Enriched Marine Oil Supplements Increase Peripheral Blood Specialized Pro-Resolving Mediators Concentrations and Reprogram Host Immune Responses: A Randomized Double-Blind Placebo-Controlled Study

Circ Res. 2020 Jan 3;126(1):75-90. doi: 10.1161/CIRCRESAHA.119.315506. Epub 2019 Dec 12.


Rationale: Specialized pro-resolving mediators (SPM-lipoxins, resolvins, protectins, and maresins) are produced via the enzymatic conversion of essential fatty acids, including the omega-3 fatty acids docosahexaenoic acid and n-3 docosapentaenoic acid. These mediators exert potent leukocyte directed actions and control vascular inflammation. Supplementation of animals and humans with essential fatty acids, in particular omega-3 fatty acids, exerts protective actions reducing vascular and systemic inflammation. Of note, the mechanism(s) activated by these supplements in exerting their protective actions remain poorly understood.

Objective: Given that essential fatty acids are precursors in the biosynthesises of SPM, the aim of the present study was to establish the relationship between supplementation and peripheral SPM concentrations. We also investigated the relationship between changes in plasma SPM concentrations and peripheral blood platelet and leukocyte responses.

Methods and results: Healthy volunteers were enrolled in a double-blinded, placebo-controlled, crossover study, and peripheral blood was collected at baseline, 2, 4, 6, and 24 hours post administration of placebo or one of 3 doses of an enriched marine oil supplement. Assessment of plasma SPM concentrations using lipid mediator profiling demonstrated a time- and dose-dependent increase in peripheral blood SPM concentration. Supplementation also led to a regulation of peripheral blood cell responses. Here we found a dose-dependent increase in neutrophil and monocyte phagocytosis of bacteria and a decrease in the diurnal activation of leukocytes and platelets, as measured by a reduction in adhesion molecule expression. In addition, transcriptomic analysis of peripheral blood cells demonstrated a marked change in transcript levels of immune and metabolic genes 24 hours post supplementation when compared with placebo.

Conclusions: Together, these findings demonstrate that supplementation with an enriched marine oil leads to an increase in peripheral blood SPM concentrations and reprograms peripheral blood cells, indicating a role for SPM in mediating the immune-directed actions of this supplement.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT03347006.

Keywords: leukocyte; lipoxins; monocytes; neutrophils; platelet.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers
  • Blood Cells / drug effects
  • Blood Cells / metabolism
  • Cell Adhesion Molecules / blood
  • Circadian Rhythm / drug effects
  • Cross-Over Studies
  • Dietary Supplements*
  • Docosahexaenoic Acids / blood*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Fatty Acids, Essential / physiology
  • Fatty Acids, Omega-3 / administration & dosage
  • Fatty Acids, Omega-3 / pharmacology*
  • Female
  • Fish Oils / administration & dosage
  • Fish Oils / pharmacology*
  • Gene Ontology
  • Humans
  • Immune System / drug effects*
  • Lipoxins / blood*
  • Male
  • Middle Aged
  • Phagocytosis / drug effects
  • Platelet Activating Factor / pharmacology
  • Platelet Aggregation / drug effects
  • Transcription, Genetic / drug effects
  • Young Adult


  • Biomarkers
  • Cell Adhesion Molecules
  • Fatty Acids, Essential
  • Fatty Acids, Omega-3
  • Fish Oils
  • Lipoxins
  • Platelet Activating Factor
  • Docosahexaenoic Acids

Associated data

  • ClinicalTrials.gov/NCT03347006