What does the research show about vitamin b12?

Vitamin B12

In people with B12 deficiency, 1,000 to 2,000 µg a day by mouth raised blood B12 about as much as injections. In people without deficiency, 16 trials found no effect on cognition or depression. B vitamin combinations lowered stroke but not heart attack. High-dose B vitamin trials reported faster kidney decline in diabetic nephropathy and more cancer in Norway.

Add to Bio HackChecked 2026-11-09

Status: Dietary supplement in the US. B12 injections are prescription drugs.
Also called: B12, cobalamin, cyanocobalamin, methylcobalamin, hydroxocobalamin, adenosylcobalamin, B12 shots, B-complex
Taken for: energy, fatigue, memory, brain health, mood, depression, heart health, vegan diets, metformin users, correcting deficiency, pregnancy, child development, chemotherapy side effects

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help4

ModerateShown to raise blood B12 by mouth about as well as injection in people with B12 deficiency. One small trial in children favored injection.
LimitedOne trial found slightly higher infant mental development scores at 250 µg than at 50 µg a day in vegetarian pregnant women in India and Nepal.
LimitedOne small trial found a multinutrient with B12 raised blood B12 markers in healthy vegan adults over 4 months.
LimitedSmall trials found fewer chemotherapy side effects in women with cancer, halving hand-foot syndrome in one and lowering nerve damage in another.

Reported risks4

LimitedLimited evidence: two Norwegian trials found more cancer with folic acid plus B12 in people with heart disease, while a larger analysis found no significant effect.Common
LimitedOne trial found faster kidney decline and more heart events on high-dose B vitamins in people with diabetic kidney disease. The tablet combined folic acid and B6.How often is not known
LimitedLinked to about twice the lung cancer rate in men taking over 55 µg a day of B12 supplements for 10 years, stronger in smokers. No link in women.How often is not known
LimitedLimited evidence: metformin doubled low or borderline B12 at 5 years in one trial. Long-term acid suppressants were linked to deficiency, though sources disagree.How often is not known

What people take it for, and what was found

Shown to help4

Moderate

Correcting B12 deficiency by mouth instead of injection

Shown to raise blood B12 by mouth about as well as injection in people with B12 deficiency. One small trial in children favored injection.

The numbers and sources

Effect: In two trials using 1,000 µg a day by mouth, blood B12 levels showed no clinically relevant difference from intramuscular injection. One trial using 2,000 µg a day by mouth found blood B12 680 pg/mL higher than injection (95% CI 392.7 to 967.3) [1]. Across 16 studies, serum B12 rose by a pooled 402.6 pg/mL (95% CI 293.6 to 511.5) and homocysteine fell by 4.83 µmol/L, with no significant difference between oral, sublingual and intramuscular routes (p = 0.270) and no dose relationship [2]. A 2026 review of 13 studies in adults found that all three routes raised serum B12, several with comparable or larger rises by mouth [3]. In a 2026 trial, hemoglobin recovery at 28 days did not differ by route after adjustment, comparing B12 given in the nose, into a vein or into muscle [4].
Population: 3 RCTs, 153 people with B12 deficiency, mean ages 38.6 to 72, treated for 3 to 4 months [1]; 16 RCTs and observational studies with 6,098 participants [2]; 13 studies of adults with an indication for replacement in 10 countries [3]; 153 adults with B12 deficiency anemia [4].
Sources: [1], [2], [3], [4]
Caveats: The Cochrane review rated its evidence low quality, and no trial reported symptoms of deficiency, quality of life or acceptability [1]. The 2025 meta-analysis pooled RCTs with observational studies, heterogeneity was above 80% in most comparisons, and it found signs of publication bias [2]. The 2026 review did not pool, judged every trial at some risk of bias, and was funded by Myralis Indústria Farmacêutica [3]. In children with deficiency anemia, the only trial, at high risk of bias, found larger rises in B12 and hemoglobin with injection [5]. Graded B rather than A because the 2025 meta-analysis mixed in observational studies and the 2026 review did not pool.

LimitedStudied in pregnancy

Infant development with B12 in pregnancy

One trial found slightly higher infant mental development scores at 250 µg than at 50 µg a day in vegetarian pregnant women in India and Nepal.

The numbers and sources

Effect: Infants of mothers given 250 µg of methylcobalamin a day had higher mental development scores at 9 to 12 months than infants of mothers given 50 µg (103.7 against 101.7, p = 0.008). Motor scores did not differ. Maternal B12 rose more on the higher dose (104.9 against 47.5 pg/mL) [9].
Population: 531 vegetarian women in India and Nepal, from the first trimester to 6 months after birth [9].
Sources: [9]
Caveats: One trial comparing two doses, with no placebo group. Newborn size, APGAR scores and illness did not differ [9].

Limited

B12 status on a vegan diet

One small trial found a multinutrient with B12 raised blood B12 markers in healthy vegan adults over 4 months.

The numbers and sources

Effect: After 4 months, a multinutrient supplement with 82 µg of B12 a day raised serum B12, holotranscobalamin and a combined B12 status indicator against placebo. Methylmalonic acid and homocysteine did not differ between groups [10].
Population: 72 healthy vegan adults aged 19 to 57 in Germany [10].
Sources: [10]
Caveats: One small trial of a supplement with several nutrients, measuring blood markers only [10].

LimitedStudied in women

Chemotherapy side effects

Small trials found fewer chemotherapy side effects in women with cancer, halving hand-foot syndrome in one and lowering nerve damage in another.

The numbers and sources

Effect: In women taking capecitabine, grade 2 or worse hand-foot syndrome occurred in 14.5% on 0.5 mg of methylcobalamin three times a day and 29.1% on placebo (risk difference -14.5%, 95% CI -24.9% to -4.1%). Dose reduction or stopping capecitabine for hand-foot syndrome did not significantly differ (7.7% against 13.7%). Other adverse events were similar [11]. In a second trial, chemotherapy nerve damage (a questionnaire score of 4 or more) occurred in 5% on oral B12 and 20% on placebo (OR 0.21, 95% CI 0.07 to 0.66). Neurotoxicity quality of life scores did not differ [12].
Population: 234 women with HER2-negative early breast cancer at 7 hospitals in China, up to 24 weeks [11]; 40 patients with gynecological cancer on taxane and platinum chemotherapy in Thailand [12].
Sources: [11], [12]
Caveats: The two trials measured different side effects. The second trial was small [12].

Mixed results1

Moderate

Stroke and heart attack

Mixed results: stroke was slightly lower, 4.3% against 5.1%, with B vitamins mostly combined with folic acid, while heart attack and death did not change.

The numbers and sources

Effect: Across 15 RCTs with 71,422 participants, homocysteine-lowering B vitamins (B6, folic acid or B12, alone or combined) did not change heart attack (RR 1.02, 95% CI 0.95 to 1.10) or death from any cause (RR 1.01, 95% CI 0.96 to 1.06). Stroke was lower: 4.3% against 5.1% (RR 0.90, 95% CI 0.82 to 0.99, 10 trials, 44,224 people) [8].
Population: Adults with and without existing cardiovascular disease, followed 1 to 7.3 years. People with end-stage kidney disease were excluded [8].
Sources: [8]
Caveats: Most trials combined B12 with folic acid, so the stroke result cannot be assigned to B12 alone. The authors rated the stroke evidence high quality [8].

Not shown to help4

Moderate

Memory and thinking in people without deficiency

Not shown to improve memory or thinking in people without B12 deficiency, alone or with folic acid.

The numbers and sources

Effect: Across 16 RCTs with 6,276 participants, neither B12 alone nor B12 combined with folic acid, with or without B6, changed any subdomain of cognitive function. Meta-regression found no factor that predicted an effect [6].
Population: People without advanced neurological disorders or overt B12 deficiency [6].
Sources: [6]
Caveats: The review excluded people with overt deficiency, so it does not describe the effect of treating a deficiency.

Moderate

Depression symptoms

Not shown to improve depression in people without B12 deficiency.

The numbers and sources

Effect: Pooled trials found no overall effect of B12 or B complex supplementation on measures of depression [6].
Population: The same 16 RCTs, people without overt deficiency [6].
Sources: [6]
Caveats: One meta-analysis. The abstract gives no pooled effect size for depression.

ModerateStudied in children

Growth and thinking in children

Not shown to improve thinking or growth in children. B12 alone lowered B12 deficiency, 1.8% against 7.6% on placebo.

The numbers and sources

Effect: B12 alone against placebo made little to no difference to cognitive function such as attention (SMD 0.09, 95% CI -0.10 to 0.28, 2 trials, 438 children) or height (MD -0.19 cm, 95% CI -2.44 to 2.06). It lowered B12 deficiency, 1.8% against 7.6% (RR 0.27, 95% CI 0.11 to 0.69, 3 trials, 642 children). Added to other micronutrients, B12 made little to no difference to cognitive function (SMD 0.00, 95% CI -0.13 to 0.13, 3 trials, 956 children) or development (SMD -0.05, 95% CI -0.18 to 0.08) [7].
Population: 16 trials with 4,083 children aged 2 days to 11 years in 10 countries, given 0.9 to 150 µg a day for 28 days to 31 months [7].
Sources: [7]
Caveats: The authors rated growth and cognition evidence low certainty. Few trials reported these outcomes, and no trial of B12 alone reported adverse effects [7].

Limited

Energy and fatigue

Limited evidence: only one trial measured fatigue in people with normal B12, too few to pool.

The numbers and sources

Effect: Only one trial in the review reported idiopathic fatigue, too few for any pooled analysis [6].
Population: People without overt deficiency [6].
Sources: [6]
Caveats: Energy is the most common reason people give for taking B12, and almost no controlled trials have measured it in people with normal B12.

Doses studied

Deficiency trials compared 1,000 or 2,000 µg a day by mouth with intramuscular injection [1]. The diabetic nephropathy trial used 1 mg of B12 a day with 2.5 mg folic acid and 25 mg B6 [13]. The Norwegian trials used 0.4 mg of B12 a day with 0.8 mg folic acid, with or without 40 mg B6 [14]. Across routes, a 2025 meta-analysis found no dose relationship for the rise in serum B12 [2]. Child trials used 0.9 to 150 µg a day [7]. The pregnancy trial compared 250 with 50 µg a day [9], the vegan trial used 82 µg a day [10], and the hand-foot syndrome trial 1.5 mg a day [11]. EFSA lists vitamin B12 as having no defined adverse effects and sets no tolerable upper intake level [15].

Risks

Reported risks3

LimitedHow often is not known

Faster kidney decline in diabetic nephropathy

One trial found faster kidney decline and more heart events on high-dose B vitamins in people with diabetic kidney disease. The tablet combined folic acid and B6.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: At 36 months, filtration rate fell 16.5 mL/min/1.73 m² on high-dose B vitamins and 10.7 on placebo, a difference of -5.8 (95% CI -10.6 to -1.1). A composite of heart attack, stroke, revascularization and death occurred more often on B vitamins (HR 2.0, 95% CI 1.0 to 4.0). Dialysis did not differ [13].
Population: 238 people with type 1 or 2 diabetes and diabetic nephropathy, mean follow-up 31.9 months [13].
Sources: [13]
Caveats: One trial of a combined tablet with folic acid and B6, so the effect cannot be assigned to B12 alone.

LimitedHow often is not known

Lung cancer in men using high-dose B12 supplements

Linked to about twice the lung cancer rate in men taking over 55 µg a day of B12 supplements for 10 years, stronger in smokers. No link in women.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: Men whose 10-year average B12 supplement dose was above 55 µg a day had a higher lung cancer rate than nonusers (HR 1.98, 95% CI 1.32 to 2.97). The association was stronger in men who smoked. No association appeared in women, or for B12 from multivitamins [17].
Population: 77,118 adults aged 50 to 76 in Washington State, 808 lung cancers [17].
Sources: [17]
Caveats: Observational cohort with self-reported supplement use. It shows an association, not a cause.

LimitedHow often is not known

Drugs that lower B12: metformin and acid suppressants

Limited evidence: metformin doubled low or borderline B12 at 5 years in one trial. Long-term acid suppressants were linked to deficiency, though sources disagree.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: After 5 years, low or borderline-low B12 (298 pg/mL or less) occurred in 19.1% on metformin and 9.5% on placebo. Low B12 was 4.3% against 2.3% at 5 years and 7.4% against 5.4% at 13 years, the latter not significant [18]. In children and adolescents on metformin for 12 months or more, pooled B12 deficiency was 1.4% in RCTs and 18.7% in observational studies, and the fall in B12 levels was not significant [19]. In a case-control study, 2 or more years of proton pump inhibitors was associated with B12 deficiency (OR 1.65, 95% CI 1.58 to 1.73), as was 2 or more years of H2 blockers (OR 1.25, 95% CI 1.17 to 1.34) [20].
Population: 2,155 adults with prediabetes in the Diabetes Prevention Program and its follow-up [18]; 5 studies of children and adolescents [19]; 25,956 people with B12 deficiency and 184,199 controls at Kaiser Permanente Northern California [20].
Sources: [18], [20], [19], [21]
Caveats: These describe drugs lowering B12, not harm from B12 itself. The acid suppressant data are observational [20]. Sources disagree on acid suppressants. A 2025 meta-analysis of 6 studies (1,587 users, 2,272 controls) found no difference in serum B12 (SMD 0.01, 95% CI -0.14 to 0.16) or homocysteine after more than 6 months of proton pump inhibitors [21].

Mixed results1

LimitedCommon

Cancer with folic acid plus B12

Limited evidence: two Norwegian trials found more cancer with folic acid plus B12 in people with heart disease, while a larger analysis found no significant effect.

The numbers and sources

How common: Common: between 1 in 100 and 1 in 10 people.
Effect: In two Norwegian trials, cancer was diagnosed in 10.0% of people given folic acid plus B12 and 8.4% of those not given it (HR 1.21, 95% CI 1.03 to 1.41). Cancer death was 4.0% against 2.9% (HR 1.38) and death from any cause 16.1% against 13.8% (HR 1.18). Lung cancer drove most of the difference. B6 alone showed no effect [14].
Population: 6,837 people with ischemic heart disease in Norway, which did not fortify food with folic acid, treated a median 39 months and followed a further 38 months [14].
Sources: [14]
Caveats: A combined analysis of two trials, with half its follow-up after treatment ended. Sources disagree. A 2013 meta-analysis of individual data from 13 folic acid trials (49,621 people) found no significant effect on overall cancer during treatment (RR 1.06, 95% CI 0.99 to 1.13) [16].

Claims tested and not found

That B12 sharpens memory in people with normal B12. Sixteen trials found no effect on any area of cognitive function [6].
That B12 lifts mood in people without deficiency. The same review found no overall effect on depression measures [6].
That B vitamins prevent heart attacks. Fifteen trials found no difference in heart attack or death from any cause [8].
That B12 supplements help children grow or think. A Cochrane review found little to no difference in height, cognitive function or development [7].

Sources

Wang H, Li L, Qin LL, et al. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane Database of Systematic Reviews. 2018. https://doi.org/10.1002/14651858.CD004655.pub3
Mazur M, Ndokaj A, Salerno C, et al. Efficacy of sublingual and oral vitamin B12 versus intramuscular administration: insights from a systematic review and meta-analysis. Frontiers in Pharmacology. 2025. https://doi.org/10.3389/fphar.2025.1602976
Debone D, Azeredo da Silva AF, Cordenonssi JT, et al. Comparative efficacy of vitamin B12 supplementation routes in adults with replacement indication: a systematic review. eClinicalMedicine. 2026. https://doi.org/10.1016/j.eclinm.2026.104214
Singh SK, Arora R, Pramanik SK, et al. Comparative Efficacy of Intranasal, Intramuscular, and Intravenous Vitamin B12 Therapy for Hematological Recovery in Vitamin B12 Deficiency Anemia: A Randomized Controlled Trial. American Journal of Hematology. 2026. https://doi.org/10.1002/ajh.70433
Sachdeva M, Purohit A, Malik M, et al. Comparison of Efficacy and Safety of Parenteral vs Oral Route of Vitamin B12 Supplementation for the Treatment of Vitamin B12 Deficiency Anemia in Children: A Systematic Review. Nutrition Reviews. 2025. https://doi.org/10.1093/nutrit/nuae227
Markun S, Gravestock I, Jäger L, et al. Effects of Vitamin B12 Supplementation on Cognitive Function, Depressive Symptoms, and Fatigue: A Systematic Review, Meta-Analysis, and Meta-Regression. Nutrients. 2021. https://doi.org/10.3390/nu13030923
Larvie DY, Güitrón Leal CE, Venkatramanan S, et al. Vitamin B12 supplementation for growth, development, and cognition in children. Cochrane Database of Systematic Reviews. 2026. https://doi.org/10.1002/14651858.CD015264.pub2
Martí-Carvajal AJ, Solà I, Lathyris D, et al. Homocysteine-lowering interventions for preventing cardiovascular events. Cochrane Database of Systematic Reviews. 2017. https://doi.org/10.1002/14651858.CD006612.pub5
Nagpal J, Mathur M, Rawat S, et al. Maternal supplementation of vitamin B12 in predominantly vegetarian pregnant women improves their vitamin B12 status and the neurodevelopment of their infants: the MATCOBIND multicentric double-blind randomised control trial. BMJ Paediatrics Open. 2026. https://doi.org/10.1136/bmjpo-2025-004112
Zerback T, Koeder C, Weder S, et al. Assessment of vitamin A, vitamin B2, vitamin B12, vitamin K, folate, and choline status following 4 months of multinutrient supplementation in healthy vegans: a randomised, double-blind, placebo-controlled trial. European Journal of Nutrition. 2025. https://doi.org/10.1007/s00394-025-03814-7
Xia Y, Zhu Y, Ling L, et al. Effect of methylcobalamin on capecitabine induced hand-foot syndrome in patients with HER2 negative early breast cancer: multicentre, double blind, randomised, placebo controlled, phase 3 trial. BMJ. 2025. https://doi.org/10.1136/bmj-2025-084290
Insin P, Chaiwongsa T, Prueksaritanond N. Oral Vitamin B12 versus Placebo for the Prevention of Chemotherapy-Induced Peripheral Neuropathy in Gynecological Cancer Patients: A Randomized, Double-Blind, Placebo-Controlled Trial. Asian Pacific Journal of Cancer Prevention. 2026. https://doi.org/10.31557/apjcp.2026.27.5.1747
House AA, Eliasziw M, Cattran DC, et al. Effect of B-Vitamin Therapy on Progression of Diabetic Nephropathy. JAMA. 2010. https://doi.org/10.1001/jama.2010.490
Ebbing M, Bønaa KH, Nygård O, et al. Cancer Incidence and Mortality After Treatment With Folic Acid and Vitamin B12. JAMA. 2009. https://doi.org/10.1001/jama.2009.1622
European Food Safety Authority. Overview on Tolerable Upper Intake Levels as derived by the Scientific Committee on Food (SCF) and the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). Version 11. 2025. https://www.efsa.europa.eu/sites/default/files/assets/UL_Summary_tables.pdf
Vollset SE, Clarke R, Lewington S, et al. Effects of folic acid supplementation on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50 000 individuals. The Lancet. 2013. https://doi.org/10.1016/S0140-6736(12)62001-7
Brasky TM, White E, Chen CL. Long-Term, Supplemental, One-Carbon Metabolism-Related Vitamin B Use in Relation to Lung Cancer Risk in the Vitamins and Lifestyle (VITAL) Cohort. Journal of Clinical Oncology. 2017. https://doi.org/10.1200/JCO.2017.72.7735
Aroda VR, Edelstein SL, Goldberg RB, et al. Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study. Journal of Clinical Endocrinology & Metabolism. 2016. https://doi.org/10.1210/jc.2015-3754
Tahir EA, Ahmed MG, Al Swayah MB, et al. The Impact of Metformin on Vitamin B12 Levels in Children and Adolescents: A Systematic Review and Single-Arm Meta-Analysis. Endocrinology, Diabetes & Metabolism. 2026. https://doi.org/10.1002/edm2.70232
Lam JR, Schneider JL, Zhao W, et al. Proton Pump Inhibitor and Histamine 2 Receptor Antagonist Use and Vitamin B12 Deficiency. JAMA. 2013. https://doi.org/10.1001/jama.2013.280490
Parnham O, Patient W. Association Between Long-Term Proton Pump Inhibitor Therapy and Vitamin B12 Status: A Systematic Review and Meta-Analysis. Cureus. 2025. https://doi.org/10.7759/cureus.90038

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