Docosahexaenoic acid is more effective than eicosapentaenoic acid in increasing the Omega-3 index measured in red blood cell membranes

Background: Whether eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids have distinct effects on cardiometabolic risk remains unclear as most studies to date have used a mixture of the two fatty acids in various forms and proportions. The Omega-3 Index (O3I) reflects the sum of EPA and DHA as percent of fatty acids in red blood cell (RBC) membranes and has been inversely associated with the risk of coronary heart diseases and coronary mortality in epidemiological studies. The objective of this study was to assess if supplementation with high dose EPA differentially modify the O3I compared with high dose DHA in men and women at risk of cardiovascular diseases. Methods: Using a randomized double-blind controlled crossover design, 48 men and 106 women with abdominal obesity and subclinical inflammation were randomized to a sequence of three treatment phases: 1-2.7g/d of EPA, 2-2.7 g/d of DHA, 3- and 0g/d of EPA+DHA (corn oil). All supplements were provided as 3×1g capsules for a total of 3g/d. Treatment phases had a duration of ten weeks each and were separated by nine-week washouts. RBC membrane fatty acid composition was measured at baseline and the end of each phase. Differences in RBC membrane fatty acid composition and in the O3I between treatments were assessed using mixed models for repeated measures. Potential confounders of the response to treatments such as weight, sex, age and O3I baseline values were considered. Results: The increase in the O3I after DHA (+87% vs. control, p<0.0001) was significantly greater than after EPA (+52% vs. control, p<0.0001; p<0.0001 between DHA and EPA). There was a significant sex∗treatment interaction (p=0.046) in the O3I response to EPA and DHA, with similar O3I changes among men and women in response to EPA (0% difference between sexes), but slightly greater O3I increase after DHA among men (+9% compared with women). EPA supplementation increased docosapentaenoic acid (DPA) proportions in RBCs (+84% vs. control, P<0.0001) while DHA decreased DPA in RBCs (-28% vs. control, p<0.0001; p<0.001 between DHA and EPA). Conclusions: High-dose DHA may be more effective than high dose EPA in increasing the O3I, perhaps even more so among men than among women. Because DPA levels are not accounted for in the O3I, in vivo elongation of EPA to DPA may partly explain the difference between EPA and DHA in modulating the O3I. Long-term intervention studies are needed to determine how this difference relates to cardiovascular risk in men and women.