Reduce Alcohol Intake Research Articles

The combination of a glucagon-like peptide-1 and amylin receptor agonists reduces alcohol consumption in both male and female rats.

Combining different pharmaceuticals may be beneficial when treating disorders with complex neurobiology, including alcohol use disorder (AUD). The gut-brain peptides amylin and GLP-1 may be of potential interest as they individually reduce alcohol intake in rodents. While the combination of amylin receptor (AMYR) and glucagon-like peptide-1 receptor (GLP-1R) agonists have been found to decrease feeding and body weight in obese male rats synergistically, their combined impact on alcohol intake is unknown. Therefore, the effect of the combination of an AMYR (salmon calcitonin (sCT)) and a GLP-1R (dulaglutide) agonist on alcohol intake in rats of both sexes was explored in two separate alcohol-drinking experiments. The first alcohol-drinking experiment evaluated the potential of adding sCT to an ongoing dulaglutide treatment, whereas the second alcohol-drinking experiment examined the effect when adding sCT and dulaglutide simultaneously. When adding sCT to an ongoing dulaglutide treatment, a reduction in alcohol intake was observed in both male and female rats. However, when combining sCT and dulaglutide simultaneously, an initial reduction in alcohol intake was observed in rats of both sexes, whereas tolerance towards treatment was observed. In both alcohol-drinking experiments, this treatment combination consistently decreased food consumption and body weight in males and females. While the treatment combination did not affect inflammatory mediators, the gene expression of AMYR or GLP-1R, it changed fat tissue morphology. Further investigation needs to be done on the combination of AMYR and GLP-1R agonists to assess their combined effects on alcohol intake.

Synergistic‐like decreases in alcohol intake following combined pharmacotherapy with GLP‐1 and amylin in male rats

Background and PurposeThe limited effectiveness of current pharmacological treatments for alcohol use disorder (AUD) highlights the need for novel therapies. These may involve the glucagon‐like peptide‐1 receptor or the amylin receptor, as treatment with agonists targeting either of these receptors lowers alcohol intake. The complexity of the mechanisms underlying AUD indicates that combining agents could enhance treatment efficacy. While a combination of amylin receptor and GLP‐1 receptor agonists reduced food intake and body weight synergistic‐like, its influence on alcohol intake is unknown.Experimental ApproachEffects of a range of dose‐combinations of GLP‐1 receptor (dulaglutide) and amylin receptor (salmon calcitonin; sCT) agonists on alcohol intake were explored in male and female rats. We used dose combinations that either lowered alcohol intake as monotherapy (0.1 mg·kg−1 + 5 μg·kg−1), or that did not affect alcohol consumption per se (0.075 mg·kg−1 + 2 μg·kg−1).Key ResultsAcute administration of dulaglutide and sCT (0.1 mg·kg−1 + 5 μg·kg−1) reduced alcohol intake in males, but not in females. When higher doses were evaluated in female rats, a decrease in alcohol intake was observed. Furthermore, the low dose combination (0.075 mg·kg−1 + 2 μg·kg−1) decreased, in in a synergistic‐like manner, alcohol intake and prevented abstinence‐induced drinking without affecting kaolin intake in males. However, tolerance developed during sub‐chronic treatment.Conclusion and ImplicationsCollectively, these findings show that the combination of dulaglutide and sCT decreased, in in a synergistic‐like manner, alcohol consumption in male rats. Contrarily, higher doses are required for females.

Kratom Alkaloids for the Treatment of Alcohol Use Disorder.

Alcohol use disorder (AUD) accounts for nearly 4.7% of all deaths and imposes a huge economic burden on society. Despite the magnitude of the problem, only a few Food and Drug Administration (FDA)/European Medicines Agency (EMA)-approved drugs are currently available for AUD treatment. Despite being efficacious, these drugs are not without problems, adverse effects being a major issue. That combined with medication adherence and compliance problems, the discovery of new drugs is imperative. Kratom (Mitragyna speciosa) alkaloids and some of their semisynthetic derivatives reduce alcohol intake and alcohol-induced withdrawal symptoms in animal models. These compounds act as G-protein-biased ligands at the μ-, δ-, and κ-opioid receptors, and their effect in reducing alcohol intake is mediated through the δ-opioid receptor. This article provides a critical overview of recent preclinical studies involving kratom alkaloids for AUD treatment, with a particular focus on the pharmacology and medicinal chemistry of these alkaloids. FDA/EMA approved drugs, repurposed drugs, and plant-based compounds for the treatment of AUD are briefly mentioned. Finally, important caveats and future research directions on this topic are discussed.

Alcohol consumption and preference in female rats induced by reward downshift reveals sex generality of the modulatory role of physical activity.

Increased voluntary consumption of alcohol has been demonstrated in male rats exposed to frustrative reward downshift (the emotional self-medication effect). Access to a wheel for voluntary running abolished this effect in male rats, suggesting an attenuating effect of physical exercise on the negative affect induced by reward downshift and its consequences on drug intake. The present study analyzed this effect in female rats. Sixty-four food-deprived female Wistar rats received 32% sucrose [4% (Experiment 1) or 2% (Experiment 2) in controls] during 10, 5-min preshift sessions followed by 4% (Experiment 1) or 2% (Experiment 2) sucrose during 5 postshift sessions. Immediately after each consummatory session, animals were exposed to a 2-h, two-bottle preference test involving 32% alcohol vs. water. Half of the animals also had access to a running wheel during the preference test. The results showed (a) lower sucrose consumption in the downshifted groups (32-4% and 32-2%) compared to the unshifted controls (4-4% and 2-2%, respectively); (b) higher alcohol preference in downshifted groups without access to a wheel compared with downshifted groups with access to the wheel (Experiments 1 and 2); and (c) increased alcohol intake (g/kg) after experiencing reward downshift in animals without access to the wheel (Experiment 1). Voluntary wheel running thus reduced alcohol intake in female rats experiencing reward downshift. These findings are comparable to previous results reported in male rats and support the usefulness of physical exercise to prevent alcohol self-medication induced by frustrative nonreward.

Treatment and Prevention Strategies of Breast Cancer

Abstract. With the increasing trend of late childbearing and low childbearing, the incidence of breast cancer is increasing rapidly worldwide. At present, breast cancer has become one of the more frequent malignant tumor diseases in women and has aroused widespread concern in society. The cause of the disease is not completely clear, with the deepening of research, the relevant detection methods are constantly updated, as far as possible early diagnosis. At present, the main methods of breast cancer prevention are lifestyle adjustment, including reducing alcohol intake, maintaining a healthy weight and chemical prevention, but the methods are limited, so the research on breast cancer prevention is particularly important. At the same time, medical workers should educate the majority of women about disease prevention, so that women can establish a correct concept of prevention and treatment, so as in order to lower the prevalence of breast cancer and improve the women health.

Tobacco use, cirrhosis, and age are predictors of readiness to change and continued drinking following brief alcohol intervention in veterans.

Alcohol use disorder is prevalent within the Veterans Health System, especially in patients being seen in hepatology clinics, and needs a point-of-care strategy. A brief alcohol intervention based on AUDIT-C (Alcohol Use Disorders Identification Test) may be needed for the management of hazardous alcohol intake, but feasibility is unclear. We aimed to define predictors of readiness to cease alcohol intake (0-10, 10 being ready to quit now) and continued drinking after using a brief alcohol intervention in veterans seen in hepatology clinics cross-sectionally and longitudinally over 6 months. A total of 414 men with liver disease (average age of 61y old, 48% with cirrhosis, 31% with concomitant psychiatric conditions, 44% with tobacco use, and 14% with prior alcohol use disorder therapy) were approached. One hundred forty-four patients (35%) had a positive AUDIT-C (8.9 ± 4.0) and were given the brief intervention. Eighty of these patients (56%) had a high readiness to change, listing "wanting to improve health" and "prior success at reducing alcohol intake" as their most frequent reasons. On regression analysis, concomitant tobacco use was associated with a significantly lower readiness to quit alcohol score. On longitudinal follow-up at 6 months, 34 (23%) patients were still drinking. These patients were older and more likely to have concomitant diagnoses of cirrhosis and anxiety. Overall, we found that in a large cohort of veterans seen in hepatology clinics in routine practice, a brief intervention targeted at alcohol use is feasible. Older patients with concomitant tobacco use, cirrhosis, and anxiety may need more longitudinal attention to ensure that the initial interest in reducing problem drinking is sustained.

Alcohol intake and patterns of multi-site musculoskeletal pain in the British Whitehall II study

Abstract Background Patterns of multi-site musculoskeletal (MSK) pain and its relationship with alcohol drinking among white-collar employees and retirees remain unclear compared to blue-collar workers. This study aimed to examine the relationship between alcohol drinking and MSK pain through latent class analysis (LCA) in current and retired white-collar employees. Methods We used the data from the 7th phase (2000-2002, n = 6,967, response rate 71.6%) of the British Whitehall II study, chosen for its availability of MSK items and approximately 1:1 ratio of employees to retirees, allowing for an evaluation of the relationship between alcohol drinking and MSK pain by employment status. LCA was used to distinguish patterns of multi-site MSK pain. A multinomial logistic regression model was used to examine the association between alcohol drinking and the identified pain patterns, with analyses conducted separately for employees and retirees. Results We identified five latent classes for pain (back/cervical: 7.1%, cervical: 28.9%, upper limb: 29.4%, combined LBP/upper limb/cervical: 13.2%, and LBP alone: 21.5%). Increased alcohol intake might be associated with elevated odds of upper limb pain in current drinkers, but this could not be statistically confirmed (OR: 1.04, 95% CI: 0.99-1.09). Employment status may modify the association with a significant interaction found between alcohol intake and retirement (p-value: 0.043). Every 7-unit increase in alcohol intake is associated with 18% and 12% higher odds of pain in LBP/UBP/cervical and upper limbs, respectively (95% CI: 1.02-1.37; 1.02-1.23). Conclusions Increased alcohol intake was associated with pain patterns only among retired white-collar employees but not the current ones. Interventions on alcohol consumption could help confirm if, reducing alcohol intake or avoiding hazardous drinking, for white-collar retirees prevents not only upper limb pain but also more complex pain patterns. Key messages • Musculoskeletal pain in white-collar employees and retirees contributes to the cervical and upper extremities, differing from low back/neck pain studies among general or blue-collar workers. • The association between alcohol drinking and pain patterns may differ across employment status. Reducing alcohol intake might be advised to retired drinkers for preventing multi-site pain.

Exploring the effects of reduced alcohol consumption on major adverse cardiovascular and cerebrovascular events in chronic heavy drinkers: a nationwide population-based cohort study

Abstract Background/Introduction Chronic heavy alcohol consumption is a well-established risk factor for cardiovascular disease (CVD), and the potential cardiovascular benefits of mild to moderate alcohol consumption need validation, particularly in the context of behavioral change from heavy drinking. Currently, there is a lack of research examining the potential benefits of reduced alcohol consumption in chronic heavy drinkers, specifically in relation to different subtypes of CVD. We hypothesized that habitual changes in alcohol consumption among chronic heavy drinkers would have a long-term prognostic effect on future CVD outcomes. Purpose We investigated the association between reduced alcohol consumption and the risk of major adverse cardiovascular and cerebrovascular events (MACCE) in chronic heavy drinkers. Methods From the Korean National Health Insurance Service-Health Screening database, we included a cohort of chronic heavy drinkers who underwent serial health examinations over two consecutive time-periods (first period: 2005–2008; second period: 2009–2012). Heavy drinking was defined according to the National Institute on Alcohol Abuse and Alcoholism criteria as >56 g/day or >196 g/week for men, and >42 g/day or >98 g/week for women. Overall, 13,854 heavy drinkers at baseline (mean age 55.84 ± 5.98 years; 91.6 % men) were categorized into two groups based on the alcohol consumption changes in the second period: sustained heavy drinking (n=9,403; 67.9%) or reduced drinking (n=4,451; 32.5%). The primary outcome was MACCE, a composite of nonfatal myocardial infarction or angina undergoing revascularization, any stroke accompanied by hospitalization, and all-cause death during follow-up. Results In this nationwide population-based cohort study, during a total follow-up of 107,102 person-years, the sustained heavy drinking group experienced a significantly higher incidence of MACCE than the reduced drinking group (incidence rate, 825 vs. 655 per 100,000 person-years; log-rank p=0.004). Reduced alcohol consumption was associated with a 28% lower risk of MACCE compared to sustained heavy drinking (adjusted-hazard ratio [HR]: 0.780, 95% confidence interval [CI] 0.656–0.928). These benefits were mostly driven by a significant reduction in the incidence of angina (adjusted-HR: 0.631, 95% CI 0.425–0.926) and ischemic stroke (adjusted-HR: 0.657, 95% CI 0.472–0.914). The preventive effects of reduced alcohol intake were consistently observed across various subgroups of heavy drinkers, except for smoking status (p-interaction=0.015) and even after including abstainers in the sensitivity analysis. Conclusion Reduced alcohol consumption in heavy drinkers could lower the future risk of CVD, with the most pronounced benefits expected for stable/unstable angina and ischemic stroke. Further research is warranted to explore the optimal strategies for promoting sustained reductions in alcohol intake.Cumulative MACCE incidence curves

Validation study of risk-reduction activities after personalized breast cancer education tool in the WISDOM study

Breast cancer risk reduction strategies have been well-validated, but barriers remain for high-risk individuals to adopt them. We performed a study among participants with high risk of breast cancer to validate whether a virtual breast health decision tool impacted a participant’s willingness to start risk-reducing activities, identify barriers to adopting these strategies, and understand if it affects breast cancer anxiety. The study sample was 318 participants in the personalized (investigational) arm of the Women Informed to Screen Depending on Measures of risk (WISDOM) clinical trial. After reviewing the tool, these participants completed a feedback survey. We demonstrated that 15 (4.7%) women were taking endocrine risk reduction, 123 (38.7%) were reducing alcohol intake, and 199 (62.6%) were exercising. In the three-month follow-up survey of 109 respondents, only 8 of 61 (13.1%) women who considered endocrine risk reduction pursued it. In contrast, 11 of 16 (68%) participants who considered alcohol reduction pursued the activity, and 14 of 24 (58%) women who considered exercise followed through. Participants listed fear of side effects as the most common barrier to endocrine risk reduction. We also present further steps to be taken to improve the effectiveness of the Breast Health Decisions tool.

Centrally administered growth hormone secretagogue receptor antagonist DLys decreases alcohol intake and preference in male mice.

Alcohol use disorder (AUD) is a highly prevalent public health problem. The ghrelin system has been identified as a potential target for therapeutic intervention for AUD. Previous work showed that systemic administration of the growth hormone secretagogue receptor (GHSR) antagonist DLys reduced alcohol intake and preference in male mice. Yet, it is unclear whether central or peripheral GHSRs mediated these effects. We hypothesized that alcohol consumption is driven by central GHSRs and addressed this hypothesis by testing the effects of central administration of DLys. Male C57BL/6J mice consumed alcohol in a two-bottle choice procedure (10% ethanol versus water). DLys (2 nmol) was administered intracerebroventricularly for 7 days to examine alcohol intake and preference. DLys decreased alcohol intake and preference but had no effect on food intake. The effects on alcohol intake and preference persisted after several administrations, indicating lack of tolerance to DLys' effects. These results suggest that central administration of DLys is sufficient to reduce alcohol drinking and that DLys remains effective after several administrations when given intracerebroventricularly. Moreover, this work suggests that the effects of intracerebroventricularly administered DLys are specific to alcohol and do not generalize to other calorie-driven behaviors.

Consumption of oxycodone prevents oxytocin from attenuating alcohol intake in rats

Alcohol and opioid polysubstance use (PSU) is common and often accompanied by higher trait anxiety. Oxytocin decreases anxiety, alcohol- and opioid-seeking and -taking but has not been assessed in the context of PSU. Here we developed a rat model of sequential oxycodone and alcohol PSU to examine the relationship between anxiety, alcohol and oxycodone intake, and the efficacy of systemic oxytocin to attenuate alcohol intake. Male and female Sprague-Dawley rats were assessed for baseline anxiety-like behavior using acoustic startle and the elevated plus maze (EPM). Rats were then given 2-bottle choice access to oxycodone and/or water for 6-hr/day for 7 days, followed by 2-bottle choice access to alcohol (20% v/v) and/or water for five 24-hr sessions across 10 days. Next, monosubstance (oxycodone- or alcohol-alone) rats continued to have access to only one substance/day while PSU rats had access to oxycodone and water for 3-hr, followed by alcohol and water for 6-hr. After 12 days, rats were tested in the EPM 20 hours after alcohol access to examine withdrawal-related anxiety. Next, oxytocin (0, 0.3 or 1.0 mg/kg IP) was administered following the oxycodone/water session, 30 minutes prior to alcohol access. Rats received intragastric oxycodone (2 mg/kg) or water followed by intragastric alcohol (2 g/kg) and blood was collected to determine blood alcohol levels. Elevated baseline anxiety-like behavior was accompanied by reduced alcohol intake. Consumption of oxycodone did not alter alcohol intake but resulted in less anxiety-like behavior during withdrawal and prevented oxytocin from attenuating alcohol intake. Oxytocin (1 mg/kg) reduced alcohol intake in the alcohol-only condition, an effect that persisted for days after a single oxytocin administration. Rats that received oxycodone prior to non-contingent alcohol displayed higher blood alcohol levels than those that did not. These results support the necessity for the testing of medications for substance use in rodent models of PSU.

Impact of Lifestyle Factors on Hypertension Risk Among Elderly: Physical Activity, Stress, Smoking, and Alcohol Consumption

Background: Hypertension is a major public health concern, particularly among the elderly, and is influenced by various modifiable risk factors such as physical activity, stress, smoking, and alcohol consumption. At the Payung Sekaki Public Health Center, these factors were investigated to understand their relationship with hypertension in the elderly population. Methods: A cross-sectional study was conducted involving 74 respondents, primarily elderly individuals, who were assessed for physical activity levels, alcohol consumption, smoking habits, and stress levels. Data were collected through structured questionnaires, and statistical analysis was performed to examine the correlations between these factors and the incidence of hypertension. Results: The findings revealed that 56.8% of respondents engaged in good physical activity, while 43.2% did not, with a significant association between reduced physical activity and an increased risk of hypertension. Stress was found to be prevalent among 74.3% of respondents, with moderate stress reported by the majority, indicating a significant relationship with hypertension. Alcohol consumption and smoking were less common among the elderly, but those who consumed alcohol or smoked were found to have a higher likelihood of developing hypertension. A large portion of respondents expressed a desire to reduce alcohol intake and quit smoking due to health concerns. Conclusion: The study highlights the importance of physical activity, stress management, and lifestyle changes, such as reducing alcohol consumption and quitting smoking, in managing hypertension among the elderly. These findings emphasize the need for public health interventions that target modifiable risk factors to reduce hypertension prevalence in older populations.

Sex-Specific Roles of Hypocretin Receptor Signaling in CRF Neurons on Alcohol Drinking, Anxiety, and BNST Neuronal Excitability.

Alcohol use disorder (AUD) is characterized by compulsive alcohol consumption and negative emotional states during withdrawal, often perpetuating a cycle of addiction through arousal dysfunction. The hypocretin/orexin (Hcrt) neuropeptide system, a key regulator of arousal, has been implicated in these processes, particularly in its interactions with corticotropin-releasing factor (CRF) neurons within the bed nucleus of the stria terminalis (BNST). We investigated the role of Hcrt receptor signaling in CRF neurons in modulating alcohol intake, anxiety behaviors, and BNST excitability, with a focus on sex-specific differences. Using CRF-specific genetic deletion of HcrtR1 and/or HcrtR2 receptors in mice, we found that deletion of HcrtR1 significantly reduced alcohol intake, with sex-specific effects on BNST excitability. CRF-specific HcrtR2 deletion, while not affecting alcohol consumption, decreased baseline anxiety-like behaviors in males relative to females. Moreover, the double deletion of both Hcrt receptors from CRF neurons led to reduced alcohol drinking in males and dampened anxiety behaviors and BNST excitability in both sexes during protracted withdrawal. These findings suggest that Hcrt signaling in CRF neurons plays a critical role in the persistence of excessive alcohol consumption and the development of negative affective states, with distinct contributions from HcrtR1 and HcrtR2. The observed sex-specific differences underscore the need for tailored therapeutic approaches targeting the Hcrt system in the treatment of AUD.

Wine intake and 45-year mortality in middle-aged men with high alcohol consumption: The Italian rural areas of the Seven Countries Study

Research into the relationship between alcohol consumption and health has a long-standing history. Previous studies have revealed the beneficial effects of moderate alcohol consumption on cardiovascular disease (CVD) and all-cause mortality compared to abstainers and heavy drinkers. To study the long-term impact of wine intake on mortality, we conducted a study involving 1284 men aged 45 – 64 years in 1965, followed over a period of 45 years. We analyzed their wine-drinking habits in relation to all-cause mortality and specific causes using the Cox model. In addition, we utilized a multiple regression model with age at death as the dependent variable adjusted for age, smoking habits, body mass index, physical activity, dietary score, and comorbidity index. At baseline, 97.7% of participants were drinkers, consuming alcohol at an average of 77.4 g/day (mostly from wine). After 45 years, 98.4% of men had passed away. Our findings revealed a J-shaped relationship between alcohol intake and mortality from major CVD and all causes, while the relationship was roughly linear for cancer and liver cirrhosis. The relationship with CVD and all-cause mortality remained J-shaped, even when abstainers were excluded from the analysis, indicating potential health benefits for those consuming an average of 52 g/day (range: 47 – 70 g) and a 34% excess in mortality for those consuming an average of 176 g/day (range: 142 – 570 g). The average age at death for the reference class was 3.5 years higher compared to abstainers and 3.8 years higher compared to the upper class (average: 176 g/day). Reducing alcohol intake during the first 20 years of follow-up was beneficial in terms of life expectancy. In a lifetime follow-up, the relationship between alcohol consumption and mortality formed a J-shaped curve for CVD and all-cause mortality, even when excluding abstainers. Thus, relatively high wine consumption is more beneficial than lower intakes, especially when associated with vigorous physical activity at work – a common practice among rural men in the 1960s.

Des-acyl ghrelin reduces alcohol intake and alcohol-induced reward in rodents

The mechanisms contributing to alcohol use disorder (AUD) are complex and the orexigenic peptide ghrelin, which enhances alcohol reward, is implied as a crucial modulator. The major proportion of circulating ghrelin is however the non-octanoylated form of ghrelin, des-acyl ghrelin (DAG), whose role in reward processes is unknown. As recent studies show that DAG decreases food intake, we hypothesize that DAG attenuates alcohol-related responses in animal models. Acute and repeated DAG treatment dose-dependently decreased alcohol drinking in male and female rats. In these alcohol-consuming male rats, repeated DAG treatment causes higher levels of dopamine metabolites in the ventral tegmental area, an area central to reward processing. The role of DAG in reward processing is further supported as DAG prevents alcohol-induced locomotor stimulation, reward in the conditioned place preference paradigm, and dopamine release in the nucleus accumbens in male rodents. On the contrary, DAG does not alter the memory of alcohol reward or affect neurotransmission in the hippocampus, an area central to memory. Further, circulating DAG levels are positively correlated with alcohol drinking in female but not male rats. Studies were conducted in attempts to identify tentative targets of DAG, which currently are unknown. Data from these recombinant cell system revealed that DAG does not bind to either of the monoamine transporters, 5HT2A, CB1, or µ-opioid receptors. Collectively, our data show that DAG attenuates alcohol-related responses in rodents, an effect opposite to that of ghrelin, and contributes towards a deeper insight into behaviors regulated by the ghrelinergic signaling pathway.

Male Infertility: Its Diagnosis and Management

Male infertility is a significant health issue affecting couples worldwide. Male infertility, a complex and increasingly prevalent issue, poses significant challenges to reproductive health both nationally and internationally. Traditionally infertility has been considered female concern, but recent studies highlighted that male factor contributes equally to fertility problems in couples. Male infertility is a significant medical condition affecting approximately 7% of men worldwide, with approximately 50% of infertility cases attributed to male factors. It is defined by the inability to conceive a child after one year of unprotected intercourse. There are different causes of male infertility, which can vary widely and may include hormonal imbalances, genetic factors, anatomical issues such as varicocele (enlarged veins within the scrotum), or lifestyle factors such as smoking or excessive alcohol consumption. Diagnosis and management strategies play crucial roles in addressing this condition and improving fertility outcomes. Diagnosis typically involves semen analysis to assess sperm count, motility, and morphology. Treatments range from medication to surgery, depending on the underlying cause, although in some cases, assisted reproductive techniques like in vitro fertilization (IVF) may be necessary 1. It is reported that Trace minerals play a crucial role in male fertility by supporting various physiological processes necessary for sperm production and function. Zinc, for instance, is essential for the synthesis of testosterone and the development of healthy sperm. Deficiencies in zinc have been linked to decreased sperm quality and infertility in men2. Selenium is another trace mineral that acts as an antioxidant, protecting sperm from oxidative damage and enhancing sperm motility. Adequate intake of these traces minerals through diet or supplementation may potentially improve fertility outcomes in men by supporting sperm health and function.3 According to WHO, Accurate diagnosis of male infertility involves a comprehensive evaluation of both medical history and physical examination, followed by specialized laboratory tests. Conventional method of Semen analysis remains the cornerstone for assessing male fertility, examining parameters such as sperm count, motility, and morphology 4. Additional tests may include hormonal assays to assess levels of testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH), which provide insights into testicular function and endocrine status 5. Advanced diagnostic techniques are also available in specialized fertility centers such as sperm DNA fragmentation testing and sperm function assays, which have gained importance in recent years for evaluating sperm quality beyond traditional parameters 6. Similarly, Genetic testing may also be indicated in cases of suspected genetic abnormalities impacting fertility, such as Y chromosome micro deletions or karyotyping analysis 7. Male infertility can be better managed, if the underlying cause is properly identified through diagnostic evaluation. It is reported that lifestyle modifications, including weight management, smoking cessation, and reduction of alcohol intake, may improve sperm quality in some cases8. Beside this, Medical interventions such as hormone replacement therapy or medications to improve sperm production (e.g., clomiphene citrate) can be beneficial for certain hormonal imbalances 9. Moreover, assisted reproductive techniques (ART), including intrauterine insemination (IUI) and in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI), are often employed when natural conception is not achievable10. These techniques offer viable options for couples facing male infertility, particularly in cases of severe sperm abnormalities or obstruction of the reproductive tract. Despite advancements, challenges however, still persist in managing male infertility, which includes access to specialized care centre and financial constraints related to ART. It is concluded that effective management of male infertility requires a multidisciplinary approach, involving urologists, reproductive endocrinologists/ andrologists, pathologists, and genetic counselors. Collaborative efforts between clinicians, researchers and policymakers are also beneficial to address the complexities of male infertility and hence enhance overall fertility care. Early and accurate diagnosis enables targeted interventions that can significantly improve fertility outcomes for couples. Continued research and technological advancements are crucial for enhancing diagnostic precision and therapeutic efficacy in addressing male infertility.

Effect of the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide on alcohol consumption in alcohol-preferring male vervet monkeys.

Glucagon-like peptide-1 (GLP-1) receptor agonists reduce alcohol consumption in rodents and non-human primates. Semaglutide is a new long-acting GLP-1 receptor agonist, widely used in the clinic against type 2 diabetes and obesity. It is also reported to reduce alcohol intake in rodents. This study investigates the possible inhibitory effect of semaglutide on alcohol intake in alcohol-preferring African green monkeys. We performed a vehicle-controlled study on male monkeys that had demonstrated a preference for alcohol. In the monkeys selected for voluntary alcohol drinking, alcohol consumption was measured for ten days at baseline (Monday to Friday for two weeks). During this period, the monkeys had access to alcohol 4h per day and free access to water 24h per day. After two weeks of baseline measurements, the monkeys were randomized to semaglutide or vehicle. Each group consisted of ten monkeys, and the two groups were balanced with respect to baseline alcohol intake. Following the baseline period, the monkeys were treated with escalating doses of semaglutide (up to 0.05mg/kg) or vehicle subcutaneously twice weekly for two weeks during which period alcohol was not available. After uptitration, the monkeys had access to alcohol 4h daily for 20 days (Monday to Friday for 4 weeks), and alcohol consumption was measured. During this alcohol exposure period, treatment with semaglutide (0.05mg/kg twice weekly) or vehicle continued for three weeks followed by a one-week washout period. Compared to the vehicle, semaglutide significantly reduced alcohol intake. There were no signs of emetic events or changes in water intake. These data demonstrate for the first time the potent effect of semaglutide in reducing voluntary alcohol intake in non-human primates and further substantiate the need for clinical trials investigating the effect of semaglutide in patients with alcohol-use disorder.

The effectiveness of a brief intervention for intensive care unit patients with hazardous alcohol use: a randomized controlled trial.

Screening for hazardous alcohol use and performing brief interventions (BIs) are recommended to reduce alcohol-related negative health consequences. We aimed to compare the effectiveness (defined as an at least 10% absolute difference) of BI with usual care in reducing alcohol intake in intensive care unit survivors with history of hazardous alcohol use. We used Alcohol Use Disorder Identification Test-Consumption (AUDIT-C) score to assess history of alcohol use. Emergency admitted adult ICU patients in three Finnish university hospitals, with an AUDIT-C score > 5 (women), or > 6 (men). We randomized consenting eligible patients to receive a BI or treatment as usual (TAU). BI was delivered by the time of ICU discharge or shortly thereafter in the hospital ward. Control patients received TAU. The primary outcome was self-reported alcohol consumption during the preceding week 6 and 12months after randomization. Secondary outcomes were the change in AUDIT-C scores from baseline to 6 and 12months, health-related quality of life, and mortality. The trial was terminated early due to slow recruitment during the pandemic. We randomized 234 patients to receive BI (N = 117) or TAU (N = 117). At 6months, the median alcohol intake in the BI and TAU groups were 6.5g (interquartile range [IQR] 0-141) and 0g (0-72), respectively (p = 0.544). At 12months, it was 24g (0-146) and 0g (0-96) in the BI and TAU groups, respectively (p = 0.157). Median change in AUDIT-C from baseline to 6months was - 1 (- 4 to 0) and 2 (- 6 to 0), (p = 0.144) in the BI and TAU groups, and to 12months - 3 (- 5 to - 1) and - 4 (- 7 to - 1), respectively (p = 0.187). In total, 4% (n = 5) of patients in the BI group and 11% (n = 13) of patients in the TAU group were abstinent at 6months, and 10% (n = 12) and 15% (n = 17), respectively, at 12months. No between-groups difference in mortality emerged. As underpowered, our study cannot reject or confirm the hypothesis that a single BI early after critical illness is effective in reducing the amount of alcohol consumed compared to TAU. However, a considerable number in both groups reduced their alcohol consumption. ClinicalTrials.gov (NCT03047577).

Role of ghrelin hormone in the development of alcohol-associated liver disease

Fatty liver is the earliest response of the liver to excessive alcohol consumption. Previously we identified that chronic alcohol administration increases levels of stomach-derived hormone, ghrelin, which by reducing circulating insulin levels, ultimately contributes to the development of alcohol-associated liver disease (ALD). In addition, ghrelin directly promotes fat accumulation in hepatocytes by enhancing de novo lipogenesis. Other than promoting ALD, ghrelin is known to increase alcohol craving and intake. In this study, we used a ghrelin receptor (GHSR) knockout (KO) rat model to characterize the specific contribution of ghrelin in the development of ALD with emphasis on energy homeostasis. Male Wistar wild type (WT) and GHSR-KO rats were pair-fed the Lieber-DeCarli control or ethanol diet for 6 weeks. At the end of the feeding period, glucose tolerance test was conducted, and tissue samples were collected. We observed reduced alcohol intake by GHSR-KOs compared to a previous study where WT rats were fed ethanol diet ad libitum. Further, when the WTs were pair-fed to GHSR-KOs, the KO rats exhibited resistance to develop ALD through improving insulin secretion/sensitivity to reduce adipose lipolysis and hepatic fatty acid uptake/synthesis and increase fatty acid oxidation. Furthermore, proteomic data revealed that ethanol-fed KO exhibit less alcohol-induced mitochondrial dysfunction and oxidative stress than WT rats. Proteomic data also confirmed that the ethanol-fed KOs are insulin sensitive and are resistant to hepatic steatosis development compared to WT rats. Together, these data confirm that inhibiting ghrelin action prevent alcohol-induced liver and adipose dysfunction independent of reducing alcohol intake.

Impact of alcohol consumption on metabolic dysfunction-associated fatty liver disease development and remission: A longitudinal cohort study.

The influence of alcohol intake on metabolic dysfunction-associated fatty liver disease (MAFLD) development and remission remains unclear; thus, we aimed to investigate their longitudinal associations. This observational cohort study included 6349 patients who underwent more than two health check-ups over >2 years between April 2013 and March 2021. Generalized estimation equations were used to analyse the longitudinal associations between changes in alcohol intake and MAFLD according to repeated measures at baseline and the most recent stage. The MAFLD development and remission rates were 20.4 and 5.1 and 9.1 and 4.7% in men and women, respectively. Although alcohol consumption was not a significant factor for MAFLD development, consuming 0.1-69.9 g/week (odds ratio [OR]: 0.672, 95% confidence interval [CI]: 0.469-0.964, p < .05) and ≥280 g/week were significant factors for MAFLD development in males (OR: 1.796, 95% CI: 1.009-3.196, p < .05) and females (OR: 16.74, 95% CI: 3.877-72.24, p < .001). Regardless of quantity and frequency, alcohol consumption was not a significant factor for MAFLD remission. Several noninvasive liver fibrosis scores were significantly associated with alcohol intake quantity and frequency in males with MAFLD development and remission (p < .05). The nonalcoholic fatty liver disease fibrosis score differed significantly between males with and without reduced alcohol intake (p < .05) who showed MAFLD remission. Although the influence of alcohol intake on MAFLD development and remission differed, alcohol consumption was not beneficial for MAFLD remission in either sex. Alcohol intake reduction or cessation is recommended to prevent liver fibrosis, even in those who achieve MAFLD remission.