Cyanocobalamin

Vitamins. Haemopoietic stimulants

ATC code: B03BA01 (Cyanocobalamin)

Brand names – drugs

Cyanokit

Brand names – supplements

Solgar Sublingual Methylcobalamin, Jarrow Formulas Methyl B-12, Thorne Methylcobalamin

Supplements are not tested in clinical trials and are not registered as medications.

Mechanism of action

Cyanocobalamin (vitamin B12) is a cofactor for two enzymes: methionine synthase (remethylation of homocysteine to methionine) and methylmalonyl-CoA mutase (branched-chain fatty acid metabolism). It is required for DNA synthesis, myelination of nerve fibres, and erythrocyte maturation. Deficiency impairs erythrocyte precursor division (megaloblastic haematopoiesis) and causes demyelination of the posterior and lateral spinal cord columns.

Indications

B12 deficiency with neurological symptoms

First line

In subacute combined degeneration and other neurological features of B12 deficiency, high-dose parenteral cyanocobalamin or hydroxocobalamin is the only disease-modifying therapy. Maximal recovery occurs in the first 6 months, before irreversible axonal degeneration develops. With late treatment, neurological deficit may partially persist. Early suspicion of B12 deficiency prompts B12 and homocysteine testing without delaying therapy until results return.

Sources

Vitamin B12 deficiency anaemia (pernicious anaemia)

First line

Cyanocobalamin or hydroxocobalamin is first-line for B12 deficiency anaemia. Standard regimen for pernicious anaemia: 1,000 µg intramuscularly daily for 1 week, weekly for 4 weeks, then monthly for life. Oral therapy uses 1,000–2,000 µg daily; the 2018 Cochrane review showed comparable efficacy of oral and parenteral routes at high oral doses. International haematology societies (BSH 2014) recognise both routes.

In pernicious anaemia with neurological features, parenteral administration is preferred in the first 2–4 weeks for rapid repletion.

Sources

Chronic fatigue without a clinical diagnosis

Not recommended

In patients without laboratory-confirmed deficiency, B12 therapy for chronic fatigue lacks evidence. The 2013 BMJ systematic review found no clinically meaningful effect on energy or quality of life in people with normal B12 levels. International guidelines do not support “energy” B12 injections – a common private-practice service without scientific basis.

Sources

NEJM: Vitamin B12 Deficiency – clinical review (2013)

Practical notes

Timing and administration

Oral forms are taken regardless of meals. Sublingual forms are placed under the tongue until dissolved – additional benefit over swallowing in people with low gastric acidity or atrophic gastritis is not proven, as intestinal absorption at high doses is comparable.

Dose titration

Deficiency treatment: 1,000–2,000 µg daily orally or 1,000 µg intramuscularly on schedule (pernicious anaemia). Prophylaxis in vegans and metformin users: 500–1,000 µg daily 1–2 times weekly or 250 µg daily. Physiological adult daily requirement is 2.4 µg – hundreds of times less than therapeutic doses because oral absorption is low (1–2% without intrinsic factor).

Monitoring

4–8 weeks after starting therapy, check complete blood count (haemoglobin, MCV) and serum B12. Haemoglobin normalises over 4–8 weeks, MCV over up to 3 months. Neurological symptoms improve more slowly – over 6–12 months. Homocysteine and methylmalonic acid are more sensitive deficiency markers, used in unclear cases.

Special situations

Patients on metformin for more than 4 years, with atrophic gastritis, after gastrectomy or ileal resection, with chronic pancreatitis, or with small intestinal bacterial overgrowth are at high risk. Vegans without supplementation inevitably develop deficiency within 3–5 years. In adults over 65, deficiency prevalence reaches 20%.

Common myths

Myth: “B12 injections give energy”. Fact: in patients with normal B12, there is no effect on energy or performance. Popular vitamin cocktails and B12 drips for healthy people lack evidence and carry injection-related risks.

Myth: “methylcobalamin is better than cyanocobalamin”. Fact: both forms are effective for deficiency correction. Methylcobalamin is more expensive, and direct RCTs showing superiority are absent. Cyanocobalamin converts to active coenzyme forms in the body.

Myth: “oral treatment doesn't work in pernicious anaemia”. Fact: the 2018 Cochrane review showed comparable efficacy of high-dose oral and parenteral routes. In neurological involvement and severe anaemia, injections are preferred in the first 2–4 weeks, then switching to tablets is possible.

Drug–nutrient interactions

Folic acid (vitamin B9)

Concurrent B12 and folate therapy is required in megaloblastic anaemia of unclear aetiology. Isolated high-dose folic acid in unrecognised B12 deficiency masks macrocytosis but does not stop neurological degeneration. B12 deficiency must be excluded before prescribing folate.

Source: BSH: Guidelines for the diagnosis and treatment of cobalamin and folate disorders (2014)

Safety

Contraindications

Hypersensitivity to cyanocobalamin or other components
Polycythaemia vera, erythrocytosis
Thromboembolic disease (relative)

Serious adverse effects

Anaphylactic reactions (very rare, more common with repeated injections)

Common adverse effects

Injection site pain
Allergic reactions (urticaria, pruritus)

Uncommon adverse effects

Headache, dizziness
Dyspepsia
Acneiform skin eruptions with high-dose parenteral use

PregnancyFDA A

Safe at recommended doses. Pregnant vegans and women with confirmed deficiency require supplementation – maternal B12 deficiency increases the risk of neural tube defects and developmental delay in the foetus.

Breastfeeding

Transfers into breast milk. Maternal B12 deficiency (especially in vegan mothers) causes infant deficiency during breastfeeding – maternal supplementation is required.