Cyanocobalamin

Vitamins. Haemopoietic stimulants

ATC code: B03BA01

Brand names – drugs: Cyanokit

Brand names – supplements: Jarrow Formulas Methyl B-12, Thorne Methylcobalamin, Solgar Sublingual MethylcobalaminSupplements are not tested in clinical trials and are not registered as medications.

Updated 19 Jun 2026 · Methodology

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

ICD-10: E53.8 · ICD-11: 5B5F

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 ( 2014) recognise both routes.

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

Sources

ICD-10: D51 · ICD-11: 3A01

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

Chronic fatigue

Not recommended

Cyanocobalamin is a form of vitamin B12, often promoted as a remedy for fatigue and an energy boost, including for people without a B12 deficiency. In patients with normal B12 levels, no convincing benefit for chronic fatigue has been shown – there is no evidence base for this use. When fatigue persists, the useful step is to look for the cause: check sleep, thyroid, iron and B12 levels, and rule out depression or chronic illness before choosing treatment. B12 makes sense when a deficiency is confirmed, but it does not replace addressing the actual cause of the fatigue.

Sources

NEJM: Vitamin B12 Deficiency – clinical review (2013)

ICD-10: R53 · ICD-11: MG22

How to read tiers A–F

AStrong evidence – first or second line in international guidelines
BRecommended in selected cases
CStudy data contradict each other
DBenefit not proven, no documented harm
FDocumented harm, or risk without benefit

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.

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

Pregnancy: can you take Cyanocobalamin?

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: can you take Cyanocobalamin?

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

Calculate RID Full profile on NIH LactMed ↗

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

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

Folate

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)

Drug–drug interactions

4 pairs found. Sorted from critical to minor.

ModerateEsomeprazoleDrugs for peptic ulcer and GORD. Proton pump inhibitors

Mechanism

Esomeprazole suppresses gastric acidity, reducing release of B12 from food (which requires HCl and pepsin). With over 2 years of therapy, B12 deficiency risk is reported.

Symptoms

Fatigue, pallor, paraesthesias in hands and feet, gait instability, memory decline. Develops over 2–4 years of unrecognised therapy.

Management

On long-term PPIs (over 2 years), check B12 yearly. Oral cyanocobalamin tablets or drops can be given regardless of acidity (passive diffusion absorption at high doses). Alternative: H2-blockers (famotidine) for short-term acid suppression.

Sources

PubMed: Metformin use and vitamin B12 deficiency: a systematic review and meta-analysis (2020)

Pair details →Esomeprazole →

ModerateMetforminBiguanides. Oral antihyperglycemic agents

Mechanism

Metformin suppresses calcium-dependent absorption of the B12-intrinsic factor complex in the terminal ileum. With over 4 years of therapy, clinically significant B12 deficiency is reported in 10–30% of patients.

Symptoms

Fatigue, pallor, paraesthesias in hands and feet, gait instability, memory decline. Develops over 2–4 years of unrecognised therapy.

Management

On long-term metformin, check B12 yearly. If it falls below 200 pg/mL, give cyanocobalamin 500–1000 mcg/day orally or 1000 mcg/week intramuscularly (in significant neuropathy). Supplementation does not cancel the metformin indication.

Sources

Pair details →Metformin →

ModeratePantoprazoleProton pump inhibitors

Mechanism

Pantoprazole reduces gastric acidity and B12 release from food. With long-term therapy, B12 deficiency risk is reported, similar to other PPIs.

Symptoms

Fatigue, pallor, paraesthesias in hands and feet, gait instability, memory decline. Develops over 2–4 years of unrecognised therapy.

Management

On long-term pantoprazole (over 2 years), check B12 yearly. Cyanocobalamin can be given regardless of acidity (passive diffusion absorption at high doses). For sustained acid suppression, consider dose reduction or periodic breaks.

Sources

PubMed: Metformin use and vitamin B12 deficiency: a systematic review and meta-analysis (2020)

Pair details →Pantoprazole →

MinorOmeprazoleProton pump inhibitors

Mechanism

Proton pump inhibitors suppress gastric acidity and reduce B12 release from food (which requires HCl and pepsin). For short courses (up to 8 weeks), clinically insignificant. With long-term therapy (over 2 years), B12 deficiency risk is reported.

Symptoms

On long-term therapy: fatigue, pallor, paraesthesias in hands and feet, gait instability, memory decline.

Management

For short omeprazole courses, no adjustment needed. On long-term therapy (over 2 years), check B12 yearly. If it falls below 200 pg/mL, give cyanocobalamin 500–1000 mcg/day orally — passive diffusion absorption at high doses works regardless of acidity.

Sources

Pair details →Omeprazole →

Label mentions12 mentions

Verbatim lines from the interaction sections, in the language of the label

From this drug’s label

aminoglucósidosclass named in the label
«La absorción de vitamina B12 a nivel del tracto gastrointestinal puede verse disminuida por antibióticos aminoglucósidos como neomicina, la colchicina, los antiulcerosos antihistamínicos H-2 y los…»
AEMPS, section 4.5 · Open on CIMA
antiepilépticosclass named in the label
«La absorción de vitamina B12 a nivel del tracto gastrointestinal puede verse disminuida por antibióticos aminoglucósidos como neomicina, la colchicina, los antiulcerosos antihistamínicos H-2 y los…»
AEMPS, section 4.5 · Open on CIMA
antihistamínicosclass named in the label
«La absorción de vitamina B12 a nivel del tracto gastrointestinal puede verse disminuida por antibióticos aminoglucósidos como neomicina, la colchicina, los antiulcerosos antihistamínicos H-2 y los…»
AEMPS, section 4.5 · Open on CIMA
Ascorbic acid
«Suplementos de ácido ascórbico: pueden disminuir la absorción de vitamina B12. Para disminuir este efecto se sugiere que el ácido ascórbico se tome 2 o más horas después de los alimentos o de…»
AEMPS, section 4.5 · Open on CIMA
Chloramphenicol
«Cloranfenicol: puede retrasar, interrumpir o atenuar la respuesta de la vitamina B12 sobre la eritropoyesis.»
AEMPS, section 4.5 · Open on CIMA
Colchicine
«La absorción de vitamina B12 a nivel del tracto gastrointestinal puede verse disminuida por antibióticos aminoglucósidos como neomicina, la colchicina, los antiulcerosos antihistamínicos H-2 y los…»
AEMPS, section 4.5 · Open on CIMA
inhibidores de la bomba de protonesclass named in the label
«La absorción de vitamina B12 a nivel del tracto gastrointestinal puede verse disminuida por antibióticos aminoglucósidos como neomicina, la colchicina, los antiulcerosos antihistamínicos H-2 y los…»
AEMPS, section 4.5 · Open on CIMA
Metformin
«La absorción de vitamina B12 a nivel del tracto gastrointestinal puede verse disminuida por antibióticos aminoglucósidos como neomicina, la colchicina, los antiulcerosos antihistamínicos H-2 y los…»
AEMPS, section 4.5 · Open on CIMA
Omeprazole
«La absorción de vitamina B12 a nivel del tracto gastrointestinal puede verse disminuida por antibióticos aminoglucósidos como neomicina, la colchicina, los antiulcerosos antihistamínicos H-2 y los…»
AEMPS, section 4.5 · Open on CIMA
Phenobarbital
«La absorción de vitamina B12 a nivel del tracto gastrointestinal puede verse disminuida por antibióticos aminoglucósidos como neomicina, la colchicina, los antiulcerosos antihistamínicos H-2 y los…»
AEMPS, section 4.5 · Open on CIMA
Phenytoin
«La absorción de vitamina B12 a nivel del tracto gastrointestinal puede verse disminuida por antibióticos aminoglucósidos como neomicina, la colchicina, los antiulcerosos antihistamínicos H-2 y los…»
AEMPS, section 4.5 · Open on CIMA

From other drugs’ labels

ModerateAscorbic acid
«Cianocobalamina (vitamina B12): el ácido ascórbico en grandes dosis podría reducir las cantidades de cianocobalamina disponibles en suero y reservas (dosis elevadas de ácido ascórbico pueden destruir…»
AEMPS, section 4.5 · Open on CIMA

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Frequently asked

What is Cyanocobalamin used for?

Cyanocobalamin is evaluated for the following indications with varying evidence strength: Vitamin B12 deficiency anaemia (pernicious anaemia) (evidence tier A), B12 deficiency with neurological symptoms (evidence tier A), Chronic fatigue (evidence tier D). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Cyanocobalamin?

Common side effects of Cyanocobalamin (≥ 1 in 100): Injection site pain, Allergic reactions (urticaria, pruritus). See the Safety section for uncommon and serious reactions.

Is Cyanocobalamin safe during pregnancy?

Is Cyanocobalamin compatible with breastfeeding?

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

Who should not take Cyanocobalamin?

Cyanocobalamin is contraindicated in: Hypersensitivity to cyanocobalamin or other components; Polycythaemia vera, erythrocytosis; Thromboembolic disease (relative). Full list in the Safety section.

“B12 injections give energy”

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.

“methylcobalamin is better than cyanocobalamin”

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.

“oral treatment doesn't work in pernicious anaemia”

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.

Official sources

Direct links to regulator labels. Open in a new tab.

AEMPS / CIMALabel dated 04/28/2021
FDA / DailyMedLabel dated 05/13/2026
GRLS

Other drugs in this group

Folic acid, Hydroxocobalamin, Iron oral (salts: sulfate, bisglycinate, fumarate, gluconate, polymaltose; heme iron polypeptide, lactoferrin), Methylcobalamin, Levomefolate (L-methylfolate, 5-MTHF), Vitamin B12 (cobalamin)