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    Resveratrol with Piperine

    In 2021 Randomized Controlled Trial, participants receive a single dose of resveratrol 2500 mg, with piperine in 0 mg, 5 mg or 25 mg dose. Despite the observation of piperine coadministration significantly increasing bioavailability (Cmax and AUC) of resveratrol in C57BL mice, no significant increase in resveratrol or decrease in resveratrol glucuronide could be observed in healthy adults taking 2500 gm of resveratrol with piperine (5 or 25 mg) as compared to resveratrol alone. [1]

    1. Bailey HH et al.: A randomized, double-blind, dose-ranging, pilot trial of piperine with resveratrol on the effects on serum levels of resveratrol. Eur J Cancer Prev 2021. (PMID 32868637) [PubMed] [DOI] [Full text] 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, Cmax for resveratrol in women showed a trend (P = 0.057) toward an increase with piperine. Pharmacokinetic values for resveratrol were: Cmax - 18.5 ± 16 ng/mL resveratrol alone, 29 ± 29 resveratrol + 5 mg piperine, 16 ± 13 resveratrol + 25 mg piperine; area under the concentration × 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.