Resveratrol in human cancer chemoprevention - Choosing the 'right' dose

• Published in: Molecular nutrition & food research Vol. 56; no. 1; pp. 7 - 13
• Main Authors: Scott, Edwina, Steward, William P., Gescher, Andreas J., Brown, Karen
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01-01-2012; WILEY‐VCH Verlag; Wiley
• Subjects: Animals; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - therapeutic use; Biological and medical sciences; Cancer chemoprevention; Dose; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Food industries; Fundamental and applied biological sciences. Psychology; Humans; Neoplasms - prevention & control; Pharmacodynamics; Pharmacokinetics; Resveratrol; Stilbenes - administration & dosage; Stilbenes - therapeutic use; Human; Cancer chemoprevention; Pharmacodynamics; Resveratrol; Right; Malignant tumor; Pharmacokinetics; Dose; Cancer
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.201100400

There is now robust preclinical evidence to suggest that resveratrol possesses cancer chemopreventive properties. A series of clinical pilot studies has provided insights into its pharmacokinetics, and data on its human antineoplastic pharmacodynamics start to emerge. It is likely that resveratrol will be developed further in the clinic as a putative cancer chemopreventive agent. The question that remains unresolved is: What is the most suitable dose of resveratrol for effective cancer preventive intervention? Mechanistic studies in cells in vitro have almost invariably used concentrations of resveratrol in the 10–5 to 10–4 M range, which is much higher than those which can be achieved in the human biophase after consumption of doses up to 1 g. Many of the preclinical efficacy studies in rodent models of carcinogenesis have employed doses which are dramatically above those which can be ingested with the diet. New experimental paradigms need to be used to obtain information on pharmacological changes elicited by resveratrol when present at very low concentrations or when administered at dietary‐relevant doses.