Dose-response effects of marine omega-3 fatty acids on apolipoproteins, apolipoprotein-defined lipoprotein subclasses, and Lp-PLA₂ in individuals with moderate hypertriglyceridemia

Background Apolipoprotein (apo) distribution and lipoprotein (Lp)-associated markers of inflammation, such as lipoprotein-associated phospholipase A₂ (Lp-PLA₂), influence the atherogenicity of circulating lipids and lipoproteins. Little evidence exists regarding the dose-response effects of the marine omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on apos, apo-defined Lps, and Lp-PLA₂. Objective The purpose of this study was to compare the effects of 0, 0.85, and 3.4 g/d of EPA + DHA on Lp-PLA₂ mass and activity in individuals with moderate hypertriglyceridemia. We also measured effects on concentrations of apoAI, apoAII, apoB, apoC, apoD, and apoE-defined Lp subclasses. Methods The study was a randomized, doubleblind, crossover design with 8-week treatment periods and 6-week washout periods. During the 3 treatment periods, subjects (n = 25) received 0 g/d EPA + DHA, 0.85 g/d EPA + DHA (low dose), and 3.4 g/d EPA + DHA (high dose) in random order. Results apoB and apoC-III were significantly decreased by the high dose relative to placebo and low dose (P <.01), as was very low-density lipoprotein cholesterol (P <.005). The low dose had no effect on Lp outcomes compared with placebo. The high- and low-dose effects differed significantly for heparin-precipitated apoC-III, LpB, LpA-I, and apoB/apoA-I ratio (P <.05). There was a trend for a decreased Lp-PLA₂ mass with the high dose (P =.1). Conclusion The effects of 3.4 g/d EPA + DHA on apoB and apoC-III may reduce atherosclerotic plaque progression in individuals with elevated triglycerides.