Cyanocobalamin (Vitamin B12)

Last Updated: March 16, 2024

Vitamin B12 is an essential water-soluble vitamin that plays a role in neurological function and is important for DNA synthesis.

Cyanocobalamin (Vitamin B12) is most often used for

What is vitamin B12?

Vitamin B12 is one of the 8 B vitamins and is water soluble. It is found bound to protein, where it is used in several metabolic processes, and is important for one-carbon metabolism. One-carbon metabolism is a series of metabolic processes that are crucial for cellular function.[3][4] Vitamin B12 acts as a cofactor in these metabolic processes throughout the body, including the production of methionine, one of the amino acids that is integral for the production of the purines that make up DNA.[4]

What are vitamin B12’s main benefits?

Vitamin B12 is often used as an over-the-counter treatment for general fatigue and also might benefit people with myalgic encephalomyelitis (chronic fatigue syndrome) (ME/CFS) as a potential treatment. A B12 deficiency may even be a potential cause of the condition. A 2022 review found that some people with ME/CFS had a low B12 level in cerebrospinal fluid (CSF) samples but a normal level in blood samples. This could imply a low B12 supply in the brain, despite a normal level in the blood. Another study found that intranasal vitamin B12 improved symptoms of fatigue in two thirds of people with ME/CFS.[5] For general fatigue symptoms in otherwise healthy people, very little research has been done on this, so we are not sure if it is effective.[6]

Vitamin B12 may be beneficial for various types of neuropathy (nerve damage). Postherpetic neuralgia is a complication after the reactivation of a herpes virus (e.g., chicken pox) causes damage to the involved nerves, and vitamin B12 may improve the outcome of treatment when added to conventional treatment for this condition.[7] Similarly, a 2020 randomized control trial[8] found that supplementing with 1000 μg of vitamin B12 improved the symptoms of diabetic neuropathy. This could be because around 20% of people with diabetes are also deficient in B12.[9]

Vitamin B12 is crucial in the first trimester of pregnancy. A deficiency, as with a deficiency of folate (vitamin B9), can lead to neural tube defects. The neural tube develops in the third week of pregnancy, around day 20-28. It is ideal to start supplementation prior to pregnancy to ensure sufficient levels are present from day 1.[10]

Vitamin B12 supplements are sometimes used to improve cognitive symptoms in people with neurodegenerative disease. However, meta-analyses have not supported this use so far.[6][11][12]

A recent review suggests that vitamin B12 could be useful in viral infections, including SARS-CoV-2 (COVID-19). It seems that many people with viral infections may have low B12 levels, or levels on the low end of the normal range that could still result in symptoms. In these cases, providing a supplement could improve outcomes. However, this still needs to be studied further, and we can’t be sure it is helpful just yet.[1]

What are vitamin B12’s main drawbacks?

Vitamin B12 is considered to be a safe supplement. At the recommended dosages, toxicity is highly unlikely. Since it is a water soluble vitamin, the body will excrete any excess through the urine. As such, no upper limit of intake has been established yet.[13]

It seems that a high vitamin B12 level could increase the risk of certain cancers and decrease the risk of others. One study[14] found an association between elevated B12 levels and prostate cancer; however, it did not establish a causal relationship. A cohort study in 2017 found an increased lung cancer risk for men who smoked and took relatively high doses of vitamin B12. While this association doesn’t necessarily mean B12 caused the increased rate of lung cancer, it is certainly worth considering before supplementing in this population group.[15]

Conversely, another study found that a higher vitamin B12 intake was associated with a lower risk of colorectal cancer.[16]

In cardiovascular disease, the data also remains uncertain. A 2024 meta-analysis found that increased B12 levels were associated with an increase in cardiovascular disease mortality. However, this study looked at endogenous vitamin B12, not vitamin B12 intake, and this might indicate that B12 levels rise in the presence of cardiovascular disease.[17] Another study found that vitamin B12 had little impact on cardiovascular disease outcomes.[18] More studies will need to be done to assess supplemental vitamin B12 as a risk factor for cardiovascular disease.

How does vitamin B12 work?

Broadly speaking, vitamin B12 is important because it’s a necessary part of many chemical reactions in the body.

Vitamin B12 and folic acid work as cofactors in the synthesis of methionine via the enzymes methionine synthase and L-malonyl-CoA mutase. A deficiency of vitamin B12 or of folate disrupts this process and leads to the production of abnormally large red blood cells, resulting in megaloblastic anemia.[19]

Vitamin B12 is also used by methyl-malonyl-CoA mutase to produce succinyl CoA. Interrupting this reaction leads to the neurological symptoms of B12 deficiency.[4]

B12 is also used in the production of the myelin sheaths that surround nerves and help with nerve signal transmission. If the sheath is damaged, the signals can become disrupted or abnormal, causing pain or loss of sensation. In vitamin B12 deficiency, peripheral neuropathy can occur, which is the result of damage to the myelin sheaths in the nerves of the hands and the feet.[19]

Vitamin B12 is part of one-carbon metabolism, the metabolic process that produces DNA in the body. It helps enzymes work in the production of the building blocks of DNA called purines and pyrimidines.[4]

What else is Cyanocobalamin (Vitamin B12) known as?
Note that Cyanocobalamin (Vitamin B12) is also known as:
  • Cyanocobalamin
  • methylcobalamin
  • 5-deoxyadenosylcobalamin
  • adenosylcobalamin
  • cobamamide
  • dibencozide
  • hydroxocobalamin
  • Cobalamin
Dosage information

The Recommended Daily Allowance (RDA) of vitamin B12 is 2.4 μg for adults without known health conditions. During pregnancy, the RDA increases to 2.6 μg.[1] For children 8 years and under, the RDA is 1.2 μg.[1] Supplementing with B12 is probably not helpful in people who are able to get enough of the vitamin through their diet and have no difficulty with absorption.

Supplements that are available over the counter contain 500 μg–2000 μg of vitamin B12 per tablet. Long-term use is not recommended without monitoring of vitamin B12 levels. For replenishing stores of vitamin B12, 1000 μg should be given by intramuscular injection three times per week for two weeks. This can then be done weekly for four weeks, then once monthly. In cases where absorption is not an issue, the maintenance dose can also be given orally.[2]

Examine Database: Cyanocobalamin (Vitamin B12)
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References
  1. ^Batista KS, Cintra VM, Lucena PAF, Manhães-de-Castro R, Toscano AE, Costa LP, Queiroz MEBS, de Andrade SM, Guzman-Quevedo O, Aquino JSThe role of vitamin B12 in viral infections: a comprehensive review of its relationship with the muscle-gut-brain axis and implications for SARS-CoV-2 infection.Nutr Rev.(2022-Feb-10)
  2. ^Hanna M, Jaqua E, Nguyen V, Clay JB Vitamins: Functions and Uses in Medicine.Perm J.(2022-Jun-29)
  3. ^Clare CE, Brassington AH, Kwong WY, Sinclair KDOne-Carbon Metabolism: Linking Nutritional Biochemistry to Epigenetic Programming of Long-Term Development.Annu Rev Anim Biosci.(2019-Feb-15)
  4. ^O'Leary F, Samman SVitamin B12 in health and disease.Nutrients.(2010-Mar)
  5. ^van Campen CLM, Riepma K, Visser FCOpen Trial of Vitamin B12 Nasal Drops in Adults With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Comparison of Responders and Non-Responders.Front Pharmacol.(2019)
  6. ^Markun S, Gravestock I, Jäger L, Rosemann T, Pichierri G, Burgstaller JMEffects of Vitamin B12 Supplementation on Cognitive Function, Depressive Symptoms, and Fatigue: A Systematic Review, Meta-Analysis, and Meta-Regression.Nutrients.(2021-Mar-12)
  7. ^Wang JY, Wu YH, Liu SJ, Lin YS, Lu PHVitamin B12 for herpetic neuralgia: A meta-analysis of randomised controlled trials.Complement Ther Med.(2018-Dec)
  8. ^Triantafyllos Didangelos, Eleni Karlafti, Evangelia Kotzakioulafi, Eleni Margariti, Parthena Giannoulaki, Georgios Batanis, Solomon Tesfaye, Kοnstantinos KantartzisVitamin B12 Supplementation in Diabetic Neuropathy: A 1-Year, Randomized, Double-Blind, Placebo-Controlled TrialNutrients.(2021 Jan 27)
  9. ^Pflipsen MC, Oh RC, Saguil A, Seehusen DA, Seaquist D, Topolski RThe prevalence of vitamin B(12) deficiency in patients with type 2 diabetes: a cross-sectional study.J Am Board Fam Med.(2009)
  10. ^Vitamin B12 – do you know everything?J Evolution Med Dent Sci.(2020 Oct.)
  11. ^Annika Behrens, Elmar Graessel, Anna Pendergrass, Carolin DonathVitamin B-Can it prevent cognitive decline? A systematic review and meta-analysisSyst Rev.(2020 May 15)
  12. ^Zhang C, Luo J, Yuan C, Ding DVitamin B12, B6, or Folate and Cognitive Function in Community-Dwelling Older Adults: A Systematic Review and Meta-Analysis.J Alzheimers Dis.(2020)
  13. ^“The B Vitamins and Choline: Overview and Methods.” in Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington (DC): National Academies Press (US)(1998)
  14. ^Collin SM, Metcalfe C, Refsum H, Lewis SJ, Zuccolo L, Smith GD, Chen L, Harris R, Davis M, Marsden G, Johnston C, Lane JA, Ebbing M, Bønaa KH, Nygård O, Ueland PM, Grau MV, Baron JA, Donovan JL, Neal DE, Hamdy FC, Smith AD, Martin RMCirculating folate, vitamin B12, homocysteine, vitamin B12 transport proteins, and risk of prostate cancer: a case-control study, systematic review, and meta-analysis.Cancer Epidemiol Biomarkers Prev.(2010-Jun)
  15. ^Brasky TM, White E, Chen CLLong-Term, Supplemental, One-Carbon Metabolism-Related Vitamin B Use in Relation to Lung Cancer Risk in the Vitamins and Lifestyle (VITAL) CohortJ Clin Oncol.(2017 Oct 20)
  16. ^Sun NH, Huang XZ, Wang SB, Li Y, Wang LY, Wang HC, Zhang CW, Zhang C, Liu HP, Wang ZNA dose-response meta-analysis reveals an association between vitamin B12 and colorectal cancer risk.Public Health Nutr.(2016-Jun)
  17. ^Liu K, Yang Z, Lu X, Zheng B, Wu S, Kang J, Sun S, Zhao JThe origin of vitamin B12 levels and risk of all-cause, cardiovascular and cancer specific mortality: A systematic review and dose-response meta-analysis.Arch Gerontol Geriatr.(2024-Feb)
  18. ^Wu S, Feng P, Li W, Zhuo S, Lu W, Chen P, Sui Y, Fang S, Yang Z, Ye YDietary Folate, Vitamin B6, and Vitamin B12 and Risk of Cardiovascular Diseases among Individuals with Type 2 Diabetes: A Case-Control Study.Ann Nutr Metab.(2023)
  19. ^Briani C, Dalla Torre C, Citton V, Manara R, Pompanin S, Binotto G, Adami FCobalamin deficiency: clinical picture and radiological findings.Nutrients.(2013-Nov-15)
  20. ^Allen LHHow common is vitamin B-12 deficiency?Am J Clin Nutr.(2009-Feb)
  21. ^Clark MDThe recovering nurse: the pre-employment interview.Nurs Manage.(1988-Jan)
  22. ^Walker-Smith DJ, Payne JWSynthesis of the peptide-transport carrier of barley scutellum during the early stages of germination.Planta.(1985-Jul)
  23. ^Depeint F, Bruce WR, Shangari N, Mehta R, O'Brien PJMitochondrial function and toxicity: role of the B vitamin family on mitochondrial energy metabolismChem Biol Interact.(2006 Oct 27)
  24. ^Selhub JFolate, vitamin B12 and vitamin B6 and one carbon metabolismJ Nutr Health Aging.(2002)
  25. ^Chen AC, Martin AJ, Choy B, Fernández-Peñas P, Dalziell RA, McKenzie CA, Scolyer RA, Dhillon HM, Vardy JL, Kricker A, St George G, Chinniah N, Halliday GM, Damian DLA Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer ChemopreventionN Engl J Med.(2015 Oct 22)
  26. ^White E, Patterson RE, Kristal AR, Thornquist M, King I, Shattuck AL, Evans I, Satia-Abouta J, Littman AJ, Potter JDVITamins And Lifestyle cohort study: study design and characteristics of supplement usersAm J Epidemiol.(2004 Jan 1)
  27. ^Kim YIFolate and colorectal cancer: an evidence-based critical reviewMol Nutr Food Res.(2007 Mar)
  28. ^Kok DE, Dhonukshe-Rutten RA, Lute C, Heil SG, Uitterlinden AG, van der Velde N, van Meurs JB, van Schoor NM, Hooiveld GJ, de Groot LC, Kampman E, Steegenga WTThe effects of long-term daily folic acid and vitamin B12 supplementation on genome-wide DNA methylation in elderly subjectsClin Epigenetics.(2015 Nov 14)
  29. ^Corbin JM, Ruiz-Echevarría MJOne-Carbon Metabolism in Prostate Cancer: The Role of Androgen SignalingInt J Mol Sci.(2016 Jul 27)
Examine Database References
  1. Fatigue Symptoms - Huijts M, van Oostenbrugge RJ, Rouhl RP, Menheere P, Duits AEffects of vitamin B12 supplementation on cognition, depression, and fatigue in patients with lacunar strokeInt Psychogeriatr.(2013 Mar)
  2. Homocysteine - Hill MH, Flatley JE, Barker ME, Garner CM, Manning NJ, Olpin SE, Moat SJ, Russell J, Powers HJA vitamin B-12 supplement of 500 μg/d for eight weeks does not normalize urinary methylmalonic acid or other biomarkers of vitamin B-12 status in elderly people with moderately poor vitamin B-12 statusJ Nutr.(2013 Feb)
  3. Depression Symptoms - Markun S, Gravestock I, Jäger L, Rosemann T, Pichierri G, Burgstaller JMEffects of Vitamin B12 Supplementation on Cognitive Function, Depressive Symptoms, and Fatigue: A Systematic Review, Meta-Analysis, and Meta-Regression.Nutrients.(2021-Mar-12)
  4. Depression Symptoms - Almeida OP, Ford AH, Flicker LSystematic review and meta-analysis of randomized placebo-controlled trials of folate and vitamin B12 for depression.Int Psychogeriatr.(2015-May)