Aim: Eicosapentaenoic acid (EPA) reduces oxidation of low-density lipoproteins (LDL) in patients with hypertriglyceridemia, a benefit that may contribute to lower cardiovascular events (REDUCE-IT).  EPA may inhibit LDL oxidation through free radical scavenging at a pharmacologic dose as measured in the micromolar range.  
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 over a range of concentration (1-10 µM). All samples were then subjected to copper-induced oxidation and LDL oxidation was measured over six hours. 
Results: EPA inhibited LDL oxidation in a highly dose- and time-dependent manner.  At the lower concentrations, EPA inhibited oxidation until ≤4 hr below 3 µM.  Only at concentrations greater than 4 µM did EPA significantly inhibit LDL oxidation through 6 hr.  Above 7.0 µM, EPA inhibited LDL oxidation by >88% (p<0.001) and the half-maximum concentration of LDL inhibition was 5 µM (50%) at 6 hrs (p<0.001). 
Conclusions: These data support concentration-dependent antioxidant effects for EPA that requires pharmacologic concentrations for sustained activity.  As LDL oxidation is an important contributor to atherosclerosis, the inhibition of this process by EPA may provide a potential mechanism for its cardiovascular benefits.

02 - EICOSAPENTAENOIC ACID (EPA) INHIBITS HUMAN LOW-DENSITY LIPOPROTEIN OXIDATION IN A CONCENTRATION- AND TIME-DEPENDENT MANNER AT PHARMACOLOGIC DOSES IN VITRO