A Randomized, Double-Blind, Dose-Ranging, Pilot Trial Of Piperine With Resveratrol On The Effects On Serum Levels Of Resveratrol

Resveratrol (3,4,5-trihydroxystilbene) is a naturally occurring phytoalexin with purported health-promoting effects, but with limited oral bioavailability. Our prior murine modeling research observed enhanced resveratrol bioavailability with piperine co-administration. In this study, single-dose pharmacokinetics of resveratrol with or without piperine and the associated toxicities were studied on a cohort of healthy volunteers. We performed a double-blind, randomized, three-arm pilot study. Participants were randomized to receive a single dose of resveratrol 2.5 g, with piperine in 0 mg, 5 mg, or 25 mg dose. An improved liquid chromatography/mass spectrometry assay was used to determine serum levels of resveratrol and resveratrol-glucuronide. Baseline through 24 h post-study drug serum analyses were performed and adverse events were followed for 30 days. Twenty-four participants were enroled. No significant relationship between dose and pharmacokinetic values were found. In the sex stratified analysis, C-max for resveratrol in women showed a trend (P = 0.057) toward an increase with piperine. Pharmacokinetic values for resveratrol were: C-max - 18.5 +/- 16 ng/mL resveratrol alone, 29 +/- 29 resveratrol + 5 mg piperine, 16 +/- 13 resveratrol + 25 mg piperine; area under the concentration x time curve - 1270 +/- 852 ng/h/mL resveratrol alone, 2083 +/- 2284 resveratrol + 5 mg piperine, 1132 +/- 222 resveratrol + 25 mg piperine. All subjects tolerated their protocol therapy with minimal to no toxicity and no evidence of differences between the three groups. The co-administration of resveratrol with piperine at 5 and 25 mg doses did not sufficiently alter the pharmacokinetics of resveratrol or resveratrol-glucuronide to demonstrate the significant enhancement observed in murine modeling.