Spread the Word: No Amount of Alcohol is Safe!

Excessive use of alcohol is prevalent in the United States, and there are a variety of adverse health effects. The Global Burden of Diseases, Injuries, and Risk Factors Study determined that no amount of alcohol is safe. The American Cancer Society's 2020 guideline for diet and physical activity for cancer prevention is their first to advise that "it is best to not drink alcohol." There is a need for increased awareness by both laypeople and health care professionals of the health and social hazards associated with alcohol. The Healthcare Professional's Core Resource on Alcohol provides such training. The World Health Organization recommends population-based interventions such as increased alcohol taxes, restrictions or bans on alcohol advertising, and limits on places that sell alcohol. Gastroenterology nurses have a special opportunity to intervene with patients because a variety of gastroenterology conditions are alcohol-related. Our advocacy responsibility is to assist with the initiation of workplace, local, state, and national policies that promote the recommendations that no amount of alcohol is safe.

Associations between lifestyle-related risk factors and back pain: a systematic review and meta-analysis of Mendelian randomization studies.

BACKGROUND: Mendelian randomization (MR) studies have an advantage over conventional observational studies when studying the causal effect of lifestyle-related risk factors on back pain. However, given the heterogeneous design of existing MR studies on back pain, the reported causal estimates of these effects remain equivocal, thus obscuring the true extent of the biological effects of back pain lifestyle-risk factors. PURPOSE: The purpose of this study was to conduct a systematic review with multiple meta-analyses on the associations between various lifestyle factors and low back pain. METHODS: We conducted a PRISMA systematic review and specifically included MR studies to investigate the associations between lifestyle factors-specifically, BMI, insomnia, smoking, alcohol consumption, and leisure sedentary behavior-and various back pain outcomes. Each meta-analysis synthesized data from three or more studies to assess the causal impact of these exposures on distinct back pain outcomes, including chronic pain, disability, and pain severity. Quality of studies was assessed according to STROBE-MR guidelines. RESULTS: A total of 1576 studies were evaluated and 20 were included. Overall, the studies included were of high quality and had a low risk of bias. Our meta-analysis demonstrates the positive causal effect of BMI (OR IVW-random effects models: 1.18 [1.08-1.30]), insomnia(OR IVW-random effects models: 1.38 [1.10-1.74]), smoking(OR IVW-fixed effects models: 1.30 [1.23-1.36]), alcohol consumption(OR IVW-fixed effects models: 1.31 [1.21-1.42]) and leisure sedentary behaviors(OR IVW-random effects models: 1.52 [1.02-2.25]) on back pain. CONCLUSION: In light of the disparate designs and causal effect estimates presented in numerous MR studies, our meta-analysis establishes a compelling argument that lifestyle-related risk factors such as BMI, insomnia, smoking, alcohol consumption, and leisure sedentary behaviors genuinely contribute to the biological development of back pain.

Astrocytes in Amyloid Generation and Alcohol Metabolism: Implications of Alcohol Use in Neurological Disorder(s).

As per the National Survey on Drug Use and Health, 10.5% of Americans aged 12 years and older are suffering from alcohol use disorder, with a wide range of neurological disorders. Alcohol-mediated neurological disorders can be linked to Alzheimer's-like pathology, which has not been well studied. We hypothesize that alcohol exposure can induce astrocytic amyloidosis, which can be corroborated by the neurological disorders observed in alcohol use disorder. In this study, we demonstrated that the exposure of astrocytes to ethanol resulted in an increase in Alzheimer's disease markers-the amyloid precursor protein, Aß1-42, and the ß-site-cleaving enzyme; an oxidative stress marker-4HNE; proinflammatory cytokines-TNF-α, IL1ß, and IL6; lncRNA BACE1-AS; and alcohol-metabolizing enzymes-alcohol dehydrogenase, aldehyde dehydrogenase-2, and cytochrome P450 2E1. A gene-silencing approach confirmed the regulatory role of lncRNA BACE1-AS in amyloid generation, alcohol metabolism, and neuroinflammation. This report is the first to suggest the involvement of lncRNA BACE1-AS in alcohol-induced astrocytic amyloid generation and alcohol metabolism. These findings will aid in developing therapies targeting astrocyte-mediated neurological disorders and cognitive deficits in alcohol users.

[Health effects of alcohol: untangling the truth from the false!] / Effets de l'alcool sur la santé : démêler le vrai du faux !

HEALTH EFFECTS OF ALCOHOL: UNTANGLING THE TRUTH FROM THE FALSE! Daily alcohol consumption is associated with an increased risk of death, even at low doses. However, it remains high in France, where a large proportion of the population consumes alcohol in excess of reasonable limits. The most recent data invalidate the idea that a low dose could reduce cardiovascular risk. Santé publique France recommended in 2017 not to exceed the dose of 100 g of pure alcohol per week and not to drink alcohol every day. Harmonizing taxes on different types of alcoholic beverages upwards and indicating on each container: "Do not exceed 10 glasses per week" would be two good public health measures.

"EFFETS DE L'ALCOOL SUR LA SANTÉ : DÉMÊLER LE VRAI DU FAUX ! La consommation quotidienne d'alcool est associée à un risque augmenté de décès, et ce même si la dose d'alcool est faible. Elle reste toutefois élevée en France où une bonne partie de la population a une consommation dépassant les limites d'une consommation raisonnable. Les données les plus récentes infirment l'idée qu'une faible dose pourrait réduire le risque cardiovasculaire. Santé publique France a recommandé en 2017 de ne pas dépasser la dose de 100 g d'alcool pur par semaine et de ne pas boire d'alcool tous les jours. Harmoniser par le haut les taxes sur les différents types de boissons alcoolisées et indiquer sur chaque contenant : « Ne pas dépasser 10 verres par semaine ¼ seraient deux bonnes mesures de santé publique."

Trend in mortality from mental and behavioral disorders due to alcohol use in Brazil, 2010-2021.

OBJECTIVE: To analyze the trend in mortality from mental and behavioral disorders due to alcohol use in Brazil, 2010-2021. METHODS: This was an time series study using Mortality Information System data. Annual percentage change (APC) and 95% confidence intervals (95% CI) were calculated using Prais-Winsten linear regression. RESULTS: Mortality showed a stationary trend for Brazil as a whole (APC = 0.6; 95%CI -4.2;3.0), a falling trend in individuals aged 20-29 years in the South (APC = -7.4; 95%CI -10.0;-4.3) and Northeast (APC = -3.4; 95%CI -6.4;-0.4) regions, in people aged 30-39 in the Midwest region (APC = -3,8; 95%CI -7.4;-0.1) and 40-49 in the South (APC = -2.1; 95%CI -3.8;-0.4), North (APC = -3.1; 95%CI -5.7;-0.5) and Midwest (APC = -2.9; 95%CI -5.5;-0.3) regions. CONCLUSION: Mortality from mental and behavioral disorders due to alcohol use showed a stationary trend nationally and a falling trend in some age groups regionally.

Association of modifiable metabolic risk factors and lifestyle with all-cause mortality in patients with hepatocellular carcinoma.

We aimed to investigate the potential impact of metabolic risk factors and lifestyles on mortality in hepatocellular carcinoma (HCC) patients. From the Korean Central Cancer Registry database (2008-2016), 8,505 HCC patients were included in the analysis. Patients with 2 or more metabolic risk factors (n = 2384, 28.0%) showed significantly worse overall survival (OS, 29 months, 95% confidence interval [CI] 27-33) than patients with 0 (n = 2269 [26.7%]; 41 months, 95% CI 37-47), or 1 (n = 3852 [45.3%]; 42 months; 95% CI 38-46) metabolic risk factor. (P < 0.001) In the multivariable Cox analysis, patients with ≥ 2 metabolic risk factors had significantly elevated risk of overall mortality (adjusted hazards ratio (HR) = 1.14 [95% CI 1.06-1.23], P < 0.001) and HCC-specific mortality (sub-distribution HR = 1.09 [95% CI 1.00-1.09], P = 0.046), compared to those without. Alcohol and smoking were also independent risk factors for worse overall and HCC-specific mortality (all P < 0.05). Metabolic comorbidities were associated with greater risk of mortality in a dose-dependent manner in HCC patients, regardless of tumor stage and liver function. Alcohol intake and smoking significantly increased mortality by themselves and even further with the presence of metabolic risk.

Association between alcohol consumption and all-cause mortality, cardiovascular disease, and chronic kidney disease: A prospective cohort study.

In recent years, significant progress has been achieved in comprehending the impact of alcohol consumption on adverse health outcomes. However, the quality of evidence remains limited. Our objective was to conduct a prospective study examining the relationship between different types of alcoholic beverages and the risk of all-cause mortality, cardiovascular disease (CVD), and chronic kidney disease (CKD), and identifying the thresholds of safe dose stratified by sex using data from the UK Biobank. 502,490 participants were enrolled. These participants were initially registered between 2006 and 2010, and underwent reassessment between 2012 and 2013. All participants completed a detailed questionnaire on their alcohol consumption, including total alcohol consumption yesterday, weekly consumption of red wine, champagne plus white wine, beer, spirits, and fortified wine. All-cause mortality and the incidence of CVD and CKD were considered as the primary outcomes. 2852 participants reported CKD during a median follow-up period of 11.94 years, while 79,958 participants reported CVD over a median follow-up period of 11.35 years. Additionally, 18,923 participants died over a median follow-up period of 11.89 years. After adjusting for variables such as age, sex, education level, smoking status, diet score, and exercise score, total alcohol consumption showed a U-shaped relationship with the risk of CVD and all-cause mortality, but showed an inverse association with the risk of CKD. Upon further classification of alcoholic beverages, our analysis revealed that red wine, champagne plus white wine, beer, spirits, and fortified wine presented a U-shaped relationship with the risk of all-cause mortality and CKD. However, spirits were positively associated with the risk of CVD, only red wine, champagne plus white wine, beer, and fortified wine showed a U-shaped relationship with the risk of CVD. The safe doses of total alcohol consumption should be < 11 g/d for males and < 10 for females, red wine consumption should be < 7 glasses/week for males and < 6 for females, champagne plus white wine consumption should be < 5 glasses/week, and fortified wine consumption should be < 4 glasses/week. Red wine, champagne plus white wine, beer, and fortified wine below the corresponding thresholds of safe dose in our analysis were significantly associated with a lower risk of all-cause mortality, CVD, and CKD. And these alcoholic beverages under safe doses exhibited a protective effect against conditions like diabetes, depression, dementia, epilepsy, liver cirrhosis, and other digestive diseases, while didn't increase the risk of cancer.

Strategies for isoniazid preventive therapy in HIV-positive patients who consume alcohol.

WHO guidance to defer isoniazid preventive therapy (IPT) among those with regular alcohol use because of hepatotoxicity concerns may exclude many people living with HIV (PLWH) at high TB risk in these settings.To evaluate hepatotoxicity during TB preventive therapy (TPT) in PLWH who report alcohol use in Uganda over 10 years.We developed a Markov model of latent TB infection, isoniazid preventive therapy (IPT - a type of TPT), and TB disease using data from the Alcohol Drinkers' Exposure to Preventive Therapy for TB (ADEPTT) study. We modeled several treatment scenarios, including no IPT, IPT with liver enzyme monitoring (AST/ALT) during treatment, and IPT with pre-screening using the tuberculin skin test (TST).The no IPT scenario had 230 TB deaths/100,000 population over 10 years, which is more than that seen in any IPT scenario. IPT, even with no monitoring, was preferred over no IPT when population TB disease incidence was >50 in 100,000.For PLWH who report alcohol use in high TB burden settings, IPT should be offered, ideally with regular AST/ALT monitoring. However, even if regular monitoring is not possible, IPT is still preferable to no IPT in almost every modeled scenario..

Lifestyle factors and their relative contributions to longitudinal progression of cardio-renal-metabolic multimorbidity: a prospective cohort study.

BACKGROUND: The role of lifestyle factors and their relative contributions to the development and mortality of cardio-renal-metabolic multimorbidity (CRMM) remains unclear. METHODS: A study was conducted with 357,554 UK Biobank participants. CRMM was defined as the coexistence of two or three cardio-renal-metabolic diseases (CRMDs), including cardiovascular disease (CVD), type 2 diabetes (T2D) and chronic kidney disease (CKD). The prospective study examined the associations of individual and combined lifestyle scores (diet, alcohol consumption, smoking, physical activity, sedentary behavior, sleep duration and social connection) with longitudinal progression from healthy to first cardio-renal-metabolic disease (FCRMD), then to CRMM, and ultimately to death, using a multistate model. Subsequently, quantile G-computation was employed to assess the relative contribution of each lifestyle factor. RESULTS: During a median follow-up of 13.62 years, lifestyle played crucial role in all transitions from healthy to FCRMD, then to CRMM, and ultimately to death. The hazard ratios (95% CIs) per score increase were 0.91 (0.90, 0.91) and 0.90 (0.89, 0.91) for healthy to FCRMD, and for FCRMD to CRMM, and 0.84 (0.83, 0.86), 0.87 (0.86, 0.89), and 0.90 (0.88, 0.93) for mortality risk from healthy, FCRMD, and CRMM, respectively. Among the seven factors, smoking status contributed to high proportions for the whole disease progression, accounting for 19.88-38.10%. High-risk diet contributed the largest proportion to the risk of transition from FCRMD to CRMM, with 22.53%. Less-frequent social connection contributed the largest proportion to the risk of transition from FCRMD to death, with 28.81%. When we further consider the disease-specific transitions, we find that lifestyle scores had slightly stronger associations with development to T2D than to CVD or CKD. CONCLUSIONS: Our study indicates that a healthy lifestyle may have a protective effect throughout the longitudinal progression of CRMM, informing more effective management and treatment. Smoking status, diet, and social connection played pivotal roles in specific disease transitions.

Exploring the impacts of risk factors on mortality patterns of global Alzheimer's disease and related dementias from 1990 to 2021.

Alzheimer's Disease and Related Dementias (ADRD) affect millions of people worldwide, with mortality rates influenced by several risk factors and exhibiting significant heterogeneity across geographical regions. This study aimed to investigate the impact of risk factors on global ADRD mortality patterns from 1990 to 2021, utilizing clustering and modeling techniques. Data on ADRD mortality rates, cardiovascular disease, and diabetes prevalence were obtained for 204 countries from the GBD platform. Additional variables such as HDI, life expectancy, alcohol consumption, and tobacco use prevalence were sourced from the UNDP and WHO. All the data were extracted for men, women, and the overall population. Longitudinal k-means clustering and generalized estimating equations were applied for data analysis. The findings revealed that cardiovascular disease had significant positive effects of 1.84, 3.94, and 4.70 on men, women, and the overall ADRD mortality rates, respectively. Tobacco showed positive effects of 0.92, 0.13, and 0.39, while alcohol consumption had negative effects of - 0.59, - 9.92, and - 2.32, on men, women, and the overall ADRD mortality rates, respectively. The countries were classified into five distinct subgroups. Overall, cardiovascular disease and tobacco use were associated with increased ADRD mortality rates, while moderate alcohol consumption exhibited a protective effect. Notably, tobacco use showed a protective effect in cluster A, as did alcohol consumption in cluster B. The effects of risk factors on ADRD mortality rates varied among the clusters, highlighting the need for further investigation into the underlying causal factors.

Epidemiologic relationship between alcohol flushing and smoking in the Korean population: the Korea National Health and Nutrition Examination Survey.

Although facial flushing after drinking alcohol (alcohol flushing response) is common in Asian populations, the epidemiological features in a large sample have been investigated in only a few studies. This study assessed the epidemiologic characteristics and associated factors for alcohol flushing in a Korean population. This study was based on data collected during the 2019 Korea National Health and Nutrition Examination Survey (KNHANES). A total of 5572 Korean adults was included in the general population group, and the alcohol flushing group consisted of 2257 participants. Smoking and physical activity were evaluated as possible associated factors for alcohol flushing. The overall prevalence of alcohol flushing was estimated at 40.56% of the general population (43.74% in males and 37.4% in females), and the prevalence was highest at 60-69 years of age and lowest in individuals older than 80 years. Occasional, frequent, and persistent alcohol flushing was reported by 11.9%, 3.7% and 15.0% of current flushers, among whom persistent flushers consumed the least amount of alcohol. Subjects who currently smoke had a higher propensity of alcohol flushing (adjusted OR 1.525, 95% CI 1.2-1.938), and subjects with smoking history of 20-29 pack-years (PYs) showed the highest association (adjusted OR 1.725, 95% CI 1.266-2.349) with alcohol flushing after adjustment for confounders. In contrast, significant association was not found between physical activity and alcohol flushing. The results demonstrated that current smoking status is shown to be significantly associated with alcohol flushing, and that current smokers with a history of smoking ≥ 20 PYs had a higher likelihood of alcohol flushing than non-smokers or ex-smokers.

Objective Assessments of Smoking and Drinking Outperform Clinical Phenotypes in Predicting Variance in Epigenetic Aging.

The reliability of the associations of the acceleration of epigenetic aging (EA) indices with clinical phenotypes other than for smoking and drinking is poorly understood. Furthermore, the majority of clinical phenotyping studies have been conducted using data from subjects of European ancestry. In order to address these limitations, we conducted clinical, physiologic, and epigenetic assessments of a cohort of 278 middle-aged African American adults and analyzed the associations with the recently described principal-components-trained version of GrimAge (i.e., PC-GrimAge) and with the DunedinPACE (PACE) index using regression analyses. We found that 74% of PC-GrimAge accelerated aging could be predicted by a simple baseline model consisting of age, sex, and methylation-sensitive digital PCR (MSdPCR) assessments of smoking and drinking. The addition of other serological, demographic, and medical history variables or PACE values did not meaningfully improve the prediction, although some variables did significantly improve the model fit. In contrast, clinical variables mapping to cardiometabolic syndrome did independently contribute to the prediction of PACE values beyond the baseline model. The PACE values were poorly correlated with the GrimAge values (r = 0.2), with little overlap in variance explained other than that conveyed by smoking and drinking. The results suggest that EA indices may differ in the clinical information that they provide and may have significant limitations as screening tools to guide patient care.

The Impact of Tobacco Smoking and Alcohol Consumption on the Development of Gastric Cancers.

Chronic infection of Helicobacter pylori is considered the principal cause of gastric cancers, but evidence has accumulated regarding the impact of tobacco smoking and alcohol consumption on the development of gastric cancers. Several possible mechanisms, including the activation of nicotinic acetylcholine receptors, have been proposed for smoking-induced gastric carcinogenesis. On the other hand, local acetaldehyde exposure and ethanol-induced mucosal inflammation have been proposed as the mechanisms involved in the development of gastric cancers in heavy alcohol drinkers. In addition, genetic polymorphisms are also considered to play a pivotal role in smoking-related and alcohol-related gastric carcinogenesis. In this review, we will discuss the molecular mechanisms involved in the development of gastric cancers in relation to tobacco smoking and alcohol consumption.

The association between alcohol consumption and herpes simplex virus type 2: A cross-sectional study from national health and nutrition examination survey 2009-2016.

BACKGROUND: The current prevalence of Herpes simplex virus type 2 (HSV-2) infection is notably high, with individuals afflicted by HSV-2 facing recurrent outbreaks, challenges in achieving remission, and an elevated risk of HIV infection. This study aims to investigate the relationship between alcohol consumption and HSV-2 infection. METHODS: The data for this study were sourced from 7257 participants who took part in the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2016. The target population consisted of adults with reliable HSV-2 plasma results, and alcohol consumption was assessed using self-report methods. We evaluated the odds ratio (OR) and 95% confidence interval (CI) for the association between alcohol consumption and HSV-2 infection. These estimations were derived from a logistic regression model that was adjusted for key confounding factors. Subgroup analysis specifically focused on alcohol consumption, and the interaction between HSV-2 infection, alcohol consumption, and other variables was assessed through stratified analysis. RESULTS: Among the 7,257 participants included, 89.8% (6,518/7,257) reported varying levels of alcohol consumption history. Compared to individuals who never drinkers, the adjusted odds ratios (ORs) for former drinkers, light drinkers, moderate drinkers, and heavy drinkers were 1.79 (95% CI: 1.34-2.4, p < 0.001), 1.38 (95% CI: 1.07-1.77, p = 0.012), 1.49 (95% CI: 1.15-1.94, p = 0.003), and 1.47 (95% CI: 1.14-1.9, p = 0.003), respectively. The results remained stable in subgroup analyses and sensitivity analyses. CONCLUSION: Current research indicates that individuals with a history of alcohol consumption exhibit a higher risk of HSV-2 infection compared to those who have never drinkers.

[Hypothetical Alcohol Consumption Interventions and Hepatic Steatosis: A Longitudinal Study in a Large Cohort]. / æ¨¡æ‹Ÿé¥®é ’å¹²é¢„ä¸Žè‚è„‚è‚ªå˜æ€§ï¼šä¸€é¡¹å¤§åž‹é˜Ÿåˆ—çš„çºµå‘ç ”ç©¶.

Objective: Non-alcoholic fatty liver disease (NAFLD) and alcohol-associated fatty liver disease (ALD) are the most common chronic liver diseases. Hepatic steatosis is an early histological subtype of both NAFLD and ALD. Excessive alcohol consumption is widely known to lead to hepatic steatosis and subsequent liver damage. However, reported findings concerning the association between moderate alcohol consumption and hepatic steatosis remain inconsistent. Notably, alcohol consumption as a modifiable lifestyle behavior is likely to change over time, but most previous studies covered alcohol intake only once at baseline. These inconsistent findings from existing studies do not inform decision-making concerning policies and clinical guidelines, which are of greater interest to health policymakers and clinician-scientists. Additionally, recommendations on the types of alcoholic beverages are not available. Usually, assessing the effects of two or more hypothetical alcohol consumption interventions on hepatic steatosis provides answers to questions concerning the population risk of hepatic steatosis if everyone changes from heavy drinking to abstinence, or if everyone keeps on drinking moderately, or if everyone of the drinking population switches from red wine to beer? Thus, we simulated a target trial to estimate the effects of several hypothetical interventions, including changes in the amount of alcohol consumption or the types of alcoholic beverages consumed, on hepatic steatosis using longitudinal data, to inform decisions about alcohol-related policymaking and clinical care. Methods: This longitudinal study included 12687 participants from the UK Biobank (UKB), all of whom participated in both baseline and repeat surveys. We excluded participants with missing data related to components of alcohol consumption and fatty liver index (FLI) in the baseline and the repeat surveys, as well as those who had reported liver diseases or cancer at the baseline survey. We used FLI as an outcome indicator and divided the participants into non-, moderate, and heavy drinkers. The surrogate marker FLI has been endorsed by many international organizations' guidelines, such as the European Association for the Study of the Liver. The calculation of FLI was based on laboratory and anthropometric data, including triglyceride, gamma-glutamyl transferase, body mass index, and waist circumference. Participants responded to questions about the types of alcoholic beverages, which were defined in 5 categories, including red wine, white wine/fortified wine/champagne, beer or cider, spirits, and mixed liqueurs, along with the average weekly or monthly amounts of alcohol consumed. Alcohol consumption was defined as pure alcohol consumed per week and was calculated according to the amount of alcoholic beverages consumed per week and the average ethanol content by volume in each alcoholic beverage. Participants were categorized as non-drinkers, moderate drinkers, and heavy drinkers according to the amount of their alcohol consumption. Moderate drinking was defined as consuming no more than 210 g of alcohol per week for men and 140 g of alcohol per week for women. We defined the following hypothetical interventions for the amount of alcohol consumed: sustaining a certain level of alcohol consumption from baseline to the repeat survey (e.g., none to none, moderate to moderate, heavy to heavy) and changing from one alcohol consumption level to another (e.g., none to moderate, moderate to heavy). The hypothetical interventions for the types of alcoholic beverages were defined in a similar way to those for the amount of alcohol consumed (e.g., red wine to red wine, red wine to beer/cider). We applied the parametric g-formula to estimate the effect of each hypothetical alcohol consumption intervention on the FLI. To implement the parametric g-formula, we first modeled the probability of time-varying confounders and FLI conditional on covariates. We then used these conditional probabilities to estimate the FLI value if the alcohol consumption level of each participant was under a specific hypothetical intervention. The confidence interval was obtained by 200 bootstrap samples. Results: For the alcohol consumption from baseline to the repeat surveys, 6.65% of the participants were sustained non-drinkers, 63.68% were sustained moderate drinkers, and 14.74% were sustained heavy drinkers, while 8.39% changed from heavy drinking to moderate drinking. Regarding the types of alcoholic beverages from baseline to the repeat surveys, 27.06% of the drinkers sustained their intake of red wine. Whatever the baseline alcohol consumption level, the hypothetical interventions for increasing alcohol consumption from the baseline alcohol consumption were associated with a higher FLI than that of the sustained baseline alcohol consumption level. When comparing sustained non-drinking with the hypothetical intervention of changing from non-drinking to moderate drinking, the mean ratio of FLI was 1.027 (95% confidence interval [CI]: 0.997-1.057). When comparing sustained non-drinking with the hypothetical intervention of changing from non-drinking to heavy drinking, the mean ratio of FLI was 1.075 (95% CI: 1.042-1.108). When comparing sustained heavy drinking with the hypothetical intervention of changing from heavy drinking to moderate drinking, the mean ratio of FLI was 0.953 (95% CI: 0.938-0.968). The hypothetical intervention of changing to red wine in the UKB was associated with lower FLI levels, compared with sustained consumption of other types of alcoholic beverages. For example, when comparing sustaining spirits with the hypothetical intervention of changing from spirits to red wine, the mean ratio of FLI was 0.981 (95% CI: 0.948-1.014). Conclusions: Regardless of the current level of alcohol consumption, interventions that increase alcohol consumption could raise the risk of hepatic steatosis in Western populations. The findings of this study could inform the formulation of future practice guidelines and health policies. If quitting drinking is challenging, red wine may be a better option than other types of alcoholic beverages in Western populations.

The impact of alcohol and illicit substance use on the pharmacokinetics of first-line TB drugs.

BACKGROUND: In South Africa, an estimated 11% of the population have high alcohol use, a major risk factor for TB. Alcohol and other substance use are also associated with poor treatment response, with a potential mechanism being altered TB drug pharmacokinetics. OBJECTIVES: To investigate the impact of alcohol and illicit substance use on the pharmacokinetics of first-line TB drugs in participants with pulmonary TB. METHODS: We prospectively enrolled participants ≥15 years old, without HIV, and initiating drug-susceptible TB treatment in Worcester, South Africa. Alcohol use was measured via self-report and blood biomarkers. Other illicit substances were captured through a urine drug test. Plasma samples were drawn 1 month into treatment pre-dose, and 1.5, 3, 5 and 8 h post-dose. Non-linear mixed-effects modelling was used to describe the pharmacokinetics of rifampicin, isoniazid, pyrazinamide and ethambutol. Alcohol and drug use were tested as covariates. RESULTS: The study included 104 participants, of whom 70% were male, with a median age of 37 years (IQR 27-48). Alcohol use was high, with 42% and 28% of participants having moderate and high alcohol use, respectively. Rifampicin and isoniazid had slightly lower pharmacokinetics compared with previous reports, whereas pyrazinamide and ethambutol were consistent. No significant alcohol use effect was detected, other than 13% higher ethambutol clearance in participants with high alcohol use. Methaqualone use reduced rifampicin bioavailability by 19%. CONCLUSION: No clinically relevant effect of alcohol use was observed on the pharmacokinetics of first-line TB drugs, suggesting that poor treatment outcome is unlikely due to pharmacokinetic alterations. That methaqualone reduced rifampicin means dose adjustment may be beneficial.