Alcohol.  People have been imbibing beer and wine for millennia, enjoying alcohol ever since someone discovered the altered sensations from fermented fruits and grains.

Archeologists recently announcing the discovery of an Egyptian brewery from the time of the great pyramid.

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

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 (toxic).  Next, the enzyme acetaldehyde dehydrogenase helps convert the acetaldehyde into acetate. This is a somewhat simplified explanation, but it covers the majority of alcohol metabolism.[ref]

Alcohol dehydrogenase is coded for by the ADH genes, and acetaldehyde dehydrogenase by the ALDH genes (there are several).

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?  Well, it is toxic and carcinogenic at certain levels.  So your body wants to get rid of it as soon as possible. Headaches, nausea… you know the drill.

 


ADH1B  – Alcohol dehydrogenase gene:

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

  • TT: faster metabolism of alcohol to acetaldehyde
  • CT: faster metabolism of alcohol to acetaldehyde
  • CC: normal

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…)

ADH1C – Alcohol dehydrogenase 1C gene:

Check your 23andMe results for rs283413 (v4, v5):

  • CC: Normal
  • AC: Slower metabolism of alcohol [ref], thus less likely to be an alcoholic[ref]
  • AA: Slower metabolism of alcohol

ALDH2 – acetaldehyde gene

Check your 23andMe results for rs671 (v4, v5)

  • AA: Alcohol flush reaction, much higher risk of lung cancer from smoking
  • AG: Alcohol flush reaction
  • GG: normal acetaldehyde metabolism

Studies on ALDH2 show:

  • Smokers with AG and AA have a much higher risk of lung cancer than those with GG. [ref] While smoking isn’t healthy for anyone, people with AA really, really shouldn’t smoke.
  • People with the AG and AA 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.

Lifehacks:

The simple answer is that alcohol is a toxin for everyone. Don’t drink it – or at least don’t drink a lot or very often.  (I know that most people are going to ignore me on this one :-)

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]   MitoQ is available on Amazon.

Zinc and niacin (B3) are both co-factors for acetaldehyde dehydrogenase [ref]

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

H2 blockers such as Zantac and 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 ALDH2 variant.  It has NAC, Quercetin (a natural antihistamine), and a couple other supplements in it.


1 Comment

Emily · September 6, 2018 at 2:24 am

This was a great article, thank you!

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