Article

Hangover symptoms in Asian Americans with variations in the aldehyde dehydrogenase (ALDH2) gene

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Abstract

Hangovers are not experienced by all people and whether they contribute to the development of alcoholism is unclear. One population that might provide some insight into the role of hangover in the etiology of alcohol use disorders is that of individuals of Asian heritage. Certain Asians have lower rates of alcohol use and alcoholism, findings associated with a mutation in the aldehyde dehydrogenase (ALDH2) gene. Asians with ALDH2*2 alleles drink less and are less likely to be alcoholic than Asians without this mutation. Following alcohol ingestion, they exhibit more intense reactions to alcohol and generate higher levels of the metabolite acetaldehyde. This study evaluated hangover symptoms in Asian Americans with variations in the ALDH2 gene. Men and women of Chinese, Japanese and Korean heritage (N = 140) were asked about their drinking history and a blood sample was collected for genotyping at the ALDH2 locus. Subjects used a Likert-type scale to estimate their severity of hangover and completed a 13-item hangover scale assessing the frequency of hangover symptoms during the previous 6 months. With abstainers (n = 17) excluded and with the effects of gender and recent drinking history controlled, ALDH2 genotype accounted for a significant amount of additional variability in the estimated severity of hangover score with a similar, but nonsignificant, trend for a five-item subscale score derived from the hangover scale. These results suggest that Asian Americans with ALDH2*2 alleles may experience more severe hangovers that may contribute, in part, to protection against the development of excessive or problematic drinking in this population.

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... A mutant allele encoding an inactive subunit of aldehyde dehydrogenase-2 (ALDH2; rs671) was carried by Han Chinese as they spread throughout East Asia, and it is not found in Caucasians or Africans [7]. Alcohol consumption by Japanese is strongly inhibited by the presence of inactive ALDH2, because ALDH2-defi- cient individuals are more susceptible to alcohol flushing responses [8, 9] and hangovers [10, 11]. Headache is a major symptom of flushing responses [9] and hangovers [11] . ...
... Individuals with migraine are at higher risk of delayed alcohol-induced headache, previously named hangover headache, than people without migraine and phenotypically both types of headache have similar clinical features [16]. Headaches associated with alcohol flushing and hangover are at least in part mediated by acetaldehyde production891011. The susceptibility of Japanese headache sufferers to alcohol-associated headaches may vary with the type of headache and their ALDH2 genotype. ...
... Any significant differences in drinking frequency were not observed between subjects with tension-type headache and subjects with ''other headaches''. Possible mechanisms by which alcohol induces headache [22, 23] include a vasodilatory effect on intracranial vasculature [12] , alteration of cytokine path- ways [24], hormonal disturbance [23] , the headache provoking effects of congeners [12] , and acetaldehydemediated mechanisms91011. Male migraineurs with alcohol flushing may be more susceptible to severe alcohol-induced headache than non-migrainous headache sufferers with alcohol flushing, and that may make them more likely to avoid alcohol. ...
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The aim of the study was to investigate associations between headache types and alcohol drinking, alcohol flushing, and hangover. Alcohol consumption is inhibited by the presence of inactive aldehyde dehydrogenase-2 (ALDH2) whose carriers are susceptible to alcohol flushing and hangovers. We conducted a cross-sectional study of the 2,577 subjects (men/women: 1,018/1,559) who reported having ever experienced headaches unrelated to common colds and alcohol hangovers among 5,408 (2,778/2,630) Tokyo health checkup examinees. We used a questionnaire inquiring about current and past facial flushing after drinking a glass of beer which identifies the presence of inactive ALDH2 with a sensitivity and specificity of approximately 90%. Based on ICHD-II criteria migraine was diagnosed in 419 (75/344) subjects, and tension-type headache (TTH) in 613 (249/364). We classified the headaches of the remaining 1,545 (694/851) of headaches sufferers into the category "other headaches (OH)". The migraineurs drank alcohol less frequently than the subjects with TTH among current/past alcohol flushers and than the subjects with OH regardless of flushing category. No such difference in drinking frequency was observed between TTH and OH. Current/past flushers drank alcohol less frequently than never flushers, and the likelihood that male migraineurs would avoid alcohol drinking than men with TTH or OH was stronger among current/past flushers than among never flushers. Flushers and women were more susceptible to hangover than never flushers and men, respectively, regardless of headache type. Among never flushers, women with migraine were more susceptible to hangover than women with OH. The difference in alcohol sensitivity may partly explain less alcohol consumption by migraineurs.
... Hangover refers to physical symptoms such as headache, nausea, and fatigue that occur after breath alcohol concentration (BrAC) has returned to near zero following an acute bout of heavy drinking (Rohsenow et al., 2007), not to be confused with withdrawal, which requires chronic administration and involves differ-ent neurological systems (Prat, Adan, & Sanchez-Turet, 2009). One survey showed that greater average quantity of drinking was associated with less intense (but more frequent) hangovers in the same period (Wall, Horn, Johnson, Smith & Carr, 2000). A second survey found a relationship between frequency of hangover and frequency of heavy drinking in early college among women more than men (Piasecki, Sher, Slutske, & Jackson, 2005); hangover severity was not studied. ...
... However, the prediction of alcohol use disorder by hangover frequency could have reflected an inability to control for quantity of drinking in that study-people with more frequent hangover could also drink more heavily, in a way conducive to developing alcohol use disorders. This would be consistent with the fact that heavier quantity of drinking correlated with more frequent but less intense hangovers (Wall et al., 2000). Thus, more frequent but less intense hangovers may indicate increased risk of clinical level of problems. ...
... Future work should relate hangover sensitivity to perceived sensitivity to the first drinks in one's life (Shuckit et al., 2009). Hangover insensitivity was greater for those with higher volumes of past-month drinking at Time 1, consistent with survey results of Wall et al. (2000). These two studies support an additional possibility that acute tolerance could play a role in reducing sensitivity to hangover. ...
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Predicting continued problematic levels of drinking after the early 20's could help with early identification of persons at risk. This study investigated whether hangover insensitivity could predict postcollege drinking and problems beyond the variance due to drinking patterns. In a preliminary study, 134 college seniors from a laboratory study of hangover (Time 1) were contacted and assessed 1-4 years (M = 2.3) later (Time 2). Hangover severity was studied after controlled alcohol administration to a specific dose while controlling sleep and environmental influences. Hangover severity at Time 1 was used to predict Time 2 drinking volume and problems while controlling for relevant demographics and Time 1 drinking volume. Hangover insensitivity at Time 1 tended to predict a clinical level of alcohol problems with a large statistical effect size. Hangover sensitivity also correlated positively with sensitivity to alcohol intoxication. Hangover severity did not predict future drinking volume. Hangover insensitivity correlates with insensitivity to intoxication and might predict more serious alcohol problems in the future, suggesting that a future larger study is warranted. Hangover insensitivity could result from physiological factors underlying low sensitivity to alcohol or risk for alcoholism.
... A relatively quick conversion from ethanol into acetaldehyde is observed in people possessing ADH1B*2, ADH1B*3 and ADH1C*1 alleles, whereas ethanol metabolism is relative slow in in people possessing the ADH1B*1 and ADH1C*2 allele [57]. The ADH1B*2 (common in people of Asian descent) and ADH1B*3 alleles (prevalent in people of African American decent) result in relative high blood concentrations of acetaldehyde (and thus lower blood ethanol concentrations) [58,59]. Additionally, subjects with an ALDH2*2 allele have a slower breakdown of acetaldehyde into acetate and water. ...
... Two studies did report that subjects with Asian descent, possessing the ALDH2*2 allele, typically report significantly worse hangovers, and are more likely to experience hangovers at relatively lower alcohol consumption levels. [58,59]. Twin study by Slutske et al. [60] and Wu et al. [61] revealed that 45% [60] to 55% [61] of the frequency of experiencing hangovers. ...
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The limited number of available studies that examined the pathology of alcohol hangover focused on biomarkers of alcohol metabolism, oxidative stress and the inflammatory response to alcohol as potentially important determinants of hangover severity. The available literature on alcohol metabolism and oxidative stress is reviewed in this article. The current body of evidence suggests a direct relationship between blood ethanol concentration and hangover severity, whereas this association is not significant for acetaldehyde. The rate of alcohol metabolism seems to be an important determinant of hangover severity. That is, fast elimination of ethanol is associated with experiencing less severe hangovers. An explanation for this observation may be the fact that ethanol—in contrast to acetaldehyde—is capable of crossing the blood–brain barrier. With slower ethanol metabolism, more ethanol is able to reach the brain and elicit hangover symptoms. Hangover severity was also significantly associated with biomarkers of oxidative stress. More oxidative stress in the first hours after alcohol consumption was associated with less severe next-day hangovers (i.e., a significant negative correlation was found between hangover severity and malondialdehyde). On the contrary, more oxidative stress at a later stage after alcohol consumption was associated with having more severe next-day hangovers (i.e., a significant positive correlation was found between hangover severity and 8-isoprostane). In conclusion, assessment of biomarkers of alcohol metabolism suggests that fast elimination of ethanol is associated with experiencing less severe hangovers. More research is needed to further examine the complex interrelationship between alcohol metabolism, the role of acetaldehyde and oxidative stress and antioxidants, and the pathology of the alcohol hangover.
... On the other hand, epidemiological studies have shown that the risk of alcohol-related digestive tract cancers, such as oro-pharynx and oesophagus, is markedly increased in Asian subjects who are deficient in the ALDH2 enzyme (Murata et al., 1999; Yokoyama et al., 1996a,b,c, 1998). The variants have also been studied for association with cancer, fetal alcohol syndrome, gout, asthma, hangover susceptibility, and clearance of xenobiotics (Crabb et al., 2004; Takada et al., 1994; Wall et al., 2000; Yokoyama et al., 2005). Extensive population frequency data on ALDH2 showed that the atypical ALDH2 gene (ALDH2⁎487Lys) is extremely rare in European, Negroids, Papua New Guineans, Australian Aborigines, and Aurocanians (South Chile), but widely prevalent among East Asian (Goedde et al., 1992). ...
... Studies have shown that this atypical allele ALDH2⁎487Lys could bring various consequences to the individuals who carry it, such as protective against alcohol dependence (Chen et al., 1999a,b; Luczak et al. 2006; Maezawa et al. 1995; Tu and Israel 1995), the risk of alcohol-related digestive tract cancers (Murata et al. 1999; Yokoyama et al. 1996a,b,c, 1998). The variants have also been studied for association with fetal alcohol syndrome, cardiovascular disease, gout, asthma, hangover susceptibility, and clearance of xenobiotics (Crabb et al., 2004; Takada et al., 1994; Wall et al., 2000; Yokoyama et al., 2005). Moreover, a recent study has shown that the activation of ALDH2 is important for protection from ischemic damage to the heart and the individuals carrying atypical ALDH2 was in an adverse situation when facing the risk of heart diseases (Chen et al., 2008). ...
Article
The East Asian respond with a marked facial flushing and mild to moderate symptoms of intoxication after drinking the amounts of alcohol that has no detectable effect on European. The alcohol sensitivity in Orientals is due to a delayed oxidation of acetaldehyde by an atypical aldehyde dehydrogenase ALDH2487Lys, which is resulted from a structural mutation in gene ALDH2. The atypical ALDH2487Lys allele has been associated with various phenotypic statuses, such as protective against alcohol dependence and the risk of alcohol-related digestive tract cancers. Here, we have examined this SNP, adjacent four non-coding SNPs, and one downstream STRP on ALDH2 gene, in total of 1072 unrelated healthy individuals from 14 Chinese populations and 130 Indian individuals. Five major haplotypes based on five SNPs across the ALDH2 gene 40 kb were found in all East Asian populations. The frequencies of the ancestral haplotype GCCTG and the East Asian special haplotype GCCTA containing the atypical ALDH2487Lys allele were 44.8% and 14.9%, respectively. The frequency of the atypical ALDH2487Lys allele or the East Asian specific haplotype GCCTA is high in Yunnan, South coastal, east coastal of China, and decreased gradually toward inland China, West, Northwest and North China. Combined with demographic history in East Asian, our results showed that the presence of ALDH2487Lys allele in peripheral regions of China might be the results of historical migration events from China to these regions. The origin of ALDH2487Lys could be possibly traced back to ancient Pai-Yuei tribe in South China.
... Though alcohol tolerance can gradually be developed over time, binge drinking can especially affect carriers of the " Asian flush " gene since they may appear to be heavily intoxicated after one or two drinks (Cook et al., 2005). These symptoms may be a deterrent to the consumption of alcohol (a similar chemical mechanism is used in the anti-alcohol treatment antabuse) and is actually considered a genetic buffer against alcoholism (Edenberg et al., 2006; Wall et al., 2000). However, individuals from South Korea have been seen to show high levels of alcoholism, suggesting that genetic polymorphisms may interact with the underlying genetic mutation or, more likely, that psycho-social factors contribute to the unusually high rates (Wall et al., 1999). ...
... Regardless of ethnic and social background, carriers of the gene mutation were more sensitive to alcohol and experienced more intense hangover symptoms than those without the gene mutation (Wall et al., 2000). Thus, when Asian American men who have a genetic propensity to alcohol sensitivity are faced with stereotypes that Asian men cannot hold their liquor, alcohol use has the potential to become substance abuse, especially in college environments that endorse binge drinking (Wall et al., 1999). ...
Article
This dissertation study examined beliefs about idealized masculine cultural identity and psychological well-being among Asian American male college students using social marginality and intersectionality perspectives. An online survey (N = 381) and semi-structured interviews (n = 20) were conducted to examine an idealized cultural identity research model. Structural Equation Modeling revealed that Perceived Asian Discrimination (b = 0.29, p < .001) and Perceived Parental Perfectionism (b = 0.13, p < .01) positively related to Model Minority Male Ideal. Model Minority Male Ideal positively related to Model Minority Pride and Pressure (b = 0.46, p < .001; b = 0.12, p < .05). Model Minority Pride positively related to John Henryism (b = 0.37, p < .001) and direct coping (b = 0.29, p < .001). Model Minority Pressure negatively related to John Henryism (b = -0.14, p < .05) and direct coping (b = -0.22, p < .001). John Henryism and direct coping negatively related to perceived stress (b = -0.20, p < .001; b = -0.27, p < .001), depressive symptoms (b = -0.19, p < .001; b = -0.40, p < .001), and anxiety symptoms (b = -0.15, p < .01; b = -0.24, p < .001), and positively related to life satisfaction (b = 0.28, p < .001; b = 0.27, p < .001). John Henryism positively related to GPA (b = .15, p < .01). Seven major themes emerged from the interviews: (a) transmission of parental messages were largely tacit; (b) parental perfectionism was both resented and valued; (c) responses to perceived Asian discrimination and stereotypes were heterogeneous; (d) masculinity was characterized as strength of character; (e) multiple referents were used to implicitly describe masculinity; (f) attitudes toward out-group dating reflected complex ideas about race relations; (g) active coping was recognized and often utilized. Overall findings indicate that social marginality contributes to the endorsement of idealized beliefs about masculine cultural identity and model minority pride and pressure, which may influence active coping, psychological well-being, and academic outcomes. The results of this study have potential implications for clinical psychology, gender psychology, and developing cultural competent student services.
... These aversive symptoms of alcohol withdrawal are thought to largely contribute to an individual's propensity to consume alcohol and to their risk for alcoholism ( 2003; Koob, 2003; Wall and Ehlers, 1995). However, discrepancies in the human literature indicate that aversive alcohol withdrawal symptoms may be associated with either increased (McCaul et al., 1991; Newlin and Pretorius, 1990; Span and Earleywine, 1999) or decreased (Wall et al., 2000) subsequent alcohol consumption. Thus, the relationship between alcohol withdrawal and alcohol drinking behavior is not well understood in humans. ...
... It is likely that both the type and the severity of the alcohol withdrawal symptom may influence subsequent alcohol drinking behavior. For instance, craving has been associated with a propensity to consume excessive amounts of alcohol (Koob, 2003), whereas headache and nausea have been associated with alcohol avoidance (Wall et al., 2000). Animal models of alcohol withdrawal are advantageous because potentially confounding variables can be better controlled, such as amount of alcohol exposure and individual (e.g., genetic) and environmental factors that are known to influence the expression of the alcohol withdrawal syndrome in humans. ...
Article
The purpose of this study was to determine if aversive effects of alcohol withdrawal could be detected in mice using the place conditioning procedure and whether the GABA(A) receptor antagonist, pentylenetetrazol (PTZ), would increase the aversive effects of alcohol withdrawal and increase the probability of detecting conditioned place aversion. Subjects were alcohol-naïve mice from a specific line selectively bred for low alcohol preference (LAP1; n=91) and were assigned to three groups: alcohol withdrawal, PTZ alone, and PTZ+alcohol withdrawal. On four trials, mice received either a 4.0 g/kg intraperitoneal (i.p.) injection of alcohol (alcohol withdrawal, PTZ+alcohol withdrawal groups) or saline (PTZ group) 8 h prior to being placed on a distinctive floor texture for a 30-min conditioning session. Five minutes before these sessions, mice in the PTZ and PTZ+alcohol withdrawal groups received PTZ (5.0 mg/kg; i.p.) and the alcohol withdrawal group received saline. On intervening days mice received two saline injections at the same time points prior to being placed on a different floor texture. Post-conditioning floor preference was assessed in two 60-min tests; the first test was drug-free and the second test was state-dependent. Neither alcohol withdrawal nor PTZ produced significant place conditioning. The PTZ+alcohol withdrawal group showed a significant place aversion during the state-dependent test. These data suggest that the combined stimulus properties of PTZ and alcohol withdrawal facilitated the expression of conditioned place aversion to alcohol withdrawal.
... The severity of hangovers is also influenced by genetic factors, for example by variability in alleles decoding for aldehyde dehydrogenase (ALDH2). For example, it has been found that Asian American students with ALDH2*2 alleles may experience more severe hangovers [53], and similar findings were reported for Japanese workers [54]. Unfortunately, in both studies, a direct relationship between hangover frequency and hangover severity was not assessed. ...
... Unfortunately, in both studies, a direct relationship between hangover frequency and hangover severity was not assessed. Nevertheless, Wall et al. [53] suggested that tolerance develops to the risk of having hangovers, as they found that higher levels of usual alcohol intake were associated with increased hangover frequency and with reduced hangover severity. This suggestion is, however, not supported by the current findings. ...
Article
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Although hangover is a common consequence of heavy alcohol consumption, the area is heavily under-researched. Hangover frequency is a potential predictor of future alcohol use disorder that may be affected by hangover severity, yet the relationship between hangover frequency and severity has not been investigated. Using different methodologies and assessment instruments, two surveys, and one naturalistic study collected data on hangover frequency, hangover severity, and alcohol consumption. The relationship between hangover frequency and severity was investigated via correlational analysis, considering potentially moderating variables including alcohol intake, estimated blood alcohol concentration, demographics, and personality characteristics. In all the three studies, a positive and significant association between hangover frequency and severity was found, which remained significant after correcting for alcohol intake and other moderating factors. These findings suggest that hangover severity increases when hangovers are experienced more frequently and may be driven by sensitization or reverse tolerance to this aspect of alcohol consumption. Future research should further investigate the relationship between hangover frequency and severity and alcohol use disorder and its implications for prevention.
... Two survey investigations have demonstrated associations between ALDH2 alleles and hangover in East Asian populations [23,24]. Wall and colleagues [24] did not find an association between the flushing-related ALDH2*2 genotype and past-year hangover frequency in a sample of college students of Chinese, Japanese, or Korean descent. ...
... Two survey investigations have demonstrated associations between ALDH2 alleles and hangover in East Asian populations [23,24]. Wall and colleagues [24] did not find an association between the flushing-related ALDH2*2 genotype and past-year hangover frequency in a sample of college students of Chinese, Japanese, or Korean descent. However, carriers of ALDH2 *2 alleles scored significantly higher on a measure asking participants to estimate the severity of the hangover they would experience after consuming 6 drinks (if male) or 4 drinks (if female) over the course of a few hours. ...
Article
Hangover may be related to propensity to develop alcohol use disorders (AUDs). However, the etiological role, if any, played by hangover in AUD is unclear. From a motivational perspective, hangover can be construed as either a deterrent to future alcohol consumption or a setting event for negative reinforcement that could promote deviant drinking practices (e.g., "hair-of-the-dog" drinking). Hangover could be related to AUD risk even if it does not play a direct role in promoting or inhibiting near-term drinking. For example, measures of hangover might serve as symptoms of AUD or as markers of individual differences that more directly account for AUD risk. Empirical evidence (though usually indirect) exists to support contentions that hangover is related to both risk for and protection from AUD. In this article, we briefly address variation in assessment strategies in existing hangover research because measures of hangover frequency and hangover susceptibility may prove to have different correlates. Next, we review the existing, limited evidence on relations between hangover and AUD risk. Finally, we sketch a variety of theoretically-informed hypotheses that might help delineate productive lines of inquiry for this emerging field.
... The ALDH2 enzyme is polymorphic in humans, having two allelic forms, ALDH2*1 and ALDH2*2 caused by a point mutation at amino acid position 487, where substitution of Lysine for Glutamic acid that results from a transition of G to A at nucleotide 1510 (Hsu et al. 1985;Yoshida et al. 1991). The ALDH2 deficiency leads to an aversive response to alcohol due to elevated levels of acetaldehyde resulting in increased hangover symptoms (Wall et al. 2000) and the alcohol flush response (Li, 2000;Tanaka et al. 1997). ALDH2*1 is a very active form found at high frequency among most ethnic groups, while the ALDH2*2 is inactive (or has very low activity) and is found at high frequency among Asians (e.g. ...
Article
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KEYWORDSFamily studies; twin studies; adoptee; candidate genes; case-control studies; linkage studies; SNPs; GABA; Dopamine system; CYP2E1; Alcohol dehydrogenase ABSTRACT Alcoholism is an extremely complex disease for which no generally accepted definition exists. There is a complex interaction between the socio-environmental context, the individual at risk, and the availability of alcohol. The result of family, twin and adoption studies suggest a significant genetic predisposition to the disease. Identifying novel genetic risk factors for common diseases is a global challenge in the post genomic era. Recent molecular genetic research into the causes of alcoholism has drawn attention to the potential role of alcohol and acetaldehyde metabolizing enzymes. Functional polymorphisms have been observed at various genes encoding these enzyme proteins that act as one of the biological determinants significantly influencing drinking behavior and the development of alcoholism and alcohol-induced organ damage. Most ethanol elimination occurs by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) systems via oxidation of ethanol to acetaldehyde and acetic acid. However, the legacy of alcoholism among certain ethnic groups suggests that genetic factors can increase an individual's vulnerability for this disease. An association study in patient cohorts and controls, from large populations involving whole genome scans, is the preferred approach for complex traits. To understand the molecular epidemiology and role of cofactors in alcoholism the standard phenotype-genotype correlation may be a useful tool. The present paper reviews various aspects of alcoholism including both the behavioural and molecular etiologies.
... The ALDH2 deficiency leads to an aversive response to alcohol due to elevated levels of acetaldehyde resulting in increased hangover symptoms (Wall et al. 2000) and the alcohol flush response (Li, 2000;Tanaka et al. 1997). ...
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Constructive community drinking: a genome based socio-cultural study on Bondo highlanders" is a holistic research work on a primitive tribal community. This work emphasized on the factors regulating alcohol habits. How genes and socio-environmental adaptability protecting the community from alcoholism is explained in this work. Some of the significant generalizations that have been derived from cross-cultural studies are also validated in this study. This book is very much useful for the students of Anthropology, Sociology, Tribal Studies, Alcohol Study, Culture Study, Human Biology, Human Genetics, and Literature and also for general reader who has interest in searching knowledge.
... Hence, the toxic effects of alcohol consumption for these individuals are much more pronounced [Gelernter, 2009]. therefore, heterozygous carriers of ALDH2*504Lys consume less alcohol and are at lower risk of alcohol dependence than those lacking this allele [Wall et al., 2000;Kim et al., 2008]. A similar protective effect, although less pronounced, was shown for the ADH1B*48His allele both in combination with ALDH2*504Lys for Japanese and Korean populations [Matsuo et al., 2006;Kim et al., 2008] and on its own for white Americans and Australians [Sherva et al., 2009;Macgregor et al., 2009]. ...
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Alcohol abuse is one of the main reasons behind the low life span in Russia. Both social and genetic factors affect the alcohol consumption level. The genetic factors are alleles of the alcohol dehydrogenase ADH1B and aldehyde dehydrogenaseALDH2 genes. We have typed and found frequencies for the alleles in a cohort of 642 men, ethnic Russians. The individuals of the cohort were asked to complete a questionnaire in the framework of the Izhevsk Family Study (Leon et al., 2007, 2009) regarding the amount of alcohol consumed and on the type of hazardous alcohol consumption (nonbeverage alcohol consumption and the so-called "zapoï" which is a Russian term for a heavy drinking bout lasting for at least 2 days, when an individual is withdrawn from the normal social life). The ADH1B*48His allele was found among heterozygous individuals only (N=68, 10.6% of the cohort). The ALDH2*504Lys allele was also found among heterozygous individuals only (N=2, 0.3%) The effect of ADH1B alleles and the influence of the education level on the amount and type of alcohol consumed had not previously been studied in Russians. We have found that the amount of consumed alcohol is 21.6% lower (1733 g of ethanol per year) for ADH1B*48His allele carriers in the cohort of Russian men. The amount of consumed alcohol was found to be 9.8% lower (793 g of ethanol per year) in the case when individuals had a higher education as compared to those who had a secondary- or elementary school education level in the same cohort. Hence, the protective effect of the genetic factor (ADH1B*48His allele carriage) has proven to be more pronounced than the influence of the social factor (education level) at the individual level in the cohort of Russian men. Both factors have also proven to have a protective effect against hazardous types of alcohol consumption. Zapoï was not scored among individuals of the cohort with ADH1B*48His allele carriage (OR=12.6, P=0.006), as compared to 8.4% of "zapoï" individuals who did not carry the ADH1B*48His allele (genotype Arg/Arg).The percentage of individuals who consume non-beverage alcohol is lower (0.6%) in the subcohort of people with a higher education degree. This percentage is higher (6.0%, OR=10.0, P=0.004) in the subcohort of people without a higher education degree.
... A potentially useful approach may be to ask drinkers how likely they would be to experience hangover after drinking various amounts of alcohol (cf. Bartholow, Henry & Lust, 2007;Wall, Horn, Johnson, Smith, & Carr, 2000;Wall, Shea, Luczak, Cook, & Carr, 2005). Laboratory alcohol challenge studies are needed to rigorously evaluate the extent to which the HSS or alternatives reflect hangover susceptibility. ...
Article
The Hangover Symptoms Scale (HSS) assesses the frequency of 13 symptoms experienced after drinking in the past year. Cross-sectional analyses in college drinkers showed preliminary evidence for the validity of the HSS (Slutske et al., 2003). The current investigation extended this work by examining the construct validity of the HSS in an ecological momentary assessment investigation. Frequent drinkers (N = 404) carried electronic diaries to track their daily experiences over 3 weeks. Each morning, the diary assessed prior-night drinking behaviors, the presence of current hangover, and intensity of current headache and nausea. Adjusting for sex and body mass, the HSS significantly predicted diary endorsement of hangover (OR = 2.11, 95% CI = 1.78 to 2.49, p < 0.001). Participants who endorsed the HSS headache and nausea items were especially likely to report the elevations of corresponding symptoms in diary records made the morning after drinking. HSS scores incrementally predicted hangover when the number of drinks consumed in the episode was covaried but did not moderate the relationship between the number of drinks and diary hangover reports. The HSS appears to be a valid tool for hangover research. Higher HSS scores identify individuals who complain of "real world" hangovers and who may be especially likely to display particular symptoms after a night of drinking. Past hangovers predicted future hangovers, suggesting hangovers do not necessarily discourage or inhibit future drinking, at least across the several-week time interval studied here. There is a need to develop and evaluate complementary measures that can more directly index individual differences in hangover susceptibility in survey designs.
... For example, it has been found that in populations of Asian descent, subjects with ALDH2*2 alleles, i.e., those who breakdown acetaldehyde more slowly, typically report significantly worse hangovers, and are more likely to experience hangovers at relatively lower alcohol consumption levels. [33,34]. Therefore, future studies should confirm the current observations in subjects of non-Asian descent. ...
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An increasing number of studies are focusing on the inflammatory response to alcohol as a potentially important determinant of hangover severity. In this article, data from two studies were re-evaluated to investigate the relationship between hangover severity and relevant biomarkers of alcohol metabolism, oxidative stress and the inflammatory response to alcohol. Hangover severity was significantly and positively correlated with blood concentrations of biomarkers of the inflammatory response to alcohol, in particular, Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and C-reactive protein (CRP). At 4 h after alcohol consumption, blood ethanol concentration (but not acetaldehyde) was significantly and positively associated with elevated levels of IL-6, suggesting a direct inflammatory effect of ethanol. In addition, biomarkers of oxidative stress, i.e., malondialdehyde and 8-isoprostrane, were significantly correlated with hangover severity, suggesting that oxidative stress also contributes to the inflammatory response. The timing of the assessments suggests initial slow elimination of ethanol in the first hours after alcohol consumption. As a consequence, more ethanol is present in the second half of the night and the next morning, which will elicit more oxidative stress and a more profound inflammatory response. Together, these processes result in more severe hangovers.
... Predictors of frequency or severity of hangover found in some studies include having personality risk for alcoholism as measured by the MacAndrew Scale (Earleywine, 1993;MacAndrew, 1965), having a family history of alcoholism (Newlin and Pretorius, 1990;Piasecki et al., 2005), and having a certain alcohol dehydrogenase polymorphism (ADH1B*2) (Wall et al., 2005). Greater average quantity of drinking correlated with less intense hangovers in two studies (Rohsenow et al., 2012;Wall et al., 2000) and with more frequent hangovers in one study (Wall et al., 2005), whereas more frequent heavy drinking correlated with more frequent hangovers among women more than among men in another study (Piasecki et al., 2005). The only previous attempt to fi nd individual difference predictors of hangover insensitivity combined data across three laboratory studies of heavy episodic drinkers in which participants achieved an estimated blood alcohol concentration (BAC) of 110 mg/dl (measured by breath alcohol analysis). ...
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Objective: Although hangover results from excessive alcohol consumption, the specific pathways through which hangover symptoms arise have not been elucidated. Research on predictors of hangover sensitivity may provide clues about such mechanisms. The present study investigated whether tobacco smoking on days of heavy drinking affects next-day hangover incidence and severity. Method: The study drew on diary data from a study on smoking and drinking among 113 students at a midwestern university in the United States. Participants completed a daily, web-based, 26-item survey for 8 weeks to assess prior-day alcohol and tobacco use as well as current-day hangover symptoms. Hierarchical linear modeling was used to test the hypothesis that amount of smoking is related to hangover, controlling for amount of alcohol consumed, sex, and other individual characteristics. Analyses were conducted after selecting only days with alcohol consumption levels that typically elicit hangover, then repeated on lighter drinking days for comparison. Validity of the hangover items was checked by comparing reports after such heavy drinking days with days of lighter drinking. Results: Across all possible person-days, 92% of daily reports were obtained. When selecting only events where an estimated blood alcohol concentration of 110 mg/dl was attained, smoking significantly increased the odds of hangover incidence and hangover severity while controlling for number of drinks consumed and sex. Additional analyses controlling for age first smoked regularly, frequency of drug use, type of drug involvement, or smoking status resulted in findings that were unchanged. Conclusions: Smoking more on heavy drinking days affects hangover sensitivity and severity, possibly because of acute pharmacological effects.
... Possession of an ALDH2*2 allele also has been associated with lower levels of self-reported alcohol-related problems (Hendershot et al., 2009;Luczak, Shea, et al., 2006) and alcohol dependence (Luczak, Glatt, et al., 2006). Individuals with ALDH2*2, however, expect to have more severe hangover symptoms from the same amount of alcohol and are more likely to report hangovers after consuming lower amounts, suggesting that lower doses of alcohol may lead to negative drinking consequences in those with ALDH2*2 (Wall, Horn, Johnson, Smith, & Carr, 2000;Yokoyama et al., 2005). Consistent with this idea, there is evidence that individuals with ALDH2*2 who develop alcohol dependence do so at lower levels of alcohol intake (Iwahashi, Matsuo, Suwaki, Nakamura, & Ichikawa, 1995). ...
Article
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The variant aldehyde dehydrogenase allele, ALDH2∗2, consistently has been associated with protection against alcohol dependence, but the mechanism underlying this process is not known. This study examined growth trajectories of alcohol consumption (frequency, average quantity, binge drinking, maximum drinks) and problems over the college years and then tested whether the ALDH2 genotype mediated or moderated the relationship between alcohol consumption and problems. Asian American college students (N = 433) reported on their drinking behavior in their first year of college and then annually for 3 consecutive years. Alcohol consumption and problems increased over the college years for both those with and without ALDH2∗2, but having an ALDH2∗2 allele was associated with less of an increase in problems over time. A mediation model was supported, with ALDH2∗2 group differences in problems fully accounted for by differences in frequency of binge drinking. Findings also supported a moderation hypothesis: All four alcohol consumption variables were significant predictors of subsequent alcohol problems, but these relationships were not as strong in those with ALDH2∗2 as in those without ALDH2∗2. Our findings suggest that the interplay between ALDH2∗2 and drinking-related problems is complex, involving both mediation and moderation processes that reduce the likelihood of developing problems via reduction of heavy drinking as well as by altering the relationship between alcohol consumption and problems. Results of this longitudinal study provide evidence that what seems like a relatively straightforward effect of a diminished ability to metabolize alcohol on drinking behavior is actually dependent on behavior and developmental stage. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
... Most reviews suggest that acetaldehyde is responsible for the hangover [11,12,13] . Markedly increased circulating acetaldehyde levels after alcohol consumption may cause vasodilation, flushing of the face, nausea, and headache in approximately one third of people originating from East Asian countries who are homozygous or heterozygous for a defective form of aldehyde dehydrogenase-2 (ALDH-2), [8,14,15,16]. In addition, disulfiram, an aldehyde dehydrogenase inhibitor, given with ethanol, causes symptoms similar to those seen in individuals expressing functionally inactive ALDH-2. ...
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The mechanism of veisalgia cephalgia or hangover headache is unknown. Despite a lack of mechanistic studies, there are a number of theories positing congeners, dehydration, or the ethanol metabolite acetaldehyde as causes of hangover headache. We used a chronic headache model to examine how pure ethanol produces increased sensitivity for nociceptive behaviors in normally hydrated rats. Ethanol initially decreased sensitivity to mechanical stimuli on the face (analgesia), followed 4 to 6 hours later by inflammatory pain. Inhibiting alcohol dehydrogenase extended the analgesia whereas inhibiting aldehyde dehydrogenase decreased analgesia. Neither treatment had nociceptive effects. Direct administration of acetate increased nociceptive behaviors suggesting that acetate, not acetaldehyde, accumulation results in hangover-like hypersensitivity in our model. Since adenosine accumulation is a result of acetate formation, we administered an adenosine antagonist that blocked hypersensitivity. Our study shows that acetate contributes to hangover headache. These findings provide insight into the mechanism of hangover headache and the mechanism of headache induction.
... Consistent with this hypothesis, drinkers report hangover avoidance as a reason for limiting alcohol use (Smith, Bookner, and Dreher, 1988). Variants of ADH1B and ALDH2 genes that result in aversive flushing responses to alcohol consumption have been associated with both decreased AUD risk and more severe anticipated hangover symptoms after drinking (Wall, Horn, Johnson, Smith, & Carr, 2000;Wall, Shea, Luczak, Cook, & Carr, 2005). Rodriguez and Span (2008) found that symptoms of attention-deficit hyperactivity disorder were cross-sectionally associated with more frequent drinking, but only among individuals who anticipated experiencing low hangover symptoms after consuming 4 standard drinks. ...
Article
Measures of hangover are associated with current and future problematic alcohol use. At present, it is not known whether these associations reflect any direct influence of hangover events on near-term drinking behaviors. The current study aimed to determine whether hangover following a drinking episode influences time to next drink (TTND) and, if so, to determine the direction of this effect and identify any moderating personal or contextual factors. Community-recruited, frequent drinkers oversampled for current smoking (N = 386) carried electronic diaries for 21 days, reporting on drinking behaviors and other experiences. Survival analysis was used to model data from 2,276 drinking episodes, including 463 episodes that were followed by self-reported hangover in morning diary entries. When tested as the sole predictor in a survival model, hangover was associated with increased TTND. The median survival time was approximately 6 hours longer after episodes with hangovers compared to those without. In a multivariate model, hangover was only significant in the presence of interaction effects involving craving at the end of the index drinking episode and the occurrence of financial stressors. Additional predictors of TTND in the final multivariate model included age, lifetime alcohol use disorder diagnosis, typical drinking frequency, day of the week, and morning reports of craving, negative affect, and stressors after the index episode. There was no association between morning reports of hangover and contemporaneous diary ratings of likelihood of drinking later the same day. The findings suggest that hangover has, at best, a modest or inconsistent influence on the timing of subsequent alcohol use among frequent drinkers.
... In non-alcoholic populations, the prevalence rates range from 24 to 30% (Chao et al., 1994;Chen et al., 1996;Higuchi, 1994;Thomasson et al., 1991), whereas it was 13% in our nonor infrequent drinkers. The preventive role of the ALDH2*2 allele in the development of hazardousharmful drinking and alcohol dependence is consistent with other studies (Peng et al., 1999;Tanaka et al., 1997;Wall et al., 2000Wall et al., , 2001. Our subjects who were heterozygous ALDH2*1y*2 were less likely to be alcohol-dependent and hazardousyharmful drinkers, compared with subjects with the homozygous ALDH2*1 allele. ...
Article
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The drinking behavior, alcohol-induced facial flushing and ALDH2 genotypes were determined in 283 Thai men comprising 85 who were alcohol-dependent, 62 hazardous/harmful drinkers and 136 non-drinkers or infrequent drinkers. A structured interview questionnaire, containing the ‘tri-level’ method and the Alcohol-Use Disorders and Associated Disabilities Schedule, was used to determine the quantity of drinking and the number of alcohol-related adverse experiences. The study revealed the mutant ALDH2*2 allele in 44 (15.5%) subjects. The risks of being alcohol-dependent and of having hazardous/harmful drinking were lower in individuals with heterozygous ALDH2*1/*2, compared with homozygous ALDH2*1/*1 [relative probability ratios (95% CI) 0.14 (0.05–0.41) and 0.23 (0.08–0.61), respectively]. Eighty percent of those who were heterozygous and 28% of those who were homozygous ALDH2*1 reported flush symptoms after drinking alcohol. Twenty-nine percent of homozygous ALDH2*1 individuals, but only 9% of heterozygous subjects, drank almost everyday (24–30 days/month). Similarly, higher percentages of people drinking beyond the safety limit (>60 g/day) and having alcohol-related problems were observed in homozygous ALDH2*1 compared with heterozygous individuals: 32% vs. 5% and 27% vs. 12%, respectively. Overall, the study supports the role of the mutant ALDH2*2 allele in preventing high alcohol consumption and the development of alcohol dependence in a Thai population.
... The mitochondrial form of aldehyde dehydrogenase (ALDH2) is the enzyme primarily responsible for the metabolism of acetaldehyde to acetate (for reviews of ethanol metabolism and dependence see Agarwal (2001); Li (2000); Ramchandani et al. (2001). ALDH2 deficiency leads to an aversive response to alcohol due to elevated levels of acetaldehyde, resulting in increased hangover symptoms (Wall et al., 2000) and the alcohol flushing response, or alcohol sensitivity (Box 5.2) (Tanaka et al., 1997;Li, 2000). ALDH2 is found on chromosome 4p which has been linked to alcohol dependence in Asians and Europeans. ...
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Melatonin is a pleiotropic signalling molecule that regulates several physiological functions, and synchronises biological rhythms. Recent evidences are beginning to reveal that a dysregulation of endogenous melatonin rhythm or action may play a larger role in the aetiology and behavioural expression of drug addiction, than was previously considered. This review, using information garnered from extant literature, examines the roles played by melatonin and its receptors in addictive behaviours, addiction related changes in brain chemistry and brain plasticity; and its possible benefits in the management of drug associated withdrawal syndrome, relapse and behavioural sensitisation.
... Twin studies showed that heritability of this genetic variation is related to about 45% of the reported hangover severity [9,10]. In this context, in populations of Asian descent, subjects with ALDH2*2 alleles, i.e., those who breakdown acetaldehyde more slowly, usually report significantly worse hangovers [11,12], and are more likely to experience hangovers at lower alcohol consumption levels than others. In such hangover-sensitive drinkers, the amount of alcohol does not need to be elevated to elicit a hangover. ...
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In 2016, the Alcohol Hangover Research Group defined the alcohol hangover as “the combination of mental and physical symptoms experienced the day after a single episode of heavy drinking, starting when blood alcohol concentration (BAC) approaches zero”. In the light of new findings and evidence, we carefully reviewed the different components of that definition. Several studies demonstrated that alcohol hangovers are not limited to heavy drinking occasions. Instead, data from both student and non-student samples revealed that at a group level, alcohol hangover may occur at much lower BAC levels than previously thought. Regression analysis further revealed that for individual drinkers, the occurrence of hangovers is more likely when subjects consume more alcohol than they usually do. However, hangovers may also occur at a drinker’s usual BAC, and in some cases even at lower BAC (e.g. in case of illness). We also carefully reviewed and modified other parts of the definition. Finally, hangovers are not necessarily limited to the ‘next day’. They can start at any time of day or night, whenever BAC approaches zero after a single dinking occasion. This may also be on the same day as the drinking occasion (e.g. when drinking in, or until the morning and subsequently having a hangover in the afternoon or evening). To better reflect the new insights and sharpen the description of the concept, we hereby propose to update the definition of the alcohol hangover as follows: “The alcohol hangover refers to the combination of negative mental and physical symptoms which can be experienced after a single episode of alcohol consumption, starting when blood alcohol concentration (BAC) approaches zero”, and recommend to use this new definition in future hangover research.
... Wide variety of symptoms are known to occur in hangover with lot of individual variations, making it impossible to evaluate all the symptoms . A better approach would be to use a validated symptom score such as hangover severity scale (Slutske, Piasecki, & Hunt-Carter, 2003), acute hangover scale (Rohsenow, Howland, Minsky, Almeida, & Roehrs, 2007), and alcohol hangover severity scale (Wall, Horn, Johnson, Smith, & Carr, 2000). ...
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Objective: To evaluate new research conducted over the past few years (2009-2016) assessing the effectiveness of potentially curative and/or preventive methods of alcohol hangover. Methods: Data were retrieved by a 4-stage systematic search process. A search of the online Pubmed and Scopus databases were performed, using a combination of keywords: "Alcohol," "Ethanol," and "C2 H5 OH," in combination with the terms "Hangover," "Treatment," and "Prevention." The search comprised studies listed between January 1, 2009 and June 30, 2016. Findings were synthesized using a systematic approach. Quantitative analysis was not done because of the heterogeneity of the included studies. Results: Six controlled human studies were identified (placebo controlled-3, controlled studies with a comparator intervention-3). Of the interventions, the use of polysaccharide rich extract of Acanthopanax senticosus, red ginseng antihangover drink, Korean pear juice, KSS formula, and the After-Effect© were associated with a significant improvement of hangover symptoms (p < .05). The highest improvement was observed for the following symptoms: tiredness, nausea/vomiting, and stomachache. None of the methods were effective for all the symptoms. Conclusion: The available evidence suggests that several products are capable of significantly improving some, but not all, of the symptoms related to alcohol hangover. Therefore, further research is necessary to develop clinically effective hangover treatments.
... Asians may experience more severe hangovers perhaps because of the common variations in the aldehyde dehydrogenase (ALDH2) gene that delay the clearance of this major metabolite of alcohol. See Wall et al. (2000) and below. Hangover symptoms in Asian Americans correlate to some extent with the presence of this genetic variant -see below. ...
Article
Hangovers represent a major source of distress to the individual and a huge source of economic loss to society. Hangovers and their associated problems have been recognised for thousands of years in both Western and Eastern cultures but only in recent years has there been any scientific research into their mechanisms and treatments. This small review contrasts Chinese and Western approaches to the question of hangovers. We also give an overview of recent research into the mechanisms that may underpin it, which may suggest new approaches to prevention or treatment of hangovers.
... A famous SNP is NCBI/Rs671, NM_000690.3 (ALDH2): c.1510G>A (p.Glu504-Lys), which is associated with acute alcohol sensitivity [14], susceptibility to hangover [15], efficacy of sublingual nitroglycerin [16], esophageal cancer [17], liver cancer [18], etc. Another example is some SNPs in CYP2C19 associated with drug response to Mephenytoin [19] and Proguanil [20]. ...
Article
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Single Nucleotide Polymorphism (SNP), not only has been used in genetic research widely, but also has magnificent clinical significance. Scientists have developed many methods to detect SNP, but few of which are available for clinic. Amplification refractory mutation system-quantitative PCR (ARMS-qPCR) has been used for detection of mutations, but its application in SNPs in genome has not been discussed well yet. Here, we genotyped three novel SNPs, NM_020630.4 (RET): c.135 G>A, NM_020630.4 (RET): c.2307 T>G and NM_018206.4 (VPS35): c.1648-24 T>C, in human genome with nested ARMS-qPCR. Nested ARMS-qPCR was accurate and available for the three SNPs. Compared with PCR-sequencing, the golden standard, nested ARMS-qPCR had no significant difference in SNP genotyping (P>0.05). We also found out the alleles and genotype frequency of three novel SNPs with nested ARMS-qPCR. Nowadays, qPCR is a conventional technique in molecular diagnosis lab, and 7500 Real time PCR System (Applied Biosystems) has been approved by authority in clinical usage. With the characteristics of accuracy, rapidity and ease of operation, ARMS-qPCR has a bright future in clinical screening of SNP.
... Reduced consumption, in turn, leads to fewer alcohol-related adverse consequences, as indicated by lower scores on questionnaires measuring hazardous alcohol use and alcohol-related problems (Hendershot et al. 2009a(Hendershot et al. , 2011. Similarly, hangovers and blackouts as consequences of heavy drinking also are inversely associated with ALDH2*2 (Luczak et al. 2006b;Wall et al. 2000). A longitudinal study found that ALDH2*2 changes the association between alcohol consumption and problems over time, with ALDH2*2 group differences in alcohol-related problems fully accounted for by differ-ences in frequency of binge drinking (Luczak et al. 2014). ...
Article
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Gene variants encoding several of the alcohol-metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), are among the largest genetic associations with risk for alcohol dependence. Certain genetic variants (i.e., alleles)-particularly the ADH1B*2, ADH1B*3, ADH1C*1, and ALDH2*2 alleles-have been associated with lower rates of alcohol dependence. These alleles may lead to an accumulation of acetaldehyde during alcohol metabolism, which can result in heightened subjective and objective effects. The prevalence of these alleles differs among ethnic groups; ADH1B*2 is found frequently in northeast Asians and occasionally Caucasians, ADH1B*3 is found predominantly in people of African ancestry, ADH1C*1 varies substantially across populations, and ALDH2*2 is found almost exclusively in northeast Asians. Differences in the prevalence of these alleles may account at least in part for ethnic differences in alcohol consumption and alcohol use disorder (AUD). However, these alleles do not act in isolation to influence the risk of AUD. For example, the gene effects of ALDH2*2 and ADH1B*2 seem to interact. Moreover, other factors have been found to influence the extent to which these alleles affect a person's alcohol involvement, including developmental stage, individual characteristics (e.g., ethnicity, antisocial behavior, and behavioral undercontrol), and environmental factors (e.g., culture, religion, family environment, and childhood adversity).
... Although the literature is in its infancy, different biobehavioral factors have been studied as potential determinants of alcohol hangover, following alcohol administration (oral or intravenous) in the lab, as well as alcohol consumption in naturalistic settings. Previous data, for example, illustrates that genetic variants of alcohol metabolizing enzymes may predict the frequency and severity of alcohol hangover symptoms (Wall et al., 2000;Wall et al., 2005;Yokoyama et al., 2005). A potential gender difference has also been reported, showing that females are more prone to alcohol hangover, compared to males (Piasecki et al., 2005;Slutske et al., 2003;Vatsalya et al., 2018;Verster et al., 2003). ...
Article
Ghrelin, an orexigenic peptide synthesized in the stomach, is a key player in the gut-brain axis. In addition to its role in regulating food intake and energy homeostasis, ghrelin has been shown to modulate alcohol-related behaviors. Alcohol consumption frequently results in hangover, an underexplored phenomenon with considerable medical, psychological, and socioeconomic consequences. While the pathophysiology of hangover is not clear, contributions of mechanisms such as alcohol-induced metabolic/endocrine changes, inflammatory/immune response, oxidative stress, and gut dysbiosis have been reported. Interestingly, these mechanisms considerably overlap with ghrelin's physiological functions. Here, we investigated whether pharmacological manipulation of the ghrelin system may affect alcohol hangover symptoms. Data were obtained from two placebo-controlled laboratory studies. The first study tested the effects of intravenous (IV) ghrelin and consisted of two experiments: a progressive-ratio IV alcohol self-administration (IV-ASA) and a fixed-dose IV alcohol clamp. The second study tested the effects of an oral ghrelin receptor inverse agonist (PF-5190457) and included a fixed-dose oral alcohol administration experiment. Alcohol hangover data were collected the morning after each alcohol administration experiment using the Acute Hangover Scale (AHS). IV ghrelin, compared to placebo, significantly reduced alcohol hangover after IV-ASA (p = 0.04) and alcohol clamp (p = 0.04); PF-5190457 had no significant effect on AHS scores. Females reported significantly higher hangover symptoms than males following the IV-ASA experiment (p = 0.04), but no gender × drug condition (ghrelin vs. placebo) effect was found. AHS total scores were positively correlated with peak subjective responses, including 'stimulation' (p = 0.08), 'sedation' (p = 0.009), 'feel high' (p = 0.05), and 'feel intoxicated' (p = 0.03) during the IV-ASA. IV ghrelin blunted the positive association between alcohol sedation and hangover as shown by trend-level drug × sedation effect (p = 0.08). This is the first study showing that exogenous ghrelin administration, but not ghrelin receptor inverse agonism, affects hangover symptoms. Future research should investigate the potential mechanism(s) underlying this effect.
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A sample of college students, oversampled for smoking (N = 127, 43% smokers), monitored their daily experiences using electronic diaries over 14 days. We examined the frequency and correlates of liberally defined hangoverlike experiences (HLEs) using data from 1,595 person-days (1,325 after abstention from drinking and 270 after drinking, including 125 HLEs). More than 40% of the sample reported at least one HLE, and nearly half of all drinking episodes were followed by HLE. Endorsement of HLE was more likely as the number of drinks increased and was associated with modest elevations of hangover symptoms. Gender did not predict rates of overall HLE endorsement, but male students were less likely than female students to report an HLE after a drinking episode and showed a weaker relation between number of drinks and HLE. Smokers were more likely to report HLE, but there was no evidence that smoking status was associated with increased HLE susceptibility. Self-reported parental alcohol problems were associated with more frequent HLE and incrementally predicted HLE endorsement when number of drinks was covaried. The findings suggest that HLE is a common outcome of college drinking and attest to the feasibility of using electronic diaries to assess its episode- and person-level correlates.
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We aimed to investigate whether ethanol (EtOH) and acetaldehyde (AcH) can affect glutamate and its receptors GluN1 and GluA1 in the hippocampus of Aldh2-knockout (Aldh2-KO) and C57BL/6N (wild-type (WT)) mice. To do this, we first examined the effect of local administration of EtOH (100 mM, 200 mM, and 500 mM) and AcH (100 μM, 200 μM, and 500 μM) on extracellular glutamate levels in freely moving mice. Retrodialysis of 200 mM and 500 mM EtOH into the hippocampus of WT and Aldh2-KO mice produced significant decreases in extracellular glutamate levels (p < 0.05). A dose of 500 mM EtOH induced a greater decrease in Aldh2-KO mice (p < 0.05) than in WT mice, indicating the action of AcH. Similarly, perfusion of 200 μM and 500 μM AcH decreased glutamate in Aldh2-KO mice (p < 0.05), but this decrease was not seen in WT mice at any AcH dose. Second, we tested whether the EtOH- and AcH-induced decrease in glutamate was associated with decreases in GluN1 and GluA1 expression, as measured by real-time PCR and Western blot. We found a significant decrease in GluN1 (p < 0.05) and GluA1 (p < 0.05) subunits after a high dose of EtOH (4.0 g/kg) and AcH (200 mg/kg) in WT mice. However, a 2.0 g/kg dose of EtOH did not produce a consistent decrease in GluN1 or GluA1 between messenger RNA and protein. In Aldh2-KO mice, all three doses of EtOH (1.0 g/kg, 2.0 g/kg, and 4.0 g/kg) and AcH (50 mg/kg, 100 mg/kg, and 200 mg/kg) decreased GluN1 expression (p < 0.05), while moderate-to-high doses of EtOH (2.0 g/kg and 4.0 g/kg) and AcH (100 mg/kg and 200 mg/kg) decreased GluA1 expression (p < 0.05). Together, these in vivo and ex vivo data suggest that EtOH and AcH decrease extracellular glutamate in the hippocampus of mice with a concomitant decrease in GluN1 and GluA1 subunits, but these effects require relatively high concentrations and may, therefore, explain the consequences of EtOH intoxication.
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Studying its history generally provides insights relevant to current understanding of a subject: the health effects of alcohol consumption is no exception to this rule. Perceiving past errors in the hopes of avoiding their repetition is crucial. Because there are clear disparities in the relationships of alcohol drinking to various cardiovascular conditions, attempts to simplify the subject of alcohol and cardiovascular diseases have delayed understanding this area. Thus, the following are considered separately: cardiomyopathy, arsenic and cobalt beer-drinkers' disease, cardiovascular beri-beri, systemic hypertension, cardiac arrhythmias, stroke, atherosclerotic coronary heart disease (CHD), total mortality, and definitions of safe drinking limits. The basic disparity underlying all alcohol-health relations is between effects of lighter and heavier drinking.
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Recent advances in the field of acetaldehyde (AcH) research have raised the need for a comprehensive review on the role of AcH in the actions of alcohol. This update is an attempt to summarize the available AcH research. The descriptive part of this article covers not only recent research but also the development of the field. Special emphasis is placed on mechanistic analyses, new hypotheses, and conclusions. Elevated AcH during alcohol intoxication causes alcohol sensitivity, which involves vasodilation associated with increased skin temperature, subjective feelings of hotness and facial flushing, increased heart and respiration rate, lowered blood pressure, sensation of dry mouth or throat associated with bronchoconstriction and allergy reactions, nausea and headache, and also reinforcing reactions like euphoria. These effects seem to involve catecholamine, opiate peptide, prostaglandin, histamine, and/or kinin mechanisms. The contribution of AcH to the pathological consequences of chronic alcohol intake is well established for different forms of cancer in the digestive tract and the upper airways. AcH seems to play a role in the etiology of liver cirrhosis. AcH may have a role in other pathological developments, which include brain damage, cardiomyopathy, pancreatitis, and fetal alcohol syndrome. AcH creates both unpleasant aversive reactions that protect against excessive alcohol drinking and euphoric sensations that may reinforce alcohol drinking. The protective effect of AcH may be used in future treatments that involve gene therapy with or without liver transplantation. AcH plays a role in most of the actions of alcohol. The individual variability in these AcH-mediated actions will depend on the genetic polymorphism, not only for the alcohol and AcH-metabolizing enzymes but also for the target sites for AcH actions. The subtle balance between aversive and reinforcing, protecting and promoting factors will determine the overall behavioral and pathological developments.
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We have previously shown that a genetic association exists between low alcohol drinking and high alcohol withdrawal magnitude after acute alcohol exposure in alcohol-naïve rats. However, the behavioral rating scale used in this prior study was not optimal for assessing the magnitude of mild alcohol withdrawal. The present study examined whether a genetic relationship is again found between alcohol preference and alcohol withdrawal magnitude when a sensitive measure is used to index mild alcohol withdrawal in rats. Alcohol-naïve, male rats selectively bred for alcohol preference (P, HAD1, HAD2) or nonpreference (NP, LAD1, LAD2) received a single intragastric infusion of alcohol (4.0 g/20.3 ml/kg body weight; 25% v/v) or water followed by acoustic startle testing. Startle probability and magnitude was greater in water-treated P than in water-treated NP rats. During alcohol withdrawal, startle probability and magnitude was suppressed in P rats and elevated in NP rats relative to water-treated controls. Startle probability and magnitude was greater in water-treated LAD1 rats than in water-treated HAD1 rats. During alcohol withdrawal, startle probability and magnitude was suppressed in HAD1 and elevated in LAD1 rats relative to water-treated controls at 20 hr after acute alcohol exposure. Startle probability and magnitude did not differ between water-treated HAD2 and water-treated LAD2 rats. During alcohol withdrawal, there was a trend toward decreased startle probability and magnitude in HAD2 rats compared with water-treated controls. The acoustic startle response to a tone stimulus is a sensitive measure of mild alcohol withdrawal in rats. Rats selectively bred for low alcohol intake showed greater alcohol withdrawal magnitude than did rats selectively bred for high alcohol intake. These results provide further evidence that an inverse genetic association exists between alcohol withdrawal magnitude and propensity toward alcohol drinking in rats.
Article
The drinking behavior, alcohol-induced facial flushing and ALDH2 genotypes were determined in 283 Thai men comprising 85 who were alcohol-dependent, 62 hazardous/harmful drinkers and 136 non-drinkers or infrequent drinkers. A structured interview questionnaire, containing the 'tri-level' method and the Alcohol-Use Disorders and Associated Disabilities Schedule, was used to determine the quantity of drinking and the number of alcohol-related adverse experiences. The study revealed the mutant ALDH2*2 allele in 44 (15.5%) subjects. The risks of being alcohol-dependent and of having hazardous/harmful drinking were lower in individuals with heterozygous ALDH2*1/*2, compared with homozygous ALDH2*1/*1 [relative probability ratios (95% CI) 0.14 (0.05-0.41) and 0.23 (0.08-0.61), respectively]. Eighty percent of those who were heterozygous and 28% of those who were homozygous ALDH2*1 reported flush symptoms after drinking alcohol. Twenty-nine percent of homozygous ALDH2*1 individuals, but only 9% of heterozygous subjects, drank almost everyday (24-30 days/month). Similarly, higher percentages of people drinking beyond the safety limit (>60 g/day) and having alcohol-related problems were observed in homozygous ALDH2*1 compared with heterozygous individuals: 32% vs. 5% and 27% vs. 12%, respectively. Overall, the study supports the role of the mutant ALDH2*2 allele in preventing high alcohol consumption and the development of alcohol dependence in a Thai population.
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The field of genetics holds great promise for furthering our understanding of the etiology of drug dependence and for identifying novel targets for treatment. Genetic studies utilizing twins and families have demonstrated a considerable role for genetics in nicotine and/or alcohol dependence. Risk for alcoholism or nicotine dependence is likely to be the result of a large number of genes, each contributing a small fraction of the overall risk. While this review will focus on studies in humans, many of the candidate genes for human nicotine and alcohol dependence listed here were originally postulated to be important, based on data from animal studies. The review will briefly summarize the results from twin and adoption studies that provide estimations of heritability, the results from chromosomal linkage studies that identify regions of chromosomes that may contain relevant genes, and the results of candidate gene studies. For each topic the data will be presented for nicotine dependence, alcohol dependence, and for nicotine and alcohol dependence together. In addition, each section will review briefly some of the confounding issues in the specific type of approach utilized.
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Despite its ubiquity, hangover has received remarkably little systematic attention in alcohol research. This may be due in part to the lack of a standard measure of hangover symptoms that cleanly taps the physiologic and subjective effects commonly experienced the morning after drinking. In the present study, we developed and evaluated a new scale, the Hangover Symptoms Scale (HSS), to potentially fill this void. Participants were 1230 currently drinking college students (62% women, 91% Caucasian). They were administered a self-report inventory in which they reported the frequency of occurrence of 13 different hangover symptoms during the past 12 months. Participants also reported their history of alcohol involvement, alcohol-related problems, and family history of alcohol-related problems. On average, participants experienced 5 out of 13 different hangover symptoms in the past year; the three most common symptoms were feeling extremely thirsty/dehydrated, feeling more tired than usual, and headache. Higher scores on the HSS were significantly positively associated with the frequency of drinking and getting drunk and the typical quantity of alcohol consumed when drinking, a personal history of alcohol-related problems, and a family history of alcohol-related problems. After controlling for sex differences in alcohol involvement, women had higher scores on the HSS than men. The HSS appears to capture a reasonably valid set of adjectives describing common hangover effects. It is hoped that the availability of a brief, valid hangover assessment such as the HSS will encourage further study of hangover's frequency, correlates, and consequences. Future research is needed to explore the performance of a re-worded HSS in laboratory settings, which may help bridge the gap between laboratory and survey investigations of hangover.
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Alcohol-induced hangover, defined by a series of symptoms, is the most commonly reported consequence of excessive alcohol consumption. Alcohol hangovers contribute to workplace absenteeism, impaired job performance, reduced productivity, poor academic achievement, and may compromise potentially dangerous daily activities such as driving a car or operating heavy machinery. These socioeconomic consequences and health risks of alcohol hangover are much higher when compared to various common diseases and other health risk factors. Nevertheless, unlike alcohol intoxication the hangover has received very little scientific attention and studies have often yielded inconclusive results. Systematic research is important to increase our knowledge on alcohol hangover and its consequences. This consensus paper of the Alcohol Hangover Research Group discusses methodological issues that should be taken into account when performing future alcohol hangover research. Future research should aim to (1) further determine the pathology of alcohol hangover, (2) examine the role of genetics, (3) determine the economic costs of alcohol hangover, (4) examine sex and age differences, (5) develop common research tools and methodologies to study hangover effects, (6) focus on factor that aggravate hangover severity (e.g., congeners), and (7) develop effective hangover remedies.
Article
AimsTo quantify the relative contributions of genetic and environmental factors to alcohol hangover.DesignBiometric models were used to partition the variance in hangover phenotypes.SettingA community-based sample of Australian twins.ParticipantsMembers of the Australian Twin Registry, Cohort II who reported consuming alcohol in the past year when surveyed in 2004-2007 (N= 4,496).MeasurementsTelephone interviews assessed participants’ frequency of drinking to intoxication and frequency of hangover the day after drinking. Analyses examined three phenotypes: hangover frequency, hangover susceptibility (i.e., residual variance in hangover frequency after accounting for intoxication frequency) and hangover resistance (a dichotomous variable defined as having been intoxicated at least once in the past year with no reported hangovers).FindingsGenetic factors accounted for 45% (95% confidence interval [CI] = 37-53%) and 40% (95% CI = 33-48%) of the variation in hangover frequency in men and women, respectively. Most of the genetic variation in hangover frequency overlapped with genetic contributions to intoxication frequency. Genetic influences accounted for 24% (95% CI = 14-35%) and 16% (95% CI 8-25%) of the residual hangover susceptibility variance in men and women, respectively. Forty-three percent (95% CI 22-63%) of the variation in hangover resistance was explained by genetic influences, with no evidence for significant sex differences. There was no evidence for shared environmental influences for any of the hangover phenotypes.Conclusions Individual differences in the propensity to experience a hangover and of being resistant to hangover at a given level of alcohol use are genetically influenced.
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Middle phalangeal hair has been a focus of study in different populations for the absence or presence of this trait. Clinically, this is often perceived as a solely cosmetic feature. However, because of a series of patients questioning the presence of hair on this location, we have performed a more in-depth literature-based evaluation of the trait. The goal of this manuscript was to examine the clinical significance of this anthropological phenomenon. A literature review was performed that focused on the differences of this trait in terms of pattern of presentation, age, race, sex, and usage as an identifiable marker for medical significance in certain medications and criteria for tailored treatment. Anatomically, middle phalangeal hair is mostly on the fourth finger and more ulnar rather than central or symmetric in pattern of deviation. Its presence has been most associated with high prenatal androgen exposure, predisposing patients to suffer from adverse side effects from oral contraceptives. Phalangeal hair may be helpful in tailoring treatment to certain patients from different ethnic backgrounds, and particularly in individuals with unknown ancestry.
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Ethnopharmacological relevance: Hovenia dulcis, known as the oriental raisin tree, is mainly found in East Asia. It has long been used as traditional folk remedies for alcohol intoxication. Aim of the study: To examine the anti-hangover effect of Hovenia dulcis Thunb. fruit extract (HDE) in a randomized controlled crossover trial. Materials and methods: Twenty-six eligible male adults with heterozygous ALDH2 (23.7 ± 0.3 years old) consumed 360mL of Korean Soju (50g alcohol) together with HDE (2,460mg) or matched placebo with subsequent crossover. The blood samples were taken at baseline and 1, 2, 4, and 12h post-treatment. Results: Blood alcohol, acetaldehyde, and total hangover scores were highest at 1h post-treatment with no difference between groups, but declines in hangover symptom scores were significant in the HDE group compared to the placebo group. Significant differences between groups were also observed on interleukin (IL)-6, IL-10, IL-10/IL-6 ratio, and aspartate aminotransferase levels, but not on endotoxins. Pearson correlation analysis revealed a positive correlation between total hangover symptom scores and IL-6 and IL-10 level. Further analyses by CYP2E1 polymorphism at rs10776687, rs2031920, rs3813867, and rs4838767 alleles showed a reversed association, suggesting that CYP2E1 polymorphism might be an effect modifier. Conclusions: The results suggest that a favorable effect of HDE on alcohol hangovers might be associated with enhancing homeostatic regulation of inflammatory response. The magnitude of impact might be different in the presence of CYP2E1 polymorphism.
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This study explored drinking patterns, alcohol-related flushing, and ways students themselves and other people respond to flushing in drinking situations. Of 1080 Chinese undergraduate university students given the survey questionnaire, 725 (67.1%) returned the completed surveys. Eighty percent of the students were drinkers (93% of males and 69% of females); 68% of the drinkers were flushers. Most of the students (59.3%) said flushing had no special meaning, that is, would ignore flushing; 54% of the flushers said they could keep drinking "but less" when they flush; 27% of the students said that a flushing person should stop drinking; however, if the flushing person is a girl, 89% of the students said the girl should drink less or stop. If the flushing person was a boy, 61% of students said he should drink less or stop. The data do suggest gender differences in the understanding of and social reaction to alcohol-related flushing, and these differences raise interesting questions as to how flushing acts as a potential protective factor against alcohol misuse.
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Rodent studies reveal that oxidative stress, much of it generated via induction/activation of NADPH oxidase, is a key mediator of a number of the pathogenic effects of chronic ethanol overconsumption. The highly reactive ethanol metabolite acetaldehyde is a key driver of this oxidative stress, and doubtless works in other ways to promote alcohol-induced pathology. Effective antioxidant measure may therefore be useful for mitigating the adverse health consequences of alcohol consumption; spirulina may have particular utility in this regard, as its chief phycochemical phycocyanobilin has recently been shown to function as an inhibitor of certain NADPH oxidase complexes, mimicking the physiological role of its chemical relatives biliverdin/bilirubin in this respect. Moreover, certain nutraceuticals, including taurine, pantethine, and lipoic acid, may have the potential to boost the activity of the mitochondrial isoform of aldehyde dehydrogenase, ALDH-2, accelerating conversion of acetaldehyde to acetate (which arguably has protective health effects). Little noticed clinical studies conducted nearly three decades ago reported that pre-ingestion of either taurine or pantethine could blunt the rise in blood acetaldehyde following ethanol consumption. Other evidence suggests that lipoic acid may function within mitochondria to maintain aldehyde dehydrogenase in a reduced active conformation; the impact of this agent on ethanol metabolism has however received little or no study. Studies evaluating the impact of nutracetical strategies on prevention of hangovers - which likely are mediated by acetaldehyde - may represent a quick, low-cost way to identify nutraceutical regimens that merit further attention for their potential impact on alcohol-induced pathology. Measures which boost or preserve ALDH-2 activity may also have important antioxidant potential, as this enzyme functions physiologically to protect cells from toxic aldehydes generated by oxidant stress.
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This is the first of a two-part article on cultural aspects of alcohol use and includes information on alcohol consumption among Koreans, British, Americans, Jews, Italians, Irish and Hispanics. Drinking practices and customs, like all other lifeways, are culture bound, multi-faceted, and learned behaviour. People from all ethno-cultural groups use alcohol in some form, even in those societies where drinking is highly stigmatised or tabooed. Behavioural problems with alcohol misuse are as important as the physiological and psychological variants. There is remarkably little correspondence between the amount of alcohol consumption and behavioural problems encountered when cross-cultural comparisons of drinking are examined. Learning about cross-culture comparisons of alcohol use and misuse can have the potential to promote more responsible and sensible drinking behaviour.
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Das Überfluten jeder einzelnen Zelle unseres Körpers mit einer großen Menge Ethanol führt zu Störungen im Stoffwechsel aller Organe. Dies erklärt die große Variationsbreite der Symptome nach zu großer Ethanolaufnahme. Gegen den Kater gibt es keine echte Heilung. “Chemie in unserer Zeit” empfiehlt: Viel reines Wasser gegen den Wasserverlust, eine Aspirin oder Ibuprofen gegen die pochenden Kopfschmerzen, Fruchtsaft gegen den Glucosemangel, Muttis kräftige Hühnerbrühe gegen den Elektrolytverlust, eine Vitamintablette wegen ihres sehr wirksamen Placebo-Effekts, Zuspruch und Mitleidsbekundungen der Lieben und dann – wenn der Kreislauf und die Kontrolle der unteren Extremitäten den aufrechten Gang es zulassen, einen Spaziergang an der frischen Luft. Dabei sollte man intensiv über die Sinnlosigkeit übermäßigen Trinkens nachdenken. Das hilft, und am nächsten Tag ist alles vorbei – zumindest bis zum nächsten Mal. Na dann: Helau und Alaaf!Flooding of every cell in our body with a huge amount of ethanol affects the entire metabolism of all organs. This explains the broad variation of symptoms after drinking to much. There is no real cure für hangover. “Chemie in unserer Zeit” recommends much pure water against the dehydration, aspirin or ibuprofen against the throbbing headaches, fruit juice against hypoglycemia, Mom's powerful chicken soup to compensate for electrolyte losses, a vitamine pill because of its powerful placebo-effect, compassion and words of comfort of the loved ones and finally – if blood circulation and control of the lower extremities admit an upright walk – a long stroll in fresh air. Meanwhile one should think deeply about the pointlessness of excessive drinking. This all helps and on the next day it will all be over – at least until next time. Well then: Cheers and Bottoms up!
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Various alcoholic beverages containing different concentrations of ethanol are widely consumed, and excessive alcohol consumption may result in serious health problems. The consumption of alcoholic beverages is often accompanied by non-alcoholic beverages, such as herbal infusions, tea and carbonated beverages to relieve drunk symptoms. The aim of this study was to supply new information on the effects of these beverages on alcohol metabolism for nutritionists and the general public, in order to reduce problems associated with excessive alcohol consumption. The effects of 57 kinds of herbal infusions, tea and carbonated beverages on alcohol dehydrogenase and aldehyde dehydrogenase activity were evaluated. Generally, the effects of these beverages on alcohol dehydrogenase and aldehyde dehydrogenase activity are very different. The results suggested that some beverages should not be drank after excessive alcohol consumption, and several beverages may be potential dietary supplements for the prevention and treatment of problems related to excessive alcohol consumption.
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This article represents the proceedings of a symposium presented at the 2003 Research Society on Alcoholism meeting in Ft. Lauderdale, Florida, organized and chaired by Carl L. Faingold. The presentations were (1) Overview, by Carl L. Faingold; (2) Stress, Multiple Alcohol Withdrawals, and Anxiety, by Darin Knapp; (3) Relationship Between Genetic Differences in Alcohol Drinking and Alcohol Withdrawal, by Julia Chester; (4) Neuronal Mechanisms in the Network for Alcohol Withdrawal Seizures: Modulation by Excitatory Amino Acid Receptors, by Carl L. Faingold; and (5) Treatment of Acute Alcohol Withdrawal and Long-Lasting Alterations in Hippocampal Neuronal Networks, by Larry P. Gonzalez. The presentations emphasized the importance of using intact behaving animals to advance the understanding of the human alcohol withdrawal syndrome. This involves applying and amplifying the neurophysiological and neurotransmitter findings observed in vitro to the network-based neurobiological mechanisms that are involved in several important aspects of the specific behaviors observed clinically. The symposium provided evidence that the organizational aspects of neuronal networks in the intact nervous system add another nexus for the action of alcohol and drugs to treat alcohol withdrawal that may not be readily studied in isolated neural elements used in in vitro approaches.
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Response differences following administration of alcohol between adult males with a positive (FHP) versus negative (FHN) family history of alcoholism have been demonstrated in previous research and are thought to be related to risk for developing alcoholism. If this is so, the pharmacological breadth of addiction risk conferred by a positive family alcoholism history might be studied by determining whether FHP subjects show different responses than FHN to drug classes other than alcohol. We have previously reported on the acute effects of ethanol as compared with secobarbital in FHP and FHN subjects and found that FHP subjects showed greater sensitivity across a variety of subjective measures than FHN subjects for both drug classes. The data reported here are based on an extended data collection period of 3 to 18 hr postingestion, following completion of the acute laboratory portion of the study. Specifically, in the present study, dose-effect timecourse functions for a variety of physiological (heart rate, blood pressure, and breath alcohol level), subjective (analog mood, drug effect, and withdrawal, Subjective High Assessment Scale (SHAS], and psychomotor measures (Digit Symbol Substitution Test and numeric recall) were examined in FHP and FHN college-aged males for secobarbital (0, 100, 200 mg daily) and ethanol (1 g/kg daily). FHP and FHN subjects were matched on light-to-moderate drinking patterns, anthropometric dimensions, age, years of schooling, and drug use. FHP subjects reported more extended intoxication and greater withdrawal effects following both ethanol and the high dose of secobarbital than did FHN subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
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Many Orientals lack the mitochondrial aldehyde dehydrogenase (ALDH2) activity responsible for the oxidation of acetaldehyde produced during ethanol metabolism. These individuals suffer the alcohol-flush reaction when they drink alcoholic beverages. The alcohol-flush reaction is the result of excessive acetaldehyde accumulation, and the unpleasant symptoms tend to reduce alcohol consumption. The subunit of this homotetrameric enzyme was sequenced and the abnormality in the inactive enzyme shown to be a substitution of lysine for glutamate at position 487. We have used the polymerase chain reaction to determine the genotypes of 24 livers from Japanese individuals. Correlating genotype with phenotype leads to the conclusion that the allele (ALDH2(2)) encoding the abnormal subunit is dominant.
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In this article, we attempt to distinguish between the properties of moderator and mediator variables at a number of levels. First, we seek to make theorists and researchers aware of the importance of not using the terms moderator and mediator interchangeably by carefully elaborating, both conceptually and strategically, the many ways in which moderators and mediators differ. We then go beyond this largely pedagogical function and delineate the conceptual and strategic implications of making use of such distinctions with regard to a wide range of phenomena, including control and stress, attitudes, and personality traits. We also provide a specific compendium of analytic procedures appropriate for making the most effective use of the moderator and mediator distinction, both separately and in terms of a broader causal system that includes both moderators and mediators.
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We investigated alcohol-induced hangovers among college men at high and low risk for alcoholism. Thirteen sons of alcoholics reported significantly (p < 0.001) greater hangover symptoms in the past year than 25 sons of nonalcoholics. The two groups reported comparable quantity-frequency of recent drinking. To the extent that hangover represents an acute withdrawal syndrome to alcohol, this raises the question of whether sons of alcoholics are “dependence-prone.”
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Asian-American men who possess ALDH2*2 alleles and who experience a facial flush after consuming alcohol were carefully matched on drinking history and demographic variables with nonflushing Asian males with only ALDH2*1 alleles. Each man was tested following placebo and a challenge dose of 0.75 ml/kg alcohol. Following alcohol, flushers reported experiencing significantly more positive feelings of intoxication than nonflushers, despite equivalent blood alcohol concentrations. These data suggest that Asians who flush after drinking, particularly those with ALDH2*1/2*2 genotype, have a more intense, although not necessarily a more negative, response to alcohol than comparable nonflushing Asians. This alcohol sensitivity reaction that many Asian flushers experience may contribute to their lower tendency to drink excessively, even though their response to alcohol is not predominantly negative.
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The determination of acetaldehyde in biologic samples is complicated by a variety of formation and disappearance reactions occurring in the present methods of acetaldehyde analyses. The acetaldehyde formation (ethanol oxidation) in deproteinized supernatant of tissue preparations is prevented by the use of thiourea. During deproteinization, however, it is not inhibited by thiourea, and this remains the main problem in blood acetaldehyde determinations. To circumvent this problem, the use of a correction curve is proposed which is generated by adding control blood samples to the deproteinizing agent such that the blood dilution, temperature, and the ethanol concentrations (the main factors affecting the artifactual acetaldehyde formation) in the controls are identical to those of the samples. Disappearance reactions mainly include loss of acetaldehyde due to binding and/or metabolism. The problem seems to be pronounced with human blood samples, and it is recommended that they be rapidly ( less than 5 sec) deproteinized.
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The post-intoxication state, commonly called hangover, has been known since antiquity; yet there has been little systematic research examining the signs and symptoms of hangover among the general population. The frequency and the various symptoms of hangovers, as well as the relationships between hangovers and alcohol consumption, were analyzed using a sample of 1041 adults 18 years and older living in Western New York State. Hangovers were experienced in the previous year by only about 50% of the population of heavier drinkers; the frequency was even less among those with lower alcohol consumption. Factor analysis of the various symptoms revealed significant clusters. The findings suggest that the aversive aspects of alcohol consumption, including the hangover syndrome, may deter excessive consumption; certain individuals in whom aversive reactions as hangover do not occur may be at high risk for excessive alcohol use.
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Asian men were genotyped for alleles of aldehyde dehydrogenase (ALDH2) and tested on two separate occasions following oral administration of placebo and 0.75 ml/kg alcohol. Sixty minutes after beverage ingestion, event-related potentials were elicited using an auditory oddball paradigm. Repeated measures ANOVA revealed that alcohol produced significant increases in P300 latency and significant decreases in P300 amplitude compared with placebo. Subjects with ALDH2*1/2*2 genotype (n = 14) demonstrated some significantly greater P300 effects after alcohol than subjects with ALDH2*1/2*1 genotype (n = 15), despite equivalent blood alcohol concentrations. These data suggest that neurocognitive functioning may be more impaired following alcohol in subjects with an ALDH2*2 allele. These findings further suggest that a genetically controlled factor (deficiency in ALDH enzyme activity) might contribute to a decreased likelihood of alcohol intake and protection from alcoholism, because of an enhanced sensitivity to alcohol.
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Previous work relating self-reported hangover symptoms and familial risk for alcoholism was extended to personality risk for alcoholism, as measured by the MacAndrew alcoholism scale (MAC). The MAC predicted a significant amount of unique variance in reported hangover symptoms after controlling for gender, average quantity consumed on a drinking occasion, and fathers' scores on the Short Michigan Alcoholism Screening Test (SMAST). Individuals at elevated personality risk for alcoholism apparently experience more acute withdrawal and hangover, which may initiate further drinking to relieve these aversive symptoms.
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This study investigated hangover as a potential mediator or moderator of the relation between personality and drinking problems. Hangover did not appear to mediate the relation, suggesting that the link between personality and drinking problems does not stem from an indirect effect via hangover. Hangover did appear to moderate the relation. Personality and drinking problems correlated significantly for subjects who reported experiencing severe hangovers, but not for those who reported mild hangovers. Those who experience greater hangover may choose to drink more alcohol in order to relieve these adverse effects, and this choice may vary with personality. The theoretical and conceptual implications of mediators and moderators are also discussed.
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Approximately 50% of Asians experience a facial flush following alcohol ingestion. These individuals have an inactive form of mitochondrial aldehyde dehydrogenase (ALDH) encoded by the ALDH2*2 allele. This study matched 15 flushing and 15 nonflushing Asian men on demographics and drinking histories. The 30 subjects were genotyped for ALDH2 and were evaluated both before and following placebo and 0.75 ml/kg alcohol. The two groups did not differ significantly on blood alcohol concentrations after drinking, but did differ in electroencephalographic (EEG) response on the falling phase of the blood alcohol curve. Nonflushing subjects displayed significant increases in slow-alpha EEG activity (7.5-9.0 Hz) at 90 and 150 min post-alcohol consumption, compared to flushing subjects who did not show characteristic increases in this frequency band at these timepoints. These data suggest flushers, those with at least one ALDH2*2 allele, have less of slow-alpha wave EEG response to alcohol than nonflushers with ALDH2*1/2*1 genotype.