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Treatment of vitamin B12 deficiency–Methylcobalamine? Cyancobalamine? Hydroxocobalamin?—clearing the confusion


Vitamin B12 (cyancobalamin, Cbl) has two active co-enzyme forms, methylcobalamin (MeCbl) and adenosylcobalamin (AdCbl). There has been a paradigm shift in the treatment of vitamin B12 deficiency such that MeCbl is being extensively used and promoted. This is despite the fact that both MeCbl and AdCbl are essential and have distinct metabolic fates and functions. MeCbl is primarily involved along with folate in hematopiesis and development of the brain during childhood. Whereas deficiency of AdCbl disturbs the carbohydrate, fat and amino-acid metabolism, and hence interferes with the formation of myelin. Thereby, it is important to treat vitamin B12 deficiency with a combination of MeCbl and AdCbl or hydroxocobalamin or Cbl. Regarding the route, it has been proved that the oral route is comparable to the intramuscular route for rectifying vitamin B12 deficiency.

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  1. Gherasim C, Lofgren M, Banerjee R . Navigating the B(12) road: assimilation, delivery, and disorders of cobalamin. J Biol Chem 2013; 288: 13186–13193.

    Article  CAS  Google Scholar 

  2. Brito A, Hertrampf E, Olivares M, Gaitán D, Sánchez H, Allen LH et al. [Folate, vitamin B12 and human health]. Rev Med Chil 2012; 140: 1464–1475.

    Article  CAS  Google Scholar 

  3. O’Leary F, Samman S . Vitamin B12 in health and disease. Nutrients 2010; 2: 299–316.

    Article  Google Scholar 

  4. Stover PJ . Physiology of folate and vitamin B12 in health and disease. Nutr Rev 2004; 62: S3–S12 (discussion S13).

    Article  Google Scholar 

  5. Tsukerman ES, Pomerantseva TI, Poznanskaia AA, Korsova TL, Klement’eva IV . Effect of methylcobalamin and adenosylcobalamin on the process of hematopoiesis and vitamin B12 exchange in experimental phenylhydrazine-induced anemia in rabbits. Vopr Med Khim 1989; 35: 106–111.

    CAS  PubMed  Google Scholar 

  6. Randaccio L, Geremia S, Demitri N, Wuerges J . Vitamin B12: unique metalorganic compounds and the most complex vitamins. Molecules 2010; 15: 3228–3259.

    Article  CAS  Google Scholar 

  7. Quadros EV . Advances in the understanding of cobalamin assimilation and metabolism. Br J Haematol 2010; 148: 195–204.

    Article  CAS  Google Scholar 

  8. Cooper BA, Rosenblatt DS . Inherited defects of vitamin B12 metabolism. Annu Rev Nutr 1987; 7: 291–320.

    Article  CAS  Google Scholar 

  9. Marsh ENG, Meléndez GDR . Adenosylcobalamin enzymes: theory and experiment begin to converge. Biochim Biophys Acta 2012; 1824: 1154–1164.

    Article  CAS  Google Scholar 

  10. Yudkoff M et al. Disorders of organic acid metabolism. In: Siegel G, Agranoff B, Albers R (eds). Basic Neurochemistry: Molecular, Cellular and Medical Aspects, 6th edn. Lippincott-Raven: Philadelphia, PA, USA, 1999.

    Google Scholar 

  11. Hall CA . Function of vitamin B12 in the central nervous system as revealed by congenital defects. Am J Hematol 1990; 34: 121–127.

    Article  CAS  Google Scholar 

  12. Castillo Lancellotti C, Tur Marí JA, Uauy Dagach R . Effect of folate and related nutrients on cognitive function in older people; systematic review. Nutr Hosp 2012; 27: 90–102.

    CAS  PubMed  Google Scholar 

  13. Morris MS . The role of B vitamins in preventing and treating cognitive impairment and decline. Adv Nutr 2012; 3: 801–812.

    Article  CAS  Google Scholar 

  14. Zhang Y-F, Ning G . Mecobalamin. Expert Opin Investig Drugs 2008; 17: 953–964.

    Article  Google Scholar 

  15. Xu Q, Pan J, Yu J, Liu X, Liu L, Zuo X 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: 99–105.

    Article  CAS  Google Scholar 

  16. Deng H, Yin J, Zhang J, Xu Q, Liu X, Liu L et al. Meta-analysis of methylcobalamin alone and in combination with prostaglandin E1 in the treatment of diabetic peripheral neuropathy. Endocrine 2014; 46: 445–454.

    Article  CAS  Google Scholar 

  17. Linnell JC, Smith AD, Smith CL, Wilson J, Matthews DM . Effects of smoking on metabolism and excretion of vitamin B12. Br Med J 1968; 2: 215–216.

    Article  CAS  Google Scholar 

  18. Freeman AG . Cyanocobalamin-a case for withdrawal: discussion paper. J R Soc Med 1992; 85: 686–687.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Freeman AG . Hydroxocobalamin versus cyanocobalamin. J R Soc Med 1996; 89: 659.

    Article  CAS  Google Scholar 

  20. Vidal-Alaball J, Butler CC, Cannings-John R, Goringe A, Hood K, McCaddon A et al. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane Database Syst Rev 2005; CD004655.

  21. Carmel R . How I treat cobalamin (vitamin B12) deficiency. Blood 2008; 112: 2214–2221.

    Article  CAS  Google Scholar 

  22. Vidal-Alaball J, Butler C, Cannings-John R, Goringe A, Hood K, McCaddon K et al. Oral Vitamin B12 versus Intramuscular Vitamin B12 for Vitamin B12 Deficiency. John Wiley and Sons, Ltd. for The Cochrane Collaboration, 2009. Available from (cited 11 June 2014).

    Google Scholar 

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Correspondence to G Billa.

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Thakkar, K., Billa, G. Treatment of vitamin B12 deficiency–Methylcobalamine? Cyancobalamine? Hydroxocobalamin?—clearing the confusion. Eur J Clin Nutr 69, 1–2 (2015).

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