NDT Advance Access originally published online on October 19, 2007
Nephrology Dialysis Transplantation 2008 23(1):120-125; doi:10.1093/ndt/gfm557
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Chemical reactions of vitamin C with intravenous-iron formulations
1Department of Health and Clinical Science, University of Massachusetts, Lowell, MA, USA, 2Vivantes Klinikum im Friedrichshain, Berlin, Germany and 3Renal Research Institute, New York, NY, USA
Correspondence to: Garry J. Handelman, Renal Research Institute, 207 E. 94th Street, New York, NY 10128, USA. Email: garry_handelman{at}uml.edu
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Background. Intravenous (IV) iron is widely prescribed for patients on haemodialysis, to replace iron losses during treatment. It releases labile iron, which can induce oxidation of vitamin C and trigger oxidant damage. We examined the stability of vitamin C in the presence of IV iron compounds. We further examined in the ability of vitamin C to release iron from these compounds.
Methods. Vitamin C was measured by high-performance liquid chromatography with electrochemical detection. Iron release from iron sucrose (FeSuc) and ferric gluconate (FeGlu) was determined with the ferrozine method.
Results. Vitamin C, in human plasma or fetal calf serum, was oxidized in this order of reactivity: FeSuc > FeGlu > blank reaction. FeSuc and FeGlu also oxidized vitamin C when added to freshly obtained whole human blood. During a 4 h incubation in buffer, vitamin C stimulated the release of 60% of the iron content of FeSuc at p 4, with lesser amounts at pH3, 5 and 6, and 5% release at pH 7.Vitamin C also triggered the release of iron from FeGlu, but less release was observed than with FeSuc. Using ferrozine reagent, no iron release was detected to heparinized human plasma, following addition of 500 µM concentrations of iron compounds.
Conclusion. Each IV-iron compound can oxidize substantial amounts of vitamin C when added to plasma or whole blood. The interaction of vitamin C is accompanied by release of iron from the particle at mildly acidic pH, which may explain the ability of high-dose vitamin C to mobilize iron from storage sites for erythropoiesis.
Keywords: ferric gluconate; haemodialysis; intravenous iron; iron sucrose; vitamin C
Received for publication: 14.12.06
Accepted in revised form: 20. 7.07