Effects of resveratrol on cerebral blood flow variables and cognitive performance in humans: a double-blind, placebo-controlled, crossover investigation.

Background: The many putative beneficial effects of the polyphenol resveratrol include an ability to bolster endogenous antioxidant defences, modulate nitric oxide synthesis and promote vasodilation, thereby improving blood flow. Resveratrol may therefore modulate aspects of brain function in humans. Objectives: The current study assessed the effects of oral resveratrol on cognitive performance and localised cerebral blood flow parameters in healthy human adults. Design: In this randomised double-blind, placebo-controlled, cross-over study 22 healthy adults received placebo and two doses (250 mg and 500 mg) of trans-resveratrol in counterbalanced order on separate days. Following a 45-min resting absorption period participants performed a selection of cognitive tasks that activate the frontal cortex for a further 36 minutes. Cerebral blood flow and haemodynamics, as indexed by concentration changes in oxygenated and deoxygenated haemoglobin, were assessed in the frontal cortex throughout the post-treatment period using Near Infrared Spectroscopy. The presence of resveratrol and its conjugates in plasma were confirmed by HPLC following the same doses in a separate cohort (n=9). Results: Resveratrol administration resulted in dose-dependent increases in cerebral blood-flow during task performance, as indexed by total concentrations of haemoglobin. There was also an increase in deoxyhaemoglobin following both doses of resveratrol, suggesting enhanced oxygen extraction, which became apparent towards the end of the 45-minute absorption phase and was sustained throughout task performance. Cognitive function was not affected. Resveratrol metabolites were present in plasma throughout the cognitive task period. Conclusions: These results show that single doses of orally administered resveratrol can modulate cerebral blood-flow parameters.