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)

Randomized, placebo-controlled trial in 80 veterans with symptomatic peripheral artery disease and intermittent claudication treated at the San Francisco VA Medical Center. The active fish oil group included 40 participants, and the cohort was predominantly older male and White.

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. Each capsule contained 325 mg EPA and 225 mg DHA, for a total daily dose of 2.6 g EPA and 1.8 g DHA; the comparator was placebo.

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.

The intervention was short term (1 month) and involved a small, single-center veteran cohort that was predominantly older male and White, limiting generalizability. The primary endpoint was negative, so the observed biomarker improvements were not linked to demonstrated clinical benefit, and about 10% of participants dropped out.