Associations of Menstrual Cycle and Progesterone-to-Estradiol Ratio With Alcohol Consumption in Alcohol Use Disorder: A Sex-Separated Multicenter Longitudinal Study.

OBJECTIVE: Alcohol use disorder (AUD) constitutes a critical public health issue and has sex-specific characteristics. Initial evidence suggests that progesterone and estradiol might reduce or increase alcohol intake, respectively. However, there is a need for a better understanding of how the menstrual cycle in females and the ratio of progesterone to estradiol in females and males influence alcohol use patterns in individuals with AUD. METHODS: In this sex-separated multicenter longitudinal study, the authors analyzed 12-month data on real-life alcohol use (from 21,460 smartphone entries), menstrual cycle, and serum progesterone-to-estradiol ratios (from 667 blood samples at four individual study visits) in 74 naturally cycling females and 278 males with AUD between 2020 and 2022, using generalized and general linear mixed modeling. RESULTS: Menstrual cycle phases were significantly associated with binge drinking and progesterone-to-estradiol ratio. During the late luteal phase, females showed a lower predicted binge drinking probability of 13% and a higher predicted marginal mean of progesterone-to-estradiol ratio of 95 compared with during the menstrual, follicular, and ovulatory phases (binge drinking probability and odds ratios vs. late luteal phase, respectively: 17%, odds ratio=1.340, 95% CI=1.031, 1.742; 19%, odds ratio=1.523, 95% CI=1.190, 1.949; and 20%, odds ratio=1.683, 95% CI=1.285, 2.206; difference in progesterone-to-estradiol ratios, respectively: -61, 95% CI=-105.492, -16.095; -78, 95% CI=-119.322, -37.039; and -71, 95% CI=-114.568, -27.534). In males, a higher progesterone-to-estradiol ratio was related to lower probabilities of binge drinking and of any alcohol use, with a 10-unit increase in the hormone ratio resulting in odds ratios of 0.918 (95% CI=0.843, 0.999) and 0.914 (95% CI=0.845, 0.988), respectively. CONCLUSIONS: These ecologically valid findings suggest that high progesterone-to-estradiol ratios can have a protective effect against problematic alcohol use in females and males with AUD, highlighting the progesterone-to-estradiol ratio as a promising treatment target. Moreover, the results indicate that females with AUD may benefit from menstrual cycle phase-tailored treatments.

Skeletal muscle satellite cell-derived mesenchymal stem cells ameliorate acute alcohol-induced liver injury.

Cultured human skeletal-muscle satellite cells have properties of mesenchymal stem cells (skeletal muscle satellite cell-derived mesenchymal stem cells, SkMSCs) and play anti-inflammatory roles by secreting prostaglandin E2 and hepatocyte growth factor (HGF). To evaluate the utility of SkMSCs in treating liver diseases, we determined whether SkMSCs could ameliorate acute liver and gut inflammation induced by binge ethanol administration. Binge drinking of ethanol led to weight loss in the body and spleen, liver inflammation and steatosis, and increased serum ALT and AST levels (markers of liver injury), along with increased IL-1ß, TNF-α, and iNOS expression levels in mice. However, levels of these binge-drinking-induced indicators were reduced by a single intraperitoneal treatment of SkMSCs. Furthermore, levels of bacteria-derived lipopolysaccharide decreased in the livers and sera of ethanol-exposed mice after SkMSC administration. SkMSCs decreased the extent of tissue inflammation and reduced villus and crypt lengths in the small intestine after alcohol binge drinking. SkMSCs also reduced the leakage of blood albumin, an indicator of leaky gut, in the stool of ethanol-exposed mice. Alcohol-induced damage to human colonic Caco-2/tc7 cells was also alleviated by HGF. Therefore, a single treatment with SkMSCs can attenuate alcoholic liver damage by reducing inflammatory responses in the liver and gut, suggesting that SkMSCs could be used in cell therapy to treat alcoholic liver diseases.

An Integrative Screening Tool of Alcohol Exposure During Early Pregnancy: Combining of the CDT Biomarker with Green Page Questionnaire.

AIMS: In current clinical practice, prenatal alcohol exposure is usually assessed by interviewing the pregnant woman by applying questionnaires. An alternative method for detecting alcohol use is to measure the biomarker carbohydrate-deficient transferrin (CDT). However, few studies measure CDT during pregnancy. This study examines the utility of CDT biomarker in the screening of alcohol exposure during early pregnancy. METHODS: A cohort of 91, first-trimester pregnant women assigned to a public reference maternity hospital, was screened using the Green Page (GP) questionnaire, an environmental exposure tool. CDT levels and other biomarkers of alcohol use were measured and compared with questionnaire data. RESULTS: About 70% of the mothers in the study consumed alcohol during early pregnancy and 22% met high-risk criteria for prenatal exposure to alcohol. CDT measurement showed a statistically significant area under the receiver operating characteristic curve with a value of 0.70. For a value of 0.95% of CDT, a specificity of 93% was observed. The most significant predictors of CDT were the number of binge drinking episodes, women's body mass index and European white race. CONCLUSION: Pregnant women with a CDT value >0.95% would be good candidates for the performance of the GP questionnaire during early pregnancy in order to detect potential high-risk pregnancy due to alcohol exposure.

Clove Bud Polyphenols Alleviate Alterations in Inflammation and Oxidative Stress Markers Associated with Binge Drinking: A Randomized Double-Blinded Placebo-Controlled Crossover Study.

Acetaldehyde, the major cytotoxin formed by the metabolism of alcohol, is responsible for liver injury, extracellular matrix alterations, inflammation, and hangover in heavy drinkers. This study aimed to demonstrate the efficacy of a standardized polyphenolic extract of clove buds (Clovinol) in ameliorating the oxidative stress and inflammation caused by the accumulation of acetaldehyde after binge drinking. We used a randomized, double-blinded crossover study with 16 male social drinkers. The subjects were randomized into two groups of eight subjects and received either placebo or Clovinol in a single hard shell gelatin capsule (250 mg × 1) per day. The dosage of alcohol was 1 g/kg body weight/day. After 2 weeks of washout period, the treatment regime was reversed. Blood samples were drawn at 0, 0.5, 2, 4, and 12 h after treatment with either placebo or Clovinol, and biochemical parameters were analyzed. Hangover severity score was determined by using a validated questionnaire as reported earlier. Results showed faster elimination of blood acetaldehyde with significant decreases in oxidative stress, lipid peroxidation, C-reactive protein, interleukin-6, and significant enhancement in glutathione and superoxide dismutase as compared with placebo along with an overall reduction of 55.34% in hangover severity in Clovinol-treated subjects. This study demonstrated the efficacy of clove bud polyphenols for alleviating alcohol-related side effects among social drinkers at the studied dose.

Increased plasma oleoylethanolamide and palmitoleoylethanolamide levels correlate with inflammatory changes in alcohol binge drinkers: the case of HMGB1 in women.

Alcohol binge drinking is a heavy pattern of alcohol consumption increasingly used by young people. In a previous study, we reported that young drinkers with a 2-year history of binge alcohol consumption had an overactivation of the innate immune system and peripheral inflammation when compared with controls. In the present study, we measured several biolipids that are fatty acid derivatives belonging to the acylethanolamide or 2-acylglycerol families in the plasma of the same subjects (n = 42; 20 men and 22 women). We found that during abstinence, alcohol binge drinkers had elevated plasma levels of oleoylethanolamide, palmitoleoylethanolamide, arachidonoylethanolamide, dihomo-γ-linolenoyl ethanolamide and linoleoyl ethanolamide, which positively correlated with changes in the mRNA expression of key inflammatory markers in peripheral blood mononuclear cells, such as toll-like receptors (TLR4), pro-inflammatory cytokines/chemokines interleukin-1 beta, interleukin-6 and monocyte chemoattractant protein-1, and cyclooxygenase-2. Additionally, plasma oleoylethanolamide positively correlated with plasma levels of high mobility group box-1, which is a danger-associated molecular pattern and an endogenous TLR4 agonist, specifically in female alcohol binge drinkers. No changes were observed in 2-acylglycerols in alcohol binge drinkers, although sex-related differences in these bioactive lipids as well as in palmitoleoylethanolamide and docosatetraenoylethanolamide levels were detected. These results extend the previous clinical findings observed in patients diagnosed with long-term alcohol use disorder to young users and suggest a prominent role for these lipids in the response to acute alcohol exposure.

Binge drinking and total alcohol consumption from 16 to 43 years of age are associated with elevated fasting plasma glucose in women: results from the northern Swedish cohort study.

BACKGROUND: Studies have indicated that moderate alcohol consumption is associated with lower incidence of diabetes in women. However, not only the amount but also the drinking pattern could be of importance when assessing the longitudinal relation between alcohol and glucose. Also, there is a lack of studies on alcohol use beginning in adolescence on adult glucose levels. The aim was to examine the association between total alcohol consumption and binge drinking between ages 16 and 43 and fasting plasma glucose at age 43. METHODS: Data were retrieved from a 27-year prospective cohort study, the Northern Swedish Cohort. In 1981, all 9th grade students (n = 1083) within a municipality in Sweden were invited to participate. There were re-assessments at ages 18, 21, 30 and 43. This particular study sample consisted of 897 participants (82.8%). Fasting plasma glucose (mmol/L) was measured at a health examination at age 43. Total alcohol consumption (in grams) and binge drinking were calculated from alcohol consumption data obtained from questionnaires. RESULTS: Descriptive analyses showed that men had higher levels of fasting plasma glucose as compared to women. Men also reported higher levels of alcohol consumption and binge drinking behavior. Linear regressions showed that total alcohol consumption in combination with binge drinking between ages 16 and 43 was associated with elevated fasting plasma glucose at age 43 in women (beta = 0.14, p = 0.003) but not in men after adjustment for BMI, hypertension and smoking at age 43. CONCLUSIONS: Our findings indicate that reducing binge drinking and alcohol consumption among young and middle-aged women with the highest consumption might be metabolically favorable for their future glucose metabolism.

Biological implications of selenium in adolescent rats exposed to binge drinking: Oxidative, immunologic and apoptotic balance.

Alcohol intermittent binge drinking (BD) during adolescence decreases the levels of selenium (Se), a trace element that plays a key biological role against oxidative damage in hepatocytes through different selenoproteins such as the antioxidant enzymes glutathione peroxidases (GPx1 and Gpx4) and selenoprotein P (SelP). In this context, it has been found that GPx4 has an essential antioxidant role in mitochondria modulating the apoptosis and NF-kB activation (a factor intimately related to apoptosis and immune function). To further investigate the effectiveness of selenium supplementation in oxidative balance, inflammation and apoptosis, the present study examined the protective effects of 0.4ppm of dietary selenite administrated to adolescent rats exposed to BD. BD consumption depleted Se deposits in all the tissues studied. In liver, GPx1 activity and expression were decreased leading to protein and lipid hepatic oxidation. Moreover GPx4 and NF-kB expression were also decreased in liver, coinciding with an increase in caspase-3 expression. This hepatic profile caused general liver damage as shown the increased serum transaminases ratio AST/ALT. Proinflammatory serum citokines and chemocines were decreased. Se supplementation therapy used restored all these values, even AST levels. These findings suggest for first time that Se supplementation is a good strategy against BD liver damage during adolescence, since it increases GPx1 and GPx4 expression and avoids NF-kB downregulation and caspase-3 upregulation, leading to a better oxidative, inflammatory and apoptotic liver profile. The therapy proposed could be considered to have a great biological efficacy and to be suitable for BD exposed teenagers in order to avoid future hepatic complications.

MicroRNA-223 ameliorates alcoholic liver injury by inhibiting the IL-6-p47phox-oxidative stress pathway in neutrophils.

OBJECTIVES: Chronic-plus-binge ethanol feeding activates neutrophils and exacerbates liver injury in mice. This study investigates how recent excessive drinking affects peripheral neutrophils and liver injury in alcoholics, and how miR-223, one of the most abundant microRNAs (miRNAs) in neutrophils, modulates neutrophil function and liver injury in ethanol-fed mice. DESIGNS: Three hundred alcoholics with (n=140) or without (n=160) recent excessive drinking and 45 healthy controls were enrolled. Mice were fed an ethanol diet for 10 days followed by a single binge of ethanol. RESULTS: Compared with healthy controls or alcoholics without recent drinking, alcoholics with recent excessive drinking had higher levels of circulating neutrophils, which correlated with serum levels of alanine transaminase (ALT) and aspartate transaminase (AST). miRNA array analysis revealed that alcoholics had elevated serum miR-223 levels compared with healthy controls. In chronic-plus-binge ethanol feeding mouse model, the levels of miR-223 were increased in both serum and neutrophils. Genetic deletion of the miR-223 gene exacerbated ethanol-induced hepatic injury, neutrophil infiltration, reactive oxygen species (ROS) and upregulated hepatic expression of interleukin (IL)-6 and phagocytic oxidase (phox) p47phox. Mechanistic studies revealed that miR-223 directly inhibited IL-6 expression and subsequently inhibited p47phox expression in neutrophils. Deletion of the p47phox gene ameliorated ethanol-induced liver injury and ROS production by neutrophils. Finally, miR-223 expression was downregulated, while IL-6 and p47phox expression were upregulated in peripheral blood neutrophils from alcoholics compared with healthy controls. CONCLUSIONS: miR-223 is an important regulator to block neutrophil infiltration in alcoholic liver disease and could be a novel therapeutic target for the treatment of this malady.

Learning and Memory in Adolescent Moderate, Binge, and Extreme-Binge Drinkers.

BACKGROUND: Binge drinking has been linked to neurocognitive disadvantages in youth, but it is unclear whether drinking at particularly heavy levels uniquely affects neurocognitive performance. This study prospectively examined (1) whether initiating moderate, binge, or extreme-binge drinking in adolescence differentially influences subsequent learning and memory performances, and (2) whether dosage of alcohol consumption is linearly associated with changes in learning and memory over 6 years of adolescence. METHODS: Participants, who later transitioned into drinking, were administered verbal learning and memory (VLM) assessments at project intake prior to the onset of substance use (age 12 to 16 years), and at follow-up approximately 6 years later (N = 112). Participants were grouped based on alcohol involvement at follow-up as follows: moderate (≤4 drinks per occasion), binge (5+ drinks per occasion), or extreme-binge (10+ drinks per occasion) drinkers. RESULTS: Despite equivalent performances prior to onset of drinking, extreme-binge drinkers performed worse than moderate drinkers on verbal learning, and cued and free short delayed recall (ps < 0.05); binge drinkers did not differ from the other groups. No distinct thresholds in alcohol quantity to differentiate the 3 groups were detected, but estimated peak blood alcohol concentrations were linearly associated with verbal learning (ß^ = -0.24), and immediate (ß^ = -0.27), short delay free (ß^ = -0.28) and cued (ß^ = -0.30), and long delay free (ß^ = -0.24) and cued (ß^ = -0.27) recall (ps < 0.05). CONCLUSIONS: Drinking quantity during adolescence appears to adversely affect VLM in a dose-dependent manner. The acquisition of new verbal information may be particularly affected, notably for those who initiated drinking 10+ drinks in an occasion. Although classification of drinkers into categories remains critical in the study of alcohol, it is important to consider that subtle differences may exist within drinking categories.

Therapeutic Benefits of Spleen Tyrosine Kinase Inhibitor Administration on Binge Drinking-Induced Alcoholic Liver Injury, Steatosis, and Inflammation in Mice.

BACKGROUND: Binge drinking is increasingly recognized as an important cause of liver disease with limited therapeutic options for patients. Binge alcohol use, similar to chronic alcohol consumption, induces numerous deregulated signaling events that drive liver damage, steatosis, and inflammation. In this article, we evaluated the role of spleen tyrosine kinase (SYK), which modulates numerous signaling events previously identified linked in the development alcohol-induced liver pathology. METHODS: A 3-day alcohol binge was administered to C57BL/6 female mice, and features of alcoholic liver disease were assessed. Some mice were treated daily with intraperitoneal injections of a SYK inhibitor (R406; 5 to 10 mg/kg body weight) or drug vehicle control. Liver and serum samples were collected and were assessed by Western blotting, biochemical, ELISA, electrophoretic mobility shift assays, real-time quantitative polymerase chain reaction, and histopathological analysis. RESULTS: We found that binge drinking induced significant SYK activation (SYK(Y525/526) ) with no change in total SYK expression in the liver. Functional inhibition of SYK activation using a potent SYK inhibitor, R406, was associated with a significant decrease in alcohol-induced hepatic inflammation as demonstrated by decreased phospho-nuclear factor kappa beta (NF-κB) p65, NF-κB nuclear binding, tumor necrosis factor-alpha, and monocyte chemoattractant protein-1 mRNA in the liver. Compared to vehicle controls, SYK inhibitor treatment decreased alcohol binge-induced hepatocyte injury indicated by histology and serum alanine aminotransferase. Strikingly, SYK inhibitor treatment also resulted in a significant reduction in alcohol-induced liver steatosis. CONCLUSIONS: Our novel observations demonstrate the role of SYK, activation in the pathomechanism of binge drinking-induced liver disease highlighting SYK a potential multifaceted therapeutic target.

Acute immunomodulatory effects of binge alcohol ingestion.

BACKGROUND: Blood alcohol is present in a third of trauma patients and has been associated with organ dysfunction. In both human studies and in animal models, it is clear that alcohol intoxication exerts immunomodulatory effects several hours to days after exposure, when blood alcohol is no longer detectable. The early immunomodulatory effects of alcohol while blood alcohol is still elevated are not well understood. METHODS: Human volunteers achieved binge alcohol intoxication after high-dose alcohol consumption. Blood was collected for analysis prior to alcohol ingestion, and 20 min, 2 h, and 5 h after alcohol ingestion. Flow cytometry was performed on isolated peripheral blood mononuclear cells, and cytokine generation in whole blood was measured by enzyme-linked immunosorbent assay (ELISA) after 24-h stimulation with lipopolysaccharide (LPS) and phytohemagglutinin-M (PHA) stimulation. RESULTS: An early pro-inflammatory state was evident at 20 min when blood alcohol levels were ∼130 mg/dL, which was characterized by an increase in total circulating leukocytes, monocytes, and natural killer cells. During this time, a transient increase in LPS-induced tumor necrosis factor (TNF)-α levels and enhanced LPS sensitivity occurred. At 2 and 5 h post-alcohol binge, an anti-inflammatory state was shown with reduced numbers of circulating monocytes and natural killer cells, attenuated LPS-induced interleukin (IL)-1ß levels, and a trend toward increased interleukin (IL)-10 levels. CONCLUSIONS: A single episode of binge alcohol intoxication exerted effects on the immune system that caused an early and transient pro-inflammatory state followed by an anti-inflammatory state.

Acute binge drinking increases serum endotoxin and bacterial DNA levels in healthy individuals.

Binge drinking, the most common form of alcohol consumption, is associated with increased mortality and morbidity; yet, its biological consequences are poorly defined. Previous studies demonstrated that chronic alcohol use results in increased gut permeability and increased serum endotoxin levels that contribute to many of the biological effects of chronic alcohol, including alcoholic liver disease. In this study, we evaluated the effects of acute binge drinking in healthy adults on serum endotoxin levels. We found that acute alcohol binge resulted in a rapid increase in serum endotoxin and 16S rDNA, a marker of bacterial translocation from the gut. Compared to men, women had higher blood alcohol and circulating endotoxin levels. In addition, alcohol binge caused a prolonged increase in acute phase protein levels in the systemic circulation. The biological significance of the in vivo endotoxin elevation was underscored by increased levels of inflammatory cytokines, TNFα and IL-6, and chemokine, MCP-1, measured in total blood after in vitro lipopolysaccharide stimulation. Our findings indicate that even a single alcohol binge results in increased serum endotoxin levels likely due to translocation of gut bacterial products and disturbs innate immune responses that can contribute to the deleterious effects of binge drinking.

Characterization of phosphatidylethanol blood concentrations for screening alcohol consumption in early pregnancy.

OBJECTIVE: Phosphatidylethanol (PEth) is formed endogenously by the direct action of ethanol, and has a half-life long enough to make it a reliable biomarker of alcohol exposure in early pregnancy. In this study, we aimed to characterize PEth blood concentrations to differentiate different levels of alcohol exposure in pregnant women. METHODS: The study consisted of 305 consecutive pregnant women who had been referred to our hospital for antenatal care. Of them, 117 self-reported alcohol ingestion in the first trimester of pregnancy and 188 were abstainers. Total PEth concentration in whole blood was quantified by liquid chromatography-mass spectrometry (LC-MS/MS). Alcohol ingestion was classified according to the United States National Institute on Alcohol Abuse and Alcoholism into light drinkers: ≤ 3 drinks/week, moderate drinkers: 3-7 drinks/week, and heavier drinkers: > 7 drinks/week (a standard drink = 14 g of ethanol). RESULTS: Participants had quantifiable PEth blood levels 3-4 weeks after the last drink. There were 4.8% abstainers who had positive PEth concentrations; all of them reported a positive history of alcohol consumption before conception. PEth blood concentrations were significantly correlated to drinks per occasion (r = 0.44; P < 0.001) and days drinking per week (r = 0.34; P < 0.001). However, almost 74% of participants with ≤ 3 drinks/week of alcohol, and 46% with 3-7 drinks/week, had PEth blood concentrations below the lower limit of quantification (LLOQ). The area under the curve (AUC) generated by a receiver operation characteristic curve (ROC) analysis increased as the cutoff value of PEth blood concentration increased. However, the cutoff values were below or close to the LLOQ. CONCLUSIONS: Our study presents a formal characterization of PEth blood concentrations for screening alcohol ingestion in first-trimester pregnant women. However, caution is recommended for overrepresenting either negative or positive results.

Associations between heavy alcohol drinking and lipid-related indices in middle-aged men.

The ratio of triglycerides to HDL cholesterol (TG/HDL-C ratio) and lipid accumulation product (LAP: a continuous marker of lipid over-accumulation determined by waist circumference and triglycerides) have been proposed to be good predictors of cardiovascular disease. The aim of this study was to clarify the relationships between heavy alcohol drinking and lipid-related indices including TG/HDL-C ratio, LAP, and ratio of LDL cholesterol to HDL cholesterol (LDL-C/HDL-C ratio). The subjects were middle-aged male nondrinkers and heavy drinkers (ethanol intake: ≥66 g per drinking day, which is 2-3 times or more than the generally recommended border level of daily alcohol consumption of 20-30 g). The levels of each lipid-related index after adjustment for age, smoking, and regular exercise were compared among nondrinkers, occasional heavy drinkers, and regular heavy drinkers. Log-transformed TG/HDL-C ratio was significantly higher in occasional heavy drinkers (mean ± standard error: 0.445 ± 0.014) than in nondrinkers (0.388 ± 0.004) and regular heavy drinkers (0.359 ± 0.013), and was not significantly different in nondrinkers and regular heavy drinkers. Log-transformed LAP was significantly higher in occasional heavy drinkers (1.51 ± 0.02) and regular heavy drinkers (1.44 ± 0.02) than in nondrinkers (1.34 ± 0.01), and was significantly higher in occasional heavy drinkers than in regular heavy drinkers. LDL-C/HDL-C ratio was significantly lower in occasional heavy drinkers (2.41 ± 0.04) and regular heavy drinkers (1.72 ± 0.04) than in nondrinkers (2.62 ± 0.01) and was significantly lower in regular heavy drinkers than in occasional heavy drinkers. Results of logistic regression analysis, using odds ratios for high lipid indices of occasional or regular heavy drinkers vs. nondrinkers, agreed with the above results of analysis of covariance. Occasional heavy drinkers showed more detrimental and less favorable levels of the lipid indices than did regular heavy drinkers, and thus heavy drinking, even if occasional, should be avoided to prevent cardiovascular disease.

Long-term binge and escalating ethanol exposure causes necroinflammation and fibrosis in rat liver.

BACKGROUND: To investigate whether "binge" and escalating alcohol exposure in the rat influences the development of pathological liver injury. METHODS: Time courses for the formation of eicosanoids by cyclooxygenase (COX), oxidative stress and nitrosative stress production, expression of hypoxia-inducible factor 1 (HIF-1), cytokines, hepatic tissue necroinflammation, and fibrosis were assessed in rats during 16 weeks of daily alcohol gavage. RESULTS: In this model of binge and escalating levels of alcohol, hepatic steatosis, necrosis, and inflammation as well as fibrosis were increased over the 16-week period. The levels of COX-2, oxidative stress, nitrosative stress, HIF-1, proinflammatory mediators (tumor necrosis factor-α, interleukin 1(ß) [IL-1(ß) ], IL-6), and procollagen-I were increased over the 16-week period. The content of IL-10 in rat serum increased at the end of 4 and 8 weeks but decreased thereafter and was significantly decreased at 12 and 16 weeks. CONCLUSIONS: A rat model of alcoholic liver disease (ALD) with long-term binge and escalating ethanol exposure was developed. Our data support the hypothesis that enhanced eicosanoid production by COX, oxidative stress and nitrosative stress, HIF-1, and the imbalance between pro- and anti-inflammatory cytokines plays an important role in the pathogenesis of ALD.

Gender-specific relationships between alcohol drinking patterns and metabolic syndrome: the Korea National Health and Nutrition Examination Survey 2008.

OBJECTIVE: To examine gender-specific relationships between alcohol drinking patterns (average drinking frequency, typical drinking quantity and frequency of binge drinking) and the prevalence of metabolic syndrome (MetS) and its components in the Korean population. DESIGN: Cross-sectional study using complex sampling design analyses. SETTING: The Korea National Health and Nutrition Examination Survey IV, which was conducted in 2008. SUBJECTS: Current drinkers (n 3793, 1963 men and 1830 women). RESULTS: After adjusting for confounders (age, educational level, income, physical activity, smoking, energy intake and drinking frequency in the analysis for drinking quantity), the associations of drinking quantity and frequency of binge drinking with the prevalence of MetS were gender-specific. Seven or more drinks for men and ≥ 3 drinks for women per typical occasion and binge drinking ≥ 1 time/week for both sexes resulted in significantly higher odds for the prevalence of MetS compared with men and women who had 1 or 2 drinks and no instances of binge drinking. The association of drinking quantity and the criteria of MetS was stronger for men with high blood pressure and abdominal obesity, whereas it was stronger for women with high glucose. Binge drinking frequency was dose-dependently associated with high TAG, high glucose, high blood pressure and abdominal obesity in men, and with high glucose and high blood pressure in women. Interestingly, average drinking frequency was not associated with the prevalence of MetS in either sex. CONCLUSIONS: Higher drinking quantity and frequent binge drinking are indicators of a higher prevalence of MetS, and the association strength is thought to be gender-specific.