Alcohol flush reaction

Alcohol flush reaction
Other names	East Asian flush syndrome, East Asian flush reaction, East Asian glow
Facial flushing. Before (left) and after (right) drinking alcohol. A 22-year-old East Asian man showing the ALDH2 heterozygote reaction.
Specialty	Toxicology
Frequency	36% (East Asians)

Alcohol flush reaction is a condition in which a person develops flushes or blotches associated with erythema on the face, neck, shoulders, and in some cases, the entire body after consuming alcoholic beverages. The reaction is the result of an accumulation of acetaldehyde, a metabolic byproduct of the catabolic metabolism of alcohol, and is caused by an acetaldehyde dehydrogenase deficiency.

This syndrome has been associated with an increased risk of esophageal cancer in those who drink. It has also been associated with lower than average rates of alcoholism, possibly due to its association with adverse effects after drinking alcohol.

Approximately 36% of East Asians (Chinese, Japanese, and Koreans) show characteristic physiological responses to drinking alcohol that includes facial flushing, nausea, head-aches and tachycardia.

Signs and symptoms

The back of an East Asian man showing alcohol flush reaction.

Individuals who experience the alcohol flushing reaction may be less prone to alcoholism. Disulfiram, a drug sometimes given as treatment for alcoholism, works by inhibiting acetaldehyde dehydrogenase, causing a five to tenfold increase in the concentration of acetaldehyde in the body. The resulting irritating flushing reaction tends to discourage affected individuals from drinking.

For measuring the level of flush reaction to alcohol, the most accurate method is to determine the level of acetaldehyde in the blood stream. This can be measured through both a breathalyzer test or a blood test. Additionally, measuring the amount of alcohol metabolizing enzymes alcohol dehydrogenases and aldehyde dehydrogenase through genetic testing can predict the amount of reaction that one would have. More crude measurements can be made through measuring the amount of redness in the face of an individual after consuming alcohol. Computer and phone applications can be used to standardize this measurement.

Other effects include "nausea, headache and general physical discomfort".

Many cases of alcohol-induced respiratory reactions, which involve rhinitis and worsening of asthma, develop within 1–60 minutes of drinking alcohol and are due to the same causes as flush reactions.

Causes

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Metabolism of alcohol (ethanol) to acetaldehyde (ethanal)
and then to acetic acid (ethanoic acid)

Around 80% of East Asians (less common in Southeast Asia and the Indian subcontinent) have a variant of the gene coding for the enzyme alcohol dehydrogenase called ADH1B, whereas almost all Chinese, Japanese, and Korean people have a variant of the gene called ADH1C, both resulting in an alcohol dehydrogenase enzyme that converts alcohol to toxic acetaldehyde at a much higher efficiency than other gene variants (40- to 100-fold in case of ADH1B).

In about 50% of East Asians, the increased acetaldehyde accumulation is worsened by another gene variant, the mitochondrial ALDH2 allele, which results in a less functional acetaldehyde dehydrogenase enzyme, responsible for the breakdown of acetaldehyde. The result is that affected people may be better at metabolizing alcohol, often not feeling the alcohol "buzz" to the same extent as others, but show far more acetaldehyde-based side effects while drinking alcohol.

Genetics

Genotype frequency distribution of ALDH2 (rs671).

Alcohol flush reaction is best known as a condition that is experienced by people of East Asian descent. According to the analysis by HapMap project, the rs671 allele of the ALDH2 responsible for the flush reaction is rare among Europeans and Sub-Saharan Africans. 30% to 50% of people of Chinese, Japanese, and Korean ancestry have at least one ALDH2 allele. The rs671 form of ALDH2, which accounts for most incidents of alcohol flush reaction worldwide, is native to East Asia and most common in southeastern China. It most likely originated among Han Chinese in central China, and it appears to have been positively selected in the past. Another analysis correlates the rise and spread of rice cultivation in Southern China with the spread of the allele. The reasons for this positive selection aren't known, but it's been hypothesized that elevated concentrations of acetaldehyde may have conferred protection against certain parasitic infections, such as Entamoeba histolytica.

Pathophysiology

Those with facial flushing due to ALDH2 deficiency may be homozygotes, with two alleles of low activity, or heterozygotes, with one low-activity and one normal allele. Homozygotes for the trait find consumption of large amounts of alcohol to be so unpleasant that they are generally protected from esophageal cancer, but heterozygotes are able to continue drinking. However, an ALDH2-deficient drinker who drinks two beers per day has six to ten times the risk of developing esophageal cancer as a drinker not deficient in the enzyme.

The idea that acetaldehyde is the cause of the flush is also shown by the clinical use of disulfiram (Antabuse), which blocks the removal of acetaldehyde from the body via ALDH inhibition. The high acetaldehyde concentrations described share similarity to symptoms of the flush (flushing of the skin, accelerated heart rate, shortness of breath, throbbing headache, mental confusion and blurred vision).

Treatment

Since the mutation is a genetic issue, there is currently no cure for the flush reaction. Clinicians and the East Asian public generally know about the alcohol flushing response. Prevention would include not drinking alcohol.

Similar conditions

• Alcohol-induced respiratory reactions including rhinitis and exacerbations of asthma appear, in many cases, due to the direct actions of ethanol.
• Rosacea, also known as gin blossoms, is a chronic facial skin condition in which capillaries are excessively reactive, leading to redness from flushing or telangiectasia. Rosacea has been mistakenly attributed to alcoholism because of its similar appearance to the temporary flushing of the face that often accompanies the ingestion of alcohol.
• Degreaser's flush—a flushing condition arising from consuming alcohol shortly before or during inhalation of trichloroethylene (TCE), an organic solvent with suspected carcinogenic properties.
• Carcinoid syndrome – episodes of severe flushing precipitated by alcohol, stress and certain foods. May also be associated with intense diarrhea, wheezing and weight loss.
• Red ear syndrome, thought by many to be triggered by alcohol among other causes.

Research

A specific dietary supplement may reduce acetaldehyde in those with the mutated ALDH2 enzyme.