Eicosapentaenoic acid improves endothelial function in hypertriglyceridemic subjects despite increased lipid oxidizability

Background: Epidemiologic investigations suggest that fish oil, which contains eicosapentaenoic acid (EPA), has favorable cardiovascular effects. Fish oil improves endothelial function in subjects with hypercholesterolemia or diabetes. However, controversy persists regarding relationships between primary hypertriglyceridemia and endothelial dysfunction. Moreover, lipoproteins are more susceptible to oxidation in vitro after incorporation of fish oil. Methods: We determined the effects of EPA on serum lipids, susceptibility of low-density lipoproteins (LDL) and very-low-density lipoproteins (VLDL) to oxidation, and endothelial function in hypertriglyceridemic (HTG) subjects. In 8 men with untreated primary hypertriglyceridemia (plasma triglyceride between 150 and 500 mg/dL) and 7 control subjects (triglyceride below 150 mg/dL), forearm blood flow (FBF) responses were tested. In HTG subjects, this was repeated 3 months after initiation of EPA (1800 mg/day). Cu2+-induced oxidation of VLDL and LDL was determined by serial measurement of conjugated dienes. We used lag time, which corresponded to the period when the lipoproteins were resistant to oxidation, as a parameter of oxidizability. FBF responses to acetylcholine and sodium nitroprusside were determined by strain-gauge plethysmography. Results: Plasma triglyceride in HTG subjects fell 31% with EPA supplementation. Before EPA, VLDL and LDL lag times in HTG subjects were shorter than in control subjects. EPA further reduced lag time for VLDL but not LDL. The FBF response to acetylcholine (but not to nitroprusside) was significantly less in HTG subjects before EPA than in control subjects. EPA normalized the FBF response to acetylcholine. Conclusions: EPA improves endothelial function in HTG subjects despite increasing in VLDL oxidizability.