Abstract
Blood alcohol concentration (BAC) differs greatly among individuals, even when people of the same sex and age drink alcohol under the same drinking conditions. In this study, we investigated the main factors involved in the internal reg-ulation of individual differences in BAC, focusing on the alcohol dehydrogenase 1B (ADH1B) genotype, blood acetal-dehyde concentration (BAcH), amount of habitual alcohol consumption, pharmacokinetic parameters of BAC, distribution volume of ethanol (Vd), and gastric emptying rate (GER) under the same drinking conditions. Twenty healthy Japanese males aged between 40 and 59 years old and having the aldehyde dehydrogenase 2 (ALDH2) genotype of ALDH 2*1/*2 were recruited for this study. The subjects were given 0.32 g ethanol/kg body weight in the form of commercially available beer (5%, v/v). The results showed that BAC-max differed greatly among individuals with a more than two-fold variation. When the BAC-time curve was compared among ADH1B genotypes (ADH1B*1/*1, *1/*2, and *2/*2), there were no differences in BAC among the genotypes. Although BAcH, monthly alcohol consumption, elimination rate of blood ethanol (β value) and ethanol disappearance rate from the body (EDR) can affect BAC, all of them had no correlations with BAC-max. However, Vd (liter/kg), ΔPlasma glucose concentration (ΔPGC = PGC30 min ? PGC0 min) and the serum concentration of gastric inhibitory polypeptide (GIP) did correlate with BAC-max. Model 2 in multiple linear regression analysis showed the optimal model for Vd and GIP with positive correlations with BAC-max. As GIP and ΔPGC are both reflected by gastric emptying rate (GER), we concluded that the individual differences in BAC after moderate drinking are mainly regulated by GER together with Vd. These findings demonstrate that together with body water content, the gastrointestinal tract plays an important role in the regulation of individual differences in BAC, involving first pass metabolism of ethanol.
Highlights
Light to moderate drinking is beneficial to cardiovascular health, heavy drinking often results in health and social problems [1]
We investigated the main factors involved in the internal regulation of individual differences in Blood alcohol concentration (BAC), focusing on the alcohol dehydrogenase 1B (ADH1B) genotype, blood acetaldehyde concentration (BAcH), amount of habitual alcohol consumption, pharmacokinetic parameters of BAC, distribution volume of ethanol (Vd), and gastric emptying rate (GER) under the same drinking conditions
When the BAC-time curve was compared among ADH1B genotypes (ADH1B*1/*1, *1/*2, and *2/*2), there were no differences in BAC among the genotypes
Summary
Light to moderate drinking is beneficial to cardiovascular health, heavy drinking often results in health and social problems [1]. Ethanol and its metabolites invoke various physiological and pharmacological effects in human bodies, which develop alcohol-related diseases. Investigation of the mechanisms of alcohol metabolism is important to regulate the levels of ethanol and its metabolites in order to diminish the harmful effects of drinking on the body. Alcohol metabolism is influenced by drinking conditions, such as the type of beverage, amount of alcohol intake, and drinking with or without food. Genetic and physiological differences in individuals affect alcohol metabolism. After alcohol distribution to the body, most of its elimination takes place by metabolic conversion via alcohol dehydrogenase (ADH) in the liver. Acetaldehyde, the product from ethanol oxidation by ADH, is oxidized to acetate by aldehyde dehydrogenase 2 (ALDH2). The genetic polymorphism of ALDH2*1 and *2 is known to regulate individual tolerance to alcohol and susceptibility
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