Clinical Significance

Vitamin B₁₂ is the name given to any one of a group of substances termed cobalamins. They are composed of a tetrapyrole ring surrounding a central cobalt atom and differ with respect to the side groups attached to the cobalt atom. The predominant form in serum is methylcobalamin while the predominant cellular form is 5' deoxyadenosylcobalamin. Cyanocabalamin is the most stable and is used as a reference compound for measuring serum cobalamin concentrations.

Cobalamins are obtained from animal products such as meat, eggs, milk, and other dairy products. When ingested, they are bound by a protein termed intrinsic factor in the gastric juice of the stomach and are subsequently absorbed in the ileum. Intrinsic factor is required for absorption. Once in circulation, cobalamins are taken up and stored in the liver. They are released into the plasma as needed where they are carried by B₁₂ binding proteins (transcobalamins).

Vitamin B₁₂ is a coenzyme that is involved in two very important metabolic functions vital to normal cell growth and DNA synthesis: 1) the synthesis of methionine, and 2) the conversion of methylmalonly CoA to succinyl CoA. Deficiency of this vitamin can lead to megaloblastic anemia and ultimately to severe neurological problems. Megaloblastic anemia is characterized by the enlargement and reduction in number of all rapidly proliferating cells of the body, including marrow cells, and is primarily a result of the decreased capacity for DNA synthesis. Because vitamin B₁₂ and folic acid are linked by the reaction pathway for methionine synthesis, a deficiency in either will disrupt this metabolic pathway and lead to the same symptoms and medical problems. It is usually necessary to measure both vitamins in a clinical workup, with the treatment depending on which of the two is deficient.

Vitamin B₁₂ deficiency can occur for one of several reasons. The most common cause is a defect in the secretion of intrinsic factor, resulting in inadequate vitamin B₁₂ absorption from foods. This condition is called pernicious anemia and is most common in people over age 50. Other causes of vitamin B₁₂ absorbed is directly proportional to the length of functional intestine. Vitamin B₁₂ deficiency due to insufficient dietary intake is rare and can occur only after years of abstinence from all animal products.

Elevated levels of vitamin B₁₂ have been associated with pregnancy, the use of oral contraceptives and multivitamins, and in myeloproliferative diseases such as chronic granulocytic leukemia and myelomonocytic leukemia. An elevated vitamin B₁₂ level in itself has not been known to cause clinical problems.

_{Source: Access Vitamin B12 IFU #33000, 12/12/16}