The clinical effects of flavonoid-rich nutritional interventions on neurocognitive function

It has been widely accepted that lifestyle and dietary habits strongly influence health and the occurrence of disease. Previous research has shown that dietary polyphenols can enhance brain function, which has been seen as improvements in both cognitive performance and mood, suggesting that they can be used as intervention strategies for the prevention, delay or treatment of neurodegenerative diseases and mental illness. The mechanisms whereby polyphenols induce those health promoting effects have been emerging but are still unclear. There is evidence suggesting that certain polyphenolic compounds can cross the blood brain barrier and positively modulate specific neurotransmitter receptors. Further, there is evidence that they can improve arterial function leading to improvements in cerebral blood flow, and that they can positively modulate glucoregulatory mechanisms. In this thesis, we investigate the effects of dietary polyphenols that naturally occur in cocoa and grapeseed on cognitive function and mood in healthy older adults and their potential underpinning mechanisms. We further explore the effects of cocoa polyphenols on executive function by systematically reviewing published clinical trials, as an attempt to implement a domain specific approach, whilst highlighting the importance of executive (dys)function in brain health. Finally, we discuss the effects of hop flavonoids on mood and neurochemical parameters. We consider their potential as mood enhancing treatments and introduce a clinical trial protocol for the investigation of those effects. We showed that 900mg of cocoa flavanol intake for 12 weeks showed a tendency towards improved vascular function, FMD response (F(2,59.26)=2.59; p=0.084) and a significantly reduced mean heart rate in the cocoa arm (mean diff=-2.39; p=0.019) and that an acute dose of 600mg total grapeseed polyphenols improved blood glucose peak time (p=0.002) and mood by increasing difference in sedation (F(1,30)=7.045; p=0.012) . We speculate that overall improvements in cognitive function observed after chronic supplementation of a cocoa polyphenol-rich treatment might be attributed to the methylxanthines found in both active treatment and control, however that is not in line with our findings regarding vascular function, therefore further investigation is required to establish whether the cocoa methylxanthines present in our treatments can have any biological or cognitive effects. In addition, we argue that grapeseed polyphenols may have protective effects against cognitive decline due to fatigue on a postprandial level. We believe that the observed changes in mood following both intervention strategies are encouraging but require further investigation on the associated biochemical mechanisms of action. We finally set the foundations for clinical research on hop phenolics, a promising area that is presently underresearched, and we discuss unanswered questions and future directions in the field