Intended for healthcare professionals

Practice Rational Testing

Investigating vitamin B12 deficiency

BMJ 2019; 365 doi: (Published 10 May 2019) Cite this as: BMJ 2019;365:l1865
  1. Nithya Sukumar, NIHR clinical lecturer1 2,
  2. Ponnusamy Saravanan, professor, honorary consultant physician1 2
  1. 1Department of Populations, Evidence and Technologies, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
  2. 2Department of Diabetes, Endocrinology and Metabolism, George Eliot Hospital, Nuneaton, UK
  3. Correspondence to: P Saravanan

What you need to know

  • Vitamin B12 deficiency may present with non-specific symptoms, but it warrants urgent evaluation and treatment when haematological or neurological features are present

  • Causes for B12 deficiency include nutritional, drug induced, and gastrointestinal; autoimmune pernicious anaemia is relatively rare

  • Consider specialist referral if there is no obvious cause for B12 deficiency, if it is refractory to treatment, or if neurological features or persistent macrocytic anaemia is present

  • Parenteral B12 replacement is indicated if urgent treatment is required, if gastrointestinal malabsorption is suspected, and in elderly people

  • Oral B12 replacement may be a suitable alternative in asymptomatic individuals with dietary B12 deficiency

A 44 year old woman attends her general practitioner with a two year history of lethargy, which has resulted in her being unable to continue her job as a primary school teacher. She had a history of anaemia a few years ago and was not taking any regular medication, except for the combined contraceptive pill. Her mother has hypothyroidism for which she takes levothyroxine; there is no other family history of note. Physical examination was unremarkable. Recent blood tests showed haemoglobin 110 g/L (reference range 115-160) and mean corpuscular volume 102 fL (range 80-100). To further investigate the cause of her macrocytic anaemia, blood tests for vitamin B12 and folate were requested, which showed vitamin B12 138 pmol/L (reference range 148-600 (to convert from pmol/L to ng/L, multiply by 1.355)) and folate 40.5 nmol/L (4.5-45 (to convert to μg/L, divide by 2.27)).


The prevalence of vitamin B12 (B12) deficiency is approximately 6-12% in adults under 60 years old and around 17% in all adults with macrocytic anaemia.123 However, elderly people, pregnant women, and vegans are more susceptible to B12 deficiency, so have a higher index of suspicion in these populations in the presence of suggestive symptoms and signs (box 1). Some …

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