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{{Infobox medical condition (new)
{{Infobox medical condition (new)
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| synonym = Acute alcohol sensitivity
| synonym = Acute alcohol sensitivity
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| image = The Alcohol Flushing Response.png
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| caption = Skin flushing, a common symptom of alcohol intolerance
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'''Alcohol intolerance''' is due to a [[Gene polymorphism|genetic polymorphism]] of the [[aldehyde dehydrogenase]] [[enzyme]], which is responsible for the metabolism of [[acetaldehyde]] (produced from the metabolism of alcohol by [[alcohol dehydrogenase]]).<ref name=":82">{{Cite book |url=https://link.springer.com/book/10.1007/978-3-642-74904-9 |title=Alcohol Metabolism, Alcohol Intolerance, and Alcoholism |pages=57-59 |language=en |doi=10.1007/978-3-642-74904-9}}</ref><ref name=":62">{{Cite journal |last=Harada |first=S. |last2=Agarwal |first2=D.P. |last3=Goedde |first3=H.W. |date=1981-10 |title=ALDEHYDE DEHYDROGENASE DEFICIENCY AS CAUSE OF FACIAL FLUSHING REACTION TO ALCOHOL IN JAPANESE |url=http://dx.doi.org/10.1016/s0140-6736(81)91172-7 |journal=The Lancet |volume=318 |issue=8253 |pages=982 |doi=10.1016/s0140-6736(81)91172-7 |issn=0140-6736}}</ref> This polymorphism is most often reported in patients of East Asian descent.<ref>{{Cite journal |last=Mizuno |first=Yuji |last2=Morita |first2=Sumio |last3=Harada |first3=Eisaku |last4=Shono |first4=Makoto |last5=Morikawa |first5=Yoshinobu |last6=Murohara |first6=Toyoaki |last7=Yasue |first7=Hirofumi |date=2013 |title=Alcohol Flushing and Positive Ethanol Patch Test in Patients with Coronary Spastic Angina: Possible Role of Aldehyde Dehydrogenase 2 Polymorphisms |url=http://dx.doi.org/10.2169/internalmedicine.52.0894 |journal=Internal Medicine |volume=52 |issue=23 |pages=2593–2598 |doi=10.2169/internalmedicine.52.0894 |issn=0918-2918}}</ref><ref>{{Cite journal |last=Tsuritani |first=Ikiko |last2=Ikai |first2=Eriko |last3=Date |first3=Takayasu |last4=Suzuki |first4=Yasuhito |last5=Ishizaki |first5=Masao |last6=Yamada |first6=Yuichi |date=1995 |title=Polymorphism in ALDH2-genotype in Japanese men and the alcohol-blood pressure relationship* |url=http://dx.doi.org/10.1016/0895-7061(95)00222-b |journal=American Journal of Hypertension |volume=8 |issue=11 |pages=1053–1059 |doi=10.1016/0895-7061(95)00222-b |issn=0895-7061}}</ref><ref name=":4">{{Cite web |title=Alcohol intolerance - Symptoms and causes |url=https://www.mayoclinic.org/diseases-conditions/alcohol-intolerance/symptoms-causes/syc-20369211 |access-date=2019-11-07 |website=Mayo Clinic |language=en}}</ref><ref name=":5">{{Cite journal |last=Aoki |first=Y. |last2=Wehage |first2=S. L. |last3=Talalay |first3=P. |date=2017-11 |title=Quantification of skin erythema response to topical alcohol in alcohol-intolerant East Asians |url=https://onlinelibrary.wiley.com/doi/10.1111/srt.12376 |journal=Skin Research and Technology |language=en |volume=23 |issue=4 |pages=593–596 |doi=10.1111/srt.12376}}</ref> 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 [[Drinking alcohol|alcohol]] ingestion.<ref name=":4" /><ref name=":5" /> It may also be characterized as [[Drug intolerance|intolerance]] causing [[Hangover#Acetaldehyde|hangover]] symptoms similar to the "disulfiram-like reaction" of [[Aldehyde dehydrogenase#Pathology (aldehyde dehydrogenase deficiency)|aldehyde dehydrogenase deficiency]] or [[chronic fatigue syndrome]].<ref>{{Cite book |last=De Sousa |first=Avinash |title=Disulfiram: Its Use in Alcohol Dependence and Other Disorders |publisher=Springer Singapore |year=2019 |isbn=978-981-32-9876-7 |edition=1st |location=Singapore |pages=9-10}}</ref><ref>{{Cite journal |last=Petersen |first=E. N. |date=1992-11 |title=The pharmacology and toxicology of disulfiram and its metabolites |url=https://onlinelibrary.wiley.com/doi/10.1111/j.1600-0447.1992.tb03309.x |journal=Acta Psychiatrica Scandinavica |language=en |volume=86 |issue=S369 |pages=7–13 |doi=10.1111/j.1600-0447.1992.tb03309.x |issn=0001-690X}}</ref><ref>{{Cite journal |last=Hald |first=Jens |last2=Jacobsen |first2=Erik |date=2009-03-13 |title=The Formation of Acetaldehyde in the Organism after Ingestion of Antabuse (Tetraethylthiuramdisulphide) and Alcohol. |url=http://dx.doi.org/10.1111/j.1600-0773.1948.tb03352.x |journal=Acta Pharmacologica et Toxicologica |volume=4 |issue=3-4 |pages=305–310 |doi=10.1111/j.1600-0773.1948.tb03352.x |issn=0001-6683}}</ref> Severe pain after drinking alcohol may indicate a more serious underlying condition.<ref name=":4" /><ref>{{Cite journal |last=Ma |first=Lucy |last2=Varma |first2=Sanskriti |last3=Niranjan-Azadi |first3=Ashwini |date=2019 |title=Hodgkin lymphoma presenting as alcohol-induced back pain |url=http://dx.doi.org/10.1136/bcr-2018-228440 |journal=BMJ Case Reports |volume=12 |issue=11 |pages=e228440 |doi=10.1136/bcr-2018-228440 |issn=1757-790X}}</ref>
'''Alcohol intolerance''' is due to a [[Gene polymorphism|genetic polymorphism]] of the [[enzyme]] [[alcohol dehydrogenase]], the enzyme that metabolises ingested alcohol. This polymorphism is most often reported in Asian patients.<ref>{{Cite web|url=https://rarediseases.info.nih.gov/diseases/12634/acute-alcohol-sensitivity|title=Acute alcohol sensitivity {{!}} Genetic and Rare Diseases Information Center (GARD) – an NCATS Program|website=rarediseases.info.nih.gov|language=en|access-date=2018-04-17}}</ref> It can also be an effect or [[side effect]] associated with certain drugs such as [[disulfiram]], [[metronidazole]], or [[nilutamide]]. Stuffy nose and skin flushing are the most common symptoms when ingesting [[drinking alcohol|alcohol]].<ref>{{Cite web|url=https://rarediseases.info.nih.gov/diseases/12634/acute-alcohol-sensitivity|title=Acute alcohol sensitivity {{!}} Genetic and Rare Diseases Information Center (GARD) – an NCATS Program|website=rarediseases.info.nih.gov|language=en|access-date=2018-04-17}}</ref> It may also be characterized as [[drug intolerance|intolerance]] causing [[Hangover#Acetaldehyde|hangover]] symptoms similar to the "disulfiram-like reaction" of [[Aldehyde dehydrogenase#Pathology (aldehyde dehydrogenase deficiency)|aldehyde dehydrogenase deficiency]] or [[chronic fatigue syndrome]]. Severe pain after drinking alcohol may indicate a more serious condition.<ref>{{Cite web|url=https://www.mayoclinic.org/diseases-conditions/alcohol-intolerance/symptoms-causes/syc-20369211|title=Alcohol intolerance - Symptoms and causes|website=Mayo Clinic|language=en|access-date=2019-11-07}}</ref>


⚫
Drinking alcohol in addition to consuming [[calcium cyanamide]] can cause permanent or long-lasting intolerance (nitrolime disease),<ref>[http://ec.europa.eu/health/scientific_committees/environmental_risks/docs/scher_o_169.pdf ''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</ref><ref>{{Cite book |url=http://doi.wiley.com/10.1002/9783527666034 |title=List of MAK and BAT Values 2012: Maximum Concentrations and Biological Tolerance Values at the Workplace. Report 48 |date=2012-10-17 |publisher=Wiley-VCH Verlag GmbH & Co. KGaA |isbn=978-3-527-66603-4 |editor-last=Deutsche Forschungsgemeinschaft DFG |location=Weinheim, Germany |language=en |doi=10.1002/9783527666034}}</ref> contributing (in conjunction with other substances) to the accumulation of harmful [[acetaldehyde]] in the body by inhibiting the [[Acetaldehyde dehydrogenase#Role in metabolism of alcohol|acetaldehyde dehydrogenase]] enzyme.
If people are intolerant, some [[non-alcoholic beverage]]s may be a problem, similar to alcohol-containing medications, [[vinegar]], [[Alcohol inhalation|inhalation of alcohol]] or the vapour of alcohol-containing [[cleaning agent]]s.{{cn|date=September 2021}}


== Signs and Symptoms ==
⚫
Drinking alcohol first or afterwards together with [[calcium cyanamide]], an inorganic compound used as a fertilizer, can cause permanent or long lasting intolerance (nitrolime disease),<ref>[http://ec.europa.eu/health/scientific_committees/environmental_risks/docs/scher_o_169.pdf ''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</ref> contributing together with other substances to the accumulation of harmful [[acetaldehyde]] by inhibiting the enzyme [[Acetaldehyde dehydrogenase#Role in metabolism of alcohol|acetaldehyde dehydrogenase]].
Individuals with alcohol intolerance will experience unpleasant reactions immediately after drinking alcohol.<ref name=":7">{{Cite journal |last=Crabb |first=D W |last2=Edenberg |first2=H J |last3=Bosron |first3=W F |last4=Li |first4=T K |date=1989-01-01 |title=Genotypes for aldehyde dehydrogenase deficiency and alcohol sensitivity. The inactive ALDH2(2) allele is dominant. |url=http://www.jci.org/articles/view/113875 |journal=Journal of Clinical Investigation |language=en |volume=83 |issue=1 |pages=314–316 |doi=10.1172/JCI113875 |issn=0021-9738}}</ref><ref name=":4" /><ref name=":5" /> Common signs and symptoms of alcohol intolerance include [[nasal congestion]], [[Flushing (physiology)|skin flushing (redness)]], [[Headache|headaches]], [[Low blood-pressure|low blood pressure]], [[nausea]], and [[vomiting]].<ref name=":4" /><ref name=":5" /><ref name=":7" />

== Causes ==

=== Genetics ===
[[File:Biotransformation_pathway_of_ethanol_(NIH_NIAAA,_2007).png|thumb|400x400px|Alcohol metabolism]]
ALDH1 is an [[isozyme]] of [[aldehyde dehydrogenase]]. A structural mutation in the gene of ALDH1, commonly found in [[East Asian people|East Asians]], results in low levels of functional ALDH1 enzyme and thus, higher blood acetaldehyde levels.<ref>{{Cite journal |last=Goedde |first=H. Werner |last2=Agarwal |first2=Dharam P. |date=1987 |title=Polymorphism of Aldehyde Dehydrogenase and Alcohol Sensitivity |url=https://www.karger.com/Article/FullText/469239 |journal=Enzyme |language=en |volume=37 |issue=1-2 |pages=29–44 |doi=10.1159/000469239 |issn=0013-9432}}</ref><ref name=":82" /><ref name=":62" /> 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.<ref name=":82" /><ref name=":62" /> 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.<ref name=":0">{{Cite journal |last=Peng |first=G. S. |last2=Wang |first2=M. F. |last3=Chen |first3=C. Y. |last4=Luu |first4=S. U. |last5=Chou |first5=H. C. |last6=Li |first6=T. K. |last7=Yin |first7=S. J. |date=1999-08 |title=Involvement of acetaldehyde for full protection against alcoholism by homozygosity of the variant allele of mitochondrial aldehyde dehydrogenase gene in Asians |url=https://pubmed.ncbi.nlm.nih.gov/10780266 |journal=Pharmacogenetics |volume=9 |issue=4 |pages=463–476 |issn=0960-314X |pmid=10780266}}</ref><ref name=":1">{{Cite journal |last=Wüthrich |first=B. |date=2018 |title=Allergic and intolerance reactions to wine |url=https://pubmed.ncbi.nlm.nih.gov/31826033/ |journal=Allergologie Select |volume=2 |issue=1 |pages=80–88 |doi=10.5414/ALX01420E |issn=2512-8957 |pmc=6883207 |pmid=31826033}}</ref><ref name=":62" /> 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.<ref>{{Cite journal |last=Thomasson |first=Holly R. |last2=Crabb |first2=David W. |last3=Edenberg |first3=Howard J. |last4=Li |first4=Ting-Kai |date=1993-03 |title=Alcohol and aldehyde dehydrogenase polymorphisms and alcoholism |url=http://link.springer.com/10.1007/BF01067417 |journal=Behavior Genetics |language=en |volume=23 |issue=2 |pages=131–136 |doi=10.1007/BF01067417 |issn=0001-8244}}</ref><ref>{{Cite journal |last=Enomoto |first=Nobuyuki |last2=Takase |first2=Shujiro |last3=Yasuhara |first3=Minoru |last4=Takada |first4=Akira |date=1991-02 |title=Acetaldehyde Metabolism in Different Aldehyde Dehydrogenase-2 Genotypes |url=https://onlinelibrary.wiley.com/doi/10.1111/j.1530-0277.1991.tb00532.x |journal=Alcoholism: Clinical and Experimental Research |language=en |volume=15 |issue=1 |pages=141–144 |doi=10.1111/j.1530-0277.1991.tb00532.x |issn=0145-6008}}</ref><ref>{{Cite journal |last=Higuchi |first=S |last2=Muramatsu |first2=T |last3=Shigemori |first3=K |last4=Saito |first4=M |last5=Kono |first5=H |last6=Dufour |first6=M C |last7=Harford |first7=T C |date=1992-03-01 |title=The relationship between low Km aldehyde dehydrogenase phenotype and drinking behavior in Japanese. |url=https://www.jsad.com/doi/10.15288/jsa.1992.53.170 |journal=Journal of Studies on Alcohol |volume=53 |issue=2 |pages=170–175 |doi=10.15288/jsa.1992.53.170 |issn=0096-882X}}</ref>

=== Risk Factors ===
Various [[Genetics|genetic]] and [[Environmental factor|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.<ref name=":0" /><ref name=":1" /><ref name=":62" /> Individuals who work with [[Dimethylformamide|DMF]] have shown a dose-related increase in alcohol intolerance complaints.<ref>{{Cite journal |last=Cai |first=Shi-Xiong |last2=Huang |first2=Mei-Yuan |last3=Xi |first3=Li-Qiang |last4=Li |first4=Yan-Lin |last5=Qu |first5=Jiang-Bin |last6=Kawai |first6=Toshio |last7=Yasugi |first7=Tomojiro |last8=Mizunuma |first8=Kazunori |last9=Watanabe |first9=Takao |last10=Ikeda |first10=Masayuki |date=1992-01-01 |title=Occupational dimethylformamide exposure |url=https://doi.org/10.1007/BF00572112 |journal=International Archives of Occupational and Environmental Health |language=en |volume=63 |issue=7 |pages=461–468 |doi=10.1007/BF00572112 |issn=1432-1246}}</ref> Exposure to [[Dimethylformamide|DMF]] can also cause facial flushing and increased sensitivity to alcohol.<ref>{{Cite journal |last=Lyle |first=W. H. |last2=Spence |first2=T. W. |last3=McKinneley |first3=W. M. |last4=Duckers |first4=K. |date=1979-02-01 |title=Dimethylformamide and alcohol intolerance. |url=https://oem.bmj.com/content/36/1/63 |journal=Occupational and Environmental Medicine |language=en |volume=36 |issue=1 |pages=63–66 |doi=10.1136/oem.36.1.63 |issn=1351-0711 |pmc=PMC1008494 |pmid=444443}}</ref><ref>{{Cite journal |last=Kilo |first=Sonja |last2=Göen |first2=Thomas |last3=Drexler |first3=Hans |date=2016-11-01 |title=Cross-sectional study on N,N-dimethylformamide (DMF); effects on liver and alcohol intolerance |url=https://doi.org/10.1007/s00420-016-1164-0 |journal=International Archives of Occupational and Environmental Health |language=en |volume=89 |issue=8 |pages=1309–1320 |doi=10.1007/s00420-016-1164-0 |issn=1432-1246}}</ref>

== 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 [[Erythema|skin redness]] occurs after 10-15 minutes, the individual is deemed to have a lack of ALDH1 associated with alcohol intolerance.<ref>{{Cite journal |last=Murarnatsu |first=Taro |last2=Higuchi |first2=Susumu |last3=Shigernori |first3=Kenji |last4=Saito |first4=Masayoshi |last5=Sasao |first5=Mitsuo |last6=Harada |first6=Shoji |last7=Shigeta |first7=Yosuke |last8=Yamada |first8=Koichi |last9=Muraoka |first9=Hideo |last10=Takagi |first10=Satoshi |last11=Maruyarna |first11=Katsuya |last12=Kono |first12=Hiroaki |date=1989-04 |title=Ethanol Patch Test-A Simple and Sensitive Method for Identifying ALDH Phenotype |url=https://onlinelibrary.wiley.com/doi/10.1111/j.1530-0277.1989.tb00317.x |journal=Alcoholism: Clinical and Experimental Research |language=en |volume=13 |issue=2 |pages=229–231 |doi=10.1111/j.1530-0277.1989.tb00317.x |issn=0145-6008}}</ref>

=== Alcohol Intolerance vs. Alcohol Allergy ===
Alcohol intolerance is not an [[allergy]].<ref name=":3">{{Cite web |title=Acute alcohol sensitivity {{!}} Genetic and Rare Diseases Information Center (GARD) – an NCATS Program |url=https://rarediseases.info.nih.gov/diseases/12634/acute-alcohol-sensitivity |access-date=2018-04-17 |website=rarediseases.info.nih.gov |language=en}}</ref> 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.<ref name=":9">{{Cite journal |date=1987-01-01 |title=ACETALDEHYDE AND ALDEHYDE DEHYDROGENASE |url=http://dx.doi.org/10.1093/oxfordjournals.alcalc.a044740 |journal=Alcohol and Alcoholism |doi=10.1093/oxfordjournals.alcalc.a044740 |issn=1464-3502}}</ref> The increased accumulation of acetaldehyde in affected individuals due to deficient aldehyde dehydrogenase enzymes often leads to the characteristic symptom of having flushed skin.<ref name=":9" /><ref name=":2">{{Cite web |title=Alcohol Intolerance: Symptoms, Tests & Alcohol Allergy |url=https://my.clevelandclinic.org/health/diseases/17659-alcohol-intolerance |access-date=2022-10-26 |website=Cleveland Clinic}}</ref><ref>{{Cite journal |last=Thomasson |first=Holly R. |last2=Crabb |first2=David W. |last3=Edenberg |first3=Howard J. |last4=Li |first4=Ting-Kai |date=1993-03-01 |title=Alcohol and aldehyde dehydrogenase polymorphisms and alcoholism |url=https://doi.org/10.1007/BF01067417 |journal=Behavior Genetics |language=en |volume=23 |issue=2 |pages=131–136 |doi=10.1007/BF01067417 |issn=1573-3297}}</ref> 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.<ref>{{Cite web |title=Alcohol allergy - Australasian Society of Clinical Immunology and Allergy (ASCIA) |url=https://www.allergy.org.au/patients/other-allergy/alcohol-allergy |access-date=2022-10-26 |website=www.allergy.org.au}}</ref><ref>{{Cite journal |last=Alcoceba Borràs |first=E. |last2=Botey Faraudo |first2=E. |last3=Gaig Jané |first3=P. |last4=Bartolomé Zavala |first4=B. |date=2007 |title=Alcohol-induced anaphylaxis to grape |url=http://dx.doi.org/10.1157/13108228 |journal=Allergologia et Immunopathologia |volume=35 |issue=4 |pages=159–161 |doi=10.1157/13108228 |issn=0301-0546}}</ref> Nausea is a symptom common to both alcohol intolerance and alcohol allergy.<ref name=":2" /> Remarkably, inhaled isopropyl alcohol can be used to provide nausea and vomiting relief.<ref>{{Cite journal |last=Merritt |first=Bret A. |last2=Okyere |first2=Charles P. |last3=Jasinski |first3=Donna M. |date=2002-03 |title=Isopropyl Alcohol Inhalation |url=http://dx.doi.org/10.1097/00006199-200203000-00009 |journal=Nursing Research |volume=51 |issue=2 |pages=125–128 |doi=10.1097/00006199-200203000-00009 |issn=0029-6562}}</ref> <ref>{{Cite journal |last=Merritt |first=Bret A. |last2=Okyere |first2=Charles P. |last3=Jasinski |first3=Donna M. |date=2002 |title=Isopropyl Alcohol Inhalation |url=http://dx.doi.org/10.1097/00006199-200203000-00009 |journal=Nursing Research |volume=51 |issue=2 |pages=125–128 |doi=10.1097/00006199-200203000-00009 |issn=0029-6562}}</ref>

== Management ==
Avoiding or restricting alcohol is the most straightforward way to prevent the symptoms of alcohol intolerance.<ref name=":4" /><ref name=":5" /><ref name=":7" /> [[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 [[Antihistamine|antihistamines]] are used to reduce the symptoms of alcohol intolerance. However, these medications simply mask these symptoms.<ref>{{Cite journal |last=Miller |first=N S |last2=Goodwin |first2=D W |last3=Jones |first3=F C |last4=Gabrielli |first4=W F |last5=Pardo |first5=M P |last6=Anand |first6=M M |last7=Hall |first7=T B |date=1988-01-01 |title=Antihistamine blockade of alcohol-induced flushing in orientals. |url=https://www.jsad.com/doi/abs/10.15288/jsa.1988.49.16 |journal=Journal of Studies on Alcohol |volume=49 |issue=1 |pages=16–20 |doi=10.15288/jsa.1988.49.16 |issn=0096-882X}}</ref> Reducing alcohol consumption lowers the risk for [[cancer]] and other serious diseases.<ref>{{Cite journal |last=Boffetta |first=Paolo |last2=Hashibe |first2=Mia |date=2006-02-01 |title=Alcohol and cancer |url=https://www.sciencedirect.com/science/article/pii/S1470204506705770 |journal=The Lancet Oncology |language=en |volume=7 |issue=2 |pages=149–156 |doi=10.1016/S1470-2045(06)70577-0 |issn=1470-2045}}</ref><ref>{{Cite journal |last=Bagnardi |first=Vincenzo |last2=Blangiardo |first2=Marta |last3=Vecchia |first3=Carlo La |last4=Corrao |first4=Giovanni |date=2001 |title=Alcohol Consumption and the Risk of Cancer: A Meta-Analysis |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6705703/ |journal=Alcohol Research & Health |language=en |volume=25 |issue=4}}</ref><ref>{{Cite journal |last=Bajaj |first=Jasmohan S. |date=2019 |title=Alcohol, liver disease and the gut microbiota |url=https://www.nature.com/articles/s41575-018-0099-1 |journal=Nature Reviews Gastroenterology & Hepatology |language=en |volume=16 |issue=4 |pages=235–246 |doi=10.1038/s41575-018-0099-1 |issn=1759-5053}}</ref>


==See also==
==See also==

* [[Disulfiram-like drug]]
* [[Disulfiram-like drug]]
* [[Alcohol flush reaction]]
* [[Alcohol flush reaction]]
* [[Alcohol tolerance]]
* [[Alcohol (drug)]]


==References==
==References==

Revision as of 21:44, 5 December 2022

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]

Alcohol Intolerance vs. 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

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  2. ^ a b c d e Harada, S.; Agarwal, D.P.; Goedde, H.W. (1981-10). "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. {{cite journal}}: Check date values in: |date= (help)
  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.
  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.
  5. ^ a b c d e f "Alcohol intolerance - Symptoms and causes". Mayo Clinic. Retrieved 2019-11-07.
  6. ^ a b c d e Aoki, Y.; Wehage, S. L.; Talalay, P. (2017-11). "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. {{cite journal}}: Check date values in: |date= (help)
  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. (1992-11). "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. {{cite journal}}: Check date values in: |date= (help)
  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.
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  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.
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  16. ^ a b 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.
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  18. ^ Enomoto, Nobuyuki; Takase, Shujiro; Yasuhara, Minoru; Takada, Akira (1991-02). "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. {{cite journal}}: Check date values in: |date= (help)
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  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.
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  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 (1989-04). "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. {{cite journal}}: Check date values in: |date= (help)
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  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.
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