Privacy Risk Assessment for Synthetic Longitudinal Health Data.

INTRODUCTION: A modern approach to ensuring privacy when sharing datasets is the use of synthetic data generation methods, which often claim to outperform classic anonymization techniques in the trade-off between data utility and privacy. Recently, it was demonstrated that various deep learning-based approaches are able to generate useful synthesized datasets, often based on domain-specific analyses. However, evaluating the privacy implications of releasing synthetic data remains a challenging problem, especially when the goal is to conform with data protection guidelines. METHODS: Therefore, the recent privacy risk quantification framework Anonymeter has been built for evaluating multiple possible vulnerabilities, which are specifically based on privacy risks that are considered by the European Data Protection Board, i.e. singling out, linkability, and attribute inference. This framework was applied to a synthetic data generation study from the epidemiological domain, where the synthesization replicates time and age trends previously found in data collected during the DONALD cohort study (1312 participants, 16 time points). The conducted privacy analyses are presented, which place a focus on the vulnerability of outliers. RESULTS: The resulting privacy scores are discussed, which vary greatly between the different types of attacks. CONCLUSION: Challenges encountered during their implementation and during the interpretation of their results are highlighted, and it is concluded that privacy risk assessment for synthetic data remains an open problem.

Metabolomics signatures of sweetened beverages and added sugar are related to anthropometric measures of adiposity in young individuals: results from a cohort study.

BACKGROUND: The associations of sweetened beverages (SBs) and added sugar (AS) intake with adiposity are still debated. Metabolomics could provide insights into the mechanisms linking their intake to adiposity. OBJECTIVES: We aimed to identify metabolomics biomarkers of intake of low- and no-calorie sweetened beverages (LNCSBs), sugar-sweetened beverages (SSBs), and ASs and to investigate their associations with body mass index, body fat percentage, and waist circumference. METHODS: We analyzed 3 data sets from the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) cohort study, of children who provided 2 urine samples (n = 297), adolescents who provided a single urine sample (n = 339), and young adults who provided a single plasma sample (n = 195). Urine and plasma were analyzed using untargeted metabolomics. Dietary intakes were assessed using 3-d weighed dietary records. The random forest, partial least squares, and least absolute shrinkage and selection operator were jointly used for metabolite selection. We examined associations of intakes with metabolites and anthropometric measures using linear and mixed-effects regression. RESULTS: In adolescents, LNCSB were positively associated with acesulfame (ß: 0.0012; 95% confidence interval [CI]: 0.0006, 0.0019) and saccharin (ß: 0.0009; 95% CI: 0.0002, 0.0015). In children, the association was observed with saccharin (ß: 0.0016; 95% CI: 0.0005, 0.0027). In urine and plasma, SSBs were positively associated with 1-methylxanthine (ß: 0.0005; 95% CI: 0.0003, 0.0008; and ß: 0.0010, 95% CI 0.0004, 0.0015, respectively) and 5-acetylamino-6-amino-3-methyluracil (ß: 0.0005; 95% CI: 0.0002, 0.0008; and ß: 0.0009; 95% CI: 0.0003, 0.0014, respectively). AS was associated with urinary sucrose (ß: 0.0095; 95% CI: 0.0069, 0.0121) in adolescents. Some of the food-related metabolomics profiles were also associated with adiposity measures. CONCLUSIONS: We identified SBs- and AS-related metabolites, which may be important for understanding the interplay between these intakes and adiposity in young individuals.

Intake of free sugar among children and adolescents in Germany declines - current results of the DONALD study.

PURPOSE: Our recent analysis reported decreasing trends in intake of free sugar in children and adolescents in Germany. Here we set out to update this analysis with current dietary intake (until 2023) because of the strong public health nutrition interest in sugar intake. METHODS: In total, 4,218 dietary records kept between 2010 and 2023 by 751 participants (46.0% females, 3-18 years) from the German Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) cohort were examined. Age and time trends in free sugar intake (%E/d) were analysed using polynomial mixed-effects regression models. RESULTS: Median intake data indicate a decline in the intake of free sugar between 2010/2011 (16.7%E) and 2022/2023 (11.7%E). Trend analyses confirmed, that intake of free sugars decreased continuously between 2017 and 2023 (Linear trend: ß = -0.4126, p < 0.0001). In addition, free sugar intake changed significantly with age (Linear trend: ß = 1.2922, p < 0.0001; quadratic trend: ß = -0.08613, p = 0.0094; cubic trend: ß = 0.001442, p = 0.1725), i.e. the intake of free sugars increases continuously up to early adolescence (9/10 years) and decreases again thereafter. CONCLUSION: The intake of free sugar among children and adolescents continued to decline, but still exceeded the WHO recommendations in 2023. Further measures to reduce free sugar intake would therefore be desirable, as well as continuous monitoring of sugar intake levels among this age groups.

Synthetic data generation for a longitudinal cohort study - evaluation, method extension and reproduction of published data analysis results.

Access to individual-level health data is essential for gaining new insights and advancing science. In particular, modern methods based on artificial intelligence rely on the availability of and access to large datasets. In the health sector, access to individual-level data is often challenging due to privacy concerns. A promising alternative is the generation of fully synthetic data, i.e., data generated through a randomised process that have similar statistical properties as the original data, but do not have a one-to-one correspondence with the original individual-level records. In this study, we use a state-of-the-art synthetic data generation method and perform in-depth quality analyses of the generated data for a specific use case in the field of nutrition. We demonstrate the need for careful analyses of synthetic data that go beyond descriptive statistics and provide valuable insights into how to realise the full potential of synthetic datasets. By extending the methods, but also by thoroughly analysing the effects of sampling from a trained model, we are able to largely reproduce significant real-world analysis results in the chosen use case.

Controversy on health-based guidance values for bisphenol A-the need of criteria for studies that serve as a basis for risk assessment.

Since 2006, the responsible regulatory bodies have proposed five health-based guidance values (HBGV) for bisphenol A (BPA) that differ by a factor of 250,000. This range of HBGVs covers a considerable part of the range from highly toxic to relatively non-toxic substances. As such heterogeneity of regulatory opinions is a challenge not only for scientific risk assessment but also for all stakeholders, the Senate Commission on Food Safety (SKLM) of the German Research Foundation (DFG) analyzed the reasons for the current discrepancy and used this example to suggest improvements for the process of HBGV recommendations. A key aspect for deriving a HBGV is the selection of appropriate studies that allow the identification of a point of departure (PoD) for risk assessment. In the case of BPA, the HBGV derived in the 2023 EFSA assessment was based on a study that reported an increase of Th17 cells in mice with a benchmark dose lower bound (BMDL40) of 0.53 µg/kg bw/day. However, this study does not comply with several criteria that are important for scientific risk assessment: (1) the selected end-point, Th17 cell frequency in the spleen of mice, is insufficiently understood with respect to health outcomes. (2) It is unclear, by which mechanism BPA may cause an increase in Th17 cell frequency. (3) It is unknown, if an increase of Th17 cell frequency in rodents is comparably observed in humans. (4) Toxicokinetics were not addressed. (5) Neither the raw data nor the experimental protocols are available. A further particularly important criterion (6) is independent data confirmation which is not available in the present case. Previous studies using other readouts did not observe immune-related adverse effects such as inflammation, even at doses orders of magnitude higher than in the Th17 cell-based study. The SKLM not only provides here key criteria for the use of such studies, but also suggests that the use of such a "checklist" requires a careful and comprehensive scientific judgement of each item. It is concluded that the Th17 cell-based study data do not represent an adequate basis for risk assessment of BPA.

Commentary of the SKLM to the EFSA opinion on risk assessment of N-nitrosamines in food.

Dietary exposure to N-nitrosamines has recently been assessed by the European Food Safety Authority (EFSA) to result in margins of exposure that are conceived to indicate concern with respect to human health risk. However, evidence from more than half a century of international research shows that N-nitroso compounds (NOC) can also be formed endogenously. In this commentary of the Senate Commission on Food Safety (SKLM) of the German Research Foundation (DFG), the complex metabolic and physiological biokinetics network of nitrate, nitrite and reactive nitrogen species is discussed with emphasis on its influence on endogenous NOC formation. Pioneering approaches to monitor endogenous NOC have been based on steady-state levels of N-nitrosodimethylamine (NDMA) in human blood and on DNA adduct levels in blood cells. Further NOC have not been considered yet to a comparable extent, although their generation from endogenous or exogenous precursors is to be expected. The evidence available to date indicates that endogenous NDMA exposure could exceed dietary exposure by about 2-3 orders of magnitude. These findings require consolidation by refined toxicokinetics and DNA adduct monitoring data to achieve a credible and comprehensive human health risk assessment.

Environmental sustainability of diets among children and adolescents in the German DONALD cohort study: age and time trends, and nutrient adequacy.

BACKGROUND: Identifying diets beneficial for both human and planetary health has become increasingly important. However, to date, there is limited research on sustainable diets for children and adolescents, a vulnerable population group with specific nutritional needs. OBJECTIVES: We aimed to identify 1) the main determinants; 2) age and time trends of greenhouse gas emissions (GHGE), land use (LU), and water use (WU) of diets of children and adolescents; and 3) analyze the associations of dietary GHGE, LU, and WU with nutrient adequacy. METHODS: A total of 5510 3-d-weighted dietary records (n = 856; 6-17 y; 48% ♀) of the DONALD (DOrtmund Nutritional and Anthropometric Longitudinally Designed) study between 2000 and 2021 were analyzed. Values of GHGE (kgCO2eq), LU (m2 × year), and WU (L) determined by life cycle assessment were assigned to all recorded foods. For nutrient adequacy, the mean adequacy ratio (MAR = ∑(nutrient intake / recommended intake) / number of nutrients) was used. Data were analyzed using polynomial mixed-effects regression models. RESULTS: The main contributors to GHGE and LU were meat products (GHGE: 25.6%; LU: 32.8%), dairy products (22.2%; 17.7%), and sweets and pastries (14.0%; 14.3%); to WU, nonalcoholic beverages (24.3%), meat products (18.9%), and vegetables and fruits (17.7%). GHGE, LU, and WU per 1000 kcal increased with age (P < 0.01). GHGE and LU per 1000 kcal increased between 2000 and 2010 and decreased after that in females (P < 0.01) and males (GHGE only: P = 0.02). No significant time trend was found for WU (P > 0.05). A higher MAR was directly associated with GHGE/1000 kcal (MAR: ß: 0.011, 95% CI: 0.008, 0.013, P < 0.0001), LU/1000 kcal (MAR: ß: 0.009, 95%CI: 0.005, 0.013, P < 0.0001), and WU/1000 kcal (MAR: ß: 0.429, 95% CI: 0.325, 0.533, P < 0.0001). CONCLUSIONS: Our findings underscore the further need and the capacity for change toward more environmentally sustainable diets. Yet, the tradeoff between environmental sustainability and nutrient adequacy in the diets of children and adolescents requires specific attention to dietary composition.

Changes in eating habits and lifestyle during the first year of the COVID-19 pandemic across metropolitan regions in Brazil and Germany: A survey-based cross-sectional study.

COVID-19 caused profound societal changes to cope rapidly with the new circumstances. The food market changed its quantity, quality, form, and frequency dynamics. Consequently, food-eating habits and lifestyles like physical exercise likely experienced changes. An online-based survey was conducted between June 2020 and January 2021 in the metropolitan regions of Rhine Ruhr Metropolis (RRM), Greater São Paulo (GSP), other metropolitan regions in São Paulo state (oMRSP), other Brazilian metropolitan regions (oBRMR), and the remaining urban areas in both countries (oUA), representing different contexts of Brazil and Germany. We assessed self-reported changes in physical activity level, diet quality, self-reported eating habits, and buying groceries during the first year of the pandemic. In Germany, indoor and outdoor activities increased for 34% of the respondents, while in Brazil, there was a decrease in physical activity for 50% of the participants. The Healthy Eating Index (HEI) scored higher among Brazilians (16.8) than Germans (15.2) on a 0-29 HEI scale. Increased awareness of healthy and sustainable eating habits was observed in GSP (0.7), oMRSP (0.63), oBRMR (0.7), and oUA (0.68) on a scale from no change (0) to change (1). In RRM, an increase in convenience foods was noticed (0.86). Participants reported discomfort with food purchasing due to hygiene measures and avoided going to the supermarket (0.7 on average in Brazil and 0.58 for females using the same 0-1 scale). Also, food supply at the grocery shops was reported to be often unavailable and in lower quantities. A real-time assessment of self-reported changes in eating habits and lifestyle during the lockdown in 2020 in different contexts is insightful for rethinking strategies to improve conditions in the post-COVID-19 era and prepare for future pandemics.

The association between dairy intake in adolescents on inflammation and risk markers of type 2 diabetes during young adulthood: results of the DONALD study.

OBJECTIVE: The aim of this analysis was to investigate whether habitual intake of total dairy (TD) or different dairy types (liquid, solid, fermented, non-fermented, low-fat, high-fat, low-sugar and high-sugar dairy) during adolescence is associated with biomarkers of low-grade inflammation as well as risk factors of type 2 diabetes in young adulthood. DESIGN: Multivariable linear regression analyses were used to investigate prospective associations between estimated TD intake as well as intake of different types of dairy and a pro-inflammatory score, based on high-sensitivity C-reactive protein, IL-6, IL-18, leptin and adiponectin, and insulin resistance assessed as Homeostasis Model Assessment Insulin Resistance in an open-cohort study. SETTING: Dortmund, Germany. PARTICIPANTS: Data from participants (n 375) of the DOrtmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study were included, for whom at least two 3-d weighed dietary records during adolescence (median age: 11 years) and one blood sample in young adulthood (>18 years) were available. RESULTS: There was no statistically significant association between TD intake or intake of any dairy type and the pro-inflammatory score (all P > 0·05). TD intake as well as each dairy type intake and insulin resistance also showed no association (all P > 0·05). CONCLUSIONS: The habitual intake of dairy or individual types of dairy during adolescence does not seem to have a major impact on low-grade systemic inflammation and insulin resistance in the long term. There was no indication regarding a restriction of dairy intake for healthy children and adolescents in terms of diabetes risk reduction.

Phosphorus Intake and Potential Dietary Influences Examined via 24-Hour Urinary Biomarker Measurements in German Children and Adolescents Over 3 Decades.

BACKGROUND: Increases in phosphorus intake have been observed over the past years in adult populations. However, biomarker-based data are lacking on whether or not phosphorus intake also increased in children. OBJECTIVE: The aim of this study was to examine 24-hour urinary phosphate excretion (PO4-Ex) and diet-related biomarkers potentially influencing phosphorus status in German children and adolescents from 1985 to 2015. DESIGN: This longitudinal noninvasive biomarker-based cohort study examined 24-hour urine samples from children and adolescents of the Dortmund Nutritional and Anthropometric Longitudinally Designed Study, collected over 3 decades. PARTICIPANTS/SETTING: Examined individuals (n = 1,057) were healthy participants of the Dortmund Nutritional and Anthropometric Longitudinally Designed Study, situated in Dortmund, Germany, who had been asked to collect one yearly 24-hour urine sample. Six thousand seven hundred thirty-seven samples collected from participants aged 3 to 17 years between 1985 (baseline) and 2015, were included. MAIN OUTCOME MEASURES: phosphorus intake was examined biomarker-based by analyzed PO4-Ex in 24-hour urine samples. Whether acid-base status and intakes of protein, salt, and fruits and vegetables, may have relevantly contributed to PO4-Ex levels was assessed by determining 24-hour excretions of net acid, urea-nitrogen, and sodium as well as specific standardized excretions of potassium plus oxalate. STATISTICAL ANALYSES PERFORMED: Trend analysis over 30 years and potentially influencing diet factors were examined using linear mixed-effect regression models (PROC-MIXED). Adjustments for sex, age, and body surface area were performed. RESULTS: No change was identifiable for PO4-Ex over the 3 decades; neither in 3 to 8, 9 to 13, nor in 14 to 17 year olds. However, sodium excretion increased (P = .001). PROC-MIXED analysis on intraindividual changes in PO4-Ex revealed direct relationships with net acid excretion, urea-nitrogen, and sodium excretion and an inverse relationship with a biomarker of fruit and vegetable intake. CONCLUSIONS: Despite a direct relationship between PO4-Ex and a biomarker of industrially processed food consumption; that is, sodium excretion, which showed an increasing time trend, phosphorus intake was found to remain stable over decades in children and adolescents.

Empirically derived portion sizes from the DOrtmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study for 4- to 18-year-old children and adolescents to simplify analysis of dietary data using FFQ.

OBJECTIVE: To apply FFQ, knowledge about portion sizes is relevant. According to increased energy and nutrient requirements, average portion sizes of foods are supposed to increase during growth. We provide empirically derived portion sizes for 4- to 18-year-olds in different age groups to facilitate analyses of FFQ data in children and adolescents. DESIGN: Using data from the dynamic DOrtmund Nutritional and Anthropometric Longitudinally Designed cohort study, quantile regression for smoothing percentiles was used to derive portion sizes as a function of age from which age- and food group-specific portion sizes were calculated as median food group intake (g). SETTING: Dortmund, Germany. PARTICIPANTS: Data from 3-day weighed dietary records (WDR) of 1,325 participants (♀: 653) were analysed. Participants provided in total 9,828 WDR (on average 7·5 per participant) between 1985 and 2022. WDR were grouped into five age groups, whereby each age group covered 3 years of age. RESULTS: In total, 11 955 food items were reported and categorised into sixteen major food groups with seventy-one sub-groups. Portion sizes tended to increase with age, except for milk- and plant-based alternatives. Comparing 4- to 6-year-olds to 16- to 18-year-olds, portion size increased between 22·2 % (processed meat: 18 g v. 22 g) and 173·3 % (savoury snacks: 15 g v. 41 g). CONCLUSION: We provide empirically derived portion sizes for children and adolescents. These data are useful to establish dietary assessment methods based on estimates of portion sizes, such as FFQ, for children and adolescents.

Cohort profile update-overview of over 35 years of research in the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study.

PURPOSE: To provide an update on the cohort profile of the DOrtmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study, including objectives, study design, methods and description of the comprehensive data pool, as well as to summarize the most important research findings of recent years. METHODS: In 1985, the open (dynamic) cohort started to collect information on diet, growth, development, and metabolism of healthy children and adolescents in Dortmund, Germany. Detailed data are collected annually during infancy, childhood, and adolescence of the participants, including a 3-day weighed dietary record, a 24-h urine sample, anthropometric and medical examinations as well as interviews on lifestyle. RESULTS: Even if the basic examination modules have not changed since the start over 35 years ago, the DONALD study has been continuously further developed by introducing new modules. As such, participants are also invited for follow-up examinations during adulthood since 2005, including an additional fasting blood withdrawal. Overall, 2375 (♂: 1177; ♀: 1198) participants were recruited in the DONALD study between 1985 and 2022. Data from ~ 30,700 anthropometric measurements, ~ 19,200 dietary records, ~ 10,600 24-h urine and ~ 1300 blood samples are available from an observation period of over 35 years. CONCLUSION: The DONALD study provides a large data pool for longitudinal studies on nutrition, growth, and health in childhood and adolescence, its impact on the development of diseases in early adult life as well as dietary intake trends over more than three decades.

Chronic disease outcome metadata from German observational studies - public availability and FAIR principles.

Metadata from epidemiological studies, including chronic disease outcome metadata (CDOM), are important to be findable to allow interpretability and reusability. We propose a comprehensive metadata schema and used it to assess public availability and findability of CDOM from German population-based observational studies participating in the consortium National Research Data Infrastructure for Personal Health Data (NFDI4Health). Additionally, principal investigators from the included studies completed a checklist evaluating consistency with FAIR principles (Findability, Accessibility, Interoperability, Reusability) within their studies. Overall, six of sixteen studies had complete publicly available CDOM. The most frequent CDOM source was scientific publications and the most frequently missing metadata were availability of codes of the International Classification of Diseases, Tenth Revision (ICD-10). Principal investigators' main perceived barriers for consistency with FAIR principles were limited human and financial resources. Our results reveal that CDOM from German population-based studies have incomplete availability and limited findability. There is a need to make CDOM publicly available in searchable platforms or metadata catalogues to improve their FAIRness, which requires human and financial resources.

An Investigation into the Relationship of Circulating Gut Microbiome Molecules and Inflammatory Markers with the Risk of Incident Dementia in Later Life.

The gut microbiome may be involved in the occurrence of dementia primarily through the molecular mechanisms of producing bioactive molecules and promoting inflammation. Epidemiological evidence linking gut microbiome molecules and inflammatory markers to dementia risk has been mixed, and the intricate interplay between these groups of biomarkers suggests that their joint investigation in the context of dementia is warranted. We aimed to simultaneously investigate the association of circulating levels of selected gut microbiome molecules and inflammatory markers with dementia risk. This case-cohort epidemiological study included 805 individuals (83 years, 66% women) free of dementia at baseline. Plasma levels of 19 selected gut microbiome molecules comprising lipopolysaccharide, short-chain fatty acids, and indole-containing tryptophan metabolites as well as four inflammatory markers measured at baseline were linked to incident all-cause (ACD) and Alzheimer's disease dementia (AD) in binary outcomes and time-to-dementia analyses. Independent of several covariates, seven gut microbiome molecules, 5-hydroxyindole-3-acetic acid, indole-3-butyric acid, indole-3-acryloylglycine, indole-3-lactic acid, indole-3-acetic acid methyl ester, isobutyric acid, and 2-methylbutyric acid, but no inflammatory markers discriminated incident dementia cases from non-cases. Furthermore, 5-hydroxyindole-3-acetic acid (hazard ratio: 0.58; 0.36-0.94, P = 0.025) was associated with time-to-ACD. These molecules underpin gut microbiome-host interactions in the development of dementia and they may be crucial in its prevention and intervention strategies. Future larger epidemiological studies are needed to confirm our findings, specifically in exploring the repeatedly measured circulating levels of these molecules and investigating their causal relationship with dementia risk.

Association between urinary iodine excretion, genetic disposition and fluid intelligence in children, adolescents and young adults: the DONALD study.

PURPOSE: Iodine deficiency increases the risk of cognitive impairment and delayed physical development in children. It is also associated with cognitive impairment in adults. Cognitive abilities are among the most inheritable behavioural traits. However, little is known about the consequences of insufficient postnatal iodine intake and whether the individual genetic disposition modifies the association between iodine intake and fluid intelligence in children and young adults. METHODS: The cultural fair intelligence test was used to assess fluid intelligence in the participants of the DONALD study (n = 238; mean age, 16.5 [SD = 7.7] years). Urinary iodine excretion, a surrogate iodine intake marker, was measured in 24-h urine. Individual genetic disposition (n = 162) was assessed using a polygenic score, associated with general cognitive function. Linear regression analyses were conducted to determine whether Urinary iodine excretion was associated with fluid intelligence and whether this association was modified by individual genetic disposition. RESULTS: Urinary iodine excretion above the age-specific estimated average requirement was associated with a five-point higher fluid intelligence score than that below the estimated average requirement (P = 0.02). The polygenic score was positively associated with the fluid intelligence score (ß = 2.3; P = 0.03). Participants with a higher polygenic score had a higher fluid intelligence score. CONCLUSION: Urinary iodine excretion above the estimated average requirement in childhood and adolescence is beneficial for fluid intelligence. In adults, fluid intelligence was positively associated with a polygenic score for general cognitive function. No evidence showed that the individual genetic disposition modifies the association between Urinary iodine excretion and fluid intelligence.

Exploring the association of physical activity with the plasma and urine metabolome in adolescents and young adults.

BACKGROUND: Regular physical activity elicits many health benefits. However, the underlying molecular mechanisms through which physical activity influences overall health are less understood. Untargeted metabolomics enables system-wide mapping of molecular perturbations which may lend insights into physiological responses to regular physical activity. In this study, we investigated the associations of habitual physical activity with plasma and urine metabolome in adolescents and young adults. METHODS: This cross-sectional study included participants from the DONALD (DOrtmund Nutritional and Anthropometric Longitudinally Designed) study with plasma samples n = 365 (median age: 18.4 (18.1, 25.0) years, 58% females) and 24 h urine samples n = 215 (median age: 18.1 (17.1, 18.2) years, 51% females). Habitual physical activity was assessed using a validated Adolescent Physical Activity Recall Questionnaire. Plasma and urine metabolite concentrations were determined using ultra-high-performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) methods. In a sex-stratified analysis, we conducted principal component analysis (PCA) to reduce the dimensionality of metabolite data and to create metabolite patterns. Multivariable linear regression models were then applied to assess the associations between self-reported physical activity (metabolic equivalent of task (MET)-hours per week) with single metabolites and metabolite patterns, adjusted for potential confounders and controlling the false discovery rate (FDR) at 5% for each set of regressions. RESULTS: Habitual physical activity was positively associated with the "lipid, amino acids and xenometabolite" pattern in the plasma samples of male participants only (ß = 1.02; 95% CI: 1.01, 1.04, p = 0.001, adjusted p = 0.042). In both sexes, no association of physical activity with single metabolites in plasma and urine and metabolite patterns in urine was found (all adjusted p > 0.05). CONCLUSIONS: Our explorative study suggests that habitual physical activity is associated with alterations of a group of metabolites reflected in the plasma metabolite pattern in males. These perturbations may lend insights into some of underlying mechanisms that modulate effects of physical activity.

Replication and mediation of the association between the metabolome and clinical markers of metabolic health in an adolescent cohort study.

Metabolomics-derived metabolites (henceforth metabolites) may mediate the relationship between modifiable risk factors and clinical biomarkers of metabolic health (henceforth clinical biomarkers). We set out to study the associations of metabolites with clinical biomarkers and a potential mediation effect in a population of young adults. First, we conducted a systematic literature review searching for metabolites associated with 11 clinical biomarkers (inflammation markers, glucose, blood pressure or blood lipids). Second, we replicated the identified associations in a study population of n = 218 (88 males and 130 females, average age of 18 years) participants of the DONALD Study. Sex-stratified linear regression models adjusted for age and BMI and corrected for multiple testing were calculated. Third, we investigated our previously reported metabolites associated with anthropometric and dietary factors mediators in sex-stratified causal mediation analysis. For all steps, both urine and blood metabolites were considered. We found 41 metabolites in the literature associated with clinical biomarkers meeting our inclusion criteria. We were able to replicate an inverse association of betaine with CRP in women, between body mass index and C-reactive protein (CRP) and between body fat and leptin. There was no evidence of mediation by lifestyle-related metabolites after correction for multiple testing. We were only able to partially replicate previous findings in our age group and did not find evidence of mediation. The complex interactions between lifestyle factors, the metabolome, and clinical biomarkers warrant further investigation.

Evaluation of the genotoxic potential of acrylamide: Arguments for the derivation of a tolerable daily intake (TDI value).

This opinion of the Senate Commission on Food Safety (SKLM) of the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) presents arguments for an updated risk assessment of diet-related exposure to acrylamide (AA), based on a critical review of scientific evidence relevant to low dose exposure. The SKLM arrives at the conclusion that as long as an appropriate exposure limit for AA is not exceeded, genotoxic effects resulting in carcinogenicity are unlikely to occur. Based on the totality of the evidence, the SKLM considers it scientifically justified to derive a tolerable daily intake (TDI) as a health-based guidance value.

A healthy lifestyle during adolescence was inversely associated with fatty liver indices in early adulthood: findings from the DONALD cohort study.

A healthy lifestyle during adolescence is associated with insulin sensitivity or liver enzyme levels and thus might contribute to the prevention of non-alcoholic fatty liver disease (NAFLD). Therefore, we examined the association between adherence to a hypothesis-based lifestyle score including dietary intake, physical activity, sedentary behaviour, sleep duration and BMI in adolescence and fatty liver indices in early adulthood. Overall, 240 participants of the DOrtmund Nutritional and Anthropometric Longitudinally Designed study completed repeated measurements of lifestyle score factors during adolescence (females: 8·5-15·5 years, males: 9·5-16·5 years). Multivariable linear regression models were used to investigate the association between adolescent lifestyle scores and NAFLD risk (hepatic steatosis index (HSI) and fatty liver index (FLI)) in early adulthood (18-30 years). Participants visited the study centre 4·9 times during adolescence and achieved on average 2·8 (min: 0·6, max: 5) out of five lifestyle score points. Inverse associations were observed between the lifestyle score and fatty liver indices (HSI: ß=-5·8 % (95 % CI -8·3, -3·1), P < 0·0001, FLI: ß=-32·4 % (95 % CI -42·9, -20·0), P < 0·0001) in the overall study population. Sex-stratified analysis confirmed these results in men, while inverse but non-significant associations were observed in women (P > 0·05). A higher lifestyle score was associated with lower HSI and FLI values, suggesting that a healthy lifestyle during adolescence might contribute to NAFLD prevention, predominantly in men. Our findings on repeatedly measured lifestyle scores in adolescents and their association with NAFLD risk in early adulthood warrant confirmation in larger study populations.