Oral Vitamin C Administration Increases Lipid Peroxidation in Hemodialysis Patients

Abstract

Background: Since vitamin C (ascorbic acid, AA) deficiency is common in hemodialysis patients, systematic supplementation has been recommended. Further, vitamin C has been advocated as a potential adjuvant to erythropoietin by virtue of its capacity to improve iron utilization. However, vitamin C may have a paradoxical pro-oxidant effect in the presence of iron. Methods: In 109 hemodialysis patients, oral vitamin C was administered at 360 and 1,500 mg/week during 3 months each, followed by a wash-out period of 3 months. Results: Serum AA increased from 0.22 to 0.33 and 0.63 mg/dl after 360 and 1,500 mg/week, respectively. However, a commensurate increase of plasma malondialdehyde (MDA), a parameter of lipid peroxidation, with 9 and 26% was observed. Serum AA and plasma MDA returned to baseline after withdrawal of vitamin C. Parameters of iron status, nutrition, inflammation, dialysis efficiency and plasma lipids remained unaltered. In a stepwise multiple regression analysis, serum AA and ferritin were strong and independent predictors of MDA. Conclusion: Oral vitamin C supplementation in hemodialysis patients increases lipid peroxidation, especially in patients with increased serum ferritin. The potential benefits of restored vitamin C status and improved erythropoiesis may be entirely overruled by the adverse consequences of oxidative tissue injury.

Effect of combined vitamins C and E supplementation on oxidant/antioxidant status in hemodialysis patients

“…It is known that hemodialysis patients have a weak of antioxidant defense system resulting in increased levels of lipid peroxidation product [2,4,5,17,29]. These observations also support our findings in which low baseline levels of antioxidants were observed.…”

“…The decrease in vitamin C levels could be related to excessive loss through the membrane and or exhaustion of vitamin C in regenerating of vitamin E from tocopheroxyl radicals and thus maintain vitamin E in its non-radical reduced form [4]. Increasing levels of plasma vitamin C during the supplementation period is in agreement with earlier reports [10,26,28,29].…”

Oxidative stress in hemodialysis: Causative mechanisms, clinical implications, and possible therapeutic interventions

“…Two more studies have reported that vitamin C, regardless the route of administration, has the surprising effect of increasing OS in HD patients . De Vriese et al, showed that after oral administration of 1500 mg vitamin C per week for 3 months, serum lipid peroxides were increased.…”

“…115,119 Two more studies have reported that vitamin C, regardless the route of administration, has the surprising effect of increasing OS in HD patients. 120 Two randomized, placebo-controlled trials reported that daily oral administration of 250 mg of vitamin C significantly reduced oxidative products in serum. 123,124 Yang et al, showed that iv administration of 1000 mg of vitamin C before each HD session significantly decreased HD-evoked OS in a group of 80 HD patients, 25 while another study reported that both iv infusion of vitamin C and use of dialysate rich in vitamin C in chronic maintenance HD patients played a significant protective role against the HD-mediated OS.…”

Ankyrin is the major oxidised protein in erythrocyte membranes from end-stage renal disease patients on chronic haemodialysis and oxidation is decreased by dialysis and vitamin C supplementation

“…There is also evidence that vitamin C is effective in increasing the haemoglobin concentrations in patients who are hyporesponsive on treatment with erythropoietin, and/or decreasing of the rHuEPO requirements [25,26]. However, there may be adverse effects of vitamin C supplementation, a) especially in relation to the hyperoxalemia [27], and b) its paradoxical pro-oxidant effect in the presence of iron [28].…”