The effects of alcohol and dietary fat on spontaneous energy and macronutrient intakes were investigated in eight male subjects who participated in a protocol including four randomly assigned 2-d sessions during which they ate ad libitum. In each session they had free access to either high- or low-fat foods, with alcohol or a placebo. The high-fat diet was associated with a substantial increase in daily energy intake. Alcohol had no inhibitory effect on food intake and its energy content was thus associated with an additional increase in energy intake. The enhancing effects of alcohol and dietary fat on daily energy intake were additive so that overfeeding was maximal (2.8 MJ/d) under the high-fat diet+alcohol condition. To further examine the effects of alcohol on energy and macronutrient intakes, reported food intake was studied in 351 men and 360 women who had been tested in the Québec Family Study. The results showed that a high alcohol intake was associated with a high daily energy intake and had no inhibitory effect on lipid intake. In conclusion, a dietary regimen providing a high fraction of energy as alcohol and fat increases the risk for positive energy balance under free-living conditions.
1. The interindividual variation and enantioselectivity of the in vitro styrene oxidation by cytochrome P450 have been investigated in 20 human microsomal liver samples. Liver samples were genotyped for the CYP2E1*6 and CYP2E1*5B alleles. 2. Kinetic analysis indicated the presence of at least two forms of styrene-metabolizing cytochrome P450. The enzyme constants for the high-affinity component were subject to appreciable interindividual variation, i.e. Vmax1 ranged from 0.39 to 3.20 nmol mg protein(-1) min(-1) (0.96+/-0.63) and Km1 ranged from 0.005 to 0.03 mM (0.011+/-0.006). Inhibition studies with chemical inhibitors of CYP2E1, CYP1A2, CYP2C8/9 and CYP3A4 demonstrated that CYP2E1 was the primary enzyme involved in the high-affinity component of styrene oxidation. No relationship between the interindividual variation in Vmax1 and Km1 and the genetic polymorphisms of the CYP2E1 gene was found. 3. Cytochrome P450-mediated oxidation of styrene demonstrated a moderate enantioselectivity, with an enantiomeric excess (ee) of (S)-styrene oxide of 15% (range 4-27%) at low styrene concentration and an ee of (R)-styrene oxide of 7% (range -11 to +22%) at high styrene concentration. This points towards the involvement of at least two cytochrome P450, with different enantioselectivities. 4. The data indicate that cytochrome P450-mediated styrene oxidation is subject to considerable interindividual variation, but only to a moderate product enantioselectivity.
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