Intrinsic factor

Intrinsic factor is a glycoprotein produced by the parietal cells of the stomach. It is necessary for the absorption of vitamin B₁₂ later on in the terminal ileum.

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Upon entry into the stomach, vitamin B₁₂ becomes bound to one of two B₁₂ binding proteins present in gastric juice. In the less acidic environment of the small intestine, these proteins dissociate from the vitamin, enabling it to bind to intrinsic factor and enter the portal circulation through a receptor in the ileal mucosa specific for the B₁₂-intrinsic factor complex.

Clinical significance

In pernicious anemia, 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.

Bariatric surgery is a known risk factor in the development of pernicious anemia. Other risk factors contributing to this condition are stomach tumors, gastric ulcers, and excessive consumption of alcohol.

Note

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. More recently, Swedish researchers discovered that sufficiently large doses of B-12 can also be absorbed sublingually, so injections are necessary only for those unable to take pills by sublingual administration.