Alcohol intolerance
Other namesAcute alcohol sensitivity
Skin flushing, a common symptom of alcohol intolerance

Alcohol intolerance is due to a genetic polymorphism of the aldehyde dehydrogenase enzyme, which is responsible for the metabolism of acetaldehyde (produced from the metabolism of alcohol by alcohol dehydrogenase).[1][2] This polymorphism is most often reported in patients of East Asian descent.[3][4][5][6] Alcohol intolerance may also be an associated side effect of certain drugs such as disulfiram, metronidazole, or nilutamide. Skin flushing and nasal congestion are the most common symptoms of intolerance after alcohol ingestion.[5][6] It may also be characterized as intolerance causing hangover symptoms similar to the "disulfiram-like reaction" of aldehyde dehydrogenase deficiency or chronic fatigue syndrome.[7][8][9] Severe pain after drinking alcohol may indicate a more serious underlying condition.[5][10]

Drinking alcohol in addition to consuming calcium cyanamide can cause permanent or long-lasting intolerance (nitrolime disease),[11][12] contributing (in conjunction with other substances) to the accumulation of harmful acetaldehyde in the body by inhibiting the acetaldehyde dehydrogenase enzyme.

Signs and symptoms

Individuals with alcohol intolerance will experience unpleasant reactions immediately after drinking alcohol.[13][5][6] Common signs and symptoms of alcohol intolerance include nasal congestion, skin flushing (redness), headaches, low blood pressure, nausea, and vomiting.[5][6][13]

Causes

Genetics

Alcohol metabolism

ALDH1 is an isozyme of aldehyde dehydrogenase. A structural mutation in the gene of ALDH1, commonly found in East Asians, results in low levels of functional ALDH1 enzyme and thus, higher blood acetaldehyde levels.[14][1][2] Higher blood acetaldehyde levels have been associated with facial flushing caused by an increase in heart rate and blood flow to the face from vasodilation of the blood vessels.[1][2] Individuals that have the ALDH2*2 allele, a variant that has a mutation when compared to the wild-type ALDH2 isozyme, are known to have higher blood acetaldehyde levels.[15][16][2] Individuals that have either mutation in the ALDH1 or ALDH2 genes may have slightly different blood acetaldehyde levels among others carrying a similar mutation and may experience varying degrees of alcohol intolerance symptoms.[17][18][19]

Risk factors

Various genetic and environmental factors exist that can lead to an increased risk for developing alcohol intolerance. Individuals with two copies of the ALDH2*2 allele are known to have high blood acetaldehyde levels and experience “hangover” symptoms such as heart palpitations for longer durations, even with low alcohol consumption.[15][16][2] Individuals who work with DMF have shown a dose-related increase in alcohol intolerance complaints.[20] Exposure to DMF can also cause facial flushing and increased sensitivity to alcohol.[21][22]

Diagnosis

Ethanol patch test

In an ethanol patch test, different concentrations of ethanol are applied onto lint pads and attached to the inner surface of the upper arm for several minutes. If skin redness occurs after 10–15 minutes, the individual is deemed to have a lack of ALDH1 associated with alcohol intolerance.[23]

Difference from alcohol allergy

Alcohol intolerance is not an allergy.[24] There are often misconceptions that alcohol intolerance and alcohol allergy are the same, but they are not. Alcohol intolerance is an inherited genetic disorder that impairs alcohol metabolism.[25] The increased accumulation of acetaldehyde in affected individuals due to deficient aldehyde dehydrogenase enzymes often leads to the characteristic symptom of having flushed skin.[25][26][27] On the other hand, the more uncommon alcohol allergy is an immune system reaction to alcohol (specifically ethanol) that causes symptoms such as rashes, difficulty breathing, and anaphylaxis in severe cases.[28][29] Nausea is a symptom common to both alcohol intolerance and alcohol allergy.[26] Remarkably, inhaled isopropyl alcohol can be used to provide nausea and vomiting relief.[30] [31]

Management

Avoiding or restricting alcohol is the most straightforward way to prevent the symptoms of alcohol intolerance.[5][6][13] Tobacco use or exposure to secondhand smoke should be avoided, as smoking may increase levels of acetaldehyde. Certain medications may interact with alcohol and worsen symptoms. Antacid or antihistamines are used to reduce the symptoms of alcohol intolerance. However, these medications simply mask these symptoms.[32] Reducing alcohol consumption lowers the risk for cancer and other serious diseases.[33][34][35]

See also

References

  1. 1 2 3 Agarwal, Dharam P.; Goedde, H. Werner (1990). Alcohol Metabolism, Alcohol Intolerance, and Alcoholism. pp. 57–59. doi:10.1007/978-3-642-74904-9. ISBN 978-3-642-74906-3. S2CID 46280438.
  2. 1 2 3 4 5 Harada, S.; Agarwal, D.P.; Goedde, H.W. (October 1981). "Aldehyde Dehydrogenase Deficiency as Cause of Facial Flushing Reaction to Alcohol in Japanese". The Lancet. 318 (8253): 982. doi:10.1016/s0140-6736(81)91172-7. ISSN 0140-6736. PMID 6117742. S2CID 6468178.
  3. ↑ Mizuno, Yuji; Morita, Sumio; Harada, Eisaku; Shono, Makoto; Morikawa, Yoshinobu; Murohara, Toyoaki; Yasue, Hirofumi (2013). "Alcohol Flushing and Positive Ethanol Patch Test in Patients with Coronary Spastic Angina: Possible Role of Aldehyde Dehydrogenase 2 Polymorphisms". Internal Medicine. 52 (23): 2593–2598. doi:10.2169/internalmedicine.52.0894. ISSN 0918-2918. PMID 24292747.
  4. ↑ Tsuritani, Ikiko; Ikai, Eriko; Date, Takayasu; Suzuki, Yasuhito; Ishizaki, Masao; Yamada, Yuichi (1995). "Polymorphism in ALDH2-genotype in Japanese men and the alcohol-blood pressure relationship*". American Journal of Hypertension. 8 (11): 1053–1059. doi:10.1016/0895-7061(95)00222-b. ISSN 0895-7061. PMID 8554727.
  5. 1 2 3 4 5 6 "Alcohol intolerance - Symptoms and causes". Mayo Clinic. Retrieved 2019-11-07.
  6. 1 2 3 4 5 Aoki, Y.; Wehage, S. L.; Talalay, P. (November 2017). "Quantification of skin erythema response to topical alcohol in alcohol-intolerant East Asians". Skin Research and Technology. 23 (4): 593–596. doi:10.1111/srt.12376. PMID 28513003. S2CID 34497300.
  7. ↑ De Sousa, Avinash (2019). Disulfiram: Its Use in Alcohol Dependence and Other Disorders (1st ed.). Singapore: Springer Singapore. pp. 9–10. ISBN 978-981-32-9876-7.
  8. ↑ Petersen, E. N. (November 1992). "The pharmacology and toxicology of disulfiram and its metabolites". Acta Psychiatrica Scandinavica. 86 (S369): 7–13. doi:10.1111/j.1600-0447.1992.tb03309.x. ISSN 0001-690X. PMID 1471556. S2CID 21475637.
  9. ↑ Hald, Jens; Jacobsen, Erik (2009-03-13). "The Formation of Acetaldehyde in the Organism after Ingestion of Antabuse (Tetraethylthiuramdisulphide) and Alcohol". Acta Pharmacologica et Toxicologica. 4 (3–4): 305–310. doi:10.1111/j.1600-0773.1948.tb03352.x. ISSN 0001-6683.
  10. ↑ Ma, Lucy; Varma, Sanskriti; Niranjan-Azadi, Ashwini (2019). "Hodgkin lymphoma presenting as alcohol-induced back pain". BMJ Case Reports. 12 (11): e228440. doi:10.1136/bcr-2018-228440. ISSN 1757-790X. PMC 6887434. PMID 31780609.
  11. ↑ Potential risks to human health and the environment from the use of calcium cyanamide as fertiliser, page 29, Scientific Committee on Health and Environmental Risks, Retrieved 14 November 2016
  12. ↑ Deutsche Forschungsgemeinschaft DFG, ed. (2012-10-17). List of MAK and BAT Values 2012: Maximum Concentrations and Biological Tolerance Values at the Workplace. Report 48. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA. doi:10.1002/9783527666034. ISBN 978-3-527-66603-4.
  13. 1 2 3 Crabb, D W; Edenberg, H J; Bosron, W F; Li, T K (1989-01-01). "Genotypes for aldehyde dehydrogenase deficiency and alcohol sensitivity. The inactive ALDH2(2) allele is dominant". Journal of Clinical Investigation. 83 (1): 314–316. doi:10.1172/JCI113875. ISSN 0021-9738. PMC 303676. PMID 2562960.
  14. ↑ Goedde, H. Werner; Agarwal, Dharam P. (1987). "Polymorphism of Aldehyde Dehydrogenase and Alcohol Sensitivity". Enzyme. 37 (1–2): 29–44. doi:10.1159/000469239. ISSN 0013-9432. PMID 3106030.
  15. 1 2 Peng, G. S.; Wang, M. F.; Chen, C. Y.; Luu, S. U.; Chou, H. C.; Li, T. K.; Yin, S. J. (August 1999). "Involvement of acetaldehyde for full protection against alcoholism by homozygosity of the variant allele of mitochondrial aldehyde dehydrogenase gene in Asians". Pharmacogenetics. 9 (4): 463–476. ISSN 0960-314X. PMID 10780266.
  16. 1 2 Wüthrich, B. (2018). "Allergic and intolerance reactions to wine". Allergologie Select. 2 (1): 80–88. doi:10.5414/ALX01420E. ISSN 2512-8957. PMC 6883207. PMID 31826033.
  17. ↑ Thomasson, Holly R.; Crabb, David W.; Edenberg, Howard J.; Li, Ting-Kai (March 1993). "Alcohol and aldehyde dehydrogenase polymorphisms and alcoholism". Behavior Genetics. 23 (2): 131–136. doi:10.1007/BF01067417. ISSN 0001-8244. PMID 8512527. S2CID 26462055.
  18. ↑ Enomoto, Nobuyuki; Takase, Shujiro; Yasuhara, Minoru; Takada, Akira (February 1991). "Acetaldehyde Metabolism in Different Aldehyde Dehydrogenase-2 Genotypes". Alcoholism: Clinical and Experimental Research. 15 (1): 141–144. doi:10.1111/j.1530-0277.1991.tb00532.x. ISSN 0145-6008. PMID 2024727.
  19. ↑ Higuchi, S; Muramatsu, T; Shigemori, K; Saito, M; Kono, H; Dufour, M C; Harford, T C (1992-03-01). "The relationship between low Km aldehyde dehydrogenase phenotype and drinking behavior in Japanese". Journal of Studies on Alcohol. 53 (2): 170–175. doi:10.15288/jsa.1992.53.170. ISSN 0096-882X. PMID 1560668.
  20. ↑ Cai, Shi-Xiong; Huang, Mei-Yuan; Xi, Li-Qiang; Li, Yan-Lin; Qu, Jiang-Bin; Kawai, Toshio; Yasugi, Tomojiro; Mizunuma, Kazunori; Watanabe, Takao; Ikeda, Masayuki (1992-01-01). "Occupational dimethylformamide exposure". International Archives of Occupational and Environmental Health. 63 (7): 461–468. doi:10.1007/BF00572112. ISSN 1432-1246. PMID 1577525. S2CID 10246564.
  21. ↑ Lyle, W. H.; Spence, T. W.; McKinneley, W. M.; Duckers, K. (1979-02-01). "Dimethylformamide and alcohol intolerance". Occupational and Environmental Medicine. 36 (1): 63–66. doi:10.1136/oem.36.1.63. ISSN 1351-0711. PMC 1008494. PMID 444443.
  22. ↑ Kilo, Sonja; Göen, Thomas; Drexler, Hans (2016-11-01). "Cross-sectional study on N,N-dimethylformamide (DMF); effects on liver and alcohol intolerance". International Archives of Occupational and Environmental Health. 89 (8): 1309–1320. doi:10.1007/s00420-016-1164-0. ISSN 1432-1246. PMID 27587219. S2CID 33581884.
  23. ↑ Murarnatsu, Taro; Higuchi, Susumu; Shigernori, Kenji; Saito, Masayoshi; Sasao, Mitsuo; Harada, Shoji; Shigeta, Yosuke; Yamada, Koichi; Muraoka, Hideo; Takagi, Satoshi; Maruyarna, Katsuya; Kono, Hiroaki (April 1989). "Ethanol Patch Test-A Simple and Sensitive Method for Identifying ALDH Phenotype". Alcoholism: Clinical and Experimental Research. 13 (2): 229–231. doi:10.1111/j.1530-0277.1989.tb00317.x. ISSN 0145-6008. PMID 2658661.
  24. ↑ "Acute alcohol sensitivity | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2018-04-17.
  25. 1 2 "Acetaldehyde and Aldehyde Dehydrogenase". Alcohol and Alcoholism. 1987-01-01. doi:10.1093/oxfordjournals.alcalc.a044740. ISSN 1464-3502.
  26. 1 2 "Alcohol Intolerance: Symptoms, Tests & Alcohol Allergy". Cleveland Clinic. Retrieved 2022-10-26.
  27. ↑ Thomasson, Holly R.; Crabb, David W.; Edenberg, Howard J.; Li, Ting-Kai (1993-03-01). "Alcohol and aldehyde dehydrogenase polymorphisms and alcoholism". Behavior Genetics. 23 (2): 131–136. doi:10.1007/BF01067417. ISSN 1573-3297. PMID 8512527. S2CID 26462055.
  28. ↑ "Alcohol allergy - Australasian Society of Clinical Immunology and Allergy (ASCIA)". www.allergy.org.au. Retrieved 2022-10-26.
  29. ↑ Alcoceba Borràs, E.; Botey Faraudo, E.; Gaig Jané, P.; Bartolomé Zavala, B. (2007). "Alcohol-induced anaphylaxis to grape". Allergologia et Immunopathologia. 35 (4): 159–161. doi:10.1157/13108228. ISSN 0301-0546. PMID 17663926.
  30. ↑ Merritt, Bret A.; Okyere, Charles P.; Jasinski, Donna M. (March 2002). "Isopropyl Alcohol Inhalation". Nursing Research. 51 (2): 125–128. doi:10.1097/00006199-200203000-00009. ISSN 0029-6562. PMID 11984383. S2CID 40170944.
  31. ↑ Merritt, Bret A.; Okyere, Charles P.; Jasinski, Donna M. (2002). "Isopropyl Alcohol Inhalation". Nursing Research. 51 (2): 125–128. doi:10.1097/00006199-200203000-00009. ISSN 0029-6562. PMID 11984383. S2CID 40170944.
  32. ↑ Miller, N S; Goodwin, D W; Jones, F C; Gabrielli, W F; Pardo, M P; Anand, M M; Hall, T B (1988-01-01). "Antihistamine blockade of alcohol-induced flushing in orientals". Journal of Studies on Alcohol. 49 (1): 16–20. doi:10.15288/jsa.1988.49.16. ISSN 0096-882X. PMID 3347071.
  33. ↑ Boffetta, Paolo; Hashibe, Mia (2006-02-01). "Alcohol and cancer". The Lancet Oncology. 7 (2): 149–156. doi:10.1016/S1470-2045(06)70577-0. ISSN 1470-2045. PMID 16455479.
  34. ↑ Bagnardi, Vincenzo; Blangiardo, Marta; Vecchia, Carlo La; Corrao, Giovanni (2001). "Alcohol Consumption and the Risk of Cancer: A Meta-Analysis". Alcohol Research & Health. 25 (4): 263–270. PMC 6705703. PMID 11910703.
  35. ↑ Bajaj, Jasmohan S. (2019). "Alcohol, liver disease and the gut microbiota". Nature Reviews Gastroenterology & Hepatology. 16 (4): 235–246. doi:10.1038/s41575-018-0099-1. ISSN 1759-5053. PMID 30643227. S2CID 58006795.
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