Alcohol… 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. Does anyone else have ‘Walk Like a (drunk) Egyptian’ running through their minds?
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:
Alcohol dehydrogenase is coded for by the ADH genes. The ALDH gene family produces acetaldehyde dehydrogenase.
There are two well studied genetic variants which 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. (yep – some of your bug guts could be fermenting that apple you ate this morning.)
Retinol (vitamin A) and bile acids are also metabolized by alcohol dehydrogenase.[ref]
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]
ADH1B – Alcohol dehydrogenase gene:
Check your genetic data for rs1229984 (23 and Me 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 buildup of acetaldehyde, known ad ADH1B*3 and more common in African populations [ref][ref]
- AA: faster metabolism of alcohol to acetaldehyde, causing a buildup of acetaldehyde, known ad ADH1B*3 and more common in African populations[ref]
Members: Your genotype for rs2066702 is —.
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 be wondering why the variant is so high in the East Asian populations since it seems to be 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.
The simple answer is that alcohol is toxic to everyone. Drinking a lot is not good 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]
There is a supplement called Sunset Asian Flush that is formulated to prevent the reactions from the ALDH2 variant. It has NAC, Quercetin (a natural antihistamine), and a couple of other supplements in it.
Related Genes and Topics:
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.
Originally published June, 2018. Revised Feb. 2020