The impact of fish oil fatty-acids on post-prandial vascular reactivity

• Main Author: Mcmanus, Sean
• Published: University of East Anglia 2014
• Subjects: 610
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.679137

Progressive loss of vascular reactivity and increased vascular tone with age are being increasingly recognised as significant cardiovascular disease (CVD) risk factors. The vasculature has emerged as a target for dietary strategies to modify these progressions. Our previous data suggest that inclusion of fish oil in a high-fat test meal improves postprandial vascular reactivity in healthy men. The primary aim of this project was to determine the individual effects of the fish oil fatty acids, eicosapentaenoic acid (EPA) versus docosahexaenoic acid (DHA) on post-prandial vascular reactivity and to identify underlying molecular mechanisms of these effects. In this study, the acute effects of a single dose (4.16g) of EPA, DHA and placebo oil on postprandial vascular reactivity were determined in men categorised as being at a 1.5 relative risk of CVD in a double-blind randomised crossover trial. Measures of vascular tone and function, alongside an endothelium dependent measure of vascular reactivity, were taken along with blood samples, at baseline and at 4 hours in order to coincide with the anticipated peak plasma concentration of these fatty acids. These blood samples were utilised for assessment of biomarkers associated with changes in vascular tone and postprandial whole blood culture (WBC). WBC was conducted to investigate the effect of changes in the postprandial lipidome, dependent on EPA and DHA consumption, on cytokine production. Response to intervention according to genotype was also determined retrospectively. We observed that DHA (p=0.04) but not EPA (p=0.06) significantly reduced Augmentation Index (AI) postprandially when compared to control. AI was reduced by 13.3% and 11.3% in response to DHA and EPA respectively. In addition, our data shows for the first time, that levels of the vasoactive n-3 PUFA epoxide and diol metabolites are subject to large changes post consumption of physiological levels of EPA and DHA. Our data also suggests there is wide inter-individual variability in circulating levels of these compounds, which may in part explain inter-individual responsiveness to EPA and DHA. We were not able to observe changes in plasma nitrite or H2S levels postprandially, suggesting that EPA and DHA dependent changes in vascular tone may be mediated in part by their vasoactive epoxide and diol metabolites. However, whole Blood Culture experiments did not show a significant effect on any of the cytokines or growth factors investigated, before or after correction for BMI and AGE. Finally, our investigations of response to treatment by genotype suggested a novel interaction between the PPAR-ƴ rs1801282 polymorphism, DHA consumption and improvements in postprandial triglyceridemia. The findings of this thesis emphasise the differential effects of EPA and DHA in the vasculature and the inter-individual responsiveness to these nutrients.