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Current Developments in Nutrition logoLink to Current Developments in Nutrition
. 2020 May 29;4(Suppl 2):662. doi: 10.1093/cdn/nzaa049_055

EPA and DHA Have Differential Effects on Cholesterol Ester Transfer Protein and Lipoprotein Lipase Activities Following Plasma Triglycerides Lowering

Jisun So 1, Bela Asztalos 1, Katalin Horvath 1, Alice Lichtenstein 2, Stefania Lamon-Fava 2
PMCID: PMC7258739

Abstract

Objectives

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are effective in reducing plasma triglyceride (TG) concentrations but have divergent effects on LDL cholesterol (LDL-C) concentrations. Differential regulations of cholesterol ester transfer protein (CETP) and lipoprotein lipase (LPL) activities are possible mechanisms of their differential effects. We assessed the effects of EPA and DHA supplementation on plasma lipid profiles and two enzyme activities involved in lipoprotein metabolism.

Methods

Nine men and twelve postmenopausal women (N = 21, 50–75y) with chronic inflammation (CRP > 2 mg/L) were enrolled in a randomized, double-blind, crossover trial consisting of a 4-wk lead-in phase with high oleic acid sunflower oil (3 g/d) followed by two 10-wk EPA and DHA supplementation phases (3 g/d each) separated by a 10-wk washout phase. Plasma was collected after the lead-in (baseline) and each n-3 fatty acid supplementation phase for analysis of TG, total cholesterol and HDL-C, and CETP and post-heparin LPL activities. LDL-C was estimated using the Friedewald formula.

Results

Subjects were recruited to have moderately elevated TG and LDL-C concentrations (mean ± SEM: 141 ± 11 and 130 ± 6 mg/dL, respectively). Compared to baseline, EPA supplementation lowered TG concentration (−28 ± 6 mg/dL, P < 0.001) and CETP activity (−1.6 ± 1.1 µg/mL/h, P < 0.05), whereas LDL-C concentration and LPL activity were unchanged. The changes in TG concentration and CETP activity were negatively correlated with baseline TG (r = −0.77 and −0.45, respectively, both P < 0.05). DHA supplementation lowered TG concentration (−31 ± 8 mg/dL, P < 0.001), and increased LDL-C concentration (+10 ± 4 mg/dL, P < 0.01) and LPL activity (+6.1 ± 4.0 mU/mL, P < 0.03), CETP activity was unchanged. The DHA-mediated increase in LPL activity was correlated with the baseline TG concentration and change in TG concentration (r = 0.64 and ρ = −0.45, respectively, both P < 0.05).

Conclusions

In the context of the established TG-lowering effects of EPA and DHA, these n-3 fatty acids affected CETP and LPL activities differently. DHA-induced change in LDL-C concentration may be related to increased LPL activity, and the conversion of very low-density lipoprotein to LDL.

Funding Sources

AFRI/NIFA; USDA.


Articles from Current Developments in Nutrition are provided here courtesy of American Society for Nutrition

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