Alcohol flush reaction

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Alcohol flush reaction
Other namesAsian flush syndrome, Asian flush reaction, Asian glow, Asian red face glow
The Alcohol Flushing Response.png
Facial flushing. Before (left) and after (right) drinking alcohol. A 22-year-old East Asian man who is ALDH2 heterozygous showing the reaction. [1]
Specialty Toxicology
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]

Contents

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. [4] [6] [7]

The reaction is informally 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. [4] [2] [3] [8]

Signs and symptoms

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

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".[ citation needed ]

Genotype frequency distribution of ALDH2 (rs671). ALDH2 rs671 genotype frequency.png
Genotype frequency distribution of ALDH2 (rs671).

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. [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. [4] [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.[ citation needed ]

Differential diagnosis

See also

Related Research Articles

A dehydrogenase is an enzyme belonging to the group of oxidoreductases that oxidizes a substrate by reducing an electron acceptor, usually NAD+/NADP+ or a flavin coenzyme such as FAD or FMN. Like all catalysts, they catalyze reverse as well as forward reactions, and in some cases this has physiological significance: for example, alcohol dehydrogenase catalyzes the oxidation of ethanol to acetaldehyde in animals, but in yeast it catalyzes the production of ethanol from acetaldehyde.

Acetaldehyde is an organic chemical compound with the formula CH3CH=O, sometimes abbreviated as MeCH=O. 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">Alcohol and cancer</span> Relationship between cancer and the consumption of alcohol

Alcohol and cancer have a complex relationship. Alcohol causes cancers of the oesophagus, liver, breast, colon, oral cavity, rectum, pharynx, and larynx, and probably causes cancers of the pancreas. Cancer risk can occur even with light to moderate drinking. The more alcohol is consumed, the higher the cancer risk, and no amount can be considered completely safe.

<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. This includes direct tolerance, speed of recovery from insobriety and resistance to the development of alcohol use disorder.

Alcohol has a number of effects on health. Short-term effects of alcohol consumption include intoxication and dehydration. Long-term effects of alcohol include changes in the metabolism of the liver and brain, with increased risk ofseveral types of cancer and alcohol use disorder. Alcohol intoxication affects the brain, causing slurred speech, clumsiness, and delayed reflexes. There is an increased risk of developing an alcohol use disorder for teenagers while their brain is still developing. Adolescents who drink have a higher probability of injury including death.

<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.

<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">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 aldehyde 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.

Amine alkylation (amino-dehalogenation) is a type of organic reaction between an alkyl halide and ammonia or an amine. The reaction is called nucleophilic aliphatic substitution, and the reaction product is a higher substituted amine. The method is widely used in the laboratory, but less so industrially, where alcohols are often preferred alkylating agents.

East Asian people are the people from East Asia, which consists of China, Japan, Mongolia, North Korea, South Korea, and Taiwan. The total population of all countries within this region is estimated to be 1.677 billion and 21% of the world's population in 2020. However, large East Asian diasporas, such as the Chinese, Japanese, Korean, and Mongolian diasporas, as well as diasporas of other East Asian ethnic groups, mean that the 1.677 billion does not necessarily represent an accurate figure for the number of East Asian people worldwide.

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">Alcohol intolerance</span> Medical condition

Alcohol intolerance is due to a genetic polymorphism of the aldehyde dehydrogenase enzyme, which is responsible for the metabolism of acetaldehyde. This polymorphism is most often reported in patients of East Asian descent. 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. It may also be characterized as intolerance causing hangover symptoms similar to the "disulfiram-like reaction" of aldehyde dehydrogenase deficiency or chronic fatigue syndrome. Severe pain after drinking alcohol may indicate a more serious underlying condition.

<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 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, et al. (2014). "Asian flushing: genetic and sociocultural factors of alcoholism among East asians". Gastroenterology Nursing. 37 (5): 327–336. doi:10.1097/SGA.0000000000000062. PMID   25271825. S2CID   206059192.
  3. 1 2 Tashiro CJ (2014). "Mixed Asian Americans and Health: Navigating Uncharted Waters". In Yoo GJ, Le MN, Oda AY (eds.). Handbook of Asian American Health. Springer. p. 129–136 (132). ISBN   978-1493913442.
  4. 1 2 3 4 5 6 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, et al. (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". National Institutes of Health (NIH). 2015-08-28. Retrieved 2024-08-18.
  7. 1 2 3 Lee CH, Lee JM, Wu DC, Goan YG, Chou SH, Wu IC, et al. (March 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): 1347–1356. doi: 10.1002/ijc.23264 . 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 SW, Bae KY, Shin HY, Kim JM, Shin IS, Youn T, et al. (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): 439–445. 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 H, Pakstis AJ, Bonne-Tamir B, Goldman D, Grigorenko E, Kajuna SL, et al. (March 2004). "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). Wiley: 93–109. doi:10.1046/j.1529-8817.2003.00060.x. 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): 647–655. doi: 10.1016/0002-9343(90)90534-k . PMID   2189310.
  17. ↑ Ye L (1969-12-31). "Alcohol and the Asian flush reaction". SURG Journal. 2 (2): 34–39. doi:10.21083/surg.v2i2.982. ISSN   2291-1367.
  18. ↑ Boulton P, Purdy RA, Bosch EP, Dodick DW (February 2007). "Primary and secondary red ear syndrome: implications for treatment". Cephalalgia. 27 (2): 107–110. doi: 10.1111/j.1468-2982.2007.01270.x . PMID   17257229. S2CID   31973969.
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