Erythropoietin and iron: the role of ascorbic acid

Provision of sufficient available iron is a prerequisite to ensure the opti mal response to recombinant human erythropoietin (rHuEpo). Functional iron deficiency (a state when iron supply is reduced to meet the demands for inc reased erythropoiesis) is the common cause of rHuEpo hyporesponsiveness in dialysis patients who have normal iron status, even when they are iron-over loaded. Iron supplementation is not justified for this hyporesponsiveness i n patients with iron overload due to the potential hazards of iron overload aggravated by intravenous iron therapy. Furthermore, in vivo studies indic ated that the promising effect of intravenous iron medication to overcome i ron-deficient erythropoiesis is not observed in iron-overloaded haemodialys is (HD) patients. Ascorbic acid, a water-soluble antioxidant as well as a r educing agent, has a number of associations with iron metabolism, Recent re search highlights that ascorbic acid can potentiate the mobilization of iro n from inert tissue stores and facilitates the incorporation of iron into p rotoporphyrin in iron-overloaded HD patients being treated with rHuEpo. Int erest has turned towards the use of ascorbic acid as an adjuvant therapy in this field. This review focuses on the improvement of rHuEpo response by a dministration of ascorbic acid and discusses its clinical implications and potential issues for nephrologists.