Resveratrol Modulates Drug- and Carcinogen-Metabolizing Enzymes in a Healthy Volunteer Study

Arizona Cancer Center, The University of Arizona, Tucson, AZ 85724, USA.
Cancer Prevention Research (Impact Factor: 4.44). 09/2010; 3(9):1168-75. DOI: 10.1158/1940-6207.CAPR-09-0155
Source: PubMed


Resveratrol has been shown to exhibit cancer-preventive activities in preclinical studies. We conducted a clinical study to determine the effect of pharmacologic doses of resveratrol on drug- and carcinogen-metabolizing enzymes. Forty-two healthy volunteers underwent baseline assessment of cytochrome P450 (CYP) and phase II detoxification enzymes. CYP1A2, CYP2D6, CYP2C9, and CYP3A4 enzyme activities were measured by the metabolism of caffeine, dextromethorphan, losartan, and buspirone, respectively. Blood lymphocyte glutathione S-transferase (GST) activity and GST-pi level and serum total and direct bilirubin, a surrogate for UDP-glucuronosyl transferase (UGT) 1A1 activity, were measured to assess phase II enzymes. After the baseline evaluation, study participants took 1 g of resveratrol once daily for 4 weeks. Enzyme assessment was repeated upon intervention completion. Resveratrol intervention was found to inhibit the phenotypic indices of CYP3A4, CYP2D6, and CYP2C9 and to induce the phenotypic index of 1A2. Overall, GST and UGT1A1 activities were minimally affected by the intervention, although an induction of GST-pi level and UGT1A1 activity was observed in individuals with low baseline enzyme level/activity. We conclude that resveratrol can modulate enzyme systems involved in carcinogen activation and detoxification, which may be one mechanism by which resveratrol inhibits carcinogenesis. However, pharmacologic doses of resveratrol could potentially lead to increased adverse drug reactions or altered drug efficacy due to inhibition or induction of certain CYPs. Further clinical development of resveratrol for cancer prevention should consider evaluation of lower doses of resveratrol to minimize adverse metabolic drug interactions.

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    • "In addition, a better understanding of the interaction of RSV with other drugs and supplements is key to reduce adverse events (MacDonald et al., 2009). The modulation of the cytochrome P450 enzyme system by RSV is worthy of note, and suggests possible impact of this polyphenol on hepatic detoxification and metabolism of drugs and xenobiotics (Chow et al., 2010). • Resveratrol dosage. "
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    • "Resveratrol also acts as anti-inflammatory (Bereswill et al., 2010), alters drug metabolizing enzymes (Chow et al., 2010), inhibits cyclooxygenases (Wendeburg et al., 2009), and, importantly, has specific effects on proteins and/or signaling cascades such as SIRT1 (silent information regulator T1) "
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    • "We did find that high-dose resveratrol supplementation is associated with gastrointestinal side effects in the majority of subjects . Similar side effects were observed previously at our centre (la Porte et al. 2010) and by other investigators (Chow et al. 2010; Brown et al. 2010; Howells et al. 2011), but the frequency of side effects in the present study was higher than reported in other studies. We do not have a definitive explanation for this. "
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