Alcohol Genes: Alcohol Metabolism Rate

Alcohol and genes?… People have been imbibing beer and wine for millennia, enjoying alcohol ever since someone discovered the altered sensations from fermented fruits and grains. In fact, archeologists recently announced the discovery of an Egyptian brewery from the time of the great pyramid.

This article examines how alcohol is metabolized and how your genes impact the rate at which it is broken down. I’ll explain how to check your 23andMe or AncestryDNA data for genes related to slow or fast alcohol metabolism.

Alcohol: Breaking it down and getting rid of it

What exactly does alcohol do in our bodies? And why do people react differently to alcohol? (yep – it’s genetic!)

First, alcohol is absorbed through the stomach into our bloodstream, making its way to our brain and to our liver.

In the liver, alcohol is first broken down with an enzyme called alcohol dehydrogenase, which helps to convert it into acetaldehyde.

In the second step of this elimination process, the enzyme acetaldehyde dehydrogenase helps convert the acetaldehyde into acetate. The acetate then can easily be excreted.

This is a  simplified explanation, but it covers the majority of alcohol metabolism.[ref]

Genetics of alcohol metabolism:

The ADH genes code for alcohol dehydrogenase.

The ALDH gene family produces acetaldehyde dehydrogenase.

Two well studied genetic variants have different ways of reaching the same endpoint:

~ an alcohol dehydrogenase (ADH1B) variant that speeds up the conversion to acetaldehyde, thus creating a buildup of acetaldehyde

~ an acetaldehyde dehydrogenase (ALDH2) variant that slows down the conversion from acetaldehyde to acetic acid, again creating a buildup of acetaldehyde.

In addition to the beer, wine, and other alcohol that we might drink, the alcohol dehydrogenase enzyme also breaks down alcohols produced by bacterial fermentation in the intestines. (For example, some of your bug guts could be fermenting the apple you ate this morning, and the ADH genes are activated.)

Retinol (vitamin A) and bile acids are also metabolized by alcohol dehydrogenase.[ref]

Acetaldehyde: flushing, nausea, and carcinogenic

So what is the big deal about too much acetaldehyde? Why does it make you feel cruddy and make you flush?  Acetaldehyde increases skin temperature, making you feel hot and flushed. It also causes nausea, headache, and allergy-like histamine release. Top it off with being carcinogenic and damaging to your DNA. Moreover, it may also be causing catecholamine release in your brain, giving you feelings of euphoria. Your body wants to get rid of it as soon as possible since it is toxic, but the euphoria makes you want to drink again.[ref]


Genetic Variants Related to Alcohol Metabolism:

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ADH1B  – Alcohol dehydrogenase gene:

Check your genetic data for rs1229984 (23andMe v4, v5):

  • TT: faster metabolism of alcohol to acetaldehyde[ref], causes a build-up of acetaldehyde, known aa ADH1B*2 and more common in Asian populations
  • CT: faster metabolism of alcohol to acetaldehyde, causing a build-up of acetaldehyde, known aa ADH1B*2 and more common in Asian populations
  • CC: typical

Members: Your genotype for rs1229984 is .

Studies of this genetic variant show:

  • increased risk of fatty liver disease with alcohol use[ref]
  • increased risk of restless leg syndrome[ref]
  • reduced risk of alcoholism (because people with the variant feel bad when they drink)[ref]
  • the variant is protective against gout[ref] (likely because people without the variant drink more alcohol, leading to gout…)

Check your genetic data for rs2066702 (23andMe v4 only; AncestryDNA):

  • GG: typical
  • AG: faster metabolism of alcohol to acetaldehyde, causing a build-up of acetaldehyde, known ad ADH1B*3 and more common in African populations [ref][ref]
  • AA: faster metabolism of alcohol to acetaldehyde, causing a build-up of acetaldehyde, known ad ADH1B*3 and more common in African populations[ref]

Members: Your genotype for rs2066702 is .

ADH1C gene:

Check your genetic data for rs698 (AncestryDNA):

  • C/C: Increased risk of pancreatitis in alcoholics[ref]; slower conversion of alcohol to acetaldehyde[ref]
  • C/T: Increased risk of pancreatitis in alcoholics; slower conversion of alcohol to acetaldehyde
  • T/T: typical

Members: Your genotype for rs698 is .

ALDH2 – acetaldehyde gene:

Check your genetic data for rs671 (23andMe v4, v5; AncestryDNA):

  • AA: Alcohol flush reaction[ref], a much higher risk of lung cancer from smoking
  • AG: Alcohol flush reaction
  • GG: typical acetaldehyde metabolism

Members: Your genotype for rs671 is .

Studies on ALDH2 show:

  • Smokers with A/G and A/A have a much higher risk of lung cancer than those with G/G.[ref] While smoking isn’t healthy for anyone, people with A/A really, really shouldn’t smoke.
  • People with the A/G and A/A variants (alcohol flush reaction) are much less likely to be alcoholics, probably because they feel so bad when they drink.
  • Candida overgrowth also produces acetaldehyde in amounts close to those considered carcinogenic.[ref]  If you carry the ALDH2 variant and are slow to clear out acetaldehyde, you may be more negatively affected by candida.
  • A little evolutionary science:  You may wonder why the variant is so high in East Asian populations since it seems detrimental. The theory is that alcohol production (from rice cultivation) began in eastern Asia about 16,000 years ago, well before alcohol production in other civilizations. Those carrying the variant were less likely to drink a lot of alcohol and thus were more ‘reproductively fit’, passing on the genetic variant.

Lifehacks for drinking alcohol:

Have you ever wondered how to make alcohol less harmful to your body?

The simple answer is that alcohol is toxic to everyone. Drinking a lot is bad for your body.

I know that many people are going to ignore the ‘don’t drink’ advice, so below are ways to help your body in the clearance of acetaldehyde.

MitoQ, a mitochondrial supplement,  has been shown in studies to enhance acetaldehyde clearance in the liver. “This study demonstrated that speeding up acetaldehyde clearance by preserving ALDH2 activity critically mediates the beneficial effect of MitoQ on alcohol-induced pathogenesis at the gut-liver axis.”[ref]

Zinc and niacin (B3) are both co-factors for acetaldehyde dehydrogenase.[ref] Make sure you have sufficient levels of both through foods or supplements.

Glutathione is also needed for the conversion of acetaldehyde into acetic acid. NAC is a precursor to glutathione.

H2 blockers such as Tagamet can help reduce the flushing symptoms of the ALDH2 variant. Note that this is just helping the flushing and not moving out the acetaldehyde faster.[ref]

 


Extras for Members:

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Related Articles and Genes:

Key Genes to check for Alcoholism
Are there key genes to check for alcoholism? Learn more about the genetic connections to alcohol addiction and what research-backed treatment options are available.

Dopamine Receptors
Dopamine is a powerful player in our cognitive function – impacting mood, movement, and motivation. Genetic variants in the dopamine receptors influence addiction, ADHD, neurological diseases, depression, psychosis, and aggression.

Bipolar Disorder, Depression, Circadian Clock Genes
New research shows that depression and bipolar disorder are linked to changes or disruption in circadian genes. Some people carry genetic variants in the circadian genes that make them more susceptible to circadian disruption.

Lithium Orotate + B12: Boosting mood and decreasing anxiety, for some people…
For some people, low-dose, supplemental lithium orotate is a game-changer for mood issues when combined with vitamin B12. But other people may have little to no response. The difference may be in your genes.

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“Antihistamines Prevent ‘Asian Flush’ — Alcohol-Induced Facial Redness — but Pose Risks.” USC News, 8 Dec. 2016, https://news.usc.edu/112489/antihistamines-prevent-asian-flush-the-red-face-some-people-get-from-alcohol-but-with-huge-risks/.
Butterworth, R. F. “Pathophysiology of Alcoholic Brain Damage: Synergistic Effects of Ethanol, Thiamine Deficiency and Alcoholic Liver Disease.” Metabolic Brain Disease, vol. 10, no. 1, Mar. 1995, pp. 1–8. PubMed, https://doi.org/10.1007/BF01991777.
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Originally published June, 2018. Revised Feb. 2020




Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University and an undergraduate degree in engineering from Colorado School of Mines. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between the research hidden in scientific journals and everyone's ability to use that information. To contact Debbie, visit the contact page.