Abstract
Studies with resVida(®) (a high purity trans-resveratrol) show that trans-resveratrol is a substance of low oral toxicity. An acceptable daily intake (ADI) in food of 450 mg/day has been defined, a level well beyond natural dietary intake of trans-resveratrol. The ADI was based on no-observed-adverse-effect-levels (NOAELs) of 750 mg/kg bw/day in 13-week developmental toxicity studies by the dietary route and a standard safety margin of 100. In studies by gavage, the kidney and bladder are target organs at very high dosages (2,000-3,000 mg/kg bw/day). Six-month studies in rat and rabbit models show no significant increase in toxicity in comparison to 4-week studies. Lower quoted NOAELs in gavage studies (ca. 300 mg/kg bw/day) potentially reflect more rapid bioavailability, but different dosage regimes complicate comparisons. Short-term studies show no genotoxicity in vivo. A 6-month mouse carcinogenicity model showed no increase in tumors. Clinical data support an ADI of at least 450 mg/day, and kinetic data from the DSM 13-week toxicity study also support the expectation of no increase in toxicity with longer term intake.
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