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 ev...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.展开更多
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 ...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.展开更多
The influence of drinking conditions on alcohol metabolism and drunkenness was investigated in healthy men with ALDH2*1/*1 genotype aged from 40 to 60 who were occasional or habitual drinkers. The investigation was pe...The influence of drinking conditions on alcohol metabolism and drunkenness was investigated in healthy men with ALDH2*1/*1 genotype aged from 40 to 60 who were occasional or habitual drinkers. The investigation was performed by open intersection competitive drinking tests at an ethanol dose of 0.32 g/kg under 4 different drinking conditions: beer without a meal [B(–)], shochu (a distilled spirit) without a meal [S(–)], beer with a meal [B(+)] and shochu with a meal [S(+)]. The blood alcohol concentration (BAC) and BAC-AUC (area under the curve) were lower in the B(–) than in the S(–). The blood acetaldehyde concentration (BAcH) and the serum acetate concentration (SAce) were also lower in the B(–) than in the S(–). The meal markedly decreased BAC, BAC-AUC and BAcH-AUC for both alcoholic beverages. Subjective drunkenness was stronger in order of B(+) + in liver cells, was higher in the S(–) than in the B(–), and was decreased by the meal for both alcoholic beverages. These results suggested that glucide increase the rate of alcohol metabolism by supplying pyruvic acid to decrease the ratio of NADH/NAD+, which lowers BAC and relieves drunkenness. Thus, the intake of glucide calories while drinking is important to reduce the pharmacological and toxicological actions of alcohol.展开更多
文摘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.
文摘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.
文摘The influence of drinking conditions on alcohol metabolism and drunkenness was investigated in healthy men with ALDH2*1/*1 genotype aged from 40 to 60 who were occasional or habitual drinkers. The investigation was performed by open intersection competitive drinking tests at an ethanol dose of 0.32 g/kg under 4 different drinking conditions: beer without a meal [B(–)], shochu (a distilled spirit) without a meal [S(–)], beer with a meal [B(+)] and shochu with a meal [S(+)]. The blood alcohol concentration (BAC) and BAC-AUC (area under the curve) were lower in the B(–) than in the S(–). The blood acetaldehyde concentration (BAcH) and the serum acetate concentration (SAce) were also lower in the B(–) than in the S(–). The meal markedly decreased BAC, BAC-AUC and BAcH-AUC for both alcoholic beverages. Subjective drunkenness was stronger in order of B(+) + in liver cells, was higher in the S(–) than in the B(–), and was decreased by the meal for both alcoholic beverages. These results suggested that glucide increase the rate of alcohol metabolism by supplying pyruvic acid to decrease the ratio of NADH/NAD+, which lowers BAC and relieves drunkenness. Thus, the intake of glucide calories while drinking is important to reduce the pharmacological and toxicological actions of alcohol.
