Intrinsic factor

Site of secretion

Intrinsic factor is secreted by parietal cells within the stomach, and so is present in the gastric juice as well as in the gastric mucous membrane. The optimum pH for its action is approximately 7. Its concentration does not correlate with the amount of HCl or pepsin in the gastric juice, e.g., intrinsic factor may be present even when pepsin is largely absent. The site of formation of the intrinsic factor varies in different species. In pigs it is obtained from the pylorus and beginning of the duodenum; in human beings it is present in the fundus and body of the stomach.

The limited amount of normal human gastric intrinsic factor limits normal efficient absorption of B12 to about 2 μg per meal, a nominally adequate intake of B12.

Insufficiency

In pernicious anemia, which is usually an autoimmune disease, autoantibodies directed against intrinsic factor or parietal cells themselves lead to an intrinsic factor deficiency, malabsorption of vitamin B12, and subsequent megaloblastic anemia. Atrophic gastritis can also cause intrinsic factor deficiency and anemia through damage to the parietal cells of the stomach wall. Pancreatic exocrine insufficiency can interfere with normal dissociation of vitamin B12 from its binding proteins in the small intestine, preventing its absorption via the intrinsic factor complex. Other risk factors contributing to pernicious anemia are anything that damages or removes a portion of the stomach's parietal cells, including bariatric surgery, gastric tumors, gastric ulcers, and excessive consumption of alcohol.

Mutations in the GIF gene are responsible for a rare inheritable disease called intrinsic factor deficiency which results in malabsorption of vitamin B12.

Treatment

In most countries, intramuscular injections of vitamin B12 are used to treat pernicious anemia. Orally administered vitamin B12 is absorbed without intrinsic factor, but at levels of less than one percent than if intrinsic factor is present. There are not enough studies on whether pills are as effective in improving or eliminating symptoms as parenteral treatment.

Vitamin B12 can also be given sublingually, but there is no evidence that this route of administration is superior to the oral route, and only Canada and Sweden routinely prescribe this route of administration.

Because vitamin B12 absorption is a multistep process that involves the stomach, pancreas and small intestine, and is mediated by two carriers: Haptocorrin and intrinsic factor, and because Haptocorrin (transcobalamin I) binds to vitamin B12, and Vitamin B12 is acid-sensitive, when vitamin B12 binds to Haptocorrin it can safely pass through the acidic stomach to the duodenum, given time in the mouth.

References

References

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