Vitamin B12 absorption: mammalian physiology and acquired and inherited disorders

Biochimie. 2013 May;95(5):1002-7. doi: 10.1016/j.biochi.2012.11.004. Epub 2012 Nov 20.


Background: Vitamin B12 (cobalamin) is a cobalt-containing compound synthesized by bacteria and an essential nutrient in mammals, which take it up from diet. The absorption and distribution of dietary vitamin B12 to the organism is a complex process involving several gene products including carrier proteins, plasma membrane receptors and transporters. Disturbed cellular entry, transit or egress of vitamin B12 may lead to low vitamin B12 status or deficiency and eventually hematological and neurological disorders.

Objective: The aim of this review is to summarize the causes leading to vitamin B12 deficiency including decreased intake, impaired absorption and increased requirements. Under physiological conditions, vitamin B12 bound to the gastric intrinsic factor is internalized in the ileum by a highly specific receptor complex composed by Cubilin (Cubn) and Amnionless (Amn). Following exit of vitamin B12 from the ileum, general cellular uptake from the circulation requires the transcobalamin receptor CD320 whereas kidney reabsorption of cobalamin depends on Megalin (Lrp2). Whereas malabsorption of vitamin B12 is most commonly seen in the elderly, selective pediatric, nondietary-induced B12 deficiency is generally due to inherited disorders including the Imerslund-Gräsbeck syndrome and the much rarer intrinsic factor deficiency. Biochemical, clinical and genetic research on these disorders considerably improved our knowledge of vitamin B12 absorption. This review describes basic and recent findings on the intestinal handling of vitamin B12 and its importance in health and disease.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Membrane Proteins
  • Proteins / metabolism
  • Receptors, Cell Surface / metabolism
  • Vitamin B 12 / metabolism
  • Vitamin B 12 Deficiency / complications*
  • Vitamin B 12 Deficiency / etiology*
  • Vitamin B 12 Deficiency / metabolism


  • AMN protein, human
  • Membrane Proteins
  • Proteins
  • Receptors, Cell Surface
  • intrinsic factor-cobalamin receptor
  • Vitamin B 12