Comparison of the Impact of High‐Dose DHA and EPA Supplementation on the Intravascular Kinetics of Very‐Low Density Lipoprotein Apolipoprotein C‐III

Abstract

BackgroundApolipoprotein C‐III (apoC‐III) is an emerging risk factor for cardiovascular disease (CVD) and its presence on very‐low density lipoproteins (VLDL) may enhance their atherogenicity, primarily by delaying their rate of catabolism. We have shown in a recent study that high‐dose supplementation with docosahexaenoic acid (DHA) led to more pronounced reductions in TG compared with eicosapentaenoic acid (EPA), but mechanisms remain unclear. The objective of this study was to compare the individual effect of EPA and DHA on VLDL‐apoC‐III metabolism in men and women at risk of CVD.MethodsIn a randomized double‐blind crossover trial, 10 men and 8 women with abdominal obesity and low‐grade inflammation were subjected to three 10‐wk supplementation phases: 1) EPA (2.7 g/d); 2) DHA (2.7 g/d); 3) corn oil (0g DHA, 0g EPA, control), separated by a 9‐wk washout. All supplements were provided as 3×1g capsules for a total of 3g/d. After each dietary intervention, subjects received a primed‐constant infusion of [5,5,5‐D(3)]‐L‐leucine for 12h under constant feeding conditions for the determination of VLDL‐apoC‐III kinetics.ResultsBoth DHA (−11.7%, p=0.01) and EPA (−6.4%, p=0.03) similarly reduced the fractional catabolism rate (FCR) of VLDL‐apoC‐III compared with control (p=0.75 between DHA and EPA). On the other hand, neither DHA nor EPA supplementation had a significant impact on VLDL‐apoC‐III concentrations and production rate (PR). Compared with control, DHA‐ and EPA‐induced reductions in TG were correlated with DHA‐ and EPA‐induced variations in VLDL‐apoC‐III PR (r=0.49, p=0.03 and r=0.48, p=0.05 respectively), but not with changes in VLDL‐apoC‐III FCR.ConclusionsHigh‐dose supplementation with DHA or EPA is associated with reduced clearance of VLDL‐apoC‐III, with no effect, however, on VLDL‐apoC‐III concentrations and production. Although the DHA‐ and EPA‐induced reductions in serum TG may be more sensitive to treatment‐induced variations in VLDL‐apoC‐III production, other mechanisms must be investigated to explain why DHA may reduce serum TG more than EPA.Support or Funding InformationFinancial support for this RCT was provided exclusively by a grant from the Canadian Institutes for Health Research (MOP‐123494). Douglas Laboratories provided the EPA, DHA and placebo capsules used in this study. The funding source was not involved in the study design, conduct of the study, or collection, management, analysis, or interpretation of the data or in the preparation or review of the manuscript and had no right to approve or disapprove of the submitted manuscript. CV is a fellow of the French Foundation for Medical Research (FRM, file code: 40303). JA is a recipient of a PhD Scholarships from the Canadian Institutes for Health Research and the Fonds de recherche du Québec – Santé.