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 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 tolerance is increased by regular drinking. [1] This reduced sensitivity to the physical effects of alcohol consumption requires that higher quantities of alcohol be consumed in order to achieve the same effects as before tolerance was established. Alcohol tolerance may lead to (or be a sign of) alcohol dependence. [1]
Heavy alcohol consumption over a period of years can lead to "reverse tolerance". A liver can be damaged by chronic alcohol use, leading to a buildup of fat and scar tissue. [2] The reduced ability of such a liver to metabolize or break down alcohol means that small amounts can lead to a high blood alcohol concentration (BAC) and more rapid intoxication.[ citation needed ] Studies have shown that 2–3 weeks of daily alcohol consumption increases tolerance. [3]
Direct alcohol tolerance is largely dependent on body size. Large-bodied people will require more alcohol to reach insobriety than lightly built people. [4] The alcohol tolerance is also connected with activity of alcohol dehydrogenases (a group of enzymes responsible for the breakdown of alcohol) in the liver, and in the bloodstream.
High level of alcohol dehydrogenase activity results in fast transformation of ethanol to more toxic acetaldehyde. Such atypical alcohol dehydrogenase levels are less frequent in alcoholics than in non-alcoholics. [5] Furthermore, among alcoholics, the carriers of this atypical enzyme consume lower ethanol doses, compared to the individuals without the allele.[ citation needed ]
An estimated one out of twenty people have an alcohol flush reaction. It is not in any way an indicator for the drunkenness of an individual. [6] [7] A mild flushing reaction occurs when the body metabolizes alcohol more quickly into acetaldehyde, a toxic metabolite. [5] [8] A more severe flushing reaction occurs when the body metabolizes the acetaldehyde more slowly, generally due to an inactive aldehyde dehydrogenase enzyme. Both of those conditions—faster conversion of alcohol to acetaldehyde and slower removal of acetaldehyde—reduce the risk for excessive drinking and alcohol dependence. [5]
To engage in alcohol consumption and the development of an alcohol use disorder appear to be common to primates, and is not a specific human phenomenon. [9] Humans have access to alcohol in far greater quantity than non-human primates, and the availability increased, particularly with the development of agriculture. [10] The tolerance to alcohol is not equally distributed throughout the world's population. [11] Genetics of alcohol dehydrogenase indicate resistance has arisen independently in different cultures. [12] In North America, Native Americans have the highest probability of developing an alcohol use disorder compared to Europeans and Asians. [13] [14] [15] [16] Different alcohol tolerance also exists within Asian groups, such as between Chinese and Koreans. [17] The health benefits of a modest alcohol consumption reported in people of European descent appear not to exist among people of African descent. [18]
Higher body masses and the prevalence of high levels of alcohol dehydrogenase in an individual increase alcohol tolerance, and both adult weight and enzymes vary with ethnicity. [19] [20] Not all differences in tolerance can be traced to biochemistry, however. [21] Differences in tolerance levels are also influenced by socio-economic and cultural difference including diet, average body weight and patterns of consumption. [22] [23]
Ethanol is nutritious but highly intoxicating for most animals, which typically tolerate only up to 4% in their diet. However, a 2024 study found that oriental hornets fed sugary solutions containing 1% to 80% ethanol for a week showed no adverse effects on behavior or lifespan. [24]
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.
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+.
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.
Acetaldehyde dehydrogenases are dehydrogenase enzymes which catalyze the conversion of acetaldehyde into acetyl-CoA. This can be summarized as follows:
Cytochrome P450 2E1 is a member of the cytochrome P450 mixed-function oxidase system, which is involved in the metabolism of xenobiotics in the body. This class of enzymes is divided up into a number of subcategories, including CYP1, CYP2, and CYP3, which as a group are largely responsible for the breakdown of foreign compounds in mammals.
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.
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.
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.
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.
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.
Alcohol dehydrogenase 1B is an enzyme that in humans is encoded by the ADH1B gene.
Alcohol dehydrogenase 1C is an enzyme that in humans is encoded by the ADH1C gene.
Alcohol dehydrogenase 1A is an enzyme that in humans is encoded by the ADH1A gene.
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.
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.
Aldehyde dehydrogenase 1 family, member A1, also known as ALDH1A1 or retinaldehyde dehydrogenase 1 (RALDH1), is an enzyme that is encoded by the ALDH1A1 gene.
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.
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.
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.
The pharmacology of ethanol involves both pharmacodynamics and pharmacokinetics. In the body, ethanol primarily affects the central nervous system, acting as a depressant and causing sedation, relaxation, and decreased anxiety. The complete list of mechanisms remains an area of research, but ethanol has been shown to affect ligand-gated ion channels, particularly the GABAA receptor.
