Sources of Vitamin B12, also known as cobalamin, include meat, eggs, milk, liver, some shellfish, and fish, and can be produced by certain bacteria. When B12 is consumed, it binds to Intrinsic Factor (IF), which is secreted by gastric parietal cells mainly in the duodenum, and then is absorbed in the terminal ileum.
Other factors are needed to help absorb B12 and take it to the bone marrow and other tissues. This is a very complex, multistep process, now found to involve about 15 different gene products. A protein known as haptocorrin (also known as transcobalamin 1*, TCN1, or R Factor) from the saliva is initially required. When haptocorrin is cleaved via a protease in the GI tract, other transport proteins play a role, such as transcobalamin 2**(TCN2). Approximately 1/3 of the body's B12 is stored in the liver, where it can be released and transported via the transcobalamin.
Of all the proteins necessary for B12 absorption and transport, IF is the most important clinically. If there is a deficiency in IF, then this type of megaloblastic anemia is called Pernicious Anemia. See the separate section on Pernicious Anemia.
Other causes of B12 deficiencies include atrophic gastritis, Crohn's Disease, celiac disease, gastric bypass surgery, alcohol misuse (which can also cause non-megaloblastic macrocytic anemia), proton pump inhibitor, and H2 blocker drugs that reduce acid, and lack of dietary intake. Other drugs can also interfere with B12 absorption or activity. Lack of dietary intake is mainly found in vegans who do not take supplements.
*formerly known as transcobalamin I
**formerly known as transcobalamin II