Active coenzyme form of vitamin B12
Brand names: Methyl B12, Methylcobalamin
Updated · Methodology
First line
Methylcobalamin corrects B12-deficiency megaloblastic anaemia. In newly diagnosed megaloblastic anaemia 2014 recommends measuring both folate and B12 in parallel before starting therapy: correcting only one when both are deficient gives incomplete response and allows progression. Dose in marked anaemia: 1000 μg/day orally or IM, tapering to weekly then monthly.
Sources
ICD-10: D53.1 · ICD-11: 3A01
First line
Methylcobalamin is one of the forms for treating confirmed vitamin B12 deficiency in patients with pernicious anaemia, after gastric or ileal resection, in vegetarians and vegans without supplementation, and during long-term metformin or PPI therapy. 2024 and 2014 regard hydroxocobalamin (the European form of choice) and cyanocobalamin as equivalent; methylcobalamin is considered an option for oral replacement. In severe deficiency with neurological symptoms, parenteral hydroxocobalamin is started first and oral methylcobalamin used for maintenance.
Sources
ICD-10: E53.8 · ICD-11: 5B5F
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Methylcobalamin is an active form of vitamin B12. For chronic fatigue it is often marketed as a supplement for energy and alertness. In people without a B12 deficiency, no convincing benefit for this condition has been shown, and there is no reliable evidence for such use. When fatigue persists, it makes sense to look for the cause with a doctor: check sleep, thyroid, iron and B12 levels, rule out depression and other conditions, and treat whatever is found. Methylcobalamin is harmless in this role, but it should not be taken instead of treatment with proven benefit, or you may miss the care you actually need.
ICD-10: R53 · ICD-11: MG22
Not recommended
Methylcobalamin has become the favoured form in the biohacking segment: marketed as «the only correct B12 form» promising relief of fatigue, anxiety, depression and cognitive decline in MTHFR-polymorphism carriers. In most people with MTHFR polymorphism without confirmed B12 deficiency, it offers no benefit over placebo or regular cyanocobalamin. 2024 and 2014 do not single out methylcobalamin as preferred. If it was prescribed after MTHFR testing with normal B12 and homocysteine, consider seeking a second opinion.
Methylcobalamin is one of two B12 coenzyme forms (the other is adenosylcobalamin). It is the cofactor for methionine synthase, converting homocysteine to methionine and linking to folate metabolism. Cyanocobalamin is also converted in the body to methylcobalamin and adenosylcobalamin, so the biological end effect is the same. In smokers methylcobalamin has a theoretical advantage (cyanocobalamin is consumed inactivating tobacco cyanide), but clinically meaningful differences for the general indication are not confirmed in RCTs.
Methylcobalamin is required in pregnancy; daily intake 2.6 μg. AEMPS allows therapeutic doses during pregnancy in confirmed deficiency.
Compatible (Hale L1). Methylcobalamin enters milk at physiological concentrations. Vegan and vegetarian lactating women without supplementation should receive 5.5 μg/day.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
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Methylcobalamin is evaluated for the following indications with varying evidence strength: Vitamin B12 (cobalamin) deficiency (evidence tier A), Megaloblastic anaemia (evidence tier A), MTHFR polymorphism and methylation (supplement marketing) (evidence tier D). See the full indication matrix with dosing and citations above on this page.
Common side effects of Methylcobalamin (≥ 1 in 100): Nausea, Headache, Pinkish skin colouration at injection site. See the Safety section for uncommon and serious reactions.
Methylcobalamin is required in pregnancy; daily intake 2.6 μg. AEMPS allows therapeutic doses during pregnancy in confirmed deficiency.
Compatible (Hale L1). Methylcobalamin enters milk at physiological concentrations. Vegan and vegetarian lactating women without supplementation should receive 5.5 μg/day.
Methylcobalamin is contraindicated in: Hypersensitivity to cobalamins; Leber hereditary optic neuropathy – risk of accelerated progression. Full list in the Safety section.
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Cyanocobalamin, Folic acid, Hydroxocobalamin, Iron oral (salts: sulfate, bisglycinate, fumarate, gluconate, polymaltose; heme iron polypeptide, lactoferrin), Levomefolate (L-methylfolate, 5-MTHF), Vitamin B12 (cobalamin)