Hangover Culprit Found

Acetaldehyde, rather than ethanol, may be the culprit behind hangovers, according to new research from Japan.

Alcohol consumption is an integral part of many cultures, not least the Japanese business culture, according to Masako Yokoyama of the Mitsukoshi Health and Welfare Foundation and colleagues. The problem many East Asians have in drinking alcohol is that their livers have a mutant form of the enzyme aldehyde dehydrogenase-2 (ALDH2), which in other people eliminates the acetaldehyde formed by ethanol metabolism, but often fails to do its job properly in East Asians, which means they suffer worse hangovers as this toxic compound stays in their system at higher concentrations than it would otherwise do so. Hangovers can have substantial economic drawbacks, leading sufferers to skip work, for instance.

“Many Japanese love the idea of group harmony,” explains Yokoyama, “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.” Hiromasa Ishii, president of the Japanese Medical Society of Alcohol Studies and Drug Dependence and Professor Emeritus at Keio University in Tokyo, concurs. “Drinking alcoholic beverages with working colleagues after a customary ten-hour day at the office is an important part of business society in Japan, despite the fact that 40 to 45% of the Japanese people possess inactive ALDH2,” he said.

Cardiovascular complications, drowsiness, nausea, asthma, and facial flushing are commonly seen in East Asians with the mutant allele ALDH2*2 which leads to inactive ALDH2. Many people with this allele avoid heavy drinking because of the unpleasant consequences, but the Japanese business drinking culture is seeing an increasing number of Japanese with inactive ALDH2 drinking more than is good for them.

Both Yokoyama and Ishii believe that, despite the initial inhibitory effects that a genetic mutation of ALDH2 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,” explains Yokoyama, “however, we know that 26% of heavy drinkers among urban working men and 12% 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.”

The researchers found in their study that 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. Further analysis 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.

Both Yokoyama and Ishii noted that this study’s findings highlight the importance that hyper-acetaldehydemia appears to play in the development of hangovers, and 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.

Research Blogging IconYokoyama, M., Yokoyama, A., Yokoyama, T., Funazu, K., Hamana, G., Kondo, S., Yamashita, T., & Nakamura, H. (2005). Hangover Susceptibility in Relation to Aldehyde Dehydrogenase-2 Genotype, Alcohol Flushing, and Mean Corpuscular Volume in Japanese Workers Alcoholism: Clinical & Experimental Research, 29 (7), 1165-1171 DOI: 10.1097/01.ALC.0000172457.62535.EE