B12 and Intrinsic Factor
Intrinsic factor is a protein produced by the cells of the stomach, parietal cells, which also produce the acid (gastric juice) for digestion. The intrinsic factor is the compound which facilitates and allows the absorption of vitamin B12 from food in the stomach and the intestines.
Once ingested the B12 becomes bound to a binding proteins present in the hydrochloric acid of the stomach. In the less acidic environment of the small intestine, these proteins separate from the vitamin, enabling it to bind to intrinsic factor and enter the bloodstream.
The intrinsic factor is an enzyme-like unidentified substance secreted by the stomach. It is present in the gastric juice as well as in the gastric mucous membrane. The optimum pH for the action of the intrinsic factor is 7 and it is inactivated at temperatures above 45oC.
In pernicious anemia, an autoimmune disease, autoantibodies direct themselves against the intrinsic factor and/or parietal cells themselves and lead to an intrinsic factor deficiency, which results in malabsorption of vitamin B12. Atrophic gastritis, an inflammation of the mucous membrane of the stomach, can also cause intrinsic factor deficiency and anemia through damage to the parietal cells. Pancreatic exocrine insufficiency can interfere with normal dissociation of vitamin B12 from the proteins, as well preventing its absorption via the intrinsic factor structure. Bariatric surgery is a known risk factor in the development of pernicious anemia, other risk factors include stomach tumors, gastric ulcers, and excessive consumption of alcohol.
Patients experiencing an insufficiency in their intrinsic factor levels cannot benefit from a low dose oral vitamin B-12 supplement, because it will not absorb through the wall of the small intestine. Historically, the disease was thought untreatable before the discovery that it could be managed with regular injections of vitamin B-12, thus bypassing the digestive tract. Other options are available nowadays if injections are not the desired method of supplementation.