Alcohol flush reaction

Alcohol flush reaction is a condition where the body cannot break down ingested alcohol completely, due to a missense polymorphism that encodes the enzyme, acetaldehyde dehydrogenase (ALDH2), normally responsible for breaking down acetaldehyde, a product of the metabolism of alcohol. Flushing, or blushing, is associated with the erythema (reddening caused by dilation of capillaries) of the face, neck, and shoulder, after consumption of alcohol.

Explanations
Alcohol, as a toxin, can result in cellular damage after prolonged effects. The first step toward metabolizing alcohol is to convert it to acetaldehyde. It has been found that 50% of the Pacific Rim Asian population (Chinese, Japanese, Koreans) possess an atypical alcohol dehydrogenase (ADH) known as ADH2*2 that leads to unusually rapid conversion of ethanol to acetaldehyde. This atypical ADH is less expressed in Caucasians, Africans Americans, Native Americans, and Asian Indian (Agarwal and Goedde, 1992). Since acetaldehyde is more toxic than alcohol, its increased accumulation causes flushing in the human body. Moreover, the normal aldehyde dehydrogenase (ALDH2), synthesized in the liver, oxidizes acetaldehyde into a carboxylic acid, acetic acid. Mutant ALDH2 enzyme (known as ALDH2*2) in 45 to 53 percent of Japanese, Chinese, Korean, Taiwanese, and Vietnamese population, however, is only 8% as effective as the normal, wild-type enzyme (ALDH*1). This mutant allele of ALDH2 is dominant, as it interferes with the formation of a fully functional ALDH2 tetramer.

Approximately half of people of Asian descent are considered to be sensitive to alcohol due to this condition. Flushing, after consuming one or two alcoholic beverages, includes a range of symptoms: dizziness, nausea, headaches, an increased pulse, occasional extreme drowsiness, and occasional skin swelling and itchiness. These unpleasant side effects often prevent further drinking that may lead to further inebriation, but the symptoms can lead to misassumption that the people affected are more easily inebriated than others.

Mitigating the effects
Because this syndrome is a result of DNA mutation, there is no treatment for alcohol flush reaction. However, much anecdotal evidence suggests that consumption of heartburn medicine containing Ranitidine or Famotidine (such as Zantac or Pepcid AC) may be able to reduce the symptoms if taken an hour before drinking.

It is not known why Ranitidine and Famotidine may in some cases, but not all, help reduce the symptoms of the alcohol flush reaction. Alcohol is known to irritate the lining of the stomach and increase production of gastric acid. While Ranitidine functions by reducing gastric acid production in the stomach, it may have an additional (unknown) side effect of inhibiting alcohol dehydrogenase, slowing metabolism of alcohol to acetaldehyde, allowing the poorly functional ALDH2 to metabolize acetaldehyde to acetic acid.

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 rats have also shown that consumption of carbohydrates (glucose & fructose) 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 alcoholism. Antabuse, a drug sometimes given as treatment 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.

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.