Vitamin B12 absorption and malabsorption

Vitam Horm. 2022;119:241-274. doi: 10.1016/bs.vh.2022.01.016. Epub 2022 Mar 1.


Vitamin B12 is assimilated and transported by complex mechanisms that involve three transport proteins, intrinsic factor (IF), haptocorrin (HC) and transcobalamin (TC) and their respective membrane receptors. Vitamin deficiency is mainly due to inadequate dietary intake in vegans, and B12 malabsorption is related to digestive diseases. This review explores the physiology of vitamin B12 absorption and the mechanisms and diseases that produce malabsorption. In the stomach, B12 is released from food carrier proteins and binds to HC. The degradation of HC by pancreatic proteases and the pH change trigger the transfer of B12 to IF in the duodenum. Cubilin and amnionless are the two components of the receptor that mediates the uptake of B12 in the distal ileum. Part of liver B12 is excreted in bile, and undergoes an enterohepatic circulation. The main causes of B12 malabsorption include inherited disorders (Intrinsic factor deficiency, Imerslund-Gräsbeck disease, Addison's pernicious anemia, obesity, bariatric surgery and gastrectomies. Other causes include pancreatic insufficiency, obstructive Jaundice, tropical sprue and celiac disease, bacterial overgrowth, parasitic infestations, Zollinger-Ellison syndrome, inflammatory bowel diseases, chronic radiation enteritis of the distal ileum and short bowel. The assessment of B12 deficit is recommended in the follow-up of subjects with bariatric surgery. The genetic causes of B12 malabsorption are probably underestimated in adult cases with B12 deficit. Despite its high prevalence in the general population and in the elderly, B12 malabsorption cannot be anymore assessed by the Schilling test, pointing out the urgent need for an equivalent reliable test.

Keywords: Cobalamin; Cubilin; Deficiency; Gastric intrinsic factor; Haptocorrin; Malabsorption; Transcobalamin; Vitamin B12.

Publication types

  • Review

MeSH terms

  • Adult
  • Aged
  • Anemia, Megaloblastic* / complications
  • Anemia, Megaloblastic* / genetics
  • Humans
  • Intrinsic Factor
  • Malabsorption Syndromes* / complications
  • Malabsorption Syndromes* / genetics
  • Malabsorption Syndromes* / metabolism
  • Male
  • Vitamin B 12 / metabolism
  • Vitamin B 12 Deficiency* / etiology
  • Vitamin B 12 Deficiency* / metabolism


  • Intrinsic Factor
  • Vitamin B 12