Vitamin B12 Research
53 peer-reviewed studies · Evidence score: 9/10
Complex Effects of B-Vitamin Combinations on Cardiovascular Diseases: A Systematic Review and Meta-Analysis of Randomized Controlled Trials over Three Decades
Ren R et al. • Nutrients (2026)
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.
- 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).
Dosage exploration of combined B-vitamin supplementation in stroke prevention: a meta-analysis and systematic review
Zhang N et al. • The American journal of clinical nutrition (2024)
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.
- 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).
Healthy lifestyle choices: new insights into vitiligo management
Liang X et al. • Frontiers in immunology (2024)
Patients with vitiligo should reduce smoking and alcohol consumption and take appropriate vitamin E, B12, copper, and zinc supplements.
- 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.
Efficacy of B-vitamins and vitamin D therapy in improving depressive and anxiety disorders: a systematic review of randomized controlled trials
Borges-Vieira JG et al. • Nutritional neuroscience (2023)
As for anxiety symptoms, the availability of results is limited to adjuvant vitamin D therapy.
- Systematic review examining Methylfolate efficacy
- Published in Nutritional neuroscience (2023)
- Further research warranted to confirm findings
Efficacy of different routes of vitamin B12 supplementation for the treatment of patients with vitamin B12 deficiency: A systematic review and network meta-analysis
Abdelwahab OA et al. • Irish journal of medical science (2024)
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.
- 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.
Vitamin B12 deficiency and use of proton pump inhibitors: a systematic review and meta-analysis
Choudhury A et al. • Expert review of gastroenterology & hepatology (2023)
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.
- 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.
Vitamin B12 levels in thyroid disorders: A systematic review and meta-analysis
Benites-Zapata VA et al. • Frontiers in endocrinology (2023)
Patients with hypothyroidism had lower levels of vitamin B12 than healthy participants.
- 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.
Vitamin B12, folate, and homocysteine in metabolic syndrome: a systematic review and meta-analysis
Ulloque-Badaracco JR et al. • Frontiers in endocrinology (2023)
Higher vitamin B12 levels were inversely associated with MetS, whereas higher Hcy levels were associated with MetS.
- Higher vitamin B12 levels were inversely associated with MetS (OR = 0.87; 95% CI: 0.81-0.93; p < 0.01; I2 = 90%).
- Higher Hcy levels were associated with MetS (OR = 1.19; 95% CI: 1.14-1.24; p < 0.01; I2 = 90%).
- Folate levels were not associated with MetS (OR = 0.83; 95% CI: 0.66-1.03; p = 0.09; I2 = 90%).
Neurological Implications of Vitamin B12 Deficiency in Diet: A Systematic Review and Meta-Analysis
Ankar A et al. • Healthcare (MDPI) (2023)
Vitamin B12 noticeably improved cognition and other neurological parameters in the short term in older adults.
- Short-term cognitive improvements in deficient elderly
- Improved neurological parameters in children
- Benefits most significant when correcting deficiency
B vitamins and prevention of cognitive decline and incident dementia: a systematic review and meta-analysis
Wang Z et al. • Nutrition reviews (2022)
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.
- 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.
- Further research warranted to confirm findings
Vitamin Status in Patients with Phenylketonuria: A Systematic Review and Meta-Analysis
Bokayeva K et al. • International journal of molecular sciences (2024)
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.
- 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.
Effects of Vitamin B12 Supplementation on Cognitive Function, Depressive Symptoms, and Fatigue: A Systematic Review, Meta-Analysis, and Meta-Regression
Markun S et al. • Nutrients (2021)
Vitamin B12 supplementation is likely ineffective for improving cognitive function and depressive symptoms in patients without advanced neurological disorders.
- 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.
Are herbal medicines alone or in combination for diabetic peripheral neuropathy more effective than methylcobalamin alone? A systematic review and meta-analysis
Lee CW et al. • Complementary therapies in clinical practice (2022)
Our study suggests that herbal medicine and CHM might be more effective than methylcobalamin alone in the management of DPN.
- Herbal medicine and CHM treatment for DPN also significantly improved the TER compared to the control group.
- Our study suggests that herbal medicine and CHM might be more effective than methylcobalamin alone in the management of DPN.
- Further rigorous studies should be conducted to make more definite conclusions.
Role of vitamin B12 and folic acid in treatment of Alzheimer's disease: a meta-analysis of randomized control trials
Chen H et al. • Aging (2024)
Administration of vitamin B12 and folic acid improved MMSE scores more than placebo after 6-month treatment.
- Improved MMSE scores after 6 months
- Benefits for Alzheimer's disease patients
- Combined B12 and folate more effective
Dapagliflozin combined with methylcobalamin in the treatment of type 2 diabetes mellitus with peripheral neuropathy: a systematic review and meta-analysis
Deng XL et al. • Frontiers in endocrinology (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.
- 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.
Association between neuropathy and B-vitamins: A systematic review and meta-analysis
Stein J et al. • European journal of neurology (2021)
PN is associated with lowered plasma vitamin B12 and elevated methylmalonic acid and homocysteine.
- 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).
Elevated Vitamin B12, Risk of Cancer, and Mortality: A Systematic Review
Amado-Garzon SB et al. • Cancer investigation (2024)
There was less consistent evidence linking vitamin B12 and mortality.
- 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.
[Vitamin B12, fatty acids EPA and DHA during pregnancy and lactation in women with a plant-based diet]
Sandoval Leiva T et al. • Nutricion hospitalaria (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.
- 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.
Hallucinations and Vitamin B12 Deficiency: A Systematic Review
Blom JD • Psychopathology (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.
- 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.
Vitamin B12 levels in children and adolescents on plant-based diets: a systematic review and meta-analysis
Jensen CF • Nutrition reviews (2023)
Despite high heterogeneity across studies, these results indicate that children and adolescents on plant-based diets, especially those on vegan and macrobiotic diets, may be at risk of developing vitamin B12 deficiency.
- Despite high heterogeneity across studies, these results indicate that children and adolescents on plant-based diets, especially those on vegan and macrobiotic diets, may be at risk of developing vitamin B12 deficiency.
- Published in Nutrition reviews (2023)
- Further research warranted to confirm findings