asian glow

References: https://en.wikipedia.org/wiki/Alcohol_flush_reaction

There seem to be three genes associated with poor alcohol tolerance, primarily in East Asians, although they apparently also occur in a few other subgroups such as Ashkenazi Jews.

Recall that ethanol is broken down in two stages: first into acetaldehyde, which is toxic, and then into acetic acid (vinegar), which is mostly harmless. The toxic acetaldehyde intermediary is the cause of many of alcohol's negative effects, including hangover symptoms and increased cancer risk. Ideally, we would like the alcohol we metabolize to spend as little time in this stage as possible.

The breakdown of ethanol into acetaldyhyde is catalyzed by alcohol dehydrogenase (ADH) enzymes, while the next step breaking down acetaldehyde into vinegar is catalyzed by aldehyde dehydrogenase enzymes (ALDH). To minimize acetaldehyde buildup we'd prefer that the first step (producing acetaldehyde) happen much slower than the second step (breaking it down). Unfortunately, the Asian flush genes have the opposite effect.

First, the gene encoding the enzyme aldehyde dehydrogenase (ALDH), which breaks down acetaldehyde, has a variant ALDH2*2; the variant enzyme is less effective. Apparently something like 30-50% of East Asians have at least one copy of this variant (heterozygotes), and 1-8% have two copies (homozygotes). People with only one copy of the variant can usually still drink alcohol but experience flushing (and increased cancer risk); people with two copies have no effective way to clear acetaldehyde and so they tend to find drinking alcohol very unpleasant.

Having really slow acetaldehyde breakdown might be okay if the production of acetaldehyde by alcohol metabolism were equally slow. But another two common genetic variants, ADH1B*2 and ADH1C*2, encode unusually effective versions of the alcohol dehydrogenase enzymes ADH1B and ADH1C respectively. You might think a more effective metabolism would be good, but in this case it means that ethanol is broken down quickly into acetaldehyde, so there's no time to experience any of its fun psychoactive effects before it is replaced by its toxic metabolite. Something like 80-90% of East Asians have at least one copy of one of these variants. People in this category who also have the ALDH2*2 variant are in the worst of all possible worlds: they produce acetaldehyde extra-quickly and break it down extra-slowly.

Because some remedies sold as hangover cures purportedly act by breaking down acetaldehyde, it's plausible that they might also help people with these gene variants have a better experience when they consume alcohol. Two candidates are:

• dihydromyricetin (DHM) (TODO research this more)
• Zbiotics, which engineers microbes to produce their own copies of aldehyde dehydrogenase. Taken orally, these can plausibly be effective at breaking down acetaldehyde in the gut, but not in the liver, so Zbiotics as a hangover cure would still rely on a functional ALDH enzyme acting in the liver. Thus it seems like it probably wouldn't help people without such an enzyme, and wouldn't be an effective treatment for Asian glow?

Another obvious remedy is to avoid drinking alcohol, replacing that consumption if desired with alcohol substitute drugs that don't go through the same toxic metabolic pathways. This is probably a good idea even for people with 'normal' alcohol processing enzymes.