Alcohol
G. Hussein Rassool in Alcohol and Drug Misuse, 2017
Alcohol is absorbed in the mouth, oesophagus and the stomach. For the most part absorption of alcohol takes place in the initial part of the small intestine. The rate of alcohol absorption varies widely among people, depending on individual differences in physiology, contents of the stomach and situational factors. Once absorbed into the circulatory system, alcohol is carried to the liver where it is metabolised. The enzyme acetaldehyde dehydrogenase is active in the breakdown of alcohol into acetaldehyde which is then changed to acetic acid. On average, the liver is able to metabolise one drink equivalent per hour. The product acetic acid is rapidly converted to carbon dioxide and water. It is worth pointing out that alcohol, although fattening, affects the body’s ability to absorb and use nutrients effectively. This adds to the problem of malnutrition or vitamin deficiencies in heavy alcohol drinkers.
Food Types, Dietary Supplements, and Roles
Chuong Pham-Huy, Bruno Pham Huy in Food and Lifestyle in Health and Disease, 2022
The balance between the various ADH and ALDH isoforms regulates the concentration of acetaldehyde, which is important as a key risk factor for the development of alcoholism (49–50). Acetaldehyde dehydrogenase 2 (ALDH2) is the key enzyme responsible for metabolism of the alcohol metabolite acetaldehyde in the liver (49). Certain individuals, usually of Asian origin (China, Japan, Korea, Vietnam), have an inactive mitochondrial ALDH2 because of a genetic ALDH deficiency. Of note, approximately 8% of the world’s population, and approximately 30–40% of the population in East Asia, carry an inactive ALDH2 gene (49). Thus, when these individuals consume ethanol, blood levels of acetaldehyde are 5-to 20-fold higher than those found in individuals with the active ALDH allele. Individuals with the inactive ALDH show marked vasodilator (facial flushing or red face), nausea, headaches, and palpitation when consuming alcohol (50). Acetaldehyde is poorly eliminated by these individuals and as a consequence, little alcohol is consumed. ALDH2 deficient individuals are at lower risk for alcoholism. In contrast, they may have possibly increased risk for liver damage and esophageal cancer if alcohol continues to be consumed due to the accumulation of acetaldehyde in these organs (49–51).
Alcohol-Induced Hepatotoxicity
Robert G. Meeks, Steadman D. Harrison, Richard J. Bull in Hepatotoxicology, 2020
All known oxidative pathways of ethanol metabolism result in the production of acetaldehyde. Its metabolism and general effects have been reviewed elsewhere (Lieber, 1982, 1988d). Acetaldehyde is converted to acetate by acetaldehyde dehydrogenase, an enzyme with an interesting polymorphism and associated striking consequences in terms of ethanol intolerance and flushing, exhibited by subjects who harbor an inactive aldehyde dehydrogenase variant (Harada et al., 1980; Yoshida et al., 1984). These aspects will not be discussed in detail here; we shall focus instead on aspects of the toxicity of acetaldehyde most conspicuously related to liver injury.
On the path toward personalized medicine: implications of pharmacogenetic studies of alcohol use disorder medications
Published in Expert Review of Precision Medicine and Drug Development, 2020
Steven J. Nieto, Erica N. Grodin, Lara A. Ray
Several candidates and genome-wide association studies implicate alcohol metabolism genes in risk for AUD. Unfortunately, few studies have examined the influence of these genes on AUD medications. For the most part, alcohol metabolism occurs in the liver wherein several enzymes oxidize alcohol. Alcohol dehydrogenase converts alcohol to acetaldehyde, a potentially toxic metabolite, which is usually rapidly converted to acetic acid by the enzyme acetaldehyde dehydrogenase. Acetaldehyde dehydrogenase (ALDH) occurs in several genetic forms with differential activity. More than one third of individuals with East Asian ancestry inherit the inactive form of ALDH2 [79]. For these individuals, alcohol consumption increases levels of acetaldehyde, causing several negative physiological consequences, such as nausea and vomiting. Thus, inactive ALDH2 may enhance treatment response to drugs that block acetaldehyde metabolism, such as disulfiram. Yoshimura et al. [80] found that alcohol dependent individuals (ICD-9 criteria) with the inactive ALDH2 genotype had higher rates of abstinence from alcohol when treated with disulfiram relative to carriers treated with placebo. Prospective clinical studies with larger sample sizes are needed to examine the influence of alcohol metabolism genes.
Boletus aereus protects against acute alcohol-induced liver damage in the C57BL/6 mouse via regulating the oxidative stress-mediated NF-κB pathway
Published in Pharmaceutical Biology, 2020
Luping Zhang, Bo Meng, Lanzhou Li, Yanzhen Wang, Yuanzhu Zhang, Xuexun Fang, Di Wang
Alcoholic liver disease (ALD), caused by the abuse and consumption of alcohol, exhibits extremely high morbidity and mortality (Ren et al. 2018). Continued heavy alcohol consumption will exacerbate alcoholic fatty liver disease (AFLD), which develops into fatty hepatitis, liver fibrosis and even hepatic carcinoma (Gao and Bataller 2011). About 90% of alcohol is metabolized in the liver to acetaldehyde by alcohol dehydrogenase (ADH), and then decomposes into acetic acid under the metabolism of acetaldehyde dehydrogenase (ALDH), before finally being converted into non-toxic and harmless substances (Jelski et al. 2008). However, heavy alcohol consumption damages the liver cells, resulting in a decrease in the activity of the above enzymes, thus causing the accumulation of acetaldehyde, which is responsible for alcoholism (Setshedi et al. 2010).
Gabapentin for the treatment of alcohol use disorder
Published in Expert Opinion on Investigational Drugs, 2018
Barbara J. Mason, Susan Quello, Farhad Shadan
There are three medications approved for alcohol dependence in the USA and throughout much of the world: disulfiram (oral), naltrexone (oral and long-acting intramuscular) and acamprosate (oral). A fourth drug, nalmefene (oral), is approved throughout the European Union, and is to be taken on an ‘as needed’ basis prior to anticipated drinking occasions. Disulfiram was the first drug approved for alcoholism (in 1951) by the US FDA. It inhibits the enzyme acetaldehyde dehydrogenase, so that if even small amounts of alcohol are consumed, acetaldehyde quickly builds up, with rapid onset of a disulfiram–alcohol interaction that includes flushing, nausea, and vomiting; changes in mental status; and multiple cardiac and respiratory symptoms that could result in death in severe reactions. Disulfiram is used as a deterrent to alcohol use and should never be given to a patient when in a state of alcohol intoxication, or without their full knowledge. The psychological threat of the disulfiram–alcohol interaction may comprise the primary mechanism of disulfiram’s deterrent effect, as opposed to the drug’s pharmacodynamic (PD) properties [15]. Medication compliance is a demonstrated problem with disulfiram [16] and outcomes are optimized with supervised administration, e.g. by a spouse, in compliant patients who wish to remain abstinent [17].