I’m not drunk, I just have a deficient enzyme…

Anytime I drink with my friends, be it wine, liquor, or beer, my skin starts to glow red even after ingesting just a little bit of alcohol. So many people considered me to be drunk once they see the red glow on my face, although I barely feel the effect of the alcohol. This makes me wonder “Why do I flush so easily after drinking alcohol?”

One day, one of my friend mentioned to me that he has read somewhere saying that the red glow does not necessarily mean I was drunk but it has something to do with missing an enzyme or something. That’s right, I have what’s colloquially known as the “Asian Flush”.

So I started digging into this. Actually I had Cath start looking up some scientific reasoning behind this flushing, I join in a bit later.

To understand this, we first have to understand what happens after we ingest the alcohol.
The process can be broken up as follows: (1) absorption of alcohol through the gastrointestinal tracts, (2) equal distribution of the alcohol in the total body water, and (3) metabolism of the alcohol primarily by the liver [1].

The metabolism of the alcohol is believed to be carried out in two steps [2,3]:
(1) conversion of alcohol to acetaldehyde
(2) conversion of acetaldehyde to acetic acid

Alcohol dehydrogenase (ADH) enzyme is responsible for step (1), whereas acetaldehyde dehydrogenase (ALDH) is responsible for step (2). Note that process in step (1) is also termed alcohol dehydrogenase, and similarly the step (2) process is called acetaldehyde dehydrogenase.

Alcohol is also metabolized with a different system, however this system is only likely to operate at high alcohol concentrations, i.e. in chronic alcoholic [3]. Otherwise, the bulk of the alcohol is metabolized with the  alcohol dehydrogenase and acetaldehyde dehydrogenase [3].

click here to skip to the short version

The longer version:
The “Asian Flush” results from a deficiency in one of the  isoenzyme in the ALDH enzyme group, specifically the ALDH2 isoenzyme [1,3,4]. ALDH2 is polymorphic, meaning the alleles, i.e. genetic coding, found at the location along the chromosome pair responsible for this enzyme may take several forms. The alleles responsible for the ALDH2 enzyme is normally expressed as ALDH2*1 but becomes ALDH2*2 when it is mutated. ALDH2*2 allele leads to a deficient ALDH2 enzyme, which inhibits the conversion of acetaldehyde to acetic acid [4]. The result of Wall et al. [4] highly suggests that it is the higher acetaldehyde levels that leads to the flushing response, and not the blood alcohol levels (BAC).

Schematic showing the effect of the mutation of the ALDH2 alleles on the flushing response after consumption of alcohol at the same blood alcohol concentration.

About half of Asian ancestry has this deficient ALDH2 enzyme [3,4,5], but is almost totally absent in Caucasian populations [5].  Asians with only one mutated ALDH2*2 allele in their genes experience only a mild flush response compared to those with two ALDH2*2 alleles[4].

Moreover, it was found in one study reviewed by Bosron et al. [3] that the alcohol metabolic rate in Japanese with and without this deficient ALDH2 enzyme is not significantly different. In other words, having this deficiency does not mean one cannot process alcohol as fast.

The Consequences..
In many studies, this deficiency in the ALDH2 enzyme has been linked to lower rate of alcoholism [1,5]. However, acetaldehyde is believed to be a mediator of toxicity [3]. Consequently, the elevated acetaldehyde levels may also contribute to increased risk of alcohol related conditions, such as liver diseases.

Bonus: so what determines the alcohol metabolism rate?
The rate of alcohol metabolism is determined by step (1) or alcohol dehydrogenase. In another study reviewed by Bosron et al. [3], it was found that the variability in the alcohol metabolism rate is largely dependent on genetics (49%), and only somewhat dependent on prior drinking experience (12%) and the combined contribution of age, weight, body fat content and lung volume (<10%).

The metabolism of alcohol is determined by the ADH enzyme. A large variation of the different ADH2 and ADH3 alleles is found across the different races [3]. With 85% of Caucasians having the ADH2*1 allele and 85% of Asians having the ADH2*2 allele [3]. The coding provided by the ADH2*2 have significantly higher reaction rate, i.e. alcohol metabolism rate [3]. In fact, one study reviewed in [3] have found that the alcohol elimination rate in male Chinese and Japanese subjects were approximately 20% higher (18% and 24% higher to be specific) than that of Caucasian of similar age, body leanness, and alcohol consumption habits.

What I have Learned from all of this…
50% of Asian has a deficiency in their ALDH2 enzyme [3,4,5]. This deficient ALDH2 enzyme cannot process the acetaldehyde resulting from the metabolism of alcohol. It is the higher acetaldehyde level that cause the flushing response not the blood alcohol level (BAC). This deficiency is almost non-existent in Caucasians [5]. This deficiency has little to do with the tolerance of an individual or how fast they metabolize alcohol.

In other words, how red (flushed) a person gets has little to do with how high their BAC is, or how drunk they are. This deficiency in the ALDH2 enzyme also has little to do with the alcohol metabolism rate.

So next time you see someone flushing after a sip of beer or booze, don’t just assume they’re already drunk. They could simply have different genetic coding.

and lastly, medical journal needs less confusing acronyms for so many different things.

References
[1] Li, T., Yin, S., Crabb, D., O’Connor, S., & Ramchandani, V. (2001). Genetic and Environmental Influences on Alcohol Metabolism in Humans Alcoholism: Clinical and Experimental Research, 25 (1), 136-144 DOI: 10.1111/j.1530-0277.2001.tb02138.x
[2] Erik Jacobsen (1952). The Metabolism of Ethyl Alcohol Pharmacol Rev
[3] Bosron, W., & Li, T. (1986). Genetic polymorphism of human liver alcohol and aldehyde dehydrogenases, and their relationship to alcohol metabolism and alcoholism Hepatology, 6 (3), 502-510 DOI: 10.1002/hep.1840060330
[4] Tamara L. Wall, Charles M. Peterson, Karen P. Peterson, Mona L. Johnson, Holly R. Thomasson, Maury Cole, & Cindy L. Ehlers (1997). Alcohol Metabolism in Asian-American Men with Genetic Polymorphisms of Aldehyde Dehydrogenase Annals of Internal Medicine
[5] Ronald C. Johnson, & Craig T. Nagoshi (1990). Asians, Asian-Americans and alcohol. Journal of Psychoactive Drugs

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16 responses to “I’m not drunk, I just have a deficient enzyme…

  1. Pingback: Plant with anti-intoxication properties now found to reduce alcoholism « Basal Science Clarified·

  2. Thank you for this post. Excellent posting! I´m caucasian, but from sometime ago I´ve acquired this flush in my face when I drink beer! Sometimes I do flush, sometimes I don´t. It does not happen everytime I drink alcohol. Weird! Also, sometimes I do get it just drinking one/two beer! Other times even drinking ten beers I dont flush. I´m about to investigate it out with particular doctor so I can understand if I got this bad enzyme! Thanks for all information provided!. Regards!

    • Rafael, glad you enjoyed the article and found it to be helpful. Genetics is definitely a very interesting but complicated area…

      • Thanks for the Article it was easier to understand than some others. I am a female of 78 years and I have Asian Enzyme Deficiency to the max and I am also allergic to alcohol. My son Is a Professor of Med.& Surgeon and he has the same thing but he isn;t allergic to alcohol, but grass outside etc but re alcohol, he just gets the glow and I think he gets amusing then very tired. We are both Blonde, pale blue eyed,Caucasion people. I live in a retirement village and all my life I’ve had this thing but my son had a background check done on me and 1200 years ago I have a full Chinese ancestor. Now when I have to tell a Dentist or Dr, especially if they are Asian they look shocked for a while, then they realise or ask how old I am and then they lightly put their hand down my cheek or just smile and say “you are like my Mother, or Grandmother, or Aunt and you look so young! Not kidding it’s just how it is. But the fact of looking younger is not much of a prize when I cannot even go to any parties because as soon as everyone starts laughing and talking the smell makes me sick or I feel as if I will faint, When I was 16 a boy spiked a glass of lemonade with gin and I was in hospital for quite a while and had sores etc all over my mouth and down my throat and a few years ago, my Sister In Law had quite a few drinks after her Mum died and was crying and leaning over and talking into my face and all of a sudden I could feel my nose and mouth swelling up and the next thing my husband was yelling “Oh my goodness, Helen’s face is bleeding!” My nose and mouth split open and there was a lot of blood – no fun!! Sorry if this is too long but I haven’t had a chance to speak about this very much as it’s hard to tell people!!! They think it’s not true but it is!!!

  3. Started reading up on alcohol dehydrogenase after references to it on “The Big Bang Theory”, hehehe… Am Asian, tried drinking but of course without much fun or success. Few people believe it when I’ve explained that I go straight to the hangover, no buzz. This article explains & confirms it! Your article described the cause of the Flush with the perfect amount of science. And all this time I thought I couldn’t digest EtOH – what a surprising discovery that maybe I’m a very efficient EtOH metabolizer. Now I can tell people it’s my ALDH gene deficiency *_*

    • You’re right, “Asian Flush” is something that’s brought up a lot in the media. But there isn’t a lot of discussion on the science behind it, so that’s why we decided to write about it. Thanks for your comments and glad you enjoyed the post!

  4. This happens to me, one half a beer or glass of wine and my face, neck, chest and back feel sunburned. I also don’t feel buzzed, no matter how much I drink, but the hangover the next day, wowza. The strange thing is that I’m Caucasian (or at least all of my mother’s family is, not entirely sure about my father). Is it that rare for caucasians?

  5. I’m also Caucasian with some American Indian and Portuguese, but no Asian. I have been suffering from this from the first time I ever took a sip of Alcohol and it still continues. I just always thought I was having some sort of reaction to alcohol, but now it’s so good to know that it’s kind of normal! Well, except for the fact that it’s almost non-existent in Caucasians. Haha. Thank you for writing this!

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  7. If you are Asian and you suffer from these side effects then there is a very good chance you have the deficient enzyme referred to in this article. If you’re not Asian then there’s still a chance the enzyme deficiency is at play, but you may also be suffering from an allergy to alcohol. Determining which is the cause is important whether you’re Asian or not. A great article about Asian flush can be found at (http://www.theasianflush.com/alcohol-flush-reaction/) where you’ll find a full overview of the disorder so you can see whether it applies to you. Good luck all 🙂

  8. Pingback: I’m not drunk, I just have a deficient enzyme… | Sober·

  9. Thank you so much for this. My non-Asian friends think I have a low tolerance for alcohol because my face turns red and then they think I’m drunk. It gets hard with explanations and disagreement, but I know when I am and not drunk. It takes awhile for my red face to go down, but I glad to see I am not the only one that suffer’s from these kinds of situations.

  10. Hello. I am Cathlyn and I am the CMO of Delta Nutrassentials. I came across this article and thought I’d share some information about our company and product as our mission is spreading awareness and improving education about ALDH2 Deficiency within communities.

    We will be launching our patent-pending flagship product, Essential AD2, which is the first product validated through 3rd party, double-blind, placebo controlled clinical data to alleviate acetaldehyde accumulation in those who suffering from ALDH2 Deficiency, who are predominantly East Asians!

    Essential AD2 is a daily nutrassential that reduces acetaldehyde circulating in the blood, which is always higher than normal in those with ALDH2 Deficiency and has long-term health consequences.

    We will be launching our product and website in November.
    In the meantime, check out this video where CEO Amy Chang talks about ALDH2 Deficiency and what it means.

    Thank you for sharing this article and creating awareness of ALDH2 Deficiency, Alcohol Flush and Acetaldehyde!

  11. Sorry if I should have put my comment here – I lost a bit of normal control to read about the thing i’ve had forever!!! Thanks so much at least I got it out of my system. Best Wishes Helen.

  12. Hi all, can anyone tell me a remedy to recover from alcohol dehydro deficiency, socially im affected a lot.

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