of variance or mixed-effects models. This trial has been registered with trial number
Results: Compared with control group, the folic acid plus vitamin B12 group had significantly greater
improvements in serum folate, homocysteine, vitamin B12 and IL-6, TNF-α, MCP-1. The folic acid plus
vitamin B12 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 B12 supplementation
was significantly more effective than folic acid alone for all endpoints.
Conclusions: The combination of oral folic acid plus vitamin B12 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 B12 was significantly superior to either folic
acid or vitamin B12 alone.