{"doi":"10.1093/ajcn/nqaa414","title":"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?","abstract":"BACKGROUND: The 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. OBJECTIVES: This 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. METHODS: A 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. CONCLUSIONS: Low 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.","journal":"American Journal of Clinical Nutrition","year":2020,"id":80809,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9474,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":419261,"name":"Edwina N. Scott","orcid":null,"position":1,"is_corresponding":false},{"id":418461,"name":"Robert G. Britton","orcid":"0000-0001-8813-1635","position":2,"is_corresponding":false},{"id":419262,"name":"Emma Parrott","orcid":null,"position":3,"is_corresponding":false},{"id":418462,"name":"Ted Ognibene","orcid":"0000-0003-4735-0764","position":4,"is_corresponding":false},{"id":313539,"name":"Michael Malfatti","orcid":"0000-0003-2431-9115","position":5,"is_corresponding":false},{"id":418463,"name":"Masood A. Khan","orcid":"0009-0006-1395-2272","position":6,"is_corresponding":false},{"id":419263,"name":"William P. Steward","orcid":null,"position":7,"is_corresponding":false},{"id":418464,"name":"Karen Brown","orcid":"0000-0002-5217-1501","position":8,"is_corresponding":false},{"id":418460,"name":"Hong Cai","orcid":"0000-0002-2711-9461","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-18T21:51:58.988919Z","pmid":"33675348","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}