Understanding Iron Metabolism: Lessons from Transfusion-dependent Thalassemia

Iron metabolism is well regulated in humans by a number of proteins, the most important one being hepcidin.1,2 Hepcidin inhibits iron absorption at the gastrointestinal (GI) luminal surface through its inhibition of ferroportin.1 Body iron stores, as well as inflammation, increase the level of hepcidin, thereby leading to decreased GI iron absorption. Additionally, high hepcidin levels lead to immobilization of iron within the reticuloendothelial system, specifically, the spleen and liver.3 The strict regulation of iron metabolism and the immobilization of iron during inflammation may have developed in animals and humans as a protective mechanism against infection by limiting the availability of iron to the infecting organism. The average daily GI absorption is 1–2 mg, which is similar to the amount shed out by the sloughing of epithelial cells in the GI system. Menstruating females lose an additional 20–40 mg every month. Other than this, humans are not equipped with any other way of removing iron.