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. The most obvious symptom is flushing on a person's face and body after drinking alcohol. 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
Around 80% of East Asians carry an allele of the gene coding for the enzymealcohol dehydrogenase called ADH1B*2, which results in the alcohol dehydrogenase enzyme converting alcohol to toxic acetaldehyde more quickly than other gene variants common outside of East Asia. In about 30–50% of East Asians, the rapid accumulation of acetaldehyde is worsened by another gene variant, the mitochondrial ALDH2*2 allele, which results in a less functional acetaldehyde dehydrogenase enzyme, responsible for the breakdown of acetaldehyde.
Genetics
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*2 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. Another analysis correlates the rise and spread of rice cultivation in South China with the spread of the allele. The reasons for this positive selection are not known, but it has 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 has four to eight times the risk of developing esophageal cancer as a drinker not deficient in the enzyme. Because most East Asians have a variant in the ADH gene, this risk is lowered somewhat because the ADH variant reduces the risk of esophageal cancer four-fold. However, ALDH2-deficient people who do not carry this ADH variant are at the highest risk of cancer as these risk factors act in a multiplicative manner through increasing exposure time to salivary acetaldehyde. The idea that acetaldehyde is the cause of the flush is also shown by the clinical use of disulfiram, which blocks the removal of acetaldehyde from the body via ALDH inhibition. The high acetaldehyde concentrations described share similarity to symptoms of the flush.
Diagnosis
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.
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, 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.
