Repeat dose study of the cancer chemopreventive agent resveratrol in healthy volunteers: safety, pharmacokinetics, and effect on the insulin-like growth factor axis

Brown VA, Patel KR, Viskaduraki M, Crowell JA, Perloff M, Booth TD · Cancer Research

No serious adverse reactions across 29 days, but the 2.5 g and 5 g doses caused mild to moderate gastrointestinal symptoms — nausea, flatulence, abdominal discomfort, diarrhoea — beginning after two to four days, arriving within an hour of each dose and resolving within two days of stopping. Resveratrol-3-O-sulfate and the two glucuronides were the major plasma metabolites, with areas under the curve exceeding parent resveratrol by up to 20.3-fold. Circulating IGF-1 and IGFBP-3 fell against each participant's own pre-dosing values (p<0.04 for both), most markedly at 2.5 g.

Population

Healthy volunteers at two centres, recruited sequentially to four dose levels

Intervention

Resveratrol 0.5, 1.0, 2.5 or 5.0 g daily for 29 days

Comparator

Each participant's own pre-dosing values; no placebo and no randomisation

Limitations

Twenty-nine days in healthy volunteers, with participants recruited sequentially to each dose rather than randomised, and no placebo: the IGF-1 fall is a before-and-after in an uncontrolled series. What it establishes is where gastrointestinal tolerance breaks down — well above the 500 mg supplement dose — and that the conjugates, not free resveratrol, dominate exposure.