Intrinsic factor
Glycoprotein produced in the stomach which binds to vitamin B12
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In the less acidic environment of the small intestine, pancreatic enzymes digest the glycoprotein carrier and vitamin B12 can then bind to intrinsic factor. This new complex is then absorbed by the epithelial cells (enterocytes) of the ileum. Inside the cells, vitamin B12 dissociates once again and binds to another protein, transcobalamin II; the new complex can then exit the epithelial cells to be carried to the liver.
Site of secretion
The site and cell type of formation of the intrinsic factor varies in different species. Intrinsic factor is secreted in oxyntic gastric glands and predominantly by parietal cells of the stomach fundus and body in humans, while it is produced by chief cells in the stomach body in rodents. In pigs it is obtained from the pylorus and beginning of the duodenum.
It 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 amount of human gastric intrinsic factor limits normal efficient absorption of B12 to about 2 μg per meal, a nominally adequate intake of B12.
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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 CBLIF gene (previously referred as GIF, gastric intrinsic factor) 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.
Vitamin B12 absorption is a multistep process that involves the stomach, pancreas and small intestine, and is mediated by two carriers: haptocorrin (transcobalamin I) and intrinsic factor. Because haptocorrin binds to the acid-sensitive vitamin B12, it can safely pass through the acidic stomach to the duodenum, given time in the mouth.