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WATCH: The genetic behind alcohol flush reaction

Alcohol has become a part of people’s lives. People drink when they are happy, excited, sad, or stressed out. It is one of the oldest recreational drugs in use. While many people can handle their drink well, some have extremely unpleasant symptoms when they consume even limited quantities of alcohol.

Alcohol Flush Reaction (AFR) is a condition that causes red patches on the skin after consuming alcohol. These red patches are mostly seen on the cheeks, neck, and shoulders. Sometimes, they can also be seen all over the body. 

If you have East Asian friends and go out for drinks with them, you may have noticed their faces turning red after just a couple of sips of their drinks.

About 30-50% of East Asians, including Koreans, Chinese, and Japanese experience alcohol flush regularly. 

Is alcohol good or bad for health? The controversial aspects of alcohol

According to 100 different studies, moderate consumption of alcohol may reduce the risk of cardiovascular diseases by up to 40%.

The right levels of alcohol consumption also increases healthy High-Density Lipoprotein (HDL) levels in the body 

Moderate drinkers may be at a lower risk of developing type II diabetes than non-drinkers. 

However, when you consume more than four drinks a day, the risks of alcohol consumption may outweigh the benefits.

Genetically, some people can handle their alcohol better and benefit from moderate drinking. For others, even small quantities of alcohol only cause increased health risks. We will discuss this in the later sections.

The Story Behind Drinking Alcohol

Scientists believe that the alcohol flush reaction has its roots in China about 10,000 years ago. This was the same time that agriculture became a staple form of livelihood here and people’s diet changed. Rice became a common food choice.

According to the experts, the change in diet and lifestyle caused changes in the gene makeup of the Chinese population. 

Alcohol flush reaction is a result of such a random change in the genes (gene mutation). It spread from here to neighboring parts of the country and is now very common with East Asians.

It is very rare for non East-Asians to carry this variant (type) of gene.

Alcohol At The Molecular Level- Getting Technical

When you consume alcohol, 90% of its processing happens in the liver. An enzyme called alcohol dehydrogenase converts ethanol into ethanal (acetaldehyde). 

Acetaldehyde is a toxic by-product. Another enzyme called aldehyde dehydrogenase quickly converts this by-product into ethanoate (acetate). 

Before the liver starts processing alcohol (in about 20 minutes after consumption), alcohol is absorbed from the stomach to the bloodstream and reaches the whole body, including the brain.

Some people experience alcohol flush and others don’t because of their genes. 

What happens in people with alcohol flush?

In people with alcohol flush, the body does not produce enough aldehyde dehydrogenase to convert acetaldehyde to acetate. This causes excess accumulation of the toxic acetaldehyde in the body. This leads to the symptoms of alcohol flush including skin blotching, nausea and general feeling of discomfort.

How does alcohol affect your brain?

Alcohol reaches your brain within minutes after you have had your drink.

Your Central Nervous System (CNS) helps with processes like thinking, reasoning, understanding, and motor functions. Alcohol slows down the CNS processes. People experience a foggy mind, inability to remember things, slowed motor functions, and dull hearing after they start drinking because the alcohol affects the nerve cells and makes them slow. 

How fast alcohol affects your brain’s activity can depend on factors like what other drugs you have had before, your age, size, and gender and also your genes.

Did You Know?

If you are a woman, then you are at a higher risk for developing alcohol-related disorders than a man! It sounds unfair but this is true.

Drinking the same amount of alcohol as a man seems to damage the woman’s health more than it does a man’s.

When it comes to alcohol disorder-based deaths, women have 50-100% more mortality rate than men

Women have lesser water content in their body than men. So, the concentration of alcohol in the body of a woman is higher and they get intoxicated faster.

Because of the presence of estrogen, more women experience liver damage because of excess alcohol consumption than men.

Recommended Values

The U.S. Dietary Guidelines for Americans suggest the below recommended values for moderate alcohol consumption.

Adult men - 2 drinks a day

Adult women - 1 drink a day

The recommended values are for normal adults without alcohol flush or alcohol abuse conditions. 

People with alcohol flush reactions will have to limit their alcohol consumption based on how intense their symptoms are. 

What Happens When You Consume Excess Alcohol?

The Body Alcohol Content (BAC) is a measure of how much alcohol has reached your Central Nervous System (CNS). BAC is measured in terms of percentage of alcohol in 100 ml of blood. Below are the values of BAC and their corresponding symptoms.

Alcohol flush is one of the earliest symptoms of alcohol consumption. 

Here are the symptoms of alcohol flushing:

What Happens During Alcohol Withdrawal?

Alcohol is a drug and depending on the tolerance levels and the years of alcohol use, symptoms of alcohol withdrawal may include:

People with alcohol flush reaction are not usually prone to overusing the drug as the side effects discourage them from drinking more. 

Non-genetic Factors Causing Alcohol Flush

Genetic Association

Genetics play an important role in determining whether or not your body can handle alcohol. 

The ALDH2 gene helps produce aldehyde dehydrogenase (ALDH) that converts the toxic acetaldehyde from alcohol into acetate. This step is very important to prevent acetaldehyde accumulation in the body that leads to alcohol flush.

Recommendations For Those With Alcohol Flush Reaction

Summary

Alcohol flush reaction is a condition that causes red patches in the skin, nausea, and general discomfort after a person drinks. This condition is very common in people with East Asian ancestry. As the person continues to drink, the symptoms get worse. Genetics play a very important role in causing alcohol flush reactions.  Knowing your limit, choosing alcohol with lowered ABV and keeping the stomach full and the body hydrated all help bring down the intensity of the condition. Certain medications can help too. 

References

  1. https://www.nationalgeographic.com/magazine/2017/02/alcohol-discovery-addiction-booze-human-culture/ 
  2. https://sciencenetlinks.com/student-teacher-sheets/alcohol-and-your-brain/ 
  3. https://www.nm.org/healthbeat/healthy-tips/alcohol-and-the-brain 
  4. https://www.cdc.gov/alcohol/fact-sheets/moderate-drinking.htm
  5. https://www.alcoholrehabguide.org/alcohol/effects/  
  6. https://medical.23andme.com/wp-content/uploads/2018/01/Alcohol-Flush-Reaction.pdf 
  7. https://www.nycpainspecialists.com/blog/2020/2/13/the-science-behind-the-asian-flush

Our affinity for alcohol is not new; in fact, we developed it ten million years ago, even before we evolved into humans! The natural source of alcohol is fruits, with usually less than 1% of ethanol in ripe fruits and up to 8% in overripe fruits. The presence of alcohol was beneficial both for our primate ancestors as well as the plants that bore the fruits. The strong smell of alcohol traveled far and wide, attracting primates. This helped primates reach food sources while they helped the plants by dispersing the seeds. Alcohol was considered highly beneficial when fruits were its major source. In the present time, where alcoholic drinks are available in large quantities and are consumed in higher concentrations, they tend to do more harm than good.

Alcohol flush reaction: What is it?

The consumption of alcohol in some individuals causes blotches of erythema on their face and neck region, and sometimes on the entire body. Such an event is called an alcohol flush reaction.

Most of the time, it happens as a result of improper digestion of alcohol.

Accumulation of acetaldehyde in the body after alcohol consumption leads to this reaction.

When you consume alcohol, it gets metabolized to its byproduct acetaldehyde.

In typical cases, acetaldehyde gets metabolized further.

An enzyme called aldehyde dehydrogenase, coded by the gene ALDH2, is responsible for this metabolism.

However, some individuals have a defective gene that prevents the further metabolism of acetaldehyde.

This causes its accumulation in the body resulting in an alcohol flush reaction.

More about the enzyme

There are two types of enzymes responsible for the breakdown of alcohol: alcohol dehydrogenase (ADH) and aldehyde dehydrogenase. Acetate is synthesized with the help of aldehyde dehydrogenases (ALDH), mostly by ALDH2, a mitochondrial enzyme, but also by ALDH1, the cytosolic enzyme. 

There are five different types of ADH enzymes based on structural similarity and kinetic properties. 

Class I enzymes: The class I enzymes are coded by the ADH1A, ADH1B, and ADH1C genes, which are associated with about 70% of the total ethanol oxidizing capacity.

II: The class II enzymes are coded by the ADH4 gene, which is associated with about 30% ethanol oxidizing capacity. 

III: The class III enzymes are coded by the ADH5 gene and is the only class of enzyme that is detected in the brain. 

IV: The class IV enzymes are coded by the ADH7 gene and are found mainly in the upper digestive tract, where it oxidizes ethanol at high concentrations. 

V: The class V enzymes coded ADH6 gene are found in a variety of substrates, including retinol but are less efficient in ethanol metabolism.

Who is more prone to alcohol flush?

People of Asian descent, especially the East Asian descent, are more susceptible to have an alcohol flush reaction.

In fact, this red face phenomenon is also called the "Asian flush or "Asian glow."

According to some studies, over 70% of East Asians have genetic polymorphisms in either ADH or ALDH2, leading to intense flushing with ethanol consumption.

What happens during an alcohol flush reaction?

Other than the primary flushing red face, the other symptoms include:

Is the reaction dangerous?

While the flushing by itself may not to be dangerous, the reaction may have other health-related implications.

A 2013 study reported that people who experience an alcohol flush reaction on drinking might have a higher chance of developing hypertension, or high blood pressure.

Another study done on East Asian men in 2017 found an association between high risk of cancer, especially esophageal cancer, and flushing reaction.

This can be due to the high levels of acetaldehyde, which can trigger the growth of cancer cells.

How's it diagnosed?

When you report with suspected alcohol flush reaction, your doctor may first perform a physical examination. Other confirmatory tests also help with the diagnosis.

Skin test 

It detects your allergy, if any, to a substance in alcoholic beverages such as grains like maize, rye, and wheat. 

A little amount of the substance is injected into your skin, and the reaction is studied. If the skin appears red and raised, you are noted positive for the test.

Blood test

A blood test is done to detect the presence of antibodies like IgE that are found in the blood when there is an allergic reaction to a substance in alcohol.

Enzyme test

Measuring the amount of alcohol metabolizing enzymes, alcohol dehydrogenase and aldehyde dehydrogenase, can predict the intensity of reaction that one may experience.

Genetic test

The gene responsible for acetaldehyde metabolism in the body is ALDH2 that produces the enzyme ALDH2 or Aldehyde Dehydrogenase 2. 

Individuals who suffer from an alcohol flush reaction may have a faulty or deficient ALDH2 gene, and this can be identified using genetic testing.

Treating alcohol flush reaction

There is no definitive treatment for the root cause of this reaction, ALDH2 deficiency.

However, there are options when it comes to managing the symptoms.

  1. Antihistamines or histamine blockers can help control facial flushing.
  2. Another treatment, brimonidine, approved by the FDA for treating rosacea (a skin condition that causes redness in your face), can be effective for managing the flushing as well.
  3. Some laser-based therapies are also helpful to control the redness in the face.

Alcohol flush prevention

The only foolproof way to prevent this reaction is to avoid or limit your alcohol intake.

A lot of people tend to use OTC antihistamines to manage the reaction, but this is strongly not advisable.

The first and foremost step is to recognize your risk for this condition by studying your ALDH2 gene variants.

Check your 23andMe raw data or your Ancestry DNA raw data to find out the variant you carry

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According to the variant you carry, you might need to limit or discontinue alcohol consumption.

Other unwanted reactions to alcohol consumption addressed

Why do I bleed after a night of drinking?

Alcohol irritates the gastric lining.

When you drink alcohol, even a small quantity of it, it causes your stomach to produce acid.

Consumption of excess alcohol leads to increased production of stomach acid, which can lead to gastritis.

In many cases, due to excess alcohol, it triggers pain in the stomach, causes diarrhea, vomiting, and even bleeding.

Why do my ears burn when I drink alcohol?

Alcohol affects almost all parts of our body.

Consumption of excess alcohol affects the part of the brain that controls hearing.

In fact, alcohol consumption affects ears and hearing in more than one way.

When we drink alcohol, it also gets absorbed in the fluid of our ears and causes a burning sensation.

Does alcohol cause hot flashes?

Alcohol causes hot flashes in women, especially those going through menopause.

Does alcohol increase body temperature?

Having even a few sips of alcohol can make you feel warmer.

This is because alcohol makes the blood vessels underneath your skin dilate and increases the blood flow in them, which can induce the 'warm feeling.'

But in reality, alcohol reduces your core temperature.

What are some steps to reduce alcohol consumption?

Reducing alcohol consumption can immensely improve your health. Here is a list of a few things you can do to help you reduce drinking:

  1. Keep track of your drinking habits, and change them if warranted
  2. Drink slowly and hydrate yourself with water between drinks
  3. Switch to low alcohol alternatives
  4. Avoid salty snacks such as peanuts, as they make you more thirsty leading you to consume more alcohol
  5. Space out your drinks along with lots of food
  6. Watch out for peer-pressure and avoid any triggers
  7. Don't be shy to reach out for support

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Updated 05 May 2020

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