Vitamin B12 (cyanocobalamin): research, side effects and doses in studies

In short

Cyanocobalamin is the synthetic form of vitamin B12, not a peptide. In the treatment of deficiency, cyanocobalamin by mouth and injected into a muscle raised B12 levels in randomised trials [5]A, but without a clear deficiency B12 supplements did not improve memory or mood [10]A. Finland has a cyanocobalamin product taken by mouth with a marketing authorisation [23]regulator.

What is vitamin B12 (cyanocobalamin)?

Vitamin B12, or cobalamin, is a B vitamin with an important role in cell metabolism, especially in making DNA, in methylation and in mitochondrial metabolism [1]. It is a vitamin, not a peptide. About peptides in general: What are peptides?.

Vitamin B12 exists in several chemical forms. Methylcobalamin, adenosylcobalamin and hydroxocobalamin are the same forms that occur in the human body and in animal foods. Cyanocobalamin is a synthetic B12 compound used to fortify foods and in some supplements. It occurs in human tissues only in small amounts, for example because of cyanide exposure from smoking [3].

In the diet, vitamin B12 comes from animal foods such as eggs, milk, red meat, poultry, fish and shellfish [18]. This page is about cyanocobalamin. Hydroxocobalamin is mentioned only where a source is about it. All substances: Peptides A-Z.

Evidence at a glance

Each cell gives the type of study and the source. The letter is the level of evidence, not the result.

Claimed effectHumansAnimalsCells
Correcting B12 levels in deficiencySimilar effect by mouth and into a muscle in three randomised trials, low-quality evidence [5]A--
Correcting blood and nerve findings in deficiencyCorrected equally fast by mouth and into a muscle, 33 patients [6]A--
Memory and mood without a clear deficiencyNo effect, 16 randomised trials [10]A--
Tiredness and staminaOnly one study of tiredness [10]A; vocal fatigue in singers did not differ from placebo [11]A--
Heart attacks and mortality (B-vitamin combinations)No difference from placebo; slightly fewer strokes, 15 trials [12]A--
PregnancyMaternal B12 deficiency possibly less common, no certainty on pregnancy outcomes [22]A--
AcneOne of ten healthy people developed acne a week after supplementation [17]B-The acne bacterium produced more porphyrins in cultures [17]D
SafetyFew and mild side effects in treatment trials [8]A; a B-vitamin combination worsened kidney function in kidney disease [13]A--

"-" = no such study is known.

What is cyanocobalamin used for?

Cyanocobalamin is used to treat vitamin B12 deficiency, either by mouth or injected into a muscle [5]A. In Finland, the authorised product that contains cyanocobalamin alone is taken by mouth [23]regulator.

Deficiency can come from too little intake in the diet (for example vegetarians and vegans, older people, pregnant people and people with alcohol use disorder), from reduced absorption (for example atrophic gastritis, malabsorption and gastrointestinal surgery) or from medicines such as acid-suppressing drugs and metformin [18]. Mild deficiency without symptoms affects 2.5-26 per cent of the population depending on the definition, but its significance is unclear [1].

Injections without a deficiency. According to the singers' study, about a third of singers and other voice professionals report a benefit from B12 injections given without a diagnosed deficiency, for example for reduced stamina and vocal fatigue. When this was tested against a placebo injection, no difference was found [11]A.

How does cyanocobalamin work?

Cyanocobalamin corrects a lack of vitamin B12. According to a review, the body converts all B12 forms, cyanocobalamin included, into the same core cobalamin molecule. From it, cells make the active forms methylcobalamin and adenosylcobalamin, and their ratio does not depend on which form was taken [3].

Deficiency is measured by total B12 and holotranscobalamin (active B12) in the blood, which fall, and by homocysteine and methylmalonic acid, which rise [1]. In treatment trials, cyanocobalamin corrected these values and the blood and nerve findings caused by the deficiency [6]A.

Laughing gas (nitrous oxide) oxidises vitamin B12 so that it no longer works as a helper for enzymes. According to a systematic review of case series, this mechanism plays a major role in the neurological disorders of nitrous oxide users [21]B.

Has cyanocobalamin been studied in humans?

Yes. Cyanocobalamin has been studied in randomised trials for the treatment of deficiency, and B12 supplements have also been studied in people without a clear deficiency [5]A [10]A.

Treating deficiency: tablet or injection

People without a clear deficiency

Pregnancy

A Cochrane review included five trials and 984 pregnant women from low- and middle-income countries. B12 supplements may have reduced maternal B12 deficiency (25.9% vs 67.9%), but the evidence is very uncertain. No clear effect was found on anaemia, preterm birth or low birth weight [22]A.

Who studies cyanocobalamin?

Tablets and injections have been compared by, among others, a US hospital group [6]A and 22 primary health care centres in Madrid [8]A; Wageningen University in the Netherlands compared different doses by mouth [7]A. The lead author of the Cochrane review works at a university in Beijing [5]A. The large trials of B-vitamin combinations were done in Canada and Norway [13]A [14]A.

One of the two authors of the review on differences between B12 forms states that he is also the chief medical officer of a company [3]. This is worth knowing when you read the review's conclusion that natural forms are better.

Who wrote this page: the editorial team

This page was written by the Molecular Recovery editorial team. The draft was made with the help of AI, and the claims were checked against the sources (AI policy). The page has not been medically reviewed. How we work: About us.

How is cyanocobalamin absorbed?

Absorption and elimination are described by pharmacokinetics. Vitamin B12 from food is absorbed in the last part of the small intestine almost entirely with the help of intrinsic factor, made in the stomach. About one per cent is absorbed passively without intrinsic factor, and this route also works in pernicious anaemia, where no intrinsic factor is made [2].

This is why studies have used large amounts by mouth. According to a review on pernicious anaemia, 1,000 µg a day by mouth was enough to correct B12 levels [2]. In mild deficiency, 647-1,032 µg a day was linked to 80-90% of the largest estimated fall in methylmalonic acid; lower doses lowered it less [7]A.

At small doses (1.5-9 µg on two days), cyanocobalamin raised active B12 (holotranscobalamin) more than twice as much as the same amount of hydroxocobalamin. The study included 101 adults with low or normal B12 status [4]B.

In the OB12 trial, fewer people in the tablet group than in the injection group still had a normal level at one year. After week eight, the tablet was taken once a week [8]A. We did not find the half-life of cyanocobalamin in our sources.

What are the side effects of cyanocobalamin?

In deficiency treatment trials, side effects were few and mild. Large trials of B-vitamin combinations did, however, find harms in certain patient groups [8]A [13]A [14]A.

Treatment trials

According to the Cochrane review, very low-quality evidence suggests the tablet is as safe as the injection. In one trial, 2 of 30 participants in the tablet group left early because of side effects [5]A. The OB12 trial reported 11 adverse events, none serious: 5 in the tablet group and 6 in the injection group. One person in the tablet group stopped because of hives, and two in the injection group because of facial redness and itching [8]A.

Acne

In a study in which ten healthy people took B12 supplements, one developed acne a week later [17]B. In bacterial cultures, B12 increased the production of porphyrins by the acne bacterium, which can increase inflammation [17]D. According to the researchers, this offers one explanation for the observation that some people get acne from B12 supplements [17]B.

Kidney disease and B-vitamin combinations

In the Canadian DIVINe trial, 238 people with diabetic kidney disease received either folic acid, vitamin B6 and vitamin B12, or placebo. At three years, kidney filtration had fallen more in the B-vitamin group (16.5 vs 10.7 mL/min/1.73 m²), and the combination of heart attack, stroke, revascularisation or death was about twice as common [13]A. One of the trial's authors later suggested in a review that the cyanide in cyanocobalamin may be harmful when kidney function is impaired [15]. This is an interpretation, not a separately tested result.

Cancer

In Norway, in the combined follow-up of two randomised trials with 6,837 patients with coronary heart disease, 10.0 per cent of those given folic acid and vitamin B12 were diagnosed with cancer, against 8.4 per cent of the others. Cancer deaths and all deaths were also more common. The difference came mainly from lung cancer [14]A. Because B12 was given together with folic acid, the trial does not show the share of B12.

In a US cohort of 77,118 people, lung cancer was 30-40 per cent more common in men who used single B12 supplements. At the highest level of use (over 55 µg a day), the risk was almost doubled. There was no link in women [16]B. A cohort study cannot show cause and effect.

High B12 in a blood test

According to a review, high blood B12 has been linked to kidney failure, liver disease, alcohol use disorder and several cancers [18]. A link alone does not tell which causes which. More: Side effects and safety.

Interactions and who lacks data

We did not find drug interactions of cyanocobalamin itself in our sources. Several medicines and substances do, however, reduce the absorption or function of vitamin B12.

Studies in pregnancy come mainly from low- and middle-income countries [22]A. This page does not cover children.

What speaks against it and what is unknown

B12 supplements help when a deficiency has been diagnosed. Without a deficiency, no benefit has been shown, and large combination trials have also found harms [10]A [13]A [14]A.

Counter-evidence

What the evidence does not support

It is not known whether long-term use of high cyanocobalamin doses is harmless in people without a deficiency. Most of the harm data come from combination products, in which the share of B12 cannot be separated [13]A [14]A, and from cohort studies [16]B.

Cyanocobalamin doses in studies

Finland has an authorised cyanocobalamin product taken by mouth [23]regulator, but this page does not show its approved dosing. Below are the amounts used in studies. They are not recommendations.

Amounts used in studies
StudyWhoDose and routeDuration
Kuzminski (1998)18 evaluable patients with deficiency2 mg by mouth every day120 days [6]A
Kuzminski (1998)15 evaluable patients with deficiency1 mg into a muscle on days 1, 3, 7, 10, 14, 21, 30, 60 and 9090 days [6]A
Eussen (2005)120 older people, mild deficiency2.5, 100, 250, 500 or 1,000 µg by mouth every day16 weeks [7]A
OB12 (2020), tablet140 people aged 65 or over, deficiency1 mg by mouth every day in weeks 1-8, then once a week52 weeks [8]A
OB12 (2020), injection143 people aged 65 or over, deficiency1 mg into a muscle every other day in weeks 1-2, once a week in weeks 3-8, then once a month52 weeks [8]A
Singers (2021)20 singers without deficiency1,000 µg into a muscle once (placebo in the other period)one week of follow-up [11]A

What the numbers do not tell you. The amounts concern diagnosed deficiency, and their effect was followed with blood tests [6, 7, 8]A. Without a deficiency, the injection did not differ from placebo [11]A. More: Vitamin B12 doses in studies. The calculator page explains why the vial calculator is not used for this substance. All dose pages: Doses in studies.

Cyanocobalamin vs methylcobalamin and hydroxocobalamin: what is the difference?

All forms have been used to correct B12 status, and according to a review the body converts them into the same core molecule from which cells make the active forms [3].

B12 in combination products

Cyanocobalamin is also found in combination products. Finland's marketing authorisation data list products taken by mouth in which it is combined with folic acid and pyridoxine (B6) or with thiamine (B1) and pyridoxine, as well as multivitamin products given into a vein [23]regulator.

Results with combinations do not show the effect of B12 itself. Homocysteine-lowering B-vitamin combinations did not reduce heart attacks or deaths [12]A, a combination was harmful in diabetic kidney disease [13]A, and the combination of folic acid and B12 increased cancers in Norwegian heart patients [14]A. B12 alone or in combination had no effect on memory or mood [10]A.

Other non-peptides on this site: NAD+ and NMN.

Is cyanocobalamin legal in Finland?

Yes. Finland has an authorised cyanocobalamin product taken by mouth, B12-vitamiini ratiopharm (cyanocobalamin) [23]regulator.

This is not legal advice. Disclaimer.

Is vitamin B12 doping?

No. The Finnish-language 2026 list of the Finnish Center for Integrity in Sports (SUEK) states under S2.1.2 that cyanocobalamin (vitamin B12) is not prohibited [25]regulator.

The note sits in the same section as cobalt, a HIF activator prohibited on the WADA list [26]regulator. WADA also prohibits, whatever the substance, intravenous infusions and injections of more than 100 mL in total per 12 hours, except in hospital treatment, surgery and clinical investigations (M2.2). An injection into a muscle is not covered by this section [26]regulator.

How is the quality of a B12 product judged?

The B12 content of a medicine and its permitted variation are part of the marketing authorisation documents and are controlled by the medicines agency [27]. In published analyses, the B12 content of food supplements and fortified foods was mostly 100-150 per cent of the amount on the label, because manufacturers add an overage to allow for breakdown [27].

In the analyses collected by the review, 87 per cent of food supplements were within the permitted limits, but 11 per cent contained more than 150 per cent of the declared B12. In the EU guidance, the permitted variation for vitamins in food supplements is 80-150 per cent [27].

Cyanocobalamin is regarded as the most stable form of vitamin B12 and is still the form most used in supplements. In an experiment described in the review, methylcobalamin and adenosylcobalamin broke down in solution within seconds under UVA light [27]. On reading a certificate of analysis in general: How to read a COA and check a test result.

The future: what comes next?

The ClinicalTrials.gov registry lists ongoing trials that compare forms and routes of vitamin B12. Registry records are not peer-reviewed [28]E, not peer-reviewed [29]E, not peer-reviewed.

FAQ

Is a B12 tablet as effective as an injection?

In the treatment of deficiency, a large dose by mouth corrected blood levels as well as injections in trials, but the quality of the evidence is low [5]A. In a one-year trial, the tablet could not be shown to be at least as good when it was taken once a week after week eight [8]A.

Does B12 help tiredness or memory without a deficiency?

Not shown. There was no effect on memory or mood in 16 randomised trials, and there is only one study of tiredness [10]A. A B12 injection in singers did not differ from placebo [11]A.

What is the difference between cyanocobalamin and methylcobalamin?

The body converts both into the same core molecule from which cells make the active forms [3]. At small doses, cyanocobalamin raised active B12 more than hydroxocobalamin [4]B.

Can B12 supplements cause harm?

In treatment trials, side effects were few and mild [8]A. A B-vitamin combination was harmful in diabetic kidney disease [13]A, and some people get acne from B12 supplements [17]B.

Who is more likely to become B12 deficient?

For example older people, vegetarians and vegans, and people with malabsorption or who take metformin or acid-suppressing drugs [18] [19, 20]B.

What happens if B12 treatment is stopped?

Stopping has not been studied as a question of its own in our sources. In pernicious anaemia, treatment is lifelong according to a review [2]. In the OB12 trial, fewer people still had a normal level at one year when the tablet was taken only once a week after week eight [8]A.

Is vitamin B12 banned in sport?

No. According to SUEK's list, cyanocobalamin is not prohibited [25]regulator.

What experiences are there with B12 injections?

User accounts of vitamin B12 have not been compiled on this site. According to a study, about a third of singers report a benefit from injections, but a placebo test found no difference [11]A.

Read the research yourself: sources

Every source opens the original publication or the regulator's page. The level shows what the source itself reports.

  1. Green R, Allen LH, Bjørke-Monsen AL, et al. Vitamin B12 deficiency. Nat Rev Dis Primers. 2017;3:17040. PMID 28660890 (review)
  2. Chan CQ, Low LL, Lee KH. Oral Vitamin B12 Replacement for the Treatment of Pernicious Anemia. Front Med (Lausanne). 2016;3:38. PMID 27602354 (review)
  3. Paul C, Brady DM. Comparative Bioavailability and Utilization of Particular Forms of B12 Supplements With Potential to Mitigate B12-related Genetic Polymorphisms. Integr Med (Encinitas). 2017;16(1):42-49. PMID 28223907 (review)
  4. Greibe E, Mahalle N, Bhide V, et al. Increase in circulating holotranscobalamin after oral administration of cyanocobalamin or hydroxocobalamin in healthy adults with low and normal cobalamin status. Eur J Nutr. 2018;57(8):2847-2855. PMID 29038891 B
  5. Wang H, Li L, Qin LL, et al. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane Database Syst Rev. 2018;3(3):CD004655. PMID 29543316 A
  6. Kuzminski AM, Del Giacco EJ, Allen RH, et al. Effective treatment of cobalamin deficiency with oral cobalamin. Blood. 1998;92(4):1191-1198. PMID 9694707 A
  7. Eussen SJ, de Groot LC, Clarke R, et al. Oral cyanocobalamin supplementation in older people with vitamin B12 deficiency: a dose-finding trial. Arch Intern Med. 2005;165(10):1167-1172. PMID 15911731 A
  8. Sanz-Cuesta T, Escortell-Mayor E, Cura-Gonzalez I, et al. Oral versus intramuscular administration of vitamin B12 for vitamin B12 deficiency in primary care: a pragmatic, randomised, non-inferiority clinical trial (OB12). BMJ Open. 2020;10(8):e033687. PMID 32819927 A
  9. Abdelwahab OA, Abdelaziz A, Diab S, et al. Efficacy of different routes of vitamin B12 supplementation for the treatment of patients with vitamin B12 deficiency: A systematic review and network meta-analysis. Ir J Med Sci. 2024;193(3):1621-1639. PMID 38231320 (review)
  10. Markun S, Gravestock I, Jäger L, et al. Effects of Vitamin B12 Supplementation on Cognitive Function, Depressive Symptoms, and Fatigue: A Systematic Review, Meta-Analysis, and Meta-Regression. Nutrients. 2021;13(3):923. PMID 33809274 A
  11. Shoffel-Havakuk H, Lava CX, Reuven Y, et al. Effect of Vitamin B12 Injection on the Vocal Performance of Professional Singers: A Randomized, Double-blind, Placebo-Controlled, Crossover Trial. JAMA Otolaryngol Head Neck Surg. 2021;147(1):9-15. PMID 33180098 A
  12. Martí-Carvajal AJ, Solà I, Lathyris D, Dayer M. Homocysteine-lowering interventions for preventing cardiovascular events. Cochrane Database Syst Rev. 2017;8(8):CD006612. PMID 28816346 A
  13. House AA, Eliasziw M, Cattran DC, et al. Effect of B-vitamin therapy on progression of diabetic nephropathy: a randomized controlled trial. JAMA. 2010;303(16):1603-1609. PMID 20424250 A
  14. Ebbing M, Bønaa KH, Nygård O, et al. Cancer incidence and mortality after treatment with folic acid and vitamin B12. JAMA. 2009;302(19):2119-2126. PMID 19920236 A
  15. Spence JD. Homocysteine lowering for stroke prevention: Unravelling the complexity of the evidence. Int J Stroke. 2016;11(7):744-747. PMID 27462097 (review)
  16. Brasky TM, White E, Chen CL. Long-Term, Supplemental, One-Carbon Metabolism-Related Vitamin B Use in Relation to Lung Cancer Risk in the Vitamins and Lifestyle (VITAL) Cohort. J Clin Oncol. 2017;35(30):3440-3448. PMID 28829668 B
  17. Kang D, Shi B, Erfe MC, Craft N, Li H. Vitamin B12 modulates the transcriptome of the skin microbiota in acne pathogenesis. Sci Transl Med. 2015;7(293):293ra103. PMID 26109103 B
  18. Pardo-Cabello AJ, Manzano-Gamero V, Puche-Cañas E. Vitamin B12: For more than just the treatment of megaloblastic anemia? Rev Clin Esp (Barc). 2023;223(2):114-119. PMID 36669740 (review)
  19. Aroda VR, Edelstein SL, Goldberg RB, et al. Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab. 2016;101(4):1754-1761. PMID 26900641 B
  20. Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA. 2013;310(22):2435-2442. PMID 24327038 B
  21. Ménétrier T, Denimal D. Vitamin B12 Status in Recreational Users of Nitrous Oxide: A Systematic Review Focusing on the Prevalence of Laboratory Abnormalities. Antioxidants (Basel). 2023;12(6):1191. PMID 37371921 B
  22. Finkelstein JL, Fothergill A, Venkatramanan S, et al. Vitamin B12 supplementation during pregnancy for maternal and child health outcomes. Cochrane Database Syst Rev. 2024;1(1):CD013823. PMID 38189492 A
  23. European Medicines Agency. Article 57 product data (EMA/518502/2018, data as of 9 Oct 2026): Finland lists B12-Vitamiini Ratiopharm (cyanocobalamin, oral use) and, for injection into a muscle, Cohemin and Hydroxocobalamin G.L. Pharma (hydroxocobalamin). EMA regulator
  24. Finland. Lääkeluettelo (Fimea medicines list), 230/2025: section 3 point 3 (vitamin and mineral preparations) and annex 1 ("Hydroksokobalamiini"; cyanocobalamin is not listed). Finlex regulator
  25. SUEK (Finnish Center for Integrity in Sports). Doping substance groups and substances 2026, based on the WADA list, section S2.1.2: "Syanokobalamiini (B12-vitamiini) ei ole kielletty" (cyanocobalamin is not prohibited). SUEK regulator
  26. World Anti-Doping Agency. 2026 Prohibited List, section S2.1.2 (hypoxia-inducible factor (HIF) activating agents, e.g. cobalt) and M2.2 (intravenous infusions and/or injections of more than a total of 100 mL per 12-hour period, except in hospital treatment, surgery or clinical diagnostic investigations). WADA regulator
  27. Temova Rakuša Ž, Roškar R, Hickey N, Geremia S. Vitamin B12 in Foods, Food Supplements, and Medicines: A Review of Its Role and Properties with a Focus on Its Stability. Molecules. 2022;28(1):240. PMID 36615431 (review)
  28. ClinicalTrials.gov. NCT05785585: Effect of Methylcobalamin and Cyanocobalamin Consumption on Vitamin B12 Nutritional Status in Vegetarians With Marginal Vitamin B12 Deficiency (sponsor Fundació Eurecat, Spain; randomised, placebo-controlled; 54 participants planned; status recruiting). Registry record, not peer-reviewed. ClinicalTrials.gov E, not peer-reviewed
  29. ClinicalTrials.gov. NCT06966856: Sublingual Versus Oral Vitamin B12 for Acute Hypovitaminosis B12 Secondary to Proton Pump Inhibitors: A Prospective Randomized Study (sponsor Tanta University; phase 3; 23 participants planned; status not yet recruiting, start planned Dec 2026). Registry record, not peer-reviewed. ClinicalTrials.gov E, not peer-reviewed

Research sources read on 15 Oct 2026. Regulatory and prohibited-list sources checked on 15 Oct 2026 (EMA Article 57 data of 9 Oct 2026).

Evidence levels: A = randomised human trial or meta-analysis · B = observational human study or case series · C = animal study · D = cell or laboratory study · E = not peer-reviewed · regulator = a regulator's assessment or decision, not research evidence. The marker official means official product information (summary of product characteristics or label); it is not research evidence. For a review, the level shows what kind of research the statement rests on. No level: statements that something has not been studied, reviews' interpretations, named hypotheses and the general rules in our certificate-of-analysis guide.

Content is general information about research, not medical advice. If you have symptoms, contact a healthcare professional.