Today it is widely known that the population of Asia – Chinese, Koreans, Indians, Mongols, peoples of the far north – have difficulties with drinking alcohol. The reason for this is the absence of alcohol dehydrogenase in their blood. Actually, this is not true. They have this enzyme, otherwise, ethanol, which is produced in the body, could not be metabolized (1). 

But, at the same time, these nationalities get drunk much faster, it is very pronounced and they much more often suffer from a hangover than other parts of the world’s population. Moreover, to be completely drunk, they need very little alcohol. Why is this happening?

To start with, there are actually two ferments responsible for metabolizing alcohol in the body. The first is alcohol dehydrogenase (ADH) (2), which is found in liver cells and has many roles in the body. The major function is to catalyze the oxidation of ethanol to acetaldehyde as the first step in the metabolism of ethanol in the liver. Alcohol dehydrogenase acts as our organism`s primary defence against ethanol, a very toxic molecule that inhibits the nervous system and destroys all the organism. ADH converts the alcohol to acetaldehyde by the oxidation of NAD+ to NADH (3). This metabolic compound is very toxic and active (4). While the concentration of acetaldehyde in the blood is much lower than the concentration of ethanol itself, the toxic effect on the body of acetaldehyde is much higher than that of alcohol. It is acetaldehyde that is the main cause of the symptoms of toxic body poisoning – a hangover. Aldehyde is removed by the second enzyme in liver cells, aldehyde dehydrogenase (ALD) (5). ALD takes away hydrogen from the aldehyde and the dangerous toxin turns into a harmless acetic acid. Acetic acid can be removed from the organism or used by it in some chemical reactions. 

Thus, these two ferments are responsible for the excretion of alcohol from the body and all mutations that can break the work of these genes are extremely dangerous for all people and animals. 

But there is so-called allele polymorphism – the appearance of gene variants encoding enzymes that differ from the “correct” variant. They can be physiological or pathological, have different reaction rates, etc. Therefore, scientists talk about “fast” and “slow” alleles of dehydrogenases (6). It is known that the “fastest” allele of alcohol dehydrogenase is a gene variant called ADH1B*47His. The enzyme “produced” by him will convert alcohol into ethyl aldehyde the fastest. And the slowest allele of aldehyde dehydrogenase is ALDH2*2. Accordingly, their carriers will experience the most severe, acute and longest alcohol poisoning (1).

The combination of these two alleles gives the ability to get drunk very quickly. For example, around 80% of East Asians carry an allele of the gene coding for the enzyme alcohol dehydrogenase called ADH1B*47His, which results in the alcohol dehydrogenase enzyme converting alcohol to toxic acetaldehyde more quickly than other gene variants common outside of East Asia (6). 

In about 30–50% of East Asians, the rapid accumulation of acetaldehyde is worsened by another gene variant, the mitochondrial ALDH2*2 allele, which results in a less functional acetaldehyde dehydrogenase enzyme, responsible for the breakdown of acetaldehyde. They show characteristic physiological responses to drinking alcohol that includes facial flushing, nausea, headaches and a fast heart rate (7). It turns out that they really quickly get drunk, and they need to drink much less for this than the Ukrainians, British or Africans.

The good news is that because of aldehyde dehydrogenase deficiency, alcoholism and alcohol-related cancers are much less prevalent in East Asian populations. This is because people feel so bad after drinking alcohol, they tend to drink very little, if at all (8).

The same time if you do have alcohol or aldehyde dehydrogenase allele mutation, but still drink, you are at a higher risk of alcohol-related cancers, such as cancer of the esophagus (the tube between your mouth and your stomach) (8). Also, as for Asians, there is evidence that, due to the lack of alcohol dehydrogenase, they have an increased risk of developing steatohepatitis, cancer, Alzheimer’s disease, etc. Drinking too much can lead to glycogen depletion, which would be aggravated in the presence of liver disease, and may lead to acidosis and hypoglycemia. Chronic drinking results in rising of the ALD level, which encompasses fatty liver, steatohepatitis, liver fibrosis, and cirrhosis and may proceed to hepatocellular carcinoma (2). In addition, people who drink heavily tend to have hyperuricemia after alcohol ingestion and exhibit hypertriglyceridemia, which may exacerbate diabetic hypertriglyceridemia.

What can be a cure for such people? It is known that the natural amount of NAD is depleted as a person abuses drugs and alcohol. This makes it more difficult for them to convert the energy that is broken down from food (2). It is even speculated that people who naturally produce less NAD are more likely to develop an addiction and potentially a co-occurring disorder. Thus, an NADH supplement, as an additional source to create NAD+ may be recommended for these patients to reduce the risks of alcohol and to alleviate the condition. At the same time, if the patient has both of allele mutations, then except for the rising of toxic aldehyde level, NADH can also be accumulated as a product of alcohol metabolism and rise the synthesis of fatty acids, which can lead to oxidative stress, since cytosol shuttles cannot oxidize such an amount of NADH (5). 

In the case of having only one allele mutation then aldehyde can accumulate too, which leads to severe damage to mitochondria and the cell as a whole. The metabolism of NAD is disrupted and the level of both NADH and NAD + falls, the mitochondria cannot produce enough energy and mitochondrial dysfunction develops, which can lead to cell death (6).

In both cases, the human body suffers from intoxication, oxidative stress and lack of energy, which contributes to the occurrence of various diseases of the liver, kidneys, heart, etc. Taking the NADH supplement in these cases can be a protector against different damage, provoked by ethanol. For example, for patients with both mutations, it is better to take NAD + precursors, which can help to restore the NADH / NAD + balance and normalize mitochondrial function. At the same time, taking an NADH supplement in a period when a person doesn’t drink helps to restore the body, increase ATP synthesis, regulate cell survival, repair DNA, recover from oxidative stress (9). 

And for patients with one allele mutation taking NADH for a long period can help to support the ATP level for normal cell functioning,  helps protect cells from damaging agents and free radicals and to maintain metabolic homeostasis (10). 

Thus, taking NADH supplements can be recommended for Asians with alcohol intolerance to help an organism recover after taking ethanol, reduce alcohol flush reaction, as a cytoprotective and anti-aging (also for hepatic cells), antioxidant, ATP booster, to reduce blood pressure, lower lipid peroxidation and normalize lipid profile and simply to avoid a hangover.

Dr. Oksana Klymenko M.D., PhD, 
SNHS Dip. (Holistic Nutrition), Medical Doctor, Researcher in the fields 
of molecular physiology and pathophysiology, 
molecular biology, genetics, cell biology

References

  1. https://dselection.ru/en/kakim-narodam-nelzya-pit-spirtnoe-o-chukotskom-pyanstve.html
  2. https://www.sciencedirect.com/science/article/pii/S166526811932143X
  3. https://www.jstor.org/stable/pdf/4628765.pdf
  4. https://www.sciencedirect.com/topics/chemistry/acetaldehyde
  5. https://www.nature.com/articles/s41598-020-62361-9
  6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1580147/
  7. https://en.wikipedia.org/wiki/Alcohol_flush_reaction
  8. https://theconversation.com/why-do-people-with-east-asian-heritage-get-flushed-after-drinking-alcohol-88767
  9. https://pubmed.ncbi.nlm.nih.gov/15312041/
  10. https://pubmed.ncbi.nlm.nih.gov/12385067/

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