Alcohol intolerance is due to a

genetic polymorphism A gene is said to be polymorphic if more than one allele occupies that gene's locus within a population. In addition to having more than one allele at a specific locus, each allele must also occur in the population at a rate of at least 1% to ge ...

of the

aldehyde dehydrogenase Aldehyde dehydrogenases () are a group of enzymes that catalyse the oxidation of aldehydes. They convert aldehydes (R–C(=O)) to carboxylic acids (R–C(=O)). The oxygen comes from a water molecule. To date, nineteen ALDH genes have b ...

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...

, which is responsible for the metabolism of

acetaldehyde Acetaldehyde (IUPAC systematic name ethanal) is an organic chemical compound with the formula CH3 CHO, sometimes abbreviated by chemists as MeCHO (Me = methyl). It is a colorless liquid or gas, boiling near room temperature. It is one of the ...

(produced from the metabolism of alcohol by

alcohol dehydrogenase Alcohol dehydrogenases (ADH) () 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 N ...

). This polymorphism is most often reported in patients of East Asian descent. Alcohol intolerance may also be an associated

side effect In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

of certain drugs such as

disulfiram Disulfiram is a medication used to support the treatment of chronic alcoholism by producing an acute sensitivity to ethanol (drinking alcohol). Disulfiram works by inhibiting the enzyme acetaldehyde dehydrogenase, causing many of the effects of ...

metronidazole Metronidazole, sold under the brand name Flagyl among others, is an antibiotic and antiprotozoal medication. It is used either alone or with other antibiotics to treat pelvic inflammatory disease, endocarditis, and bacterial vaginosis. It is e ...

, or

nilutamide Nilutamide, sold under the brand names Nilandron and Anandron, is a nonsteroidal antiandrogen (NSAA) which is used in the treatment of prostate cancer.https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020169s008lbl.pdf It has also been ...

. Skin flushing and nasal congestion are the most common symptoms of intolerance after

alcohol Alcohol most commonly refers to: * Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom * Alcohol (drug), an intoxicant found in alcoholic drinks Alcohol may also refer to: Chemicals * Ethanol, one of sev ...

ingestion. It may also be characterized as

intolerance Intolerance may refer to: * Hypersensitivity or intolerance, undesirable reactions produced by the immune system * ''Intolerance'' (film), a 1916 film by D. W. Griffith * ''Intolerance'' (album), the first solo album from Grant Hart, formerly o ...

causing

hangover 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 sympto ...

symptoms similar to the "disulfiram-like reaction" of aldehyde dehydrogenase deficiency or

chronic fatigue syndrome Chronic fatigue syndrome (CFS), also called myalgic encephalomyelitis (ME) or ME/CFS, is a complex, debilitating, long-term medical condition. The Pathophysiology, causes and mechanisms of the disease are not fully understood. Distinguishing c ...

. Severe pain after drinking alcohol may indicate a more serious underlying condition. Drinking alcohol in addition to consuming

calcium cyanamide Calcium cyanamide is the inorganic compound with the formula CaCN2. It is the calcium salt of the cyanamide () anion. This chemical is used as fertilizer and is commercially known as nitrolime. It was first synthesized in 1898 by Adolph Frank and ...

can cause permanent or long-lasting intolerance (nitrolime disease), contributing (in conjunction with other substances) to the accumulation of harmful

in the body by inhibiting the

acetaldehyde dehydrogenase Acetaldehyde dehydrogenases () are dehydrogenase enzymes which catalyze the conversion of acetaldehyde into acetic acid. The oxidation of acetaldehyde to acetate can be summarized as follows: Acetaldehyde + NAD+ + Coenzyme A ↔ Acetyl-CoA + NADH ...

enzyme.

Signs and symptoms

Individuals with alcohol intolerance will experience unpleasant reactions immediately after drinking alcohol. Common signs and symptoms of alcohol intolerance include

nasal congestion Nasal congestion is the blockage of nasal breathing usually due to membranes lining the nose becoming swollen from inflamed blood vessels. Background In about 85% of cases, nasal congestion leads to mouth breathing rather than nasal breathing. ...

, skin flushing (redness),

headaches Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a resul ...

low blood pressure Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dia ...

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

, and

vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteri ...

Causes

Genetics

ALDH1 is an

isozyme In biochemistry, isozymes (also known as isoenzymes or more generally as multiple forms of enzymes) are enzymes that differ in amino acid sequence but catalyze the same chemical reaction. Isozymes usually have different kinetic parameters (e.g. dif ...

. A structural mutation in the gene of ALDH1, commonly found in

East Asians East Asian people (East Asians) are the people from East Asia, which consists of China, Taiwan, Japan, Mongolia, North Korea, and South Korea. The total population of all countries within this region is estimated to be 1.677 billion and 21% of t ...

, results in low levels of functional ALDH1 enzyme and thus, higher blood acetaldehyde levels. 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. 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. 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.

Risk Factors

Various

genetic Genetic may refer to: *Genetics, in biology, the science of genes, heredity, and the variation of organisms **Genetic, used as an adjective, refers to genes ***Genetic disorder, any disorder caused by a genetic mutation, whether inherited or de nov ...

and

environmental factors An environmental factor, ecological factor or eco factor is any factor, abiotic or biotic, that influences living organisms. Abiotic factors include ambient temperature, amount of sunlight, and pH of the water soil in which an organism lives. ...

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. Individuals who work with DMF have shown a dose-related increase in alcohol intolerance complaints. Exposure to DMF can also cause facial flushing and increased sensitivity to alcohol.

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.

Alcohol Intolerance vs. Alcohol Allergy

Alcohol intolerance is not an

allergy Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include Allergic rhinitis, hay fever, Food allerg ...

. There are often misconceptions that alcohol intolerance and alcohol allergy are the same, but they are not. Alcohol intolerance is an inherited

genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorde ...

that impairs alcohol metabolism. The increased accumulation of acetaldehyde in affected individuals due to deficient aldehyde dehydrogenase enzymes often leads to the characteristic symptom of having flushed skin. On the other hand, the more uncommon alcohol allergy is an

immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as Tumor immunology, cancer cells and objects such ...

reaction to alcohol (specifically ethanol) that causes symptoms such as rashes, difficulty breathing, and anaphylaxis in severe cases. Nausea is a symptom common to both alcohol intolerance and alcohol allergy. Remarkably, inhaled isopropyl alcohol can be used to provide nausea and vomiting relief.

Management

Avoiding or restricting alcohol is the most straightforward way to prevent the symptoms of alcohol intolerance.

Tobacco use Tobacco smoking is the practice of burning tobacco and ingesting the resulting smoke. The smoke may be inhaled, as is done with cigarettes, or simply released from the mouth, as is generally done with pipes and cigars. The practice is believe ...

or exposure to

secondhand smoke Passive smoking is the inhalation of tobacco smoke, called secondhand smoke (SHS), or environmental tobacco smoke (ETS), by persons other than the intended "active" smoker. It occurs when tobacco smoke enters an environment, causing its inhala ...

should be avoided, as smoking may increase levels of acetaldehyde. Certain medications may interact with alcohol and worsen symptoms.

Antacid An antacid is a substance which neutralizes stomach acidity and is used to relieve heartburn, indigestion or an upset stomach. Some antacids have been used in the treatment of constipation and diarrhea. Marketed antacids contain salts of alumi ...

antihistamines Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provides ...

are used to reduce the symptoms of alcohol intolerance. However, these medications simply mask these symptoms. Reducing alcohol consumption lowers the risk for

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bl ...

and other serious diseases.

References

Symptoms and signs Alcohol and health {{genetic-disorder-stub