Alcohol flush reaction

An Asian man experiences alcohol flush reaction.

Alcohol flush reaction (also known as Oriental flushing syndrome, Asian flush syndrome, Asian flush, Asian glow, among others) is a condition in which an individual's face and/or body experiences flushes or blotches as a result of an accumulation of acetaldehyde, a metabolic byproduct of the catabolic metabolism of alcohol.

This syndrome has been associated with a high risk of esophageal cancer in those who drink.

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.

Causes

Acetaldehyde accumulation may be caused by a missense polymorphism that encodes acetaldehyde dehydrogenase (ALDH2), an enzyme normally responsible for breaking down acetaldehyde.

Acetaldehyde accumulation may also be caused by a polymorphism in the gene encoding the ADH1B enzyme, increasing production of acetaldehyde by more rapid metabolism of alcohol.

Genetics

Alcohol flush reaction is best known as a condition that is experienced by people of Asian descent. According to the analysis by HapMap project, the defective allele of ALDH2 is virtually non-existent among Europeans and Africans, and it is very rare among Mexican-Americans. 30% to 50% of people of Chinese and Japanese ancestry have at least one defective allele. One of the defective forms 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. 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.

Epidemiology

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.

Treatment and prevention

Some sufferers feel that ingestion of low doses of heartburn medicine, containing ranitidine 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. This has not been a subject of scientific study, and was popularized by word of mouth communication and Wikipedia. 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 have 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 (or rather, the lack thereof) 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.^{[citation needed]}

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.

Alcohol consumption should be reduced to avoid esophageal cancer.

Other effects

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 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."

Other similar conditions

• 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 diarrhea, wheezing and weight loss.
• Red ear syndrome, thought by many to be triggered by alcohol among other causes.^{[citation needed]}

External links

• ClinicalTrials.gov NCT00661141 Phase IIa Study of Fomepizole for Acetaldehyde Toxicity After Ethanol Exposure in Subjects With Altered Ethanol Metabolism
• Wall TL, Peterson CM, Peterson KP, et al. (1997). "Alcohol metabolism in Asian-American men with genetic polymorphisms of aldehyde dehydrogenase". Ann. Intern. Med. 127 (5): 376–9. PMID 9273829. http://www.annals.org/cgi/content/full/127/5/376. 
• BBC News Article