The effect of concentrated n-3 fatty acids versus gemfibrozil on plasma lipoproteins, low density lipoprotein heterogeneity and oxidizability in patients with hypertrygliceridemia

We evaluated in a double-blind randomized trial with a double-dummy design in 28 patients with primary hypertriglyceridemia, the effect of gemfibrozil (1200 mg/day) versus Omacor (4 g/day), a drug containing the n-3 fatty aci ds eicosapentaenoic (EPA) and docosahexaenoic acid (DI-IA), on lipid and li poprotein levels, low density lipoprotein (LDL) subfraction profile and LDL oxidizability. Both Omacor and gemfibrozil therapy resulted in a similar s ignificant decrease in serum triglyceride (TG), very low density lipoprotei n (VLDL) triglyceride and VLDL cholesterol concentrations and an increase i n high density lipoprotein (HDL) and LDL cholesterol concentrations. The in crease in LDL cholesterol was due to a significant increase in cholesterol content of the relatively buoyant LDL subfractions LDL1, LDL? and LDL3, whe reas the relative contribution of the dense LDL subfractions LDL4 and LDL5 to total LDL tended to decrease. So, both therapies resulted in a more buoy ant LDL subfraction profile, reflected by a significant increase of the val ue of parameter K (+ 10.3% on Omacor vs + 26.5% on gemfibrozil therapy, gem fibrozil vs Omacor P > 0.05). Cu2+-induced oxidation of LDL was measured by continuous monitoring of conjugated dienes. After 12 weeks of Omacor treat ment LDL appeared more prone to oxidative modification in vitro than LDL af ter gemfibrozil treatment, as measured by the significantly decreased lag t ime, preceding the onset of the lipid peroxidation. In both groups the rate of oxidation did not change with therapy. The amount of dienes formed duri ng oxidation increased significantly on Omacor treatment, but not on gemfib rozil treatment. Plasma thiobarbituric acid reactive substances were higher after Omacor and lower after gemfibrozil treatment, although not significa ntly. We conclude that both Omacor and gemfibrozil have favorable effects o n lipid and lipoprotein concentrations and the LDL subfraction profile. How ever, Omacor increased the susceptibility of LDL to oxidation, whereas gemf ibrozil did not affect the resistance of LDL to oxidative modification in v itro. The clinical relevance of these changes remains to be established in the light of other postulated favorable effects of n-3 fatty acids on the c ourse of cardiovascular disease. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.