Ethyl EPA and ethyl DHA cause similar and differential changes in plasma lipid concentrations and lipid metabolism in subjects with low-grade chronic inflammation

Authors: SO, JISUN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; ASZTALOS, BELA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; HORVATH, KATALIN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; LAMON-FAVA, STEFANIA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Journal of Clinical Lipidology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/11/2022
Publication Date: 10/17/2022
Citation: So, J., Asztalos, B.F., Horvath, K., Lamon-Fava, S. 2022. Ethyl EPA and ethyl DHA cause similar and differential changes in plasma lipid concentrations and lipid metabolism in subjects with low-grade chronic inflammation. Journal of Clinical Lipidology. https://doi.org/10.1016/j.jacl.2022.10.002.
DOI: https://doi.org/10.1016/j.jacl.2022.10.002

Interpretive Summary: Elevated plasma concentrations of triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) are established risk factors for cardiovascular disease. Fish oil, which contains the omega-3 fatty acids EPA and DHA, has been shown to reduce plasma TG concentrations, but the contribution of EPA versus DHA to this effect has not been clearly established. We supplemented 21 middle-age and older overweight individuals (9 men and 12 women) with 3 g/day of pure EPA or pure DHA for 10 weeks. Each participant received the two supplements in random order. Plasma TG concentrations were lowered by both EPA and DHA via the activation of lipoprotein lipase, a protein involved in TG clearance from circulation. DHA, but not EPA, increased plasma LDL-C concentrations, possibly mediated by a faster conversion of TG-containing lipoproteins to LDL by lipoprotein lipase. In addition, EPA and DHA worked differently in men and women, supporting sex-specific variations in lipoprotein metabolism.

Technical Abstract: Background: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been shown to similarly lower plasma TG concentrations but differentially regulate plasma LDL-C and HDL-C concentrations. Objective: The aim of this study was to evaluate the common and differential effects of these Omega-3 fatty acids on plasma lipids and lipoproteins and to assess the metabolic mechanisms of the effects. Methods: In a randomized, double-blind, crossover study, we assessed the effect of 10-week supplementation with 3 g/d pure EPA and pure DHA on plasma lipid and lipoprotein concentrations and activities of lipoprotein lipase (LPL), cholesteryl ester transfer protein (CETP) and lecithin:cholesterol acyl transferase (LCAT) in 21 older (>50 y) men and postmenopausal women with some characteristics of metabolic syndrome and low-grade chronic inflammation. Results: Both EPA and DHA lowered plasma TG concentrations and increased LDL-C/apoB and HDL-C/apoA-I ratios, but only DHA increased LDL-C concentrations. The reductions in plasma TG were inversely associated with the changes in LPL activity after both EPA and DHA supplementation. EPA lowered CETP, while DHA lowered LCAT activity. EPA and DHA worked differently in men and women, with DHA increasing LPL activity and LDL-C concentrations in women, but not in men. Conclusions: EPA and DHA exerted similar effects on plasma TG, but differences were observed in LDL-C concentrations and activities of some enzymes involved in lipoprotein metabolism. It was also noted that EPA and DHA worked differently in men and women, supporting sex-specific variations in lipoprotein metabolism.