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<   No. 4435   2021-01-22   >

Comic #4435

1 Jamie: I’ve crunched some numbers on hangover cures.
1 Adam: Cool!!
2 Jamie: This blue curve is how you felt over time. Red is the cumulative metabolism rate of acetaldehyde, the primary toxic metabolite of ethanol.
3 Jamie: This implies that despite all the “hangover cures”, the only thing that made you feel better was the passage of time.
4 Adam: But correlation does not imply causation! “Time cures a hangover”... Busted!

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The human body deals with alcohol—more specifically ethanol, the type of alcohol found in alcoholic drinks—by breaking it down chemically. The set of chemical reactions occurring in a living body is termed metabolism.

The first step in breaking down, or metabolising, ethanol is the action of an enzyme produced by the liver and also found in the stomach lining, known as alcohol dehydrogenase. This acts as a catalyst to oxidise the ethanol, turning it into acetaldehyde. The enzyme aldehyde dehydrogenase then catalyses acetaldehyde to react with water to produce acetic acid. A further two enzymes known as acyl-coenzyme A synthetase short-chain family member 2 and acetyl-CoA synthase 2 then break down the acetic acid into a substance known as acetyl-CoA.

Acetyl-CoA is also a chemical that occurs in the metabolism of citric acid (found in citrus fruits), and the citric acid metabolism pathways take over the rest of the job.

Acetaldehyde, it turns out, is toxic. The effects it causes on the human body are... those associated with a hangover. It's actually the acetaldehyde produced by metabolising alcohol that causes the hangover, not the alcohol itself. Fortunately, the body naturally gets rid of the acetaldehyde it produces with the subsequent steps of the metabolism chain. But if you've drunk too much, then the hangover is going to hang around until the acetaldehyde can all be broken down.

And that is pretty much the only way to really get rid of a hangover. Wait for your body to do its job.

Interestingly, there's a very good reason for why the human body evolved the ability to metabolise alcohol. Alcohol is produced by fermentation of sugars by anaerobic microorganisms such as yeast, producing ethanol. If you leave any sort of organic material somewhere moist and warm, it'll almost certainly start fermenting and producing alcohol. Where's there a constant supply of organic material in a nice warm, moist environment?

Your digestive tract!

Yes, as you sit reading this, microbes in your stomach and intestines are merrily converting some of the food you ate into alcohol, which your body is then absorbing. Gut fermentation produces about 3 grams of ethanol per day in an average human being. This is equal to only 0.3 standard drinks[1], spread out over a full day, so it's not enough to make you feel any noticeable effects. Similar things happen in the digestive tracts of most animals. But animal bodies need to do something with that alcohol, so they long ago evolved the ability to metabolise it and get rid of it.

In some people, the gut microflora can be seriously imbalanced, leading to excessive alcohol production, to the point where they can end up with symptoms of drunkenness without having ingested any alcohol whatsoever. This condition is known as auto-brewery syndrome, and is quite thankfully extremely rare.

[1] As defined by the World Health Organisation and by most countries where a standard drink is 10 g of alcohol, although it's 0.375 standard UK drinks (8 g of alcohol), and only 0.21 standard US drinks (14 g of alcohol). It's interesting that a "standard drink" in the US contains nearly one and a half times as much alcohol as most of the rest of the world, and almost twice as much as the UK.

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