Grenon, S MarleneOwens, Christopher DNosova, Emily VHughes-Fulford, MillieAlley, Hugh FChong, KarenPerez, SandraYen, Priscilla KBoscardin, JohnHellmann, JasonSpite, MatthewConte, Michael S2015-11-032015Grenon, S. M., C. D. Owens, E. V. Nosova, M. Hughes-Fulford, H. F. Alley, K. Chong, S. Perez, et al. 2015. “Short-Term, High-Dose Fish Oil Supplementation Increases the Production of Omega-3 Fatty Acid–Derived Mediators in Patients With Peripheral Artery Disease (the OMEGA-PAD I Trial).” Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease 4 (8): e002034. doi:10.1161/JAHA.115.002034. http://dx.doi.org/10.1161/JAHA.115.002034.2047-9980http://nrs.harvard.edu/urn-3:HUL.InstRepos:23473875Background: Patients with peripheral artery disease (PAD) experience significant morbidity and mortality. The OMEGA-PAD I Trial, a randomized, double-blinded, placebo-controlled trial, addressed the hypothesis that short-duration, high-dose n-3 polyunsaturated fatty acids (n-3 PUFA) oral supplementation improves endothelial function and inflammation in PAD. Methods and Results: Eighty patients with stable claudication received 4.4 g of fish oil or placebo for 1 month. The primary end point was endothelial function as measured by brachial artery flow-mediated vasodilation. Secondary end points included biomarkers of inflammation, n-3 polyunsaturated fatty acids metabolome changes, lipid profile, and walking impairment questionnaires. Although there was a significant increase in FMD in the fish oil group following treatment (0.7±1.8% increase from baseline, P=0.04), this response was not different then the placebo group (0.6±2.5% increase from baseline, P=0.18; between-group P=0.86) leading to a negative finding for the primary endpoint. There was, however, a significant reduction in triglycerides (fish oil: −34±46 mg/dL, P<0.001; placebo −10±43 mg/dL, P=0.20; between-group differential P-value: 0.02), and an increase in the omega-3 index of 4±1% (P<0.001) in the fish oil group (placebo 0.1±0.9%, P=0.49; between-group P<0.0001). We observed a significant increase in the production of pathway markers of specialized pro-resolving mediators generated from n-3 polyunsaturated fatty acids in the fish oil group. Conclusions: High-dose, short-duration fish oil supplementation did not lead to a different response in the primary end point of endothelial function between the treatment and placebo group, but improved serum triglycerides and increased the production of downstream n-3 polyunsaturated fatty acids–derived products and mediators in patients with PAD. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01310270.en-USfish oiln-3 polyunsaturated fatty acidsperipheral artery diseasespecialized pro-resolving mediatorsvascular functionJournal Article2015-11-0310.1161/JAHA.115.002034