NDT Advance Access originally published online on October 4, 2005
Nephrology Dialysis Transplantation 2006 21(1):234-235; doi:10.1093/ndt/gfi154
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Effect of ascorbic acid supplementation on plasma isoprostanes in haemodialysis patients
Email: dochan{at}ausdoctors.netSir,
We would like to report the effect of ascorbic acid (AA) supplementation on plasma F2-isoprostanes in haemodialysis patients with anaemia and hyperferritinaemia. The F2-isoprostanes, free-radical oxidation products of arachidonic acid, have been quantified in human models of increased oxidative stress [1], including haemodialysis patients [2], and are a useful measure of in vivo lipid peroxidative damage [3]. While AA supplementation may improve anaemia in haemodialysis patients with iron-overload and normal iron status [4,5], the effects on parameters of oxidative stress are conflicting. Studies have shown an extra-cellular pro-oxidant effect in vitro with bolus doses of AA [6], but intracellular anti-oxidant effects in vivo over 8 weeks of AA supplementation [7]. Recently, Fumeron and colleagues have demonstrated that there is no effect of short-term oral AA administration on oxidative stress markers [8]. As discussed in their paper, these paradoxical effects may relate to increased presence of catalytic transition metal ions such as iron and oxalate which favour pro-oxidant activity, AA doses used, whether AA was administered orally or intravenously (IV), and differing assays for Reactive Oxygen Species detection. We have extended the findings of Fumeron et al. by examining the effect of both oral and i.v. AA administration on plasma F2-isoprostanes and serum oxalate levels, as the latter may counteract the antioxidant effects of ascorbic acid.
In a sequential study, we randomly assigned 21 haemodialysis patients with mild anaemia (mean Hb 114 g/l ± SE 2.2) and hyperferritinaemia (mean ferritin 632.0 ug/l±59.4) to either 250 mg of oral (n = 10) or IV (n = 11) AA three times a week post-dialysis [9]. We measured plasma F2-isoprostanes before treatment with AA, after 8 weeks of AA and finally following a 4 week washout period. Plasma F2-isoprostanes were measured on EDTA plasma samples collected into cold tubes protected from in vitro oxidation by the addition of 20 µg of butylated hydroxytoluene, and assayed using a combination of silica and reverse-phase cartridges, high-performance liquid chromatography and gas chromatography mass spectrometry using electron capture negative ionization [10]. As previously reported [9], plasma ascorbic acid and serum oxalate levels increased significantly following treatment with oral and IV AA, and the increase was not significantly different between the two routes of administration. We did not observe a significant change in the plasma F2-isoprostane level with either oral or IV AA from baseline to week 8 [week 0: 1992.0 pmol/l (95% CI 1603.8–2472.3) vs 1908.4 pmol/l (95% CI 1473.9–2470.6), P = 0.60]. Additionally, plasma F2-isoprostane level was not statistically different after the washout period [week 8: 1908.4 pmol/l 95% CI (1473.9–2470.6) vs week 12: 1979.7 pmol/l (95% CI 1586.0–2471.3), P = 0.62]. Furthermore, the route of AA administration, IV or oral, had no effect on plasma F2-isoprostane level when adjusted for baseline values (P = 0.68).
We acknowledge that the lack of effect on oxidative stress may relate to the low dose of AA used, short duration of therapy and lack of co-administration with vitamin E. The lack of observed antioxidant activity with AA supplementation may also be due to the associated elevation in serum oxalate levels [11] and hyperferritinaemia, which are known to increase pro-oxidant activity. Finally, although we did not specifically measure for markers of inflammation, ferritin, a known acute-phase protein, was unchanged during the study period.
In summary, our study provides further supportive evidence that short-term treatment with either oral or IV AA has no effect on markers of oxidative stress despite an increase in plasma ascorbic acid levels.
Conflict of interest statement. None declared.
1 Department of Nephrology Royal Perth Hospital2 School of Medicine and Pharmacology and Western Australian Heart Research Institute University of Western Australia, Perth WA6001, Australia
Acknowledgments
We acknowledge financial support from the Janssen-Cilag Clinical Research Grant Scheme. Dr Ashley Irish has received honorariums from Amgen and Janssen-Cilag.
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