"Many Japanese love the idea of group harmony," said Masako Yokoyama of the Mitsukoshi Health and Welfare Foundation and corresponding author for the study. "Going out drinking with various colleagues after work is an essential element of Japanese business society. It is socially acceptable to get fairly drunk on such occasions."
Aldehyde dehydrogenase (ALDH) is a key enzyme in the elimination of alcohol-induced acetaldehyde, which is a toxic compound. If the ALDH enzyme is normal, then acetaldehyde is metabolized very quickly. If it is not, people can experience cardiovascular complications, drowsiness, nausea, asthma and facial flushing. Many East Asians who have a mutant allele called ALDH2*2 also have inactive ALDH2, which usually inhibits them from heavy drinking because of the unpleasant consequences. However, an increasing number of Japanese who have inactive ALDH2 are also heavy drinkers.
Both Yokoyama and Ishii believe that, despite the initial inhibitory effects that a genetic mutation of ALDH can have on alcohol consumption, tolerance to the negative effects of alcohol and acetaldehyde may nonetheless develop if heavy drinking continues.
"Understanding the inhibitory effects of ALDH2 on drinking is incomplete," said Yokoyama, "however, we know that 26 percent of heavy drinkers among urban working men and 12 percent of alcoholics in Japan have inactive heterozygous ALDH2. It would appear that alcohol flushing diminishes in intensity in individuals with long or frequent drinking histories, suggesting the development of tolerance to acetaldehydemia."
Greater Susceptibility to HangoversFor this study, researchers contacted an earlier cancer-study pool of 326 Japanese workers; 77 percent or 251 participants (139 males, 112 females) agreed to participate once again. In the earlier study, each participant answered a questionnaire about their flushing responses to alcohol; for this study, participants also completed a structured questionnaire about their drinking as well as hangovers. In addition, participants provided DNA samples, as well as mean corpuscular volume (MCV) samples, recently identified as a marker of acetaldehyde exposure in persons with inactive ALDH2.
Results indicate that individuals with inactive heterozygous ALDH2, a tendency to alcohol flushing, and increased MCV, also had a greater susceptibility to hangovers.
Hangover and Alcohol Flushing"The amount of drinking reported that led to a hangover was significantly less for both men and women who were heterozygous for the inactive ALDH2 compared to those with active ALDH2," said Yokoyama. "Further analyses of male participants indicated that those who had experienced more than three hangovers during the past year were more likely to report alcohol flushing and have elevated MCV, both of which are indicators of high acetaldehyde exposure due to drinking in persons with inactive ALDH2."
In other words, individuals with inactive ALDH2 do not appear to have the capability to eliminate acetaldehyde from their systems, which is why they are more susceptible to hangovers.
Damage of Living Human CellsBoth Yokoyama and Ishii noted that this study's findings highlight the importance that hyper-acetaldehydemia appears to play in the development of hangovers, help to reconfirm the more general role that alcohol-induced acetaldehyde plays in the damage of living human cells, and also point out the need for future research to focus on the damage caused by acetaldehyde rather than its precursor, alcohol.
Results of the study were published in the July 2005 issue of Alcoholism: Clinical & Experimental Research.