Clinical development of resveratrol

Mounting preclinical data support the concept that consumption of resveratrol can offer numerous health benefits for humans. Evidence suggests that it may play a role in the management of a wide variety of diseases including cardiovascular, diabetes and cancer.Encouragingly, doses of up to 5 g/day, taken for a month, have been show to be safe and reasonably well tolerated. However, the occurrence of dose-related mild to moderate gastrointestinal side effects and the ability of resveratrol to interfere with drug metabolizing enzymes are likely to dictate the upper dosage limit and it has been recommended that future studies be restricted to doses of less than 1.0 g/day. Further assessment of the long-term toxicity of resveratrol is needed at doses within this range. In humans, as in rodent models, resveratrol is efficiently absorbed when taken orally but rapid phase II metabolism drastically limits its plasma bioavailability and this may also be the case for tissues that are distant to the gastrointestinal tract. It is important to exploit the clinical pharmacokinetic data now available to guide the range of concentrations used in preclinical in vitro experiments. Currently there are no published clinical reports indicating therapeutic or protective effects of resveratrol and only a handful of studies have attempted to gain evidence of pharmacological activity in terms of pharmacodynamic changes in humans. However, the research focus is now clearly shifting towards the assessment of efficacy and the mechanisms engaged in humans and results emanating from the many trials that are either scheduled or ongoing should begin to address this knowledge gap. This chapter summarises the available data from published human studies and describes how it supports the further development of resveratrol for disease prevention and treatment.