OPINION Inflammation and diminished iron status: mechanisms and functional outcomes

Iron (Fe) is an essential trace element, and optimal Fe status is critical for human performance. Most of the body’s demand for Fe is met through efficient recycling from senescent red blood cells, and the remainder is gleaned from the diet. The daily recommended dietary allowance for Fe is approximately 8 mg for adult men and postmenopausal women and 18 mg for premenopausal women, and the average adult absorbs only 1–2 mg of Fe each day [1]. Fe status is regulated through the interplay between three cell systems: the duodenal enterocytes that absorb Fe, splenic and hepatic macrophages that scavenge Fe to release into circulation as necessary, and hepatocytes that store and release Fe into circulation. Iron in the diet is present in both heme and nonheme forms. Heme Fe, absorbed through hemecarrier protein-1 (HCP-1), is subsequently released in the cytosol by heme oxygenase-1 (HO-1). Ferric Fe (Fe3þ) is reduced to ferrous Fe (Fe2þ) by duodenal cytochrome-b (Dcytb) prior to uptake into the enterocyte through divalent metal transporter-1 (DMT1). Ascorbic acid also enhances Fe absorption in part by reducing Fe3þ to Fe2þ and possibly by chelating Fe [2]. Once inside the cell, Fe2þ is stored bound to