Aetiology

Causes of vitamin B12 deficiency (1,2):

• inadequate vitamin B12 in diet
  • strict vegan
• oral contraceptive pill
  • reduced serum B12 level is thought to be due to a reduction in the level of the vitamin B12-carrying protein (transcobalamin) rather than deficiency of vitamin B12
• vitamin B12 malabsorption
  • pernicious anaemia (PA)
    • caused by loss of gastric parietal cells due to autoimmune atrophic gastritis resulting in reduced IF production
    • commonly associated with other autoimmune conditions (esp. vitiligo and thyroid disease) and slightly increased risk of gastric carcinoma
    • familial tendency
  • atrophic gastritis (1)
  • Zollinger-Ellison syndrome (1)
  • long term use of PPI or H2-antagonist drugs
  • chronic alcoholism
  • pancreatic failure
    • reduces pH and calcium concentration of terminal ileal fluid below that optimal for absorption
  • coeliac disease
    • this much more commonly causes iron and/or folate deficiency
    • but 10-30% of coeliac patients can have evidence of vitamin B12 deficiency
  • gastrectomy
  • small bowel (esp. terminal ileal) surgery
  • inflammatory bowel disease
    • esp. that affecting the terminal ileum e.g. Crohn's disease
  • blind loop syndrome and/or small bowel bacterial overgrowth
    • bacteria compete for and break down IF-B12 complex
  • drugs
    • biguanide (e.g. Metformin) therapy (inhibits vitamin B12 absorption)
    • cholestyramine
    • slow K
  • fish tapeworm (Diphyllobothrium latum) infestation
    • mostly seen in Scandinavia where eating raw fish is more common practice
      
• increased requirements:
  • pregnancy
  • haemolysis
• rarities, e.g.:
  • nitrous oxide (N2O)
    • cob(I)alamin oxidised to cob(III)alamin
  • deficient/defective IF
  • disorders of cobalamin transport
    • e.g. defective transcobalamin II or TC II receptor
  • inborn errors of metabolism

A careful history concentrating on the patient's diet, drug therapy and previous medical history is important in elucidating the cause of vitamin B12 deficiency. Other features such as family history and signs of autoimmune disorders (esp. thyroid disease and vitiligo) may point towards a diagnosis of pernicious anaemia (2).

Reference:

• (1) National Institutes for Health. Vitamin B12 dietary fact sheet (accessed 13/05/2022).
• (2) Royal United Hospital Bath NHS Trust. Guidelines for the Investigation & Management of vitamin B12 deficiency (accessed 13/05/2022).