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vitamin B12 deficiency

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Vitamin B12 deficiency causes distinctive dyserythropoietic abnormalities in the bone marrow - megaloblastic erythropoiesis - associated with abnormally large red cells in the peripheral blood i.e. macrocytosis.

Vitamin B12 deficiency in developed countries is commonly due to pernicious anaemia; in developing countries, often more vegan-based, undernourishment is a more common cause.

Vitamin B12 is found in foods of animal origin including milk, cheese, yoghurt and eggs

  • recommended daily requirement of vitamin B12 is small (1-2 µg/day) compared with total body stores (2000-5000 µg) much of which is stored in the liver. This explains why it takes a long time, usually years, for vitamin B12 deficiency to develop
  • dietary vitamin B12 is freed from the food protein by pepsin in the acid gastric environment and binds to haptocorrin, a protein secreted in saliva. In the small intestine, haptocorrin is degraded by pancreatic enzymes, the vitamin B12 is released and binds with intrinsic factor (IF), itself secreted by gastric parietal cells
    • the IF-B12 complex is carried through the small intestine and binds to receptors in the terminal ileum where it is actively absorbed. A small fraction (1-2%) of the daily intake is passively absorbed across the entire absorptive surface of the intestinal tract

Interpretation is difficult. The following observations are offered (2,3):

  • serum B12 180-1000 pg/ml
    • reference ranges provided are for adults
    • reference ranges for infants and children are dependant on age. Results should be interpreted along with clinical features and other laboratory results

  • B12 levels fall physiologically in pregnancy and this usually does not represent deficiency at a biochemical level
    • if the mother has otherwise unexplained anaemia (or has other clinical signs of B12 deficiency), consider a treatment trial of B12 replacement as suggested below (following local standard advice for non-pregnant individuals with low serum B12 values).
  • in clear cut deficiency, levels of B12 are nearly always <150 pg/ml and usually <100 pg/ml (2,3)
    • Pernicious anaemia is the cause of the majority of severe deficiencies in adults
      • around 50% of patients with pernicious anaemia have intrinsic factor antibodies while this antibody is rarely seen in normal controls
      • parietal cell antibodies are present in 90% of patients but are also seen in 1 - 2% of normal controls
  • patients with B12 in the borderline range (150 - 180 pg/ml) may have either early B12 deficiency or be healthy "low normal".
  • neurological disease or glossitis may occur without anaemia or macrocytosis and may be irreversible (3)
  • interpretation of early megaloblastic change in the marrow is difficult and cannot be reliably distinguished from myelodysplasia (3)

Note that reference ranges may vary between laboratories.


Last edited 04/2020 and last reviewed 10/2020