This thesis aims to integrate functional and nutrigenomics analyses to examine how dietary polyphenols affect human platelet function and thus may contribute to the prevention of cardiovascular diseases. Initially, 26 low molecular weight phenolic compounds were screened for their effects on platelet aggregation and P-selectin expression in vitro. Only high, non-physiological concentrations of some phenolics showed anti-platelet effects. In parallel we conducted a systematic review of the literature to assess how polyphenol-rich foodstuffs, beverages, or extracts affect platelet function in humans. Cocoa-derived flavan-3-ols were the only class of dietary polyphenols that consistently showed anti-platelet effects in both, acute and chronic settings. Consequently we conducted an acute randomised-controlled human intervention study in which healthy volunteers consumed three different types of chocolates containing different amounts of flavan-3-ols. We found that flavan-3-ol-enriched dark chocolate beneficially affected ex vivo bleeding time, platelet aggregation and P-selectin expression. These effects were gender-dependent. Bioavailability of cocoa-derived flavan-3-ols, as assessed by a targeted metabolomics approach, was also gender-dependent. Using a platelet proteomics approach, we found subtle changes in platelet protein levels 2 h after consumption of flavan-3-ol-enriched chocolate in men, which may partly explain the observed anti-platelet effects. Finally, we assessed whether flavan-3-ols are internalised in platelets after consumption of dark chocolate. No internalisation could be found up to 2.5 h after chocolate ingestion, despite these compounds appearing in plasma. In conclusion, flavan- 3-ol-enriched dark chocolate beneficially affects platelet function in a gender-dependent way, but underpinning mechanisms are still unknown. Furthermore, current insights into their bioavailability cannot fully explain the ability of flavan-3-ols to affect platelet function. Successful future progress of research into the bioavailability and mechanisms of flavan-3- ols in vitro and in vivo will depend on the availability of pure standards for the major human metabolites of flavan-3-ols.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:558602 |
| Date | January 2011 |
| Creators | Ostertag, Luisa Martha |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=185749 |
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