Alcohol, health, and the ruthless logic of the Asian flush

by dynomight7 min read4th Jun 202143 comments

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Say you're an evil scientist. One day at work you discover a protein that crosses the blood-brain barrier and causes crippling migraine headaches if someone's attention drifts while driving. Despite being evil, you're a loving parent with a kid learning to drive. Like everyone else, your kid is completely addicted to their phone, and keep refreshing their feeds while driving. Your suggestions that the latest squirrel memes be enjoyed later at home are repeatedly rejected.

Then you realize: You could just sneak into your kid's room at night, anesthetize them, and bring them to your lair! One of your goons could then extract their bone marrow and use CRISPR to recode the stem-cells for an enzyme to make the migraine protein. Sure, the headache itself might distract them, but they'll probably just stop using their phone while driving. Wouldn't you be at least tempted?

This is an analogy for something about alcoholism, East Asians, Odysseus, evolution, tension between different kinds of freedoms, and an idea I thought was good but apparently isn't.

It's not good to drink too much

This is a surprise to no one, but let's look at some numbers. Here's data from a meta review on the relative risk of various health conditions as a function of the number of US standard drinks (14g of alcohol) someone has in a day:

alcohol health

The three small dots show that having 10 drinks a day associated with a 9x risk of getting lip/oral cancer, a 3x risk of epilepsy, and a 1.5x risk of diabetes, as compared with not drinking at all. These are all associations, controlling only for age, sex, and drinking history. This makes the little dip around 1-2 drinks for heart disease and diabetes controversial. Still, the causal link is pretty clear in many cases, and for our purposes, all that matters is that heavy drinking is not good.

But who averages 10 drinks per day, you ask? The answer is an astonishing number of people. Half of Americans drink almost nothing, but the top 10% average more than 10 drinks per day. They're responsible for around 75% of all alcohol consumption.

Some East Asians struggle with alcohol

Humans metabolize alcohol in various ways. The "normal" way is that an ADH enzyme converts alcohol to acetaldehyde after which an ALDH enzyme breaks the acetaldehyde down into acetate. Eventually the acetate is broken down into water and carbon dioxide. The intermediate product (acetaldehyde) is highly toxic and carcinogenic, while acetate is much less active. It appears that ethanol itself isn't carcinogenic, but acetaldehyde is.

But guess what: Around 80% of East Asians have a variant of ADH (ADH1B or ADH1C) that converts alcohol to acetaldehyde more quickly. Also, around 50% of East Asians have a variant ALDH isoenzyme (ALDH2*2) that is much less effective. Both of these mean that acetaldehyde tends to accumulate, leading to a "flush" reaction.

Kang et al. (2014), recruited a bunch of healthy 20-something male Koreans. Here is the peak acetaldehyde concentration (ng/ml) of people with different genes after consuming 0.25 g/kg of ethanol (around 1.25 standard drinks for someone who weighs 70 kg / 154 lb.)

ALDH \ ADH half variant full variant
standard 167.9 190.1
full variant 736.6 1,613.6

The variant enzymes lead to much higher peak concentrations. Remember, we have two copies of every gene, one from mom and one from dad. The middle column shows people with one copy of the ADH1B variant that produces acetaldehyde faster, while the right column shows people with two copies. This doesn't even include people with zero copies of the ADH1B variant, presumably because they couldn't find enough of them. The top row shows people with the standard ALDH2 enzyme, the bottom row with the East Asian variant. This is dominant so you don't have to worry about half-effects.

It's likely that having these variant enzymes means that if you do drink, alcohol causes more problems. This is hard to study since you can't do randomized tests and people with the mutation drink less, but there's pretty strong evidence of this in humans for esophageal cancer. In mice, removing the ALDH enzyme greatly increases the DNA damage that alcohol causes to the stomach.

Those East Asians drink less

Now, why do East Asians have these genetic variants? I long assumed that this is because other people had a longer tradition of drinking alcohol, and so had evolved to do it painlessly. This is totally incorrect.

Let's back up. When Homo Sapiens left Africa, these variants basically didn't exist. We evolved to be able to consume alcohol, probably because we're fond of not starving to death. (If rotting fruit is the only source of calories, it's better if you can eat it without getting incapacitated.) Rather, the genes for these variant enzymes probably arose in China.

Alcoholic beverage production started early in China. It's hard to say exactly when, since it pre-dates recorded history, but 9000 years old Chinese pottery already has residues of early beers. Alcohol production in Egypt seems to have started around 5000 years ago, and in Europe around 4000 years ago.

So, China is where alcohol first became common. China is also where genes that make alcohol consumption difficult first became common. Why would such "defective" genes arise in the place where alcohol has been around the longest?

The simplest explanation is that these genes are adaptive. It's obvious in retrospect: Humans are prone to alcoholism. Alcoholics tend to get sick, commit suicide, and have accidents, all of which interfere with the business of having and raising kids.

A study in Taiwan found that 48% of the control population had a copy of the (dominant) ALDH2*2 mutation that slows the breakdown of acetaldehyde, but only 12% of alcoholics. Similarly, 93% had at least one copy of the ADH1B gene that speeds acetaldehyde production, compared to 64% of alcoholics. Other studies (Muramatsu et al. 1995, Hurley and Edenberg, 2012, Bierut et al., 2012) confirm the same basic picture, which is that these genes reduce alcoholism.

If these genes really are an adaptation, it shows how ruthless evolution can be. If you implanted a device in your kid that mildly poisoned them every time they drank, you'd be a monster. But evolution basically did that.

Constraints are sometimes a kind of freedom

No one cares about my freedom to rob convenience stores or burn down public buildings. We all understand that different people's freedoms are in conflict, and we've invented things like "manners" and "property" and "noise ordinances" to navigate the tradeoff.

There's a different tradeoff I think about a lot. We all know the story of Odysseus having his men block their ears and tie him to the mast of his ship. He knew he would go temporarily insane when going past the Sirens, so he wanted to remove freedom from himself to overcome that.

odysseus and the sirens

It's a cute story, but it's not typical. Odysseus constrained his future self with technology. Most real-world scenarios are different:

  • We need society to enforce constraints.
  • Those constraints affect everyone to some degree, even those who don't want them.

For example, I almost never buy snack foods because once home, I can't resist the urge to eat them. This works OK for me, but they're sometimes available at conferences or parties or whatever, and I have a hard time saying no. What I'd really like is for society to criminalize all mint-chocolate flavored snacks.

(We'll will get back to alcohol in a second.)

Cookies are laughable, but how about fentanyl? Some of the reason drugs are illegal is because of externalities or the idea that people don't know what's good for them. However, there's no doubt that some former or potential addicts would choose criminalization if it was up to them. Say you used to be addicted but now you've quit. If you could snap your fingers and make all drugs disappear, wouldn't you do that?

Obviously, criminalizing cookies (or fentanyl) is bad for both responsible users and people who can't or don't want to quit. I'm just trying to point out that there is a tradeoff. Society has decided that tradeoff in favor of responsible Twinkie users and against responsible fentanyl users.

Just as society made a different tradeoff for Twinkies and drugs, biology made a different one for alcohol, depending on if you got the East Asian variants or not.

Sometimes we can give people the chance to "Odysseus" themselves without intruding too much on the freedom of others. An example is gambling. Some locations allow people to "self-exclude" from gambling, after which casinos won't let you play for a time period of your choice. This isn't perfect, since now responsible gamblers have their ID checked, and addicts can still cross state lines or play the lotto or whatever.

We can informally picture the different regimes like so:

freedoms and freedoms from temptation

A self-ban for alcohol

Roughly 10% of people in the US are raging alcoholics. Could we offer them the chance to self-exclude from alcohol?

Unfortunately, it seems very difficult. We'd have to force some heavyweight process of checking IDs on all bars and liquor stores. Even then, it wouldn't be very effective, since people could still have their friends buy it for them. Do we want to make it illegal to hand out drinks at a party without checking everyone's ID against a database? It would be a nightmare.

A while ago, I had a strange idea. In principle, instead of having people ban themselves from alcohol legally, couldn't it be done biologically? After all, this is the solution evolution came up with. Can we allow people to opt-in to getting the Asian flush?

freedoms from temptation with an invention

Obviously, this is just hypothetical. For one thing, is it even possible? It seems hard, but perhaps with the full might of our modern nano RNAi cell-therapy quantum stem-cell CAR-T gene therapy arsenal, we could figure something out. It doesn't matter though. We could never actually give such a drug to people, since it's equivalent to poisoning them.

Just kidding. It's called disulfiram, and it was approved by the FDA in 1951.

Does disulfiram work?

Still today, we don't really know.

To be sure, disulfiram does what's asked of it. It definitely blocks the ALDH enzyme and this definitely does lead to 5-10x higher acetaldehyde concentrations. This definitely causes "flushing" and other symptoms typical of those with a genetic predisposition against drinking. Early on, it was prescribed in such massive doses that patients who drank anyway sometimes went into cardiac arrest, or even died.

What's unknown is if it helps with alcohol addiction. There have been a huge number of studies, but none of them give clear answers. As far as I can tell, there are three problems.

First, just imagine you give alcoholics a bottle of pills, explain that they make alcohol (more) toxic, and send them on their way. Obviously, almost nobody takes them, and those that do are ultra-determined and would probably have quit anyway. You can ask patients to come into the office to take the drugs, but then people drop out. It's just incredibly hard.

Second, there's all sorts of confounders and weirdness. Some show effects on number of days without alcohol but not on number of drinks or vice-versa. Some studies show great results for people who are married but not for single people.

Third, most of the studies are kind of.. crap? Hughes and Cook reviewed the studies up to 1997. Their paper is a marvel of inventive euphemisms like "Nothing can be said directly", and "not strictly a controlled study", and "a very poor study, but the authors subsequently stated that they 'made no claims for methodological sophistication or statistical significance'."

The drug is still available today, though not much used for alcoholism except in Denmark, where it's widely prescribed. (This seems to be pharma-nationalism, resulting from the drug being invented there.)

If people refuse to take the pills, couldn't we just make some kind of implant? This too has been experimented with since 1968, and again we have no clear answers. One major problem is that it's not clear how well the drug is absorbed from the implant. Another is that randomized trials require "sham implants" to blind participants. A third is that various trials used ridiculously low doses of the drug, far below the level that's physiologically plausible.

Update: People have pointed out that disulfiram implants are apparently fairly popular in Eastern Europe (1, 2, 3). However, these implants typically contain does around 1-2g and are dispensed over something like 6-24 months. If you assume 1g dispensed over a year, that would be 2.7 mg / day, only around 1% of a typical oral dose of 250 mg per day. On top of that, there's evidence that bioavailability of implanted disulfiram is lower than oral. So I suspect these implants are almost entirely placebo.

So, it's hardly been revolutionary. What explains this?

One possibility is that the drug could cure alcoholism, we just haven't done enough studies, or found a sufficiently reliable way to deliver it yet.

Another possibility is that the alcohol intolerance in East Asians is just a "nudge", which is often enough to prevent alcoholism from forming in the first place, but not strong enough to displace alcoholism once it's taken root.

I favor the second possibility. Disulfiram definitely does make acetaldehyde build up when you drink. If that had a massive effect on alcoholism, it shouldn't be that hard to see it! Yet we still don't see much after 70 years. These days, the first-line drug treatments for alcoholism are acamprosate which reduces the physical symptoms of alcohol withdrawal and naltrexone which screws around with the opiod receptors and probably reduces the pleasure people get from drinking.

What are we supposed to conclude from all this? That we should be careful about cute evolutionary explanations? That human fallibility means your individual freedom is in tension with my freedom from temptation? That "Odysseusing" is a way to resolve that tension? That our addictions run deep into us, and aren't easy to remove? That there's nothing new under the sun? That human behavior is complex, and harder to manipulate than mere biology? Take your pick. Honestly, I just thought it was a good story.

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I have some patients on disulfiram and it works very well when they take it. The problem is definitely that they can choose not to take it if they want alcohol (or sometimes just forget for normal reasons, then opportunistically drink after they realize they've forgotten). 

The implants are a great idea. As far as I know, the reason they're not used is because someone would have to pay for lots and lots of studies and the economics don't work out. Also because there are vague concerns about safety (if something went catastrophically wrong and the entire implant got released at once and then the patient drank, it would be potentially fatal) and ethics (should a realistically-probably-heavily-pressured patient be allowed to make decisions that bind their future selves)? I think this is dumb and we should just do the implant, but I don't think it's mysterious why we don't, or why (in the absence of the implant) disulfiram doesn't solve everything.

Wait, you don't know? Disulfiram implants are widely used in Eastern Europe.

Just kidding. It’s called disulfiram, and it was approved by the FDA in 1951.

Cute turnaround + mention of FDA = instant feeling of reading Scott.

Maybe Scott has a secret identity.

Throw in some Roman numerals and this entire post would fit right in on acx.

I also thought I was reading SSC / the new thing. 

I had the "Europeans evolved to metabolize alcohol" belief that this post aims to destroy. Thanks!

This post gave me the impression that the evolutionary explanation it gives is novel, but I don't think that's the case; here's a paper (https://bmcecolevol.biomedcentral.com/articles/10.1186/1471-2148-10-15#Sec6) that mentions the same hypothesis.

Any other, alternative hypotheses to explain why Europeans and European-descended peoples drink far more than most others (this holds true for country to country comparisons though some places like Nigeria with little European descent are high, and less so but somewhat true within places like the US where whites seem to drink a bit more than racial minorities)?

I'm struck that "Europeans drink more than most of the world" is a bigger thing than "East Asians drink less than most of the world" by a long shot. That still seems to ask for an explanation, even if not genetic (e.g. cultural, historical etc.).

From Wikipedia: "Disulfiram does not reduce alcohol cravings, so a major problem associated with this drug is extremely poor compliance. Methods to improve compliance include subdermal implants, which release the drug continuously over a period of up to 12 weeks, and supervised administration practices, for example, having the drug regularly administered by one's spouse."

My guess is that for a strategy like this to work better, you'd need the pain to come right away, strong enough to build an immediate association between alcohol and suffering. Instead, "about 5 to 10 minutes after alcohol intake, the patient may experience the effects of a severe hangover for a period of 30 minutes up to several hours." By contrast, here's how one Reddit user describes alcohol cravings:

It isn't so much a thirst like for water after a long run, it is more like a thirst for the body buzz and mental clarity that comes with drinking. You cannot enjoy any activity until you have that drink in you, and once you do, ON THE FIRST SIP, your body finally releases you from the tenseness and uncertainty you've been feeling all day. It is an indescribable release.

Note that the effect is immediate and intensely pleasurable. Yet alcohol only reaches the brain 5 minutes after consumption, and only takes effect 10 minutes after consumption. So there's something psychological, not just chemical, going on here. I'm skeptical that a delayed-onset pain that's potentially not even shifting the same motivational mechanism that caused the cravings would be effective.

The fact that people self-harm, despite the fact that the pain must be immediate and intense, should be at least some evidence against the idea that strategies like this would work. My money is on the idea that disulfiram's apparent effectiveness when taken is mainly a third variable problem. People who take it are likely to be highly organized or highly motivated to quit.

Roughly 10% of people in the US are raging alcoholics. Could we offer them the chance to self-exclude from alcohol? Unfortunately, it seems very difficult. We'd have to force some heavyweight process of checking IDs on all bars and liquor stores. Even then, it wouldn't be very effective, since people could still have their friends buy it for them. Do we want to make it illegal to hand out drinks at a party without checking everyone's ID against a database? It would be a nightmare.

I presume you're being ironic here, but part of me worries that you forgot that this already describes the way we handle underage drinking.

I wasn't (intentionally?) being ironic. I guess that for underage drinking we have the advantage that you can sort of guess how old someone looks, but still... good point.

The main advantage for underage drinking is that a bartender only has to check the birth date on the ID, whereas for self-exclusion, they would have to check the id against a database or there would have to be some kind of icon on the id.

In principle, I guess you could also think about low-tech solutions. For example, people who want to opt out of alcohol might have some slowly dissolving tattoo / dye placed somewhere on their hand or something. This would eliminate the need for any extra ID checks, but has the big disadvantage it would be visible most of the time.

Combine it with getting entrance to a place. It doesn't have last too long, just long enough.

Looking at alcohol consumption by country, however, East Asia seems pretty middle of the pack. The main trends seem to be Europe and majority European-settled countries are rather high, and the Middle East and North Africa are very low (religious prohibition). 

https://ourworldindata.org/alcohol-consumption

Since the west is high, the rest is low, or not so-high, with parts of East Asia overlapping parts of the west, it seems like these genetic predispositions aren't as strong in effect as someone might predict given the culture. I have heard Japanese and Korean drinking culture rivals European ones.

Within the US, whites and racial minorities (e.g. African Americans, Asian Americans, Native Americans etc.) do somewhat differ in drinking rates, alcohol problems, but the differences aren't nearly as drastic as super strong "innate" differences would predict (e.g. https://pubs.niaaa.nih.gov/publications/arh40/152-160.htm

It also seems like a religious prohibition making entire regions in the Islamic world far lower in alcohol consumption which is (almost?) entirely cultural has a strong effect with no need to resort to genes, unless there have been studies on if other non-East Asian populations are predisposed to be disadvantaged by alcohol consumption.

I don't think observing that folks in the Middle East drink much less, due to a religious prohibition, is evidence for or against this post's hypothesis. It can simultaneously be the case that evolution discovered this way of preventing alcoholism, and also that religious prohibitions are a much more effective way of preventing alcoholism.

Yes, but it seems like the genetic predisposition hypothesis is about or at least usually framed as "East Asians vs. others (unless there are other groups where genetic predispositions are relevant)". Implying to test the protective effect of one trait, you want to see if East Asians who have the trait at higher levels differ from all others (presumably not having the trait at all, or at lower levels?). Yet the patterns/statistics for alcohol consumption or problems with alcoholism doesn't line up with "East Asian vs. the rest" as opposed to the West and the rest. What seems more notable to me is why the West is higher than everyone else. As opposed to East Asians who drink a middling amount (relative to the world) neither particularly high or low, and many East Asian countries are within the range of the west.

I suppose you could make the argument that East Asians would drink even more (perhaps as much as or even greater than the highest western countries) if not for the genetic predisposition that puts a brake on it. But counterfactuals are hard, and I don't know what would be an easy way to test that. 

Such implants are legal in Poland and some other Eastern European countries ( webiste in polsih that offers such product: https://alko-implant.pl/nasza-oferta/wszywka-alkoholowa/disulfiram-i-esperal ). It's really surprising for me that it's not legal in the US: while reading this piece I was thinking "yeah, there's an implant one can get". I have no idea how effective those things are, though.

Very interesting! Do you know how much disulfiram the implant gives out per day? There's a bunch of papers on implants, but there's usually concerns about (a) that the dosage might be much smaller than the typical oral dosage and/or (b) that there's poor absorption.

Thanks, I enjoyed reading this. I'm half Japanese, so this might explain why I don't enjoy drinking so much. But I wonder, could we do the opposite, in order to make drinking more enjoyable? 

Nice piece. My own Asian flush has definitely turned me away from drinking. I wanted to like drinking due to the culture surrounding it, but the side effects I get from alcohol (headache and asthma) make the experience quite miserable.

Do you wish you didn't have it?

I don't quite understand why we needed the speculative evolutionary intro here. For me it seems to be a distraction and a bit questionable.

Convincing. Good question re: Disulfiram. Maybe drugs that make it easier to ride out physical dependency (+ alcohol withdrawal poisoning) are of greater practical use/demand - methadone seems popular [for rehabilitating opiate addicts, not alcohol, obv.].

One day at work you discover a protein that crosses the blood-brain barrier and causes crippling migraine headaches if someone's attention drifts while driving.

Seems way too specific. This is going to go off under at least some other condition.


 

If these genes really are an adaptation, it shows how ruthless evolution can be. If you implanted a device in your kid that mildly poisoned them every time they drank, you'd be a monster. But evolution basically did that.

It doesn't make them get drunk faster?


 

No one cares about my freedom to rob convenience stores or burn down public buildings.

Unless you live in a tyrannical regime.


 

so he wanted to remove freedom from himself to overcome that.

He wanted to enjoy the beauty of the song, without the downside of the actions he'd take in response (drowning). It's like someone wanting to try heroine without getting addicted. There's a metaphor involving alcohol here. (And he's lucky that he didn't get addicted to siren song.)

 

Most real-world scenarios are different:

  • We need society to enforce constraints.
  • Those constraints affect everyone to some degree, even those who don't want them.

...

What I'd really like is for society to criminalize all mint-chocolate flavored snacks.

Tell us more about your dystopian dictatorship, where people are free from temptation.

I still think there's arguably a fix which doesn't have problem 2 "Those constraints affect everyone to some degree, even those who don't want them." - having opt-in constraints. This might work if you can voluntarily get yourself banned from something (say for the next week), but open tables with snacks don't quite mix with this. 

Less distantly, maybe places could share info about what snacks they will have, in advance.

 

Say you used to be addicted but now you've quit. If you could snap your fingers and make all drugs disappear, wouldn't you do that?

No. There's a difference between all drugs, and a specific drug. 'Snapping' here, would literally kill people.

Interesting consequentialist question here - do drugs save (and help) more people than they kill (and destroy)?

 

Obviously, criminalizing cookies (or fentanyl) is bad for both responsible users and people who can't or don't want to quit. I'm just trying to point out that there is a tradeoff. Society has decided that tradeoff in favor of responsible Twinkie users and against responsible fentanyl users.

Are there responsible cookie users? Or do we just resist the urge to buy it, but give in when it's available as a free snack? You want to not have 'mint chocolate' options - you want them banned. You want to stop, but you're having trouble doing so. Are you addicted to mint chocolate sweets? Are we addicted to cookies?

 

Sometimes we can give people the chance to "Odysseus" themselves without intruding too much on the freedom of others. An example is gambling. Some locations allow people to "self-exclude" from gambling, after which casinos won't let you play for a time period of your choice. This isn't perfect, since now responsible gamblers have their ID checked, and addicts can still cross state lines or play the lotto or whatever.

This is perfect. It's perfect for you, and particular style of irresponsible mint chocolate consumption. 

 

We can informally picture the different regimes like so:

You're still distinguishing freedom and constraints. From your perspective isn't there just a line, instead of two dimensions?

 

Roughly 10% of people in the US are raging alcoholics. Could we offer them the chance to self-exclude from alcohol?

Unfortunately, it seems very difficult.

We're back at ignoring the simpler policy that would work for someone like you -  i.e., I want to not buy it, and would opt in to 'not having the option to buy it'.

 

quantum stem-cell

What?

 

Some studies show great results for people who are married but not for single people.

Maybe friends aren't the weak link you made them out to be.

This reminded me of an essay on artificial pain, where people whose hands could no longer feel pain in some part of their body would get a computer controlled device attached to another part of their body that would hurt them where they were sensitive if they did something that could damage their insensitive body parts.

One problem was calibrating the mechanism to really detect damaging actions (preferably before damage became at all severe). 

The deeper problem was that the entire mechanism was optional.

Even the patients who were most "adherent" to the treatment and the most intellectually "bought in" to the idea that pain could protect them from damage would sometimes briefly turn the device off to do things that would cause damage to their hands that they just "really wanted to do" in that moment.

It feels like there's a lurking idea here related to agency operating on longer time scales?  Something something months, years, and decades? Something something low pass filter?  Something something Parfit?

I had not heard of casino self exclusion before! Thanks for that pointer :-)

If

[It] is just a "nudge", which is often enough to prevent alcoholism from forming in the first place, but not strong enough to displace alcoholism once it's taken root.

then it would work best early on or in combination with someone helping you, e.g. your spouse

Some studies show great results for people who are married but not for single people.

Or your parent. Could parents give it to their teenagers before they go to a party: "You can go but take this pill first."

The drug is still available today, though not much used for alcoholism except in Denmark, where it's widely prescribed.

 

This is not quite true. Disulfiram is currently used in Russia (and other former USSR countries) to treat alcohol addiction. (Random clinic website that offers disulfiram implants for ~$200.)
 

_________________________________________________________


Also in the 90s disulfiram apparently was used to treat alcohol addiction in a quite questionable form:

Coding (kodirovanie) is a catch-all term for various Russian alternative therapeutic methods used to treat addictions, in which the therapist attempts to scare patients into abstinence from a substance they are addicted to by convincing them that they will be harmed or killed if they use it again.

https://en.wikipedia.org/wiki/Coding_(therapy)

Thanks. Are you able to determine what the typical daily dose is for implanted disulfiram in Eastern Europe? People who take oral disulfiram typically need something like 0.25g / day to have a significant physiological effect. However, most of the evidence I've been able to find (e.g. this paper) suggest that the total amount of disulfiram in implants is around 1g. If that's dispensed over a year, you're getting like 1% of the dosage that's active orally. On top of that, the evidence seems pretty strong that bioavailability from implants is lower than from oral doses, so it's effectively even less.

Of course, there's nothing stopping someone implanting 100x as large a dose, and maybe bioavailability can be improved (or isn't that big a concern). But if not, my impression was that most implants are effectively pure placebo effect.

Yep, the first google result http://xn--80akpciegnlg.xn--p1ai/preparaty-dlya-kodirovaniya/disulfiram-implant/ (in Russian) says that you use an implant with 1-2g of the substance for up to 5-24 months and that "the minimum blood level of disulfiram is 20 ng/ml; ". This paper https://www.ncbi.nlm.nih.gov/books/NBK64036/ says "Mild effects may occur at blood alcohol concentrations of 5 to 10 mg/100 mL."

This is awesome, I've been curious about Asian flush for ages but never put in the work to research it. Thanks!

Your discussion would suggest that disulfiram might not work at curing alcoholism but could be a useful prophylactic. Lace the drinking water with it and people will avoid alcohol or stop earlier! What could go wrong?

Someone dies and you get sued. (All it takes is one allergic reaction, or someone who already had asthma, and you're a murderer.)

I was joking ;) But the distinction between prophylaxis and treatment I think is useful because even if "it doesn't work" as one or both, it could work for the other and still be helpful.

The straightforward conclusion is that human evolution is continuing, in fact accelerating.

There's a drug called Orlistat for treating obesity which works by preventing you from absorbing fats when you eat them. I've heard (somewhat anecdotally) that one of the main effects is forcing you to eat a low fat diet, because otherwise there are quite unpleasant 'gastrointestinal side effects' if you eat a lot of fat. 

But who averages 10 drinks per day, you ask? The answer is an astonishing number of people

My question would be "What's a drink?" It doesn't seem to be an intuitive unit.

Ironically, there is no standard for what a "standard drink" is, with different countries defining it to be anything from 8g to 20g of ethanol.

Then it makes a lot of sense to specify what standard is used in the statistics you cite. Without a defined standard a claim like the one you made feels bullshitty to me. 

In this case, 1 drink = 10 g of ethanol, per the linked paper.

Measuring alcohol in drinks is quite normal, I agree it is weird that there is no international standard, but dynomight probably wasn't aware of that when writing this post, so it seems harsh to say the claim feels bullshitty when the source defines precise units for a commonly used measure.

I specified (right before the first graph) that I was using the US standard of 14g. (I know the paper uses 10g. There's no conflict because I use their raw data which is in g, not drinks.)

Sorry, my oversight.

I do have instincts that ask me "What claim I'm making when I say: A sizeable portion of people do X." and failure to know what claim is made rings my bullshit alarm bells. This isn't very serious in this case, but I do endorse my mental reflex.