Vitamin B12
Vitamin B12 is essential for healthy red blood cell formation, DNA synthesis, and the development, myelination and function of the central nervous system. It occurs naturally only in animal foods (some plant foods are fortified with it), so vegans and vegetarians are at higher risk of deficiency, as are older adults, many of whom absorb the B12 in food less well.
Research & evidence
Strong support Some support Weak or no supportColours show how well the sources back each point. The reason is next to each one.
B12 deficiency causes megaloblastic anemia, and can independently damage the nervous system even in people who don't have anemia — so correcting a deficiency early, before nerve symptoms progress, is important for full recovery.
Strong evidenceStrong support. Stated plainly by NIH or an FDA label
Study details
NIH's consumer fact sheet on vitamin B12 (updated December 2023) states: "Vitamin B12 deficiency can damage the nervous system even in people who don't have megaloblastic anemia." Nerve damage can happen without anemia. It isn't only a later consequence of long-lasting anemia.
Source: NIH Office of Dietary Supplements, Vitamin B12 — Consumer Fact Sheet (updated December 15, 2023). View source
B12 deficiency is associated with fatigue, cognitive symptoms, and mood disturbance (including depression), which can appear before megaloblastic anemia develops. This refers to true deficiency, not simply low-normal B12 levels — trials of B12 supplementation in people without confirmed deficiency have found no benefit for cognitive function or depression, and fatigue specifically hasn't been adequately studied in that population.
Moderate evidenceSome support. Shown only in certain groups, uses, strains or doses
Study details
In people with a diagnosed deficiency, the link is well supported. A 2013 clinical review (Briani et al.) states: "Cobalamin deficiency may present with neuropsychiatric syndromes also in the absence of hematological signs. Among the psychiatric presentations mood disorders (both depression and mania), chronic fatigue syndrome and psychosis are notable." In people without a confirmed deficiency, a 2021 review of 16 trials with 6,276 participants (Markun et al.) found "no evidence for an effect of B12... supplementation on any subdomain of cognitive function outcomes" or on depression. That review could not assess fatigue: "only one study reported effects on idiopathic fatigue, and therefore, no analysis was possible."
Source: Briani C, Dalla Torre C, Citton V, et al. "Cobalamin Deficiency: Clinical Picture and Radiological Findings." Nutrients. 2013 Nov 15;5(11):4521-4539; and Markun S, et al. "Effects of Vitamin B12 Supplementation on Cognitive Function, Depressive Symptoms, and Fatigue: A Systematic Review, Meta-Analysis, and Meta-Regression." Nutrients. 2021 Mar 12;13(3):923. View source
Vegans and vegetarians might not get enough B12 from their diets without supplements or fortified foods.
Strong evidenceStrong support. Stated plainly by NIH or an FDA label
Study details
NIH's consumer fact sheet (December 2023) states: "People who eat little or no animal foods, such as vegetarians and vegans, might not get enough vitamin B12 from their diets." NIH's health professional fact sheet also lists vegetarians and infants of vegan mothers among the groups at risk. Both note that some breakfast cereals and nutritional yeasts are fortified with B12; the health professional fact sheet calls them "readily available sources of vitamin B12."
Source: NIH Office of Dietary Supplements, Vitamin B12 — Consumer Fact Sheet (updated December 15, 2023) and Health Professional Fact Sheet (updated July 2, 2025). View source
Dosage
| Form | Amount |
|---|---|
| Capsule | Single-ingredient B12 supplements typically contain 500–1,000 mcg. Only a small share of a large dose is absorbed (about 2% at 500 mcg and 1.3% at 1,000 mcg). The recommended daily amount for adults is 2.4 mcg. Diagnosed deficiency is usually treated with injections, though high oral doses may also work. |
| Sublingual | Sublingual (under-the-tongue) forms are available, but studies show no difference in effectiveness between sublingual and swallowed B12. |
Side effects
Well documented Reported (case reports, anecdotal or one study) None reportedThe circle shows how well documented an effect is, not how serious it is. A rarely reported effect can still be serious, so always read ‘When to stop’.
| Effect | Frequency | When to stop |
|---|---|---|
| Acute skin irritation (rosacea fulminans in the one reported case)ReportedCase reports only | One case report, after high doses of vitamins B6 and B12 taken together for 2 weeks | Stop and see a doctor if a new rash or skin flare-up appears. |
Safety & interactions
Safety
Generally considered safe, even at high doses: it's water-soluble, the body doesn't store excess amounts, and there's no upper intake limit. Some observational studies and clinical trials suggest higher intakes or blood levels might raise cancer risk, but the evidence is mixed.
Contraindications
Don't take vitamin B12 if you're undergoing a coronary stenting procedure — MSK warns it may increase the risk of the stented artery narrowing again (restenosis). The trial MSK cites for this gave B12 together with folic acid and vitamin B6, not B12 on its own.
Drug interactions
Metformin can reduce the absorption of vitamin B12 and significantly reduce serum B12 concentrations, particularly with prolonged use (NIH ODS; MSK About Herbs). NIH lists prolonged metformin use among the causes of B12 deficiency. Anyone on long-term metformin should discuss their B12 status with their healthcare provider.
Proton pump inhibitors (such as omeprazole and lansoprazole) and H2-receptor antagonists (such as cimetidine) reduce stomach acid, which the body needs to release vitamin B12 from food. With long-term use this can reduce B12 absorption and lead to deficiency (NIH ODS; MSK About Herbs). MSK also attributes the effect to reduced production of intrinsic factor. Anyone taking these medications regularly should discuss their B12 status with their healthcare provider.
Oral contraceptives may lower serum vitamin B12 concentrations (MSK About Herbs). MSK gives no detail on how this happens or how much it matters, and NIH's vitamin B12 fact sheet doesn't mention it.
Folic acid intake above the Tolerable Upper Intake Level may mask the anemia symptoms of a vitamin B12 deficiency without correcting its neurological damage (MSK About Herbs; NIH ODS Folate fact sheet). NIH says this masking concern is still an open question. It also notes a related worry, that high folate intake could worsen, rather than simply hide, the anemia and cognitive symptoms of B12 deficiency. This is a caution, not a settled finding.
In this case, vitamin B12 itself may be the risk, rather than a medication lowering B12. MSK About Herbs lists coronary stenting under "Do Not Take If": vitamin B12 may increase the risk of narrowing blood vessels (restenosis) after a coronary stenting procedure. The trial MSK cites for this gave B12 together with folic acid and vitamin B6, not B12 on its own. NIH ODS doesn't address this.
Established: stated plainly by an authoritative source. Documented: supported by case reports or trial data. Theoretical: based on mechanism, animal data, or a cautious listing. Always check with your pharmacist or prescriber.
Which form to buy
Cyanocobalamin, methylcobalamin, adenosylcobalamin or hydroxocobalamin
Good choiceAll common forms work about the same (per NIH)
No form has been shown to be absorbed better. Cyanocobalamin is the most common.
Sublingual (under the tongue) vs swallowed
Good choiceAll common forms work about the same (per NIH)
Under-the-tongue tablets and lozenges haven't been shown to work better than regular ones.