Vitamin B12

Vitamin B12 is a water-soluble vitamin that contains the trace mineral cobalt — the source of its alternative name, cobalamin. It exists in several chemically distinct forms: methylcobalamin and 5-deoxyadenosylcobalamin are the two metabolically active forms used by the body's enzymes, while cyanocobalamin and hydroxocobalamin are the forms most commonly used in dietary supplements and pharmaceuticals due to their stability.¹ Vitamin B12 is naturally present in animal-source foods including fish, meat, poultry, eggs, and dairy; it is not naturally present in plant foods unless fortified.¹

Absorption of food-bound vitamin B12 involves several sequential steps. The vitamin must first be released from food proteins by gastric acid and pepsin in the stomach, then bound to intrinsic factor — a glycoprotein secreted by gastric parietal cells — for receptor-mediated uptake in the terminal ileum. Free B12 from supplements and fortified foods does not require the protein-release step but still requires intrinsic factor for efficient absorption at typical dietary doses.¹

Vitamin B12 is essential for the function of two enzymes: methionine synthase, which is required for one-carbon metabolism and DNA synthesis, and methylmalonyl-CoA mutase, which is involved in fatty acid and amino acid metabolism. Adequate B12 status is necessary for normal red blood cell formation, neurological function, and DNA synthesis.¹

Vitamin B12 supplementation is used to treat and prevent B12 deficiency, which can result from inadequate dietary intake (particularly in strict vegan diets without fortified foods or supplementation), impaired absorption (such as in pernicious anemia, atrophic gastritis, or following gastric or ileal surgery), or certain medication use (notably metformin and long-term proton pump inhibitors).¹ Untreated B12 deficiency can cause megaloblastic anemia and progressive neurological symptoms including peripheral neuropathy, balance problems, and cognitive changes.¹

Recommended Dietary Allowances for adults aged 19 and older:¹

• Men and women: 2.4 mcg/day
• Pregnant individuals: 2.6 mcg/day
• Lactating individuals: 2.8 mcg/day

For treatment of B12 deficiency, much higher doses are used. Common approaches include oral or sublingual cyanocobalamin at 1,000–2,000 mcg/day, or intramuscular injection at doses such as 1,000 mcg given on a weekly basis initially and then less frequently for maintenance. A Cochrane review found that high-dose oral B12 (1,000–2,000 mcg/day) appears comparable to intramuscular B12 for correcting deficiency in most patients, since a small fraction of B12 is absorbed by passive diffusion at pharmacologic doses even without intrinsic factor.¹

No Tolerable Upper Intake Level has been established for vitamin B12 because of its low toxicity at any documented intake level.¹

Oral (tablets, capsules, liquid drops), sublingual (dissolves under the tongue), intramuscular injection (typically administered in a clinical setting or self-administered for known deficiency states), or intranasal spray (prescription).

Standard storage in a cool, dry place out of direct sunlight; B12 is light-sensitive in solution. Injection formulations should be stored according to label directions.

Several populations are at higher risk for B12 inadequacy and may benefit from monitoring or supplementation:¹

• Older adults: atrophic gastritis is common with aging and can impair absorption of food-bound B12 even when intrinsic factor is intact
• People with pernicious anemia: an autoimmune condition that destroys gastric parietal cells, eliminating intrinsic factor production
• People who have had gastrointestinal surgery: gastric bypass, ileal resection, or other surgeries affecting the stomach or terminal ileum
• People taking long-term metformin: associated with reduced B12 absorption, particularly with sustained use
• People taking long-term proton pump inhibitors or H2 receptor antagonists: reduced gastric acid impairs B12 release from food
• Vegans and strict vegetarians: no reliable dietary B12 unless fortified foods or supplements are used

B12 status can be assessed with serum vitamin B12 and complementary markers including methylmalonic acid (MMA) and homocysteine, both of which become elevated when functional B12 is inadequate.¹