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B127.5
Vitamin B12 Research
Likely helps
335 peer-reviewed studies
What the evidence says
Probably helps
Vitamin B12 helped in about half (16/23) of the studies that measured an effect — promising, but not unanimous.
Most evidence is from high-quality meta-analyses and randomised trials published 1966–2026 with a typical study size of 770 participants.
Based on 331 studies · 42 meta-analyses · 229 RCTs · 496,170 total participants
Confidence
High confidence
What the studies found
16helped3unclear4didn't help· 308 more without graded effect data
By outcome
B12 deficiency & anemia
Likely helps223 studies
Heart & blood pressure
Likely helps73 studies
Therapeutic & clinical
Probably helps57 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 / observational7 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 / observational3 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 60 studies with measurable effects
Likely real effects
89%
across studies
People studied
496k
typical study: 770 people
Strongest designs
271
42 pooled, 229 randomised
Showed benefit
70%
16/23 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
Patients with vitiligo1
Active research area
107 studies in the last 5 years · Latest meta-analysis: 2026
196619962026
1major adverse cardiovascular eventsMeta-Analysisn=68,363 · very large study2026
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)
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).
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-Analysisn=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)
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.
4Stroke risk reductionMeta-Analysisn=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 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).
6Vitamin B12 deficiency riskMeta-Analysisn=2,852 · 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)
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-Analysisn=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)
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.
11Folate levelsMeta-Analysisn=770 · large study2024
In plain English: 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 decline preventionMeta-Analysisn=3,814 · 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)
Decreased cognitive decline with interventions >12 months
16Glycemic control in T2DM with peripheral neuropathyMeta-Analysis2025
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)
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.