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.
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.
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] Thus men, being larger than women on average, will typically have a higher alcohol tolerance. 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 nonalcoholics. [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 on 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]
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.
Alcohol flush reaction is a condition in which a person develops flushes or blotches associated with erythema on the face, neck, shoulders, 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.
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.
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 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.
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, sometimes referred to by the chemical name ethanol, is a depressant drug that is the active ingredient in fermented drinks such as beer, wine, and distilled spirits. It is one of the oldest and most commonly consumed recreational drugs, causing the characteristic effects of alcohol intoxication ("drunkenness"). Among other effects, alcohol produces happiness and euphoria, decreased anxiety, increased sociability, sedation, impairment of cognitive, memory, motor, and sensory function, and generalized depression of central nervous system (CNS) function.
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.
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.
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.
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