Abstract 15015: Eicosapentaenoic Acid, but Not Docosahexaenoic Acid or a Mixed Omega-3 Fatty Acid Supplement, Inhibits Low-density Lipoprotein Oxidation in a Time-dependent Manner

Background: Eicosapentaenoic acid (EPA), an omega-3 fatty acid (O3FA), reduces oxidation of low-density lipoproteins (LDL) in patients with hypertriglyceridemia, an effect that may contribute to lower cardiovascular (CV) events as reported in the REDUCE-IT trial. By contrast, DHA-containing products have failed to show a reduction in CV events, which may be due, in part, to differences in antioxidant activity. We compared the effects of EPA versus DHA and a mixed O3FA (EPA/DHA) supplement on oxidation of human LDL in vitro . Methods: LDL was isolated from human plasma by isopycnic centrifugation, separated into test samples of 100 μg/mL, and incubated at 37°C for 30 min in the absence (vehicle) or presence of EPA, DHA, or mixed O3FA supplement at equimolar levels (2.5 μM). All samples were then subjected to copper-induced oxidation (20 μM) as measured by formation of malondialdehyde (MDA). The FA content of the O3FA supplement was measured using gas chromatography/mass spectrometry. Results: EPA significantly inhibited LDL oxidation in a time-dependent manner compared with vehicle; after 4 hours, EPA inhibited MDA levels by 96% compared with the vehicle oxidation level (0.51 ± 0.01 vs 11.4 ± 0.4 μM; p <0.001). While DHA exhibited antioxidant activity at 2 hours at a level below EPA (2.5 ± 0.1 vs 11.4 ± 0.4; p <0.001), even this level of activity was lost by 4 hours. The mixed O3FA supplement failed to show any antioxidant activity through 4 hours (11.4 ± 0.5 μM). Fatty acid analysis showed that the O3FA supplement, in addition to EPA and DHA, contained more than 30 other fatty acids, including saturated fats, that may have nullified any potential benefits. Conclusions: These data support potent LDL antioxidant effects of EPA that were sustained over time compared with DHA, which had a weaker, transient effect, or a mixed O3FA supplement, which had no beneficial effect at all. This potent antioxidant mechanism of EPA may contribute to reduced CV risks seen in REDUCE-IT compared with negative findings from trials using DHA-containing formulations.