Alcohol intolerance

Last updated
Alcohol intolerance
Other namesAcute alcohol sensitivity
The Alcohol Flushing Response.png
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]

Contents

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 Biotransformation pathway of ethanol (NIH NIAAA, 2007).png
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

Related Research Articles

Acetaldehyde (IUPAC systematic name ethanal) is an organic chemical compound with the formula CH3 CHO, sometimes abbreviated as MeCHO. It is a colorless liquid or gas, boiling near room temperature. It is one of the most important aldehydes, occurring widely in nature and being produced on a large scale in industry. Acetaldehyde occurs naturally in coffee, bread, and ripe fruit, and is produced by plants. It is also produced by the partial oxidation of ethanol by the liver enzyme alcohol dehydrogenase and is a contributing cause of hangover after alcohol consumption. Pathways of exposure include air, water, land, or groundwater, as well as drink and smoke. Consumption of disulfiram inhibits acetaldehyde dehydrogenase, the enzyme responsible for the metabolism of acetaldehyde, thereby causing it to build up in the body.

<span class="mw-page-title-main">Alcohol dehydrogenase</span> Group of dehydrogenase enzymes

Alcohol dehydrogenases (ADH) (EC 1.1.1.1) are a group of dehydrogenase enzymes that occur in many organisms and facilitate the interconversion between alcohols and aldehydes or ketones with the reduction of nicotinamide adenine dinucleotide (NAD+) to NADH. In humans and many other animals, they serve to break down alcohols that are otherwise toxic, and they also participate in the generation of useful aldehyde, ketone, or alcohol groups during the biosynthesis of various metabolites. In yeast, plants, and many bacteria, some alcohol dehydrogenases catalyze the opposite reaction as part of fermentation to ensure a constant supply of NAD+.

<span class="mw-page-title-main">Disulfiram</span> Chemical compound

Disulfiram is a medication used to support the treatment of chronic alcoholism by producing an acute sensitivity to ethanol. Disulfiram works by inhibiting the enzyme aldehyde dehydrogenase, causing many of the effects of a hangover to be felt immediately following alcohol consumption. Disulfiram plus alcohol, even small amounts, produces flushing, throbbing in the head and neck, a throbbing headache, respiratory difficulty, nausea, copious vomiting, sweating, thirst, chest pain, palpitation, dyspnea, hyperventilation, fast heart rate, low blood pressure, fainting, marked uneasiness, weakness, vertigo, blurred vision, and confusion. In severe reactions there may be respiratory depression, cardiovascular collapse, abnormal heart rhythms, heart attack, acute congestive heart failure, unconsciousness, convulsions, and death.

<span class="mw-page-title-main">Acetaldehyde dehydrogenase</span> Class of enzymes

Acetaldehyde dehydrogenases are dehydrogenase enzymes which catalyze the conversion of acetaldehyde into acetyl-CoA. This can be summarized as follows:

<span class="mw-page-title-main">Alcoholic polyneuropathy</span> Medical condition

Alcoholic polyneuropathy is a neurological disorder in which peripheral nerves throughout the body malfunction simultaneously. It is defined by axonal degeneration in neurons of both the sensory and motor systems and initially occurs at the distal ends of the longest axons in the body. This nerve damage causes an individual to experience pain and motor weakness, first in the feet and hands and then progressing centrally. Alcoholic polyneuropathy is caused primarily by chronic alcoholism; however, vitamin deficiencies are also known to contribute to its development. This disease typically occurs in chronic alcoholics who have some sort of nutritional deficiency. Treatment may involve nutritional supplementation, pain management, and abstaining from alcohol.

<span class="mw-page-title-main">Alcohol flush reaction</span> Effect of alcohol consumption on the human body

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.

<span class="mw-page-title-main">Fomepizole</span> Medication

Fomepizole, also known as 4-methylpyrazole, is a medication used to treat methanol and ethylene glycol poisoning. It may be used alone or together with hemodialysis. It is given by injection into a vein.

<span class="mw-page-title-main">Alcohol tolerance</span> Bodily responses to the functional effects of ethanol in alcoholic beverages

Alcohol tolerance refers to the bodily responses to the functional effects of ethanol in alcoholic beverages. This includes direct tolerance, speed of recovery from insobriety and resistance to the development of alcohol use disorder.

<span class="mw-page-title-main">Aldehyde dehydrogenase</span> Group of enzymes

Aldehyde dehydrogenases are a group of enzymes that catalyse the oxidation of aldehydes. They convert aldehydes to carboxylic acids. The oxygen comes from a water molecule. To date, nineteen ALDH genes have been identified within the human genome. These genes participate in a wide variety of biological processes including the detoxification of exogenously and endogenously generated aldehydes.

Ethanol, an alcohol found in nature and in alcoholic drinks, is metabolized through a complex catabolic metabolic pathway. In humans, several enzymes are involved in processing ethanol first into acetaldehyde and further into acetic acid and acetyl-CoA. Once acetyl-CoA is formed, it becomes a substrate for the citric acid cycle ultimately producing cellular energy and releasing water and carbon dioxide. Due to differences in enzyme presence and availability, human adults and fetuses process ethanol through different pathways. Gene variation in these enzymes can lead to variation in catalytic efficiency between individuals. The liver is the major organ that metabolizes ethanol due to its high concentration of these enzymes.

<span class="mw-page-title-main">ALDH2</span> Enzyme

Aldehyde dehydrogenase, mitochondrial is an enzyme that in humans is encoded by the ALDH2 gene located on chromosome 12. ALDH2 belongs to the aldehyde dehydrogenase family of enzymes. Aldehyde dehydrogenase is the second enzyme of the major oxidative pathway of alcohol metabolism. ALDH2 has a low Km for acetaldehyde, and is localized in mitochondrial matrix. The other liver isozyme, ALDH1, localizes to the cytosol.

<span class="mw-page-title-main">Hangover</span> Discomfort following alcohol consumption

A hangover is the experience of various unpleasant physiological and psychological effects usually following the consumption of alcohol, such as wine, beer, and liquor. Hangovers can last for several hours or for more than 24 hours. Typical symptoms of a hangover may include headache, drowsiness, concentration problems, dry mouth, dizziness, fatigue, gastrointestinal distress, absence of hunger, light sensitivity, depression, sweating, hyper-excitability, irritability, and anxiety.

<span class="mw-page-title-main">Retinal dehydrogenase</span>

In enzymology, a retinal dehydrogenase, also known as retinaldehyde dehydrogenase (RALDH), catalyzes the chemical reaction converting retinal to retinoic acid. This enzyme belongs to the family of oxidoreductases, specifically the class acting on aldehyde or oxo- donor groups with NAD+ or NADP+ as acceptor groups, the systematic name being retinal:NAD+ oxidoreductase. This enzyme participates in retinol metabolism. The general scheme for the reaction catalyzed by this enzyme is:

<span class="mw-page-title-main">ADH1B</span> Protein-coding gene in the species Homo sapiens

Alcohol dehydrogenase 1B is an enzyme that in humans is encoded by the ADH1B gene.

<span class="mw-page-title-main">Short-term effects of alcohol consumption</span> Overview of the short-term effects of the consumption of alcoholic beverages

The short-term effects of alcohol consumption range from a decrease in anxiety and motor skills and euphoria at lower doses to intoxication (drunkenness), to stupor, unconsciousness, anterograde amnesia, and central nervous system depression at higher doses. Cell membranes are highly permeable to alcohol, so once it is in the bloodstream, it can diffuse into nearly every cell in the body.

<span class="mw-page-title-main">Coprine</span> Chemical compound

Coprine is a mycotoxin. It was first isolated from common inkcap. It occurs in mushrooms in the genera Coprinopsis. When combined with alcohol, it causes "Coprinus syndrome". It inhibits the enzyme acetaldehyde dehydrogenase, which is involved in the metabolism of alcohol. This inhibition leads to a buildup of acetaldehyde, causing an alcohol flush reaction. Because of this, the mushroom is commonly referred to as Tippler's Bane.

Alcohol-induced respiratory reactions, also termed alcohol-induced asthma and alcohol-induced respiratory symptoms, are increasingly recognized as a pathological bronchoconstriction response to the consumption of alcohol that afflicts many people with a "classical" form of asthma, the airway constriction disease evoked by the inhalation of allergens. Alcohol-induced respiratory reactions reflect the operation of different and often racially related mechanisms that differ from those of classical, allergen-induced asthma.

<span class="mw-page-title-main">Disulfiram-like drug</span> Drug that causes an adverse reaction to alcohol

A disulfiram-like drug is a drug that causes an adverse reaction to alcohol leading to nausea, vomiting, flushing, dizziness, throbbing headache, chest and abdominal discomfort, and general hangover-like symptoms among others. These effects are caused by accumulation of acetaldehyde, a major but toxic metabolite of alcohol formed by the enzyme alcohol dehydrogenase. The reaction has been variously termed a disulfiram-like reaction, alcohol intolerance, and acetaldehyde syndrome.

<span class="mw-page-title-main">Alda-1</span> Organic compound

Alda-1 is an organic compound that enhances the enzymatic activity of human ALDH2. Alda-1 has been proposed as a potential treatment for the alcohol flush reaction experienced by people with genetically deficient ALDH2.

<span class="mw-page-title-main">Disulfiram-alcohol reaction</span> Medical condition

Disulfiram-alcohol reaction (DAR) is the effect of the interaction in the human body of alcohol drunk with disulfiram or some mushrooms. The DAR is key to disulfiram therapy that is widely used for alcohol-aversive treatment and management of other addictions. Once disulfiram-treated patients take alcohol, even in small doses, they experience strong unpleasant sensations.

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.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.