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# Cobalamin (vitamin B12)

Vitamin B12 contains cobalt and only two enzymes use it, but its lack causes megaloblastic anaemia and spinal cord damage.

Updated 2026-11-01

## Key facts

- Two active forms: methylcobalamin (methionine synthase: homocysteine → methionine) and adenosylcobalamin (methylmalonyl-CoA mutase: methylmalonyl-CoA → succinyl-CoA).
- Found only in animal foods: vegans need fortified foods or supplements.
- Its absorption needs intrinsic factor from gastric parietal cells and the terminal ileum.
- The liver holds stores for several years, so deficiency develops slowly.

## In detail

- Commercial and lab forms: cyanocobalamin and hydroxocobalamin; the body converts them into methyl- and adenosylcobalamin.
- Absorption path: acid and pepsin free it from proteins; it binds haptocorrin (saliva); in the duodenum pancreatic proteases release it; it binds intrinsic factor; the complex enters through the cubam (cubilin) receptor in the terminal ileum; in blood it travels with transcobalamin II.
- Methionine synthase: B12 takes the methyl from 5-methyl-THF and passes it to homocysteine. Without B12, folate is 'trapped' as 5-methyl-THF (the folate trap) and THF runs short for DNA: megaloblastic anaemia.
- Methylmalonyl-CoA mutase: without B12, methylmalonic acid and propionate accumulate and disturb myelin synthesis: subacute combined degeneration of the dorsal and lateral columns.
- Causes of deficiency: pernicious anaemia (autoimmune), gastrectomy or bariatric surgery, atrophic gastritis in older adults, ileal resection or disease (Crohn), metformin, long-term proton pump inhibitors, vegan diet, nitrous oxide, fish tapeworm (Diphyllobothrium latum).
- Excess: not toxic; a very high serum B12 without supplements can point to liver or myeloproliferative disease.
- Lab: serum B12 (low), methylmalonic acid and homocysteine (both high, more sensitive), blood count with high MCV and hypersegmented neutrophils; antibodies to intrinsic factor and to parietal cells.

**Also called**
Vitamin B12, Cyanocobalamin, Methylcobalamin, Adenosylcobalamin, Hydroxocobalamin

## Clinical notes

- Nerve damage (paraesthesia, loss of vibration and position sense, ataxia, dementia) can appear without anaemia and become permanent if treatment is delayed.
- When intrinsic factor is missing, B12 is replaced intramuscularly or with high oral doses, a little of which is absorbed by diffusion.
- Years of metformin and long-term proton pump inhibitors lower B12: it is monitored in people with diabetes and neuropathy.

## Drugs that act here

- [Cyanocobalamin](https://durgical.com/en/pharmacology/cyanocobalamin/)

## Related conditions

- [Pernicious anaemia](https://durgical.com/en/conditions/pernicious-anaemia/)
- [Megaloblastic anaemia (B12 or folate deficiency)](https://durgical.com/en/conditions/megaloblastic-anaemia/)
- [Crohn disease](https://durgical.com/en/conditions/crohn-disease/)
- [Helicobacter pylori gastritis](https://durgical.com/en/conditions/helicobacter-pylori-gastritis/)

## Related

- [Folate (vitamin B9)](https://durgical.com/en/biochemistry/molecules/folate/)
- [Biotin (vitamin B7)](https://durgical.com/en/biochemistry/molecules/biotin/)
- [Vitamin B6 (pyridoxal phosphate)](https://durgical.com/en/biochemistry/molecules/vitamin-b6/)

## Test yourself

Think of the answer, then tap the question to see it.

## Which two reactions depend on vitamin B12?

Methionine synthase (homocysteine → methionine, with methylcobalamin) and methylmalonyl-CoA mutase (→ succinyl-CoA, with adenosylcobalamin).

## What is the folate trap?

Without B12, 5-methyl-THF cannot give up its methyl and accumulates; THF runs short for thymidylate and megaloblastic anaemia follows.

## Why does B12 deficiency damage the spinal cord while folate deficiency does not?

Failure of methylmalonyl-CoA mutase builds up methylmalonic acid, which disturbs myelin in the dorsal and lateral columns.

## Where is vitamin B12 absorbed and what does it need?

In the terminal ileum, bound to intrinsic factor made by the stomach's parietal cells.

## Which test is most sensitive for B12 deficiency?

Serum methylmalonic acid, which rises even when B12 is borderline low.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: [Vitamin B12: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/002403.htm) (MedlinePlus, US National Library of Medicine, 2026); [Vitamin B12 deficiency anemia: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/000574.htm) (MedlinePlus, US National Library of Medicine, 2026); [Vitamin B12 level: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/003705.htm) (MedlinePlus, US National Library of Medicine, 2026); [Methylmalonic Acid (MMA) Test: MedlinePlus Medical Test](https://medlineplus.gov/lab-tests/methylmalonic-acid-mma-test/) (MedlinePlus, US National Library of Medicine, 2026); [Imerslund-Gräsbeck syndrome: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/imerslund-grasbeck-syndrome/) (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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