Literature suggests that there may be overlap between proneness to overeating-induced obesity and excessive alcohol drinking, and that this may occur in part via the endogenous opioid system in the nucleus accumbens (NAc). To investigate this, we used rats selectively bred for their susceptibility or resistance to diet-induced obesity (obesity-prone, OP, and obesity-resistant, OR), and examined their (1) ethanol drinking under the intermittent access two-bottle-choice procedure, (2) sucrose drinking under the intermittent access two-bottle-choice procedure, and (3) enkephalin, dynorphin, and opioid receptor mRNA in the NAc core and NAc shell. While we found no major differences in measures of sucrose drinking, male OP compared to OR rats had higher levels of 24-hour ethanol drinking and preference, while female OP compared to OR rats had higher levels of binge-like (30-minute) ethanol drinking and corresponding blood ethanol concentrations. In parallel, both male and female OP compared to OR rats had higher expression of enkephalin but not dynorphin mRNA in the NAc core, and males had higher expression of mRNAs encoding mu, delta, and kappa opioid receptors in the NAc core. Together, these results show that proneness to obesity is associated with excessive ethanol drinking prior to the onset of obesity. Further, they suggest that this could be driven in part through differences in the NAc endogenous opioid system, particularly for males and via the NAc core. This supports the idea that proneness to excessive alcohol drinking may share neurobehavioral mechanisms with susceptibility to diet-induced obesity.
Chronic ethanol exposure, a key feature of alcohol use disorder (AUD), can affect the nervous system, but its molecular impact on the olfactory bulb remains unclear. In this study, an intermittent two-bottle voluntary drinking model was established in male mice, and transcriptome sequencing was performed on olfactory bulb tissues. DESeq2 analysis identified 188 differentially expressed genes, including 68 upregulated and 120 downregulated genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome pathway database (Reactome) analyses indicated that ethanol-responsive genes were predominantly enriched in receptor-mediated signaling pathways, particularly those linked to G protein-coupled receptor (GPCR) signaling. Protein-protein interaction analysis further identified eight core GPCR-related genes. quantitative real-time PCR (qRT-PCR) validation revealed that Cxcl10, Grp, Pcp2, and Pdyn were markedly downregulated in the ethanol group. These results suggest that chronic ethanol exposure is associated with transcriptional alterations in the male mouse olfactory bulb and may selectively affect several GPCR-related signaling components. This study provides candidate molecular evidence for further investigation of ethanol-associated olfactory dysfunction.
BACKGROUND:The oral microbiome has emerged as a potential biomarker and pharmacological target in alcohol use disorder (AUD) due to its associations with alcohol use and related biological processes. However, its temporal variability and reproducibility remain poorly understood, limiting its utility. METHODS:Saliva samples were obtained from participants enrolled in a randomized controlled trial of young adults with AUD. Temporal variability and reproducibility were evaluated using within-visit samples (∼4 h apart; before and after sesame oil placebo and standardized snack) and between visits (∼25 days; pre-treatment). Alpha diversity, beta diversity, differential abundance, and intraclass correlation coefficients (ICCs) were calculated at the genus and species levels. RESULTS:Significant within-visit differences were observed in alpha diversity, beta diversity, and the abundance of several genera and species. Snack type and time since last alcohol use explained comparable or greater variance in microbial composition than within-visit timepoint (4-6%). Although reproducibility of alpha diversity within-visit was generally low, most genera (70.3%) and species (74.6%) demonstrated at least moderate reproducibility. In contrast, no detectable systematic between-visit differences were observed in diversity or taxon abundance, and reproducibility was generally moderate for alpha diversity measures and most genera (67.6%) and species (72.2%). CONCLUSIONS:Despite group-level microbial shifts within-visit, individual-level microbial features were generally reproducible both within (∼4 h) and between (∼25 days) visits. No systematic group-level differences were detected between-visits. These findings support the use of the oral microbiome in AUD research while emphasizing the importance of longitudinal designs and accounting for recent exposures.
Rodent models of prenatal alcohol exposure are a powerful tool for studying causal factors of prenatal exposure effects. Under the New Mexico Alcohol Research Center, we combined a voluntary drinking-in-the-dark (DID) paradigm with a Volumetric Drinking Monitor (VDM) system to quantify maternal ethanol (EtOH) intake, drinking duration, and drinking patterns throughout gestation and determined whether these variables altered breeding success or early offspring development. Female C57BL/6J mice received daily 2-h access to either 20% EtOH or water using the VDM system. Following a two-week acclimation period, breeding was initiated while daily drinking continued throughout gestation until parturition. Breeding success, litter characteristics, and early growth were evaluated from 176 dam-sire pairings across three breeding cohorts, yielding over 800 offspring for demographic analyses. Maternal EtOH exposure did not affect pregnancy success, litter loss, litter size, pup weight at postnatal day 10, offspring sex distribution, or weaning weight. Average daily gestational EtOH consumption and duration of preconception EtOH exposure did not predict offspring outcomes. Although EtOH-exposed dams consistently exhibited front-loading behavior, neither front-loading status nor front-loading intensity was associated with litter characteristics or early offspring growth. Moderate voluntary maternal EtOH consumption, duration of exposure, or drinking pattern did not drive litter characteristics that may affect the early-life environment (pup number and sex) or early growth markers (P10 and weaning weight). These data indicate that differences in the early postnatal environment are not likely to be responsible for long-term behavioral and neurobiological phenotypes reported in offspring produced using this paradigm.
Background In the central nervous system (CNS), microglial cells regulate the immune response by mediating neuroinflammation. Alcohol abuse leads to neuroinflammation and neurodegeneration in CNS. In the context of COVID-19, neuroinflammation and glial reactivity are mediated by the infection of human glial cells by SARS-CoV-2, which recognizes the angiotensin-converting enzyme 2 (ACE2) and other proteins, such as transmembrane serine protease 2 (TMPRSS2), through its surface Spike-1 protein. Although several risk factors for COVID-19 progression have been described, it remains unknown how alcohol consumption affects SARS-CoV-2 Spike protein-induced microglial reactivity. In this study, murine microglial cultures (BV-2) were exposed to ethanol alone and subsequently challenged with the Spike protein. Immunofluorescence analysis revealed that ethanol treatment (1%) did not affect the levels of the reactivity-related proteins C3 and CD86 or the phagocytic potential of microglial cells, although it reduced the number of cells exhibiting an amoeboid morphology. However, ethanol treatment prevented the Spike protein-induced increase in C3 levels, amoeboid cell numbers, and phagocytic activity. Furthermore, chronic in vivo exposure to ethanol decreased ACE2 and TMPRSS2 levels in the cerebral cortex of mice, whereas treatment with higher ethanol concentrations in vitro decreased only TMPRSS2 levels. These data suggest that ethanol exposure suppresses the ability of microglia to respond to the pro-inflammatory effects induced by the Spike protein. This impairment may contribute to the loss of microglial function in regulating the immune response and neuroinflammation in the CNS in the context of COVID-19.
Alcohol intake is known to influence serum high-density lipoprotein cholesterol (HDL-C), yet how drinking patterns shape this association is less researched. We examined whether frequency of drinking versus amount per occasion was differently related to HDL-C in a large population sample. Data were taken from a cross-sectional study of 18,614 respondents aged 40-79 years in the Tromsø general population health study. Alcohol use was assessed by self-report. Fasting HDL-C was measured using standardized laboratory protocols. Mean alcohol intake was 6.7 g/day and mean HDL-C 1.57 mmol/L. Total alcohol consumption correlated positively with HDL-C (r = 0.075; p < 0.001). In regression models, each additional gram/day was associated with an increase of 0.005 mmol/L HDL-C (95% CI 0.004-0.005; p < 0.001). Drinking frequency showed a positive correlation to HDL-C (r = 0.183; p < 0.001), whereas amount per occasion was inversely related to HDL-C (r = -0.128; p < 0.001). A significant frequency × amount interaction indicated that higher amounts per occasion were linked to lower HDL-C primarily among the infrequent drinkers (p < 0.001). The results indicate that the alcohol-HDL-C association was driven by how often alcohol was consumed rather than how much was consumed per occasion. Frequent, lower-dose drinking related to higher HDL-C, whereas infrequent, higher-dose occasions related to lower HDL-C. These findings underscore the need to consider drinking patterns, beyond average intake, when interpreting HDL-C and appraising alcohol-related cardiovascular risk.
BACKGROUND:Sex differences in the escalation of drinking after brief abstinence have been documented. The possibility that changes in alcohol metabolism may explain these differences has not been previously examined. We tested whether short-term abstinence alters the alcohol elimination rate (AER) across sex and compared three methods for its estimation. METHODS:Sixty-six adults (56% female) aged 21-35 years reporting moderate-to-heavy drinking completed two counterbalanced intravenous alcohol clamp sessions under two conditions: one during a period of usual drinking and one after two weeks of monitored abstinence. AER was quantified with three approaches: a manual steady-state method, a deterministic infusion rate profile-based curve-fitting algorithm, and an automated, model-based parameter identification procedure (PID). The effects of condition, method, and sex were examined using linear mixed-effects models, and agreement among methods was examined with concordance statistics. RESULTS:Short-term abstinence did not consistently change AER, overall or differently across sex. A significant abstinence effect (p = 0.01) was observed in females with the PID method only. Males exhibited higher AER than females across both conditions (p < 0.001). The PID method yielded lower alcohol elimination estimates than Manual (p < 0.001) and Deterministic AER approaches, whereas the manual and deterministic methods did not differ. CONCLUSIONS:Sex differences in alcohol consumption following short-term abstinence are likely not explained by changes in AER. When comparing methodologies, the selection of a methodology should be consistent within analyses and selected based on experimental design.
Alcohol use disorder (AUD) is a leading cause of morbidity and mortality worldwide, characterized by cycles of heightened craving and excessive, uncontrolled consumption of alcohol despite progressive decline in physical and mental health. Voluntary alcohol consumption is influenced by a variety of environmental and genetic factors, including circadian clock genes, whose effects are modulated in a sex-specific manner. The sex-specific role of clock genes in alcohol drinking was identified through selective ablation of Bmal1 and Per2 from neurons of the mouse striatum; however, the contribution of specific striatal subregions to the observed drinking behavior remains unclear. Thus, alcohol intake and preference were investigated in male and female mice with a conditional knockout of Bmal1 or Per2 from cells in the nucleus accumbens (NAc), a key area of the brain's reward center. Alcohol consumption and preference were increased in male and female mice with a conditional knockout of Bmal1, whereas the deletion of Per2 increased consumption and preference in males only. The changes in alcohol consumption can be attributed to the manipulation of the circadian clock genes in the NAc exclusively, because affective behaviors were largely unchanged. The results show that Bmal1 and Per2 in the NAc are negative regulators of alcohol drinking in mice, with sex-dependent differences in their effects.
Chronic alcohol use disorder (AUD) is associated with a transition from reward-driven to negative affect-driven alcohol seeking. However, the circuit-level mechanisms linking motivational, affective, and stress systems remain unclear. We develop a reduced computational model that integrates the basolateral amygdala (BLA), bed nucleus of the stria terminalis (BNST), and ventral tegmental area (VTA) into a closed feedback loop to examine how chronic alcohol exposure reshapes circuit dynamics. The model includes antagonistic BLA reward- and aversion-encoding populations, CRF-positive and CRF-negative BNST interneurons and projection neurons, and VTA GABA and dopamine (DA) neurons. Simulated DA modulation of recurrent inhibition in the BLA completes the feedback loop, with core behaviors governed by BLA competition, BNST-mediated control of DA levels, and DA-modulated BLA inhibition. Parameter changes mimicking chronic alcohol exposure are constrained by experimental data and implemented as alterations in BLA→BNST connectivity, BNST excitability, and paraventricular thalamus inputs. Simulations show that these adaptations (i) shift the system from a moderately high, "safe" reward/anxiolytic state to a hypodopaminergic, anxiety-prone state with reduced BNST CRF+ projection activity and elevated BNST anxiogenic interneuron activity, and (ii) concurrently amplify cue-evoked DA transients in response to alcohol-paired stimuli while blunting responses to natural rewards. A key mechanism is the weakening of BLA reward→BNST CRF+ projections and strengthening of BLA aversion→BNST CRF- projections, which drive a sharp decrease in DA tone and collapse of differentiation between BLA reward and aversion populations into a "mixed" state. In this regime, salient cues can evoke stochastic, exaggerated reward or aversion responses, providing a mechanism for maladaptive motivation, negative affect, and potential exacerbation of mood pathology in chronic AUD.
Prenatal alcohol exposure (PAE) can disrupt development, leading to alterations in physical, health, and behavioral outcomes, referred to as fetal alcohol spectrum disorders (FASD). Although alcohol likely impacts fetal development through many mechanisms, PAE could impact metabolism of choline, an essential nutrient that is important for brain development and function. Importantly, both preclinical and clinical studies show that choline supplementation can improve performance on hippocampal-dependent behavioral tasks, even when administered postnatally. However, the mechanisms by which choline mitigates prenatal alcohol-induced neurocognitive deficits are not well understood. Thus, the present study examined whether PAE leads to long-lasting changes in choline metabolism in the hippocampus and plasma of adolescent animals and if effects are modified by choline. From postnatal day (PD) 4-9, rat pups were given ethanol (EtOH; 5.25 g/kg/day) or sham intubations. From PD 10-30, subjects received s.c. choline chloride (100 mg/kg/day) or saline. Plasma and hippocampus were collected on PD 35 and choline metabolite levels were analyzed. Neither EtOH nor choline led to long-lasting changes in choline levels. However, EtOH-exposed females had reduced hippocampal betaine and plasma betaine:choline ratios. Plasma cystathionine was elevated in EtOH-exposed females treated with choline, suggesting choline activates anti-oxidative stress and anti-inflammation pathways among EtOH-exposed subjects. Choline alone increased homocysteine among females. In contrast, choline supplementation increased plasma SAM:SAH ratios in EtOH-exposed males, suggesting choline is modifying DNA methylation. Overall, these results provide insights to sex-specific mechanisms of action in which choline supplementation alters choline metabolic pathways in FASD.
Prenatal alcohol (ethanol) exposure (PAE) produces enduring neurobehavioral alterations, but the contribution of gut integrity to this vulnerability remains unclear. This study examined if moderate-intermittent PAE, induced via voluntary ethanol intake during pregnancy and early lactation, alters colonic structure and barrier integrity-related markers in adolescent offspring, and whether these changes are associated with compulsive/perseverative behavior and increased ethanol intake. Pregnant C57BL/6 mice were exposed to a Drinking-in-the-Dark-based regimen or to water. In offspring, colonic tight junction-related gene expression (ZO-1, occludin, claudin), histological parameters (crypt length, lamina propria cell infiltration), immunofluorescence for junctional proteins, anxiety- and compulsive-like behavior, and voluntary ethanol intake were evaluated. Dams were later exposed to intragastric ethanol to evaluate intoxication sensitivity and subsequent voluntary drinking. PAE offspring showed a robust shortening of colonic crypts, and marked increased immune cell infiltration within the lamina propria, without significant changes in the levels of junctional proteins. PAE did not alter anxiety but increased marble burying and open field activity, enhanced object-directed perseveration (more object visits and shorter return latencies), and significantly elevated ethanol intake in adolescence. These effects were non-sex-specific. PAE induced minimal effects on ethanol sensitivity or intake in the dams. These findings indicate that PAE disrupts colonic integrity and immune status associated with compulsion-perseveration and heightened adolescent ethanol consumption, supporting a putative gut-brain-behavior pathway in PAE-related risk for alcohol use disorder.
BACKGROUND:Self-medicating pain with alcohol is common. Chronic heavy alcohol use is associated with increased risk for chronic pain and alcohol-related consequences. The anterior (AIC) and posterior (PIC) insula play key, but distinct, roles in pain processing. Because insula dysregulation is implicated in both chronic pain and alcohol use disorder, we hypothesized alcohol intake would reduce pain-related insula activation and modulate pain-related functional connectivity, with subdivision-specific effects. METHODS:N = 97 moderate drinkers (Mage = 26.1 years) completed double-blind laboratory sessions where they received alcohol (0.08 g/dL target BAC) or placebo. Then, T2∗-weighted BOLD fMRI was collected using a 3T MRI Scanner during heat pain stimulation. Repeated measures ANOVA characterized alcohol effects on AIC and PIC functional activation. Alcohol effects on pain-related FC were assessed using whole-brain generalized psychophysiological interaction (gPPI) analysis (pFDR<0.05). RESULTS:Alcohol significantly decreased pain-related AIC activation, but increased PIC activation. Alcohol increased pain-related FC of AIC with bilateral postcentral gyrus, left precentral gyrus, and lateral occipital cortex. In contrast, alcohol increased FC of PIC with bilateral supramarginal gyrus, right frontal pole, right orbitofrontal cortex, right angular gyrus, and right middle frontal gyrus. Increased PIC FC with angular gyrus predicted greater subjective pain relief. FC with orbitofrontal gyrus was associated with reduced pain intensity. CONCLUSION:Alcohol had subregion-specific effects on functional activation and FC during painful heat. Alcohol-induced changes in FC during heat pain were associated with pain relief and pain intensity. Our findings suggest an important contribution of the IC to alcohol's analgesic and pain-relieving effects.
Alcohol is commonly reported to produce analgesic effects, yet the mechanisms underlying alcohol-induced analgesia and the long-term impact of adolescent alcohol exposure on pain processing remain poorly understood. The present study examined whether a history of adolescent alcohol exposure alters ethanol-induced analgesic responses in adulthood and whether these effects are associated with changes in neuronal activation within the ventrolateral periaqueductal gray (vlPAG). Male and female mice were exposed to adolescent intermittent ethanol (AIE) vapor or air, followed by longitudinal assessment of mechanical sensitivity using the von Frey test during abstinence. In adulthood, mice received acute intragastric ethanol, and mechanical withdrawal thresholds were reassessed. Neural activation of mu-opioid receptor- and kappa-opioid receptor (KOR)-expressing vlPAG neurons was quantified using RNAscope in situ hybridization. Mice with a history of AIE exhibited persistent mechanical hypersensitivity during abstinence. Acute ethanol produced dose-dependent analgesia across sexes. Follow-up analyses revealed that AIE exposure selectively modulated ethanol responsiveness in females. Higher ethanol doses increased withdrawal thresholds in both air and AIE females, whereas an intermediate dose produced analgesic effects only in AIE females. Notably, at a low ethanol dose that did not significantly alter mechanical sensitivity in males, AIE females exhibited higher withdrawal thresholds than air controls, accompanied by reduced activation of KOR-expressing neurons in the vlPAG. Together, these findings indicate that adolescent alcohol exposure produces long-lasting alterations in pain sensitivity and ethanol responsiveness and suggest that altered recruitment of KOR-expressing vlPAG neurons may contribute to ethanol sensitivity in females.
Background Relapse after inpatient treatment for alcohol dependence is frequent, particularly within the first three months post-discharge. Cognitive Bias Modification (CBM), and specifically alcohol Approach Bias Modification (ABM), has demonstrated benefits in inpatient care, but its efficacy for aftercare remains uncertain. Methods A two-phase research program was conducted. The pilot study tested the feasibility of a desktop-based, home-delivered ABM. A total of 308 patients were randomized into two intervention groups, differing in reminder intensity, or a control group without any intervention. The main study built on these findings by developing a smartphone-based, gamified ABM using an active control design. A total of 273 active app users were randomized to training or control, and participants were instructed to use the app as often as they liked over a three month period. Gamification features included team competitions, rewards, and peer interaction to enhance engagement. Results In the pilot study, adherence proved low (mean 7.7 sessions out of 25 instructed sessions), and reminders did not improve participation. No group-level differences in abstinence were observed. In the main study, engagement was markedly higher: participants completed on average 57 sessions, and nearly half reached the adherence threshold of ≥25 sessions. Among those meeting this threshold, the ABM group achieved significantly higher abstinence rates at one-year follow-up compared to active controls. Feedback indicated general satisfaction, willingness to continue use, and offered suggestions for further app refinement. Conclusions Gamification and mobile delivery improved adherence, and sufficient engagement with ABM produced specific and clinically meaningful aftercare benefits at one-year follow-up.
The gut microbiome includes a large and diverse microbial community that plays a central role in host health, supported by an extensive genomic repertoire that is distinct from and complementary to mammalian enzymatic pathways. Alcohol consumption disrupts this ecosystem, inducing microbial dysbiosis and altering functional interactions between the host and its gut bacteria that can lead to systemic effects. In this review, we examine how alcohol affects gut bacteria, and how these changes impair essential bacterial functions, including short-chain fatty acid production, mucin metabolism, biofilm formation, and bile acid metabolism, that support intestinal, liver, and brain health. We further describe how certain gut bacteria tolerate or produce ethanol, and how these traits contribute to the systemic harms associated with alcohol-induced dysbiosis. Finally, we highlight therapeutic strategies aimed at targeting ethanol-tolerant or ethanol-producing bacteria as potential avenues for preventing or mitigating intestinal inflammation, liver injury, and other metabolic disorders.
BACKGROUND:Acute alcohol intoxication at the time of burn injury is associated with increased morbidity and worsened systemic inflammation. While the detrimental effects of ethanol on peripheral organs after burn injury are well established, its impact on neuroinflammation and the blood-brain barrier (BBB) integrity remains to be defined. We hypothesized that ethanol exposure prior to burn injury heightens neuroinflammation through disruption of intestinal and cerebrovascular barriers and alterations in the gut microbiome. METHODS:Using a clinically relevant murine model, mice received acute ethanol exposure 30 min prior to burn injury. Brains were analyzed 24 h later for inflammatory gene and protein expression. Microglial activation was determined by IBA-1 immunofluorescence and quantitative PCR of isolated microglia. Intestinal barrier dysfunction was evaluated by bacterial translocation to mesenteric lymph nodes (MLN) and serum lipopolysaccharide (LPS) levels. BBB permeability was assessed in brain tissue by albumin accumulation. Fecal microbiome composition was characterized by 16S rRNA gene sequencing. RESULTS:Burn injury alone induced morphological evidence of reactivity, yet did not significantly increase brain pro-inflammatory cytokine transcription. In contrast, ethanol exposure prior to burn injury elevated brain expression of Ccl2, Tnfa, and S100a8. Isolated microglia from the brains of mice given ethanol and burn injury exhibited enhanced expression of Ccl2 compared to burn alone. Ethanol exposure also resulted in an 8-fold increase in bacterial translocation to MLNs and a 5-fold increase in brain albumin levels, indicating exacerbated intestinal and BBB permeability. Microbiome analysis revealed expansion of Escherichia species in mice subjected to ethanol and burn injury, which positively correlated with brain S100a8 expression. CONCLUSIONS:Ethanol exposure prior to burn injury potentiates neuroinflammation, enhances microglial pro-inflammatory reactivity, disrupts BBB integrity, and is associated with gut microbial dysbiosis. These findings implicate dysregulation of the gut-brain axis as a mechanistic contributor to worsened neuroinflammation in intoxicated burn injury and identify potential therapeutic targets to mitigate neurologic complications in this high-risk population.
Chronic ethanol exposure is detrimental, leading to neurodegeneration through mechanisms such as oxidative stress, inflammation, and interference with neuronal signaling pathways. In this study, a solid lipid nanoparticle formulation of remdesivir (RDV-SLNs) was evaluated for its neuroprotective effects against ethanol-induced neurodegeneration as compared to RDV dispersion. Adult male albino mice were administered ethanol, and various behavioral paradigms were used to evaluate cognitive decline. Mice exposed to ethanol exhibited notable deficits in recognition, spatial learning, and working memory. However, these impairments were significantly restored following treatment with RDV-SLNs. Furthermore, our data demonstrated a significant interaction between triggering receptors expressed on myeloid cells 1 (TREM1) (pro-inflammatory) and triggering receptor expressed on myeloid cells 2 (TREM2) (neuroprotective) in ethanol neurotoxicity, wherein their dysregulation results in NLRP3 inflammasome overactivation. Additionally, the downregulation of peroxisome proliferator-activated receptor (PPARγ) intensified this inflammatory cascade, coupled to hyper-elevated malondialdehyde (MDA) and nitric oxide (NO) levels in the ethanol-intoxicated group. Moreover, treatment with RDV-SLNs or RDV alone restored PPARγ activity and antioxidant enzymes such as catalase (CAT), glutathione (GSH), and glutathione S-transferase (GST). This restoration of PPARγ, coupled to the TREM signaling pathway balanced by RDV-SLNs, alleviated ethanol-induced neurodegeneration. These findings highlight the dual role of RDV by protecting against ethanol-induced neurodegeneration both as a modulator of neuroinflammation/oxidative stress and a metabolic regulator.
Sang Kwe Hwan® (SKH), a Korean product for hangover relief that contains yeast extract, was developed as an anti-hangover compound. However, no studies have assessed the effects of yeast mixtures on alcohol hangover. Therefore, the aim of this study was to evaluate the effects of SKH on ethanol and acetaldehyde pharmacokinetics and alcohol hangover symptoms. In this randomized, double-blind, placebo-controlled, single-dose, two-sequence, two-period, crossover study, participants received SKH or a placebo after consuming alcohol in each period. Blood ethanol and acetaldehyde pharmacokinetics and product-related complications were assessed for 15 h; in addition, hangover symptoms were evaluated using the Acute Hangover Scale (AHS) during this period. In total, 27 participants completed the study. The geometric mean ratio for the mean maximum blood concentration of ethanol and the area under the concentration-time curve from zero to the time of the last quantifiable concentration of SKH to the placebo were 1.03 and 1.00, respectively. The corresponding values for acetaldehyde were 0.82 and 0.85, respectively. AHS scores tended to be lower after SKH consumption than after placebo consumption. None of the parameters showed significant between-group differences. In conclusion, SKH reduced the blood acetaldehyde concentration after alcohol consumption. This study can provide a foundation for more definitive human trials aimed at elucidating the effects of yeast extract on alcohol hangover.
