Induction of the procarcinogen-activating CYP1A2 by a herbal dietary supplement in rats and humans

Herbal dietary supplements to promote health may be double-edge swords. A herbal dietary supplement, FastOne™, which contains extracts of kola nut, grape, green tea and Ginkgo biloba, and is used as an agent for weight management, was administered to rats to test whether it induced CYP1A2, a procarcinogen-activating enzyme. Western blot analysis indicated that treatments with 0.15, 0.3, 0.5, 1 and 2 g/kg of the supplement for 3 days increased CYP1A2 expression in rat liver microsomes in a dose-dependent manner. The 0.3, 0.5, 1 and 2 g/kg treatments increased rat liver microsomal CYP1A2 activity measures as the conversion of caffeine to paraxanthine to 166, 212, 331 and 473% of normal, respectively. In humans, the intake of 2 and 4 capsules of the supplement for 3 days increased CYP1A2 activity to 194 and 203%, respectively, as assessed by the change in the urinary ratio of 1,7-dimethylxanthine plus paraxanthine to unmetabolized caffeine. Intake of the herbal supplement increased CYP1A2 activity to levels higher than that observed from smoking (179%). This study suggests that the long-term intake of the dietary supplement inducing CYP1A2 may increase the incidence of colorectal cancers caused by procarcinogens activated by CYP1A2 in rapid N-acetyltransferase-2 acetylators and of lung adenocarcinoma in slow acetylators.