Effects of Vitamin B12 Supplementation on Cognitive Function, Depressive Symptoms, and Fatigue: A Systematic Review, Meta-Analysis, and Meta-Regression

Nutrients
Q1
Mar 2021
Citations:73
Influential Citations:1
Systematic Reviews / Meta-Analyses
74
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Enhanced Details

Methods
Randomized, double-blind, placebo-controlled trials conducted in elderly adults without advanced neurological disorders; at least 20 participants per group; included B12 alone and B12 with B9 (folic acid), with or without B6.
Intervention
Vitamin B12 supplementation regimens: B12 alone or with folic acid (B9), with or without vitamin B6 (B6); mostly oral administration 0.1–1 mg daily; some trials used intramuscular B12 1 mg weekly or twice weekly; treatment durations ranged from 4 to 117 weeks.
Results
B12 supplementation did not improve cognitive function subdomains or depressive symptoms compared with placebo. For fatigue, evidence is insufficient. High-quality evidence discourages B12 supplementation for cognitive function and depressive symptoms in older adults with normal B12 status.
Limitations
Heterogeneity of trials and outcomes; potential inclusion of individuals with subclinical or undiagnosed B12 deficiency; possible replacement vs supplementation effects; limited data on fatigue; longest treatment durations up to two years; generalizability limited to elderly without advanced neurological disorders.

Abstract

Vitamin B12 is often used to improve cognitive function, depressive symptoms, and fatigue. In most cases, such complaints are not associated with overt vitamin B12 deficiency or advanced neurological disorders and the effectiveness of vitamin B12 sup...