The Impact of Fish-oil Fatty Acids on Postprandial Vascular Reactivity
Condition: Cardiovascular Physiological Phenomena; Endothelial Nitric Oxide Synthase; Eicosapentaenoic Acid; Docosahexaenoic Acid (All-Z Isomer)
Study type: Interventional

Summary: 
      The primary aim of this study is to determine the impact of individual fish oil fatty acids
      on vascular reactivity and to identify underlying physiological and molecular mechanism of
      any observed effects. In addition response to intervention according to genotype will be
      determined retrospectively.
    

Detailed description: 
      A loss of vascular reactivity and increased vascular tone is being increasingly recognised as
      a significant cardiovascular disease (CVD) risk factor and highly predictive of future CVD
      events. A previous study by our group has shown the inclusion of a fish oil mixture
      administered alongside a high fat meal preserves postprandial vascular function in healthy
      men [1]. In this three arm, placebo controlled cross over study, the impact of individual
      fatty acids contained within fish-oil on postprandial vascular reactivity (measured at 4 hour
      post test meal) will be assessed for the first time. Clinical measurements of vascular
      function which correlate with CVD risk factors and are predictive of future CVD events will
      be undertaken in order to assess any potentially beneficial effects. In addition plasma
      samples will be taken at 0 and 4 hours to determine the change in concentration of modulators
      of vascular tone. Accordingly, our nutrients of interest which will be administered in the
      intervention arms of the study, will be present in this lipoprotein rich fraction. By
      exposing cells in culture to these EPA- and DHA-enriched lipoproteins, mechanisms underlying
      the vascular response in our human volunteers will be investigated. Finally we will measure
      the plasma fatty acid profile to confirm that circulating concentrations of EPA and DHA are
      increasing postprandially according to intake.

      As it is now recognised that genetic variation, in addition to being an important determinant
      of the risk of all known chronic diseases, plays a large part in determining an individual's
      response to dietary change, DNA will be extracted from whole blood taken at the clinical
      screening and stored for subsequent genotyping for variants likely to be important in the
      regulation of EPA and DHA metabolism and vascular tone. Although the current study will not
      be fully powered to generate definite conclusion regarding genotype*diet interactions, it
      will serve to generate pilot data for future studies.
    

Intervention name(s): EPA; DHA; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement; Dietary Supplement
Intervention description(s): High fat meal containing EPA; High fat meal containing DHA; High fat meal containing negligible EPA/DHA content
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science