What dose of vitamin E is required to reduce susceptibility of LDL to oxidation?

Background: Oxidative modification of low density lipoprotein (LDL) may play a role in the pathogenesis of atherosclerosis. Ingestion of vitamin E in high dosage has been shown to reduce the susceptibility of LDL to copper-induced oxidation, as assessed ex vivo. Aim: To determine a minimum dose of supplementary vitamin E which will significantly reduce the susceptibility of LDL to oxidation, Methods: A single centre, double-blind, parallel placebo-controlled trial. Healthy volunteers (total n=42) were randomised to receive placebo, 500, 1000 or 1500 IU/day of vitamin E (D-alpha-tocopherol) for a period of six weeks. Primary outcomes were change in lag time or oxidation rate to copper-induced LDL oxidation. Secondary outcomes were changes in plasma vitamin E levels and clinical tolerance. Results: Lag time to LDL oxidation was significantly prolonged and oxidation rate significantly slowed at all dose levels of vitamin E, indicating a threshold effect from 500 IU/day. Compared to placebo, the median prolongation in lag time on 500 IU/day was 26%, on 1000 IU/day 24% and on 1500 IU/day 35%. The corresponding slowing in oxidation rates was 14%, 19% and 25% respectively. The per cent change in plasma vitamin E concentration was highly correlated with the change in lag time (r=0.61, p<0.001) and oxidation rate (r=-0.55, p<0.001). Vitamin E was generally well tolerated. Conclusions: Vitamin E in a dose of 500 IU/day will significantly reduce the susceptibility of LDL to oxidation. Whether or not this treatment will consistently reduce the future incidence of coronary artery disease will only be answered by further clinical trials.