Vitamin B12 (cobalamin) is an essential, water-soluble vitamin that the body needs to make red blood cells, DNA and myelin, the fatty sheath around nerves. People get it only from animal foods, fortified foods, supplements or medicines. Deficiency causes a megaloblastic anemia (large, immature red cells) and nerve damage that can become permanent if it goes untreated.

B12 is sold as an over-the-counter supplement and as prescription injections, a nasal spray and a high-dose antidote for cyanide poisoning. Injections are approved for deficiency caused by poor absorption, such as pernicious anemia. B12 shots are also used for “energy” or athletic performance by people with normal levels. Controlled trials do not show a benefit for that use.

This page summarizes what the National Academies’ dietary reference report, the FDA labels and clinical trials report. It is for education only and is not medical advice.

Property	Detail
Class	Water-soluble vitamin; cobalt-containing cobalamins
Forms in products	Cyanocobalamin, hydroxocobalamin, methylcobalamin, adenosylcobalamin
Adult RDA (IOM 1998)	2.4 µg/day; 2.6 µg/day in pregnancy; 2.8 µg/day in lactation
Upper limit	None set; IOM found insufficient evidence of harm to set one
US prescription products	Cyanocobalamin injection 1,000 µg/mL (IM or deep SC); hydroxocobalamin injection 1,000 µg/mL (IM); Nascobal nasal spray 500 µg; Cyanokit 5 g IV for cyanide poisoning
Labeled maintenance dose (pernicious anemia)	Cyanocobalamin 100 µg IM monthly for life
Half-life	No single value. Injected cyanocobalamin peaks within 1 h, and 50–98% of a 100–1,000 µg dose can appear in urine within 48 h. Body stores turn over at 0.1–0.2% per day
Key mechanism	Cofactor for methionine synthase and methylmalonyl-CoA mutase
WADA status	Not named on the 2026 Prohibited List; IV infusions over 100 mL per 12 h are a prohibited method

What it is

“Vitamin B12” covers a family of cobalamins. Each has a cobalt atom held inside a corrin ring, and they differ only in the group attached to the cobalt (IOM 1998). Inside cells, B12 works as two coenzymes:

methylcobalamin, which methionine synthase needs to convert homocysteine to methionine (this reaction also recycles folate);
adenosylcobalamin, which methylmalonyl-CoA mutase needs to convert methylmalonyl-CoA to succinyl-CoA.

When B12 runs short, homocysteine and methylmalonic acid (MMA) build up in the blood. That is why these two markers are used to confirm deficiency.

The main forms found in products:

Form	Molecular formula	Molecular weight	Where it is used
Cyanocobalamin	C₆₃H₈₈CoN₁₄O₁₄P	1,355.4 g/mol	US injections, Nascobal; the traditional supplement form
Hydroxocobalamin	C₆₂H₈₉CoN₁₃O₁₅P	1,346.4 g/mol	IM injection; Cyanokit (high-dose IV antidote)
Methylcobalamin (mecobalamin)	C₆₃H₉₁CoN₁₃O₁₄P	1,344.4 g/mol	Supplements

Sources: cyanocobalamin and hydroxocobalamin from their FDA labels (cyanocobalamin injection; hydroxocobalamin injection); methylcobalamin from PubChem.

Does the form matter?

Cyanocobalamin does not occur naturally in food. It was first isolated from liver because of an artifact of the purification method. It has traditionally been used in supplements and medicines mainly because it is more stable than the other forms (Temova Rakuša et al., Molecules 2022).

Supplements are often marketed on the claim that methylcobalamin or adenosylcobalamin is “active” and therefore better. The same 2022 review found these claims “not necessarily scientifically based.” In cells, all four forms are stripped to a common intermediate, cob(II)alamin, which is then rebuilt into the two coenzymes. Some studies show lower tissue retention and higher urinary loss with cyanocobalamin than with the natural forms. Hydroxocobalamin has a real advantage only in certain rare inherited disorders of B12 metabolism.

The IOM report notes that, compared with hydroxocobalamin, cyanocobalamin binds serum proteins less well and is excreted faster.

How it works in the body

Absorption from food and pills

B12 in food is bound to protein. Stomach acid and enzymes release it, and it then binds intrinsic factor, a protein made by the stomach lining. The B12–intrinsic factor complex is absorbed in the last part of the small intestine (the terminal ileum) (IOM 1998).

This active route saturates quickly. The share absorbed falls as the dose rises, measured with radiolabeled cyanocobalamin:

Single oral dose	Share retained
1 µg	Nearly 50%
5 µg	About 20%
25 µg	Just over 5%

A second, passive route absorbs about 1% of a large oral dose, even with no intrinsic factor. This is why high-dose oral tablets can treat deficiency in people who cannot absorb B12 normally (see below).

Storage and turnover

The liver is the main store. Most estimates of total body B12 in adults are 2–3 mg. The body loses about 0.1–0.2% of its pool per day, and the higher figure applies to people with pernicious anemia, who cannot reabsorb B12 secreted in bile (IOM 1998). Because stores are large compared with daily losses, deficiency usually develops slowly.

Injected B12

Measure	Value	Source
Time to peak after IM cyanocobalamin	Within 1 hour	Cyanocobalamin label
Urinary loss after 100 or 1,000 µg cyanocobalamin	50–98% of the dose within 48 h, most in the first 8 h	Cyanocobalamin label
Retention of an IM dose	80–90% up to 50 µg; 55% at 100 µg; 15% at 1,000 µg	Nascobal label
Hydroxocobalamin leaving the injection site	50% in 2.5 h	Hydroxocobalamin label
Urinary loss after 500–1,000 µg hydroxocobalamin	16–66% within 72 h	Hydroxocobalamin label
Half-life of total cobalamins after 5–10 g IV (Cyanokit)	About 26–31 h	Cyanokit label

Once the binding proteins in blood and the liver are saturated, extra B12 is lost in urine. The cyanocobalamin label tells prescribers to avoid the IV route for deficiency because almost all of the vitamin would be lost in urine.

Requirements and who becomes deficient

The Institute of Medicine (now the National Academy of Medicine) set the adult RDA at 2.4 µg/day (IOM 1998). The RDA assumes 50% absorption from food.

Group	RDA
Children 1–3 years	0.9 µg/day
Children 4–8 years	1.2 µg/day
Ages 9–13	1.8 µg/day
Ages 14 and older	2.4 µg/day
Pregnancy	2.6 µg/day
Lactation	2.8 µg/day

The IOM estimated that 10–30% of people over 50 have atrophic gastritis with low stomach acid, which impairs release of B12 from food. It therefore advised people over 50 to get most of their RDA from fortified foods or supplements, whose crystalline B12 is not bound to protein.

The IOM lists these causes of deficiency:

a diet with no animal products (strict vegans);
pernicious anemia (an autoimmune loss of intrinsic factor);
gastrectomy or atrophic gastritis;
bacterial overgrowth of the small intestine;
fish tapeworm infection;
disease or removal of the terminal ileum;
pancreatic insufficiency.

Common drugs also lower B12 (see “Interactions” below).

Approved medical use

Cyanocobalamin injection

The label covers B12 deficiency due to malabsorption, including pernicious anemia, gastrointestinal disease or surgery (such as gastrectomy, sprue and small-bowel bacterial overgrowth), fish tapeworm and cancer of the pancreas or bowel (cyanocobalamin label). It states that higher needs from pregnancy, hemolysis and similar states can usually be met with oral supplements.

Labeled dosing for pernicious anemia, given IM or by deep subcutaneous injection:

Phase	Dose
Start	100 µg daily for 6–7 days
If there is a clinical and reticulocyte response	100 µg on alternate days for 7 doses, then every 3–4 days for 2–3 weeks
Maintenance	100 µg monthly for life

The label says oral treatment is “not dependable” in pernicious anemia. For people with normal intestinal absorption, it says long-term treatment should be oral.

Hydroxocobalamin injection

The IM-only hydroxocobalamin label lists pernicious anemia, dietary deficiency in strict vegetarians and their breastfed infants, and malabsorption from stomach or ileal disease (hydroxocobalamin label). The labeled adult dose is 30 µg daily for 5–10 days, then 100–200 µg monthly.

Nascobal nasal spray

Nascobal (cyanocobalamin 500 µg per spray) is approved for maintenance in pernicious anemia that is in remission after IM therapy without nervous-system involvement, for other deficiency not caused by pernicious anemia, and for prevention when needs are higher than normal (Nascobal label). The starting dose is one spray in one nostril once weekly, with a B12 level and blood count after one month and then every 3–6 months.

Cyanokit (high-dose hydroxocobalamin)

Cyanokit is a different use altogether. Hydroxocobalamin binds cyanide to form cyanocobalamin, which is excreted in urine. The adult starting dose is 5 g by IV infusion over 15 minutes, with a possible second 5 g dose (Cyanokit label).

What the research shows

Oral versus injected B12 for deficiency

A Cochrane review found three randomized trials with 153 participants comparing oral and IM B12 over 3–4 months (Wang et al., Cochrane 2018):

In two trials using 1,000 µg/day orally, serum B12 did not differ in a clinically relevant way from IM treatment.
One trial using 2,000 µg/day orally found serum B12 higher by a mean of 680 pg/mL (95% CI 392.7–967.3) than with IM treatment.
The quality of evidence was rated low, and no trial reported symptoms or quality of life.

The best-known of these trials randomized 38 newly diagnosed patients to 2 mg oral cyanocobalamin daily or 1 mg IM on days 1, 3, 7, 10, 14, 21, 30, 60 and 90 (Kuzminski et al., Blood 1998). Five turned out to have folate deficiency, leaving 33 evaluable patients:

Measure (mean)	Oral, before	Oral, 4 months	IM, before	IM, 4 months
Serum B12 (pg/mL)	93	1,005	95	325
Methylmalonic acid (nmol/L)	3,850	169	3,630	265
Homocysteine (µmol/L)	37.2	10.6	40.0	12.2

Blood counts and nerve symptoms improved promptly and equally in both groups. Serum B12 was significantly higher and MMA lower in the oral group at 4 months.

Metformin, the first-line drug for type 2 diabetes, lowers B12. Its label suggests the cause may be interference with absorption of the B12–intrinsic factor complex (metformin label). In 29-week trials, about 7% of patients with normal levels fell to subnormal levels. The label now advises measuring B12 every 2–3 years and blood counts yearly.

Two long-term studies quantify the effect:

Study	Design	Main B12 finding
HOME trial (de Jager et al., BMJ 2010)	RCT, 390 insulin-treated type 2 diabetes patients; metformin 850 mg three times daily vs placebo for 4.3 years	B12 fell 19% vs placebo (95% CI −24% to −14%). Deficiency (under 150 pmol/L) was 7.2 percentage points more common (95% CI 2.3–12.1), a number needed to harm of 13.8 over 4.3 years
DPP/DPPOS (Aroda et al., JCEM 2016)	Secondary analysis of a prediabetes trial; metformin 850 mg twice daily vs placebo, then open-label metformin; follow-up to 13 years	Low B12 (≤ 203 pg/mL): 4.3% vs 2.3% at 5 years; 7.4% vs 5.4% at 13 years (not significant). Low or borderline (≤ 298 pg/mL): 19.1% vs 9.5% at 5 years and 20.3% vs 15.6% at 13 years

In the DPPOS, each year of metformin use raised the odds of B12 deficiency by 13% (OR 1.13, 95% CI 1.06–1.20). Neuropathy was more common in metformin users with low B12. In the HOME trial, patients who became deficient had higher homocysteine.

Energy and performance in people who are not deficient

B12 shots are used by some athletes, especially in endurance sports (Krzywański et al., Nutrients 2020). The rationale is that B12 is needed to make red cells, and severe B12 or folate deficiency does cause anemia and reduce endurance (Lukaski, Nutrition 2004). The question is whether extra B12 helps someone whose levels are already adequate.

The controlled evidence says it does not:

Injection trial. In a double-blind trial, 31 non-anemic young men (aged 18.7–20.8) received 1 mg cyanocobalamin or a placebo injection three times weekly for 6 weeks. There was no significant difference between groups in any measure of physical performance capacity (Tin-May-Than et al., Br J Nutr 1978).
Review of vitamins and performance. A USDA review concluded that vitamin and mineral supplements do not improve measures of performance in people eating adequate diets (Lukaski 2004).
Use among elite athletes. In 243 Polish track-and-field athletes (1,131 blood samples over 6 years), 34% reported using B12 injections, more often in endurance events. Mean serum B12 was 739 pg/mL and no athlete was deficient (Krzywański et al. 2020). Hemoglobin rose with B12 only up to about 400 pg/mL and did not change from 700 pg/mL upward. The study was observational and did not test injections.

The pharmacokinetics also work against the idea. Only about 15% of a 1,000 µg IM dose is retained, and much of a large injection appears in urine within hours (Nascobal label; cyanocobalamin label). We found no randomized trial showing that B12 injections improve energy, fatigue, fat loss or athletic performance in people with normal B12 status.

About “B12 for energy.” Tiredness is a real symptom of B12 deficiency, because deficiency causes anemia. Correcting a true deficiency can therefore restore energy. That does not mean extra B12 adds energy above normal; a controlled injection trial in non-anemic men found no effect on performance.

Side effects and risks

From food and supplements

The IOM found no adverse effects from excess B12 intake from food or supplements in healthy people, and so set no Tolerable Upper Intake Level (IOM 1998). Only a small share of a large oral dose is absorbed, which may explain the low toxicity. Some older reports linked high-dose injected B12 (0.5–5 mg) to acne. These cases mostly involved hydroxocobalamin, and iodine contamination in the products may have been the cause.

Injection warnings (labels)

The cyanocobalamin and hydroxocobalamin labels list these risks (cyanocobalamin label; hydroxocobalamin label):

Anaphylaxis. Anaphylactic shock and death have been reported after injected B12. The cyanocobalamin label recommends an intradermal test dose in people suspected of being sensitive. Sensitivity to cobalt or B12 is a contraindication.
Leber’s disease. Patients with early Leber’s hereditary optic atrophy treated with cyanocobalamin developed severe and rapid optic atrophy.
Low potassium. Hypokalemia and sudden death can occur when severe megaloblastic anemia is treated intensively. Potassium should be watched closely in the first 48 hours.
Early treatment effects. Pulmonary edema and heart failure early in treatment, peripheral vascular thrombosis, and thrombocytosis.
Polycythemia vera. B12 deficiency can hide this blood disorder, and treatment may unmask it.
Minor reactions. Mild transient diarrhea, itching, rash, a feeling of swelling of the whole body, and pain at the injection site.
Benzyl alcohol. Multi-dose vials contain benzyl alcohol, which has been linked to a fatal “gasping syndrome” in premature infants.

Folic acid masking

Folic acid can correct the anemia of B12 deficiency but not the nerve damage. Both labels warn that treating B12 deficiency with folic acid alone can allow irreversible neurological damage to progress. The cyanocobalamin label states that deficiency lasting longer than 3 months may cause permanent degenerative lesions of the spinal cord.

High-dose B vitamins in kidney disease

In the DIVINe trial, 238 people with diabetic kidney disease received a daily tablet of folic acid 2.5 mg, vitamin B6 25 mg and B12 1 mg, or placebo (House et al., JAMA 2010). At 36 months, kidney function (GFR) fell more in the vitamin group: by 16.5 vs 10.7 mL/min/1.73 m² (mean difference −5.8, 95% CI −10.6 to −1.1). The composite of heart attack, stroke, revascularization and death was also more common (HR 2.0, 95% CI 1.0–4.0). The combination design means the effect cannot be assigned to B12 alone.

High-dose IV hydroxocobalamin

At antidote doses, Cyanokit turns the skin and urine red. Its label lists allergic reactions, kidney injury (including oxalate crystals in urine) and rises in blood pressure as serious reactions (Cyanokit label).

Interactions

Drug or factor	Effect	Source
Metformin	Lowers serum B12; label advises checking B12 every 2–3 years	Metformin label
Proton pump inhibitors (2+ years’ supply)	Linked to deficiency, OR 1.65 (95% CI 1.58–1.73) in a case-control study of 25,956 cases	Lam et al., JAMA 2013
H2 blockers (2+ years’ supply)	OR 1.25 (95% CI 1.17–1.34) in the same study	Lam et al. 2013
Colchicine, para-aminosalicylic acid, heavy alcohol use over 2 weeks	May cause B12 malabsorption	Cyanocobalamin label
Chloramphenicol	May blunt the blood response to B12	Nascobal label; hydroxocobalamin label
Most antibiotics, methotrexate, pyrimethamine	Can invalidate B12 and folate blood tests	Cyanocobalamin label

Legal status and quality

In the US, B12 injections and Nascobal are prescription (“Rx only”) products, while oral B12 is sold as a dietary supplement. The FDA requires B12 added to supplements to be present at 100% or more of the labeled amount but sets no maximum. Manufacturers often add overages to make up for breakdown during storage (Temova Rakuša et al. 2022).

B12 is unstable in light and in some mixtures. The same review describes studies of B-complex injectable solutions in which four of six products had B12 contents between 5% and 80% of the labeled amount, with further losses during storage. The labels for both injectable forms say to protect them from light.

For athletes, vitamin B12 is not named on the WADA 2026 Prohibited List. However, IV infusions or injections of more than 100 mL in total per 12 hours are a prohibited method (M2.2), except when received legitimately in hospital treatment, surgery or clinical investigations. That rule applies to vitamin “drips” regardless of what they contain.

Key takeaways

Essential, but needed in tiny amounts. The adult RDA is 2.4 µg/day. Deficiency causes anemia and nerve damage that can become permanent.
Injections treat malabsorption. Labels approve IM cyanocobalamin (100 µg monthly for life in pernicious anemia) and hydroxocobalamin. In trials, high-dose oral B12 (1–2 mg/day) corrected deficiency as well as injections did.
Form matters less than marketing suggests. All forms are converted to the same intermediate in cells. Claims that methylcobalamin is superior are not well supported.
Metformin lowers B12. In a 4.3-year RCT, metformin cut B12 by 19% versus placebo. The label advises checking B12 every 2–3 years.
No proven boost for people with normal levels. A double-blind injection trial found no effect on performance, and most of a 1,000 µg shot is lost in urine.
Low toxicity, but not risk-free. No upper limit is set for oral intake. Injections carry rare anaphylaxis, and early treatment of severe anemia needs potassium monitoring.

Sources

Institute of Medicine. Vitamin B12. In: Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academies Press; 1998:306–356. doi:10.17226/6015. NAP.
Hikma Pharmaceuticals USA. Cyanocobalamin injection, USP, prescribing information. DailyMed.
Actavis Pharma. Hydroxocobalamin injection USP, prescribing information. DailyMed.
Par Health USA. Nascobal (cyanocobalamin) nasal spray, prescribing information. DailyMed.
BTG International. Cyanokit (hydroxocobalamin) for injection, prescribing information. DailyMed.
Laurus Labs. Metformin hydrochloride tablets and extended-release tablets, prescribing information. DailyMed.
National Center for Biotechnology Information. Mecobalamin, PubChem CID 60196341. PubChem.
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de Jager J, Kooy A, Lehert P, et al. Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial. BMJ. 2010;340:c2181. PubMed.
Aroda VR, Edelstein SL, Goldberg RB, et al. Long-term metformin use and vitamin B12 deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab. 2016;101(4):1754–1761. PubMed.
Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA. 2013;310(22):2435–2442. PubMed.
Tin-May-Than, Ma-Win-May, Khin-Sann-Aung, Mya-Tu M. The effect of vitamin B12 on physical performance capacity. Br J Nutr. 1978;40(2):269–273. PubMed.
Lukaski HC. Vitamin and mineral status: effects on physical performance. Nutrition. 2004;20(7-8):632–644. PubMed.
Krzywański J, Mikulski T, Pokrywka A, et al. Vitamin B12 status and optimal range for hemoglobin formation in elite athletes. Nutrients. 2020;12(4):1038. PubMed.
House AA, Eliasziw M, Cattran DC, et al. Effect of B-vitamin therapy on progression of diabetic nephropathy: a randomized controlled trial. JAMA. 2010;303(16):1603–1609. PubMed.
World Anti-Doping Agency. The 2026 Prohibited List. WADA 2026 Prohibited List.

Vitamin B12