Abstract
Few studies have assessed the difference in adaptive changes of alcohol metabolism in the case of chronic alcohol consumption pertaining to the genetic polymorphism of aldehyde dehydrogenase 2 (ALDH2) in humans. To evaluate the influences of ALDH2 genotypes on changes in alcohol metabolism due to continuous alcohol intake, we conducted an intervention study by setting a continuous drinking period between two abstinence periods. The subjects in this study comprised 20 - 25-year-old males, including 15 males carrying ALDH2*1/*1 and 16 carrying ALDH2*1/*2 genotypes. Following the abstinence period of 4 weeks (from day 1 to day 28), all subjects drank commercially available beer (500 ml) every evening for 6 weeks (from day 30 to day 71) and subsequently abstained from drinking again for 4 weeks (from day 73 to day 100). The next morning, after the end of each period, drinking tests (DTs) were performed on each subject (DT1 on day 29, DT2 on day 72, and DT3 on day 101) to examine alcohol metabolism. The subjects drank shochu (a distilled alcoholic beverage), with an ethanol dose of 0.32 g/kg, within 20 minutes after overnight fasting. The alcohol elimination rate in subjects with ALDH2*1/*1 genotype was significantly higher during DT2 after the drinking period as compared with those at both DT1 and DT3 after the abstinence periods, whereas the elimination rate in subjects with ALDH2*1/*2 genotype did not change significantly during 3 DTs. However, blood acetaldehyde levels significantly decreased in subjects with both ALDH2 genotypes during DT2 as compared with those during DT1. The physiological subjective responses to alcohol also significantly decreased during DT2 in subjects with ALDH2*1/*2 genotype. Moreover, serum lipids, gamma-glutamyltransferase (GGT), and uric acid concentrations also varied between subjects with different ALDH2 genotypes due to continuous drinking. These results suggested that ALDH2 polymorphism modified adaptive changes in alcohol metabolism and physiological responses to continuous moderate alcohol consumption.
Highlights
Previous studies have reported a U-shaped relationship between alcohol consumption and mortality [1]-[5] that indicates health benefits of moderate alcohol consumption as compared with its complete abstinence or heavy alcohol use
These results suggested that aldehyde dehydrogenase 2 (ALDH2) polymorphism modified adaptive changes in alcohol metabolism and physiological responses to continuous moderate alcohol consumption
The influences of ALDH2 polymorphism on adaptations of ethanol and acetaldehyde metabolism to chronic moderate alcohol consumption remain poorly understood in normal subjects
Summary
Previous studies have reported a U-shaped relationship between alcohol consumption and mortality [1]-[5] that indicates health benefits of moderate alcohol consumption as compared with its complete abstinence or heavy alcohol use. Numerous animal studies have demonstrated an increase in alcohol metabolism following chronic alcohol intake [6]-[12]. Misra et al [13] reported that chronic consumption of ethanol for one month under specific dietary conditions results in acceleration in the clearance of ethanol from blood in both alcoholics and nonalcoholics. In alcoholics, an elevation of blood acetaldehyde levels was often observed [14], because of the acceleration of alcohol metabolism or the decrease of low-Km aldehyde dehydrogenase (ALDH2) activity in the liver following excessive alcohol intake [15] [16]. There has been only limited information about the influences of continuous moderate consumption of alcohol on adaptive changes in ethanol and acetaldehyde metabolisms in subjects with different ALDH2 genotypes
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