Beneficial effect of gemfibrozil on the chemical composition and oxidative susceptibility of low density lipoprotein: a randomized, double-blind, placebo-controlled study.
Previous reports have shown that administration of fibrates can reduce coronary events and also improve plasma lipid levels. Oxidative modification of low density lipoprotein has been implicated in the pathogenesis of atherosclerosis, and the resistance of low density lipoprotein (LDL) to in vitro oxidation has been found to be correlated with the extent of atherosclerosis. We performed a double-blind, placebo-controlled intervention trial to establish whether gemfibrozil could improve resistance of LDL to oxidation in patients with hyperlipidemia. Patients were randomly assigned to treatment with gemfibrozil (450 mg, twice a day, n = 10) or placebo (n = 9) for 8 weeks. Blood samples were obtained after an overnight (12 h) fast. Gemfibrozil administration significantly reduced total plasma cholesterol and triglyceride levels and changed the LDL from small, dense particles (pattern B, < or = 25.5 nm) to larger, more buoyant particles (pattern A, > 25.5 nm). Gemfibrozil significantly increased the lag time of LDL oxidation in vitro by 18.2% from 45.5 +/- 8.0 min at week 0 to 53.4 +/- 11.4 min at week 8, but did not change LDL vitamin E and beta-carotene concentrations. Surprisingly, gemfibrozil significantly decreased LDL lipid peroxides by -33.1% and increased the LDL vitamin E/lipid peroxide ratio by 67.6% from 1.3 +/- 0.5 at week 0 to 2.1 +/- 0.9 at week 8. These results demonstrate that gemfibrozil treatment can render LDL less susceptible to oxidative modification while reducing plasma cholesterol and triglyceride and improving LDL subclass pattern. This antioxidative effect of gemfibrozil on LDL may be one of the factors which could delay the progression of atherosclerosis.
First Department of Internal Medicine, National Defense Medical College, Tokorozawa, Saitama, Japan.
H
H
Yoshida
T
T
Ishikawa
M
M
Ayaori
H
H
Shige
T
T
Ito
M
M
Suzukawa
H
H
Nakamura
D000328:Adult; D000368:Aged; D001053:Apolipoproteins / Q000097:blood; D001161:Arteriosclerosis / Q000188:drug therapy / Q000378:metabolism; D004311:Double-Blind Method; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D015248:Gemfibrozil / Q000627:therapeutic use*; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008054:Lipid Peroxides / Q000097:blood; D008055:Lipids / Q000097:blood; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D014810:Vitamin E / Q000097:blood
D001053:Apolipoproteins; D005230:Fatty Acids, Nonesterified; D000960:Hypolipidemic Agents; D008054:Lipid Peroxides; D008055:Lipids; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D014810:Vitamin E; D015248:Gemfibrozil