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)

Background: 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. © 2015 the authors. published on behalf of the american heart association,inc.,by wiley blackwell.