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)
What this study found
Fish oil did not improve the primary clinical endpoint of brachial artery flow-mediated dilation versus placebo. Change in FMD was 0.7 ± 1.8% with fish oil and 0.6 ± 2.5% with placebo, with no between-group difference (P=0.86). However, fish oil significantly improved the omega-3 index (+4 ± 1% vs +0.1 ± 0.9%, P<0.0001) and reduced triglycerides (−34 ± 46 mg/dL vs −10 ± 43 mg/dL, between-group P=0.02). EPA- and DHA-derived lipid mediators increased with fish oil, and no adverse events were reported.
- Study & population
- Randomized, placebo-controlled trial in 80 veterans with symptomatic peripheral artery disease and intermittent claudication treated at the San Francisco VA Medical Center.
- Intervention
- Fish oil (ProOmega) was given orally at 4.4 g/day of n-3 PUFA for 1 month, administered as 2.2 g twice daily.
- Key limitation
- The intervention was short term (1 month) and involved a small, single-center veteran cohort that was predominantly older male and White, limiting generalizability.
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Open PDFOriginal abstract
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.