Well, obviously, you might think, and so did I. But it turns out that some people claim that the alcohol (ethanol) in drinks isn't the only thing responsible for their effects - they say that acetaldehyde may be important, perhaps even more so.South Korean researchers Kim et al report that it's acetaldehyde, rather than ethanol, which explains alcohol's immediate effects on cognitive and motor skills. During the metabolism of ethanol in the body, it's first converted into acetaldehyde, which then gets converted into acetate and excreted. Acetaldehyde build-up is popularly renowned as a cause of hangovers (although it's unclear how true this is), but could it also be involved in the acute effects?
Kim et al gave 24 male volunteers a range of doses of ethanol (in the form of vodka and orange juice). Half of them carried a genetic variant (ALDH2*2) which impairs the breakdown of acetaldehyde in the body. About 50% of people of East Asian origin, e.g. Koreans, carry this variant, which is rare in other parts of the world.
As expected, compared to the others, the ALDH2*2 carriers had much higher blood acetaldehyde levels after drinking alcohol, while there was little or no difference in their blood ethanol levels.Interestingly, though, the ALDH2*2 group also showed much more impairment of cognitive and motor skills, such as reaction time or a simulated driving task. On most measures, the non-carriers showed very little effect of alcohol, while the carriers were strongly affected, especially at high doses. Blood acetaldehyde was more strongly correlated with poor performance than blood alcohol was.
So the authors concluded that:
Acetaldehyde might be more important than alcohol in determining the effects on human psychomotor function and skills.So is acetaldehyde to blame when you spend half an hour trying and failing to unlock your front door after a hard nights drinking? Should we be breathalyzing drivers for it? Maybe: this is an interesting finding, and there's quite a lot of animal evidence that acetaldehyde has acute sedative, hypnotic and amnesic effects, amongst others.
Still, there's another explanation for these results: maybe the ALDH2*2 carriers just weren't paying much attention to the tasks, because they felt ill, as ALDH2*2 carriers generally do after drinking, as a result of acetaldehyde build-up. No-one's going to be operating at peak performance if they're suffering the notorious flush reaction or "Asian glow", which includes skin flushing, nausea, headache, and increased pulse...
Kim SW, Bae KY, Shin HY, Kim JM, Shin IS, Youn T, Kim J, Kim JK, & Yoon JS (2009). The Role of Acetaldehyde in Human Psychomotor Function: A Double-Blind Placebo-Controlled Crossover Study. Biological psychiatry PMID: 19914598
7 comments:
I didn't check the paper but did they also control for, shall we say, the "experience effect." ALDH2*2 carriers are also likely to drink less on average than their counterparts. Regardless of the molecules causing the intoxicating effects exposure will change tolerance levels I am sure as well as learning to cope and counteract the intoxication in order to perform tasks better while drunk.
Interesting study, but not surprising, as it confirms what I learned in when I took a psychopharmacology class in college 10 years ago. I think a lot of the undesirable effects of a night of drinking have long been attributed in large part to acetaldehyde, paralleling the discovery that methanol poisoning is due not to the methanol, but to its metabolism into formaldehyde. Fun fact: if poisoned with methanol, you should get drunk really quick, as ethanol can outcompete methanol for alcohol dehydrogenase and prevent the buildup of toxic levels formaldehyde in the blood.
Digressions aside, I think this study deserves attention because it highlights the importance of pharmacokinetics, which I consistently see given short shrift in both course curricula and scientific research.
DG: Not per se, which they admitted was a weakness, but they did give people an alcoholism screening questionnaire, and the *2 carriers were a bit lower, as you might expect, though only slightly. Still, you can be a regular drinker without being an alcoholic and some of the non-carriers probably were.
There is much evidence for "Acetaldehydism" instead of "ethylism" but other evidence still supports a mutual cause (ethanol + acetaldehyde). In testing the effect on people one should take care as dose effects are important and very different in younger versus older people. Where in older people the sedation effects tend to become more important (at higher dose) in youngsters the excitation effects continue even in higher dose levels.
Then again we all know those patients who on disulfiram have managed to take small dosoes of it together with low dose alcohol to experience that ebriety effect at much lower "cost" (depend on how one defines "cost". :-). it is rare but exists. So maybe the acetaldehyde story could be a lead to consider for therapeutic implications ?
I haven't looked into yet, but I wonder if there are any binding studies for Acetaldehyde as there are for ethanol. Alcohol is popularly reported to bind the GABAa receptors, but in reality, ethanol, which is a simple molecule, affects the neuron from inside, outside, and even between the phospholipid bilayer. It will be interesting to learn how acetaldehyde affects the brain in that respect.
Hey all, great blog!
I have Asian flush, but also sometimes confuse it with an allergy.
There are many sources that claim that mere facial flushing is not an alcohol allergy. There are also many sources that state that most doctors are incorrect in saying that Asian flush is not an alcohol allergy and that if you speak to a geneticist they will tell you that Asian flush is in actual fact an allergic reaction, albeit, a result of an enzyme deficiency.
Despite all that i did find a short term solution - i will link it if you dont mind: this provides a solution for the asian flush and the allergy.
Again, thankyou for the blog guys - i love it.
Great stuff from you, man. I have read your stuff before and youre just too awesome. I love what youve got here, love what youre saying and the way you say it. You make it entertaining and you still manage to keep it smart. I cant wait to read more from you. This is really a great blog.
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