Moderate Alcohol Research Articles

Moderate alcohol use, total brain volume, and white matter hyperintensities among racially and ethnically diverse middle‐aged adults

AbstractBackgroundModerate alcohol use may provide later life cognitive benefits compared to heavy alcohol use. However, results have been mixed, with reports of both increased and decreased gray and white matter volumes with moderate drinking. Additionally, alcohol use on brain health may differ by sex and race/ethnicity. Understanding the association between brain health and moderate drinking in a representative, community‐based study will provide insight into the reported cognitive benefits. We investigated the relationship between alcohol use and total brain volume (TBV) and white matter hyperintensities (WMH) in a diverse sample of middle‐aged non‐alcohol dependent community‐dwelling adults.MethodParticipants (N = 350; Mage = 54±10 years; 33 Black Men, 38 Black Women, 66 Latinx Men, 166 Latinx Women, 7 White Men, 20 White Women) from the Offspring study of Racial and Ethnic Disparities in Alzheimer’s Disease, a community‐based study in Northern Manhattan, underwent structural (TBV = 1051±106cm3) and vascular (WMH = 3±4cm3) MRI. Alcohol use was assessed by the Alcohol Use Disorder Identification Test–Concise (AUDIT‐C). Individuals likely to be alcohol dependent (AUDIT‐C = 9) were excluded (n = 16). We assessed alcohol use and TBV or WMH, adjusting for age, in the overall group, and stratified by sex/gender groups, racial/ethnic groups, and sex/gender by race/ethnicity groups.ResultOverall, greater TBV was associated with younger age (‐3.5cm3 [‐4.7, ‐2.3], p = 9E‐10) and greater alcohol use (5.1cm3 [‐6.8, 10.8], p = 0.085). No associations were found within men and women separately. Within race/ethnic groups, greater alcohol use was associated with greater TBV only among Latinx (7.6cm3 [0.1, 15.3], p = 0.055). Within sex/gender by race/ethnicity groups, greater alcohol use was associated with lower TBV among White men (‐36.8cm3 [‐45.0, ‐28.5], p = 1E‐3). There were no associations with WMH.ConclusionModerate alcohol use was not reliably associated with brain health, but the effect was on the order of 1‐2 years of aging, in a diverse sample of middle‐aged non‐alcohol dependent community‐dwelling adults. However, moderate alcohol use may have effects on brain volume within specific sex/gender and race/ethnicity groups with implications for later life cognitive impairment. Future work should explore region specific associations, alcohol use factors (i.e., context of use, alcohol type, duration of use), and its relationship to change over time.

Acetaldehyde-mediated increase in glutamatergic and N-acetylaspartate neurometabolite levels in the midcingulate cortex of ALDH2*1/*2 heterozygous young adults.

To elucidate the neurobiology underlying alcohol's effect on the human brain, we examined the acute effects of moderate alcohol administration on levels of glutamatergic neurometabolites and N-acetylaspartate, an amino acid found in neurons, may reflect disordered neuronal integrity. Eighteen healthy Japanese participants (7 males/11 females) aged 20-30 years who were heterozygous for an inactive allele of acetaldehyde dehydrogenase-2 (ALDH/*1/*2) were included. Participants underwent an intravenous alcohol infusion using the clamp method at a target blood alcohol concentration (BAC) of 0.50 mg/mL for 90 min within a range of ±0.05 mg/mL. We examined glutamate + glutamine (Glx) and N-acetylaspartate N-acetylaspartylglutamate (NAA) levels in the midcingulate cortex (MCC) using 3 T 1 H-MRS PRESS at baseline, 90 min, and 180 min (i.e., 90 min after alcohol infusion was finished). A two-way repeated-measures analysis of variance was used to assess longitudinal changes in Glx and NAA levels, with time and sex as within- and between-subject factors, respectively. Pearson's correlation coefficients were calculated among neurometabolite levels and BAC or blood acetaldehyde concentration (BAAC). Both Glx (F(2,32) = 8.15, p = 0.004, η2 = 0.15) and NAA (F(2,32) = 5.01, p = 0.04, η2 = 0.07) levels were increased after alcohol injection. There were no sex or time × sex interaction effects observed. NAA levels were positively correlated with BAAC at 90 min (r(13) = 0.77, p = 0.01). There were no associations between neurometabolite levels and BAC. Both Glx and NAA levels in the MCC increased in response to the administration of moderate concentrations of alcohol. Given positive associations between NAA levels and BAAC and the hypothetical glutamate release via dopamine pathways, the effects of drinking on the MCC in the acute phase may be ascribed to acetaldehyde metabolized from alcohol.

Exploring Successful Cognitive Aging: Insights Regarding Brain Structure, Function, and Demographics.

In the realm of cognitive science, the phenomenon of "successful cognitive aging" stands as a hallmark of individuals who exhibit cognitive abilities surpassing those of their age-matched counterparts. However, it is paramount to underscore a significant gap in the current research, which is marked by a paucity of comprehensive inquiries that deploy substantial sample sizes to methodically investigate the cerebral biomarkers and contributory elements underpinning this cognitive success. It is within this context that our present study emerges, harnessing data derived from the UK Biobank. In this study, a highly selective cohort of 1060 individuals aged 65 and above was meticulously curated from a larger pool of 17,072 subjects. The selection process was guided by their striking cognitive resilience, ascertained via rigorous evaluation encompassing both generic and specific cognitive assessments, compared to their peers within the same age stratum. Notably, the cognitive abilities of the chosen participants closely aligned with the cognitive acumen commonly observed in middle-aged individuals. Our study leveraged a comprehensive array of neuroimaging-derived metrics, obtained from three Tesla MRI scans (T1-weighted images, dMRI, and resting-state fMRI). The metrics included image-derived phenotypes (IDPs) that addressed grey matter morphology, the strength of brain network connectivity, and the microstructural attributes of white matter. Statistical analyses were performed employing ANOVA, Mann-Whitney U tests, and chi-square tests to evaluate the distinctive aspects of IDPs pertinent to the domain of successful cognitive aging. Furthermore, these analyses aimed to elucidate lifestyle practices that potentially underpin the maintenance of cognitive acumen throughout the aging process. Our findings unveiled a robust and compelling association between heightened cognitive aptitude and the integrity of white matter structures within the brain. Furthermore, individuals who exhibited successful cognitive aging demonstrated markedly enhanced activity in the cerebral regions responsible for auditory perception, voluntary motor control, memory retention, and emotional regulation. These advantageous cognitive attributes were mirrored in the health-related lifestyle choices of the surveyed cohort, characterized by elevated educational attainment, a lower incidence of smoking, and a penchant for moderate alcohol consumption. Moreover, they displayed superior grip strength and enhanced walking speeds. Collectively, these findings furnish valuable insights into the multifaceted determinants of successful cognitive aging, encompassing both neurobiological constituents and lifestyle practices. Such comprehensive comprehension significantly contributes to the broader discourse on aging, thereby establishing a solid foundation for the formulation of targeted interventions aimed at fostering cognitive well-being among aging populations.

Chronic Alcohol Exposure Causes Myeloid-Biased Hematopoiesis Via Double-Strand RNA Sensors and Type 1 Interferon Response

Excessive alcohol use is well-known to cause cytopenias and bone marrow (BM) suppression. However, the mechanisms by which alcohol suppresses BM are poorly understood. Moreover, even though the prevalence of moderate drinking is high worldwide, the effects of chronic moderate alcohol consumption on the human hematopoietic system remain unknown. To fill this knowledge gap, we sought to investigate the effects of chronic moderate alcohol consumption on human hematopoiesis using cell-based and animal models. To examine the effects of alcohol on hematopoietic cells in vitro, we tested varying doses of alcohol (0-100 mM) on four leukemia cell lines (Jurkat, MOLM13, MV-4-11, and THP1) and measured population doubling over 6 days. Population doubling levels significantly decreased in a dose-dependent manner in all cell lines tested. We also measured mitochondrial (mt) ROS by MitoSOX-Red flow cytometry in Jurkat, which showed a dose-dependent increase of mtROS (trends only at 10, 25 mM; significantly increased at 50, 100 mM alcohol) compared to untreated. These findings confirm that alcohol negatively affects cell growth and increases mtROS in a physiologic range of doses. To determine the effects of alcohol on human hematopoietic stem progenitor cells (HSPCs) in vitro, we treated human BM CD34+ cells with 0 vs. 50 mM alcohol for 48 hours and performed bulk RNA-sequencing in triplicate. Gene Set Enrichment Analysis (GSEA) revealed that multiple pathways related to platelet activation and coagulation were enriched in alcohol-treated HSPCs, suggesting the induction of inflammation and/or platelet-biased differentiation by alcohol. To assess the effects of chronic moderate alcohol consumption on HSPCs in vivo, we employed a xenotransplant model. In brief, human BM CD34+ cells were transplanted to 5-to-6-week-old female NBSGW mice. We confirmed their engraftment by bone marrow aspiration at six weeks post-transplant, and then they were randomly assigned to the alcohol vs. control groups. After 2 weeks of adjustment, mice were fed a liquid diet (their only source of water and food) containing alcohol 5% vol/vol vs. iso-caloric control diet for 8 weeks. At 4 and 8 weeks, the alcohol-fed group showed significant myeloid bias, reaching greater than 3 times higher myeloid-to-lymphoid ratio than the control group at 8 weeks, while overall engraftment levels were not different. We will report the results of the secondary transplantation of this experiment at the annual meeting. After 8-week alcohol feeding, sorted human CD45+CD34+ cells from mouse BM were subject to 10x Genomics Chromium X 3' HT single-cell RNA-sequencing (scRNA-seq). Complementing the flow data, our transcriptomic data portrayed stark differences between the two groups. Over 50% of cells in the alcohol group comprised granulocyte progenitors, with B cell progenitors representing less than 25%. Inversely, control group data revealed approximately 30% granulocyte progenitors and 55% B cell progenitors, confirming the myeloid bias of HSPC caused by alcohol. Examining differentially expressed genes and GSEA highlighted a significant upregulation of genes associated with the response to virus and type 1 interferon (IFN-1) signature across all HSPC types. A closer look into the gene set showed increased expression of genes tied to cytosolic double-strand (ds) RNA sensing pathways and subsequent interferon type 1 response. Specifically, dsRNA sensors like MDA5, RIG1, PKR, and OAS1-3, as well as interferon regulatory or responsive genes, such as IRF7, ISG15, IFI6, IFI44L, MX1, and STAT1, were notably increased in HSCs and most progenitor populations. Unexpectedly, alcohol-exposed HSCs tended to be in the G0/G1 phase rather than the S or M phase compared to their counterpart upon cell cycle analysis using scRNA-seq data. This may be due to the activation of the PKR pathway, a known cell cycle inhibitor in mouse HSCs. In summary, our findings demonstrate that chronic moderate alcohol consumption can significantly reshape the hematopoietic system through myeloid-biased differentiation and potentiate inflammation by activating the cytosolic dsRNA sensing pathways and IFN-1 response.

Does habitual moderate alcohol consumption enhance working memory performance?

The present study aimed to establish whether habitual alcohol consumption benefits verbal and spatial working memory performance after addressing the main criticisms that have been raised against the finding that alcohol benefits cognition. An adult lifespan sample of 1,652 healthy adults between 21 and 80 years of age participated in the study. Participants were classified as lifetime nondrinkers or drinkers, and several demographic and biological variables were controlled. Alcohol consumption was assessed through a lifestyle questionnaire created for the study. Working memory was measured through a 2-back computerized task. Discrimination and speed in verbal and spatial working memory among drinkers were superior to those among nondrinkers. Total alcohol intake across life and the amount of alcohol intake per week predicted higher verbal and spatial working memory discrimination. Beer drinkers showed more accurate and faster responses in verbal and spatial working memory than nondrinkers, wine drinkers and spirit drinkers. The optimal amount of alcohol intake to benefit working memory for women and men was 100 g per week, which is equivalent to one drink per day. After consuming 350 g of alcohol per week, equivalent to 25 drinks per week, the effects of alcohol on working memory become more negative than the effects of alcohol abstinence. While alcohol consumption is considered a risk factor for several diseases, we found that moderate alcohol intake benefits working memory performance throughout the adult lifespan to a greater extent than whole-life abstinence.

Effect of a moderate alcohol dose on physiological responses during rest and prolonged cycling.

We examined the acute effects of a moderate alcohol dose (48g) ingested before prolonged cycling on acute physiological responses in eight healthy males (mean ± SD; 23 ± 2years; 1.77 ± 0.04m; 75.8 ± 4.1kg). In a randomized order, euhydrated participants completed two experimental sessions with the sequence of 150-min seated at rest, 90-min of cycling at 50% of the maximal rate of oxygen consumption ($\dot{\textrm V}\textrm O$2max), 120-min seated at rest. Participants drank 250mL of flavored squash with or without alcohol (vodka; ~16g) at 10, 40, and 70min of the initial resting phase, giving a cumulative fluid intake of 750mL with 48g of alcohol. Heart rate, blood glucose, breath alcohol concentration, and respiratory gasses were recorded throughout the entire trial with cumulative urine volume recorded during both rest phases. Total carbohydrate (control = 115 ± 19g: alcohol = 119 ± 21g; P= 0.303) and lipid (control = 17 ± 4g: alcohol = 20 ± 7g; P= 0.169) oxidation was similar between conditions. Average heart rate was 7% higher in the alcohol condition (control = 111 ± 12bpm; alcohol = 119 ± 11bpm; P= 0.003). Blood glucose concentrations were similar between conditions during (P= 0.782) and after exercise (P= 0.247). Urine output was initially increased between conditions following alcohol ingestion before diminishing (P< 0.001) with no difference in total cumulative urine output (P= 0.331). Consuming an alcoholic drink containing 48g of alcohol in the hour before moderate intensity sub-maximal aerobic exercise led to detectable increases in heart rate and rate of urine production with no effect on substrate use.

Multi-omics analysis of alcohol effects on the liver in young and aged mice.

Excessive alcohol consumption has detrimental effects on the entire organism, especially on the liver. The toxicity is partly dependent on age, as older individuals metabolize alcohol more slowly leading to increased cellular injury. This study aimed to investigate the effects of moderate binge drinking on the liver of young and aged mice in a genome-wide multi-omics approach. We determined DNA methylation (DNAm) using the Illumina MouseMethylation array and gene expression by RNA sequencing in 18 female Balb/c mice in a 2 × 2 design. The animals underwent three moderate binge drinking cycles (ethanol vs. vehicle) and liver tissue was harvested at 4 or 19 months of age. We tested differential gene expression (DE) and DNAm associated with ethanol intake in linear models separately in young and aged mice, performed enrichment analyses for pathways and GWAS signatures of problematic alcohol use, and analysed the overlap of DNAm and gene expression. We observed DE in young and aged animals and substantial overlap in genes such as Bhlhe40, Klf10, and Frmd8. DE genes in aged animals were enriched for biological processes related to alcohol metabolism, inflammation, liver fibrosis, and GWAS signatures of problematic alcohol use. We identified overlapping signatures from DNAm and gene expression, for example, Frmd8 in aged and St6galnac4 in young mice. This study offers converging evidence of novel age-related targets in a moderate alcohol consumption model highlighting dysregulations in genes related to alcohol metabolism, inflammation, and liver fibrosis. Future studies are needed to confirm these results and elucidate the underlying mechanisms.

Development and validation of a questionnaire for assessment of happiness with reference to behavioral determinants of health. The Indian happiness rating scale III

Background: Recent surveys indicate that the prevalence of happiness is more common in developed countries compared to developing countries, which is considered due to better availability of affordable medical care, more satisfaction in life and economic development. It is possible that chronic anxiety, aggression and depression may be associated with lack of happiness which may predispose poor social, and physical health, leading to unhappiness. This study aims to develop and validate questionnaire for assessment of happiness with greater accuracy, in the behavioral risk factors, so that the same can be used as a tool in the population studies. Subjects and methods: This cross-sectional survey was conducted at Halberg Hospital and Research Institute, Moradabad, India. All subjects; 980 urban (495 men and 485 women), 900 rural (510 men and 390 women) above 25 years of age were randomly selected and recruited from urban and rural populations. Clinical data as well as risk factors were recorded with the help of case record form using the validated questionnaires. Assessment of happiness was made by a new more detailed modified questionnaire involving happiness of mind by including questions related to social, emotional and psychological health behaviours with reference to behavioural risk factors. Results: The prevalence of happiness was 62.2% (n=612) among urban and 63.2% (n=569) among rural subjects. The prevalence of very happy and satisfied (20.2 vs 22.2 %), moderately happy and satisfied (23.7 vs 22.9 %) and the modestly happy and satisfied (18.4 vs 17.9 %) were not significantly different among urban and rural subjects. It seems that the accuracy of the Indian Happiness Rating Scale III is good enough to assess happiness in other populations. The prevalence of behavioral risk factors; alcoholism, alcohol intake in moderation, sedentary behavior, western type diet intake, sleep disorders, emotional stress disorders, breakfast missing, late night dinner, night shift work, were significantly greater among urban subjects compared with rural subjects. However, among subjects with happiness, the frequency of moderate alcohol intake was significantly greater compared to subjects with no happiness among urbans. There were no gender differences in happiness. Conclusions: It is possible that this modified questionnaire with 16 attributes, may accurately assess the status of happiness and successfully used for assessment of happiness rates in urban and rural populations. The questionnaire allowed us to identify approximately two third subjects with happiness, among both urban and rural populations. Similar prevalence of happiness among urban and rural subjects, despite more behavioral risk factors among urbans, indicate that economic development may not be necessary for happiness. Further studies are necessary to find out the role of happiness in relations to health and behavioral risk factors.

Abstract 14327: Association Between Alcohol Intake and Incidence of Heart Failure With and Without Reduced Ejection Fraction Among Participants of the VA Million Veteran Program

Introduction: Little is known about the relation of total alcohol intake and beverage types on risk of heart failure (HF). This study aims to examine the relation between amount of alcohol consumed and type of alcohol with risk for HF including subtypes [heart failure with reduced (HFrEF) and preserved (HFpEF) ejection fraction] in a large cohort of US Veterans. Methods: The study cohort included 329,543 Million Veteran Program participants who completed a baseline and lifestyle survey. Subjects with prevalent HF at baseline and incomplete alcohol information were excluded. Moderate alcohol intake was defined as consuming 12-24 g/day for men and 12g/day for women. We used ICD-9-10 codes and EF to define HFpEF and HFrEF. The associations between alcohol intake, beverage preference, and incidence of HFpEF and HFrEF were assessed using Cox proportional hazard model (CPHM) adjusted for age, sex, race, body mass index, cigarette smoking, education, exercise, diet, baseline prevalence of high cholesterol, hypertension, diabetes mellitus, statin use and atrial fibrillation. Results: Mean age was 65 years and 91.4% were men. With mean follow-up of 4.5 years, we observed 20,694 incident HF events (6078 HFrEF and 4531 HFpEF). The CPHM showed J shaped relationship between alcohol consumption and HF risk. Compared to never drinkers, adjusted HRs (95% CI) for HF were 0.89 (0.85, 0.95), 0.85 (0.79,0.91), 0.80 (0.74, 0.86), 0.80 (0.72, 0.88), 0.93 (0.84, 1.04) and 1.03(0.95, 1.12) for categories of current drinkers of ≤6 g/d, &gt;6-12 g/d, &gt;12-24g/d, &gt;24-36g/d, &gt;36-48 g/d and heavy drinking (&gt; 48 g/d)/alcohol use disorder, respectively. We found a similar association pattern between alcohol intake and risk of HFpEF and HFrEF (Fig). There was no difference in alcohol preference and HF risk among light and moderate drinkers. Conclusion: Light to moderate alcohol consumption is associated with a lower risk of heart failure irrespective of subtypes.

Abstract 18866: Binge Alcohol Drinking and Myocardial Infarction Mortality in the United States

Introduction: Although moderate alcohol intake is related to decrease all cause and ischemic heart disease mortality, intake of large amounts at a time remains controversial. Some studies have shown that binge drinking (BD) could have a protective effect. Hypothesis: The aim of this study is to study life-style risk factors associated with cardiovascular mortality in the U.S. population. Methods: The CDC National Environmental Public Health Tracking Network was used to identify age-adjusted mortality rate due to myocardial infarction (MMI) per county among people ≥35 years between 2018 and 2019. County's age-adjusted prevalence of current smoking (CS), binge alcohol drinking (BD), no-leisure time physical activity (NLTPA) and obesity were also identified as potential community life-style risk factors for MMI. Multivariable regression model predicting MMI rate was used to identify relationship between county MMI rate and those 4 life-style risk factors. Results: A total of 3106 counties were included in this study. Median county age-adjusted MMI rate was 61.00 [46.30, 85.38] per 100.000. Median county age-adjusted prevalence of CS was 19.80% [17.40, 22.80], BD 17.70% [15.70, 19.90], Obesity 35.60% [32.70, 38.10], and NLTPA 26.50% [23.30, 30.68]. In a multivariable regression model, CS prevalence above 20% increased the MMI rate by 9.83 (6.82 to 12.84, p&lt;0.001) per 100.000, NLTPA prevalence above 29% increased the MMI rate by 21.57 (18.12 to 25.02, p&lt;0.001) per 100.000, and obesity prevalence above 36% increased the MMI rate by 8.30 (5.54 to 11.07, p&lt;0.001) per 100.000. On the other hand, BD prevalence above 18% was not associated with a significant increase in the MMI rate. [0.67 (-2.11 to 3.44, p=0.638) per 100.000]. Conclusions: Community life-style risk-factors associated with myocardial infarction mortality include current smoking, no-leisure physical activity, and obesity. Alcohol binge drinking did not reduce myocardial infarction mortality rate.

The gut microbiome modulates associations between adherence to a Mediterranean-style diet, abdominal adiposity, and C-reactive protein in population-level analysis

BackgroundAdherence to a Mediterranean-style dietary pattern is likely to have variable effects on body composition, but the impact of gut microbiome on this relationship is unknown. ObjectivesTo examine the potential mediating effect of the gut microbiome on the associations between Alternate Mediterranean Diet (aMed) scores, abdominal adiposity, and inflammation in population-level analysis. DesignIn a community-based sample aged 25 to 83 y (n = 620; 41% female) from Northern Germany, we assessed the role of the gut microbiome, sequenced from 16S rRNA genes, on the associations between aMed scores, estimated using validated food-frequency questionnaires, magnetic resonance imaging-determined visceral (VAT) and subcutaneous (SAT) adipose tissue and C-reactive protein (CRP). ResultsHigher aMed scores were associated with lower SAT (-0.86 L (95% CI: -1.56, -0.17), P = 0.01), VAT (-0.65 L (95% CI: -1.03,-0.27), P = 0.01) and CRP concentrations (-0.35 mg/L; β: −20.1% (95% CI: 35.5, -1.09), P = 0.04) in the highest versus lowest tertile after multivariate adjustment. Of the taxa significantly associated with aMed scores, higher abundance of Porphyromonadaceae mediated 11.6%, 9.3%, and 8.7% of the associations with lower SAT, VAT, and CRP, respectively. Conversely, a lower abundance of Peptostreptococcaceae mediated 13.1% and 18.2% of the association with SAT and CRP levels. Of the individual components of the aMed score, moderate alcohol intake was associated with lower VAT (-0.2 (95% CI: -0.4, -0.1), P =0.01) with a higher abundance of Oxalobacteraceae and lower abundance of Burkholderiaceae explaining 8.3% and 9.6% of this association, respectively. ConclusionThese novel data suggest that abundance of specific taxa in the Porphyromonadaceae and Peptostreptococcaceae families may contribute to the association between aMed scores, lower abdominal adipose tissue, and inflammation.

Association of Alcohol Consumption With CD4 Recovery After Antiretroviral Therapy Initiation in St. Petersburg, Russia.

Delayed CD4 recovery after initiating antiretroviral therapy (ART) is a novel potential mechanism by which alcohol consumption leads to increased morbidity and mortality in people with HIV. We hypothesized that alcohol consumption at ART initiation is associated with slower CD4 recovery. We retrospectively analyzed 2 pooled longitudinal alcohol/HIV cohorts (2014-2019) in St. Petersburg, Russia. Eligible participants initiated the first ART during parent studies; had alcohol consumption assessed by the blood biomarker, phosphatidylethanol (PEth), at the last research visit before ART initiation; and had ≥1 CD4 count measurement before and after initiating ART. Participants were stratified by low, moderate, and high PEth (<8, 8-80, and >80 ng/mL, respectively). We used random-effects piecewise linear regression models to estimate CD4 recovery, defined as CD4 count change per 30 days after ART initiation, by the alcohol group. Of 60 eligible participants, median age was 34 years and 28% were female. The median pre-ART PEth in the low, moderate, and high PEth groups were <8, 23, and 232 ng/mL, respectively. After starting ART, the CD4 count increased by 13.60 cells/mm3/mo (95% CI: 0.33 to 26.87) with low PEth, 0.93 cells/mm3/mo (95% CI: -6.18 to 8.04) with moderate PEth, and 2.33 cells/mm3/mo (95% CI: -3.44 to 8.09) with high PEth. Among Russians with HIV, we observed faster CD4 recovery after ART initiation in those with low alcohol consumption compared with those with moderate and high alcohol consumption, as assessed by PEth. This analysis provides further evidence for the possible value of alcohol reduction interventions for people with HIV who are initiating ART.

Early-life risk factors, accelerated biological aging and the late-life risk of mortality and morbidity.

Early-life exposure increases health risks throughout an individual's lifetime. Biological aging is influenced by early-life risks as a key process of disease development, but whether early-life risks could accelerate biological aging and elevate late-life mortality and morbidity risks remains unknown. Knowledge is also limited on the potential moderating role of healthy lifestyle. We investigate associations of three early-life risks around birth, breastfeeding, maternal smoking and birth weight, with biological aging of 202 580 UK Biobank participants (54.9 ± 8.1 years old). Biological aging was quantified as KDM-BA, PhenoAge and frailty. Moderate alcohol intake, no current smoking, healthy diet, BMI <30 kg/m2 and regular physical activity were considered as healthy lifestyles. Mortality and morbidity data were retrieved from health records. Individual early-life risk factors were robustly associated with accelerated biological aging. A one-unit increase in the 'early-life risk score' integrating the three factors was associated with 0.060 (SE=0.0019) and 0.036-unit (SE = 0.0027) increase in z-scored KDM-BA acceleration and PhenoAge acceleration, respectively, and with 22.3% higher odds (95% CI: 1.185-1.262) of frailty. Increased chronological age and healthy lifestyles could mitigate the accelerations of KDM-BA and PhenoAge, respectively. Associations of early-life risk score with late-life mortality and morbidity were mediated by biological aging (proportions: 5.66-43.12%). KDM-BA and PhenoAge accelerations could significantly mediate the impact on most outcomes except anxiety, and frailty could not mediate the impact on T2D. Biological aging could capture and mediate the late-life health risks stemming from the early-life risks, and could be potentially targeted for healthy longevity promotion.

Healthy lifestyle scores associate with incidence of type 2 diabetes mediated by uric acid.

Whether and to what extent serum uric acid (SUA) mediates the association between combined lifestyle behaviors and type 2 diabetes mellitus (T2DM) remain unclear. This study aimed to investigate the role of SUA in the relationship between healthy lifestyle scores (HLS) and the incidence of T2DM. This prospective study used data from Zhejiang Metabolic Syndrome cohort. A HLS (5-point scale including healthy waist circumference (WC), never smoking, high physical activity, healthy diet and moderate alcohol intake) was estimated in 13,919 participants, who had SUA at baseline examination in 2009-2014, and were followed-up to 2021-2022 to ascertain incident of T2DM. Cox proportional hazards models and mediation analysis were used to examine the associations between HLS, SUA and T2DM. We included 13,919 participants aged 18years or older without diabetes at baseline (mean age 54.6 [SD 13.9] years, 58.7% female). During a median follow-up of 9.94years, 645 cases of T2DM occurred. Compared with participants with a poor HLS, those with 4-5 low-risk lifestyle factors showed a 60% reduction in the risk of developing T2DM (adjusted HR, 0.40; 95% CI: 0.28-0.57). Further, the population-attributable risk percent (95% CI) of T2DM for poor adherence to the overall healthy lifestyle (< 4 low-risk factors) was 43.24% (30.02%, 56.46%). The HLS was inversely associated with SUA level. With per score increased in HLS, the beta (95% CI) of SUA (log transformed) was - 0.03 (- 0.03, - 0.02), and the odds ratio (95% CI) of hyperuricemia was 0.82 (0.77, 0.86). The relationship between the HLS and risk of T2DM was mediated by SUA with a 13.06% mediation effect. There was no significant combined effect of HLS and SUA on risk of T2DM (P = 0.097). The relationship between overall healthy lifestyle behaviors and T2DM was reconfirmed and the association appeared to be mediated by SUA. The mediation effect of baseline SUA was more pronounced among women who were below 60years old.

A clinical case of fatty liver disease. How the new nomenclature can be applied in practice

Metabolic dysfunction‑associated steatotic liver disease (MASLD) is an urgent problem, as this condition is diagnosed in about 35% of the world’s population. Manifestations of metabolic dysfunction in MASLD include excessive body weight (abdominal obesity is the most dangerous), manifestations of dyslipidemia, hepatomegaly, signs of diabetes, arterial hypertension, and moderate alcohol consumption (&gt; 20 g/30 g of alcohol per day in women and men, respectively). According to a new meta‑analysis, MASLD significantly increases the risk of cardiovascular, metabolic, oncological and reproductive consequences. This disorder was associated with a significantly increased risk of cardiovascular outcomes (hazard ratio [HR], 1.43), metabolic outcomes such as incident hypertension (HR, 1.75), prediabetes (HR, 1.69), diabetes (HR, 2.56) and metabolic syndrome (HR, 2.57), chronic kidney disease (HR, 1.38), and various liver‑related outcomes (HR, 3.92). MASLD is also associated with all types of cancer (HR, 1.54); the highest risk is observed for hepatocellular carcinoma (HR, 4.37). Currently, there are no FDA‑approved drugs for the treatment of MASLD, but there are some drugs to treat comorbidities with potential benefit in MASLD that may be considered in the appropriate clinical setting. It is important to understand that MASLD is a complex and multifaceted condition that requires a comprehensive approach to diagnostics and treatment, in addition to the approach of a gastroenterologist‑hepatologist alone. The increasing MASLD prevalence will remain a major global health threat that requires the implementation of effective mechanisms of the disease management.&#x0D; The authors present a clinical case of metabolic dysfunction‑associated steatohepatitis, associated with the I degree obesity. Liver dysfunction, metabolic and asthenovegetative disorders were revealed on the basis of complaints, anthropometric and anamnestic data, and the results of laboratory studies. Treatment with the use of S‑adenosylmethionine (Agepta, manufactured by Italy, developed by the company Omnifarma, Ukraine) was proposed, which contributed to the stabilization of indicators, according to the data of repeated clinical examinations. The lifestyle changes, physical activity, compliance to the treatment scheme and doctor’s recommendations enabled improving the patient’s state of health.&#x0D;

Observational study of patients from a Lipid Unit on lipid-modifying therapy for primary and secondary prevention: ULFI Study

ObjectivesTo evaluate the achievement of low-density lipoprotein cholesterol (LDLc) goals established by the 2019 European Guidelines for the Management of Dyslipidemias and 2021 Cardiovascular Disease Prevention Guidelines, describe the lipid-lowering treatment received, analyze the achievement of goals according to the lipid-lowering treatment received and study the factors associated with therapeutic success. DesignObservational study that included 185 patients of both sexes aged 18 or over undergoing lipid-lowering treatment for primary or secondary prevention, attended at the Lipid Unit. Results62,1% of the patients had a very high cardiovascular risk (CVR) according to the 2019 guidelines, and 60,5% according to the 2021 guidelines. Of the total cases, 22,7% achieved adequate control of LDLc according to the 2019 guidelines and 20% according to the 2021 guidelines. 47,6% of the patients received very high intensity lipid-lowering treatment, and 14,1% received extremely high intensity lipid-lowering treatment. 76% of subjects with very high CVR on extremely high intensity lipid-lowering treatment achieved the therapeutic objectives of both guides. In the multivariate analysis, factors associated with therapeutic success were the presence of arteriosclerotic cardiovascular disease, the intensity of lipid-lowering treatment, diabetes mellitus, and low to moderate alcohol consumption. ConclusionsDyslipidemia control is improvable. High or extremely high intensity lipid-lowering treatments can contribute to optimizing control of patients with higher CVR.

The Relationship Between Alcohol Consumption, BMI, and Type 2 Diabetes: A Systematic Review and Dose-Response Meta-analysis.

Moderate alcohol use may be associated with lower risk of type 2 diabetes mellitus (T2DM). Previous reviews have reached mixed conclusions. To quantify the dose-response relationship between alcohol consumption and T2DM, accounting for differential effects by sex and BMI. Medline, Embase, Web of Science, and one secondary data source. Cohort studies on the relationship between alcohol use and T2DM. Fifty-five studies, and one secondary data source, were included with a combined sample size of 1,363,355 men and 1,290,628 women, with 89,983 and 57,974 individuals, respectively, diagnosed with T2DM. Multivariate dose-response meta-analytic random-effect models were used. For women, a J-shaped relationship was found with a maximum risk reduction of 31% (relative risk [RR] 0.69, 95% CI 0.64-0.74) at an intake of 16 g of pure alcohol per day compared with lifetime abstainers. The protective association ceased above 49 g per day (RR 0.82, 95% CI 0.68-0.99). For men, no statistically significant relationship was identified. When results were stratified by BMI, the protective association was only found in overweight and obese women. Our analysis relied on aggregate data. We included some articles that determined exposure and cases via self-report, and the studies did not account for temporal variations in alcohol use. The observed reduced risk seems to be specific to women in general and women with a BMI ≥25 kg/m2. Our findings allow for a more precise prediction of the sex-specific relationship between T2DM and alcohol use, as our results differ from those of previous studies.

Behavior-related risk factors and time to death among persons with alcohol consumption versus persons without: A general population study with mortality follow-up after 20 years

BackgroundEvidence shows that low to moderate alcohol consumers seem to live longer than abstainers. Insufficient consideration of subgroups among abstainers and of further behavior-related risk factors for death might be reasons. The aim of this study was to compare alcohol lifetime abstainers, former drinkers, and current consumers with regard to mortality considering tobacco smoking, body overweight, and physical inactivity. MethodsA general adult population sample of residents aged 18 to 64 had been drawn at random in northern Germany. Among eligible persons, 4093 (70.2%) participated. Assessments included alcohol consumption by the Alcohol Use Disorders Identification Test Consumption in addition to lifetime alcohol abstinence and former drinking. A score of behavior-related risk factors was built from tobacco smoking, body overweight, and physical inactivity. Twenty years later, a mortality follow-up was conducted. Data of 4028 study participants were analyzed. ResultsAt baseline, former alcohol consumers but not current low to moderate alcohol drinkers had more behavior-related risk factors than lifetime abstainers. At follow-up, former alcohol drinkers with two or more behavior-related risk factors had a shorter time to death than lifetime abstainers with 0 or one behavior-related risk factor (hazard ratio 3.43, 95% confidence interval: 1.63–7.20). Low to moderate alcohol drinkers did not survive longer than lifetime alcohol abstainers with 0 or one behavior-related risk factor. ConclusionThe results provide evidence against the assumption that alcohol consumption has a beneficial effect on health and longevity.

Women’s views on moderate and low alcohol consumption: stages of the subjective transition from pregnancy to postpartum

Women’s views on moderate and low alcohol consumption: stages of the subjective transition from pregnancy to postpartum

Guidelines for alcohol consumption in the era of ‘no safe levels’ - where do we stand?

Abstract Background Despite claims that moderation consumption could improve health outcomes, namely cardiovascular health, the latest scientific evidence shows there is no safe amount of alcohol consumption. This study sought to determine the current definitions of standard drink and alcohol consumption guidelines across different nations. Methods Based on information from the WHO and the authors’ own judgment, a pool of countries with available data was created. In order to gather the required information, structured internet searches of relevant terms for each country were conducted. Results In 2015, a similar study was conducted but no actualizations were made afterwards. Currently, there has yet to be a standard drink definition agreed upon by every national government, and there are differences between what constitutes this standard drink. Countries have different guidelines for how much alcohol is safe to consume, and low-risk consumption guidelines vary considerably. There are also double standards for men and women. There are few governments that explicitly state that alcohol consumption should be zero. Conclusions National drinking recommendations and guidelines and standard drinking units differ considerably from country to country. It should be evaluated how this impacts public health since this is information available to the general public and can influence how citizens view what they should consume. Public dissemination of messages about so-called safe alcohol consumption levels, moderate alcohol consumption, or protective effects of alcohol consumption is against WHO recommendations, so state governments and national health institutes should consider this matter. Key messages • Countries do not have standardized public health definitions and messages concerning alcohol consumption. • Public health practitioners should update the content of alcohol guidelines accessible to the public to accommodate the latest scientific evidence.