A randomized, single-blind, placebo-controlled trial of the effects of 200 mg alpha-tocopherol on the oxidation resistance of atherogenic lipoproteins

Supplementation with high doses of alpha-tocopherol has increased the oxidation resistance of LDL in many clinical trials. There have been only a few placebo-controlled trials in healthy persons of alpha-tocopherol doses usually contained in dietary supplements. We carried out a single-blind, placebo-controlled, randomized trial to examine the effect of 200 mg RRR-alpha-tocopheryl acetate/d on the oxidation resistance of atherogenic lipoproteins (VLDL+LDL including intermediate-density lipoproteins) in 40 smoking men. VLDL+LDL oxidation resistance was assessed as conjugated dienes after copper induction and hemin degradation after hydrogen peroxide induction. Also, the LDL total peroxyl-radical trapping antioxidant parameter (LDL TRAP) and plasma malondialdehyde were measured at baseline and after 2 mo of supplementation. Plasma RRR-alpha-tocopherol concentrations were measured at 2-h intervals for 12 h at baseline and after 2 mo of supplementation. Compared with placebo, 200-mg RRR-alpha-tocopheryl acetate supplementation elevated plasma and VLDL+LDL alpha-tocopherol concentrations, LDL TRAP, and oxidation resistance of VLDL+LDL. Plasma alpha-tocopherol increased by 88% (P < 0.0001), VLDL+LDL alpha-tocopherol increased by 90% (P < 0.0001), and LDL TRAP by 58% (P < 0.0001). The time to the start of oxidation (lag time) was prolonged by 34% when assessed with a copper-induced method and by 109% when assessed with a hemin + hydrogen peroxide-induced method; the time to maximal oxidation was prolonged by 21% (copper-induced method) in the vitamin E-supplemented group. Changes in plasma alpha-tocopherol, lipid-standardized alpha-tocopherol, and VLDL+LDL alpha-tocopherol correlated significantly with changes in LDL TRAP, lag time, and time to maximal oxidation. Differences in changes between groups in the area under the curve for plasma alpha-tocopherol were significant (P < 0.009). Our results suggest that 200 mg oral RRR-alpha-tocopheryl acetate/d had a clear effect on the in vitro oxidation of VLDL+LDL in smoking men.