THE EFFECT OF ALPHA-TOCOPHEROL SUPPLEMENTATION ON LDL OXIDATION - A DOSE-RESPONSE STUDY

Because much data have accrued to support the concept that oxidatively modified LDL (Ox-LDL) can promote atherogenesis, the role of antioxidants in decreasing LDL oxidation has assumed great importance. High-dose alpha-tocopherol supplementation in humans decreases the susceptibility of LDL to oxidation. Hence, the aim of the present study was to ascertain the minimum dose of cu-tocopherol that would decrease the susceptibility of LDL to oxidation. The effect of alpha-tocopherol in doses of 60, 200, 400, 800, and 1200 IU/d on copper-catalyzed LDL oxidation was tested in a randomized placebo-controlled study over 8 weeks. There were eight subjects in each group. Oxidation of LDL was monitored by measuring the formation of conjugated dienes and lipid peroxides by the thiobarbituric acid-reacting substances (TBARS) assay over an 8-hour time course at baseline and after 8 weeks of supplementation. Neither placebo nor any of the doses of alpha-tocopherol resulted in any side effects or exerted an adverse effect on the plasma lipoprotein profile. However, there was a dose-dependent increase in plasma and lipid-standardized alpha-tocopherol levels with increasing doses of alpha-tocopherol supplementation. LDL alpha-tocopherol appeared to follow a similar trend. When the time-course curves of LDL oxidation and the kinetics of LDL oxidation were examined, there was no significant effect at 8 weeks compared with baseline in the groups that received placebo or alpha-tocopherol 60 or 200 IU/d. However, in the groups that received at least 400 IU/d alpha-tocopherol, there was a decreased susceptibility of LDL to oxidation, as shown by the mean levels in the time-course curves, prolongation in the lag phase, and a decrease in the oxidation rate. Furthermore, both plasma and LDL alpha-tocopherol correlated significantly with the lag phase of oxidation and inversely with the oxidation rate. The results of the present study show that the minimum dose of oc-tocopherol needed to significantly decrease the susceptibility of LDL to oxidation is 400 IU/d.