The effects of alcohol and diallyl sulphide on CYP2E1 activity in humans: a phenotyping study using chlorzoxazone

The effects of acute administration of dietary levels of ethanol and the ga rlic oil extract, diallyl sulphide (DAS), on cytochrome P450 2E1 (CYP2E1) a ctivity in volunteers were studied using the selective probe substrate, chl orzoxazone (CZX). The ratio of the CZX metabolite 6-hydroxychlorzoxazone (6 -OHCZX) to CZX was taken to indicate CYP2E1 activity. The mean differences between the baseline and DAS-treated (0.2 mg/kg) CYP2E1 activities were sig nificantly different (two-tailed p value = 0.0242, n = 8). Likewise, the me an differences between the baseline and ethanol-treated (0.8 g/kg) CYP2E1 a ctivities were also significantly different (two-tailed p value = 0.0005, n = 7). The reduction in in vivo CYP2E1 activity by DAS is consistent with r eported inhibition observed in vitro. The marked reduction in CYP2E1 activi ty following acute ingestion of ethanol is consistent with a competitive in hibition mechanism of CZX metabolism. The inhibitory effect of DAS maybe ad ditive with daily consumption of Allium vegetables in particular. This may explain the lower 6-OHCZX/CZX metabolic ratios measured in various European and Mexican cohorts and is consistent with the lower incidence of stomach, liver and colon cancers observed in southern Europeans.