Abstract Context Supplementation with high dose of docosahexaenoic acid (DHA) increases serum LDL-cholesterol (C) concentrations more than high dose eicosapentaenoic acid (EPA). Mechanisms underlying this difference are unknown. Objective To examine the phenotypic change in LDL and mechanisms responsible for the differential LDL-C response to EPA and DHA supplementation in men and women at risk for cardiovascular disease. Design, setting, participants and intervention In a double-blind controlled crossover study, 48 men and 106 women with abdominal obesity and subclinical inflammation were randomized to a sequence of three treatment phases: 1- 2.7 g/d of EPA, 2- 2.7 g/d of DHA, and 3- 3 g/d of corn oil. All supplements were provided as 3x1 g capsules for a total of 3 g/d. The 10-week treatment phases were separated by nine-week washouts. Main outcome measure In vivo kinetics of apolipoprotein (apo) B-100-containing lipoproteins were assessed using primed-constant infusion of deuterated leucine at the end of each treatment in a subset of participants (n=19). Results Compared with EPA, DHA increased LDL-C concentrations (+3.3%, P=0.038) and mean LDL particle size (+0.7 Å, P<0.001) and reduced the proportion of small LDL (-3.2%, P<0.01). Both EPA and DHA decreased proprotein convertase subtilisin/kexin type 9 concentrations similarly (-18.2% vs. -25.0%, P<0.0001 vs. control). Compared with EPA, DHA supplementation increased both LDL apo B-100 fractional catabolic rate (+11.4%, P=0.008) and production rate (+9.4%, P=0.03). Conclusions This study shows for the first time that supplementation with high-dose DHA increases LDL turnover and contributes to larger LDL particles compared with high-dose EPA. Copyright © 2018 Endocrine Society
Journal of Clinical Endocrinology and Metabolism – Oxford University Press
Published: May 25, 2018
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