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Vitamin B12

Cyanocobalamin

Prepared by the ezGLP team. Sources last checked . Profile reviewed .

Also known as Vitamin B12, B12 injection

Routes represented in the knowledgebase: Subcutaneous (SubQ) / Oral / Sublingual.

Educational overview

FDA-approved prescription injection for vitamin B12 deficiency; intramuscular and subcutaneous products are available.

Cyanocobalamin is the synthetic form of vitamin B12, a cobalt-containing corrinoid. What distinguishes the cobalamins from one another is the group bound to the central cobalt atom: a cyanide ligand in cyanocobalamin, a methyl group in methylcobalamin, a deoxyadenosyl group in adenosylcobalamin, and a hydroxyl group in hydroxocobalamin. The cyanide ligand makes the molecule unusually stable to light and heat and inexpensive to manufacture, which is why it dominates fortified foods, multivitamins, and approved injections. After absorption, cells remove the upper ligand and rebuild the two coenzymes the body requires, methylcobalamin for methionine synthase and adenosylcobalamin for methylmalonyl-CoA mutase.

Vitamin B12 deficiency and its correction are among the best-characterised topics in clinical nutrition, established from decades of observation and biochemistry rather than from modern placebo-controlled trials. The NIH Office of Dietary Supplements states that research has not shown any one supplemental form to be superior to the others, and a 2015 review in Molecular Nutrition and Food Research reached the same conclusion for the coenzyme forms specifically. A 2018 Cochrane review found high-dose oral vitamin B12 comparable to intramuscular injection for raising serum concentrations in deficient adults, though the evidence was graded low quality. Trials in people without deficiency have not demonstrated benefit for fatigue, mood, or cognition.

Cyanocobalamin has the widest approved-product footprint of any B12 form. Cyanocobalamin Injection USP is an FDA-approved prescription drug marketed under abbreviated new drug applications for intramuscular or subcutaneous administration in pernicious anemia and other malabsorptive deficiency states, and Nascobal, a cyanocobalamin nasal spray, is separately approved for maintenance therapy in adults already stabilised on intramuscular treatment. Methylcobalamin, by contrast, has no FDA-approved injectable product and its listings are categorised as unapproved drugs. Oral and sublingual cyanocobalamin tablets are dietary supplements in the United States and food supplements in the European Union, while NICE guidance describes hydroxocobalamin as the injectable form in routine United Kingdom practice.

Approved cyanocobalamin injection is a clear red solution labelled for controlled room temperature with protection from light, and the nasal spray label directs upright storage in its carton, protected from light and from freezing. Oral tablets are stable in a closed container away from heat and moisture. For a dose log or inventory record, the informative fields are the form and route, the concentration for injectable vials, the lot number, and any concurrent medicines that lower B12 absorption, notably metformin and acid-suppressing drugs. Because any B12 administration raises serum concentrations for weeks, dating doses against laboratory draws helps a clinician interpret a result; methylmalonic acid is the marker least disturbed by recent supplementation.

Category
Vitamin B12
Routes represented
Subcutaneous (SubQ) / Oral / Sublingual
Storage context
Protect from light and follow the product label.
Authoritative overview

Published literature

No verified PubMed or DOI link is available for this entry.

Safety evidence

Common or reported: injection-site reaction, rash or itching, mild diarrhea.

Serious or important: rare anaphylaxis, hypokalemia during rapid correction of severe deficiency.

Effects vary substantially by chemical form and route.

Safety evidence source

Interaction evidence

These are general, pairwise evidence notes. Green identifies the potential-synergy category, while Lv3/Lv2/Lv1 communicates evidence strength; it does not guarantee benefit or cancel a safety warning.

With metformin

Safety flag

Long-term metformin use can reduce vitamin B12 absorption and serum B12 concentration.

Interaction evidence source

Common questions

What is the difference between cyanocobalamin and methylcobalamin?

Both are forms of vitamin B12 and differ only in the group attached to the central cobalt atom: a cyanide ligand in cyanocobalamin, a methyl group in methylcobalamin. Cells strip that upper ligand from either form and rebuild the same two coenzymes, and the NIH Office of Dietary Supplements reports no evidence that one supplemental form outperforms another. Cyanocobalamin is markedly more stable to light and is the form in FDA-approved injections.

Is cyanocobalamin injection FDA approved?

Yes. Cyanocobalamin Injection USP is an FDA-approved prescription product for intramuscular or subcutaneous administration, marketed by several manufacturers under abbreviated new drug applications for vitamin B12 deficiency caused by malabsorption, including pernicious anemia. A cyanocobalamin nasal spray, Nascobal, is separately approved for maintenance therapy in adults already stabilised on intramuscular B12. Methylcobalamin injections sold in the United States hold no equivalent approval.

Is the cyanide in cyanocobalamin dangerous?

The quantity is very small. Each molecule releases a single cyanide ion when cells remove the upper ligand, an amount far below toxic exposure that is cleared in urine as thiocyanate. The caution that does appear on labelling is unrelated to that trace: cyanocobalamin is not advised in early Leber's hereditary optic neuropathy, where severe optic atrophy has followed vitamin B12 treatment and hydroxocobalamin is named as the alternative.

Can vitamin B12 be swallowed instead of injected?

A 2018 Cochrane review concluded that high-dose oral vitamin B12 appears comparable to intramuscular injection for raising serum B12 in deficient adults, although the included studies were small and the evidence was rated low quality. Guidance still reserves injections for pernicious anemia, other malabsorption, and neurological presentations, where reliable absorption through the gut cannot be assumed. A nasal spray is a third approved route in the United States.

Does metformin cause B12 deficiency?

Long-term metformin is associated with lower serum vitamin B12, and the NIH Office of Dietary Supplements lists it among the drugs that interfere with B12 status, alongside proton pump inhibitors and H2 blockers that reduce absorption of food-bound B12. The association appears related to duration of treatment. Clinical guidance in several countries describes periodic measurement of B12 in people on long-term metformin.

Further reading

Summarised from published literature for reference only, with citations to the source. Evidence is graded as reported and is not a recommendation to combine, dose, or use any compound.

For personal tracking and education only. Not medical advice, diagnosis, or treatment, and not a medical device. Peptides may be prescription-only or unapproved where you live. Consult a licensed healthcare professional.