The acute effects of ethanol and acetaldehyde on physiological responses after ethanol ingestion in young healthy men with different ALDH2 genotypes

Abstract

Background. This study investigated the acute effects of ethanol and acetaldehyde on physiological responses in healthy men according to ALDH2 genotype by measuring them directly in human blood. Methods. Twenty-four men, 12 with the ALDH2*1/*1 genotype and 12 with the ALDH2*1/*2 genotype, were selected. In a double-blind placebo-controlled crossover design, each subject was administered one of three doses of ethanol (0.25, 0.5 or 0.75 g/kg) or a placebo on four separate occasions. The blood ethanol concentration (BEC), blood acetaldehyde concentration (BAAC) and physiological responses including facial redness, pulse rate and systolic and diastolic blood pressures were assessed. Results. Significant differences were observed in the physiological responses between the ALDH2*1/*2 and ALDH2*1/*1 groups. Significant gene effects were observed for pulse rate and facial flushing (F-values = 62.344; p values < 0.001 and F-values = 7.062; p values = 0.010, respectively, by repeated-measures analysis of variance), which were significantly greater in subjects with the ALDH2*1/*2 genotype. In a linear regression analysis, BAAC significantly predicted increased facial redness at 30 minutes (adjusted R: 0.209; p values < 0.001) and pulse rate at 30, 60, 90 and 120 minutes (adjusted R: 0.454, 0.490, 0.428 and 0.193, respectively; all p values < 0.001), whereas BEC was not associated with any physiological response measure at any time. Conclusions. Facial redness and pulse rate after ethanol ingestion were significantly higher in the ALDH2*1/*2 genotype, and were significantly associated with blood acetaldehyde concentrations. The acute effects of ethanol on the physiological responses were mediated mainly by acetaldehyde, the active metabolite of ethanol, rather than by ethanol itself.