Aim: Progressive microvascular dysfunction in T2DM may impair the ability of cerebral vessels to supply blood to brain regions during local metabolic demand, thereby predisposing one to greater risk of dementia. Having previously demonstrated that resveratrol can enhance vasodilator function in the systemic circulation, we hypothesised that resveratrol would also benefit cerebral circulation. We aimed to determine the most efficacious dose of resveratrol to improve cerebral vasodilator responsiveness (CVR) in T2DM.
Method: In a double-blind, placebo-controlled crossover intervention trial, 36 well-controlled T2DM adults aged 40-80 years were randomised to consume a single dose of synthetic trans-resveratrol (0, 75, 150, 300mg) at weekly intervals. Transcranial Doppler ultrasound was used to assess CVR to a hypercapnic stimulus, viz. breathing Carbogen gas (95%O2; 5%CO2) for 3 min, both before and 45 mins after resveratrol or placebo consumption. CVR was measured in both left and right middle cerebral arteries (MCA) and expressed as the percentage change in mean blood flow velocity from baseline to the peak velocity attained during the stimulus.
Results: Using repeated measures ANOVA, consumption of each resveratrol dose resulted in significant within-individual increases in CVR compared with placebo (75mg: 13.8±3.5%, P=0.001; 150mg: 8.9±3.5%, P=0.016; 300mg: 13.7±3.3%, P>0.001).
Conclusion: Our results provide the first ever clinical evidence of an acute improvement of vasodilator responsiveness in cerebral vessels which was maximal following the lowest dose of resveratrol (75mg) in a population who are known to have endothelial dysfunction and sub-clinical cognitive impairment.
Funding sources: Dementia Collaborative Research Centre (NHMRC); DSM Nutritional Products