Evidence map›Paper›PMID 33675348›Full record

ArticleThe American journal of clinical nutrition2021

Distribution and metabolism of [14C]-resveratrol in human prostate tissue after oral administration of a "dietary-achievable" or "pharmacological" dose: what are the implications for anticancer activity?

Hong Cai, Edwina N Scott, Robert G Britton, Emma Parrott, Ted J Ognibene, Michael Malfatti, Masood Khan, William P Steward, Karen Brown

Open access · hybridAbstract read
In one paragraph

Article in The American journal of clinical nutrition, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
0.8field-weighted citation impact, top 28% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Review
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  7. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 2 countries.

Hong CaiLeicester Cancer Research Centre, University of Leicester, Leicester, United Kingdom.
Edwina N ScottLeicester Cancer Research Centre, University of Leicester, Leicester, United Kingdom.
Robert G BrittonLeicester Cancer Research Centre, University of Leicester, Leicester, United Kingdom.
Emma ParrottLeicester Cancer Research Centre, University of Leicester, Leicester, United Kingdom.
Ted J OgnibeneLawrence Livermore National Laboratory, Livermore, CA, USA.
Michael MalfattiLawrence Livermore National Laboratory, Livermore, CA, USA.
Masood KhanUniversity Hospitals of Leicester NHS Trust, Leicester, United Kingdom.
William P StewardLeicester Cancer Research Centre, University of Leicester, Leicester, United Kingdom.
Karen BrownLeicester Cancer Research Centre, University of Leicester, Leicester, United Kingdom.
University of Leicester · GBLawrence Livermore National Laboratory · USUniversity Hospitals of Leicester NHS Trust · GB

Funding

Resource for the Development of Biomedical Accelerator Mass Spectrometry (AMS)P41GM103483 · NIGMS · UNIVERSITY OF CALIF-LAWRNC LVRMR NAT LAB · PI TURTELTAUB, KENNETH W. · 2012 to 2019
$12.0M
National User Resource for Biological Accelerator Mass SpectrometryR24GM137748 · NIGMS · LAWRENCE LIVERMORE NATIONAL SECURITY, LLC · PI BENCH, GRAHAM · 2020 to 2024
$6.5M
Cancer Research UK 13101NIGMS NIH HHS P41 GM103483NIGMS NIH HHS R24 GM137748
6 · The paper itself

Abstract

backgroundThe dietary polyphenol resveratrol prevents various malignancies in preclinical models, including prostate cancer. Despite attempts to translate findings to humans, gaps remain in understanding pharmacokinetic-pharmacodynamic relations and how tissue concentrations affect efficacy. Such information is necessary for dose selection and is particularly important given the low bioavailability of resveratrol.

objectivesThis study aimed to determine concentrations of resveratrol in prostate tissue of men after a dietary-achievable (5 mg) or pharmacological (1 g) dose. We then examined whether clinically relevant concentrations of resveratrol/its metabolites had direct anticancer activity in prostate cell lines.

methodsA window trial was performed in which patients were allocated to 5 mg or 1 g resveratrol daily, or no intervention, before prostate biopsy. Patients (10/group) ingested resveratrol capsules for 7-14 d before biopsy, with the last dose [14C]-labeled, allowing detection of resveratrol species in prostate tissue using accelerator MS. Cellular uptake and antiproliferative properties of resveratrol/metabolites were assessed in cancer and nonmalignant cell cultures using HPLC with UV detection and cell counting, respectively.

results[14C]-Resveratrol species were detectable in prostate tissue of all patients analyzed, with mean ± SD concentrations of 0.08 ± 0.04 compared with 22.1 ± 8.2 pmol/mg tissue for the 5 mg and the 1 g dose, respectively. However, total [14C]-resveratrol equivalents in prostate were lower than we previously reported in plasma and colorectum after identical doses. Furthermore, resveratrol was undetectable in prostate tissue; instead, sulfate and glucuronide metabolites dominated. Although resveratrol reduced prostate cell numbers in vitro over 7 d, the concentrations required (≥10 µM) exceeded the plasma maximum concentration. Resveratrol mono-sulfates and glucuronides failed to consistently inhibit cell growth, partly due to poor cellular uptake.

conclusionsLow tissue concentrations of resveratrol species, coupled with weak antiproliferative activity of its conjugates, suggest daily doses of ≤1 g may not have direct effects on human prostate.This trial was registered at clinicaltrialsregister.eu as EudraCT 2007-002131-91.

Indexed as

Administration, OralAntioxidantsCarbon RadioisotopesCell Line, TumorDietDose-Response Relationship, DrugDrug Administration RoutesHumansIsotope LabelingMaleProstateProstatic NeoplasmsResveratrolAntioxidantsCarbon RadioisotopesResveratrolaccelerator mass spectrometrycancer preventionmetabolismpharmacokineticsprostateresveratroltissue distributionwindow trial

Identifiers

PMID33675348
PMCPMC8106746
OpenAlexW3133611895

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.