Is This Alcohol-Metabolizing Gene Responsible For Your Hangovers? (ALDH2)

The ALDH2 gene encodes for part of an enzyme named aldehyde dehydrogenase (ALDH), which is involved in the breakdown of alcohol in the liver.

ADH enzymes are responsible for the first step of alcohol metabolism, where alcohol is converted to potentially toxic acetaldehyde. ALDH enzymes are responsible for the second step, breaking down acetaldehyde to acetic acid.

The ALDH2 gene encodes an enzyme involved in the conversion of potentially toxic acetaldehyde to acetic acid.

ALDH2 variants are thought to influence alcohol consumption and alcohol dependence. Variants can affect ALDH enzyme production and, in turn, the body’s ability to break down acetaldehyde.

Certain ALDH2 variants produce fewer or less active ALDH enzymes, and may reduce the enzyme activity to zero, largely reducing the rate at which acetaldehyde is converted to acetic acid. This can lead to a build-up of acetaldehyde following alcohol consumption. Acetaldehyde build-up is toxic and bad for your health, and can result in negative effects such as [R, R, R]:

• Flushing
• Sweating
• Nausea
• Accelerated heart rate
• Vomiting

More severe ‘hangover’ effects may discourage ALDH2 variant carriers from drinking alcohol. This is in comparison to non-variant carriers, who can drink alcohol without experiencing these symptoms [R].

ALDH2 variants impact the activity of ALDH enzymes, which may lead to negative effects that influence overall alcohol consumption.

A study of 251 Japanese people found that carriers of an ‘A’ allele of the rs671 variant, a SNP in the ALDH2 gene, were more likely to experience a hangover. As a result, carriers drink less and are less likely to be alcohol-dependent than non-carriers [R].

Carriers of the ‘A’ allele have been reported to get drunk faster and are more likely to experience a hangover, especially if they have vitamin B12 deficiency. Vitamin B12 can assist in acetaldehyde breakdown. Variant carriers who drink alcohol with this deficiency may be more at risk of the negative health effects associated with acetaldehyde buildup [R, R].

The rs671 SNP is most prevalent in Asian populations, and is almost non-existent in other populations. 31% of individuals of East Asian descent carry at least one copy of the ‘A’ allele, however less than 1% of any other ethnicity carry a copy [R].

Enzyme activity is completely reduced in those who carry two copies of the ‘A’ allele, and by 50-70% for those who carry one [R].

A study in mice showed that mice lacking ALDH2 avoided alcohol. This was linked to increased brain and blood acetaldehyde levels [R].

Despite the severe hangover effects of rs671, alcoholism in carriers of the variant has increased in Japan, emphasizing the role that environmental factors (such as social pressure) play in alcohol drinking [R].

Carriers of ALDH2 variants are more likely to experience severe hangover effects following drinking, and as a result are more likely to consume less alcohol than non-carriers. However, social pressures may alter this behavior.

Acetaldehyde is toxic and has also been shown to damage DNA. This means that the acetaldehyde buildup caused by drinking alcohol whilst carrying the rs671 variant may inflict nerve pain. This may also put the carrier at increased risk of cancer, such as throat, stomach, liver, bowel, and mouth [R, R, R, R, R].

In fact, one study noted that carriers of the rs671 variant were at 20% higher relative risk of developing cancers than non-carriers, although this was not related to alcohol intake [R].

The rs671 variant has also been linked to:

• Heart disease [R]
• Nonalcoholic fatty liver disease [R]
• Alzheimer’s disease [R]
• Parkinson’s disease [R] 

Drinking alcohol whilst carrying an ALDH2 variant may increase the risk of certain cancers.

SNP Summary and Table

ALDH2 rs671

• ‘AA’ = Associated with a reduced conversion of acetaldehyde into acetic acid, may be associated with flushing, nausea, and worse hangovers when drinking, often resulting in lower alcohol consumption [R]
• ‘AG’ = Associated with a reduced conversion of acetaldehyde into acetic acid, may be associated with flushing, nausea, and worse hangovers when drinking, often resulting in lower alcohol consumption [R]
• ‘GG’ = Associated with normal conversion of acetaldehyde to acetic acid [R]

31% of East Asians carry the ‘A’ allele. The ‘A’ allele is much less common in the rest of the world, where around 1% are carriers [R].