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B127.5
Vitamin B12 Research
Probably helps
339 peer-reviewed studies
What the evidence says
Likely helps
Vitamin B12 appears to help in 18 of 25 studies with measurable effects — the evidence leans clearly favourable.
Most evidence is from high-quality meta-analyses and randomised trials published 1966–2026 with a typical study size of 612 participants.
Based on 339 studies · 50 meta-analyses · 235 RCTs · 515,826 total participants
Confidence
High confidence
What the studies found
18helped2unclear5didn't help· 314 more without graded effect data
By outcome
B12 deficiency & anemia
Likely helps227 studies
Heart & blood pressure
Likely helps77 studies
Therapeutic & clinical
Probably helps60 studies
Cognitive functionMethylation support essential for neurotransmitter synthesis and memory · 4-8 weeks
Depression & moodCorrecting deficiency improves depression and cognitive fog · 4-8 weeks
Mostly mechanism / observational9 studies
Bone healthSupports bone mineral density and skeletal strength · 8-12 weeks
Mostly mechanism / observational7 studies
Energy & fatigueRestored energy if deficient; modest benefit if replete · 2-4 weeks
Mostly mechanism / observational4 studies
ALS & motor-neuron disease
Too few graded studies2 studies
Immune support
Too few graded studies2 studies
Anxiety & stress
Too few graded studies1 study
By the numbers
Pulled from 64 studies with measurable effects
Likely real effects
85%
across studies
People studied
516k
typical study: 612 people
Strongest designs
285
50 pooled, 235 randomised
Showed benefit
72%
18/25 studies
How long studies ran
1–3 months
3
3+ months
8
Populations Studied
Pregnant women6
Type 2 diabetes mellitus patients2
adults at cardiovascular risk1
Adults in areas without/with partial folic acid fortification1
Active research area
107 studies in the last 5 years · Latest meta-analysis: 2026
196619962026
1Meta-Analysisn=48,626 · very large study2026
These findings underscore the need for careful dietary planning and supplementation in lacto-ovo-vegetarian and vegan children.
Lotti S, Panizza G, Martini D, Marx W, Beasley JM, Colombini B, Dinu M. · Critical reviews in food science and nutrition (2026)
Biomarkers showed lower ferritin and 25(OH)D in lacto-ovo-vegetarians, and lower hemoglobin and ferritin in vegans.
Although group averages for most nutrients and biomarkers remained within pediatric reference ranges, increased odds of iron deficiency and anemia were observed in lacto-ovo-vegetarians, and vitamin B12 deficiency in vegans.
Both groups showed lower total and LDL cholesterol.
2major adverse cardiovascular eventsMeta-Analysisn=68,363 · very large study2026
Overall, B-vitamin combinations do not confer consistent benefit for major cardiovascular outcomes but may reduce stroke and MACE in selected primary prevention populations, suggesting that baseline cardiovascular risk and regional folic acid fortification modify treatment effects and should guide future trial design and clinical use.
Ren R et al. · Nutrients (2026)
No clear effect
← WorseNo effectBetter →
Random-effects models were used in this meta-analysis to calculate pooled risk ratios (RRs) and 95% confidence intervals (CIs).
B-vitamin combinations were associated with a nonsignificant reduction in stroke and 3-point major adverse cardiovascular events (MACE) (stroke: RR 0.91, 95% CI 0.81-1.04; MACE: RR 0.93, 95% CI 0.86-1.01).
No significant effects were observed for all-cause mortality (RR 1.01, 95% CI 0.96-1.06), cardiovascular mortality (RR 0.97, 95% CI 0.88-1.07), or MI (RR 0.97, 95% CI 0.91-1.03).
3Stroke risk reductionMeta-AnalysisCited 12×n=76,664 · very large study2024
Our meta-analysis found that the folic acid combined with vitamin B12 and vitamin B6 supplementation strategy significantly reduced the risk of stroke in areas without and with partial folic acid fortification.
Zhang N et al. · The American journal of clinical nutrition (2024)
Large benefit
← WorseNo effectBetter →
In areas without and with partial folic acid fortification, combined B-vitamin supplementation significantly reduced the risk of stroke by 34% [RR: 0.66; 95% confidence interval (CI): 0.50, 0.86] and 11% (RR: 0.89; 95% CI: 0.79, 1.00), respectively.
Further analysis showed that a dosage of folic acid ≤0.8 mg/d and vitamin B12 ≤0.4 mg/d was best for stroke prevention (RR: 0.65; 95% CI: 0.48, 0.86) in these areas.
In contrast, no benefit of combined supplementation was found in fortified areas (RR: 1.04; 95% CI: 0.94, 1.16).
4Serum iron levelsMeta-AnalysisCited 3×n=8,542 · very large study2024
Patients with vitiligo should reduce smoking and alcohol consumption and take appropriate vitamin E, B12, copper, and zinc supplements.
Liang X et al. · Frontiers in immunology (2024)
Noticeable benefit
← WorseNo effectBetter →
Vitamin C [mean difference (MD), -0.342; 95% confidence interval (CI), -1.090-0.407; p >0.05), folic acid (MD, -1.463; 95% CI, -7.133-4.208; p >0.05), and selenium (MD, 0.350; 95% CI, -0.687-1.387; p >0.05) levels did not differ between the groups.
The serum iron level of the vitiligo group was significantly higher than that of the control group (MD, 1.181; 95% CI, 0.390-1.972; p <0.005).
Patients with vitiligo should reduce smoking and alcohol consumption and take appropriate vitamin E, B12, copper, and zinc supplements.
6Vitamin B12 level increaseMeta-AnalysisCited 19×n=4,275 · very large study2024
All IM, oral, and SL routes of administration of vitamin B12 can effectively increase the level of vitamin B12 without significant differences between them, as thought previously.
Abdelwahab OA et al. · Irish journal of medical science (2024)
Regarding the hemoglobin level, the pooled effect sizes showed no difference between all routes of administration that could reach statistical significance.
However, the IM route was the top-ranked statistically but without clinical significance.
We found no significant difference among studied administrated routes in all other CBC parameters and homocysteine levels.
7Vitamin B12 deficiency riskMeta-AnalysisCited 25×n=2,852 · very large study2023
Although the pooled OR of vitamin B12 deficiency was slightly increased in PPI users, but there was significant heterogeneity, and the pooled OR was too low to imply an association clearly.
Choudhury A et al. · Expert review of gastroenterology & hepatology (2023)
Large harm
← WorseNo effectBetter →
The pooled OR of vitamin B12 deficiency among PPI users (2852 participants) was higher than non-users (28070 participants) (OR 1.42, 95% CI: 1.16-1.73; I2 = 54%).
Overall risk of PPI use among vitamin B12 deficient individuals was higher than those without deficiency (OR 1.49, 1.20-1.85; I2 = 68%).
Although the pooled OR of vitamin B12 deficiency was slightly increased in PPI users, but there was significant heterogeneity, and the pooled OR was too low to imply an association clearly.
8Vitamin B12 levels in hypothyroidism vs healthy controlsMeta-AnalysisCited 22×n=28,597 · very large study2023
Patients with hypothyroidism had lower levels of vitamin B12 than healthy participants.
Benites-Zapata VA et al. · Frontiers in endocrinology (2023)
Noticeable benefit
← WorseNo effectBetter →
Likely real
We found that patients with hypothyroidism had lower vitamin B12 levels than healthy participants (MD: -60.67 pg/mL; 95% CI: -107.31 to -14.03 pg/mL; p = 0.01).
No significant differences in vitamin B12 levels were observed between healthy participants and patients with hyperthyroidism (p = 0.78), autoimmune thyroid disease (AITD) (p = 0.22), or subclinical hypothyroidism (SH) (p = 0.79).
The frequencies of vitamin B12 deficiency among patients with hypothyroidism, hyperthyroidism, SH, and AITD were 27%, 6%, 27%, and 18%, respectively.
11Cognitive decline preventionMeta-AnalysisCited 100×n=46,175 · very large study2022
This meta-analysis suggests that B vitamin supplementation is associated with slowing of cognitive decline, especially in populations who received early intervention and intervention of long duration; the study also indicates that higher intake of dietary folate, but not B12 or B6, is associated with a reduced risk of incident dementia in non-dementia aged population.
Wang Z et al. · Nutrition reviews (2022)
Noticeable benefit
← WorseNo effectBetter →
In the non-dementia population, B vitamin supplementation slowed cognitive decline (3431 participants; MD, 0.15, 95%CI 0.04 to 0.25) compared to placebo; this outcome was not found for the dementia population (642 participants; MD, 0.20, 95%CI -0.35 to 0.75).
Given the prevalence of dementia cases in many countries with aging populations, public health policies should be introduced to ensure that subgroups of the population at risk have an adequate B vitamin status.
12Folate levelsMeta-AnalysisCited 12×n=770 · large study2024
Our study provides valuable insights into the nutritional status of PKU patients, but further research is required to confirm these findings and explore additional factors influencing vitamin status in PKU.
Bokayeva K et al. · International journal of molecular sciences (2024)
Huge benefit
← WorseNo effectBetter →
Likely real
The effect sizes were expressed as standardised mean differences.
The calculation of effect sizes with 95% CI using fixed-effects models and random-effects models was performed.
A p-value < 0.05 was considered statistically significant.
13Cognitive function improvementMeta-AnalysisCited 65×n=6,276 · very large study2021
Vitamin B12 supplementation is likely ineffective for improving cognitive function and depressive symptoms in patients without advanced neurological disorders.
Markun S et al. · Nutrients (2021)
Further, meta-regression showed no significant associations of treatment effects with any of the potential predictors.
We also found no overall effect of vitamin supplementation on measures of depression.
Further, only one study reported effects on idiopathic fatigue, and therefore, no analysis was possible.