biostudies-literatureCai HNIH National Centre for Research ResourcesCancer Research UKLeicester Experimental Cancer Medicine CentreNCRR NIH HHSNIGMS NIH HHS298ra117https://www.ebi.ac.uk/biostudies/studies/S-EPMC4827609biostudies-literatureUnknown7(298)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 proteiScience translational medicineCancer chemoprevention: Evidence of a nonlinear dose response for the protective effects of resveratrol in humans and mice.PMC4827609P41 GM103483P41 RR013461C325/A13101C325/A15575P41RR1346113101#P41RR13461Rufini AWest KScott EKarmokar AGreaves PBritton RGJawad DWalsh JGescher AJKholghi ACai HHowells LGoldring CSteward WPHorner-Glister EJames MHemingway DKitteringham NBrown KAndreadi CViskaduraki MMalfatti MOgnibene TMiller AfalseCancer chemoprevention: Evidence of a nonlinear dose response for the protective effects of resveratrol in humans and mice.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 protei2015-01-01T00:00:00Z2015 Jul2025-04-18T16:20:56.772Z2019-03-27T03:11:44ZS-EPMC48276092622330010.1126/scitranslmed.aaa7619