Alcohol flush reaction

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

The most obvious symptom of alcohol flush reaction is flushing on a person's face and body after drinking alcohol.[4] Other effects include "nausea, headache and general physical discomfort".[9] People who experience the reaction may be less prone to alcoholism as it tends to discourage them from drinking.

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.[10]

Disulfiram, a drug sometimes given as treatment for alcoholism, works by inhibiting acetaldehyde dehydrogenase, causing a five-to ten-fold increase in the concentration of acetaldehyde in the body after drinking alcohol, as happens spontaneously in people subject to flush.[11][12]

${\displaystyle {\ce {H}}{-}{\overset {\displaystyle {\ce {H}} \atop |}{\underset {| \atop \displaystyle {\ce {H}}}{\ce {C}}}}{-}{\overset {\displaystyle {\ce {H}} \atop |}{\underset {| \atop \displaystyle {\ce {H}}}{\ce {C}}}}{\ce {-O-H->[{\ce {ADH}}]H}}{-}{\overset {\displaystyle {\ce {H}} \atop |}{\underset {| \atop \displaystyle {\ce {H}}}{\ce {C}}}}{-}{\overset {\displaystyle {\ce {H}} \atop |}{\underset {\| \atop \displaystyle {\ce {O}}}{\ce {C}}}}{\ce {->[{\ce {ALDH}}]H}}{-}{\overset {\displaystyle {\ce {H}} \atop |}{\underset {| \atop \displaystyle {\ce {H}}}{\ce {C}}}}{-}{\overset {\color {white}{\displaystyle {\ce {H}} \atop |}}{\underset {\| \atop \displaystyle {\ce {O}}}{\ce {C}}}}{\ce {-O-H}}}$

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

Alcohol flush reaction is a condition that is experienced more frequently by people of East Asian descent, giving rise to names such as "Asian flush" or "Asian glow".

Genotype frequency distribution of ALDH2 (rs671).

Around 30–50% of East Asians carry the rs671 (ALDH2*2) allele on chromosome 12, which results in a less functional acetaldehyde dehydrogenase enzyme, responsible for the breakdown of acetaldehyde, and accounts for most incidents of alcohol flush reaction worldwide. According to the analysis by HapMap project, 30% to 50% of people of Chinese, Japanese, and Korean ancestry have at least one ALDH2*2 allele, while it is rare among Europeans and sub-Saharan Africans.[8]

The rs671 allele is native to East Asia and most common in southeastern China. Analysis correlates the rise and spread of rice cultivation in South China with the spread of the allele.[5] 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.[13]

Additionally, in around 80% of East Asians, the rapid accumulation of acetaldehyde is worsened by another gene variant; in this case the allele ADH1B*2, which results in the alcohol dehydrogenase enzyme converting alcohol to toxic acetaldehyde more quickly than other gene variants common outside East Asia.[5][14]

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.[1][7]

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.[7]

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).[15]

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 a breathalyzer test or blood test.[16] 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.