Intended for healthcare professionals

Clinical Review

Vitamin B12 deficiency

BMJ 2014; 349 doi: (Published 04 September 2014) Cite this as: BMJ 2014;349:g5226
  1. Alesia Hunt, haematology specialist registrar,
  2. Dominic Harrington, consultant clinical scientist, and scientific director of Viapath LLP,
  3. Susan Robinson, haematology consultant
  1. 1Haematology, Guy’s and St Thomas’ NHS Foundation Trust, London, UK
  1. Correspondence to: A Hunt alesiahunt{at}

Summary points

  • Vitamin B12 deficiency is a common but serious condition

  • Clinical presentation may not be obvious thus leading to complex issues around diagnosis and treatment

  • There is no ideal test to define deficiency and therefore the clinical condition of patients is of the utmost importance

  • There is evidence that new techniques such as the measurement of holotranscobalamin and methylmalonic acid levels seem useful in more accurately defining deficiency

  • If the clinical features suggest deficiency then it is important to treat patients to avoid neurological impairment even if there may be discordance between the results and clinical features

Vitamin B12 is an essential cofactor that is integral to methylation processes important in reactions related to DNA and cell metabolism, thus a deficiency may lead to disruption of DNA and cell metabolism and thus have serious clinical consequences.1 Intracellular conversion of vitamin B12 to two active coenzymes, adenosylcobalamin in mitochondria and methylcobalamin in the cytoplasm, is necessary for the homeostasis of methylmalonic acid and homocysteine, respectively.2 3 Methylmalonic acid is converted into succinyl-CoA, of which vitamin B12 is a cofactor for the reaction. Homocysteine is biosynthesised from methionine then resynthesised into methionine or converted into amino acid cysteine.

Vitamin B12 (also referred to as cobalamin) deficiency is relatively common, with important and variable clinical consequences. This review presents a concise summary of the most up to date evidence on how to diagnose and manage vitamin B12 deficiency.

Sources and selection criteria

We searched PubMed and Google Scholar using the terms “vitamin B12 deficiency” and “cobalamin deficiency”, and hand selected the most relevant and appropriate articles. We also used evidence based guidelines from the British Committee for Standards in Haematology; however, evidence, especially in the form of randomised controlled trials, is lacking.4

What causes vitamin B12 deficiency?

Foods containing vitamin B12 are …

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