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)

J Am Heart Assoc. 2015 Aug 21;4(8):e002034. doi: 10.1161/JAHA.115.002034.


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: Unique identifier: NCT01310270.

Keywords: fish oil; n‐3 polyunsaturated fatty acids; peripheral artery disease; specialized pro‐resolving mediators; vascular function.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Biomarkers / blood
  • Brachial Artery / drug effects
  • Brachial Artery / physiopathology
  • Dietary Supplements*
  • Double-Blind Method
  • Exercise Tolerance / drug effects
  • Fatty Acids, Omega-3 / administration & dosage*
  • Fatty Acids, Omega-3 / blood
  • Female
  • Fish Oils / administration & dosage*
  • Fish Oils / blood
  • Humans
  • Inflammation Mediators / blood
  • Male
  • Middle Aged
  • Peripheral Arterial Disease / blood
  • Peripheral Arterial Disease / diagnosis
  • Peripheral Arterial Disease / drug therapy*
  • Peripheral Arterial Disease / physiopathology
  • San Francisco
  • Surveys and Questionnaires
  • Time Factors
  • Treatment Outcome
  • Triglycerides / blood
  • Vasodilation / drug effects


  • Biomarkers
  • Fatty Acids, Omega-3
  • Fish Oils
  • Inflammation Mediators
  • Triglycerides

Associated data