Iron in Health and Disease: An Update

Iron is an essential micronutrient for oxygen transport, cellular energy metabolism, and many enzymatic reactions. Complex physiological processes have evolved for iron acquisition to meet metabolic needs while avoiding toxicity from iron-generated free radicals. Systemic iron homeostasis is centered around the regulation of iron absorption from duodenum and iron release from stores by hepcidin. Intracellular iron is maintained under tight control by iron regulatory proteins acting at post-transcriptional level. Despite these elaborate mechanisms, iron status is frequently altered by environmental or genetic influences. Iron deficiency anemia is the most common nutritional disorder affecting a quarter of the world population. Iron deficiency is associated with impaired cognitive development and reduced capacity for physical work, making it a high priority for public health initiatives. Chronic inflammation from infections or other causes limits iron availability and contributes to anemia of chronic disease. At the opposite end are conditions where iron overload leads to serious complications from organ damage. Mutations in HFE gene are the most frequent cause of hereditary hemochromatosis in European population, but rare elsewhere in the world. Iron overload develops in dyserythropoietic anemias from increased intestinal absorption. Transfusional iron overload, most often observed in thalassemia, is increasing among cancer survivors due to the use of protocols requiring intensive transfusion support. Tissue-specific brain iron overload is observed in some degenerative neurological diseases without an increase in systemic iron. New insights into iron metabolism are guiding the development of novel therapies for iron deficiency and iron overload.