Intravenous iron preparations and ascorbic acid: effects on chelatable and bioavailable iron

There is growing interest to use ascorbic acid as adjuvant therapy for patients with recombinant human erythropoietin-hyporesponsiveness (rHuEpo). Several clinical studies showed the beneficial effect of ascorbic acid treatment on hematologic parameters in rHuEpo-treated hemodialysis patients with elevated or even normal iron stores. However, whether ascorbic acid directly affects stability and cellular metabolism of intravenous iron preparations (IVI) is not well understood.

The preparations for testing were iron sucrose (Venofer), ferric gluconate (Ferrlecit), and iron dextran (INFeD). HepG2-cells were used to investigate effects of ascorbic acid on iron bioavailability for the intracellular labile iron pool (LIP) from IVI by using the fluorescent calcein-assay, and cellular ferritin content was measured by enzyme-linked immunosorbent assay (ELISA). Transferrin-chelatable iron was assessed by fluorescent-apotransferrin, and cell toxicity was assayed by neutral red cytotoxicity test.

The effects of vitamin C on different preparations do not reflect their known chemical stability (i.e., iron dextran >iron sucrose >ferric gluconate). Effects of ascorbic acid on the increase of the intracellular LIP, as well as on increasing mobilization to transferrin in serum, were limited to iron sucrose. Ascorbic acid did not increase cell toxicity and the amount of low molecular weight iron in serum.

We conclude that corrected ascorbic acid levels in hemodialysis (HD) patients could increase the amount of bioavailable iron from iron sucrose, but not from other classes of IVI. Vitamin C administration could therefore result in a lower need of iron sucrose to correct anemia.