EFFECT OF ANTIOXIDANTS ON OXIDATIVE MODIFICATION OF LDL

Human low density lipoprotein (LDL) with a molecular mass of average 1300 molecules of polyunsaturated fatty acids (PUFAs) bound in the different lipid classes. The predominant antioxidant in LDL is alpha-tocopherol, with an average of 6 molecules in each LDL particle. The other substances with potential antioxidant activity are: gamma-tocopherol, beta-carotene, alpha-carotene, lycopene, cryptoxanthin, cantaxanthin, phytofluene and ubiquinol-10. Each is present in amounts of only 1/20th to 1/300th of that of alpha-tocopherol. If LDL is exposed to oxidative conditions (Cu++ions, macrophages) a lag phase precedes the oxidation of PUFAs. During the lag phase the antioxidants disappear with alpha-tocopherol the first to go and beta-carotene the last. The lag phase, which can readily be determined, is an index of the oxidation resistance of LDL. If LDL is loaded with vitamin E in vitro its oxidation resistance increases linearly with its alpha-tocopherol content according to the equation, y = kx + a. The same relationship is applicable it the alpha-tocopherol content of LDL is increased by taking oral vitamin E. Daily doses of 150, 225, 800 and 1200 IU RRR-alpha-tocopherol increased the LDL alpha-tocopherol on average to 138%, 158%, 144% and 215% of the initial value, the oxidation resistance being increased to 118%, 156%, 135% and 175%, respectively. The efficiency ot vitamin E-dependent (= k) and the vitamin E independent (= a) oxidation resistance seem to be subject specific with strong individual variation. The k values ranged from 1.38 to 34.1 min (mean 4.5 +/- 3.3, n = 36) and the value of a ranged from -49 to +97 min (mean 43.9 +/- 31.5). The variability of k and a explains why the alpha-tocopherol content of an individual LDL sample is per se not predictive for its resistance to oxidation.