Abstract 14882: Change in Serum PCSK9 Does Not Explain the Difference in the LDL-C Response Between EPA and DHA Supplementation: The ComparED Study
Introduction: Supplementation with high dose docosahexaenoic acid (DHA) increases serum LDL-C concentrations more than with eicosapentaenoic acid (EPA). Mechanisms underlying this difference are unknown. The objective of this study was to examine how protein convertase subtilisin/kexin type 9 (PCSK9) regulation is involved in the differential LDL-C responses to EPA and DHA supplementation in men and women at risk for cardiovascular disease.
Hypothesis: We hypothesized that the greater increase in LDL-C after DHA compared with EPA is partly mediated by an increase in serum PCSK9 concentrations, reflecting reduced LDL receptor activity.
Methods: In a double-blind, randomized, controlled, crossover study, 48 men and 106 women with abdominal obesity and low-grade systemic inflammation were subjected to three consecutive 10-wk treatment phases: 1- EPA (2.7g/d), 2- DHA (2.7g/d), 3- control (corn oil), each separated by a 9-wk washout. All supplements were provided as 1g capsules for a total of 3g/d. Post treatment concentrations of serum PCSK9 and LDL-C were compared using mixed models.
Results: Serum LDL-C concentrations increased compared with control with both EPA and DHA in 39% of participants, were reduced with both EPA and DHA in 28%, while 33% had discordant responses. On the other hand, both EPA and DHA decreased serum PCSK9 concentrations significantly and equally compared with control (-5.6±22.9% and -8.9±22.9% respectively, both P<0.001; P=0.15 between treatments). The reduction in serum PCSK9 concentrations was of similar magnitude among individuals with concordant and discordant LDL-C responses to EPA and DHA. Within-treatment changes in PCSK9 and LDL-C were not correlated (EPA rs=0.03, P=0.74; DHA rs=0.13, P=0.15).
Conclusions: While there is important intra-individual heterogeneity in the LDL-C response to EPA and DHA, the reduction in serum PCSK9 concentrations appears to be more consistent. Results also suggest that the variations in the LDL-C response to long chain omega-3 fatty acids is unrelated to changes in serum PCSK9 concentrations, and hence in estimated LDL particle clearance. Further research is required to examine how EPA and DHA may differentially regulate other genes and proteins involved in cholesterol metabolism.
Author Disclosures: J. Allaire: Other; Modest; Canadian Institutes of Health Research (CIHR), Fonds de recherche du Québec - Santé (FRQ-S). P. Couture: None. A. Charest: None. J. Marin: None. M. Lépine: None. A. Tchernof: Research Grant; Significant; Investigator-initiated support grant from Johnson & Johnson Medical Companies. B. Lamarche: Research Grant; Modest; Canadian Institutes of Health Research (CIHR). Other Research Support; Modest; Atrium Innovations.
- © 2016 by American Heart Association, Inc.