Alpha-tocopherol supplementation decreases the oxidative susceptibility ofLDL in renal failure patients on dialysis therapy

Atherosclerotic cardiovascular disease is the leading cause of death in pat ients with end stage renal disease (ESRD) who have undergone dialysis treat ment. The oxidation of low density lipoprotein (LDL) appears to be a crucia l step in the pathogenesis of atherosclerosis. The increased oxidative stre ss and attendant increased oxidizability of lipoproteins, such as LDL could contribute to the accelerated atherosclerosis in dialysis patients. Since cc-tocopherol (AT) is the major antioxidant in LDL, the aim of the present study was to test the effectiveness of RRR-AT supplementation (800 I.U. per day) for 12 weeks on the susceptibility of LDL to oxidation, The study sub jects comprised patients with chronic renal failure on hemodialysis (HD), p eritoneal dialysis (PD), and age and sex matched controls (C). Plasma fatty acids, lipoproteins and AT levels were measured in these subjects before a nd after supplementation. Also, LDL AT and oxidizability was studied. LDL w as isolated by ultracentrifugation at baseline and after 12 weeks of supple mentation, and subjected to a 5-h time course of copper catalyzed oxidation . Oxidation was measured by the formation of conjugated dienes (CD) and lip id peroxides (LP). Supplementation with AT did not alter the plasma lipid o r lipoprotein profile of these subjects. Plasma lipid-standardized AT and L DL AT concentrations were not different among the groups at baseline. AT su pplementation significantly increased plasma lipid-standardized AT (C = 150 %, HD = 149%, PD = 217%, P< 0.001) and LDL AT concentrations (C = 94%, HD = 94%, PD = 135%, P < 0.003), AT enrichment of LDL resulted in a significant prolongation in conjugated diene lag phase in all groups (C = 34%, HD = 21 %, PD = 54%, P < 0.02). Lipid peroxide lag phase was also increased signifi cantly in C (27%,) and PD (40%) groups after AT supplementation (P < 0.01). There was a significant positive correlation between plasma lipid standard ized AT and lag phase (I = 0.54, P = 0.0003). Overall, AT decreased the sus ceptibility of LDL to oxidation in patients with chronic renal failure but the benefit appears to be greater in patients on PD. Therefore, AT suppleme ntation may also provide a measure of protection against CAD in patients wi th chronic renal failure on dialysis therapy. (C) 2000 Elsevier Science Ire land Ltd. All rights reserved.