Fish Oil Increases Specialized Pro-resolving Lipid Mediators in PAD (The OMEGA-PAD II Trial)

Background: N-3 polyunsaturated fatty acid (PUFA) supplementation has been associated with reduced mortality and inflammation in patients with cardiovascular disease. There are limited data on the effects of n-3 PUFA supplementation in patients with peripheral artery disease (PAD). Materials and methods: The OMEGA-PAD II trial was a double-blinded, randomized, placebo-controlled trial to assess the effect of 3 mo of high-dose oral n-3 PUFA supplementation on inflammation, endothelial function, and walking ability in patients with PAD. Results: Twenty-four patients with claudication received 4.4 g/d of fish oil or placebo for 3 mo. Outcomes measured included high-sensitivity C-reactive protein levels, the omega-3 index, endothelial function as measured via flow-mediated vasodilation, walking impairment questionnaire, and a 6-min walk test. Plasma levels of specialized pro-resolving lipid mediators (SPMs) were measured by liquid-chromatography-tandem mass spectrometry. In patients treated with fish oil, the absolute mean omega-3 index significantly increased from baseline (fish oil: 7.2 +/- 1.2%, P < 0.001; placebo: -0.4 +/- 0.9%, P = 0.31; between-group P < 0.001). Furthermore, there were significant increases in several pathway markers of SPM biosynthesis, including several mono-hydroxyeicosapentaenoic acids and monohydroxydocosahexaenoic acids. We also observed significant increases in the SPM lipoxin A(5) (fish oil: 0.57 +/- 0.70 pg/mL, P = 0.05; placebo: 0.01 +/- 0.38 pg/mL, P = 0.93; between-group P = 0.04) and resolvin E3 (fish oil: 154 +/- 171 pg/mL, P = 0.04; placebo: 32 +/- 54 pg/mL, P = 0.08; between-group P = 0.04). There were no significant changes in high-sensitivity Creactive protein, flow-mediated vasodilation, walking impairment questionnaire, or 6-min walk test in the fish oil group. Conclusions: Fish oil increases SPMs in plasma of patients with PAD. Further studies are required to determine whether these early changes translate to clinical improvements in patients with PAD. (C) 2019 Elsevier Inc. All rights reserved.