ArticleScience translational medicine2015
Cancer chemoprevention: Evidence of a nonlinear dose response for the protective effects of resveratrol in humans and mice.
Article in Science translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 2 of them syntheses that pooled it.
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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.
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.
Who cites it
88 citing papers in PubMed, 2 syntheses or guidelines pooled it, 176 citations in OpenAlex.
- Resveratrol for the Management of Human Health: How Far Have We Come? A Systematic Review of Resveratrol Clinical Trials to Highlight Gaps and Opportunities.International journal of molecular sciences · 2024Pooled it
- The Effect of Resveratrol on Blood Lipid Profile: A Dose-Response Meta-Analysis of Randomized Controlled Trials.Nutrients · 2022Pooled it
- Lingguizhugan Decoction, a Chinese herbal formula, improves insulin resistance in overweight/obese subjects with non-alcoholic fatty liver disease: a translational approach.Frontiers of medicine · 2022Trial
- Structural Modification of Resveratrol: Biological Activities and Anticancer Potential of Emerging Methoxylated Analogs.International journal of molecular sciences · 2026Review
- Autophagy modulation in cancer.Nature reviews. Drug discovery · 2026Review
- Effects of a resveratrol-containing nutraceutical on cardiac biomarkers, echocardiographic parameters, and oxidative stress in dogs with naturally occurring cardiac disease.Frontiers in veterinary science · 2026Article
- Preclinical Risk Assessment of Plant Lectins with Pharmacological Applications: A Narrative Review.Molecules (Basel, Switzerland) · 2025Review
- Dietary Polyphenol Combinations Have a Multifaceted Inhibitory Effect on Metabolic Rewiring and Signaling Pathways in Neuroblastoma.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Metabolites as agents and targets for cancer immunotherapy.Nature reviews. Drug discovery · 2025Review
- Precision Prevention Studies: A Targeted Approach to Cancer Prevention.Cancer prevention research (Philadelphia, Pa.) · 2025Review
- Cancer chemoprevention: signaling pathways and strategic approaches.Signal transduction and targeted therapy · 2025Review
- The Impact of Resveratrol and Melatonin on the Genome and Oxidative Status in Ageing Rats.Nutrients · 2025Article
- Resveratrol does not mimic the positive effects of calorie restriction on lifespan in Microcebus murinus.Communications biology · 2025Article
- Article
- The Therapeutic Effects of Bioactive Compounds on Colorectal Cancer via PI3K/Akt/mTOR Signaling Pathway: A Critical Review.Food science & nutrition · 2024Review
- Advancements in 3D In Vitro Models for Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- Resveratrol prevents the release of neutrophil extracellular traps (NETs) by controlling hydrogen peroxide levels and nuclear elastase migration.Scientific reports · 2024Article
- Resveratrol Promotes Self-digestion to Put Cancer to Sleep.Journal of cancer prevention · 2024Article
- Article
- Chinese Dietary Indices and Glioma: New Insights of a Case-Control Study in the Chinese Population.Nutrients · 2023Article
28 more citing papers are in PubMed but not listed here.
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Authors and funding
24 authors at 3 institutions in 2 countries.
Funding
Abstract
Resveratrol is widely promoted as a potential cancer chemopreventive agent, but a lack of information on the optimal dose prohibits rationally designed trials to assess efficacy. To challenge the assumption that "more is better," we compared the pharmacokinetics and activity of a dietary dose with an intake 200 times higher. The dose-response relationship for concentrations generated and the metabolite profile of [(14)C]-resveratrol in colorectal tissue of cancer patients helped us to define clinically achievable levels. In Apc(Min) mice (a model of colorectal carcinogenesis) that received a high-fat diet, the low resveratrol dose suppressed intestinal adenoma development more potently than did the higher dose. Efficacy correlated with activation of adenosine monophosphate-activated protein kinase (AMPK) and increased expression of the senescence marker p21. Nonlinear dose responses were observed for AMPK and mechanistic target of rapamycin (mTOR) signaling in mouse adenoma cells, culminating in autophagy and senescence. In human colorectal tissues exposed to low dietary concentrations of resveratrol ex vivo, we measured enhanced AMPK phosphorylation and autophagy. The expression of the cytoprotective NAD(P)H dehydrogenase, quinone 1 (NQO1) enzyme was also increased in tissues from cancer patients participating in our [(14)C]-resveratrol trial. These findings warrant a revision of developmental strategies for diet-derived agents designed to achieve cancer chemoprevention.
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Registered trials
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.