Effects of Lovastatin Therapy on Susceptibility of LDL to Oxidation During a-Tocopherol Supplementation

A randomized, double-masked, crossover clinical trial was carried out to evaluate whether lovastatin therapy (60 mg daily) affects the initiation of oxidation of low density lipoprotein (LDL) in cardiac patients on a-tocopherol supplementation therapy (450 IU daily). Twenty-eight men with verified coronary heart disease and hypercholesterolemia received a-tocopherol with lovastatin or with dummy tablets in random order. The two 6-week, active-treatment periods were preceded by a washout period of at least 8 weeks. The oxidizability of LDL was determined by 2 methods ex vivo. The depletion times for LDL ubiquinol and LDL a-tocopherol were determined in timed samples taken during oxidation induced by 2,2-azobis(2,4-dimethylvaleronitrile). Copper-mediated oxidation of LDL isolated by rapid density-gradient ultracentrifugation was used to measure the lag time to the propagation phase of conjugated-diene formation. a-Tocopherol supplementation led to a 1.9-fold concentration of reduced a-tocopherol in LDL (P,0.0001) and to a 2.0-fold longer depletion time (P,0.0001) of a-tocopherol compared with determinations after the washout period. A 43% prolongation (P,0.0001) was seen in the lag time of conjugated-diene formation. Lovastatin decreased the depletion time of reduced a-tocopherol in metal ion–independent oxidation by 44% and shortened the lag time of conjugated-diene formation in metal ion–dependent oxidation by 7%. In conclusion, a-tocopherol supplementation significantly increased the antioxidative capacity of LDL when measured ex vivo, which was partially abolished by concomitant lovastatin therapy. (Arterioscler Thromb Vasc Biol. 1999;19:1541-1548.)