# Alcohol flush reaction

Asian flush as seen on the back
An Asian man suffers alcohol flush reaction.

Alcohol flush reaction (also known as Asian flush syndrome, Asian flush, Asian glow, among others) is a condition in which an individual's face 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 an increased risk of esophageal cancer in those who drink.[1] It has also been associated with lower than average rates of alcoholism, possibly due to its association with adverse effects after drinking alcohol.[2]

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.

## Signs and symptoms

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.[3][4]

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.[5] 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."[6]

## Causes

It is commonly thought that the flush reaction is caused by an inability to metabolize alcohol. To the contrary, around 80% of Asian people (less common in Thailand and India) have a variant of the gene coding for the enzyme alcohol dehydrogenase called ADH1B, and almost all Japanese, Chinese and Korean people have a variant of the gene called ADH1C,[7] both resulting in an alcohol dehydrogenase enzyme that converts alcohol to toxic acetaldehyde at a much higher efficiency than other gene variants (40 to 100-fold in case of ADH1B).[2] In about 50% of Asians, the increased acetaldehyde accumulation is worsened by another gene variant, the mitochondrial ALDH2 allele, which results in a less functional acetaldehyde dehydrogenase enzyme, responsible for the breakdown of acetaldehyde.[7] The result is that affected people may be better at metabolizing alcohol, often not feeling the alcohol "buzz" to the same extent as others, but show far more acetaldehyde-based side effects while drinking.

$\begin{smallmatrix} &\text{H}& &\text{H}& & & &\text{H}& &\text{H}& & &\text{H}& & & \\ & | & & | & &\mathsf{ADH} & & | & & | &\mathsf{ALDH} & & | & & & \\ \text{H}\,-\!&\text{C}&\!-\!&\text{C}&\!-\,\text{O}\,-\,\text{H}&\xrightarrow{\qquad}&\text{H}\,-\!&\text{C}&\!-\!&\text{C}&\xrightarrow{\qquad\ }&\text{H}\,-\!&\text{C}&\!-\!&\text{C}&\!-\,\text{O}\,-\,\text{H}\\ & | & & | & & & & | & & \| & & & | & & \| & \\ &\text{H}& &\text{H}& & & &\text{H}& &\text{O}& & &\text{H}& &\text{O}& \\ \end{smallmatrix}$
Metabolism of alcohol (ethanol) to acetaldehyde (ethanal) and then acetic acid (ethanoic acid)

### 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 rs671 allele of the ALDH2 gene responsible for the flush reaction is rare 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 ALDH2 allele.[8] The rs671 form 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,[9] and it appears to have been positively selected in the past. Another analysis correlates the rise and spread of rice cultivation in Southern China with the spread of the allele.[2] 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.[10]

## Pathophysiology

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 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.[11][12]

## Treatment

Since the mutation is a genetic issue, there is no cure for the flush reaction. Prevention would include not drinking alcohol.

One 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,[13] 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).[14]

## 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,[15] thought by many to be triggered by alcohol among other causes.[citation needed]

## References

1. ^ Alcohol Flush Signals Increased Cancer Risk among East Asians March 23, 2009 News Release - National Institutes of Health (NIH)
2. ^ a b c Yi Peng, Hong Shi, Xue-bin Qi, Chun-jie Xiao, Hua Zhong, Run-lin Z Ma, Bing Su (2010). "The ADH1B Arg47His polymorphism in East Asian populations and expansion of rice domestication in history". BMC Evolutionary Biology 10: 15. doi:10.1186/1471-2148-10-15. PMC 2823730. PMID 20089146.
3. ^ "Disulfiram". MedlinePlus Drug Information. Retrieved 15 November 2012.
4. ^
5. ^ http://www.criticalimprov.com/index.php/surg/article/viewArticle/982/
6. ^ http://dujs.dartmouth.edu/fall-2009/esophageal-cancer-and-the-‘asian-glow’
7. ^ a b http://www.ncbi.nlm.nih.gov/pubmed/17718397
8. ^
9. ^ Hui Li et al (2009). "Refined Geographic Distribution of the Oriental ALDH2*504Lys (nee 487Lys) Variant". Ann Hum Genet 73 (Pt 3): 335–45. doi:10.1111/j.1469-1809.2009.00517.x. PMC 2846302. PMID 19456322.
10. ^ Oota et al (2004). "The evolution and population genetics of the ALDH2 locus: random genetic drift, selection, and low levels of recombination". Annals of Human Genetics.
11. ^ Red Face May Signal Cancer Risk , New York Times, March 23, 2009
12. ^ Brooks PJ, Enoch M-A, Goldman D, Li T-K, Yokoyama A (2009). "The Alcohol Flushing Response: An Unrecognized Risk Factor for Esophageal Cancer from Alcohol Consumption". Public Library of Science Medicine 6 (3): e50. doi:10.1371/journal.pmed.1000050. PMC 2659709. PMID 19320537.
13. ^ Joan Caballería, et al. (1991). "Effects of H2-receptor antagonists on gastric alcohol dehydrogenase activity". Digestive Diseases and Sciences 36 (12): 1673–1679. doi:10.1007/BF01296608. PMID 1684149.
14. ^ Wright C, Moore RD (June 1990). "Disulfiram treatment of alcoholism". Am. J. Med. 88 (6): 647–55. doi:10.1016/0002-9343(90)90534-K. PMID 2189310.
15. ^ Boulton, P; Purdy, RA; Bosch, EP; Dodick, DW (2007). "Primary and secondary red ear syndrome: implications for treatment". Cephalalgia : an international journal of headache 27 (2): 107–10. doi:10.1111/j.1468-2982.2007.01270.x. PMID 17257229.