B vitamins (vitamin B6, vitamin B12, folate) and global cognition: grade C

Limited evidence. Direction: No effect.

C Limited

Educational guidance, not medical advice

Why this grade

Rubric condition met: Meta-analyses conflict: null in cognitively healthy older adults and in an 11-trial collaboration, a very small benefit in later analyses that pool people with and without cognitive impairment; older-only evidence caps at C and mixed direction gives C, none. Not N because a 2025 high-certainty estimate is positive

The 2018 Cochrane review (14 trials, 27,882 participants, mostly over 60 with vascular history) found folic acid, vitamin B12, vitamin B6 or combinations probably have little or no effect on global cognition up to 5 years. The B-Vitamin Treatment Trialists' Collaboration (11 trials, mostly folic acid plus vitamin B12) found no significant effect. A 2025 meta-analysis of vitamin B6, B9 or B12 in adults aged 60 or older found a very small benefit (g = 0.110, high certainty after outliers were removed), and a 2022 meta-analysis found MMSE score changes 0.14 points better in its trial analysis (6,155 participants), both pooling people with and without cognitive impairment. A 2024 meta-analysis of trials in adults aged 60 or older found a small overall benefit of folate-based B vitamins (SMD 0.18) but none where folic acid fortification of food is mandatory (SMD 0.03). A 2021 meta-analysis of vitamin B12 alone or B complex found no effect.

How we grade evidence

Studies this grade rests on

each study this grade rests on, by publication year and design. Solid: effect versus the comparator; half-filled: mixed; hollow: no effect; dashed: result not recorded yet. Larger marks had more participants.

Show the numbers

Study	Year	Design	Participants	Result
Clarke 2014	2014	meta-analysis	22000	result not recorded
Rutjes 2018	2018	systematic review	27882	result not recorded
Markun 2021	2021	meta-analysis	6276	result not recorded
Wang 2022	2022	meta-analysis	46175	result not recorded
Zhang 2024	2024	meta-analysis	42768	result not recorded
Berg 2025	2025	meta-analysis	5275	result not recorded

A Comparative Study Evaluating the Effectiveness of Folate-Based B Vitamin Intervention on Cognitive Function of Older Adults under Mandatory Folic Acid Fortification Policy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Zhang L, Chen X, Chen Y. A Comparative Study Evaluating the Effectiveness of Folate-Based B Vitamin Intervention on Cognitive Function of Older Adults under Mandatory Folic Acid Fortification Policy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials Nutrients, 2024. PMID 39064642

Result not recorded

Design: Systematic review (51 articles) and meta-analysis (23 articles) of RCTs
Sample: n = 42,768
Population: Adults aged 60 or older, by national folic acid fortification policy
Funding: Funding: not stated in the PubMed or Crossref record; full text not read. Authors declare no conflicts of interest.

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

Markun S, Gravestock I, Jäger L. Effects of Vitamin B12 Supplementation on Cognitive Function, Depressive Symptoms, and Fatigue: A Systematic Review, Meta-Analysis, and Meta-Regression Nutrients, 2021. PMID 33809274

Result not recorded

Design: Systematic review, meta-analysis and meta-regression of 16 RCTs
Sample: n = 6,276
Population: Adults without advanced neurological disorders or overt vitamin B12 deficiency
Funding: Funding: not stated in the PubMed or Crossref record; full text not read. Authors declare no conflict of interest.

B vitamins and prevention of cognitive decline and incident dementia: a systematic review and meta-analysis.

Wang Z, Zhu W, Xing Y. B vitamins and prevention of cognitive decline and incident dementia: a systematic review and meta-analysis Nutr Rev, 2022. PMID 34432056

Result not recorded

Design: Systematic review and meta-analysis (25 RCTs, 20 cohort and 50 cross-sectional studies)
Sample: n = 46,175
Population: Mixed: trial participants with and without dementia; observational cohorts aged 50 and over
Funding: Beijing Natural Science Foundation; National Natural Science Foundation of China

Efficacy of B Vitamin Supplementation on Global Cognitive Function in Older Adults: A Systematic Review and Meta-analysis.

Berg J, Grant R, Siervo M. Efficacy of B Vitamin Supplementation on Global Cognitive Function in Older Adults: A Systematic Review and Meta-analysis Nutr Rev, 2025. PMID 40966571

Result not recorded

Design: Systematic review and meta-analysis of 17 RCTs
Sample: n = 5,275
Population: Adults aged 60 or more, with intact cognition, mild cognitive impairment or dementia
Funding: Funding: not stated in the PubMed or Crossref record; full text not read.

Effects of homocysteine lowering with B vitamins on cognitive aging: meta-analysis of 11 trials with cognitive data on 22,000 individuals.

Clarke R, Bennett D, Parish S. Effects of homocysteine lowering with B vitamins on cognitive aging: meta-analysis of 11 trials with cognitive data on 22,000 individuals Am J Clin Nutr, 2014. PMID 24965307

Result not recorded

Design: Meta-analysis of 11 large placebo-controlled trials (individual trial data)
Sample: n = 22,000
Population: Adults in homocysteine-lowering trials, unselected for cognition-related disease other than heart attack or stroke
Funding: British Heart Foundation, UK Medical Research Council, Cancer Research UK, UK Food Standards Agency, Department of Health; authors declared no conflict of interest

Vitamin and mineral supplementation for maintaining cognitive function in cognitively healthy people in mid and late life.

Rutjes AW, Denton DA, Di Nisio M. Vitamin and mineral supplementation for maintaining cognitive function in cognitively healthy people in mid and late life Cochrane Database Syst Rev, 2018. PMID 30556597

Result not recorded

Design: Cochrane systematic review of 28 RCTs (14 B-vitamin trials, 27,882 participants)
Sample: n = 27,882
Population: Cognitively healthy adults aged 40 or more, mainly in their 60s and 70s
Funding: Department of Health (UK; PubMed grant list)

Search and history

Search (November 11, 2026): (folic acid[ti] OR vitamin B12[ti] OR B vitamins[ti] OR homocysteine lowering[ti]) AND cognitive[tiab] AND meta-analysis[pt]

November 12, 2026 Graded C (proposed): Proposed in the monograph draft
November 13, 2026 C to C (approved): Editor sign-off November 13, 2026: grade matches the editor-approved final page