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B127.5
Vitamin B12 Research
Likely helps
328 peer-reviewed studies
What the evidence says
Likely helps
Vitamin B12 appears to help in 4 of 5 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 2,256 participants.
Based on 324 studies · 41 meta-analyses · 226 RCTs · 303,822 total participants
Confidence
High confidence
What the studies found
4helped1unclear· 319 more without graded effect data
By outcome
B12 deficiency & anemia
Likely helps221 studies
Heart & blood pressure
Probably helps72 studies
Therapeutic & clinical
Too few graded studies56 studies
Cognitive functionNeeded for methylation. Supplements did not improve memory in people without deficiency · 4-8 weeks
Too few graded studies32 studies
Women's healthNo cited study measured hormones or cycle symptoms. B12 is lower in hypothyroidism in observational data · 4-8 weeks · Keeps maternal B12 status up through pregnancy and after birth, most important for vegetarian and vegan mothers · Ongoing
Too few graded studies21 studies
Safety profile
Too few graded studies13 studies
Glucose & metabolic
Too few graded studies11 studies
Depression & moodCorrecting deficiency improves depression and cognitive fog · 4-8 weeks
In plain English: 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)
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).
In plain English: 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.
3Serum vitamin and mineral levelsMeta-AnalysisCited 4×n=8,542 · very large study2024
In plain English: 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)
41 studies with 8,542 patients with vitiligo compared serum levels against controls. These are observational comparisons, not supplementation trials.
Vitamin B12 (MD -0.951, 95% CI -1.672 to -0.275), vitamin E, copper and zinc levels were lower in the vitiligo group.
Vitamin C, folic acid and selenium levels did not differ, and serum iron was higher in the vitiligo group.
4Stroke risk reductionMeta-AnalysisCited 15×n=76,664 · very large study2024
In plain English: 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 benefitCombination product. Contains: folic acid, vitamin B12, vitamin B6
← 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).
In plain English: Vitamin B12's role in the improvement of neurological functions over a long-term period remains somewhat inconclusive to date, as the majority of our selected control trials did not display much correlation between the two factors.
Alruwaili M et al. · Healthcare (MDPI) (2023)
Vitamin B12 noticeably improved cognition and other neurological parameters in the short term in older adults and the short-to-medium term in children.
There was no improvement when the vitamin was given in the longer term, either alone or with other similar nutritional interventions.
Vitamin B12's role in improving neurological function over a long-term period remains somewhat inconclusive.
6Vitamin B12 deficiency riskMeta-AnalysisCited 31×n=30,922 · very large study2023
In plain English: 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)
Twenty-five studies were included. 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%).
Most studies found no difference between serum vitamin B12 levels among PPI users compared to non-users.
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 26×n=28,597 · very large study2023
In plain English: Patients with hypothyroidism had lower levels of vitamin B12 than healthy participants.
Benites-Zapata VA et al. · Frontiers in endocrinology (2023)
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.
8Depressive and anxiety disorders improvementSystematic ReviewCited 51×n=2,256 · very large study2023
In plain English: Our results suggest that intervention with B vitamins and/or vitamin D may be an effective and well-tolerated adjuvant strategy for improving the symptoms of depression and anxiety, according to the patient's clinical status and nutritional biomarkers.
Borges-Vieira JG et al. · Nutritional neuroscience (2023)
20 RCTs with 2,256 subjects with MDD, GAD, or depressive or anxiety symptoms were included. The review covered B vitamins and vitamin D, not B12 alone.
Folic acid or L-methylfolate, B1, B12 or methylcobalamin, and vitamin D significantly decreased depression scores, as adjuncts to standard treatment or as monotherapy.
Some trials combined the vitamins with other compounds, so the improvement cannot be attributed strictly to them.
11Cognitive function improvementMeta-AnalysisCited 71×n=6,276 · very large study2021
In plain English: 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.
12Folate levelsMeta-AnalysisCited 16×n=3,157 · very large study2024
In plain English: Our findings suggest that individuals with PKU under nutritional guidance can achieve a vitamin status comparable to that of healthy subjects.
Bokayeva K et al. · International journal of molecular sciences (2024)
24 studies compared 770 people with early-treated PKU and 2387 healthy controls.
There were no significant differences in vitamin A, E, B6, B12 or 25-hydroxyvitamin D levels.
PKU patients had significantly higher folate (SMD 1.378, 95% CI 0.436 to 2.320) and 1,25-dihydroxyvitamin D than controls.
13Cognitive decline preventionMeta-AnalysisCited 108×n=46,175 · very large study2022
In plain English: B vitamin supplementation is associated with slowing of cognitive decline, especially in populations who received early intervention.
Wang Z et al. · Nutrition Reviews (2022)
95 studies with 46175 participants (25 RCTs, 20 cohort and 50 cross-sectional studies) were included. The trials supplied B vitamins, not B12 alone.
B vitamin supplementation slowed cognitive decline on MMSE (MD 0.14, 95% CI 0.04 to 0.23), in trials longer than 12 months and in people without dementia. No effect was found in shorter trials or in people with dementia.
Higher intake of dietary folate, but not B12 or B6, was associated with a reduced risk of incident dementia, and B12 deficiency was not associated with dementia risk.
14Nerve conduction and overall effective rate in T2DM with peripheral neuropathyMeta-AnalysisCited 3×2025
In plain English: 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)
Seven RCTs tested dapagliflozin (an SGLT-2 inhibitor) combined with methylcobalamin in type 2 diabetes with peripheral neuropathy. The abstract gives no participant total.
The combination improved the overall effective rate (OR 5.05) and nerve conduction velocities in the common peroneal and median nerves.
FPG, 2hPG and HbA1c also fell. Because the trials tested the combination, the glycemic effects cannot be attributed to methylcobalamin.