Effects of a Prescription Omega-3 Fatty Acid Concentrate on Induced Inflammation
Condition: Inflammatory Responses
MeSH terms: Inflammation
Study type: Interventional

Summary: 
      The purpose of this study is to assess whether the marine omega-3 fatty acids can attenuate
      inflammatory responses to endotoxin challenge.
    

Detailed description: 
      Controlled endotoxin infusion has been used widely as a model system to evaluate
      anti-inflammatory mediators and therapies in a controlled, in vivo setting. It is well
      established that infusion of bacterial endotoxin (also known as lipopolysaccharide or LPS) in
      humans results in a marked increase in inflammatory cytokines, most notably TNF-α, IL-1, IL-6
      and IL-8, CRP, granulocyte colony stimulating factor (GCSF); eicosanoids, such as
      prostaglandin (PG) E2 and other mediators. Administration of endotoxin, even at a low dose
      (0.6 ng/kg) elevates circulating concentrations of inflammatory cytokines, and mimics the
      inflammatory effects of chronic diseases. This model has been used for decades and has proved
      to be safe and informative for evaluating anti-inflammatory therapeutic interventions on
      human inflammation and downstream consequences.

      Prolonged or chronic inflammation is involved in the etiology of several diseases such as
      cardiovascular disease (CVD), diabetes, rheumatoid arthritis, cancer, and neurodegenerative
      diseases such as Alzheimer's disease. The evidence base clearly demonstrates benefits of diet
      in ameliorating inflammation and reducing the burden of chronic disease. With respect to
      marine-derived omega-3 fatty acids and various markers of inflammation related to
      cardiovascular disease (CVD), both population studies and randomized controlled
      supplementation trials have yielded mixed results. It is well established that these omega-3
      fatty acids are precursors of series-3 prostanoids, thromboxanes, 5-series leukotrienes, and
      novel lipid mediators such as resolvins and protectins that have anti-inflammatory effects.
      We hypothesize that supplementation of omega-3 fatty acids will blunt the response to an
      inflammatory stimulus and/or enhance the resolution phase.

      We propose to test this hypothesis using an in vivo endotoxin challenge with a
      pharmacological dose of omega-3 fatty acid ethyl esters (P-OM3, 3.4 g/d EPA + DHA) in healthy
      volunteers. Our proposed approach is novel in that we will provoke an in vivo inflammatory
      response by infusing human subjects with a low dose (0.6 ng/kg body weight) of sterile
      endotoxin (lipopolysaccharide [LPS]) in contrast to studies that have attempted to reverse
      established inflammatory pathology. Results from our proposed research will advance our
      understanding of the effect of omega-3 fatty acids on prevention/attenuation of an
      inflammatory response.
    

Intervention name(s): 4 g prescription omega-3 concentrate; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 4 g/d prescription omega-3 fatty acid concentrate taken orally for 8-12 weeks; olive oil
Other intervention name(s): Lovaza; Omacor; No other name (control)
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: inflammation; omega-3; fish oil