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

  • Jisun So
    Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, United States (Drs So, Asztalos, Horvath, and Lamon-Fava)

    Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy; Tufts University, Boston, MA, United States (Drs So and Lamon-Fava)
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  • Bela F. Asztalos
    Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, United States (Drs So, Asztalos, Horvath, and Lamon-Fava)
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  • Katalin Horvath
    Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, United States (Drs So, Asztalos, Horvath, and Lamon-Fava)
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  • Stefania Lamon-Fava
    Corresponding author: Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington Street, Boston, MA 02111, United States.
    Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, United States (Drs So, Asztalos, Horvath, and Lamon-Fava)

    Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy; Tufts University, Boston, MA, United States (Drs So and Lamon-Fava)
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Published:October 15, 2022DOI:


      • EPA and DHA lowered plasma TG concentrations.
      • Changes in TG concentrations were inversely associated with changes in LPL activity.
      • DHA increased LDL-C concentrations.
      • EPA and DHA plasma lipid changes varied by sex.


      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.


      The aim of this study was to evaluate the common and differential effects of these ω-3 fatty acids on plasma lipids and lipoproteins and to assess the metabolic mechanisms of the effects.


      In a randomized, double-blind, crossover study, we assessed the effect of 10-week supplementation with 3 g/d pure EPA and pure DHA (both as ethyl ester, ≥97% purity) 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.


      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.


      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.


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