Berry (poly)phenols and cardiovascular health

: efficacy, bioavailability, and mechanistic insights

Abstract

Berry (poly)phenols are associated with cardiovascular health and are potent candidates in the primary prevention of cardiovascular diseases. It is hypothesised in this thesis that berry (poly)phenols are bioavailable, and that their circulating metabolites can improve endothelial function, measured as flow-mediated dilation (FMD), in healthy subjects by modulating genes involved in the early development of atherosclerosis. To address this, a number of randomised controlled human intervention studies were conducted in parallel with extensive targeted metabolomics. 
Intake of 200 and 400 g of frozen raspberries improved endothelial function by 1.6% (95% CI: 1.3, 1.9) and 1.2% (95% CI: 0.9, 1.5) 2 h post-consumption, respectively in healthy men. Significant effects were maintained 24 h after intake of 200 (1.0%; 95% CI: 0.6, 1.2) and 400 g (0.7%; 95% CI: 0.2, 0.9). Secondly, a randomised controlled trial with freeze-dried cranberry demonstrated improved endothelial function by 1.5% (95% CI: 0.9, 2.1) and 1.2% (95% CI: 0.5, 1.8) respective to acute (2 h) and daily intake for 4 weeks in healthy men. In a third intervention study, aronia berries improved endothelial function in healthy men acutely (2 h) after intake of a (poly)phenol-rich extract by 1.4% (95% CI: 0.9, 2.0), but also chronically (after 12 weeks) by 1.0% (95% CI: 0.4, 1.7) when consumed as a (poly)phenol-rich extract, or as a whole fruit powder (0.8% (95% CI: 0.05, 1.5). Furthermore, berry (poly)phenols were found to be bioavailable in plasma and urine and their metabolites were significantly associated with acute and chronic increases in FMD. No significant changes were found after intake of berries in other vascular outcomes, such as blood pressure and arterial stiffness. (Poly)phenol metabolites injected in vivo in mice demonstrated bioactivity and human nutrigenomic analysis revealed new molecular targets that may be underlying the health properties of berries. 
In conclusion, berry (poly)phenols are bioavailable, their circulating metabolites improve endothelial function in healthy subjects modulating important gene programs. The data support that berry (poly)phenol metabolites are important mediators of primary prevention of cardiovascular disease.

Date of Award	1 Mar 2019
Original language	English
Awarding Institution	King's College London
Supervisor	Ana Maria Rodriguez Mateos (Supervisor)