Associations of lifestyle characteristics with circulating immune markers in the general population based on NHANES 1999 to 2014.

Lifestyles maybe associated with the immune and inflammatory state of human body. We aimed to comprehensively explore the relationship between lifestyles and circulating immune-inflammatory markers in the general population. Data from NHANES 1999-2014 was used. Lifestyle factors included leisure-time physical activity (LTPA), diet quality (Healthy Eating Index-2015, HEI-2015), alcohol consumption, cigarettes smoking, sleep hour and sedentary time. Immune makers included C-reactive protein (CRP), neutrophil-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), platelet-lymphocyte ratio (PLR) and monocyte-lymphocyte ratio (MLR). Generalized linear regression models were used to adjust confounders. Regressions of restricted cubic splines were utilized to evaluate the potentially non-linear relationships between exposures and outcomes. As results, HEI was negatively associated with CRP (P < 0.001), SII (P < 0.001), and NLR (P < 0.001). Cigarettes per day was positively associated with CRP (P < 0.001), SII (P < 0.001), and NLR (P = 0.008). Alcohol consumption was negatively associated with CRP (P < 0.001), but positively associated with PLR (P = 0.012) and MLR (P < 0.001). Physical activity was negatively associated with CRP (P < 0.001), SII (P = 0.005), and NLR (P = 0.002), but positively associated with PLR (P = 0.010). Participants with higher healthy lifestyle score had significantly lower CRP, SII and NLR (all P values < 0.05). Most of the sensitivity analyses found similar results. In conclusion, we found significant associations between lifestyles and immune markers in the general population, which may reflect a systemic inflammatory response to unhealthy lifestyles.

Contribution of ferritin and zinc to adverse infant outcomes among pregnancies with prenatal alcohol exposure in South Africa.

Nutritional status during pregnancy can impact fetal development, yet less is known about how alcohol may interact with nutritional status to influence infant outcomes. Pregnant women (n=196) completed 2, 24-hour dietary recalls and provided a venous blood sample to be analyzed for liver enzymes (GGT -gamma-glutamyl transferase; ALT -alanine transaminase; and AST -aspartate transferase), iron, ferritin, and zinc concentrations. Infants were assessed at 6 weeks of age. Women who consumed alcohol had significantly higher ferritin levels compared to non-drinkers (51.8 vs. 34.2). While 44% of women had ferritin <30 ug/L (an indicator of iron deficiency), and 24% of women were low in serum iron, and 72% were low in serum zinc. All six drinking measures for 1st trimester and previous week were significantly correlated with GGT and AST levels while 4 out of 6 alcohol measures were associated with levels of ALT and ferritin. At six weeks of age, nearly all physical measures differentiated infants with alcohol exposure from infants without exposure. Controlling for six covariates, maternal ferritin was significantly and inversely associated with infant head circumference (OFC) centile among infants with alcohol exposure. GGT was inversely associated with infant height and weight centile among unexposed infants. Seventy-four percent (74%) of mothers who consumed alcohol were found to be low in serum zinc, yet higher maternal zinc was associated with more dysmorphology. This may indicate that higher zinc status is not protecting the fetus from the teratogenic effects of alcohol. Prenatal alcohol exposure, ferritin, and zinc status influence infant growth and neurodevelopment.

High-density lipoprotein (HDL) as an indicator for alcohol use in a psychiatrically ill population.

AIMS: To examine the cross sectional and longitudinal associations between the Alcohol Use Disorders Identification Test-Concise (AUDIT-C) and differences in high-density lipoprotein (HDL) in a psychiatrically ill population. METHODS: Retrospective observational study using electronic health record data from a large healthcare system, of patients hospitalized for a mental health/substance use disorder (MH/SUD) from 1 July 2016 to 31 May 2023, who had a proximal AUDIT-C and HDL (N = 15 915) and the subset who had a repeat AUDIT-C and HDL 1 year later (N = 2915). Linear regression models examined the association between cross-sectional and longitudinal AUDIT-C scores and HDL, adjusting for demographic and clinical characteristics that affect HDL. RESULTS: Compared with AUDIT-C score = 0, HDL was higher among patients with greater AUDIT-C severity (e.g. moderate AUDIT-C score = 8.70[7.65, 9.75] mg/dl; severe AUDIT-C score = 13.02 [12.13, 13.90] mg/dL[95% confidence interval (CI)] mg/dl). The associations between cross-sectional HDL and AUDIT-C scores were similar with and without adjusting for patient demographic and clinical characteristics. HDL levels increased for patients with mild alcohol use at baseline and moderate or severe alcohol use at follow-up (15.06[2.77, 27.69] and 19.58[2.77, 36.39] mg/dL[95%CI] increase for moderate and severe, respectively). CONCLUSIONS: HDL levels correlate with AUDIT-C scores among patients with MH/SUD. Longitudinally, there were some (but not consistent) increases in HDL associated with increases in AUDIT-C. The increases were within range of typical year-to-year variation in HDL across the population independent of alcohol use, limiting the ability to use HDL as a longitudinal clinical indicator for alcohol use in routine care.

A systematic review of the association between modifiable lifestyle factors and circulating anti-Müllerian hormone.

BACKGROUND: Levels of anti-Müllerian hormone (AMH) are known to be associated with lifestyle determinants such as smoking and oral contraception (OC) use. When measuring AMH in clinical practice, it is essential to know which factors may influence circulating levels or ovarian reserve in general. OBJECTIVE AND RATIONALE: To date, there is no systematic review or summarizing consensus of the nature and magnitude of the relation between AMH and modifiable lifestyle factors. The purpose of this review was to systematically assess the evidence on association of lifestyle behaviors with circulating AMH levels. SEARCH METHODS: We performed a pre-registered systematic review of publications in Embase and PubMed on the lifestyle factors BMI, smoking, OC use, alcohol consumption, caffeine consumption, physical activity, and waist-hip ratio (WHR) in relation to circulating AMH levels up to 1 November 2023. The search strategy included terms such as 'Anti-Mullerian hormone', 'lifestyle', and 'women'. Studies were considered eligible if the association between at least one of the lifestyle factors of interest and AMH was assessed in adult women. The quality of included studies was assessed using the Study Quality Assessment Tools of the National Heart, Lung, and Blood Institute. The results were presented as ranges of the most frequently used association measure for studies that found a significant association in the same direction. OUTCOMES: A total of 15 072 records were identified, of which 65 studies were eligible for inclusion, and 66.2% of the studies used a cross-sectional design. The majority of studies investigating BMI, smoking, OC use, and physical activity reported significant inverse associations with AMH levels. For WHR, alcohol, and caffeine use, the majority of studies did not find an association with AMH. For all determinants, the effect measures of the reported associations were heterogeneous. The mean difference in AMH levels per unit increase in BMI ranged from -0.015 to -0.2 ng/ml in studies that found a significant inverse association. The mean difference in AMH levels for current smokers versus non-smokers ranged from -0.4 to -1.1 ng/ml, and -4% to -44%, respectively. For current OC use, results included a range in relative mean differences in AMH levels of -17% to -31.1%, in addition to a decrease of 11 age-standardized percentiles, and an average decrease of 1.97 ng/ml after 9 weeks of OC use. Exercise interventions led to a decrease in AMH levels of 2.8 pmol/l to 13.2 pmol/l after 12 weeks in women with polycystic ovary syndrome or a sedentary lifestyle. WIDER IMPLICATIONS: Lifestyle factors are associated with differences in AMH levels and thus should be taken into account when interpreting individual AMH measurements. Furthermore, AMH levels can be influenced by the alteration of lifestyle behaviors. While this can be a helpful tool for clinical and lifestyle counseling, the nature of the relation between the observed differences in AMH and the true ovarian reserve remains to be assessed. REGISTRATION NUMBER: PROSPERO registration ID: CRD42022322575.

Subjective intoxication predicts alcohol-related consequences at equivalent alcohol concentrations in young adults using ecological momentary assessment and alcohol sensors.

OBJECTIVE: Subjective intoxication (SI) when drinking may serve as an internal barometer of whether to continue drinking or engage in potentially unsafe behavior. Mobile assessments offer the potential to use SI as a prospective risk indicator during drinking episodes; little evidence exists for the validity of real-time SI measures. We test the correspondence of SI with estimated blood alcohol concentration and transdermal alcohol concentration (TAC) in young adults' natural settings. We provide a novel test of whether SI features (peak and mean SI) uniquely predict consequences adjusting for alcohol concentration. METHOD: Two hundred twenty-two heavy-drinking young adults (Mage = 22.3, 64% female, 79% non-Hispanic White, 84% undergraduates) participated in a 6-day study that used ecological momentary assessment of drinking and TAC sensors. SI was assessed every 30 min during drinking episodes. Multilevel modeling was used to test hypotheses. RESULTS: Momentary SI and estimated blood alcohol concentration had moderate associations at the moment and day levels (standardized ßs = 0.5-0.6); SI was moderately associated with TAC at the day level (ßs = 0.5). Associations between SI and alcohol concentration varied widely between persons and across days. Day-level SI features predicted consequences when adjusting for alcohol concentration (incidence rate ratios, IRRs = 1.29-1.70). CONCLUSIONS: Our two-item SI measure shows evidence of validity in real-world settings with heavy-drinking young adults. SI was significantly correlated with alcohol concentration and was a unique predictor of consequences. The strength of these associations varied greatly across persons and days. Real-time SI measurement may be useful in preventive interventions, but continued research is needed into when and for whom momentary SI is most predictive of risk. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

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

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

High-'n'-dry? A comparison of cannabis and alcohol use in drivers presenting to hospital after a vehicular collision.

DESIGN: This was a prospective observational study. BACKGROUND AND AIMS: The characteristics of cannabis-involved motor vehicle collisions are poorly understood. This study of injured drivers identifies demographic and collision characteristics associated with high tetrahydrocannabinol (THC) concentrations. SETTING: The study was conducted in 15 Canadian trauma centres between January 2018 and December 2021. CASES: The cases (n = 6956) comprised injured drivers who required blood testing as part of routine trauma care. MEASUREMENTS: We quantified whole blood THC and blood alcohol concentration (BAC) and recorded driver sex, age and postal code, time of crash, crash type and injury severity. We defined three driver groups: high THC (THC ≥ 5 ng/ml and BAC = 0), high alcohol (BAC ≥ 0.08% and THC = 0) and THC/BAC-negative (THC = 0 = BAC). We used logistic regression techniques to identify factors associated with group membership. FINDINGS: Most injured drivers (70.2%) were THC/BAC-negative; 1274 (18.3%) had THC > 0, including 186 (2.7%) in the high THC group; 1161 (16.7%) had BAC > 0, including 606 (8.7%) in the high BAC group. Males and drivers aged less than 45 years had higher adjusted odds of being in the high THC group (versus the THC/BAC-negative group). Importantly, 4.6% of drivers aged less than 19 years had THC ≥ 5 ng/ml, and drivers aged less than 19 years had higher unadjusted odds of being in the high THC group than drivers aged 45-54 years. Males, drivers aged 19-44 years, rural drivers, seriously injured drivers and drivers injured in single-vehicle, night-time or weekend collisions had higher adjusted odds ratios (aORs) for being in the high alcohol group (versus THC/BAC-negative). Drivers aged less than 35 or more than 65 years and drivers involved in multi-vehicle, daytime or weekday collisions had higher adjusted odds for being in the high THC group (versus the high BAC group). CONCLUSIONS: In Canada, risk factors for cannabis-related motor vehicle collisions appear to differ from those for alcohol-related motor vehicle collisions. The collision factors associated with alcohol (single-vehicle, night-time, weekend, rural, serious injury) are not associated with cannabis-related collisions. Demographic factors (young drivers, male drivers) are associated with both alcohol and cannabis-related collisions, but are more strongly associated with cannabis-related collisions.

Transdermal sensor features correlate with ecological momentary assessment drinking reports and predict alcohol-related consequences in young adults' natural settings.

BACKGROUND: Wearable transdermal alcohol concentration (TAC) sensors allow passive monitoring of alcohol concentration in natural settings and measurement of multiple features from drinking episodes, including peak intoxication level, speed of intoxication (absorption rate) and elimination, and duration. These passively collected features extend commonly used self-reported drink counts and may facilitate the prediction of alcohol-related consequences in natural settings, aiding risk stratification and prevention efforts. METHOD: A total of 222 young adults aged 21-29 (M age = 22.3, 64% female, 79% non-Hispanic white, 84% undergraduates) who regularly drink heavily participated in a 5-day study that included the ecological momentary assessment (EMA) of alcohol consumption (daily morning reports and participant-initiated episodic EMA sequences) and the wearing of TAC sensors (SCRAM-CAM anklets). The analytic sample contained 218 participants and 1274 days (including 554 self-reported drinking days). Five features-area under the curve (AUC), peak TAC, rise rate (rate of absorption), fall rate (rate of elimination), and duration-were extracted from TAC-positive trajectories for each drinking day. Day- and person-level associations of TAC features with drink counts (morning and episodic EMA) and alcohol-related consequences were tested using multilevel modeling. RESULTS: TAC features were strongly associated with morning drink reports (r = 0.6-0.7) but only moderately associated with episodic EMA drink counts (r = 0.3-0.5) at both day and person levels. Higher peaks, larger AUCs, faster rise rates, and faster fall rates were significantly predictive of day-level alcohol-related consequences after adjusting for both morning and episodic EMA drink counts in separate models. Person means of TAC features added little above daily scores to the prediction of alcohol-related consequences. CONCLUSIONS: These results support the utility of TAC sensors in studies of alcohol misuse among young adults in natural settings and outline the specific TAC features that contribute to the day-level prediction of alcohol-related consequences. TAC sensors provide a passive option for obtaining valid and unique information predictive of drinking risk in natural settings.

Development and validation of an analytical method for the simultaneous determination of the alcohol biomarkers ethyl glucuronide, ethyl sulfate, N-acetyltaurine, and 16:0/18:1-phosphatidylethanol in human blood.

As alcohol is the most common addictive substance worldwide, it is inevitable to advance the established research. New and more substantial analytical methods can be applied to reply to complex questions in legal or forensic contexts. Therefore, an analytical method for the simultaneous determination of four different alcohol biomarkers-ethyl glucuronide, ethyl sulfate, N-acetyltaurine, and 16:0/18:1-phosphatidylethanol-in human blood was developed, validated, and verified. Despite the different chemical properties of the analytes, a specific determination via HPLC-MS/MS was achieved using a novel type of a Phenomenex Luna® Omega Sugar column. Furthermore, all criteria for a successful validation were fulfilled according to forensic guidelines. The method proved to be linear and demonstrates selectivity and sufficient sensitivity for every biomarker. LODs obtained with this method of 2.6 ng/ml (EtG), 4.7 ng/ml (EtS), 12.5 ng/ml (NAcT), and 6.9 ng/ml (PEth) were in an acceptable range for routine applications, and the stability of all analytes over a range of 12 h is given. The verification of the new developed method was performed with authentic samples. Thus, whole blood and postmortem samples were analyzed to obtain information about the drinking behavior, which can answer complex questions regarding alcohol consumption.

Serum metabolomic analysis reveals several novel metabolites in association with excessive alcohol use - an exploratory study.

Appropriate screening tool for excessive alcohol use (EAU) is clinically important as it may help providers encourage early intervention and prevent adverse outcomes. We hypothesized that patients with excessive alcohol use will have distinct serum metabolites when compared to healthy controls. Serum metabolic profiling of 22 healthy controls and 147 patients with a history of EAU was performed. We employed seemingly unrelated regression to identify the unique metabolites and found 67 metabolites (out of 556), which were differentially expressed in patients with EAU. Sixteen metabolites belong to the sphingolipid metabolism, 13 belong to phospholipid metabolism, and the remaining 38 were metabolites of 25 different pathways. We also found 93 serum metabolites that were significantly associated with the total quantity of alcohol consumption in the last 30 days. A total of 15 metabolites belong to the sphingolipid metabolism, 11 belong to phospholipid metabolism, and 7 metabolites belong to lysolipid. Using a Venn diagram approach, we found the top 10 metabolites with differentially expressed in EAU and significantly associated with the quantity of alcohol consumption, sphingomyelin (d18:2/18:1), sphingomyelin (d18:2/21:0,d16:2/23:0), guanosine, S-methylmethionine, 10-undecenoate (11:1n1), sphingomyelin (d18:1/20:1, d18:2/20:0), sphingomyelin (d18:1/17:0, d17:1/18:0, d19:1/16:0), N-acetylasparagine, sphingomyelin (d18:1/19:0, d19:1/18:0), and 1-palmitoyl-2-palmitoleoyl-GPC (16:0/16:1). The diagnostic performance of the top 10 metabolites, using the area under the ROC curve, was significantly higher than that of commonly used markers. We have identified a unique metaboloic signature among patients with EAU. Future studies to validate and determine the kinetics of these markers as a function of alcohol consumption are needed.

Profiling of extracellular vesicle-bound miRNA to identify candidate biomarkers of chronic alcohol drinking in nonhuman primates.

BACKGROUND: Long-term alcohol drinking is associated with numerous health complications including susceptibility to infection, cancer, and organ damage. However, due to the complex nature of human drinking behavior, it has been challenging to identify reliable biomarkers of alcohol drinking behavior prior to signs of overt organ damage. Recently, extracellular vesicle-bound microRNAs (EV-miRNAs) have been found to be consistent biomarkers of conditions that include cancer and liver disease. METHODS: In this study, we profiled the plasma EV-miRNA content by miRNA-Seq from 80 nonhuman primates after 12 months of voluntary alcohol drinking. RESULTS: We identified a list of up- and downregulated EV-miRNA candidate biomarkers of heavy drinking and those positively correlated with ethanol dose. We overexpressed these candidate miRNAs in control primary peripheral immune cells to assess their potential functional mechanisms. We found that overexpression of miR-155, miR-154, miR-34c, miR-450a, and miR-204 led to increased production of the inflammatory cytokines TNFα or IL-6 in peripheral blood mononuclear cells after stimulation. CONCLUSION: This exploratory study identified several EV-miRNAs that could serve as biomarkers of long-term alcohol drinking and provide a mechanism to explain alcohol-induced peripheral inflammation.

The alcohol marker phosphatidylethanol is closely related to AST, GGT, ferritin and HDL-C.

BACKGROUND: The aim of this study was to evaluate the quantitative relation between common clinical chemical analyses and ethanol use, measured by a combination of the two alcohol markers phosphatidylethanol (PEth) and carbohydrate-deficient transferrin (CDT). METHODS: Results of PEth and CDT in whole blood and serum, respectively, were included, together with information on 10 different commonly measured clinical chemical analytes, as well as age and sex. PEth was analysed by UPC2 -MS/MS and CDT was measured by capillary electrophoresis. RESULTS: Samples from 4873 patients were included. The strongest relation to alcohol consumption as measured by PEth, when correcting for age and sex, was found for HDL-C (standardized ß = 0.472, p < 0.001), AST (standardized ß = 0.372, p < 0.001), ferritin (standardized ß = 0.332, p < 0.001) and GGT (standardized ß = 0.325, p < 0.001). The relation to PEth was weak for total cholesterol, TG and ALP. No relation was found for Hb and LDL-C. CONCLUSIONS: When using PEth as a marker for alcohol consumption, this study demonstrated the quantitative relation to commonly used test as AST or GGT, but also an important relation to ferritin or HDL-C. In clinical practice, elevated levels of these clinical chemical analytes should initiate further work-up on possibly harmful alcohol use.

Alcohol Consumption Moderated the Association Between Levels of High Blood Lead or Total Urinary Arsenic and Bone Loss.

Metal exposure and lifestyle are important risk factors for osteoporosis. Our study aimed to investigate the association between red blood cell lead and cadmium, total urinary arsenic, and plasma selenium levels and bone mineral density (BMD). In addition, we explored whether alcohol and coffee consumption modified the association between BMD and metals and metalloids. In total, 437 participants who underwent adult or senile physical examinations were recruited. Bone loss was defined as a calcaneus BMD T-score of <-1. Blood cadmium and lead and plasma selenium levels were measured using inductively coupled plasma mass spectrometry. Levels of urinary arsenic species were determined using high-performance liquid chromatography-hydride generator-atomic absorption spectrometry. The total urinary arsenic level was defined as the sum of the levels of urinary arsenic species. The BMD T-scores decreased significantly with increasing blood lead levels. The BMD T-scores also showed a downward trend with increasing total urinary arsenic levels. The odds ratio (OR) and 95% confidence interval (CI) for bone loss in patients with blood lead levels >57.58 versus 35.74 µg/dL were 1.98 and 1.17-3.34. In addition, the greater the lead or arsenic exposure and alcohol intake was the higher the OR for bone loss with multivariate ORs of 2.57 (95% CI 1.45-4.56) and 2.96 (95% CI 1.67-5.22), respectively. To the best of our knowledge, this study is the first to demonstrate that high total urinary arsenic or blood lead levels and frequent or occasional alcohol consumption had a significant multiplicative interaction for increasing the OR for bone loss.

Validating biomarkers and models for epigenetic inference of alcohol consumption from blood.

BACKGROUND: Information on long-term alcohol consumption is relevant for medical and public health research, disease therapy, and other areas. Recently, DNA methylation-based inference of alcohol consumption from blood was reported with high accuracy, but these results were based on employing the same dataset for model training and testing, which can lead to accuracy overestimation. Moreover, only subsets of alcohol consumption categories were used, which makes it impossible to extrapolate such models to the general population. By using data from eight population-based European cohorts (N = 4677), we internally and externally validated the previously reported biomarkers and models for epigenetic inference of alcohol consumption from blood and developed new models comprising all data from all categories. RESULTS: By employing data from six European cohorts (N = 2883), we empirically tested the reproducibility of the previously suggested biomarkers and prediction models via ten-fold internal cross-validation. In contrast to previous findings, all seven models based on 144-CpGs yielded lower mean AUCs compared to the models with less CpGs. For instance, the 144-CpG heavy versus non-drinkers model gave an AUC of 0.78 ± 0.06, while the 5 and 23 CpG models achieved 0.83 ± 0.05, respectively. The transportability of the models was empirically tested via external validation in three independent European cohorts (N = 1794), revealing high AUC variance between datasets within models. For instance, the 144-CpG heavy versus non-drinkers model yielded AUCs ranging from 0.60 to 0.84 between datasets. The newly developed models that considered data from all categories showed low AUCs but gave low AUC variation in the external validation. For instance, the 144-CpG heavy and at-risk versus light and non-drinkers model achieved AUCs of 0.67 ± 0.02 in the internal cross-validation and 0.61-0.66 in the external validation datasets. CONCLUSIONS: The outcomes of our internal and external validation demonstrate that the previously reported prediction models suffer from both overfitting and accuracy overestimation. Our results show that the previously proposed biomarkers are not yet sufficient for accurate and robust inference of alcohol consumption from blood. Overall, our findings imply that DNA methylation prediction biomarkers and models need to be improved considerably before epigenetic inference of alcohol consumption from blood can be considered for practical applications.

Low density lipoprotein cholesterol and all-cause mortality rate: findings from a study on Japanese community-dwelling persons.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) independently impacts aging-related health outcomes and plays a critical role in cardiovascular diseases (CVDs). However, there are limited predictive data on all-cause mortality, especially for the Japanese community population. In this study, it was examined whether LDL-C is related to survival prognosis based on 7 or 10 years of follow-up. METHODS: Participants included 1610 men (63 ± 14 years old) and 2074 women (65 ± 12 years old) who participated in the Nomura cohort study conducted in 2002 (first cohort) and 2014 (second cohort) and who continued throughout the follow-up periods (follow-up rates: 94.8 and 98.0%). Adjusted relative risk estimates were obtained for all-cause mortality using a basic resident register. The data were analyzed by a Cox regression with the time variable defined as the length between the age at the time of recruitment and that at the end of the study (the age of death or censoring), and risk factors including gender, age, body mass index (BMI), presence of diabetes, lipid levels, renal function, serum uric acid levels, blood pressure, and history of smoking, drinking, and CVD. RESULTS: Of the 3684 participants, 326 (8.8%) were confirmed to be deceased. Of these, 180 were men (11.2% of all men) and 146 were women (7.0% of all women). Lower LDL-C levels, gender (male), older age, BMI under 18.5 kg/m2, and the presence of diabetes were significant predictors for all-cause mortality. Compared with individuals with LDL-C levels of 144 mg/dL or higher, the multivariable-adjusted Hazard ratio (and 95% confidence interval) for all-cause mortality was 2.54 (1.58-4.07) for those with LDL-C levels below 70 mg/dL, 1.71 (1.15-2.54) for those with LDL-C levels between 70 mg/dL and 92 mg/dL, and 1.21 (0.87-1.68) for those with LDL-C levels between 93 mg/dL and 143 mg/dL. This association was particularly significant among participants who were male (P for interaction = 0.039) and had CKD (P for interaction = 0.015). CONCLUSIONS: There is an inverse relationship between LDL-C levels and the risk of all-cause mortality, and this association is statistically significant.

Skeletal muscle bioenergetic health and function in people living with HIV: association with glucose tolerance and alcohol use.

At-risk alcohol use is prevalent and increases dysglycemia among people living with human immunodeficiency virus (PLWH). Skeletal muscle (SKM) bioenergetic dysregulation is implicated in dysglycemia and type 2 diabetes. The objective of this study was to determine the relationship between at-risk alcohol, glucose tolerance, and SKM bioenergetic function in PLWH. Thirty-five PLWH (11 females, 24 males, age: 53 ± 9 yr, body mass index: 29.0 ± 6.6 kg/m2) with elevated fasting glucose enrolled in the ALIVE-Ex study provided medical history and alcohol use information [Alcohol Use Disorders Identification Test (AUDIT)], then underwent an oral glucose tolerance test (OGTT) and SKM biopsy. Bioenergetic health and function and mitochondrial volume were measured in isolated myoblasts. Mitochondrial gene expression was measured in SKM. Linear regression adjusting for age, sex, and smoking was performed to examine the relationship between glucose tolerance (2-h glucose post-OGTT), AUDIT, and their interaction with each outcome measure. Negative indicators of bioenergetic health were significantly (P < 0.05) greater with higher 2-h glucose (proton leak) and AUDIT (proton leak, nonmitochondrial oxygen consumption, and bioenergetic health index). Mitochondrial volume was increased with the interaction of higher 2-h glucose and AUDIT. Mitochondrial gene expression decreased with higher 2-h glucose (TFAM, PGC1B, PPARG, MFN1), AUDIT (MFN1, DRP1, MFF), and their interaction (PPARG, PPARD, MFF). Decreased expression of mitochondrial genes were coupled with increased mitochondrial volume and decreased bioenergetic health in SKM of PLWH with higher AUDIT and 2-h glucose. We hypothesize these mechanisms reflect poorer mitochondrial health and may precede overt SKM bioenergetic dysregulation observed in type 2 diabetes.

The effect of triglycerides to high-density lipoprotein cholesterol ratio on the reduction of renal function: findings from China health and retirement longitudinal study (CHARLS).

BACKGROUND: Previous studies show that abnormal lipoprotein metabolism can increase the prevalence of chronic kidney disease (CKD). This study prospectively investigated the association of triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio and renal dysfunction in the Chinese population. METHODS: This longitudinal cohort research examined 7,316 participants (age range: 22-93) from the China Health and Retirement Longitudinal Study (CHARLS), including 6,560 individuals with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 (normal renal function, NRF) group and 756 with eGFR < 60 mL/min/1.73 m2 (impaired renal function, IRF) group. In NRF group, reduction in renal function was defined as eGFR < 60 mL/min/1.73 m2 at exit visit and in IRF group, it was defined as decline in eGFR category, average eGFR decline > 5 mL/min/1.73 m2 per year or > 30 % decrease in eGFR from baseline. RESULTS: The study results showed that TG/HDL-C ratio was positively associated with the risk of renal function decline in the NRF group (OR 1.30, 95 %CI 1.03-1.65, P = 0.03) and the IRF group (OR 1.90, 95 %CI 1.21-3.23, P = 0.02) when adjusting for age, gender, obesity, diabetes, hypertension, waist circumference, drinking, smoking, history of heart disease and stroke, low-density lipoprotein cholesterol and eGFR category. Analysis of the IRF group indicated that relative to the group of TG/HDL-C < 1.60, the group of TG/HDL-C ≥ 2.97 had an increased risk for the decline of eGFR category (OR 1.89, 95 %CI 1.12-3.21, P = 0.02) and > 30 % decline in eGFR (OR 2.56, 95 %CI 1.05-6.38, P = 0.04). CONCLUSIONS: The high TG/HDL-C ratio was an independent risk factor for declining renal function in the Chinese population.

Determinants and Reference Ranges of Serum Immunoglobulins in Middle-Aged and Elderly Individuals: a Population-Based Study.

PURPOSE: In clinical practice, currently one reference range for serum immunoglobulin (Ig) A, G, and M is applied to all adults, although various factors may influence Ig serum levels. Population-based data on determinants of IgA, IgG, and IgM and recommendations for subgroup specific reference ranges are lacking. We aimed to provide an overview of determinants of IgA, IgG, and IgM in community-dwelling middle-aged and elderly individuals and explore determinants that influence Ig reference ranges. METHODS: Within the Rotterdam Study, we performed linear regression analyses for the association of demographic, lifestyle, and cardiovascular factors with serum IgA, IgG, and IgM. We furthermore calculated Ig reference ranges (based on percentiles), both overall and within relevant subgroups. RESULTS: We included 8768 participants (median age 62 years). IgA and IgG increased non-linearly with higher age (P < .0001 for both). Women had lower IgA (beta: - 0.24; 95% confidence interval [95% CI]: - 0.29; - 0.20) and IgG (beta: - 0.33; 95% CI: - 0.44; - 0.23), but higher IgM levels (beta: 0.08; 95% CI: 0.04;0.13) than men. Former and particularly current smoking were associated with lower IgA and IgG (betas between - 0.07 and - 1.03). Higher alcohol consumption was associated with lower IgG (beta for heavy drinking: - 0.70; 95% CI: - 0.91; - 0.48). Corticosteroid use was associated with lower IgG (beta: - 1.12; 95% CI: - 1.58; - 0.66). Associations with cardiovascular factors were heterogeneous and differed between sexes. CONCLUSION: Age, sex, smoking, alcohol consumption, corticosteroid use, and cardiovascular factors are determinants that should be considered when interpreting serum Ig levels in middle-aged and elderly individuals and may require adjusted reference ranges.

Intake of Lactobacillus rhamnosus GG (LGG) fermented milk before drinking alcohol reduces acetaldehyde levels and duration of flushing in drinkers with wild-type and heterozygous mutant ALDH2: a randomized, blinded crossover controlled trial.

Alcohol consumption leads to acetaldehyde accumulation, especially in people with mutant aldehyde dehydrogenase 2 gene (ALDH2). Novel strategies to promote acetaldehyde detoxification are required to prevent alcohol-related toxicity. Probiotic bacteria such as Lactobacillus rhamnosus GG (LGG) were shown to have in vitro capacity to detoxify acetaldehyde. This randomized, blinded, placebo-controlled cross-over trial investigated the effect of LGG fermented milk in people with ALDH2 polymorphisms after moderate alcohol intake. Ten healthy wild-type and ten heterozygous mutant ALDH2 Thai men were block randomized into two groups. Each group consumed a different sequence of 150 mL fermented milk containing 108 CFU mL-1 LGG and lactic-acidified milk (placebo), followed by five glasses of beer (0.4 g ethanol per kg body weight), with a one-week wash-out. Consuming LGG fermented milk before alcohol reduced areas under the response curves of blood and salivary acetaldehyde in wild-type and heterozygous mutant ALDH2 individuals (p < 0.05 and p < 0.01, respectively). Interestingly, participants with mutant ALDH2 responded better than wild-type participants for salivary acetaldehyde (90% vs. 70%, p < 0.001). Their durations of flushing were reduced when consuming LGG milk. Regardless of ALDH2 status, 105 CFU mL-1 LGG was retained in saliva at least 3.5 h after milk consumption. In conclusion, intake of LGG fermented milk before drinking alcohol reduces blood and salivary acetaldehyde levels and duration of flushing in drinkers with wild-type and heterozygous mutant ALDH2. The addition of exogenous capacity to detoxify acetaldehyde using the probiotic product could be a potential strategy to promote the alleviation of exposure to reactive and carcinogenic acetaldehyde associated with alcohol drinking in individuals with defective ALDH2 enzyme.

Evaluation of neurotrophic factors and education level as predictors of cognitive decline in alcohol use disorder.

Cognitive reserve (CR) is the capability of an individual to cope with a brain pathology through compensatory mechanisms developed through cognitive stimulation by mental and physical activity. Recently, it has been suggested that CR has a protective role against the initiation of substance use, substance consumption patterns and cognitive decline and can improve responses to treatment. However, CR has never been linked to cognitive function and neurotrophic factors in the context of alcohol consumption. The present cross-sectional study aims to evaluate the association between CR (evaluated by educational level), cognitive impairment (assessed using a frontal and memory loss assessment battery) and circulating levels of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) in patients with alcohol use disorder (AUD). Our results indicated that lower educational levels were accompanied by earlier onset of alcohol consumption and earlier development of alcohol dependence, as well as impaired frontal cognitive function. They also suggest that CR, NT-3 and BDNF may act as compensatory mechanisms for cognitive decline in the early stages of AUD, but not in later phases. These parameters allow the identification of patients with AUD who are at risk of cognitive deterioration and the implementation of personalized interventions to preserve cognitive function.