THE EFFECT OF PROBUCOL AND VITAMIN-E TREATMENT ON THE OXIDATION OF LOW-DENSITY-LIPOPROTEIN AND FOREARM VASCULAR-RESPONSES IN HUMANS

This study investigates the hypothesis that lipid soluble antioxidants may increase the resistance of low-density lipoprotein (LDL) to oxida tion and also enhance vascular endothelial responses in humans. In a d ouble-blind parallel group study, 24 hypercholesterolaemic patients, a lready on treatment with simvastatin (20 mg day(-1)), were randomized to supplementary treatment with probucol (500 mg bd), vitamin E (400 I U daily) or placebo for 8 weeks. Mean serum cholesterol before antioxi dant treatment was 7.00 mmol l(-1). Resistance of LDL to oxidation by copper was increased by 830% in the probucol group and by 30% in the v itamin E group. However, thiobarbituric acid reacting substances in wh ole serum were not altered by either antioxidant. Probucol lowered HDL -and LDL-cholesterol levels and increased the QT interval. Forearm vas cular responses, as measured by venous occlusion plethysmography, to a cetylcholine, glyceryl trinitrate and N-G-monomethyl-L-arginine, were not significantly changed by antioxidant treatment. Probucol has a maj or, and vitamin E a minor, effect on LDL resistance to oxidation but n either compound appears to alter forearm vascular responses in vivo.