Background Dioxin and per- and polyfluoroalkyl substances (PFAS) exposure in fetal life and early infancy may be harmful for the male reproductive system. Objectives We investigated the associations between pre- and postnatal dioxin/PFAS exposure and semen quality in young adulthood. Methods The Ulm Birth Cohort Study is a population-based longitudinal birth cohort study (recruited 11/2000-11/2001). Maternal serum was collected shortly after delivery (mostly taken within the first two days) and maternal milk 6 weeks postpartum, immediately aliquoted, and stored at -80 ⁰C. Concentrations of dioxins (PCDDs, PCFDs and dioxin-like PCBs) were analyzed in milk in the year 2022 and PFAS in maternal serum in the year 2023. Semen provided by male offspring in 2021/22 was analyzed according to the 2010 WHO manual. Multivariable linear regression models were used to analyze the associations of (1) maternal dioxin/PFAS concentrations and of (2) cumulative dioxin/PFAS exposure with semen quality. Results Semen was available for n=98 males (age 20.4 ± 0.4 years; 86% were breastfed at 6 weeks). Median WHO2005-PCDD/F+PCB-TEQ concentration was 0.516 pg/g milk (n=77, IQR 0.296-0.715), median serum PFAS level (EFSA sum) was 10.8 µg/L (n=92, IQR 8.3-13.8). In adjusted analyses, we found no associations between concentrations of dioxin on a continuous scale with various measures of semen quality. For the continuous analysis of PFAS, a positive association with sperm concentration was seen in the partly adjusted cumulative exposure model, which was, however, not present after full adjustment. The mutual adjustment for dioxins and PFAS in statistical analysis revealed a significant negative association between dioxin levels in milk with sperm concentration and %-progressive motility and a significant positive association between PFAS levels in postpartum serum and sperm concentration. Conclusion While our data do not suggest an adverse association between early PFAS exposure and semen quality in adulthood, an adverse association with early dioxin exposure cannot be excluded. The small sample size and potential sources of bias or confounding call for cautious interpretation.

Per- and polyfluoroalkyl substances (PFAS) may elevate blood lipids, suggesting that PFAS may also target the cardiovascular system. This systematic review aimed to investigate the relationship between internal human exposure to main PFAS, i.e., perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexanesulfonic acid (PFHxS) and ischemic heart diseases (IHD). Two systematic literature searches were performed in MEDLINE and EMBASE - most recently on January 8, 2025. Eligible studies analyzed associations between individual blood PFAS exposure and IHD among humans. Risk of bias was assessed using the OHAT Risk of Bias Rating Tool and evidence was synthesized using structured tables and vote counting based on direction of effect, as meta-analyses and dose-response analyses did not provide meaningfully interpretable results. The 16 studies included comprised 79,313 participants. Seven studies estimated rate ratios (RR) and nine estimated odds ratios (OR). Associations between PFOA exposure and IHD (RR) were small and exposure levels were heterogeneous. In the vote counting analysis of the association between PFOA exposure and IHD, 82.4% (95%-CI: 56.6%-96.2%) of effect estimates (RR) pointed in the harmful direction (low certainty). A harmful tendency was less pronounced for PFOS and IHD, with 60.0% (95%-CI: 14.7%-94.7%) of RR and 46.4% (95%-CI 27.5%-66.1%) of OR indicating a harmful relationship. For PFHxS, PFNA, and the sum of PFAS, the overall direction of the vote counting results differed between RR and OR (very low or low certainty). The relationship between PFAS and IHD remains unclear, so further longitudinal studies investigating dose-dependent effects are required.

The widespread application of per- and polyfluoroalkyl substances (PFAS) resulted in ubiquitous environmental contamination. Understanding the PFAS tissue distribution in mammals and humans is crucial for the assessment of potential health risks. The levels of eleven PFAS were determined by UPLC-MS/MS in plasma and various tissues of wild boar (n = 82) hunted in Germany. The most prevalent PFAS (PFOA, PFNA, PFHxS and PFOS) were detected in all analyzed samples. The median level of the sum (Σ 4PFAS) was highest in liver (90.2 μg/kg), followed by kidney (9.45 μg/kg), plasma (7.63 μg/L), lung (6.84 μg/kg), heart muscle (2.60 μg/kg), spleen (2.46 μg/kg), and skeletal muscle (1.03 μg/kg). Consumption of a single portion (125 g) of liver containing the Σ 4PFAS median level would result in a 36.6-fold exceedance of the tolerable weekly intake (TWI) of EFSA in a 70 kg-person. The accumulation (calculated as tissue/plasma ratio) of perfluoroalkyl carboxylic acids with ηpfc = 8-13 in lung, spleen, muscle and heart tissues increased with molecule size, indicating passive mechanisms of distribution driven by hydrophobicity. In contrast, liver and kidney distribution coefficients scattered, indicating additional involvement of chain-length dependent active transport processes. The highest accumulation was observed for PFOS in the liver (median tissue/plasma ratio 18.0). The shortest PFAS included in the study (PFHxA, PFHpA, PFOA, PFBS and PFHxS) did not accumulate in any of the tissues, probably due to strong binding to blood proteins like serum albumin and their relative polarity impeding passive membrane diffusion.

In recent years, acute cardiovascular effects of high energy drink (ED) consumption have been described, but no data are available on chronic high consumption of EDs and cardiovascular risk in adolescents. As a first study, the present study investigated differences in a variety of cardiological parameters in adolescents (aged 15–18 years) with a chronic high consumption of EDs (ED consumption: ≥ four days/week for ≥ last 12 months, > 3 mg caffeine from EDs/kg bodyweight/day) compared to a control group. In study phase 1 of the cross-sectional EDKAR-study, data from 5100 pupils in Berlin (Germany) on their ED consumption and lifestyle factors were assessed using an online questionnaire. Based on these, adolescents with a chronic high ED consumption (n = 97) and a control group (n = 160) were cardiologically examined at Charité - Universitätsmedizin Berlin. Blood pressure, heart rate, electrocardiographic and echocardiographic parameters were assessed. Cardiological risk factors like educational background, smoking, alcohol consumption and sleep duration were investigated. The study noticed no significant and/or clinically relevant differences in any of the cardiological parameters e.g., heart rate (Chronic high ED consumption: Geometric mean (95

BACKGROUND & AIMS:Previous studies have described benefits and risks on human health associated with a vegan diet. Although it is recognized that diet affects the gut microbiota, there is no consensus on the effects of a vegan diet compared to omnivorous diet on the gut microbiota. We have conducted a pilot study to assess the differences between the gut microbiome of vegans and omnivores in 2017 and 2021. METHODS:Fecal samples of 23 vegans and 23 omnivores (n = 46) were collected in 2017 and 2021 together with more than 300 dietary, lifestyle, and health related characteristics. The fecal microbiome was assessed comparing both amplicon sequencing and metagenome sequencing, to determine robust signals agnostic of sequencing approaches. RESULTS:Dietary grouping itself explained a small (∼4 %) but significant proportion of the individual variation between microbiota. Natural clustering of microbiomes explained an even larger proportion. We found Ruminococcus torques to be relatively enriched in omnivores compared to vegans across methods and years. Interestingly, this species has been previously associated with unfavorable health outcomes. Despite a low sample size, we found some consistent differences between microbiota of individuals consuming either a vegan or omnivorous diet. CONCLUSIONS:These results were consistent with recently published gut microbiome signatures of vegans and omnivores across three different countries. Therefore, this small dataset allows a first insight into the gut microbiota of another county's omnivores and vegans whereby detailed and relevant dietary, lifestyle and health related characteristics collected in this study aid in understanding of the connection between respective diets and the microbiome.

Plant-based diets are gaining popularity due to their well-documented cardiometabolic benefits and environmental sustainability. However, these diets are often lower in specific micronutrients such as iodine, raising concerns about their potential impact on thyroid health. Therefore, we examined the associations between plant-based diets and the risk of hypothyroidism. We analysed data from the UK (United Kingdom) Biobank cohort. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95

Background: Globally, plant-based diets are gaining in popularity. Whilst their cardiometabolic benefits are well-documented, there is a lack of studies examining the associations between plant-based diets and risk of hypothyroidism. Methods: We analysed data from the UK Biobank cohort. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for incident hypothyroidism across vegans, vegetarians, pescatarians, poultry eaters, low meat eaters, and high meat eaters aged 40-69 years. Ancillary to this, we carried out logistic regression analyses to evaluate associations between the diet groups and prevalent hypothyroidism (according to International Classification of Diseases (ICD) codes at baseline. Results: We included 494,437 individuals from the UK Biobank, of which 231,906 followed a high-meat, 236,510 a low-meat, 5,662 a poultry-based, 11,286 a pescatarian, 8,654 a vegetarian, and 419 a vegan diet. During a median (SD) follow-up of 12.7 (+/- 3.2) years, 24,240 participants developed hypothyroidism. In multivariable Cox regression models without adjustment for body mass index (BMI), none of the diets were significantly associated with the risk of hypothyroidism. However, there was a tendency for a higher risk of hypothyroidism among vegetarians compared to people following a high-meat diet (HR: 1.08, 95% CI: 0.98 - 1.19). After controlling for BMI the association for vegetarians (HR = 1.18, 95% CI 1.07 - 1.30) became stronger and statistically significant. Furthermore, we observed a positive association between a vegetarian (OR: 1.37, 95% CI: 1.14 - 1.63) and a poultry diet (OR: 1.35, 95% CI: 1.10 - 1.63) with hypothyroidism prevalence. Conclusion: In the present study, we found a moderately higher risk of hypothyroidism among vegetarians, after controlling for BMI, a potential collider. This slightly higher risk of hypothyroidism among vegetarians, requires further investigation, taking iodine status and thyroid hormone levels into account. Keywords Plant-based diets, hypothyroidism, vegan, vegetarian, thyroid, iodine ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: UK Biobank Access Management System (AMS) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors

ObjectivesTo investigate the association of musical activity with mental health during the COVID-19 pandemic.MethodsA total of 3,666 participants reported their musical activity before and mental health indicators before and during the pandemic. Depression was assessed with the Patient Health Questionnaire, anxiety with the Generalized Anxiety Disorder scale. The association between mental health scores and musical activities was investigated using linear regression.ResultsWithin the last 12 months, 22.1% of the participants reported musical activity (15.1% singing, 14.5% playing an instrument). Individuals with frequent singing as their main musical activity had higher scores before the pandemic than non-musicians and the worsening during the pandemic was more pronounced compared to non-musicians. Instrumentalists tended to have slightly lower scores than non-musicians indicating a possible beneficial effect of playing an instrument on mental health.ConclusionThe pandemic led to a worsening of mental health, with singers being particularly affected. Singers showed poorer mental health before the pandemic. The tendency for instrumentalists to report lower depression scores compared to non-musicians may support the hypothesis that music-making has a beneficial effect on health.

Fatty acid esters of 2/3-monochloropropanediol (2/3-MCPD) and glycidol are formed mainly during heat processing (deodorization) of vegetable oils, and are hydrolyzed by lipases in the gastrointestinal tract leading to the absorption of 2/3-MCPD and glycidol. The International Agency for Research on Cancer (IARC) has classified 3-MCPD as possibly and glycidol as probably carcinogenic to humans. The aims of the current work were to clarify the exposure to 2/3-MCPD and glycidol associated with different dietary habits (omnivore, vegan, raw-food eating), and the exposure development between 2017 and 2021 in German study participants. The questions were addressed using the daily urinary excretion of 2/3-MCPD and the hemoglobin adduct N-(2,3-dihydroxypropyl)-Val (DHP-Val) formed from glycidol as biomarkers of exposure, which were determined in two dietary studies including 36 omnivores, 36 vegans and 16 strict raw food eaters (abstaining from any heated food for at least four months). The median urinary excretion of 2- and 3-MCPD in non-smoking omnivores and vegans was 0.87 and 1.35 µg/day (2-MCPD), respectively, and 0.79 and 1.03 µg/day (3-MCPD), respectively. The 2/3-MCPD concentrations in urine samples of raw food eaters were usually below the limit of detection. The median DHP-Val levels in non-smoking vegans and omnivores were 3.9 pmol/g Hb each, and 1.9 pmol/g Hb in raw food eaters. Between 2017 and 2021, the exposure to 3-MCPD and glycidol did not change, however, the median 2-MCPD excretion decreased (p = 0.02, omnivores and vegans combined). The correlation between daily excretions of 2/3-MCPD determined 4 years apart was weak, whereas a moderate correlation was observed for DHP-Val (rS = 0.66) in this timeframe. In conclusion, the exposure to glycidol in omnivores and vegans was alike, whereas the 2/3-MCPD exposure was somewhat (albeit not significantly) higher in vegans. While 2/3-MCPD were hardly detectable in urine samples of raw food eaters, the median DHP-Val level (about 50

The urinary mercapturic acids N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA) and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA) are short-term biomarkers of exposure from acrylamide and its metabolite glycidamide, respectively. The medium-term exposure to acrylamide and glycidamide is monitored by the adducts N-(2-carbamoylethyl)-Val (AA-Val) and N-(2-carbamoyl-2-hydroxyethyl)-Val (GA-Val) in hemoglobin (Hb), respectively. Three questions were addressed by application of these biomarkers in two diet studies including 36 omnivores, 36 vegans and 16 strict raw food eaters (abstaining from any warmed or heated food for at least four months): first, what is the internal acrylamide exposure following a vegan or a raw food diet in comparison to that in omnivores? Second, did the exposure change between 2017 and 2021? And third, what is the stability over time of AAMA/GAMA excretion compared to that of AA-Val/GA-Val levels in Hb between both time points? Median urinary AAMA excretion per day in non-smoking omnivores, vegans and raw food eaters were 62.4, 85.4 and 15.4 µg/day, respectively; the corresponding median AA-Val levels were 27.7, 39.7 and 13.3 pmol/g Hb, respectively. Median levels in strict raw food eaters were about 25

Background A number of biomarkers denoting various pathophysiological pathways have been implicated in the aetiology and risk of age-related diseases. Hence, the combined impact of multiple biomarkers in relation to ageing free of major chronic diseases, such as cancer, cardiovascular disease and type 2 diabetes, has not been sufficiently explored.Methods We measured concentrations of 13 biomarkers in a random subcohort of 2,500 participants in the European Prospective Investigation into Cancer and Nutrition Potsdam study. Chronic disease-free ageing was defined as reaching the age of 70 years within study follow-up without major chronic diseases, including cardiovascular disease, type 2 diabetes or cancer. Using a novel machine-learning technique, we aimed to identify biomarker clusters and explore their association with chronic disease-free ageing in multivariable-adjusted logistic regression analysis taking socio-demographic, lifestyle and anthropometric factors into account.Results Of the participants who reached the age of 70 years, 321 met our criteria for chronic-disease free ageing. Machine learning analysis identified three distinct biomarker clusters, among which a signature characterised by high concentrations of high-density lipoprotein cholesterol, adiponectin and insulin-like growth factor-binding protein 2 and low concentrations of triglycerides was associated with highest odds for ageing free of major chronic diseases. After multivariable adjustment, the association was attenuated by socio-demographic, lifestyle and adiposity indicators, pointing to the relative importance of these factors as determinants of healthy ageing.Conclusion These data underline the importance of exploring combinations of biomarkers rather than single molecules in understanding complex biological pathways underpinning healthy ageing.

Abstract Musical activities (MA) such as singing, playing instruments, and listening to music may be associated with health benefits. However, evidence from epidemiological studies is still limited. This study aims at describing the relation between MA and both sociodemographic and health-related factors in a cross-sectional approach. A total of 6717 adults (50.3% women, 49.7% men, median age: 51 years (IQR 43–60) were recruited from the study center Berlin-Mitte of the German National Cohort (NAKO), a population-based prospective study. This study is based on a sample randomly selected from the population registry of Berlin, Germany, aged 20 to 69 years. 53% of the participants had been musically active at least once in their life (56.1% women, 43.9% men). Playing keyboard instruments (30%) and singing (21%) were the most frequent MA. Participants listened to music in median 90 min per day (IQR 30.0–150.0). Musically active individuals were more likely to have a higher education, higher alcohol consumption, were less likely to be physically active, and had a lower BMI compared to musically inactive individuals. This large population-based study offers a comprehensive description of demographic, health, and lifestyle characteristics associated with MA. Our findings may aid in assessing long-term health consequences of MA.

Dietary biomarkers can potentially overcome the limitations of self-reported dietary data. While in ecology and archaeology, stable isotope ratios of carbon and nitrogen are widely used as biomarkers, this is not the case in nutrition research. Since the abundance of the 13C and the 15N isotope differ in food sources from plant and animal origin, stable isotope ratios of carbon and nitrogen (δ13C and δ15N) may differ in human biological material. Here, we investigated the stable isotope ratios of nitrogen and carbon in serum and urine from vegans and omnivores. Measurement of δ15N and δ13C in serum and 24 h urine was performed by Elemental Analyzer–Isotope Ratio Mass Spectrometer in the cross-sectional study “Risks and Benefits of a Vegan Diet”. The study included 36 vegans and 36 omnivores with a median age of 37.5 years (matched for age and sex), who adhered to their diet for at least 1 year. Both δ15N and δ13C were significantly lower in both the serum and 24 h urine of vegans compared to omnivores. δ15N either in serum or urine had 100

Supplementary Table 1. Spearman Partial Correlationsa of Omentin with Metabolic Biomarkers within the subcohort by adiposity status (n = 2295): The EPIC Potsdam Case-Cohort Study

Biomarker measurements in spot urine are often adjusted for creatinine to control for dilution resulting from individual hydration. We here report on results of a study involving age- and sex-matched vegans and omnivores (n = 36 each). The daily urinary excretion of 2,3-dihydroxypropylmercapturic acid (DHPMA, a diet-independent endogenous C3-metabolite used as an example compound) was found not to be different in vegans and omnivores (median 433 mu g/24 h each), however, creatinine-adjusted levels were 26% lower in omnivores (median 285 mu g/g creatinine) than in vegans (median 383 mu g/g creatinine, p = 0.003). This difference results from the higher urinary excretion of creatinine in the omnivores compared to vegans (median 1.51 vs. 1.21 g/24 h, p = 0.009). Linear regression showed - besides the fat-free mass - a significant impact of the factor diet (vegans vs. omnivores). This may be due to the consumption of meat and fish as exogenous sources of creatinine. A literature search revealed broad evidence for this interpretation, as creatinine is formed from creatine during heating of meat and fish. Accordingly, consumption leads to temporary increase of serum/plasma creatinine and urinary creatinine excretion, resulting in higher levels in omnivores compared to vegans/vegetarians. An adjustment of the urinary DHPMA concentrations using specific gravity revealed 13% lower values in omnivores (median 225 mu g/L) than in vegans (median 260 mu g/L, p = 0.07). Compared to creatinine-adjustment, adjustment for specific gravity introduces a smaller but still obvious difference between omnivores and vegans. Especially with respect to future studies comparing vegans, vegetarians and omnivores, researchers should be aware of the risks of severe misinterpretations if biomarker measurements in spot urine are adjusted for creatinine.

Supplementary Figures 1-3 Supplementary Figure 1. Pictorial representation of the case-cohort study design: the EPIC Potsdam Case-Cohort Study Supplementary Figure 2: Multivariable-adjusted Relative Risks (95% Confidence Intervals) of Circulating Omentin Concentrations with Risk of Colorectal Cancer with Additional Adjustment for Metabolic Biomarkers: The EPIC Potsdam Case-Cohort Study Supplementary Figure 3. Predictive ability of pre-diagnostic omentin concentrations beyond established lifestyle and metabolic risk factors for colorectal cancer (Panel A) men and (Panel B) women: The EPIC Potsdam Case-Cohort Study