Alcohol flush reaction
Other namesAsian flush syndrome, Asian flush reaction, Asian glow, Asian red face glow
Facial flushing. Before (left) and after (right) drinking alcohol. A 22-year-old East Asian man who is ALDH2 heterozygous showing the reaction.[1]
SpecialtyToxicology
Frequency36% of East Asians[2][1][3]

Alcohol flush reaction is a condition in which a person develops flushes or blotches associated with erythema on the face, neck, shoulders, ears, and in some cases, the entire body after consuming alcoholic beverages. The reaction is the result of an accumulation of acetaldehyde, a metabolic byproduct of the catabolic metabolism of alcohol, and is caused by an aldehyde dehydrogenase 2 deficiency.[4]

This syndrome has been associated with lower than average rates of alcoholism, possibly due to its association with adverse effects after drinking alcohol.[5] However, it has also been associated with an increased risk of esophageal cancer in those who do drink.[1][6][7]

The reaction is also termed "Asian flush" due to its frequent occurrence in East Asians, with approximately 30 to 50% of Chinese, Japanese, and Koreans showing characteristic physiological responses to drinking alcohol that includes facial flushing, nausea, headaches and a fast heart rate. The condition may be also highly prevalent in some Southeast Asian and Inuit populations.[1][2][3][8]

Signs and symptoms

The back of an East Asian man showing alcohol flush reaction.

The most obvious symptom of alcohol flush reaction is flushing on a person's face and body after drinking alcohol.[4] Other effects include "nausea, headache and general physical discomfort".[9] People affected by this condition show greater reduction in psychomotor functions on alcohol consumption than those without.[10]

People who experience the reaction may be less prone to alcoholism as it tends to discourage them from drinking.

Many cases of alcohol-induced respiratory reactions, which involve rhinitis and worsening of asthma, develop within 1–60 minutes of drinking alcohol and are due to the same causes as flush reactions.[11]

Disulfiram, a drug sometimes given as treatment for alcoholism, induces effects similar to alcohol flush or hangover causing the disulfiram-alcohol reaction. It inhibits acetaldehyde dehydrogenase, 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.[12][13]

Genetics

Metabolism of alcohol (ethanol) to acetaldehyde (ethanal)
and then to acetic acid (ethanoic acid)

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".

Genotype frequency distribution of ALDH2 (rs671).

Around 30–50% of East Asians carry the rs671 (ALDH2*2) allele on chromosome 12, which results in a less functional acetaldehyde dehydrogenase enzyme, responsible for the breakdown of acetaldehyde, and accounts for most incidents of alcohol flush reaction worldwide. According to the analysis by HapMap 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.[8]

The rs671 allele is native to East Asia and most common in southeastern China. Analysis correlates the rise and spread of rice cultivation in South China with the spread of the allele.[5] 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.[14]

Additionally, in around 80% of East Asians, the rapid accumulation of acetaldehyde is worsened by another gene variant; in this case the allele ADH1B*2, which results in the alcohol dehydrogenase enzyme converting alcohol to toxic acetaldehyde more quickly than other gene variants common outside East Asia.[5][15]

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 has four to eight times the risk of developing esophageal cancer as a drinker not deficient in the enzyme.[1][7]

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.[7]

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).[16]

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.[17] 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.

Differential diagnosis

  • Alcohol-induced respiratory reactions including rhinitis and exacerbations of asthma appear, in many cases, due to the direct actions of ethanol.
  • 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 intense diarrhea, wheezing and weight loss.
  • Red ear syndrome,[18] thought by many to be triggered by alcohol among other causes.
  • Ethanol Patch Test - Place an ethanol-soaked band-aid directly of the skin for 20 mins. The skin will turn red if positive[19]

References

  1. 1 2 3 4 5 Brooks PJ, Enoch MA, Goldman D, Li TK, Yokoyama A (March 2009). "The alcohol flushing response: an unrecognized risk factor for esophageal cancer from alcohol consumption". PLOS Medicine. 6 (3): e50. doi:10.1371/journal.pmed.1000050. PMC 2659709. PMID 19320537.
  2. 1 2 Lee H, Kim SS, You KS, Park W, Yang JH, Kim M, Hayman LL (2014). "Asian flushing: genetic and sociocultural factors of alcoholism among East asians". Gastroenterology Nursing. 37 (5): 327–36. doi:10.1097/SGA.0000000000000062. PMID 25271825. S2CID 206059192.
  3. 1 2 J. Yoo, Grace; Odar, Alan Y. (2014). Handbook of Asian American Health. Springer. p. 132. ISBN 978-1493913442.
  4. 1 2 Brooks PJ, Enoch MA, Goldman D, Li TK, Yokoyama A (March 2009). "The alcohol flushing response: an unrecognized risk factor for esophageal cancer from alcohol consumption". PLOS Medicine. 6 (3): e50. doi:10.1371/journal.pmed.1000050. PMC 2659709. PMID 19320537.
  5. 1 2 3 Peng Y, Shi H, Qi XB, Xiao CJ, Zhong H, Ma RL, Su B (January 2010). "The ADH1B Arg47His polymorphism in east Asian populations and expansion of rice domestication in history". BMC Evolutionary Biology. 10 (1): 15. Bibcode:2010BMCEE..10...15P. doi:10.1186/1471-2148-10-15. PMC 2823730. PMID 20089146.
  6. ↑ Alcohol Flush Signals Increased Cancer Risk among East Asians Archived 2012-02-16 at the Wayback Machine March 23, 2009 News Release – National Institutes of Health (NIH)
  7. 1 2 3 Lee, Chien-Hung; Lee, Jang-Ming; Wu, Deng-Chyang; Goan, Yih-Gang; Chou, Shah-Hwa; Wu, I.-Chen; Kao, Ein-Long; Chan, Te-Fu; Huang, Meng-Chuan; Chen, Pei-Shih; Lee, Chun-Ying (2008). "Carcinogenetic impact of ADH1B and ALDH2 genes on squamous cell carcinoma risk of the esophagus with regard to the consumption of alcohol, tobacco and betel quid". International Journal of Cancer. 122 (6): 1347–56. doi:10.1002/ijc.23264. ISSN 1097-0215. PMID 18033686.
  8. 1 2 "rs671 is a classic SNP (Single Nucleotide Polymorphism)". SNPedia. 18 November 2020. Archived from the original on 2018-10-22.
  9. ↑ "Esophageal Cancer and the 'Asian Glow'". Dartmouth Undergraduate Journal of Science. 21 November 2009. Archived from the original on 2016-01-12.
  10. ↑ Kim, Sung-Wan; Bae, Kyung-Yeol; Shin, Hee-Young; Kim, Jae-Min; Shin, Il-Seon; Youn, Tak; Kim, Jin; Kim, Jong-Keun; Yoon, Jin-Sang (May 2010). "The Role of Acetaldehyde in Human Psychomotor Function: A Double-Blind Placebo-Controlled Crossover Study". Biological Psychiatry. 67 (9): 840–845. doi:10.1016/j.biopsych.2009.10.005. PMID 19914598. S2CID 21491905.
  11. ↑ Adams KE, Rans TS (December 2013). "Adverse reactions to alcohol and alcoholic beverages". Annals of Allergy, Asthma & Immunology. 111 (6): 439–45. doi:10.1016/j.anai.2013.09.016. PMID 24267355.
  12. ↑ "Disulfiram". MedlinePlus Drug Information. Archived from the original on 1 October 2008. Retrieved 15 November 2012.
  13. ↑ Toxicity, Disulfiram at eMedicine
  14. ↑ Oota, Hiroki; Pakstis, Andrew J.; Bonne-Tamir, Batsheva; Goldman, David; Grigorenko, Elena; Kajuna, Sylvester L. B.; Karoma, Nganyirwa J.; Kungulilo, Selemani; Lu, Ru-Band; Odunsi, Kunle; Okonofua, Friday; Zhukova, Olga V.; Kidd, Judith R.; Kidd, Kenneth K. (2004). "The evolution and population genetics of the ALDH2 locus: random genetic drift, selection, and low levels of recombination". Annals of Human Genetics. Wiley. 68 (2): 93–109. doi:10.1046/j.1529-8817.2003.00060.x. ISSN 0003-4800. PMID 15008789. S2CID 31026948.
  15. ↑ Eng MY, Luczak SE, Wall TL (2007). "ALDH2, ADH1B, and ADH1C genotypes in Asians: a literature review". Alcohol Research & Health. 30 (1): 22–27. PMC 3860439. PMID 17718397.
  16. ↑ Wright C, Moore RD (June 1990). "Disulfiram treatment of alcoholism". The American Journal of Medicine. 88 (6): 647–55. doi:10.1016/0002-9343(90)90534-K. PMID 2189310.
  17. ↑ "Alcohol and the Asian flush reaction | Ye | Studies by Undergraduate Researchers at Guelph". Archived from the original on 2014-02-21. Retrieved 2010-07-29.
  18. ↑ Boulton P, Purdy RA, Bosch EP, Dodick DW (February 2007). "Primary and secondary red ear syndrome: implications for treatment". Cephalalgia. 27 (2): 107–10. doi:10.1111/j.1468-2982.2007.01270.x. PMID 17257229. S2CID 31973969.
  19. ↑ Brooks, P.J., Enoch, M., Goldman, D., et al. (2009) The Alcohol Flushing Response: An Unrecognized Rish Factor for Esophageal Cancer from Alcohol Consumption. PLOS Medicine. https://doi.org/10.1371/journal.pmed.1000050
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