Alcohol flush reaction
Encyclopedia
Alcohol flush reaction or Oriental Flushing Syndrome http://www.foodreactions.org/intolerance/alcohol/index.html (colloquially referred to as Asian Flush, Asian Turn Red Syndrome, Asian Red, Asian Glow, or Lash Rash) is a condition in which the face and/or body experiences flushes or blotches, due to an accumulation of acetaldehyde
. The acetaldehyde accumulation can be caused by a missense
polymorphism
that encodes the enzyme
, acetaldehyde dehydrogenase
(ALDH2
), normally responsible for breaking down acetaldehyde, a product of the metabolism of alcohol. The acetaldehyde accumulation can also be caused by a polymorphism in the gene encoding the ADH1B
enzyme, increasing production of acetaldehyde by more rapid metabolism of alcohol. Flushing, or blushing, is associated with the erythema
(reddening caused by dilation of capillaries) of the face, neck, shoulder, and in some cases, the entire body after consumption of alcohol.
Research has shown that a history of facial flushing when drinking is indicative of ALDH2 deficiency, and that 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.
or famotidine
(such as Zantac or Pepcid AC), may be able to relieve the body of the symptoms if taken 30–60 minutes before drinking. Although, ranitidine has been proven in studies to significantly increase blood alcohol content
levels. Care should be given before driving or operating heavy machinery.
Several hypotheses exist on the true nature of the flush. Unfortunately due to the lack of randomized controlled studies, none has been proven in humans.
One hypothesis that may explain the effects of famotidine (and similar classed drugs) on the skin erythema or redness secondary to alcohol consumption is because the drugs are H2-antagonists or H2 antihistamines, which are used to treat peptic/gastric ulcers. However, H2-antagonists do not actually reduce blood concentrations of histamine, but rather work by blocking the effect of histamine on the H2 receptor, and so this theory is disputed.
Another hypothesis is that acetaldehyde causes the redness and vasodilation, and because the H2-antagonist class of medicine inhibits the ADH enzyme (the conversion from ethanol to acetaldehyde) both in the GI tract and in the liver, the conversion happens at a much slower pace, reducing the effects acetaldehyde has on the drinker. 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).
Although many people with this condition view it as a lifetime inconvenience, some people have suggested that they can condition their body to be more tolerant of alcohol with repeated, moderate drinking, perhaps increasing the concentration of ALDH2 to metabolize acetaldehyde. Unfortunately, acetaldehyde is a known carcinogen; recent research suggests that alcohol flush-afflicted individuals consuming alcohol continually may be at a higher risk for alcohol-related diseases, such as liver and esophageal cancers and digestive tract cancer.
Studies in pinto rats have also shown that consumption of carbohydrates (glucose
and fructose
) significantly increase the metabolism of ethanol through a yet unknown pathway, and without affecting alcohol dehydrogenase activity.
. 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 is intended to discourage alcoholics from drinking.
Persons prone to the condition also have lower blood pressure, perhaps as a result of their much lower levels of drinking alcohol.
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 though 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."
Acetaldehyde
Acetaldehyde is an organic chemical compound with the formula CH3CHO or MeCHO. It is one of the most important aldehydes, occurring widely in nature and being produced on a large scale industrially. Acetaldehyde occurs naturally in coffee, bread, and ripe fruit, and is produced by plants as part...
. The acetaldehyde accumulation can be caused by a missense
Missense mutation
In genetics, a missense mutation is a point mutation in which a single nucleotide is changed, resulting in a codon that codes for a different amino acid . This can render the resulting protein nonfunctional...
polymorphism
Polymorphism
Polymorphism or dimorphism may refer to:-Biology:* Polymorphism , including:** having multiple phenotypes within a population; the switch that determines which phenotype an individual displays can be genetic or environmental...
that encodes the enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
, acetaldehyde dehydrogenase
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:...
(ALDH2
ALDH2
Aldehyde dehydrogenase 2 family , also known as ALDH2, is a human gene found on chromosome 12.-Function:The enzyme encoded by this gene belongs to the aldehyde dehydrogenase family of enzymes that catalyze the chemical transformation from acetaldehyde to acetic acid...
), normally responsible for breaking down acetaldehyde, a product of the metabolism of alcohol. The acetaldehyde accumulation can also be caused by a polymorphism in the gene encoding the ADH1B
ADH1B
Alcohol dehydrogenase 1B is an enzyme that in humans is encoded by the ADH1B gene.The protein encoded by this gene is a member of the alcohol dehydrogenase family. Members of this enzyme family metabolize a wide variety of substrates, including ethanol, retinol, other aliphatic alcohols,...
enzyme, increasing production of acetaldehyde by more rapid metabolism of alcohol. Flushing, or blushing, is associated with the erythema
Erythema
Erythema is redness of the skin, caused by hyperemia of the capillaries in the lower layers of the skin. It occurs with any skin injury, infection, or inflammation...
(reddening caused by dilation of capillaries) of the face, neck, shoulder, and in some cases, the entire body after consumption of alcohol.
Research has shown that a history of facial flushing when drinking is indicative of ALDH2 deficiency, and that an ALDH2-deficient drinker who drinks two beers per day has six to ten times the risk of developing esophageal cancer
Esophageal cancer
Esophageal cancer is malignancy of the esophagus. There are various subtypes, primarily squamous cell cancer and adenocarcinoma . Squamous cell cancer arises from the cells that line the upper part of the esophagus...
as a drinker not deficient in the enzyme.
Mitigating the effects
Anecdotal evidence suggests that ingestion of low doses of heartburn medicine, containing ranitidineRanitidine
Ranitidine is a histamine H2-receptor antagonist that inhibits stomach acid production. It is commonly used in treatment of peptic ulcer disease and gastroesophageal reflux disease . Ranitidine is also used alongside fexofenadine and other antihistamines for the treatment of skin conditions...
or famotidine
Famotidine
Famotidine is a histamine H2-receptor antagonist that inhibits stomach acid production, and it is commonly used in the treatment of peptic ulcer disease and gastroesophageal reflux disease . It is commonly marketed by Johnson & Johnson/Merck under the trade names Pepcidine and Pepcid and by...
(such as Zantac or Pepcid AC), may be able to relieve the body of the symptoms if taken 30–60 minutes before drinking. Although, ranitidine has been proven in studies to significantly increase blood alcohol content
Blood alcohol content
Blood alcohol content , also called blood alcohol concentration, blood ethanol concentration, or blood alcohol level is most commonly used as a metric of alcohol intoxication for legal or medical purposes....
levels. Care should be given before driving or operating heavy machinery.
Several hypotheses exist on the true nature of the flush. Unfortunately due to the lack of randomized controlled studies, none has been proven in humans.
One hypothesis that may explain the effects of famotidine (and similar classed drugs) on the skin erythema or redness secondary to alcohol consumption is because the drugs are H2-antagonists or H2 antihistamines, which are used to treat peptic/gastric ulcers. However, H2-antagonists do not actually reduce blood concentrations of histamine, but rather work by blocking the effect of histamine on the H2 receptor, and so this theory is disputed.
Another hypothesis is that acetaldehyde causes the redness and vasodilation, and because the H2-antagonist class of medicine inhibits the ADH enzyme (the conversion from ethanol to acetaldehyde) both in the GI tract and in the liver, the conversion happens at a much slower pace, reducing the effects acetaldehyde has on the drinker. The idea that acetaldehyde is the cause of the flush is also shown by the clinical use of disulfiram
Disulfiram
Disulfiram is a drug discovered in the 1920s and used to support the treatment of chronic alcoholism by producing an acute sensitivity to alcohol. Trade names for disulfiram in different countries are Antabuse and Antabus manufactured by Odyssey Pharmaceuticals...
(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).
Although many people with this condition view it as a lifetime inconvenience, some people have suggested that they can condition their body to be more tolerant of alcohol with repeated, moderate drinking, perhaps increasing the concentration of ALDH2 to metabolize acetaldehyde. Unfortunately, acetaldehyde is a known carcinogen; recent research suggests that alcohol flush-afflicted individuals consuming alcohol continually may be at a higher risk for alcohol-related diseases, such as liver and esophageal cancers and digestive tract cancer.
Studies in pinto rats have also shown that consumption of carbohydrates (glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
and fructose
Fructose
Fructose, or fruit sugar, is a simple monosaccharide found in many plants. It is one of the three dietary monosaccharides, along with glucose and galactose, that are absorbed directly into the bloodstream during digestion. Fructose was discovered by French chemist Augustin-Pierre Dubrunfaut in 1847...
) significantly increase the metabolism of ethanol through a yet unknown pathway, and without affecting alcohol dehydrogenase activity.
Other effects
Individuals who experience the alcohol flushing reaction may be less prone to alcoholismAlcoholism
Alcoholism is a broad term for problems with alcohol, and is generally used to mean compulsive and uncontrolled consumption of alcoholic beverages, usually to the detriment of the drinker's health, personal relationships, and social standing...
. Disulfiram
Disulfiram
Disulfiram is a drug discovered in the 1920s and used to support the treatment of chronic alcoholism by producing an acute sensitivity to alcohol. Trade names for disulfiram in different countries are Antabuse and Antabus manufactured by Odyssey Pharmaceuticals...
, a drug sometimes given as treatment for alcoholism, works by inhibiting acetaldehyde dehydrogenase
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:...
, causing a five to tenfold increase in the concentration of acetaldehyde in the body. The resulting irritating flushing reaction is intended to discourage alcoholics from drinking.
Persons prone to the condition also have lower blood pressure, perhaps as a result of their much lower levels of drinking alcohol.
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
Aldehyde dehydrogenase
Aldehyde dehydrogenases are a group of enzymes that catalyse the oxidation of aldehydes.- Function :Aldehyde dehydrogenase is a polymorphic enzyme responsible for the oxidation of aldehydes to carboxylic acids, which leave the liver and are metabolized by the body’s muscle and heart...
through genetic testing can predict the amount of reaction that one would have. More crude measurements can be made though 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."
Other similar conditions
- RosaceaRosaceaRosacea is a chronic condition characterized by facial erythema . Pimples are sometimes included as part of the definition. Unless it affects the eyes, it is typically a harmless cosmetic condition...
, 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 trichloroethyleneTrichloroethyleneThe chemical compound trichloroethylene is a chlorinated hydrocarbon commonly used as an industrial solvent. It is a clear non-flammable liquid with a sweet smell. It should not be confused with the similar 1,1,1-trichloroethane, which is commonly known as chlorothene.The IUPAC name is...
(TCE), an organic solvent with suspected carcinogenic properties. - Carcinoid syndromeCarcinoid syndromeCarcinoid syndrome refers to the array of symptoms that occur secondary to carcinoid tumors. The syndrome includes flushing and diarrhea, and, less frequently, heart failure and bronchoconstriction...
– episodes of severe flushing precipitated by alcohol, stress and certain foods. May also be associated with diarrhea, wheezing and weight loss. - Red ear syndromeRed ear syndromeRed ear syndrome is a rare disorder of unknown etiology which was originally described in 1994. It typically involves pain in and around the ear including the pinna and associated autonomic phenomena. The most significant symptom of Red ear syndrome of is cutaneous erythema of the ear ipsilateral...
, thought by many to be triggered by alcohol among other causes.