Intrinsic Factor is a glycoprotein produced in the stomach by the parietal cells, the cells that produce the stomach’s hydrochloric acid. In patients with a condition often called Pernicious anemia these gastric parietal cells are damaged by antibodies produced by the body in an autoimmune disorder and patients fail to produce hydrochloric acid and intrinsic factor. Intrinsic factor is required as a transport agent and to allow efficient absorption if vitamin B12 from the intestine. When bound to intrinsic factor vitamin B12 is absorbed by specialized cells in the distal part of the small bowel called the ileum. B12 is very inefficiently absorbed in patients with Pernicious anemia who lack intrinsic factor. For many years it was felt that in order to treat b12 deficiency in patients with Pernicious anemia it was necessary to use parenterally injected B12, but in recent years both oral B12 and sublingual B12 in very high doses have been found to be effective in treating this disorder.
The discovery of intrinsic factor is as bizarre and intriguing as any medical discovery. For much of history pernicious anemia lived up to its name, and patients became increasingly B12 deficient and developed the hematologic and neurologic symptoms of B12 deficiency. Prior to the discovery of vitamin B12 as the cause of Pernicious anemia and the possibility of treatment with B12 rich foods like liver the average life expectancy of patients with this disorder was 1-3 years. The name intrinsic factor was introduced by British physician William Bosworth Castle who found that when he ate raw hamburger and after 1 hour regurgitated the hamburger and fed it to patients with B12 deficiency it effectively treated the disorder, whereas raw hamburger alone was ineffective. This proved that something intrinsic to the gastric juices seemed to be needed to treat Pernicious anemia.
Subsequently it was found that large amounts of raw liver, or liver juice taken orally daily was somewhat effective in the treatment of pernicious anemia. Later a more concentrated form of liver extract was found to be effective when injected and finally B12 was isolated and by the 1950’s production using bacteria was perfected allowing less expensive larger quantities to be produced and injected vitamin B12 therapy became widespread.
This circumvented the need for intrinsic factor by injecting the B12 so that it could be absorbed from the tissues into the bloodstream. Vitamin B12 is primarily stored in the liver, and normal stores of vitamin B12 are sufficient to last for several months.
In people with normal gastric parietal cell function and who produce intrinsic factor about 1-2.5 mcg of vitamin B12 absorption is required to meet the needs of the typical human. Without intrinsic factor only about 1% of an ingested dose of B12 is absorbed making it necessary to take very high doses of B12 orally of sublingually to assure adequate absorption. In people with normal production of intrinsic factor only small amounts of meat are needed to provide adequate B12 in the diet, so B12 deficiency is seldom encountered except in vegans.