Whatever your job and background, drunken conversations between work colleagues have much in common. However, a phrase that I often heard in Japan but have heard nowhere else is, “I have an inactive form of aldehyde dehydrogenase.”

Drunken biologists we might have been, but even through the fog of Suntory whisky on a Saturday night, we still knew something about the genetics of drinking.

Aldehyde dehydrogenase (ALDH) is the enzyme that in large part determines how much you can drink and how bad you’re going to feel the next morning. In the liver, ethanol from your cocktail or beer or whisky is converted into acetaldehyde, a nasty compound more toxic than alcohol. ALDH then swiftly converts acetaldehyde to harmless acetic acid (vinegar).

However, if you don’t have a good working form of ALDH, then very quickly you will feel (and others will see) the consequences: facial flushing, nausea and drowsiness. Before long you’re sprawled unconscious in the middle of JR Shinjuku Station. There can even be cardiovascular complications and alcohol-induced asthma.

Forty to 45 percent of Japanese people have an inactive form of ALDH called ALDH2, which means they suffer those unpleasant consequences if they drink alcohol.

But here’s the funny thing: Despite that high proportion of the population with inactive ALDH, many Japanese are heavy drinkers — and heavy drinking is increasing in Japan.

These people are unlikely to become alcoholics, but are at risk of liver damage and asthma. Cancers of the mouth and throat due to acetaldehyde are also more common. What’s more, if you have toxic acetaldehyde in your system the next morning because your body hasn’t been able to break it all down, then obviously you’re going to feel rough.

Hangovers, therefore, are as much down to your genes as they are to your boozing habits. That’s the conclusion of a report published in the July issue of the journal Alcoholism: Clinical & Experimental Research.

“Many Japanese love the idea of group harmony,” said Masako Yokoyama of the Mitsukoshi Health and Welfare Foundation, an author of 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.”

In practice, “fairly drunk” seems to mean anything from blowing gales of alcohol-laden fumes over fellow commuters on the last train home, to groping the bottoms of office ladies.

Yokoyama, and co-author Hiromasa Ishii, president of the Japanese Medical Society of Alcohol Studies and Drug Dependence, and emeritus professor at Keio University in Tokyo, believe that despite the initial inhibitory effects that the inactive form of ALDH can have on alcohol consumption, tolerance to the negative effects of alcohol and acetaldehyde may nevertheless develop if heavy drinking continues.

And for the sake of group harmony, heavy drinking among business colleagues will certainly continue.

“Understanding of 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 [the inability to process acetaldehyde].”

For the study, Yokoyama and Ishii contacted an earlier cancer-study pool of 326 Japanese workers; 77 percent, or 251 participants (139 males, 112 females), agreed to participate a second time. In the earlier study, each participant answered a questionnaire about their flushing responses to alcohol; for the new study, they also completed a questionnaire about their drinking as well as their hangovers (a nice touch would have been to ask about hangover cures, but that wasn’t one of the questions).

In addition, participants provided DNA samples, and a measure of their red-blood cell volume, called the mean corpuscular volume (MCV), was also taken. MCV has recently been identified as a marker of acetaldehyde exposure in people with inactive ALDH2.

As might be expected, the results showed that individuals with inactive ALDH2 have a greater tendency to flush after consuming alcohol, increased MCV, and a greater susceptibility to hangovers.

“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. They can only look with genetic envy, perhaps, at their heavy-drinking colleagues who are first into the office the next morning, and whose work doesn’t seem to suffer as a result of a hangover.

The drug disulfiram (trade name: Antabuse) is sometimes used to treat alcoholics, as it effectively makes them the same as people with inactive ALDH2, by preventing the oxidation of acetaldehyde to acetic acid. As a result, if you drink you end up with an absolute stinker of a hangover. Now what we really need is a pill that accelerates the conversion of acetaldehyde. But that might be asking for trouble.

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