Alcohol flush reaction explained

Alcohol flush reaction
Synonyms:Asian flush syndrome, Asian flush reaction, Asian glow, Asian red face glow
Field:Toxicology
Frequency:36% of East Asians[1] [2]

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.[3]

This syndrome has been associated with lower than average rates of alcoholism, possibly due to its association with adverse effects after drinking alcohol.[4] However, it has also been associated with an increased risk of esophageal cancer in those who do drink.[5] [6]

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]

Signs and symptoms

The most obvious symptom of alcohol flush reaction is flushing on a person's face and body after drinking alcohol. Other effects include "nausea, headache and general physical discomfort".[7] People affected by this condition show greater reduction in psychomotor functions on alcohol consumption than those without.[8]

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.[9]

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.[10]

Genetics

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".

Around 20–30% 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, 20% to 30% 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.[11]

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.[4] 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.[12]

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.[4] [13]

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.

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.

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]

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.[15] 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

See also

Notes and References

  1. Lee H, Kim SS, You KS, Park W, Yang JH, Kim M, Hayman LL . Asian flushing: genetic and sociocultural factors of alcoholism among East asians . Gastroenterology Nursing . 37 . 5 . 327–336 . 2014 . 25271825 . 10.1097/SGA.0000000000000062 . 206059192 .
  2. Book: Tashiro CJ . Mixed Asian Americans and Health: Navigating Uncharted Waters . Handbook of Asian American Health . Yoo GJ, Le MN, Oda AY . Springer . 2014 . 978-1493913442 . 129–136 (132) .
  3. Brooks PJ, Enoch MA, Goldman D, Li TK, Yokoyama A . The alcohol flushing response: an unrecognized risk factor for esophageal cancer from alcohol consumption . PLoS Medicine . 6 . 3 . e50 . March 2009 . 19320537 . 2659709 . 10.1371/journal.pmed.1000050 . free .
  4. Peng Y, Shi H, Qi XB, Xiao CJ, Zhong H, Ma RL, Su B . The ADH1B Arg47His polymorphism in east Asian populations and expansion of rice domestication in history . BMC Evolutionary Biology . 10 . 1 . 15 . January 2010 . 20089146 . 2823730 . 10.1186/1471-2148-10-15 . 2010BMCEE..10...15P . free .
  5. Web site: 2015-08-28 . Alcohol Flush Signals Increased Cancer Risk among East Asians . 2024-08-18 . National Institutes of Health (NIH) . EN.
  6. Lee CH, Lee JM, Wu DC, Goan YG, Chou SH, Wu IC, Kao EL, Chan TF, Huang MC, Chen PS, Lee CY, Huang CT, Huang HL, Hu CY, Hung YH, Wu MT . 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 . 1347–1356 . March 2008 . 18033686 . 10.1002/ijc.23264 . free .
  7. Web site: Esophageal Cancer and the 'Asian Glow'. Dartmouth Undergraduate Journal of Science. 21 November 2009 . 2016-01-12 . https://web.archive.org/web/20160112231737/http://dujs.dartmouth.edu/fall-2009/esophageal-cancer-and-the-%e2%80%98asian-glow%e2%80%99 . live.
  8. Kim SW, Bae KY, Shin HY, Kim JM, Shin IS, Youn T, Kim J, Kim JK, Yoon JS . The role of acetaldehyde in human psychomotor function: a double-blind placebo-controlled crossover study . Biological Psychiatry . 67 . 9 . 840–845 . May 2010 . 19914598 . 10.1016/j.biopsych.2009.10.005 . 21491905 .
  9. Adams KE, Rans TS . Adverse reactions to alcohol and alcoholic beverages . Annals of Allergy, Asthma & Immunology . 111 . 6 . 439–445 . December 2013 . 24267355 . 10.1016/j.anai.2013.09.016 .
  10. Web site: Disulfiram . MedlinePlus Drug Information . 15 November 2012 . 1 October 2008 . https://web.archive.org/web/20081001224410/http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682602.html . live .
  11. Web site: rs671 is a classic SNP (Single Nucleotide Polymorphism). SNPedia. 18 November 2020. 2018-10-22. https://web.archive.org/web/20181022030021/https://www.snpedia.com/index.php/Rs671. live.
  12. Oota H, Pakstis AJ, Bonne-Tamir B, Goldman D, Grigorenko E, Kajuna SL, Karoma NJ, Kungulilo S, Lu RB, Odunsi K, Okonofua F, Zhukova OV, Kidd JR, Kidd KK . The evolution and population genetics of the ALDH2 locus: random genetic drift, selection, and low levels of recombination . Annals of Human Genetics . 68 . Pt 2 . 93–109 . March 2004 . 15008789 . 10.1046/j.1529-8817.2003.00060.x . Kenneth Kidd . Wiley . 31026948 .
  13. Eng MY, Luczak SE, Wall TL . ALDH2, ADH1B, and ADH1C genotypes in Asians: a literature review . Alcohol Research & Health . 30 . 1 . 22–27 . 2007 . 17718397 . 3860439 .
  14. Wright C, Moore RD . Disulfiram treatment of alcoholism . The American Journal of Medicine . 88 . 6 . 647–655 . June 1990 . 2189310 . 10.1016/0002-9343(90)90534-k .
  15. Ye L . 1969-12-31 . Alcohol and the Asian flush reaction . SURG Journal . 2 . 2 . 34–39 . 10.21083/surg.v2i2.982 . 2291-1367.
  16. Boulton P, Purdy RA, Bosch EP, Dodick DW . Primary and secondary red ear syndrome: implications for treatment . Cephalalgia . 27 . 2 . 107–110 . February 2007 . 17257229 . 10.1111/j.1468-2982.2007.01270.x . 31973969 . free .