Alcohol Metabolism - An Introduction
Alcohol metabolism is the process of breaking down ethanol, a type of alcohol used in the production of alcoholic beverages. It is a flammable, colorless liquid. Several enzymes act on ethanol, and this chemical goes through a complex metabolic process from the second it is consumed.
The ability to tolerate alcohol levels depends on factors such as genetic makeup, weight, gender, and nutritional state.
Once alcohol is consumed, about 25% of the content directly reaches the bloodstream from the stomach. The remaining 75% is absorbed from the small intestine.
Most of the alcohol in the body (90-98%) is processed and cleared by the liver. The remaining alcohol content is excreted out through sweat and urine.
Alcohol from the stomach and the small intestine reach the liver through small blood vessels called capillaries. The capillaries send ethanol to the hepatic (liver) cells.
Once ethanol reaches the liver, different enzymes act on it and metabolize it.
There are two significant phases of alcohol metabolism.
Phase 1: Ethanol to acetaldehyde
Phase 1 is the first stage of metabolism. Once ethanol reaches the liver, an enzyme called alcohol dehydrogenase (ADH) starts converting ethanol into acetaldehyde.
Ethanol loses some of its hydrogen molecules when it attaches itself to ADH. As a result, it is converted into another substance called acetaldehyde.
Acetaldehyde is listed as a Group 1 Carcinogen (cancer-causing agent) by The International Agency for Research on Cancer (IARC).
Mild amounts of acetaldehyde in the body lead to hangover symptoms like nausea, vomiting, headaches, and an increased heart rate.
Phase 2: Acetaldehyde to acetic acid
Since acetaldehyde is toxic, the liver rushes to clear it out from the body. The next phase of alcohol metabolism uses an enzyme called acetaldehyde dehydrogenase (ALDH) to clear acetaldehyde.
ALDH is also produced in the liver and converts acetaldehyde into a harmless substance called acetic acid. Acetic acid is also called ethanoic acid.
Acetic acid is later cleared out from the body in the form of carbon dioxide and water.
For a person’s body to process alcohol effectively, both these enzymes need to work effectively.
Alcohol Detoxification Genetic Variations
Alcohol dehydrogenase (ADH) enzyme is produced by two genes - ADH1B and ADH1C.
The ALDH2 gene contains instructions for the production of acetaldehyde dehydrogenase (ALDH).
ADH1B Alcohol Dehydrogenase 1B (class I), Beta Polypeptide
The ADH1B enzyme metabolizes ethanol, retinol, and other types of alcohol. Higher levels of ADH1B protein activity in the body lead to an increased risk of acetaldehyde toxicity.
ADH1C Alcohol Dehydrogenase 1C (class I), Gamma Polypeptide
The ADH1C enzyme also helps in the metabolism of ethanol, retinol, and other types of alcohol.
Low enzyme activity increases alcohol intoxication. Higher enzyme activity can lead to acetaldehyde toxicity.
Aldehyde dehydrogenase 2 (ALDH2)
The ALDH2 enzyme converts acetaldehyde to acetic acid. This enzyme also helps metabolize 4-hydroxynonenal and malondialdehyde and plays a role in preventing oxidative stress.
The Asian Glow
In more than 50% of East Asians, a particular change in the ALDH2 gene leads to lowered levels of ALDH2 enzyme in the body. As a result, the body may not be able to convert acetaldehyde into acetic acid efficiently. This leads to acetaldehyde build-up and extreme symptoms like face flushing, nausea, and increased heart rate.
Increased Blood Alcohol Concentration
Depending on how much ADH is available in the body, people can be rapid, normal, and slow metabolizers of alcohol.
Rapid metabolizers have higher ADH enzymes in the body. As a result, they can handle higher levels of alcohol better (provided acetaldehyde is cleared out efficiently).
Certain changes in the ADH1B and ADH1C genes may lead to a lowered production of ADH. As a result, only limited ethanol molecules are metabolized in the liver. The remaining ethanol molecules are sent back to the bloodstream.
This increases Blood Alcohol Concentration (BAC) and increases intoxication. This condition is common in slow metabolizers.
Below are the effects of different types of the ADH and ALDH2 genes.
| Haplotype | Effects | Implications |
| ADH1B*2 | Increased enzyme activity | Lowered risk of alcohol intoxication |
| ADH1B*3 | Increased enzyme activity | Lowered risk of alcohol intoxication |
| ADH1C*2 | Decreased enzyme activity | Increased risk of alcohol intoxication and hangover symptoms |
| ALDH2 *2 | Decreased enzyme activity | Increased risk of acetaldehyde toxicity |
The *2 and *3 are star alleles. Star alleles are used to name different haplotypes. A haplotype is a group of gene changes that are inherited together.
Alcohol Metabolism and Cancer Risk
Acetaldehyde - a possible carcinogen
As mentioned above, acetaldehyde is a Group 1 Carcinogen. This substance has already shown cancer-causing properties in animal studies.
Acetaldehyde may cause the following changes in the body.
- Acetaldehyde causes chromosomal changes leading to abnormal cell division.
- Acetaldehyde inhibits the enzyme that helps in DNA repair. This leads to DNA damage.
- Acetaldehyde encourages the formation of DNA adducts (A segment of the DNA that attaches to cancer-causing chemicals). DNA adducts increase the risk of cancer formation.
- Higher levels of acetaldehyde in the mouth increase the risk of oropharyngeal cancer.
ALDH2*2 allele
The ALDH2*2 allele is associated with an increased risk for esophagus and oropharynx (the part of the throat behind the oral cavity) cancers.
ADH1B*1 allele
Few studies relate the ADH1B*1 allele with an increased risk for colorectal and squamous cell cancers.
Recommendations To Boost Alcohol Metabolism
Genetic testing
Genetic testing helps understand if a person has a risk for increased or decreased ADH and ALDH enzyme activities in the body. Alcohol consumption can then be moderated based on the results to avoid dangerous side effects.
Genetic testing will also tell if the person is at a higher risk for alcohol-induced damages like liver cirrhosis and cancers because of alcohol consumption.
Foods that increase and decrease ADH and ALDH activities
Here is a list of foods that increase ADH and ALDH activities in the body.
- Musa nana, a banana species native to India, Sri Lanka, and other parts of Southeast Asia, increased ADH activity
- Elaeagnus conferta (wild olive)
- Mangifera indica (mango)
Here is a list of foods that decrease ADH and ALDH activities in the body.
- Prunus salicina juice (Chinese plum)
- Averrhoa carambola juice (star fruit)
- Ribes nigrum juice (blackcurrant)
- Lycopersicon esculentum (tomato)
Video
Summary
- Alcohol metabolism is the process by which alcohol is processed and cleared from the body.
- About 25% of alcohol consumed goes to the bloodstream directly, and 75% reaches the small intestine from where it goes to the liver.
- There are two phases of alcohol metabolism in the liver - ethanol to acetaldehyde and acetaldehyde to acetic acid.
- The first phase uses the alcohol dehydrogenase (ADH) enzyme to convert ethanol to acetaldehyde. In the second phase, the acetaldehyde dehydrogenase (ALDH) enzyme converts acetaldehyde to acetic acid.
- Certain changes in the ADH1B, ADH1C, and ALDH2 genes increase or decrease the activities of these enzymes.
- There are three kinds of alcohol metabolizers based on the levels of ADH and ALDH2 enzymes in the body – rapid, normal, and slow.
- Slow metabolizers struggle with alcohol toxicity and increased Blood Alcohol Concentration (BAC) levels.
- Excess acetaldehyde in the body can increase the risk of developing cancer. Certain types of the ADH1B, ADH1C, and ALDH2 genes also increase the risk for cancer.
- Genetic testing helps know if a person is at higher risk for alcohol intoxication, hangover, or acetaldehyde toxicity.
References
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484320/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761819
