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

Br J Nutr. 2014 Jul 28;112(2):203-13. doi: 10.1017/S0007114514000737. Epub 2014 May 7.


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.

Trial registration: ClinicalTrials.gov NCT01331382.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Alkaloids / blood
  • Alkaloids / metabolism*
  • Alkaloids / therapeutic use
  • Benzodioxoles / blood
  • Benzodioxoles / metabolism*
  • Benzodioxoles / therapeutic use
  • Cerebrovascular Circulation*
  • Cognition Disorders / blood
  • Cognition Disorders / metabolism
  • Cognition Disorders / prevention & control
  • Cognition*
  • Cohort Studies
  • Cross-Over Studies
  • Dietary Supplements*
  • Double-Blind Method
  • Female
  • Frontal Lobe / blood supply*
  • Humans
  • Intestinal Absorption
  • Male
  • Nootropic Agents / agonists
  • Nootropic Agents / blood
  • Nootropic Agents / metabolism*
  • Nootropic Agents / therapeutic use
  • Pilot Projects
  • Piperidines / blood
  • Piperidines / metabolism*
  • Piperidines / therapeutic use
  • Polyunsaturated Alkamides / blood
  • Polyunsaturated Alkamides / metabolism*
  • Polyunsaturated Alkamides / therapeutic use
  • Resveratrol
  • Spectroscopy, Near-Infrared
  • Stilbenes / agonists
  • Stilbenes / blood
  • Stilbenes / metabolism*
  • Stilbenes / therapeutic use
  • Task Performance and Analysis
  • Young Adult


  • Alkaloids
  • Benzodioxoles
  • Nootropic Agents
  • Piperidines
  • Polyunsaturated Alkamides
  • Stilbenes
  • Resveratrol
  • piperine

Associated data

  • ClinicalTrials.gov/NCT01331382