SUPPLEMENTATION WITH LOW-DOSES OF VITAMIN-E PROTECTS LDL FROM LIPID-PEROXIDATION IN MEN AND WOMEN

There is accumulating evidence that oxidative modification of LDL is a n important step in the process of atherogenesis and that antioxidants may protect LDL from oxidation. We and others have previously shown t hat ingestion of pharmacological doses of the antioxidant D,L-alpha-to copherol (vitamin E), far above the recommended daily intake (ie, 12 t o 15 IU/d for adults), increases the oxidation resistance of LDL. In t his study, we ascertained the minimal supplementary dose of vitamin E necessary to protect LDL against oxidation in vitro. Twenty healthy vo lunteers (10 men and 10 women, aged 21 to 31 years) ingested consecuti vely 25, 50, 100, 200, 400, and 800 IU/d D,L-alpha-tocopherol acetate during six 2-week periods. No changes were observed in LDL triglycerid e content, fatty acid composition of LDL, or LDL size during the inter vention. Concentrations of alpha-tocopherol in plasma and LDL were bot h 1.2 times the baseline values after the first period (25 IU/d) and 2 .6 and 2.2 times, respectively, after the last period (800 IU/d). Ther e was a linear increase in LDL alpha-tocopherol levels up to an intake of 800 IU/d (r=.79, P<.0001) and a good correlation between alpha-toc opherol in plasma and LDL (r=.66, P<.0001). Simultaneously, the resist ance of LDL to oxidation was elevated dose-dependently (+28% after the last period) and differed significantly from the baseline resistance time even after ingestion of only 25 IU/d. Correlation between alpha-t ocopherol content of LDL and resistance time for all data was r=.57 (P <.0001), whereas the correlation between plasma alpha-tocopherol and r esistance time was r=.69 (P<.0001). The rate of oxidation was decrease d significantly at 400 and 800 IU/d (-13% and -17%, respectively). Bas eline resistance time was not significantly different between men and women, but propagation rate was higher with LDL from men at baseline a nd after intake of 25 and 50 IU/d. Minor differences in LDL vitamin E levels and resistance time were found between men and women in respons e to vitamin E intake. Statistical evaluation of the relations between alpha-tocopherol content of LDL and resistance time in each of the 20 individual subjects showed strong and significant correlations for 14 individuals, indicating that vitamin E was the most important paramet er that determined the oxidation resistance of LDL in these subjects. ANOVA indicated that LDL alpha-tocopherol content (47%) and interindiv idual variation (39%) were the most prominent parameters that contribu ted to the total variance in resistance time.