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Common Name(s): Cobalamin, Cyanocobalamin, MeB12, MeCbl, Mecobalamin, Methylcobalamin, Vitamin B12
Drug class: Vitamins

Medically reviewed by Last updated on Nov 2, 2021.

Clinical Overview


Methylcobalamin has been used as a supplement in patients with vitamin B12 deficiency and in those with diabetes and other neuropathies. Although use in dementia is advocated, aside from correcting deficiencies, clinical trials are limited.


The Dietary Reference Intake (DRI, also known as Recommended Daily Allowance [RDA]) for vitamin B12 is 2.4 mcg/day.

Clinical trials with specific dosage recommendations for methylcobalamin are lacking. Dosage is based on recommended dosages for vitamin B12. High dosages of methylcobalamin (1,500 mcg/day orally) have been used in limited studies.


None identified.


Compatible at usual dosages.


Medicines considered to reduce the absorption of vitamin B12 include alcohol, aminosalicylic acid, chloramphenicol, colchicine, metformin, neomycin, and proton pump inhibitors.

Adverse Reactions

Vitamin B12 at dosages found in foods or from supplements is well tolerated. GI effects from methylcobalamin may include anorexia, diarrhea, headache, nausea, and vomiting.


Specific toxicological studies are lacking. Vitamin B12 has a long history of safe use even at high dosages. At usual dosages, the cobalt and cyanide content are not considered to be toxicologically relevant.


Vitamin B12 is obtained from animal products (eg, meat, fish, shellfish, poultry, eggs, milk, milk products). Tempeh, made from fermented soybeans, contains the beneficial bacteria responsible for producing vitamin B12. Commercial forms of methylcobalamin are produced in the laboratory through the conversion of cyanocobalamin.1


Early empirical work on the structure and function of cobalamins as coenzymes was conducted using vitamin B12-dependent bacteria in the 1950s.2 Prior to this date, Addison anemia (pernicious anemia) had been described and the involvement of intrinsic factor was recognized through experiments involving regurgitated raw meat. The discovery of liver as a treatment for pernicious anemia in the 1920s led to the Nobel Prize in Medicine, and in 1948 Karl Folkers and Alexander Todd identified cobalamin as the active principle in liver.3


Methylcobalamin is the methyl form of cobalamin obtained from hydroxycobalamin, either by chemical manipulation in the laboratory or in the body as a natural process. Cyano- and hydroxocobalamin are considered the storage or transport forms of cobalamin, while methylcobalamin and deoxyadenosylcobalamin are the active forms involved in enzymatic reactions. Methylcobalamin is involved specifically in the normal metabolism of folate and the consequent maintenance of normal homocysteine serum levels.4

The 4 cobalamins collectively are often referred to as vitamin B12, and are essential cofactors in the bone marrow and myeloid cells where the replication of chromosomes and cellular division occurs.4

Uses and Pharmacology

Vitamin B12 deficiency

The prevalence of vitamin B12 deficiency among elderly Americans is thought to be about 20%.1, 5 Dietary deficiency of vitamin B12 can result from poor diets or among strict vegetarians who choose not to consume any animal products. A lack of stomach acid occurs in elderly patients and among people taking proton pump inhibitors, leading to poor digestion of the vitamin from animal products. People with a lack of intrinsic factor (also known as pernicious anemia), as well as those with severe GI disorders with impaired small intestine function (eg, Crohn disease) or those who have undergone gastric bypass surgery may also be deficient in vitamin B12.1, 6, 7, 8

The deficiency can lead to subtle cognitive and neurologic changes, as well as to more severe anemia and dementia.6, 7, 8 Neonatal development may also be impaired in infants breastfed by mothers who have a vitamin B12 deficiency.1, 9

Animal data

Specific data on the correction of methylcobalamin deficiencies in animals is lacking.

Clinical data

Vitamin B12 deficiency can be corrected with the administration of cobalamin. Usually either cyano- or hydroxocobalamin is used to restore normal levels. Clinical trials specifically evaluating methylcobalamin supplementation are lacking. However, there is no reason to suggest lack of efficacy, and reports exist of therapeutic efficacy of methylcobalamin.10, 11, 12


Animal data

In animal models of vitamin B12-related neuropathy, ultra-high dose methylcobalamin (500 mcg/kg) resulted in regeneration of motor neurons.10

Clinical data

Limited clinical trials have evaluated the effect of supplemental methylcobalamin on diabetic peripheral neuropathy, as well as neuropathy associated with renal disease. Subjective measures were reported to have improved.10, 11

Reversal of moderate cognitive impairment (dementia) with oral methylcobalamin, but not hydroxocobalamin, was reported in an 83-year-old female despite B12 levels being within normal limits. Therapy was inspired by the VITACOG trial and consisted of daily oral methylcobalamin (3,000 mcg) and folic acid (1,200 mcg). Two months later, her Mini Mental State Examination improved from 14 to 29 and her body mass index improved from 17.1 to 22.6 kg/m2.25

The American Academy of Neurology (AAN) updated practice guideline for mild cognitive impairment (2018) states that insufficient evidence is available to support or refute the use of homocysteine-lowering B vitamins, including vitamin B12, in patients with mild cognitive impairment (Very Low Level, Class II).29

Other uses

Animal studies and clinical data suggest a role for vitamin B12 parenteral therapy in the care of the critically ill, especially in shock; however, clinical trials are lacking and information specifically regarding methylcobalamin is lacking.13

A systematic review showed little evidence supporting vitamin B12 supplementation to reduce the risk of diabetes or cardiovascular disease.14, 15 A 2013 meta-analysis that included 15 studies and 1,106 diabetic patients found combination therapy for 2 to 4 weeks with intravenous (IV) alpha lipoic acid 300 to 600 mg/day plus IV methylcobalamin 500 to 1,000 mg/day to be superior to methylcobalamin monotherapy for improving nerve conduction.24 Similarly, combination therapy with prostaglandin E1 (10 or 20 mcg IV), methylcobalamin (500 to 1,500 mcg IV/intramuscularly [IM]) plus lipoic acid (300 or 600 mg/day IV) significantly improved nerve conduction velocity compared with combination therapy without the lipoic acid in a 2015 meta-analysis of 18 randomized clinical trials (N = 1,410) involving patients with diabetic peripheral neuropathy.26

Limited information suggests methylcobalamin may play a role in immune modulation and in cancer.16

Methylcobalamin has been used in clinical studies to reduce serum homocysteine levels.17, 18

A Cochrane systematic review and meta-analysis of antioxidants for male subfertility identified 1 double-blind, randomized, parallel study that administered vitamin B12 (N=396); however, the lack of useable data prevented its inclusion in the meta-analysis. Japanese men with abnormal sperm count or motility received mecobalamin at a dose of either 1,500 or 6,000 mcg/day for 12 weeks. No statistically significant difference was observed in sperm parameters compared to placebo.27


The DRI of vitamin B12 is 2.4 mcg. The FDA has set the Daily Reference Value (DRV) at 6 mcg.1, 19

Methylcobalamin 1,000 mcg IM 3 times a week for 2 weeks followed by weekly doses was reported to reverse neuropsychiatric symptoms in 1 case study.12

Clinical trials evaluating the effect of methylcobalamin in diabetic neuropathy have used dosages of saline 2,500 micrograms in 10 mL injected intrathecally 10 and oral methylcobalamin 500 mcg taken 3 times a day. 11 Trials in patients with renal failure-associated neuropathy utilized daily dosages of oral methylcobalamin 1,500 mcg for 6 months.10

Methylcobalamin is at least as bioavailable as cyano- and hydroxycobalamin.19

Pregnancy / Lactation

In pregnant women the recommended intake of vitamin B12 increases to 2.6 mcg/day to meet the needs of the developing fetus. Supplementation with methylcobalamin may improve the nutritional status of pregnant women but data from clinical trials is lacking.9 No reports linking high doses of vitamin B12 with maternal or fetal complications have been found.20


Information on interactions caused by methylcobalamin supplementation is lacking. Certain medicines are considered to reduce the absorption of vitamin B12 including alcohol, aminosalicylic acid, chloramphenicol, colchicine, metformin, neomycin, and proton pump inhibitors.4, 6, 21, 28

Most antibiotics, methotrexate, or pyrimethamine invalidate folic acid and vitamin B12 diagnostic blood assays.4

Adverse Reactions

Vitamin B12 at dosages found in foods, or from supplements is well tolerated.22 GI effects from methylcobalamin may include anorexia, nausea, vomiting, and diarrhea. Headache has been reported.4


Specific toxicological studies are lacking. Vitamin B12 (as cyanocobalamin or hydroxocobalamin) has a long history of safe use even at high doses (cyanocobalamin 1 mg IM at weekly intervals for 1 month, followed by monthly injections for 6 months). At usual doses, the cobalt and cyanide content are not considered to be toxicologically relevant.22, 23

Hydroxocobalamin is used at 5 g doses in the management of cyanide poisoning.

A study conducted in rats in the 1950s suggested vitamin B12 might exert tumor-promoting effects, while another study suggested reduced survival rates among rats with Walker carcinosarcoma treated with methyl- and cyanocobalamin.23


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2. Beck WS. Cobalamin as coenzyme: A twisting trail of research. Am J Hematol. 1990;34(2):83-89.2187340
3. Olson RE. Karl August Folkers (1906-1997). J Nutr. 2001;131(9):2227-2230.11533258
4. Cyanocobalamin (Vitamin B12). Drug Facts & Comparisons. Facts & Comparisons [database online]. St. Louis, MO: Wolters Kluwer Health Inc; 2011. Accessed August 14, 2012.
5. Andres E, Fothergill H, Mecili M. Efficacy of oral cobalamin (vitamin B12) therapy. Expert Opin Pharmacother. 2010;11(2):249-256.20088746
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11. Maladkar M, Rajadhyaksha G, Venkataswamy N, et al. Efficacy, safety, and tolerability of epalrestat compared to methylcobalamine in patients with diabetic neuropathy. Int J Diabetes Dev Ctries. 2009;29(1):28-34.20062561
12. Sharma V, Biswas D. Cobalamin deficiency presenting as obsessive compulsive disorder: Case report. Gen Hosp Psychiatry. 2012.22227032
13. Manzanares W, Hardy G. Vitamin B12: The forgotten micronutrient for critical care. Curr Opin Clin Nutr Metab Care. 2010;13(6):662-668.20717016
14. Rafnsson SB, Saravanan P, Bhopal RS, Yajnik CS. Is a low blood level of vitamin B12 a cardiovascular and diabetes risk factor? A systematic review of cohort studies. Eur J Nutr. 2011;50(2):97-106.20585951
15. Pezzini A, Del Zotto E, Padovani A. Homocysteine and cerebral ischemia: pathogenic and therapeutical implications. Curr Med Chem. 2007;14(3):249-263.17305530
16. Wheatley C. Cobalamin in inflammation III - glutathionylcobalamin and methylcobalamin/adenosylcobalamin coenzymes: The sword in the stone? how cobalamin may directly regulate the nitric oxide synthases. J Nutr Environ Med. 2007;16(3-4):212-226.18923642
17. Guttuso T Jr, McDermott MP, Ng P, Kieburtz K. Effect of L-methionine on hot flashes in postmenopausal women: a randomized controlled trial. Menopause. 2009;16(5):1004-1008.19407666
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19. Tanaka N, Yamazaki Y, Yamada H et al. Fate of cobalamins in humans following oral and intramuscular administration of cyanocobalamin, hydroxycobalamin, adenosylcobalamin and methylcobalamin. Vitamins. 1981;55:155–161.
20. Methylcobalamin. In: Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk. 9th ed. Philadelphia, PA: Wolters Kluwer Health Inc/Lippincott Williams & Wilkins; 2011.
21. Vitamin B12 Substances. In: Sweetman SC, ed. Martindale: The Complete Drug Reference. 37th ed. London, England: Pharmaceutical Press; 2011.
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23. European Commission. Opinion of the scientific committee on food on the tolerable upper intake level of vitamin B12. 2000;SCF/CS/NUT/UPPLEV/42 Final. Accessed May 2012.
24. Xu Q, Pan J, Yu J, et al. Meta-analysis of methylcobalamin alone and in combination with lipoic acid in patients with diabetic peripheral neuropathy. Diabetes Res Clin Pract . 2013;101(2):99-105.23664235
25. Rietsema WJ. Unexpected recovery of moderate cognitive impairment on treatment with oral methylcobalamin. J Am Geriatr Soc. 2014;62(8):1611-1612.25116994
26. Jiang DQ, Li MX, Wang Y, Wang Y. Effects of prostaglandin E1 plus methylcobalamin alone and in combination with lipoic acid on nerve conduction velocity in patients with diabetic peripheral neuropathy: a meta-analysis. Neurosci Lett. 2015;594:23-29.25800109
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