August 17, 2006

Alcohol "allergy"

If you happen to be Asian, you might have noticed a difference in your playful drinking habits compared to other ethnicities. Still, it's summer and you want to enjoy your last few days carefree! So you go out and have a beer with your buddies. You feel a flush creeping over your face. After a few more drinks, your face turns noticably red and perhaps it is brought up by your good natured friends. You persist in alcohol consumption and you start to feel nauseous. A few hours later, you excuse your self to the bathroom as best as an intoxicated person can. Your dinner takes a shortcut to the toilet.

"Oh, I'm allergic to alcohol..." you might say. The flushing reaction, the nausea, vomiting and headache sound like good symptoms.

Not quite. You actually have a mitochondrial enzyme deficiency in "ALDH2." What is that? Well, alcohol is absorbed in your stomach and your liver starts grinding away at it with alcohol dehydrogenase (ADH.) The byproduct of this reaction is acetaldehyde. In most people, this acetaldehyde is converted into acetate with the enzyme aldehyde dehydrogenase (ALDH.) However, some asian people lack this enzyme and the aldehyde builds up. The high concentration of aldehyde (along with alcohol) builds up in the blood, leading to those unpleasant feelings that other people might get after having 10x as much alcohol.

The fact that this is a "mitochondrial enzyme" made me wonder if this meant that you could blame your mom for your intolerance to alcohol. After all, you inherit all of your mitochondria from the parent that bore you into the world. I poked through a few scientific journals on PubMed. I learned that it was a dominant allele (meaning that your parents are much more likely to pass on to you and affect you.) ALDH is active in mitochondria AND the rest of the cell (likely by ALDH1 or something like that)... so you actually clear acetaldehyde slowly... and your dad might be to blame.

"Why would evolution punish me so?!?" you might ask, being afflicted with this horrible, party-pooping disability that cripples your now-withering social life. Well, there's a theory that it has to do with cancer. HepB is a sexually-transmitted virus that you can get from your mom at birth if she has it -- and a lot of women in Asia have this virus. HepB greatly increases your chance for liver cancer. Drinking adds to this risk by causing liver damage and cirrhosis, so having ALDH2(2) might be a historic marker helping to prevent cancer! Nowadays, we have a vaccine that prevents Hepatitis B, as I've mentioned before.

If that is not enough for you, be glad that it prevents alcohol toxicity, which can lead to serious problems like blackouts, coma and death. You just get minor aldehyde toxicity instead. Just remember, there's a reason why it is called inTOXICation.


References
Crabb, DW. Genotypes for aldehyde dehydrogenase deficiency and alcohol sensitivity. The inactive ALDH2(2) allele is dominant. J Clin Invest. 1989 Jan;83(1):314-6. PMID: 2562960

Jenkins, WJ. Subcellular localization of acetaldehyde dehydrogenase in human liver. Cell Biochem Funct. 1983 Apr;1(1):37-40.

Lin, YP. Why can't Chinese Han drink alcohol? Hepatitis B virus infection and the evolution of acetaldehyde dehydrogenase deficiency. Med Hypotheses. 2002 Aug;59(2):204-7. PMID: 12208210

33 comments:

  1. Interesting. I have flushing, nausea, and headache upon consumption of about two ounces of wine. But I'm of documented northern European heritage both sides, about six generations back. I wonder where it came from.

    I've just always blamed it on the fibromyalgia. That I DID inherit from mom's side.

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  2. This is obviously a very critical metabolic disorder. Is there anything to be done about it?

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  3. Welcome, Grand Rounds Readers!

    I don't think that this genetic deficiency is necessarily limited to people of Asian descent, nor do I see it as a critical metabolic disorder.

    Interestingly enough, ALDH also metabolizes formaldehyde, the result of drinking methanol (the bad alcohol that they supposedly mix into chemical "ethyl alcohol" mixes so lab people don't get drunk on the solvent supposed to be used for cleaning.)

    Anyway, methanol turns into formaldehyde and then into formic acid. Formic acid corrodes optic nerves, making you go blind!

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  4. I'm not buying the "cancer protective" hypothesis. The gene is so widespread that there would have had to have been a tremendous selection pressure for the phenotype to arise. In order for that to be true, HepB-promoted cancer would have had to have been a leading killer of reproduction-age individuals. Twentieth century demographics show Hepatocellular carcinoma to be a predominantly blood-borne disease (rather than transmitted via birth canal or sex), afflicting adults primarily in later adulthood. Cirrhosis likewise takes decades to manifest. I'm not sure you could establish that during the majority of evolution either disease was a killer of young alcoholics. It seems to me you would need that as a pre-condition to favor survival of non-drinkers.

    And why so predominantly in Asia?

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  5. True, correletion does not prove causation. I don't really buy into the idea also, but I thought I'd toss it in as something interesting to think about.

    I suspect it is similar to an Asian disposition of adult lactose-intolerance -- a mix of culture and genes slowly eliminated heavy drinking of alcohol and milk from the diet.

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  6. The explaination I heard was that it was all down to how our ancestors coped with water that wasn't safe to drink - Europeans/Middle Easterners fermented grapes or grain to make ale or wine, and Asians boiled water and made tea. Either method sterilised your water (pretty important in the days when most people died of infectious diseases before they hit what we'd consider middle age), but only one meant your whole population had to adapt to metabolise alcohol.

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  7. "Europeans/Middle Easterners fermented grapes or grain to make ale or wine, and Asians boiled water and made tea."

    What about those cultures of the Middle East that boiled water and made tea or coffee because alcohol isn't halal?

    I'm half European and half Middle Eastern and I still turn red when I drink beer.

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  8. How bout an alternative explanation? People who got drunk had lowered barriers to reproduction, and therefore tended to reproduce MORE, selecting for an advantageous gene. This makes more sense to me and certainly is more consistent with my -- er, experiences.

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  9. Is there any time when people have delayed adverse reactions to alcohol, say around 3 or 4 the next day? Often I feel fine until the next day at that time, when I will start throwing up, develop a throbbing headache and not be able to stop for a few hours. Sometimes it actually stretches into the next day after (2 days after the consumption). It also doesn't seem to matter whether I have 2 drinks or 12, I feel just as bad. And sometimes (rarely) I feel fine. I'm wondering if others are out there with this same problem, and if so, what is it because it feels like an alcohol allergy.

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  10. I don't just get the "asian flush". After a couple of hours, I get this crazy itching that lasts for the next day or so. This is accompanied by splotchiness and hives on various parts of my body that stick around for a couple of weeks to months!!! One interesting thing is that my lymph glands also tend to swell...like under the armpits and such. I wish I could be less of a party-pooper, but wouldn't you try avoid or cut down the alcohol if you were stuck with all this?!

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  11. anonymous,

    it sounds like you DO have an allergic reaction to alcohol. The combination of urticaria (hives) and lymphadenopathy (swollen bumps in the armpit and elsewhere) is suggestive of this... and it brings up a good point.

    your body is an amazing self-run machine, but you can develop allergies to pretty much any sort of stimuli.

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  12. Glad I stumbled up this blog! I suffer from the "redness" and am of Asian decent. I definitley, cannot drink as heavily as some of my peers but I can say that I don't get nauseated and can actually drink pretty well considering I look like a tomato! I've been suggested Pepcid or other antacids can curb the reaction. I tried tums chewalbes but it did absolutley nothing, but one friend said it HAD to be Pepcid AC. Can you shed light on if this a myth before I buy some? Thanks in advance!

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  13. I'm puzzled why Pepcid AC would work... but if you try it, let me know how it goes.

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  14. I'm a quarter japanese, and I have an asthmatic reaction to alchohol, I turn bright red, and get red patches on my body which my friends refer to as my "sweater"Usually the asthmatic portion of the reaction wears off after 15-20 minutes, but the rash lasts for 10-18 hours. Do you think this is a allergic reaction?
    and there is absolutely nothing I can do to counter it?
    Is it possible to build of a tolerance..Curse my ancestors.

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  15. I'm of European descent, but I have an intense reaction to alcohol. From just one glass of wine or beer I'll be left nauseous and hungover the next day. Three glasses of wine or three beers and I'll be sick all night and will have to stay in bed the following day. Last time I drank three glasses of wine, I was still feeling nauseous two days later. My Mum and brother have the same problem. As I far as I know we have no Asian descent. I did find one abstract that mentioned specific alleles (ADH1B*2, ADH1B*3, and ADHIC*), as well as the aldehyde dehydrogenase gene, which can also cause high sensitivity to alcohol and which could help explain why the problem occurs in people of European descent, but with less frequency (see http://cat.inist.fr/?aModele=afficheN&cpsidt=17342668).

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  16. My Japanese friend has even more serious symptoms with just half a glass of wine.

    He blood pressure falls and he falls asleep (faints) in the dinner table. He hyperventilates while unconscious, gaps for breath, sometimes he vomits and after a few minutes- from 10 to 20- he comes to his senses and doesn't remember anything. Needless to say, he doesn't drink at all anymore. So be
    happy when you only get the "flush". It is a scary experience.

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  17. I am a 25 year old girl from California. I have always experienced an adverse reaction to alcohol where my hangovers seem to be abnormal in length and severity. They also seem to have gotten worse as I've aged. Usually, if I drink anything more than 2-3 drinks, I am up early the next morning mildly incoherent, with a killer headache and am vomitting on the half-hour all day long. I can't eat or drink all day, and end up weak and exhaused in the evening. The hangovers seem to subside the more frequently that I drink. I've also found that my grandmother and mother have suffered from the same symptoms after drinking. I can't find any literature explaining why and what is happening physiologically and how I can prevent it (while still drinking alcohol of course). =)

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  18. I have the same thing! I'm a 39 year old woman of European descent and I experience nausea and vomiting the next day on sometimes as little as two drinks. Cheap alcohol or various wines seem to trigger this reaction. More expensive vodkas seem to be purer and don't cause this reaction or to a lesser degree. My mother has had the same problem too.

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  19. I usually take aspirin before I go to bed to prevent the headaches (I know this is bad, but fortunately being in med school hasn't alloted me the opportunity to indulge in drinking like I used to) so this little habit has subsided a bit.
    I usually stand up the entire time I'm drinking to prevent myself from getting too nauseous or sleepy and I drink verrrrryy slowllllly. Like 1 drink an hour, if that.
    The benefit of the "asian flush," - wow Jen, you loook nice, did you put makeup on? get a suntan today?
    and I'll never be an alcoholic and hopefully my kids won't be able to be either (whenever I have them).

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  20. I'm of Asian descent, but funny no one described what I get. I do get red, headachy, and nauseous after half a beer or glass of wine.

    Usually the first sip of alcohol is fine, but the second sip tastes awful. Never fails. Someone said I'm tasting formaldehyde, which i believe. It's amazing, first sip always tastes fine, so I have to make sure it's a big one.

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  21. Hey, it's great to hear from so many other people who suffer like I do. I get a bit of the 'flush' but my main problem with drinking is the headache, nausea, sinus congestion and jaw clenching I get. The headache starts straight after my first drink and includes photophobia (light sensitivity). I think the jaw clenching may be to do with the pain I'm in because I can see no other explanation for it, it sure doesn't help though. Anyway, the next day as well as the headache I get really itchy skin, which leads me to believe that I have an intolerance to the Histamines in alcohol and not 'the Asian flush'. I'd be interested to hear what others thoughts on this are and if others have the same itching, sinus problems or hives like me, try taking some antihistamines and see if it helps, I haven't tried it yet, but theoretically it should work right?

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  22. I don't get a hangover or vomit or anything when I drink. Sometimes hives form on my arms and sometimes they don't but either way my arms start to itch unbearably. My arms also swell up and when the swelling goes down my skin peels off in large chunks. Last time I drank, I basically peeled off an entire layer of my skin. The itching also lingers for a week or two. Isn't there any sort of counter to this?

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  23. im half japanese. my redness or makeup as my friends call it happens every once in awhile. i think it has to do with my diet. my wife told me about the pepcid ac thing so ill try it. ive dealt with this for years and just learn to live with it.

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  24. Wow..I have had a problem with alcohol for years. I am of european descent. If I drink just a 1/4 glass of anything with alcohol, a will have a very rapid heart, panic attacks, hot and cold flashes, feeling of fainting and dieing, all within I would say 1 to 6 hours after just a small amount. It really is aweful! Very early in my life I was able to drink, then this "problem" crept up on me! It hit me all of a sudden in the middle of the night with such intesity I thought I was dying and actually lost control of my bladder. I wish I could find something to help!

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  25. I'm so glad I stumbled across this blog.

    I'm of European (English) descent and have never been able to drink alcohol without nausea, weakness, the shakes and blinding headache for the next 12 hours. My mother and son are the same. I have at times had these symptoms from as little as one small bottle of beer.

    I Had heard of the Asian intolerance and was starting to doubt my parentage :) now I see it's much more common than I thought (Although I never actually met another British person with this problem outside my direct family)

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  26. Interesting read. Also came across this on the same topic: "Alcohol flush signals cancer risk for East Asians" http://www.chinadaily.com.cn/life/2009-03/24/content_7610684.htm

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  27. I feel that a number of people who commented here are describing extreme hangovers or alcohol sensitivity, rather than the "flush reaction". I am of Eastern European descent and I experience pounding headache, extreme redness(which begins in the face and can extend to my chest and back), vomiting, and rapid heartbeat. These sensations occur immediately, not the next day. The discomfort is so great and immediate that "2-3 drinks" is impossibility. A half glass of wine is enough to trigger these reactions.

    I wonder among those who claimed to be of European descent were not also of Eastern European Descent, and therefore more likely to come from common mtDNA haplogroups. There are various haplogroups present in any given country, so being English may help narrow down your likely haplogroups, but it really doesn't mean much.

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  28. I am of Korean decent and have a reaction to alcohol. After the first few sips, my head starts pounding, ears are throbbing, skin is red and with hives and a little wheezing. I found out the hard way, after a beer + 1/2 I blacked out. I exhibited signs of being drunk, couldn't walk w/o help...about ready to pass out again.

    Here's the strange part, about 10 mins. later, I was fine. Completely fine. I've found that Pepcid does work for whatever reason. And at 1 time I developed a tolerance for alcohol, at least to a certain degree.

    My question is does all that qualify as an allergy? It must be more than the "asian flush". Anyone who might shed some light on the subject would be greatly helpful.

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  29. Along with some others on this blog, I am of (Western/Northern) European descent completely, but still have an abnormal reaction to alcohol. Drinking more than one drink in an evening leads to intense vomiting the next day, usually starting at 2 PM or later. This reaction gets triggered by less and less alcohol each year--I had no problems when I was 18, but now two beers in a night make me throw up the next day.
    Interestingly enough, I NEVER throw up while drinking, or just after it. I always have a delayed reaction.
    Has anyone talked to a doctor or medical professional about this phenomenon?

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  30. I'm mixed European and Asian. I think I got the double whammy. Though, the redness, asthma and hangovers are much, much tamer drinking good scotch whisky. Screw the cheap stuff.

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  31. im kind of confused about the hep b part. So saying you are infected with hep b you will have the aldh(2) deficiency? is this implying when you have hep b you also have the aldh (2) deficiency?

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  32. I'm Filipino and I get the allergic reaction as well.

    did some good research tho, in a nut shell...

    A "yeast" is type of fungus organism. Some yeasts feed on sugars and produce gas - which is how bread-making yeast gets the dough to rise. Other yeasts cause grains and starchy vegetables like potatoes to ferment and excrete alcohol as a waste product - which is how liquors and beers are produced.

    Alcohol is made from yeast and sugar. You have good and bad bacteria in your body...and you also have good and bad fungi in your body. The beneficial bacteria keeps yeast in check. When you drink, it kills off alot of beneficial bacteria.

    Acetaldehyde is a paraticularly toxic substance which, in addition to being produced by threonine and ethanol,is a product of the metabolism (i.e. fermentation) of carbohydrate in yeast (its a fungal waste product). They are known to poison tissues -- accumulating in the brain, spinal cord, joints, muscles and tissues. The body has an enzyme which breaks down the aldehydes to less toxic substances. This enzyme is aldehyde oxidase, or sometimes, aldehyde dehydrogenase.


    Acetaldehyde cannot be excreted from the body; it accumulates. Acetic acid can be, though, and the body naturally removes it or changes it into acetyl coenzyme A, a major player in the body's energy system. Molybdenum, not medication but a nutrient/mineral, is chemically responsible for breaking down acetaldehyde into acetic acid.


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