Fish Oil Increases Specialized Pro-resolving Lipid Mediators in PAD (The OMEGA-PAD II Trial)

J Surg Res. 2019 Jun;238:164-174. doi: 10.1016/j.jss.2019.01.038. Epub 2019 Feb 13.


Background: N-3 polyunsaturated fatty acid (PUFA) supplementation has been associated with reduced mortality and inflammation in patients with cardiovascular disease. There are limited data on the effects of n-3 PUFA supplementation in patients with peripheral artery disease (PAD).

Materials and methods: The OMEGA-PAD II trial was a double-blinded, randomized, placebo-controlled trial to assess the effect of 3 mo of high-dose oral n-3 PUFA supplementation on inflammation, endothelial function, and walking ability in patients with PAD.

Results: Twenty-four patients with claudication received 4.4 g/d of fish oil or placebo for 3 mo. Outcomes measured included high-sensitivity C-reactive protein levels, the omega-3 index, endothelial function as measured via flow-mediated vasodilation, walking impairment questionnaire, and a 6-min walk test. Plasma levels of specialized pro-resolving lipid mediators (SPMs) were measured by liquid-chromatography-tandem mass spectrometry. In patients treated with fish oil, the absolute mean omega-3 index significantly increased from baseline (fish oil: 7.2 ± 1.2%, P < 0.001; placebo: -0.4 ± 0.9%, P = 0.31; between-group P < 0.001). Furthermore, there were significant increases in several pathway markers of SPM biosynthesis, including several mono-hydroxyeicosapentaenoic acids and mono-hydroxydocosahexaenoic acids. We also observed significant increases in the SPM lipoxin A5 (fish oil: 0.57 ± 0.70 pg/mL, P = 0.05; placebo: 0.01 ± 0.38 pg/mL, P = 0.93; between-group P = 0.04) and resolvin E3 (fish oil: 154 ± 171 pg/mL, P = 0.04; placebo: 32 ± 54 pg/mL, P = 0.08; between-group P = 0.04). There were no significant changes in high-sensitivity C-reactive protein, flow-mediated vasodilation, walking impairment questionnaire, or 6-min walk test in the fish oil group.

Conclusions: Fish oil increases SPMs in plasma of patients with PAD. Further studies are required to determine whether these early changes translate to clinical improvements in patients with PAD.

Keywords: Fish oils; Other pharmacotherapy; Peripheral artery disease; Specialized pro-resolving lipid mediators; n-3 polyunsaturated fatty acids.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Dietary Supplements
  • Docosahexaenoic Acids / blood*
  • Docosahexaenoic Acids / immunology
  • Double-Blind Method
  • Eicosapentaenoic Acid / blood*
  • Eicosapentaenoic Acid / immunology
  • Fatty Acids, Omega-3 / administration & dosage*
  • Female
  • Humans
  • Inflammation / blood
  • Inflammation / diet therapy*
  • Inflammation / immunology
  • Male
  • Middle Aged
  • Peripheral Arterial Disease / blood
  • Peripheral Arterial Disease / diet therapy*
  • Peripheral Arterial Disease / immunology
  • Placebos / administration & dosage
  • Placebos / adverse effects
  • Treatment Outcome


  • Fatty Acids, Omega-3
  • Placebos
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid