The relationship between genes and alcohol metabolism
When alcohol is consumed, there are individual differences in the speed at which it is broken down in the body and how it affects people. One of the major factors in these differences is “genes.” Recent genetic research has revealed that the ability to metabolize alcohol is determined by genes. In particular, the ADH1B gene, which breaks down alcohol into acetaldehyde, and the ALDH2 gene , which converts acetaldehyde into acetic acid, play important roles.
Key genes involved in alcohol metabolism
ADH1B (alcohol dehydrogenase 1B) The ADH1B gene determines the activity of the enzyme that converts alcohol into acetaldehyde. Depending on the difference in this gene, some people break down alcohol faster than others。
Fast type (ADH1B*2) : This type is mainly seen in East Asians, and alcohol is quickly converted into acetaldehyde, causing the face to become red easily.
Slow type (ADH1B*1) : Common in Westerners, this type breaks down alcohol slowly so people are less likely to get drunk but tend to drink more.
ALDH2 (aldehyde dehydrogenase 2) The ALDH2 gene produces an enzyme that converts acetaldehyde into harmless acetic acid。
Activated type (ALDH2*1/*1) : Can efficiently break down acetaldehyde, so is less affected by alcohol.
Low activity type (ALDH2*1/*2) : The ability to break down acetaldehyde is low, and the face becomes red immediately after drinking alcohol.
Inactive type (ALDH2*2/*2) : People with this type are unable to break down acetaldehyde, making it difficult for them to drink alcohol.
Common genotypes in Japanese people and alcohol tolerance
It has been reported that approximately 40% of Japanese people have low ALDH2 activity and approximately 5% have inactive ALDH2. For this reason, many Japanese people experience the “flushing reaction” in which their face turns red after drinking alcohol. On the other hand, many people have the fast type of ADH1B, which means that alcohol is quickly converted into acetaldehyde, making them more likely to get drunk.
What genetic testing can tell you
By taking a genetic test, you can find out your ADH1B and ALDH2 types. This will allow you to understand your alcohol tolerance and avoid excessive drinking. People with inactive ALDH2 types are particularly at risk of health problems from alcohol, so they need to be careful.
1. The basics of genes and alcohol metabolism
Alcohol affects people differently. Some people get drunk quickly, while others barely get drunk, even if they drink the same amount. One of the main factors behind this difference is genetic factors. In particular, two genes, ADH1B (alcohol dehydrogenase 1B) and ALDH2 (aldehyde dehydrogenase 2), are deeply involved in alcohol metabolism.
Knowing these genotypes can help you understand how you break down alcohol and help you manage your drinking risks. In recent years, genetic testing technology has advanced, making it possible to analyze alcohol metabolism capabilities from simple saliva or blood samples.
2. Alcohol metabolism
Alcohol is metabolized in the body in the following ways:
Ethanol (alcohol) is converted to acetaldehyde by the action of the ADH1B enzyme.
Acetaldehyde is broken down into harmless acetic acid by the ALDH2 enzyme .
Acetic acid is eventually broken down into water and carbon dioxide and excreted from the body.
If there is a problem with this process, acetaldehyde can accumulate in the body, causing a red face, nausea, and palpitations. People with low activity of the ALDH2 gene in particular are more susceptible to alcohol because the breakdown of acetaldehyde is slower.
3. ADH1B gene polymorphisms and their effects
**The type of ADH1B gene determines how quickly alcohol is converted into acetaldehyde.** There are three main types:
ADH1B*1/*1 (low activity type) : Alcohol is broken down slowly, making it difficult to get drunk, but there is a tendency to become more susceptible to alcohol dependence.
ADH1B*1/*2 (intermediate type) : Alcohol is broken down somewhat quickly.
ADH1B*2/*2 (high activity type) : Quickly converts alcohol into acetaldehyde, making people more susceptible to getting drunk and experiencing a flushing reaction.
Many Japanese people have type 1B*2 ADH, which quickly converts alcohol into acetaldehyde, making them more susceptible to getting drunk.
4. ALDH2 gene polymorphisms and their effects
The type of ALDH2 gene determines the body’s ability to break down acetaldehyde.
ALDH2*1/*1 (active form) : It can quickly break down acetaldehyde, so it is less affected by alcohol consumption.
ALDH2*1/*2 (low activity type) : The breakdown of acetaldehyde is slow, causing the face to turn red after drinking alcohol (flushing reaction).
ALDH2*2/*2 (inactive type) : The body is barely able to break down acetaldehyde, making it extremely difficult to drink alcohol.
In particular , people with ALDH2*2 type often experience a rapid heart rate and nausea even with a small amount of alcohol . This is due to the accumulation of acetaldehyde.
5. Genotype distribution and alcohol tolerance in Japanese people
According to research, the genotype ratios of Japanese people are as follows:
**ALDH2 active type (ALDH2 1/1): approximately 55%
**ALDH2 low activity type (ALDH2 1/2): approximately 40%
**ALDH2 inactive type (ALDH2 2/2): approximately 5%
In other words, while roughly half of Japanese people have the genetic makeup that makes them “highly tolerant of alcohol,” more than 40% are likely to have a constitution that makes them “low-tolerant of alcohol.”
6. Benefits of Genetic Testing
The benefits of undergoing genetic testing include:
① Know your alcohol tolerance
You can avoid excessive drinking and find out the appropriate amount that is right for you.
② Health risk management
People with low or inactive ALDH2 activity are at higher risk of esophageal cancer and liver disease, so they may want to reconsider their drinking habits.
3) Preventing alcoholism
People with low ADH1B activity are prone to alcoholism, so they need to be careful about their drinking habits.
7. Genotype and risk of alcohol-related disorders
The fact that the ability to metabolize alcohol is determined by genes is not just related to whether one is “tolerant or tolerant of alcohol,” but is also related to various health risks. In particular, people with low or inactive ALDH2 are known to be at higher risk of alcohol-related diseases.
7-1. Association with esophageal cancer
People with low or inactive ALDH2 genes have a reduced ability to break down acetaldehyde, which remains in the body for a long time after drinking alcohol. Acetaldehyde is a carcinogen, and numerous studies have shown that it increases the risk of esophageal cancer in particular.
Scientific evidence
According to a study by the National Cancer Center , people with low ALDH2 activity have a risk of esophageal cancer that is more than seven times higher than normal ( reference study ).
Epidemiological studies in Japan have shown that people with inactive ALDH2 type who have drinking habits have a particularly high incidence of esophageal cancer.
Therefore, it is important to know the type of ALDH2 gene in order to predict future health risks and review drinking habits.
7-2. Association with liver disease (cirrhosis and liver cancer)
Excessive alcohol intake puts a strain on the liver and can lead to cirrhosis and liver cancer. It is known that the rate at which alcohol is broken down and the metabolic burden it inflicts differ depending on the genotype of ADH1B and ALDH2, and the impact on the liver also differs .
Genotype-specific risks
People with activated ALDH2 (ALDH2*1/*1) tend to drink more alcohol, and chronic drinking increases their risk of liver disease.
For people with low ALDH2 activity (ALDH2*1/*2), even small amounts of alcohol can cause accumulation of acetaldehyde, which puts a strain on the liver.
People with low ADH1B activity (ADH1B*1/*1) metabolize alcohol slowly, and chronic high concentrations of ethanol put a strain on the liver.
Scientific evidence
According to a WHO report , alcohol-related liver disease is closely related to genetic factors in East Asians.
7-3. Association with alcoholism
Alcoholism is known to be caused by both genetic and environmental factors. It has been reported that people with low activity of the ADH1B gene (ADH1B*1/*1) are more likely to experience pleasure when drinking alcohol because alcohol is broken down more slowly, increasing the risk of alcoholism .
Scientific evidence
A US study has shown that people with low activity of ADH1B are more than twice as likely to develop alcohol dependence.
By finding out through genetic testing whether you are predisposed to alcoholism, you can take appropriate measures.
8. Actual procedures and methods of genetic testing
Genetic testing can be easily done at specialized testing institutions. The general process is as follows:
8-1. Genetic testing process
Application : Apply for genetic testing online or at a medical institution.
Sample collection : Saliva and cheek mucosa are collected using a special kit.
Send : Send the sample to the testing facility.
Analysis : Genotypes of ADH1B and ALDH2 were analyzed.
Results : Test results will be sent to you a few weeks later.
8-2. Information obtained through genetic testing
Alcohol metabolism ability (ADH1B, ALDH2 types)
Health risks of drinking alcohol (risk of cancer, liver disease, addiction)
Advice on appropriate drinking habits
9. How to use genetic testing
Based on the results of your genetic test, you may be able to make lifestyle changes, such as:
9-1. Know the appropriate amount of alcohol
By choosing the appropriate amount of alcohol to drink based on your ability to metabolize alcohol, you can minimize the health risks.
9-2. Reducing health risks
In particular, people with low or inactive ALDH2 activity can reduce their risk of cancer and liver disease by reviewing their drinking habits.
9-3. Preventing alcoholism
People with low ADH1B activity can reduce their risk of developing addiction by properly managing their drinking habits.
10. Future Research and Prospects
Due to recent advances in genetic research, new findings about alcohol metabolism are being published one after another. The following themes are attracting attention for future research:
Discovery of new genetic markers : Genes other than ADH1B and ALDH2 may also be involved in alcohol metabolism.
Development of personalized medicine : Establishment of personalized drinking advice based on genotype.
Developing new treatments : The potential of gene therapy to prevent and treat alcoholism.
11. Global distribution of alcohol metabolism genes
The ability to metabolize alcohol varies greatly between different ethnic groups and regions, as genetic factors play a role and certain genotypes tend to be more prevalent in certain regions .
11-1. Genetic characteristics of East Asians
It is known that in East Asia (Japan, China, and Korea), the proportion of people with low or inactive ALDH2 activity is very high .
Distribution of the ALDH2 gene in East Asians
**ALDH2 active type (ALDH2 1/1): approximately 55-60%
**ALDH2 low activity type (ALDH2 1/2): approximately 35-40%
**ALDH2 inactive type (ALDH2 2/2): approximately 5%
It is believed that the reason why East Asians have a high prevalence of low ALDH2 activity is due to the fixation of certain gene mutations during the evolutionary process. In particular, it has been suggested that this may be related to the fact that East Asians have historically consumed a lot of fermented foods .
11-2. Genetic characteristics of Westerners
Westerners (Europeans and Americans) are characterized by having almost no low activity or inactive ALDH2 .
Distribution of ALDH2 genes in Westerners
**ALDH2 active type (ALDH2 1/1): 99% or more
**ALDH2 low activity type (ALDH2 1/2): 1% or less
**Inactive ALDH2 (ALDH2 2/2): Almost zero
Therefore, Westerners tend to have a higher tolerance to alcohol. However, because many of them have low ADH1B activity (ADH1B*1/*1), they tend to be at higher risk of alcoholism .
11-3. Genetic characteristics of Africa, the Middle East, and South Asia
People of African descent : They have a higher incidence of high activity ADH1B, which allows them to break down alcohol quickly and therefore reduces the risk of addiction.
People of Middle Eastern or Indian descent : There is a large variation in genotype depending on the region, but the proportion of ADH1B low activity genotypes is relatively high.
Southeast Asia (Thailand, Vietnam, Philippines, etc.) : Low activity of ALDH2 is present in some populations, but is not as common as in East Asia.
12. Relationship between genotype and alcohol sensitivity
The way alcohol affects you depends on your genotype. There are the following types:
12-1. Highly alcohol-resistant type
**ADH1B low activity type (ADH1B 1/1) + ALDH2 active type (ALDH21/1)
It breaks down alcohol slowly, so you won’t get drunk easily.
High risk of addiction
12-2. Slightly tolerant to alcohol
**ADH1B highly active type (ADH1B 2/2) + ALDH2 active type (ALDH21/1)
Alcohol is broken down quickly, but is not affected by acetaldehyde
Your face won’t turn red after drinking, so you can drink comfortably.
12-3. People who are sensitive to alcohol
**ADH1B high activity type (ADH1B 2/2) + ALDH2 low activity type (ALDH21/2)
The breakdown of acetaldehyde is slow, so your face turns red soon after drinking alcohol.
Alcohol consumption increases risk of esophageal cancer
12-4. People who can barely tolerate alcohol
**ADH1B highly active type (ADH1B 2/2) + ALDH2 inactive type (ALDH22/2)
Even small amounts of alcohol can cause palpitations and nausea
I can barely tolerate alcohol
13. Health management using genetic testing
13-1. Drinking rules based on genotype
Depending on the results of your genetic test, you may be able to set drinking rules, such as:
Genotype
Recommended drinking rules
ALDH2 active type + ADH1B low active type
Avoid excessive drinking and be aware of the risk of addiction
ALDH2 active type + ADH1B highly active type
Moderate drinking is permitted
ALDH2 low activity type
Reduce alcohol consumption and get regular health checks
ALDH2 inactive type
Abstinence from alcohol is recommended
13-2. Application to preventive medicine
Utilizing information from genetic testing makes the following preventive medical treatments possible:
Early detection of alcohol-related cancer : People with low ALDH2 activity should undergo regular endoscopic examinations.
Make liver function tests a habit : People with a genetic type that puts a strain on the liver should have regular blood tests.
Addiction prevention : People with low ADH1B activity learn to control their drinking habits.
14. Future genetic research and alcohol metabolism
In recent years, as genetic research has progressed, new genes involved in alcohol metabolism have been discovered.
14-1. Discovery of new genetic markers
CYP2E1 gene : Involved in the process of metabolizing alcohol in the liver.
GABRA2 gene : Associated with risk of alcoholism.
14-2. The potential of gene therapy
Treatments for people with inactive ALDH2 are being investigated, which may in the future reduce the effects of drinking alcohol.
15. Genotype-based drinking risk management
By utilizing the results of genetic testing, it is possible to establish optimal drinking habits for each individual. Here, we will introduce appropriate drinking risk management methods for each genotype .
15-1. Risk management for people with activated ALDH2 (ALDH2 1/1)
People with this genotype tend to have a higher tolerance to alcohol because they can break down acetaldehyde quickly . However, if they are not careful, they may drink more alcohol and have a higher risk of long-term health problems.
Countermeasure
・ Take two days off from drinking alcohol per week ・ Drink plenty of water when drinking alcohol to reduce the effects of alcohol. ・ Have regular liver function tests (AST, ALT, γ-GTP, etc.). ・ Limit your daily alcohol intake to less than one cup of sake.
15-2. Risk management for people with low ALDH2 activity (ALDH2 1/2)
People with this type of alcoholic beverage tend to have red faces after drinking alcohol because the breakdown of acetaldehyde is slow . The accumulation of acetaldehyde increases the risk of cancer, so careful management is required.
Countermeasure
・ Limit your drinking frequency to no more than twice a week ・ Avoid strong alcohol (shochu, whiskey, vodka, etc.) and choose low-alcohol drinks ・ As you are at higher risk of esophageal cancer, undergo regular endoscopic examinations after the age of 40 ・ When drinking alcohol, take B vitamins (especially B1 and B6) to support liver function
15-3. Risk management for people with inactive ALDH2 (ALDH2 2/2)
People with this type of alcohol disorder are almost completely unable to break down acetaldehyde, posing a significant risk to their health when they consume alcohol.
Countermeasure
・ It is generally recommended to abstain from alcohol (even small amounts are harmful to the body) ・ If forced to drink alcohol, use non-alcoholic drinks ・ Get regular liver and esophageal checkups (cancer risk management） ・ Consult with family and doctors to establish a lifestyle without drinking alcohol
16. Relationship between genotype and alcohol intake
Recent studies have shown that natural alcohol intake varies based on genotype .
Genotype
Average amount of alcohol consumed per week
Health risks
ALDH2 active type + ADH1B low active type
High (approximately 14 to 21 units)
High risk of liver cirrhosis and addiction
ALDH2 active type + ADH1B highly active type
Moderate (approximately 7-14 units)
Moderate drinking is permitted
ALDH2 low activity type
Low (approximately 3 to 7 units)
Even small amounts can cause cancer
ALDH2 inactive type
Nearly zero
Abstinence from alcohol is recommended
(1 unit = about 1 cup of sake or 1 medium mug of beer)
As such, natural drinking tendencies vary depending on genotype, so it is important to develop appropriate drinking habits based on the results of genetic testing .
17. Methods for improving alcohol metabolism taking into account genotype
Although alcohol metabolism capacity is determined by genotype, it is possible to improve metabolic capacity to some extent by improving lifestyle habits .
17-1. Nutrients that enhance the body’s detoxification function
You can reduce the burden caused by drinking alcohol by actively consuming nutrients that help the enzymes that break down alcohol .
Nutrients and foods that improve liver function
Nutrients
Effect
Foods included
Vitamin B1
Supports alcohol breakdown
Pork, brown rice, soybeans
Vitamin B6
Improving liver function
Bananas, nuts, chicken
Cysteine
Accelerates the breakdown of alcohol
Eggs, garlic, onions
Curcumin
Suppression of liver inflammation
Turmeric
17-2. Lifestyle habits to reduce the effects of alcohol
To minimize the effects of alcohol, try to follow these habits:
・ Drink plenty of water before drinking alcohol (to prevent dehydration) ・ Avoid drinking on an empty stomach (to reduce stress on the stomach) ・ Avoid drinking on an empty stomach (to reduce stress on the stomach) ・ Avoid exercising after drinking alcohol (to reduce stress on the liver）
18. The future of genetic testing and personalized medicine
With recent advances in genetic research, personalized medicine is becoming increasingly important .
18-1. Drinking risk management using genetic information
In the future, it is likely that optimal drinking habits and health management methods will be suggested based on an individual’s genotype .
Potential technological innovations ・ Genotype-specific drinking advice via smartphone app ・ Real-time monitoring of alcohol metabolism via wearable devices ・ Development of treatment for inactive ALDH2 using gene editing technology
As these technologies evolve, safer and healthier drinking habits will become possible .
Summary
The ability to metabolize alcohol is largely determined by two genes , ADH1B and ALDH2 . People with low or inactive ALDH2 tend to have red faces after drinking alcohol due to the accumulation of acetaldehyde and are at higher risk of developing cancer. On the other hand, people with low ADH1B activity tend to have a harder time getting drunk and are at higher risk of alcoholism .
By utilizing genetic testing, it is possible to correctly understand one’s alcohol tolerance and establish appropriate drinking habits to protect one’s health . In the future, advances in personalized medicine will enable more precise risk management.
