Skip to main content


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

Medically reviewed by Last updated on Nov 29, 2022.

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.Harvard 2005


Early empirical work on the structure and function of cobalamins as coenzymes was conducted using vitamin B12-dependent bacteria in the 1950s.Beck 1990 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.Olson 2001


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.Facts & Comparisons 2011

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.Facts & Comparisons 2011

Uses and Pharmacology

Vitamin B12 deficiency

The prevalence of vitamin B12 deficiency among elderly Americans is thought to be about 20%.(Andres 2010, Harvard 2005) 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.(Harvard 2005, Ito 2010, McCaddon 2010, Stover 2010)

The deficiency can lead to subtle cognitive and neurologic changes, as well as to more severe anemia and dementia.(Ito 2010, McCaddon 2010, Stover 2010) Neonatal development may also be impaired in infants breastfed by mothers who have a vitamin B12 deficiency.(Harvard 2005, Pepper 2011)

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.(Head 2006, Maladkar 2009, Sharma 2012)

The 2016 Academy of Nutrition and Dietetics' (AND) position statement on vegetarian diets states that because vitamin B12 is not found in plant foods, its intake is lower among vegetarians than non-vegetarians. Additionally, it states that neither fermented soy products nor unfortified plant foods are reliable sources of vitamin B12. Pregnant and lactating individuals, as well as infants breastfed by mothers with inadequate vitamin B12 intake, should receive a vitamin B12 supplement. Similarly, older vegetarian adults should use vitamin B12-fortified foods or supplements; poor vitamin B12 status has been linked to an increased risk of dementia.(Melina 2016)(Melina 2016) A review of guidelines that addressed nutrition, physical activity, and nutrient supplementation before and after bariatric surgery identified one guideline that included recommendations for micronutrients; the American Society for Metabolic and Bariatric Surgery Integrated Health Nutritional Guidelines for the Surgical Weight Loss Patient 2016 Update: Micronutrients. Vitamin B12 supplementation was recommended for all post-weight loss bariatric surgery patients (Grade B, Level 2) at an oral dose of 350 to 500 mg/day (disintegrating tablet, sublingual, liquid) or nasal spray as directed by the manufacturer. For treating postsurgical deficiency, a dose of 1,000 mg/day was recommended until normal limits were achieved, and then doses needed to maintain normal levels were resumed (Grade B, Level 2).(Tabesh 2019)


Animal data

In animal models of vitamin B12-related neuropathy, ultra-high dose methylcobalamin (500 mcg/kg) resulted in regeneration of motor neurons.(Head 2006)

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.(Head 2006, Maladkar 2009)

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.(Rietsema 2014)

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).(Petersen 2018) Additionally, the British Association for Psychopharmacology's updated consensus statement on clinical practice with anti-dementia drugs (2016) recommendeds against the use of vitamin B12, either alone or in combination with folate, as treatment for dementia prevention based on type I evidence (level A).(O’Brien 2017)

Vegetarian diet

Clinical diet

The Academy of Nutrition and Dietetics' updated position paper on vegetarian diets (2016) states that adequate nutrition can be provided by a well-planned vegetarian diet that includes legumes. Therapeutic vegetarian diets are useful in maintaining a healthy weight and body mass index and are associated with a reduction in cardiovascular disease risk and type 2 diabetes. Vitamin B12 is not found in plant foods so it is important that vegetarians (especially vegans) regularly consume reliable sources of vitamin B12, such as B12-fortified foods or supplements, to prevent deficiency. Special consideration for vitamin B12 is required for pregnant vegetarians as well as children and older adults.(Melina 2016)

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.(Manzanares 2010)

A systematic review showed little evidence supporting vitamin B12 supplementation to reduce the risk of diabetes or cardiovascular disease.(Pezzini 2007, Rafnsson 2011) 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.(Xu 2013) 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.(Jiang 2015)

Limited information suggests methylcobalamin may play a role in immune modulation and in cancer.(Wheatley 2007)

Methylcobalamin has been used in clinical studies to reduce serum homocysteine levels.(Guttuso 2009, Zoccolella 2010)

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.(Showell 2014)


The DRI of vitamin B12 is 2.4 mcg. The FDA has set the Daily Reference Value (DRV) at 6 mcg.Harvard 2005, Tanaka 1981

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.Sharma 2012

Clinical trials evaluating the effect of methylcobalamin in diabetic neuropathy have used dosages of saline 2,500 micrograms in 10 mL injected intrathecally Head 2006 and oral methylcobalamin 500 mcg taken 3 times a day. Maladkar 2009 Trials in patients with renal failure-associated neuropathy utilized daily dosages of oral methylcobalamin 1,500 mcg for 6 months.Head 2006

Methylcobalamin is at least as bioavailable as cyano- and hydroxycobalamin.Tanaka 1981

The American Society for Metabolic and Bariatric Surgery Integrated Health Nutritional Guidelines for the Surgical Weight Loss Patient 2016 Update recommends an oral dose of 350 to 500 mg/day (disintegrating tablet, sublingual, liquid) or nasal spray as directed by the manufacturer was recommended for all post-weight loss bariatric surgery patients (Grade B, Level 2). For treating post-surgical deficiency, a dose of 1,000 mg/day was recommended until within normal limits and then doses needed to maintain normal levels (Grade B, Level 2). (Tabesh 2019)

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.Pepper 2011 No reports linking high doses of vitamin B12 with maternal or fetal complications have been found.Drugs in Pregnancy 2011


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.Facts & Comparisons 2011, Ito 2010, Martindale 2011, Saidi 1961

Most antibiotics, methotrexate, or pyrimethamine invalidate folic acid and vitamin B12 diagnostic blood assays.Facts & Comparisons 2011

Adverse Reactions

Vitamin B12 at dosages found in foods, or from supplements is well tolerated.(Bistrian 2010) GI effects from methylcobalamin may include anorexia, nausea, vomiting, and diarrhea. Headache has been reported.(Facts & Comparisons 2011) High doses of vitamin B12 (more than 5 to 10 mg/week) or long durations of use have been associated with worsening acne, particularly in females.(Zamil 2020)


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.Bistrian 2010, European Commission 2012

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.European Commission 2012



This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

Andres E, Fothergill H, Mecili M. Efficacy of oral cobalamin (vitamin B12) therapy. Expert Opin Pharmacother. 2010;11(2):249-256.20088746
Are you getting enough of this vitamin? Harv Health Lett. 2005;30(10):1-2.16206385
Beck WS. Cobalamin as coenzyme: A twisting trail of research. Am J Hematol. 1990;34(2):83-89.2187340
Bistrian B. Should I stop taking these vitamins? Harv Health Lett. 2010;35(7):2.20583349
Cyanocobalamin (Vitamin B12). Drug Facts & Comparisons. Facts & Comparisons [database online]. St. Louis, MO: Wolters Kluwer Health Inc; 2011. Accessed August 14, 2012.
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.
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
Head KA. Peripheral neuropathy: Pathogenic mechanisms and alternative therapies. Altern Med Rev. 2006;11(4):294-329.17176168
Ito T, Jensen RT. Association of long-term proton pump inhibitor therapy with bone fractures and effects on absorption of calcium, vitamin B12, iron, and magnesium. Curr Gastroenterol Rep. 2010;12(6):448-457.20882439
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
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
Manzanares W, Hardy G. Vitamin B12: The forgotten micronutrient for critical care. Curr Opin Clin Nutr Metab Care. 2010;13(6):662-668.20717016
McCaddon A, Hudson PR. L-methylfolate, methylcobalamin, and N-acetylcysteine in the treatment of alzheimer's disease-related cognitive decline. CNS Spectr. 2010;15(1 Suppl 1):2-5; discussion 6.20397369
Melina V, Craig W, Levin S. Position of the Academy of Nutrition and Dietetics: Vegetarian diets. J Acad Nutr Diet. 2016;116(12):1970-1980. doi:10.1016/j.jand.2016.09.02527886704
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.
O'Brien JT, Holmes C, Jones M, et al. Clinical practice with anti-dementia drugs: A revised (third) consensus statement from the British Association for Psychopharmacology. J Psychopharmacol. 2017;31(2):147-168. doi:10.1177/026988111668092428103749
Olson RE. Karl August Folkers (1906-1997). J Nutr. 2001;131(9):2227-2230.11533258
Pepper MR, Black MM. B12 in fetal development. Semin Cell Dev Biol. 2011;22(6):619-623.21664980
Petersen RC, Lopez O, Armstrong MJ, et al. Practice guideline update summary: Mild cognitive impairment. Neurology. 2018;90(3):1-10.29282327
Pezzini A, Del Zotto E, Padovani A. Homocysteine and cerebral ischemia: pathogenic and therapeutical implications. Curr Med Chem. 2007;14(3):249-263.17305530
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
Rietsema WJ. Unexpected recovery of moderate cognitive impairment on treatment with oral methylcobalamin. J Am Geriatr Soc. 2014;62(8):1611-1612.25116994
Saidi P, Wallerstein RO, Aggeler PM. Effect of chloramphenicol on erythropoiesis. J Lab Clin Med. 1961;57:247-256.13745416
Sharma V, Biswas D. Cobalamin deficiency presenting as obsessive compulsive disorder: Case report. Gen Hosp Psychiatry. 2012.22227032
Showell MG, Mackenzie-Proctor R, Brown J, Yazdani A, Stankiewicz MT, Hart RJ. Antioxidants for male subfertility. Cochrane Database Sys Rev. 2014;(12):CD007411.25504418
Stover PJ. Vitamin B12 and older adults. Curr Opin Clin Nutr Metab Care. 2010;13(1):24-27.19904199
Tabesh MR, Maleklou F, Ejtehadi F, Alizadeh Z. Nutrition, physical activity, and prescription of supplements in pre- and post-bariatric surgery patients: a practical guideline. Obes Surg. 2019;Jul 31.[Epub ahead of print]31367987
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.
Vitamin B12 Substances. In: Sweetman SC, ed. Martindale: The Complete Drug Reference. 37th ed. London, England: Pharmaceutical Press; 2011.
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
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
Zamil DH, Perez-Sanchez A, Rajani K. Acne related to dietary supplements. Dermatol Online J. 2020;26(8). Accessed February 2021.
Zoccolella S, Bendotti C, Beghi E, Logroscino G. Homocysteine levels and amyotrophic lateral sclerosis: A possible link. Amyotroph Lateral Scler. 2010;11(1-2):140-147.19551535

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.