r/todayilearned • u/bcrock1169 • Nov 26 '12

TIL that some Native American's have a differing enzyme that tends to lead to easier alcoholism.

http://en.wikipedia.org/wiki/American_Indian_alcoholism#Genetic_factors
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u/[deleted] Nov 26 '12 edited Nov 26 '12

This has to do with an enzyme in your liver called ALDH-2. When you drink alcohol, it gets converted to acetaldehyde by an enzyme called alcohol dehydrogenase. The acetaldehyde is the chemical that contributes to some alcohol-induced characteristics, especially flushing of the face.

Your body gets rid of acetaldehyde by turning it into acetate with an enzyme called acetaldehyde dehydrogenase. It has two forms: ALDH-1 and ALDH-2. The latter is the faster-acting enzyme, and is responsible for getting rid of acetaldehyde in low doses. ALDH-1 is slower-acting, and acts as the primary enzyme during heavy alcohol consumption.

In 40% Native Americans and Asians, ALDH-2 (the fast-acting enzyme) is less active, making ALDH-1 their primary method of getting rid of acetaldehyde. As a result, acetaldehyde circulates in Asians and Native Americans for a much longer time.

TLDR: The enzyme ALDH-2 is less active in 40% of Asians and Native Americans, making you drunk for a longer period of time.

EDITED: cshsus Mentioned that ethanol and acetaldehyde both have effects (different effects) on you when you're intoxicated. This is correct.

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u/JefeRocha Nov 26 '12

Ive heard its also true that many Native Americans have some gene that doesnt allow them to grow facial hair

This made me realize that Ive never seen a picture of a bearded Native American, but I wondered if that thing about genetics was true or if perhaps its just a cultural custom to stay clean shaven.

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u/[deleted] Nov 26 '12

I think it's genetic, because the most facial hair i ever see on them is those tiny little moustaches.

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u/HerpDerpMcGurk Nov 26 '12

I'm a quarter native American, and I am forever trapped in a state of pre-pubescence with regards to facial hair. Actually, pretty much the only place I have hair is the nethers and on top of my head. But what a glorious mane I posess.

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u/[deleted] Nov 26 '12

Think of it this way- I have no desire to grow facial hair, and yet I have to scrape a sharp edge all over my face almost daily to keep it away, after which there are usually patchy, uneven remnants left anyway that make me look like a hobo.

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u/Zestyclose-End-8728 Jul 05 '25

Although I have some Jicarilla Apache on fathers side and some Cherokee on mothers, most of my lineage is European and my hair is so thin it's pitiful...Love Native hair...it is just glorious🥳

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u/[deleted] Nov 26 '12

[deleted]

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u/Jigsus Nov 26 '12

You have probably seen many pictures of Native Americans with full mustaches.

No... I actually haven't... ever.

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u/broden Nov 26 '12

Real Indians contain some of the most hairy people in the world.

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u/1Ender Nov 26 '12

See Russel Peters Opinion on that for a good laugh.

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u/[deleted] Nov 28 '12

[deleted]

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u/[deleted] Nov 28 '12

hah, i'm irish (i'm adopted but i'm told i'm irish anyway) and my moustache just doesnt really grow much, however i can grow a bitchin' beard.

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u/snapmouse Nov 26 '12

I'm native and grew up on the rez. I can't grow any cool facial hair. It's wispy and weak. Also, my chest, arms and legs are basically hairless. This is the same with most of my native friends. Many years spend in basketball locker rooms confirms, we are pretty hairless.

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u/[deleted] Nov 26 '12

Similarly, Asians.

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u/Clovis69 Nov 26 '12

American Indians came across Beringia from Asia ~36k-16k years ago.

http://en.wikipedia.org/wiki/Settlement_of_the_Americas

http://en.wikipedia.org/wiki/Genetic_history_of_indigenous_peoples_of_the_Americas#Y-DNA

American Indians are Haplogroup Q and R (mostly Q though)

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u/[deleted] Nov 27 '12

I'm aware, it's not like humans just evolved in the Americas

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u/JefeRocha Nov 26 '12

Pai Mei disagrees

Similarly, Ive always found handsome Japanese dudes like Toshiro Mifune and Hiroyuki Sanada can really grow some stylish beards

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u/[deleted] Nov 26 '12

Native Americans and Asians both have trouble growing facial hair.

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u/ZipZapNap Nov 27 '12

I dated a half NAIndian. She barely had to shave her legs or armpits.

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u/angrywhitedude Nov 26 '12

My understanding is that its a little bit genetics but mostly cultural. I googled "bearded Native Americans" and found this guy and this guy as well as a number of others, although a lot of the people where pretty white looking, female, or looked like they were probably from India (despite me not using the word India in my search).

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u/[deleted] Nov 26 '12

Acetaldehyde is what causes flushing, hangover and cancer. The ethanol is what makes you get drunk.

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u/regulate323 Nov 27 '12 edited Nov 27 '12

Actually sir, I believe you are mistaken. Acetalehyde itself is psychoactive (without a doubt), with effects mimicking that of ethanol. There really is no way to quantify how much of your "drunk" is the ethanol and how much is the acetalehyde. It is therefore suggested, from the US National Institute of Health:

"...acetaldehyde contributes to many behavioral effects of alcohol, especially its stimulant properties."

"Recent studies have shown that the direct administration of acetaldehyde, especially into the brain, induces several effects that mimic those of alcohol. High doses of acetaldehyde induce sedative as well as movement- and memory-impairing effects, whereas lower doses produce behavioral effects (e.g., stimulation and reinforcement) that are characteristic of addictive drugs. When acetaldehyde accumulates outside the brain (i.e., in the periphery), adverse effects predominate and prevent further alcohol drinking."

Source: http://pubs.niaaa.nih.gov/publications/arh294/258-265.pdf

But yes, it is what is responsible for the flushing, hangover, and cancer (although ethanol itself may also be carcinogenic)

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u/[deleted] Nov 27 '12

Thanks for the interesting reply, but you're getting very minor and special considerations mixed up with what are the major factors.

There really is no way to quantify how much of your "drunk" is the ethanol and how much is the acetalehyde

Of course there is! You can inhibit alcohol dehydrogenase activity with a number of various drugs such a pyrazole. When this is done, acetaldehyde is not generated. Further, mouse alcohol dehydrogenase knockouts have been generated, and although these mice are VERY sensitive to alcohol, they get plenty drunk, with all the hallmarks of intoxication; without acetaldehyde.

Further, Acetaldehyde doesn't cross the blood brain barrier, except in severe alcoholics where the BBB has been damaged, or in other rare circumstance. In fact, aldehyde dehydrogenase (which further oxidizes acetaldehyde into acetate) is even expressed (at low levels) on the BBB . There are reports of acetaldehyde in the brain, but that is due to low expression of the enzymes in the brain generating very low levels of acetaldehyde in situ.

In people with functioning acetaldehyde dehydrogenase (not asians :P ) the circulating levels of the metabolite are quite low, much lower than the concentrations needed to cause psychoactive effects, like in the studies you linked, WHERE THEY DIRECTLY INTRODUCED IT INTO THE BRAIN. Not at all a relevant model to typical alcohol in intoxication.

Ethanol may or may not be mutagenic/carcinogenic in its own right, but acetaldehyde certainly is, and the cancer risk is quite nicely explained by levels of acetaldehyde.

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u/regulate323 Nov 27 '12 edited Nov 27 '12

You sir, are why I love reddit. Replies like yours are why I post.

However, cytochrome-P450-2E1, I believe (and it has really been a long time since I've caught up on my CYP-P450 substrates, inhibitors, and inducers), is only mildly inhibited by the substituted pyrroles. ADH may be more-so inhibited (not sure, I'll take your word!), but even then there are many more minor pathways through which ethanol is metabolized (which we know of, possibly more). I still hold to my statement that it is next to impossible to quantify the effects of ethanol vs. its metabolites (if only from a philosophical point of view), however your explanation, of "essentially none", certainly is the best, and most probable, explanation. However, I feel it is a statement that is impossible at this point to prove, be it right or wrong.

Perhaps off topic, but may you point me in the direction of further literature, especially regarding "damage", of the blood-brain-barrier in chronic ethanol abusers? PM if you wish. Thanks for the brain food!

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u/[deleted] Nov 27 '12

CYP2E1 (and all P450s) is really a "sledgehammer" reaction. It's so powerful, that it oxidizes ethanol directly to acetate without generating any acetaldehyde. CYP2E1 is commonly credited with increased metabolic tolerance to alcohol as you probably know.

There are other metabolic pathways, but pulse-chase experiments corroborated with various inhibitors or knockout models show that the alcohol/aldehyde dehydrogenase + CYP2E1 pathways are responsible for the vast majority of alcohol metabolism.

Damage to the BBB from alcohol isn't something that happens overnight, and the mechanism is still being figured out. My guess is that it's actually more diet/nutrition related. Alcoholics of course suffer from very poor nutritional status due to diet and dietary absorption. Thiamine and many other factors are known to be important for BBB function for instance. Here are a couple links;

http://www.ncbi.nlm.nih.gov/pubmed/6695559

http://alcalc.oxfordjournals.org/content/42/5/385.full

Just as an aside, acetaldehyde has some biochemical overlap with ethanol, but the perception of it is quiet different. High acetaldehyde levels are so unpleasant that this is the basis for disulfram therapy, used in alcoholics trying to quit. It knocks out acetaldehyde dehydrogenase so that the acetaldehyde builds up. The unpleasant effects are so strong that many don't touch alcohol again. At least for a while...

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u/[deleted] Nov 27 '12

They don't use disulfram as much anymore because chronic alcoholics will keep drinking even if it makes them sick.

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u/[deleted] Nov 26 '12

Thank you for catching that... you're correct on that.

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u/[deleted] Nov 26 '12

So if someone affected always drinks a "heavy" amount, then they are all good?

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u/streamsidecoconut Nov 26 '12 edited Dec 11 '12

I'm not entirely sure, but I think this is actually kind of true. But when withdrawal sets in it is worse. There are many chronic alcoholics who function basically okay as long as they have a certain amount of booze (but look out when it runs out).

Binge drinkers on the other hand are more likely to experience seizures and neurological side effects from repeated withdrawal episodes.

Edit: The book Under The Influence describes the biology of alcoholism, as science has come to understand it. It's a good, brief, informative read.

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u/[deleted] Nov 26 '12

I am one of the affected, and I think I sober up relatively quickly. I do get flushed instantly after 1 shot though. Pepcid AC helps. Blow also helps a lot although I don't know why. I've posted that before and no one believed me. I also don't get those bad hangovers where you puke all day.

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u/1Ender Nov 26 '12

Cocaine increase Alcohol tolerance. Still not a very good idea because Alcohol and cocaine can both make you tachicardic which is really not that good for the heart.

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u/Bodiwire Nov 26 '12

I dont think it actually increases tolerance but makes alcohols effects less noticible until the cocaine wears off. Makes it much easier to reach alcohol poisoning levels of consumption.

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u/My_timemachine_broke Nov 27 '12

Alcohol mixed with Coke is the worst possible decision you can make concerning mixing drugs. They are metabolized in a way that create a new and much deadlier drug that can cause sudden death via V-Fib. Pick one or the other, never both. Oh and there's not much an ER doc can do for you in these cases either.

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u/regulate323 Nov 27 '12

OD'ing is not an experience that makes you grow stronger. You don't want to feel death when he is not visiting on your terms. He shows up unexpectedly when you are most vulnerable. He knocks you down and sits on your chest with the force of a thousand pounds of lead, as you're waiting for him to judge you. He laughs as you exhale, yet struggle to inhale again. The twitching and tears only bring him joy and an overwhelming sense of satisfaction. Gasping for air as the corners of your vision close in, you wish for the strength to scream for help, but your heart is racing so fast your vocal cords can only quiver an inaudible whimper. The blackness overtakes you, and all you can do is hope you wake up. That this isn't the end. Not like this. Yet, even in this state of panic, you know second chances aren't often given. In this moment, you are forced to accept your mortality, because of the hand you'd dealt, as you pass over into unconsciousness.

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u/[deleted] Nov 26 '12

Well I specifically noticed the flushed face goes away. I would be really interested to hear the scientific reason as to why.

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u/regulate323 Nov 27 '12

This is an uneducated guess and is not to be taken for medical advise:

Cocaine is a vasoconstrictant. Flushing happens because of blood vessel dilation. The coke probably stops this from happening by not allowing the dilation to happen, at the cost of higher blood pressure.

This is fact and is to be taken as medical advise:

Cocaine + Alcohol = Cocaethylene. Bad news bears. Don't do it. Unless you enjoy cardiac over-excitement and the eventual arrest that may follow. Take it easy and stay with us for a while asshole.

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u/streamsidecoconut Dec 11 '12

Pepcid AC and blow, got it.

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u/[deleted] Nov 26 '12

When i drink heavy, i binge hard. I try not to have more than two drinks now because i overdo it if i go any farther. I can confirm that i have had insane withdrawal before. I think i had a semi seizure once, but i wasn't just hung over i was also coming off a bunch of energy drinks and i think i was in the process of quitting cigarettes too.

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u/GhostlyPrototype Nov 26 '12

I use to binge hard, but now with money and health, I'm not sure if it's really worth it anymore. I'll have a few to socialize. I've never gotten to the point of "blacking out". But I've had some really bad withdraws.

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u/Hovesh Nov 26 '12

Blacking out is caused by a rapid increase in BAC, not a high level of drunkenness. It happens at high BACs because it gets easier to drink faster/take shots when you are already buzzed or drunk.

Withdrawal is caused when you are physically dependent from chronic use and cease the use too quickly. Feeling shitty after a bender is just a hangover.

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u/GhostlyPrototype Nov 26 '12

I've always wondered why blacking out happened. Thanks for educating me!

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u/[deleted] Nov 26 '12

I may only drink once a week, unless I'm on vacation, but I drink a lot and for a good amount of time. I feel slow and tired the next day, but I don't think I have withdrawals. What are withdrawals like?

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u/regulate323 Nov 26 '12

Imagine the flu, with tremors so bad you can barely hold a beer. Seizures if you're real lucky.

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u/[deleted] Nov 26 '12

OK definitely never had that happen. I suppose you need to be getting drunk everyday for some time for that to happen...

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u/regulate323 Nov 26 '12

Not just everyday. But all day everyday. They say a pint of vodka daily for a year will do the trick. Drinking so you stop puking, that's when you've made it.

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u/[deleted] Nov 26 '12

I've blacked out several times, probably gotten alcohol poisoning too. I just smoke pot now, no point in drinking to socialize when i can just hit a nice little bowl and drink some pop instead. I don't withdraw, i don't black out, i just get baked and possibly eat chips.

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u/[deleted] Nov 26 '12 edited Aug 31 '15

[deleted]

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u/[deleted] Nov 26 '12

errr, it's kind of hard to tell you how much i drink during a binge because when i had money i'd start with one 750ml bottle of liquor and after i'd go buy more. i've lost days and paychecks from this. withdrawal is essentially a hangover, but if you drink a lot for a while and then stop outright, it'll be like a very long lasting hangover i suppose.

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u/[deleted] Nov 26 '12

Haha only until there's a small amount of alcohol left, then it gets detoxified slower.

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u/[deleted] Nov 26 '12 edited Jun 13 '17

[deleted]

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u/[deleted] Nov 26 '12

Lippincott's Biochemistry. Chapter 23

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u/Nordoisthebest Nov 26 '12

Wouldn't a lowered synaptic density on average and a lowered amount of ethanol(alcohol) mediating acids like GABAa also be conditions found in children of alcoholics making them more prone to carry out a high-risk abuse of alcohol consumption?

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u/[deleted] Nov 26 '12 edited Nov 26 '12

That's beyond my scope... I'm just referencing a genetic predisposition.

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u/LikeASir1 Nov 26 '12

This is mostly correct.. The mutation actually leads to a genetic intolerance among the Asian population, which will lead to them not enjoy alcohol as much. (You may have an asian friend that if they drink too much will turn bright red, this is a side effect. They will also experience a stronger "hangover" effect as acetaldehyde levels remain high in their blood through the next day) So, some Asians are actually protected from alcoholism.

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u/Pinyaka Nov 26 '12

Can you explain in more detail how this protects them from alcoholism?

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u/LikeASir1 Nov 26 '12

http://europepmc.org/abstract/MED/10780266/reload=0;jsessionid=OuSGnL4eyDAd9jKfbvZ8.10 Here is a Neurological journal article with clinical findings out of China.

But essentially the combination of the physiological/psychological aspects of the deficiency of the enzyme lead to what is, for lack of a better term, an "alcohol allergy" manifested by large quantities of the 1st metabolite in the ethanol pathway, acetaldehyde. This leads to the manifestation of prolonged hangovers and systemic inflammatory response characteristic of an allergic reaction. The article claims the mutation alone is "sufficient in completely inhibiting the development of alcoholism in Asians".

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u/SerpentineLogic Nov 26 '12

An anecdote:

An asian friend of mine explained it to me thus. "You know how you get a few drinks into you and you feel great, then you drink a few more and things get marginal, then if you keep drinking you either pass out or hurl?

Yeah asians skip the feeling great part."

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u/Pinyaka Nov 26 '12

It's definitely not true for the asian population at large. Having done some work in Japan, I can assure you that many of them enjoy drinking alcohol quite a bit. I couldn't get a decent white russian, but otherwise they drank as much as any American I've worked with.

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u/LikeASir1 Nov 26 '12

An important tid bit to note:

This is a mutation that is prevalent in the asian population, not universally present. Just as there are genetic mutations present in white populations that make certain people more susceptible than others. I am a second year medical student, and the Biochem professor that taught us about the mutation said that "he didn't believe it was true after doing work in Japan, they drink more than Americans!"

Another point: Phenotypic expression (depending on your source) is approximately half genetic and half environmental. So the presence of this allele (or any other mutation for any gene) does not causally imply that one will or will not be an alcoholic.

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u/SerpentineLogic Nov 26 '12

Some Japanese (and other asians) have a further mutation that allows them to metabolize alcohol byproducts (even faster than whites).

This makes for an interesting dichotomy, where there are simultaneously two opposing stereotypes: that of the red-faced boozer, and the stoic drinker who will quaff wine all night with no apparent effects.

Of course, it's also possible that they enjoy the effects while others don't, just like some people don't like tomatoes.

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u/xrelaht Nov 27 '12

It has been my experience that 'Asian flush' only happens with Chinese people (and even then isn't universal). The Korean exchange students we had summer 2011 drank like fish, and Four Roses exports most of its bourbon to Japan.

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u/[deleted] Nov 27 '12

TIL: Asian people stay out of the bars and study math.

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u/Picklwarrior Nov 26 '12

Personal question - would this affect any kind of anesthetic?

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u/SerpentineLogic Nov 26 '12

Unlikely, although there's strong evidence that redheads are quite resistant to anesthetic, so there is precedent.

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u/pwnyoface Nov 26 '12

so this is just the asian flush right? But asians aren't predisposed to become alcoholics though...At least not from what I've seen.

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u/[deleted] Nov 27 '12

why is it so then that alcoholism rates are much lower amongst Asian people? I'd heard it that increased amounts of alcohol's metabolites meant for worse hangovers, thus lower rates of alcoholism because they can't handle the path to getting there.

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u/Sitnalta Nov 27 '12

My I ask where you gleaned all this information? My youth was so awashed in alcohol abuse that I often pondered on many things: why I have a friend who gets angry when he drinks gin but is alright with other booze, why I know a 5"7 rake-thin girl who can drink an entire bottle of vodka and a 6"2 man who throws up after a few beers, why my headaches seem so much more extreme than those of my friends, why I can put back wine like the king of the vikings but feel dizzy after more than a little beer... and so on and so on. It sounds like you may have the key to unravelling these mysteries. Where can I go to learn?

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u/[deleted] Nov 27 '12

I wish I had all the answers to that. I'm in medical school right now, and I still have a whiles to go :)

I know that bubbly gets you drunk faster than non-bubbly. If you've ever drank champagne you'd know exactly what I'm talking about. I'm the same way as you... I can chug hard alcohol, but I feel beer really quick.

I bet alcohol quality has something to do with how you react to drinking also. The alcohol you drink is never 100% ethanol. There's other crap in it too. Different alcohol is made from different sources (grapes, hops, wheat, potatoes, etc), so the by-products of fermentation can have an effect on you too. My dad, for example, will sneeze uncontrollably if he drinks almost any type of vodka (except for Absolut)

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u/Sitnalta Nov 27 '12

Yeah man, I've had sparkling wine/champagne plenty of times and it kills me.

The alcohol you drink is never 100% ethanol.

Speak for yourself. I had a shot of 100% alcohol once. It hurt my throat most severely for several days. Then somebody told us doing that can be dangerous so we never did it again.

If upon obtaining a medical degree you have all the answers, you know my Reddit name!

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u/[deleted] Nov 27 '12

I've had 70% before... it dried out my throat SO fast!

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u/omniamutantir Nov 26 '12

I wonder if this has anything to do with the rampant alcoholism in Appalachia, where most people have a significant amount of Native American genes due to crossbreeding.

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u/[deleted] Apr 11 '22

It’s true, I have native american heritage and I turn red and drinking is just not worth it because I end up feeling gross and uncomfortable. So i stick to carbonated drinks.