Effects of resveratrol alone or in combination with piperine on cerebral blood flow parameters and cognitive performance in human subjects: a randomised, double-blind, placebo-controlled, cross-over investigation

Abstract

Previous research has shown that resveratrol can increase cerebral blood flow (CBF) in the absence of improved cognitive performance in healthy, young human subjects during the performance of cognitively demanding tasks. This lack of cognitive effects may be due to low bioavailability and, in turn, reduced bioefficacy of resveratrol in vivo. Piperine can alter polyphenol pharmacokinetics, but previous studies have not investigated whether this affects the efficacy of the target compound. Therefore, the objective of the present study was to ascertain whether co-supplementation of piperine with resveratrol affects the bioavailability and efficacy of resveratrol with regard to cognition and CBF. The present study utilised a randomised, double-blind, placebo-controlled, within-subjects design, where twenty-three adults were given placebo, trans-resveratrol (250 mg) and trans-resveratrol with 20 mg piperine on separate days at least a week apart. After a 40 min rest/absorption period, the participants performed a selection of cognitive tasks and CBF was assessed throughout the period, in the frontal cortex, using near-IR spectroscopy. The presence of resveratrol and its conjugates in the plasma was confirmed by liquid chromatography -MS analysis carried out following the administration of the same doses in a separate cohort (n 6). The results indicated that when co-supplemented, piperine and resveratrol significantly augmented CBF during task performance in comparison with placebo and resveratrol alone. Cognitive function, mood and blood pressure were not affected. The plasma concentrations of resveratrol and its metabolites were not significantly different between the treatments, which indicates that co-supplementation of piperine with resveratrol enhances the bioefficacy of resveratrol with regard to CBF effects, but not cognitive performance, and does this without altering bioavailability.

Preclinical and clinical evidence for the role of resveratrol in the treatment of cardiovascular diseases

“…Several other studies have attributed the protective effects of resveratrol from stroke to its neuroprotective effects [145][146][147][148][149][150], which have been reviewed previously [151]. Although there is no human clinical trial that investigated the protective effects of resveratrol in stroke patients, a single dose of resveratrol has been shown to increase the cerebral blood flow during a performance task in healthy adult subjects [152,153].…”

Resveratrol and cancer: Challenges for clinical translation

“…However, this study did not examine whether or not the addition of piperine affects the bioavailability of resveratrol, as they were focused on determining the mechanism of action. In another recent study, Wightman and colleagues demonstrated that piperine can increase the bioefficacy of resveratrol when co-supplemented in healthy human subjects with regard to cerebral blood flow effects [25]. In this study, co-supplementation of piperine and resveratrol were found to significantly augment cerebral blood flow during task performance without affecting cognitive function, mood or blood pressure.…”

Bioavailability of dietary polyphenols: Factors contributing to their clinical application in CNS diseases

“…It is possible that poor bioavailability could contribute to reduced brain effects in humans (Wightman et al 2012). In a related study, co-supplementation with the pepper alkaloid Piperine, improved resveratrol's effects on CBF during memory task performance compared to placebo and resveratrol alone (Wightman et al 2014). These data indicate that bioefficacy of resveratrol with regard to CBF effects is related to its bioavailability and the same could be relevant to other polypenols.…”