Jane Ferguson
Last active: 4/2/2019

Omega-3 PUFA supplementation and the response to evoked endotoxemia in healthy volunteers.

Ferguson JF, Mulvey CK, Patel PN, Shah RY, Doveikis J, Zhang W, Tabita-Martinez J, Terembula K, Eiden M, Koulman A, Griffin JL, Mehta NN, Shah R, Propert KJ, Song WL, Reilly MP
Mol Nutr Food Res. 2014 58 (3): 601-13

PMID: 24190860 · PMCID: PMC3947472 · DOI:10.1002/mnfr.201300368

SCOPE - 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.

METHODS AND 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.

CONCLUSION - 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.

© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

MeSH Terms (20)

Adolescent Adult Dietary Supplements Docosahexaenoic Acids Dose-Response Relationship, Drug Drug Combinations Eicosapentaenoic Acid Endotoxemia Fatty Acids, Omega-3 Female Fish Oils Healthy Volunteers Humans Inflammation Isoprostanes Lipopolysaccharides Lipoproteins Male Middle Aged Young Adult

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