Alcohol Flush Reaction
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Alcohol flush reaction is a condition in which a person develops flushes or blotches associated with
erythema Erythema (from the Greek , meaning red) is redness of the skin or mucous membranes, caused by hyperemia (increased blood flow) in superficial capillaries. It occurs with any skin injury, infection, or inflammation. Examples of erythema not asso ...
on the face, neck, shoulders, and in some cases, the entire body after consuming
alcoholic beverages An alcoholic beverage (also called an alcoholic drink, adult beverage, or a drink) is a drink that contains ethanol, a type of alcohol that acts as a drug and is produced by fermentation of grains, fruits, or other sources of sugar. The cons ...
. The reaction is the result of an accumulation of acetaldehyde, a metabolic byproduct of the
catabolic Catabolism () is the set of metabolic pathways that breaks down molecules into smaller units that are either oxidized to release energy or used in other anabolic reactions. Catabolism breaks down large molecules (such as polysaccharides, lipid ...
metabolism of alcohol, and is caused by an aldehyde dehydrogenase 2 deficiency. This syndrome has been associated with lower than average rates of alcoholism, possibly due to its association with adverse effects after drinking alcohol. However, it has also been associated with an increased risk of esophageal cancer in those who do drink. "Asian flush" is common in
East Asians East Asian people (East Asians) are the people from East Asia, which consists of China, Taiwan, Japan, Mongolia, North Korea, and South Korea. The total population of all countries within this region is estimated to be 1.677 billion and 21% of t ...
, with approximately 30 to 50% of Chinese, Japanese, and Koreans showing characteristic physiological responses to drinking alcohol that includes facial flushing,
nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
, headaches and a
fast heart rate Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal (su ...
. The condition may be also highly prevalent in some Southeast Asian and
Inuit Inuit (; iu, ᐃᓄᐃᑦ 'the people', singular: Inuk, , dual: Inuuk, ) are a group of culturally similar indigenous peoples inhabiting the Arctic and subarctic regions of Greenland, Labrador, Quebec, Nunavut, the Northwest Territories ...
populations.


Signs and symptoms

The most obvious symptom of alcohol flush reaction is flushing on a person's face and body after drinking alcohol. Other effects include "nausea, headache and general physical discomfort". People who experience the reaction may be less prone to
alcoholism Alcoholism is, broadly, any drinking of alcohol that results in significant mental or physical health problems. Because there is disagreement on the definition of the word ''alcoholism'', it is not a recognized diagnostic entity. Predomi ...
as it tends to discourage them from drinking. Many cases of
alcohol-induced respiratory reactions Alcohol-induced respiratory reactions, also termed alcohol-induced asthma and alcohol-induced respiratory symptoms, are increasingly recognized as a pathological bronchoconstriction response to the consumption of alcohol that afflicts many people w ...
, which involve
rhinitis Rhinitis, also known as coryza, is irritation and inflammation of the mucous membrane inside the nose. Common symptoms are a stuffy nose, runny nose, sneezing, and post-nasal drip. The inflammation is caused by viruses, bacteria, irrita ...
and worsening of
asthma Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, co ...
, develop within 1–60 minutes of drinking alcohol and are due to the same causes as flush reactions.
Disulfiram Disulfiram is a medication used to support the treatment of chronic alcoholism by producing an acute sensitivity to ethanol (drinking alcohol). Disulfiram works by inhibiting the enzyme acetaldehyde dehydrogenase, causing many of the effects of ...
, a drug sometimes given as treatment for alcoholism, works by inhibiting
acetaldehyde dehydrogenase Acetaldehyde dehydrogenases () are dehydrogenase enzymes which catalyze the conversion of acetaldehyde into acetic acid. The oxidation of acetaldehyde to acetate can be summarized as follows: Acetaldehyde + NAD+ + Coenzyme A ↔ Acetyl-CoA + NA ...
, 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.


Genetics

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". Around 30–50% of East Asians carry the rs671 (ALDH2*2) allele on chromosome 12, which results in a less functional
acetaldehyde dehydrogenase Acetaldehyde dehydrogenases () are dehydrogenase enzymes which catalyze the conversion of acetaldehyde into acetic acid. The oxidation of acetaldehyde to acetate can be summarized as follows: Acetaldehyde + NAD+ + Coenzyme A ↔ Acetyl-CoA + NA ...
enzyme, responsible for the breakdown of acetaldehyde, and accounts for most incidents of alcohol flush reaction worldwide. According to the analysis by
HapMap The International HapMap Project was an organization that aimed to develop a haplotype map (HapMap) of the human genome, to describe the common patterns of human genetic variation. HapMap is used to find genetic variants affecting health, disease a ...
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. The rs671 allele is native to
East Asia East Asia is the eastern region of Asia, which is defined in both Geography, geographical and culture, ethno-cultural terms. The modern State (polity), states of East Asia include China, Japan, Mongolia, North Korea, South Korea, and Taiwan. ...
and most common in southeastern China. 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 ''Entamoeba histolytica'' is an anaerobic parasitic amoebozoan, part of the genus ''Entamoeba''. Predominantly infecting humans and other primates causing amoebiasis, ''E. histolytica'' is estimated to infect about 35-50 million people worldwid ...
''. Additionally, in around 80% of
East Asians East Asian people (East Asians) are the people from East Asia, which consists of China, Taiwan, Japan, Mongolia, North Korea, and South Korea. The total population of all countries within this region is estimated to be 1.677 billion and 21% of t ...
, the rapid accumulation of acetaldehyde is worsened by another gene variant; in this case the allele '' ADH1B*2,'' which results in the
alcohol dehydrogenase Alcohol dehydrogenases (ADH) () are a group of dehydrogenase enzymes that occur in many organisms and facilitate the interconversion between alcohols and aldehydes or ketones with the reduction of nicotinamide adenine dinucleotide (NAD+) to NA ...
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
converting alcohol to toxic acetaldehyde more quickly than other gene variants common outside East Asia.


Pathophysiology

Those with facial flushing due to ALDH2 deficiency may be
homozygote Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...
s, with two alleles of low activity, or
heterozygote Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...
s, 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 Disulfiram is a medication used to support the treatment of chronic alcoholism by producing an acute sensitivity to ethanol (drinking alcohol). Disulfiram works by inhibiting the enzyme acetaldehyde dehydrogenase, causing many of the effects of ...
(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).


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 a breathalyzer test or blood test. Additionally, measuring the amount of alcohol metabolizing enzymes alcohol dehydrogenases and
aldehyde dehydrogenase Aldehyde dehydrogenases () are a group of enzymes that catalyse the oxidation of aldehydes. They convert aldehydes (R–C(=O)) to carboxylic acids (R–C(=O)). The oxygen comes from a water molecule. To date, nineteen ALDH genes have b ...
through genetic testing can predict the amount of reaction that one would have.


Differential diagnosis

*
Alcohol-induced respiratory reactions Alcohol-induced respiratory reactions, also termed alcohol-induced asthma and alcohol-induced respiratory symptoms, are increasingly recognized as a pathological bronchoconstriction response to the consumption of alcohol that afflicts many people w ...
including
rhinitis Rhinitis, also known as coryza, is irritation and inflammation of the mucous membrane inside the nose. Common symptoms are a stuffy nose, runny nose, sneezing, and post-nasal drip. The inflammation is caused by viruses, bacteria, irrita ...
and exacerbations of
asthma Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, co ...
appear, in many cases, due to the direct actions of ethanol. *
Rosacea Rosacea is a long-term skin condition that typically affects the face. It results in redness, pimples, swelling, and small and superficial dilated blood vessels. Often, the nose, cheeks, forehead, and chin are most involved. A red, enlarg ...
, 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 The chemical compound trichloroethylene is a halocarbon commonly used as an industrial solvent. It is a clear, colourless non-flammable liquid with a chloroform-like sweet smell. It should not be confused with the similar 1,1,1-trichloroethane, w ...
(TCE), an organic solvent with suspected carcinogenic properties. *
Carcinoid syndrome Carcinoid syndrome is a paraneoplastic syndrome comprising the signs and symptoms that occur secondary to carcinoid tumors. The syndrome includes flushing and diarrhea, and less frequently, heart failure, vomiting and bronchoconstriction. It ...
– 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.


References


External links

{{Gastroenterology Digestive diseases Health in East Asia
Flush Flush may refer to: Places * Flush, Kansas, a community in the United States Architecture, construction and manufacturing * Flush cut, a type of cut made with a French flush-cut saw or diagonal pliers * Flush deck, in naval architecture * Fl ...
Metabolic disorders East Asia East Asian people