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).
Biomarkers of Toxicant Susceptibility
Anthony P. DeCaprio in Toxicologic Biomarkers, 2006
Aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme and one of the two main isoenzymes of aldehyde dehydrogenase (ALDH1 with high Km; ALDH2 with low Km). Together with alcohol dehydrogenase, ALDH2 is the main metabolizer of ethyl alcohol. It is also involved in the metabolism of toluene (in particular, in the step from benzyl alcohol to benzoic acid) and also appears to be implicated in that of vinyl chloride monomer (VCM; ethylene oxide chloride→chloroacetaldehyde). About half the Japanese population lacks ALDH2 activity (9). This means that, after alcohol intake, the metabolism of acetaldehyde is inefficient and it accumulates in the organism, giving rise to nausea, hypotension, and tachycardia. This lack of catalytic activity results from a homozygous point mutation of the amino acid in position 487 (Glu >Lys; ALDH2*2/*2) of the wild allele of the ALDH2 gene (ALDH2* 1). The same mutation has also been found in American and Caucasian populations, but at much lower frequencies than in Asiatic ones. Subjects with ALDH2* 1/*2 genotype have reduced ALDH2 activity.
Diet and Cancer Prevention
James M. Rippe in Lifestyle Medicine, 2019
Polymorphisms in ethanol- and acetaldehyde-metabolizing enzymes, especially ADH and ALDH, have been closely associated with ethnic and individual differences in susceptibility to alcohol-related cancers. For example, many individuals of Chinese, Korean, and Japanese descent carry a version of the gene for ADH that codes for a “superactive” form of the enzyme. As a result, they have a quicker conversion of ethanol to acetaldehyde and a higher risk of pancreatic cancer.71 In addition, a genetic variant in ALDH2 that codes for a defective form of the enzyme with no detectable activity causes acetaldehyde accumulation after alcohol drinking; individuals experience facial flushing, tachycardia, nausea, and hypotension.72 This variant is prevalent in Asians, with a frequency of up to 40%, whereas it does not exceed 5% in European and African populations.73 Prospective studies in cancer-free alcoholics have shown that the hazard ratio for future aerodigestive tract cancers in individuals with the inactive protein is approximately 12 times higher than in individuals with the active protein.74 A true understanding of the effect of dietary alcohol may be clouded because of the compounds found in alcoholic beverages including flavonoids, such as resveratrol, which can potentially suppress tumorigenesis.
Hypermethylation of the OPRM1 and ALDH2 promoter regions in Chinese Han males with alcohol use disorder in Yunnan Province
Published in The American Journal of Drug and Alcohol Abuse, 2021
Linlin Liu, Xiaopei Yang, Fei Zhao, Changqing Gao, Ning Zhang, Jianjun Bao, Kuan Li, Xulan Zhang, Xiaoxiao Lu, Ye Ruan, Shurong Zhong
The ALDH2 gene encodes aldehyde dehydrogenase 2, which is the key enzyme in the metabolism of ethanol-derived acetaldehyde in hepatocytes and plays a major role in the kinetics of alcohol clearance. A genome-wide association study (GWAS) found that rs671 in the ALDH2 gene was significantly associated with AUD and its two related phenotypes (blush response and 24-hour maximum alcohol consumption) in the Chinese population (29). Studies showed that rs671 can significantly affect drinking behavior (30,31). The rs671 variant genotype (G > A) is a protective factor of drinking behavior, and individuals with the rs671 variant genotype are less likely to drink (32). Epigenetic studies on AUD have shown that the ALDH2 promoter region is hypermethylated in patients with AUD and that the methylation level correlated significantly with the rs886205 genotype in the disease group (33,34). Interestingly, in the disease group, the methylation level continued to decline to the normal level within 1–14 days of withdrawal treatment (34). Overall, the findings suggest that ALDH2 gene polymorphisms and epigenetics are closely related to AUD in different populations.
Improving mitochondrial function in preclinical models of heart failure: therapeutic targets for future clinical therapies?
Published in Expert Opinion on Therapeutic Targets, 2023
Anna Gorący, Jakub Rosik, Joanna Szostak, Bartosz Szostak, Szymon Retfiński, Filip Machaj, Andrzej Pawlik
Mitochondrial dysfunction also leads to increased lipid peroxidation, resulting in the production of highly reactive carbonyls, such as various ketones, alkanes, and aldehydes. A key role in these processes is played by aldehyde dehydrogenase (ALDH2). ALDH2 is involved in the removal and metabolism of exogenous chemicals and endogenous reactive aldehydes to maintain homeostasis and normal mitochondrial function [200]. This enzyme appears to be a promising target for therapy aimed at improving mitochondrial function in patients with HF. In an animal model of HF induced by myocardial infarction, ALDH2 activation was shown to reduce the concentration of reactive aldehydes in cardiomyocytes and limited. Most therapies to date affecting mitochondrial metabolism have focused on single factors or processes disrupted in HF. However, in this disease, there are multidirectional disorders improve mitochondrial bioenergetics [201]. Moreover, sustained ALDH2 activation prevented myocardial hypertrophy, fibrosis, and cardiac dysfunction.
College students’ use of strategies to hide facial flushing: A target for alcohol education
Published in Journal of American College Health, 2020
Karen G. Chartier, E. Clare Tiarsmith, Taryn O'Shea, Kenneth S. Kendler, Danielle M. Dick
The alcohol flushing response is an adverse reaction to the metabolism of ethanol,1 which occurs when deficient enzymes for metabolizing ethanol result in a buildup of acetaldehyde in the body.2 Alcohol-related flushing has a genetic basis. Two genetic markers associated with flushing are ADH1B*2 and ALDH2*2. They have different mechanisms affecting flushing; ADH1B*2 initiates a faster metabolism of ethanol to acetaldehyde whereas ALDH2*2 has a slower metabolism of acetaldehyde to acetate. The frequency of these genetic markers varies across populations groups. ADH1B*2 is found in 80% or more of northeast Asians (Chinese, Japanese, and Koreans) and about 10% of individuals of European ancestry.1 The ALDH2*2 variant is found almost exclusively in people of northeast Asian descent with the prevalence varying across specific Asian groups.1
Related Knowledge Centers
- Acetaldehyde
- Alcohol
- Aldehyde Dehydrogenase
- Catalysis
- Chromosome 12
- Enzyme
- Cytosol
- Gene
- Redox
- White People