Why Do Some People Handle Alcohol Better Than Others?

Author: Rebecca Ortega

Read Time: 1 glass of a 2015 Amavi Cab Franc or 1.5 oz of Laphroaig Quarter Cask

Why Do Some People Handle Alcohol Better Than Others?

If you’re over the legal drinking age, you likely remember a time when you had a sip too many.  Maybe you were at a party, out with friends, or maybe you were alone and  wallowing in self-pity about not getting a lead role in your favorite musical production.  Maybe you “spilled your cookies,” so to speak, in a not-so-private place, and don’t even get me started on the hangover the next morning, right?  The head-pounding, the dizziness, nausea, and sometimes rapid heartbeat is enough for most people to vow, “Never again!”  Until their next night out, of course.

We are not surprised when people can handle their alcohol much better than others, but what if I told you that some people start feeling hungover almost immediately after their first sip?  What if I told you that similar genetic mechanisms that interact with the nuts and bolts of alcohol metabolism cause not one, but both of the phenomena I just mentioned?

Not only that, but neither of these genetic mutations are rare (we call them “polymorphisms” in science-world), each with frequencies of up to 60% in certain geographic populations (5).  To understand how these work, we need a basic understanding of what happens to your favorite cocktail from first sip to last drop.

When you take a sip of that martini, slam that shot, or casually sip that beer, the alcohol in the drink lands in your stomach and is slowly transferred down your gastro-intestinal tract to your small intestine.  Most alcohol is absorbed into the bloodstream here and is processed in the liver.  The rates of absorption and distribution into the liver and other body tissues are affected by many variables, including total body water, fat composition, the alcoholic content of your drink of choice, the rate that your stomach empties, food consumption, and the sex of the drinker (2).  In fact, females experience higher peak blood alcohol-levels than men due to the factors listed previously.

Figure 1. Typical metabolism of ethanol. Two other pathways exist, known as the CYP and catalase pathways, but 90% of ethanol metabolism occurs in the one displayed above.

Once absorbed into the liver, alcohol undergoes what is called “first-pass metabolism”, which is simply just your body’s first shot at getting rid of this stuff before it goes and makes friends with the rest of your tissues and eventually comes back to its hepatic home base.  In liver cells, called hepatocytes, alcohol is first broken down by an enzyme called alcohol dehydrogenase (ADH) into a nasty carcinogenic chemical that is responsible for your hangovers, called acetaldehyde.  From there, acetaldehyde is moved into the infamous cellular powerhouses, mitochondria.  An enzyme called aldehyde dehydrogenase (ALDH2) neutralizes acetaldehyde so this poison can be instead used to make cellular energy.  This process repeats until the alcohol and acetaldehyde are no longer present in the body.

Figure 2. ADH1B*2 Mutation Rates in People with European and East Asian Ancestry

So what of our heavy-weights and our light-weights?  Well, they have special versions of one or both of these enzymes.  Looking at the figure above, we can see that in order for a heavy-weight to “feel” less of their alcohol, they need to be converting it to acetaldehyde and neutralizing it as soon as possible.  There is a mutation in a gene coding for a subunit of ADH that results in an enzyme capable of 40 times greater alcohol turnover.  This mutation, called ADH1B*2, is found in 60-85% of individuals of East Asian descent, yet is found in less than 15% of Europeans (5).

This mutation is thought to have emerged alongside the advent of rice agriculture, creating hot spots of ADH1B*2 in both the Middle East and East Asia3.  Prior to what biodemographers call the “demographic transition” from hunting and gathering to agriculture, humans typically encountered ethanol in the form of fermented fruit, which has a miniscule percent alcohol by volume (ABV).  With agriculture, traditional alcoholic beverages became popular, but even then, traditional drinks such as chicha—better known as saliva beer from the hunter-gatherer Tsimane people in South America— rarely gets above 5% alcohol6.  Modern distillation that came with the advent of industrialization afforded the human race alcoholic beverages up to a hair-raising 95% ABV.  That’s a lot of energy that can be harvested!  So it makes sense that with rising alcohol content, a faster ADH enzyme would be favored, alongside a fast ALDH2.  Unfortunately, no fast-metabolizing ALDH2 exists commonly, so alcohol will never truly “run right through” someone.

However, our heavy-weights may experience less intoxication due to the rapid removal of alcohol from their bloodstream by a fast-ADH.  While in the short-term, this may seem advantageous, individuals with fast-ADH may also suffer an increased risk of head, neck, liver, and other cancers (4,5,7).

So what happens with our light-weights?  Are they simply not metabolizing the alcohol as fast?  Believe it or not, it’s possible that they have the exact same ADH polymorphism as our heavy-weights!  I bet some of you have a friend who becomes beet red in the face after just a few sips, and I’m also willing to bet money on that friend of yours being of Chinese, Japanese, Korean, or Taiwanese descent.  This negative physiological reaction to meager amounts of alcohol is called the “alcohol flush response” or the “Asian glow”, since it is present in 30 to 60% of individuals of East Asian origin5.  The flush response involves unpleasant symptoms including increased heart rate, a heightened sense of intoxication, nausea, and the most conspicuous side-effect, facial reddening (1,5).  The origin of flushing is acetaldehyde, the notorious hangover chemical mentioned previously.  Now, based on our knowledge of alcohol metabolism pictured above, we see that there are two potential sources of acetaldehyde build-up: an ADH that works too well, or an ALDH2 that doesn’t work well, if at all.

As it turns out, a “broken” ALDH2 enzyme is the key to the mechanics (…err or lack thereof) of the flush response.  A switch of a single base in DNA within the ALDH2 gene yields an enzyme (ALDH2*2) with less than 15% of the activity it should have to neutralize poisonous acetaldehyde1.  This mutation alone is often enough to reduce an individual’s alcohol consumption and afford them 66-99% protection against alcoholism1.

The story for our flushers doesn’t end here, though.  Although ALDH2*2 is the main culprit to this physiological response, a flusher’s acetaldehyde load can be further compounded by the fast-ADH that our heavy-weights may enjoy.  This “acetaldehyde burst protection”1 from individuals carrying both ADH1B*2 and ALDH2*2 results in a rapid influx of blood acetaldehyde the bathes the body’s tissues in the sickening chemical, both accelerating and worsening the symptoms of the Asian glow.

I don’t know about you, but I’d certainly put down my glass after a few sips if this was happening to me, which makes it no surprise that mouse models of fast-ADH flushers reduce their voluntary ethanol consumption by 50-60%1.  Now, not every flusher is the same; they’re special snowflakes just like the rest of us, with symptoms varying widely in severity.  Some flushers (including yours truly!) react so harshly that they cannot drink, let alone have too much alcohol used in the preparation of their food, while others can still handle a beer or two.  This is potentially dangerous for our flushers who still drink, since the carcinogenic action of acetaldehyde increases in a dose-dependent manner, leaving our flushers at increased risk for a multitude of cancers (4,5).

Most individuals who flush listen to their body, either voluntarily or involuntarily, but there is mounting evidence in the literature that perhaps a select subset of flushers can indeed become alcohol-dependent (1).  Because the entire body is bathed in acetaldehyde when a flusher drinks, some of this acetaldehyde ends up in the brain where it sets off a chain reaction in the reward system that ultimately mediates the reinforcing effects of alcohol consumption, in addition to ethanol-seeking after a period of abstinence (1).

So it seems that the question of interest is that of a threshold of tolerance in an individual to peripheral levels of acetaldehyde.  Perhaps, then, some individuals are either genetically, metabolically, or even epigenetically predisposed to have either a much higher threshold of tolerance or an easier time building tolerance to their flush response.  While being able to “put up” with flushing may make the drinking experience more pleasant, this does not in any way change the action of the genes discussed above, so a tolerant flusher’s blood acetaldehyde levels likely do not change in a significant way.  Alcoholic flushers, therefore, may suffer not only from the risk for liver cancer from their addiction, but an additional hazard from continual acetaldehyde exposure subsequent to chronic alcohol use.     So what’s the answer here?  Well, if you are possessed by a flush response, the literature tells us that it may be in your best interest to keep the spirits away.

About the Author

Rebecca Ortega is a graduate student at University of Washington in the Biocultural Anthropology PhD program.  She graduated from Western Washington University in Bellingham with a combined bachelor’s of science in biology and anthropology.  Her previous research was selected for WWU’s Taylor-Anastasio Award for Outstanding Undergraduate Research in 2013, and examined possible co-evolution of the alcohol flush response with local disease ecology in Asia.

She is now focusing on the effects of alcohol consumption, both modern and traditional, on the composition of the microbiome in indigenous and non-indigenous individuals.  By exploring this topic, she hopes to specifically elucidate the community-wide changes associated with alcoholic microbiome dysbiosis, and more broadly explain why a drop in microbiome diversity is observed between individuals from developed industrialized nations and hunter-gatherers.  When her busy schedule permits, Becca is an avid member of the Seattle, Bellingham, and Vancouver, BC blues and fusion dance communities.

Did you enjoy this article? If you love our content and want to help us grow we would love your support. You can support our work HERE via Patreon.

References

1.Israel, Y., M. Rivera-Meza, et al. (2013). Gene specific modification unravel ethanol and acetaldehyde actions. Frontiers in Behavioral Neuroscience, 7:80.

2.Kent, W. (2012). The pharmacokinetics of alcohol in healthy adults. Webmed Central 3(5), WMC003291.

3.Li, H., S. Gu, et al. (2011). Diversification of the ADH1B gene during expansion of modern humans. Ann. Hum. Genet., 75(4):497-507.

4.Liu, J., H-I. Yang, et al. (2016). Alcohol drinking mediates the association between polymorphisms of ADH1B and ALDH2 and hepatitis B related hepatocellular carcinoma. Cancer Epidemiol. Biomarkers Prev., pii: cebp.0961.2015.

5.Tsial, S-T., T-Y. Wong, et al. (2014). The interplay between alcohol consumption, oral hygiene, ALDH2, and ADH1B in the risk of head and neck cancer. International Journal of Cancer, 135(10):2424-2436.

6.Vallejo, J.A., P. Miranda, et al. (2013). Atypical yeasts identified as Saccaromyces cervisiae by MALDI-TOF MS and gene sequencing are the main responsible of fermentation of chicha, a traditional beverage from Peru. Systematic and Applied Microbiology, 36(8):560-4.

7.Zhang, Y., N. Gu, et al. (2015). Alcohol dehydrogenase-1B Arg47His polymorphism is associated with head and neck cancer risk in Asian: a meta-analysis. Tumour Biol., 36(2):1023-7.

One thought on “Why Do Some People Handle Alcohol Better Than Others?

  • It is true that few people can easily handle alcohol, but few people get out of control in just one glass. Thanks for such nice information about the process of body and how it tackles the alcohol. It’s really informative and useful.

Comments are closed.