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B129.0
Vitamin B12 Research
Likely helpsHigh safety
63 peer-reviewed studies
What the evidence says
Likely helps
Vitamin B12 appears to help in 14 of 19 studies with measurable effects — the evidence leans clearly favourable.
Most evidence is from high-quality meta-analyses and randomised trials published 2006–2026 with a typical study size of 770 participants.
Based on 63 studies · 23 meta-analyses · 18 RCTs · 443,898 total participants
Confidence
High
What the studies found
14helped1unclear4didn't help· 44 more without graded effect data
By outcome
B12 deficiency & anemia
Probably helps48 studies
Therapeutic & clinical
Probably helps20 studies
Cognitive functionMethylation support essential for neurotransmitter synthesis and memory · 4-8 weeks
Depression & moodCorrecting deficiency improves depression and cognitive fog · 4-8 weeks
Too few graded studies2 studies
Bone healthSupports bone mineral density and skeletal strength · 8-12 weeks
Too few graded studies2 studies
Energy & fatigueRestored energy if deficient; modest benefit if replete · 2-4 weeks
Too few graded studies1 study
Anxiety & stress
Too few graded studies1 study
By the numbers
Pulled from 51 studies with measurable effects
Likely real effects
81%
across studies
People studied
444k
typical study: 770 people
Strongest designs
41
23 pooled, 18 randomised
Showed benefit
74%
14/19 studies
How long studies ran
1–3 months
3
3+ months
8
Populations Studied
Pregnant women2
adults at cardiovascular risk1
Adults in areas without/with partial folic acid fortification1
Patients with vitiligo1
Active research area
55 studies in the last 5 years · Latest meta-analysis: 2026
200620162026
1major 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).
2Stroke 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).
3Serum 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.
5Vitamin 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.
6Vitamin 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.
7Vitamin 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.
10Cognitive 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.
11Folate 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.
12Cognitive 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.
15Glycemic control in T2DM with peripheral neuropathyMeta-AnalysisCited 1×2025
Dapagliflozin combined with methylcobalamin appears to be an effective and safe therapeutic strategy for managing DPN in T2DM patients, improving both nerve function and glycemic control.
Deng XL et al. · Frontiers in endocrinology (2025)
Glycemic control also improved, with reductions in FPG (MD, 95% CI: -1.19 mmol/L [-1.40, -0.98]; P<0.01), 2hPG (MD, 95% CI: -1.36 mmol/L[-1.44, -1.27]; P<0.01), and HbA1c levels (MD, 95% CI: -0.87% [-1.04, -0.71]; P<0.01).
There was no significant increase in adverse events (OR: 0.37; 95% CI: 0.07-2.03; P=0.25).
Dapagliflozin combined with methylcobalamin appears to be an effective and safe therapeutic strategy for managing DPN in T2DM patients, improving both nerve function and glycemic control.
16Neuropathy symptom improvementMeta-AnalysisCited 49×n=46 · small study2021
PN is associated with lowered plasma vitamin B12 and elevated methylmalonic acid and homocysteine.
Stein J et al. · European journal of neurology (2021)
Huge harm
← WorseNo effectBetter →
Borderline
B12 treatment (vs. the comparators) showed a non-significant association with symptom improvement (1.36 (0.66-2.79), n = 4, I2 = 28.9%).
Treatment with B1 was associated with a significant improvement in symptoms (5.34 [1.87-15.19], n = 3, I2 = 64.6%, p = 0.059).
Analysis of seven trials combined showed a non-significant higher odds ratio for improvement under treatment with the B-vitamins (2.58 [0.98-6.79], I2 = 80.0%, p < 0.001).
17Cancer risk and all-cause mortality with elevated vitamin B12Systematic ReviewCited 9×2024
There was less consistent evidence linking vitamin B12 and mortality.
Amado-Garzon SB et al. · Cancer investigation (2024)
Huge harm
← WorseNo effectBetter →
The objective of this review was to summarize the current evidence on the associations of elevated B12 and the development of cancer, and all-cause mortality in adults.
Six references looking at mortality and seven looking at cancer risk were included.
The evidence suggests an association between elevated B12 with a higher risk of cancer, with risk ratios ranging 1,88 to 5,9.
18Vitamin B12, EPA and DHA status during pregnancy and lactationMeta-AnalysisCited 2×2024
However, it is important to continue with research in this area that considers an adequate dietary anamnesis, integral evaluation of nutritional status, estimation of nutritional requirements and an individualized nutritional plan.
Sandoval Leiva T et al. · Nutricion hospitalaria (2024)
Eleven articles were selected in this review.
Well-planned vegetarian and vegan diets, with adequate supplementation of vitamin B12, EPA and DHA, are compatible during pregnancy and lactation, being a positive predictor of their content in breast milk.
A similar situation was observed in plasma levels in women supplemented with B12.
19Resolution of hallucinations with vitamin B12 treatmentSystematic ReviewCited 7×2024
In the light of the high prevalence rate of vitamin B12 deficiency in the general population, the findings here presented should be interpreted with great caution.
Blom JD · Psychopathology (2024)
Huge benefit
← WorseNo effectBetter →
The hallucinations described therein are predominantly visual and/or auditory in nature, with 20% being specified as complex, compound, or panoramic.
Within an average of 2 months, full amelioration was thus obtained in 75% of the cases and partial amelioration in the remaining 25%.
Remarkably, a quarter of the cases involved therapy-resistant hallucinations that fully resolved under cobalamin monotherapy, while other neuropsychiatric manifestations of vitamin B12 deficiency disappeared in 60% of the treated cases.
20Health outcomes in vegan vs non-vegan childrenMeta-AnalysisCited 22×n=18 · very small study2024
Overall, the available evidence points to both risks and benefits associated with a vegan diet among children, although more and better designed studies are needed.
Koller A et al. · Critical reviews in food science and nutrition (2024)
Single study results suggested further differences between vegan and non-vegan children, such as lower bone mineral content or urinary iodine among vegan children.
Risk of Bias was rated as high or very high in 7 out of 18 studies.
The certainty of evidence for the meta-analyses was low (n = 2) or very low (n = 46).