Figure 1.

Iron regulation in the infant in response to iron supplementation. TOP—Iron regulation in the breast-fed infant in the absence of iron supplementation (1) The kidney secretes erythropoietin (EPO) to support the expansion of blood volume in response to low iron and low oxygen sensing; (2) EPO enters circulation and travels to the bone marrow, (3) where it drives erythropoiesis and secretion of erythroferrone (ERFE); (4) ERFE travels to the liver and suppresses hepcidin (HAMP) production, which allows for increased transferrin-bound iron in circulation; suppression of HAMP allows export of iron from the (5) spleen via ferroportin, as well as increased intestinal absorption of iron through ferroportin, both of which further increases iron in circulation. BOTTOM—Iron regulation in response to iron supplementation: (1) iron from supplementation is absorbed through the duodenal mucosa, is picked up by transferrin, and travels to the liver (2), increasing iron stores and up-regulating HAMP; (3) HAMP enters the circulation; (4) transferrin-bound iron supports increased erythropoiesis; in the spleen (5) erythrocytes are recycled but iron is sequestered because HAMP prevents export through ferroportin; (6) elevated iron and blood volume suppresses EPO production in the kidney.