title: Omega-3 PUFA supplementation and the response to evoked endotoxemia in healthy volunteers.
abstract: METHODS
  Fish oil-derived n-3 PUFA may improve cardiometabolic health through modulation of innate immunity. However, findings in clinical studies are conflicting. We hypothesized that n-3 PUFA supplementation would dose-dependently reduce the systemic inflammatory response to experimental endotoxemia in healthy humans.
  
  
  RESULTS
  The Fenofibrate and omega-3 Fatty Acid Modulation of Endotoxemia (FFAME) study was an 8-wk randomized double-blind trial of placebo or n-3 PUFA supplementation (Lovaza 465 mg eicosapentaenoic acid (EPA) + 375 mg docosahexaenoic acid (DHA)) at "low" (1/day, 900 mg) or "high" (4/day, 3600 mg) dose in healthy individuals (N = 60; age 18-45; BMI 18-30; 43% female; 65% European-, 20% African-, 15% Asian-ancestry) before a low-dose endotoxin challenge (LPS 0.6 ng/kg intravenous bolus). The endotoxemia-induced temperature increase was significantly reduced with high-dose (p = 0.03) but not low-dose EPA + DHA compared to placebo. Although there was no statistically significant impact of EPA + DHA on individual inflammatory responses (tumor necrosis factor-α (TNF-α), IL-6, monocyte chemotactic protein (MCP-1), IL-1 receptor agonist (IL-1RA), IL-10, C-reactive protein (CRP), serum amyloid A (SAA)), there was a pattern of lower responses across all biomarkers with high-dose (nine of nine observed), but not low-dose EPA + DHA.
  
  
  CONCLUSIONS
  EPA + DHA at 3600 mg/day, but not 900 mg/day, reduced fever and had a pattern of attenuated LPS induction of plasma inflammatory markers during endotoxemia. Clinically and nutritionally relevant long-chain n-3 PUFA regimens may have specific, dose-dependent, anti-inflammatory actions.
authors.affiliation: Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Jane F
authors.initials: JF
authors.lastname: Ferguson
authors.forename: Claire K
authors.initials: CK
authors.lastname: Mulvey
authors.forename: Parth N
authors.initials: PN
authors.lastname: Patel
authors.forename: Rhia Y
authors.initials: RY
authors.lastname: Shah
authors.forename: Julia
authors.initials: J
authors.lastname: Doveikis
authors.forename: Weiyu
authors.initials: W
authors.lastname: Zhang
authors.forename: Jennifer
authors.initials: J
authors.lastname: Tabita-Martinez
authors.forename: Karen
authors.initials: K
authors.lastname: Terembula
authors.forename: Michael
authors.initials: M
authors.lastname: Eiden
authors.forename: Albert
authors.initials: A
authors.lastname: Koulman
authors.forename: Julian L
authors.initials: JL
authors.lastname: Griffin
authors.forename: Nehal N
authors.initials: NN
authors.lastname: Mehta
authors.forename: Rachana
authors.initials: R
authors.lastname: Shah
authors.forename: Kathleen J
authors.initials: KJ
authors.lastname: Propert
authors.forename: Wen-Liang
authors.initials: WL
authors.lastname: Song
authors.forename: Muredach P
authors.initials: MP
authors.lastname: Reilly
mesh_terms: D000293:Adolescent; D000328:Adult; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D019446:Endotoxemia / Q000178:diet therapy*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology* / Q000652:urine; D005260:Female; D005395:Fish Oils / Q000494:pharmacology; D064368:Healthy Volunteers; D006801:Humans; D007249:Inflammation / Q000178:diet therapy / Q000378:metabolism; D028421:Isoprostanes / Q000652:urine; D008070:Lipopolysaccharides / Q000633:toxicity; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D004338:Drug Combinations; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D028421:Isoprostanes; D008070:Lipopolysaccharides; D008074:Lipoproteins; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; C405603:Omacor
keywords: Endotoxemia; Fish oil; Inflammation; LPS; n-3 PUFA