Association of Ultraprocessed Foods Intake with Untargeted Metabolomics Profiles in Adolescents and Young Adults in the DONALD Cohort Study.

BACKGROUND: High consumption of ultraprocessed foods (UPFs) continues to draw significant public health interest because of the associated negative health outcomes. Metabolomics can contribute to the understanding of the biological mechanisms through which UPFs may influence health. OBJECTIVES: To investigate urine and plasma metabolomic biomarkers of UPF intake in adolescents and young adults. METHODS: We used data from the Dortmund Nutritional and Anthropometric Longitudinally Designed study to investigate cross-sectional associations of UPF intake with concentrations of urine metabolites in adolescents using 3d weighed dietary records (3d-WDR) and 24-h urine samples (n = 339), and associations of repeatedly assessed UPF intake with concentrations of circulating plasma metabolites in young adults with 3-6 3d-WDRs within 5 y preceding blood measurement (n = 195). Urine and plasma samples were analyzed using mass spectrometry-based metabolomics. Biosample-specific metabolite patterns (MPs) were determined using robust sparse principal components analysis. Multivariable linear regression models were applied to assess the associations of UPF consumption (as a percentage of total food intake in g/d) with concentrations of individual metabolites and MP scores. RESULTS: The median proportion of UPF intake was 22.0% [interquartile range (IQR): 12.3, 32.9] in adolescents and 23.2% (IQR: 16.0, 31.6) in young adults. We identified 42 and 6 UPF intake-associated metabolites in urine and plasma samples, respectively. One urinary MP, "xenobiotics and amino acids" [ß = 0.042, 95% confidence interval (CI): 0.014, 0.070] and 1 plasma MP, "lipids, xenobiotics, and amino acids" (ß = 0.074, 95% CI: 0.031, 0.117) showed positive association with UPF intake. Both patterns shared 29 metabolites, mostly of xenobiotic metabolism. CONCLUSIONS: We identified urine and plasma metabolites associated with UPF intake in adolescents and young adults, which may represent some of the biological mechanisms through which UPFs may influence metabolism and health.

Identification and Replication of Urine Metabolites Associated With Short-Term and Habitual Intake of Sweet and Fatty Snacks in European Children and Adolescents.

BACKGROUND: Intake of sweet and fatty snacks may partly contribute to the occurrence of obesity and other health conditions in childhood. Traditional dietary assessment methods may be limited in accurately assessing the intake of sweet and fatty snacks in children. Metabolite biomarkers may aid the objective assessment of children's food intake and support establishing diet-disease relationships. OBJECTIVES: The present study aimed to identify biomarkers of sweet and fatty snack intake in 2 independent cohorts of European children. METHODS: We used data from the IDEFICS/I.Family cohort from baseline (2007/2008) and 2 follow-up examination waves (2009/2010 and 2013/2014). In total, 1788 urine samples from 599 children were analyzed for untargeted metabolomics using high-resolution liquid chromatography-mass spectrometry. Short-term dietary intake was assessed by 24-h dietary recalls, and habitual dietary intake was calculated with the National Cancer Institute method. Data from the Dortmund Nutritional and Anthropometric Longitudinal Designed (DONALD) cohort of 24-h urine samples (n = 567) and 3-d weighted dietary records were used for external replication of results. Multivariate modeling with unbiased variable selection in R algorithms and linear mixed models were used to identify novel biomarkers. Metabolite features significantly associated with dietary intake were then annotated. RESULTS: In total, 66 metabolites were discovered and found to be statistically significant for chocolate candy; cakes, puddings, and cookies; candy and sweets; ice cream; and crisps. Most of the features (n = 62) could not be annotated. Short-term and habitual chocolate intake were positively associated with theobromine, xanthosine, and cyclo(L-prolyl-L-valyl). These results were replicated in the DONALD cohort. Short-term candy and sweet intake was negatively associated with octenoylcarnitine. CONCLUSIONS: Of the potential metabolite biomarkers of sweet and fatty snacks in children, 3 biomarkers of chocolate intake, namely theobromine, xanthosine, and cyclo(L-prolyl-L-valyl), are externally replicated. However, these potential biomarkers require further validation in children.

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.

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.

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.

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.

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.

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.

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.

Analysis of associations between dietary patterns, genetic disposition, and cognitive function in data from UK Biobank.

PURPOSE: Research suggests that diet influences cognitive function and the risk for neurodegenerative disease. The present study aimed to determine whether a recently developed diet score, based on recommendations for dietary priorities for cardio metabolic health, was associated with fluid intelligence, and whether these associations were modified by individual genetic disposition. METHODS: This research has been conducted using the UK Biobank Resource. Analyses were performed using self-report data on diet and the results for the verbal-numerical reasoning test of fluid intelligence of 104,895 individuals (46% male: mean age at recruitment 57.1 years (range 40-70)). For each participant, a diet score and a polygenic score (PGS) were constructed, which evaluated predefined cut-offs for the intake of fruit, vegetables, fish, processed meat, unprocessed meat, whole grain, and refined grain, and ranged from 0 (unfavorable) to 7 (favorable). To investigate whether the diet score was associated with fluid intelligence, and whether the association was modified by PGS, linear regression analyses were performed. RESULTS: The average diet score was 3.9 (SD 1.4). After adjustment for selected confounders, a positive association was found between baseline fluid intelligence and PGS (P < 0.001). No association was found between baseline fluid intelligence and diet score (P = 0.601), even after stratification for PGS, or in participants with longitudinal data available (n = 9,482). CONCLUSION: In this middle-aged cohort, no evidence was found for an association between the investigated diet score and either baseline or longitudinal fluid intelligence. However, as in previous reports, fluid intelligence was strongly associated with a PGS for general cognitive function.

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.

Associations of Adherence to a Dietary Index Based on the EAT-Lancet Reference Diet with Nutritional, Anthropometric, and Ecological Sustainability Parameters: Results from the German DONALD Cohort Study.

BACKGROUND: Validation of the EAT-Lancet reference diet (ELR-diet), recently proposed by the EAT-Lancet Commission, within the context of real-life studies is necessary to elucidate its feasibility, nutritional value, sustainability, and health effects. OBJECTIVES: We aimed to develop a dietary index (DI) score to measure adherence to the ELR-diet. We further aimed to study the association between the DI score and 1) nutritional characteristics, 2) indicators of ecological sustainability, and 3) anthropometric markers and biomarkers for cardiometabolic health. METHODS: A DI score was constructed by comparing the categories defined by the ELR-diet with the dietary data of 2-5 sets of 3-d weighed dietary records from DONALD (Dortmund Nutritional and Anthropometric Longitudinal Designed) study participants (n = 298; ≥15 y of age). Prospective associations between the DI score and risk markers (anthropometric and cardiometabolic) in young adulthood (≥18 y old) were investigated using multivariate linear regression. RESULTS: Adherence to the DI score components was considerable (majority > 50%), but varied within the population (2%-100%). The highest tertile of the DI score was inversely associated with the intake of protein (tertile 3 compared with tertile 1: 13.5 compared with 14.5 energy %), added sugars (10.5 compared with 12.4 energy %), and cholesterol (100 compared with 116 mg/1000 kcal), but positively associated with fiber intake (10.0 compared with 8.82 g/1000 kcal) (all P < 0.05). The DI score was inversely associated with greenhouse-gas emissions (tertile 1 compared with tertile 3: 6.48 compared with 5.85 kg of carbon dioxide equivalents/2500 kcal; P < 0.001) and land use (8.24 compared with 7.16 m2 × y/2500 kcal; P < 0.001). Inverse associations between the DI score and anthropometric markers during young adulthood were observed (e.g., BMI: tertile 1 compared with tertile 3: 22.9 compared with 21.9 kg/m2; P = 0.03) (all P < 0.05). No associations between the DI score and cardiometabolic risk markers were found (all P ≥ 0.05). CONCLUSIONS: Adherence to the ELR-diet was associated with favorable nutritional characteristics and reduced environmental impact. Adherence to the DI score in adolescence was also beneficial with respect to anthropometric markers in early adulthood, although not for further cardiometabolic risk markers.

Cohort profile: the Food Chain Plus (FoCus) cohort.

The Food Chain Plus (FoCus) cohort was launched in 2011 for population-based research related to metabolic inflammation. To characterize this novel pathology in a comprehensive manner, data collection included multiple omics layers such as phenomics, microbiomics, metabolomics, genomics, and metagenomics as well as nutrition profiling, taste perception phenotyping and social network analysis. The cohort was set-up to represent a Northern German population of the Kiel region. Two-step recruitment included the randomised enrolment of participants via residents' registration offices and via the Obesity Outpatient Centre of the University Medical Center Schleswig-Holstein (UKSH). Hence, both a population- and metabolic inflammation- based cohort was created. In total, 1795 individuals were analysed at baseline. Baseline data collection took place between 2011 and 2014, including 63% females and 37% males with an age range of 18-83 years. The median age of all participants was 52.0 years [IQR: 42.5; 63.0 years] and the median baseline BMI in the study population was 27.7 kg/m2 [IQR: 23.7; 35.9 kg/m2]. In the baseline cohort, 14.1% of participants had type 2 diabetes mellitus, which was more prevalent in the subjects of the metabolic inflammation group (MIG; 31.8%). Follow-up for the assessment of disease progression, as well as the onset of new diseases with changes in subject's phenotype, diet or lifestyle factors is planned every 5 years. The first follow-up period was finished in 2020 and included 820 subjects.

A lifestyle score in childhood and adolescence was positively associated with subsequently measured fluid intelligence in the DONALD cohort study.

PURPOSE: Lifestyle scores which combine single factors such as diet, activity, or sleep duration showed associations with cognitive decline in adults. However, the role of a favourable lifestyle in younger age and the build-up of cognitive reserve is less clear, which is why we investigated longitudinal associations between a lifestyle score in childhood and adolescence and fluid intelligence obtained on average 6 years later. METHODS: In the DONALD cohort, a lifestyle score of 0 to 4 points including healthy diet and duration of moderate-to-vigorous physical activity, sedentary behaviour and sleep was repeatedly assessed in participants aged 5 and 19 years. Data on fluid intelligence were assessed via a German version of the culture fair intelligence test (CFT), using CFT 1-R in children 8.5 years of age or younger (n = 62) or CFT 20-R in participants older than 8.5 years (n = 192). Multivariable linear regression models were used to investigate prospective associations between the lifestyle score and the fluid intelligence score. RESULTS: Mean lifestyle score of all participants was 2.2 (0.7-4) points. A one-point increase in the lifestyle score was associated with a higher fluid intelligence score (4.8 points [0.3-7.3], p = 0.0343) for participants completing the CFT 20-R. Furthermore, each additional hour of sedentary behaviour was associated with a lower fluid intelligence score (- 3.0 points [- 5.7 to - 0.3], p = 0.0313). For younger participants (CFT 1-R), no association was found in any analysis (p > 0.05). CONCLUSION: A healthy lifestyle was positively associated with fluid intelligence, whereby sedentary behaviour itself seemed to play a prominent role.

Relative validity of a glycemic index extended food-frequency questionnaire.

BACKGROUND AND AIMS: The dietary glycemic index (GI) and glycemic load (GL) are increasingly recognized as important for the prevention and management of diabetes mellitus. To extend the portfolio of assessment methods for large-scale epidemiological studies, we propose a GI-specific addition to an already established FFQ. METHODS AND RESULTS: The German version of the EPIC-FFQ was extended by GI-specific questions for major carbohydrate sources varying notably in GI (breakfast cereals, bread, pasta, rice, potato etc.). We performed relative validation analyses comparing the GI-extended FFQ to three to four 3-day weighted dietary records (3-d WDR) in 100 middle-aged individuals with diabetes mellitus participating in the German Diabetes Study (GDS). Level of agreement between the two methods was assessed by correlation and cross-classification analyses as well as Bland-Altman-Plots, conducted separately for women and men. Spearman correlation analysis for female participants suggested good agreement between the GI-extended FFQ and 3-d WDRs for energy adjusted dietary GL (r = 0.52, p = 0.0004). For both women and men, agreement with the estimations of dietary GI, GL (for men) and carbohydrates from low and higher-GI food sources from the GI-extended FFQ was acceptable (r: 0.28-0.45). Classification of the dietary GI and GL in the opposite quartile was <10% comparing the GI-extended FFQ and 3-d WDR. Bland-Altman plots suggested a tendency for an overestimation of the dietary GI from the GI-extended FFQ in the lower GI-ranges, particularly for men. CONCLUSION: Compared to the 3-d WDR, the GI-extended FFQ showed a moderate to good relative validity for parameters of carbohydrate quality.

Salivary nitrate/nitrite and acetaldehyde in humans: potential combination effects in the upper gastrointestinal tract and possible consequences for the in vivo formation of N-nitroso compounds-a hypothesis.

Subsequent to the dietary uptake of nitrate/nitrite in combination with acetaldehyde/ethanol, combination effects resulting from the sustained endogenous exposure to nitrite and acetaldehyde may be expected. This may imply locoregional effects in the upper gastrointestinal tract as well as systemic effects, such as a potential influence on endogenous formation of N-nitroso compounds (NOC). Salivary concentrations of the individual components nitrate and nitrite and acetaldehyde are known to rise after ingestion, absorption and systemic distribution, thereby reflecting their respective plasma kinetics and parallel secretion through the salivary glands as well as the microbial/enzymatic metabolism in the oral cavity. Salivary excretion may also occur with certain drug molecules and food constituents and their metabolites. Therefore, putative combination effects in the oral cavity and the upper digestive tract may occur, but this has remained largely unexplored up to now. In this Guest Editorial, published evidence on exposure levels and biokinetics of nitrate/nitrite/NOx, NOC and acetaldehyde in the organism is reviewed and knowledge gaps concerning combination effects are identified. Research is suggested to be initiated to study the related unresolved issues.

Dietary Macronutrient Composition in Relation to Circulating HDL and Non-HDL Cholesterol: A Federated Individual-Level Analysis of Cross-Sectional Data from Adolescents and Adults in 8 European Studies.

BACKGROUND: Associations between increased dietary fat and decreased carbohydrate intake with circulating HDL and non-HDL cholesterol have not been conclusively determined. OBJECTIVE: We assessed these relations in 8 European observational human studies participating in the European Nutritional Phenotype Assessment and Data Sharing Initiative (ENPADASI) using harmonized data. METHODS: Dietary macronutrient intake was recorded using study-specific dietary assessment tools. Main outcome measures were lipoprotein cholesterol concentrations: HDL cholesterol (mg/dL) and non-HDL cholesterol (mg/dL). A cross-sectional analysis on 5919 participants (54% female) aged 13-80 y was undertaken using the statistical platform DataSHIELD that allows remote/federated nondisclosive analysis of individual-level data. Generalized linear models (GLM) were fitted to assess associations between replacing 5% of energy from carbohydrates with equivalent energy from total fats, SFAs, MUFAs, or PUFAs with circulating HDL cholesterol and non-HDL cholesterol. GLM were adjusted for study source, age, sex, smoking status, alcohol intake and BMI. RESULTS: The replacement of 5% of energy from carbohydrates with total fats or MUFAs was statistically significantly associated with 0.67 mg/dL (95% CI: 0.40, 0.94) or 0.99 mg/dL (95% CI: 0.37, 1.60) higher HDL cholesterol, respectively, but not with non-HDL cholesterol concentrations. The replacement of 5% of energy from carbohydrates with SFAs or PUFAs was not associated with HDL cholesterol, but SFAs were statistically significantly associated with 1.94 mg/dL (95% CI: 0.08, 3.79) higher non-HDL cholesterol, and PUFAs with -3.91 mg/dL (95% CI: -6.98, -0.84) lower non-HDL cholesterol concentrations. A statistically significant interaction by sex for the association of replacing carbohydrates with MUFAs and non-HDL cholesterol was observed, showing a statistically significant inverse association in males and no statistically significant association in females. We observed no statistically significant interaction by age. CONCLUSIONS: The replacement of dietary carbohydrates with fats had favorable effects on lipoprotein cholesterol concentrations in European adolescents and adults when fats were consumed as MUFAs or PUFAs but not as SFAs.

Advances in dietary pattern analysis in nutritional epidemiology.

BACKGROUND AND PURPOSE: It used to be a common practice in the field of nutritional epidemiology to analyze separate nutrients, foods, or food groups. However, in reality, nutrients and foods are consumed in combination. The introduction of dietary patterns (DP) and their analysis has revolutionized this field, making it possible to take into account the synergistic effects of foods and to account for the complex interaction among nutrients and foods. Three approaches of DP analysis exist: (1) the hypothesis-based approach (based on prior knowledge regarding the current understanding of dietary components and their health relation), (2) the exploratory approach (solely relying on dietary intake data), and (3) the hybrid approach (a combination of both approaches). During the recent past, complementary approaches for DP analysis have emerged both conceptually and methodologically. METHOD: We have summarized the recent developments that include incorporating the Treelet transformation method as a complementary exploratory approach in a narrative review. RESULTS: Uses, peculiarities, strengths, limitations, and scope of recent developments in DP analysis are outlined. Next, the narrative review gives an overview of the literature that takes into account potential relevant dietary-related factors, specifically the metabolome and the gut microbiome in DP analysis. Then the review deals with the aspect of data processing that is needed prior to DP analysis, particularly when dietary data arise from assessment methods other than the long-established food frequency questionnaire. Lastly, potential opportunities for upcoming DP analysis are summarized in the outlook. CONCLUSION: Biological factors like the metabolome and the microbiome are crucial to understand diet-disease relationships. Therefore, the inclusion of these factors in DP analysis might provide deeper insights.

Validation of the web-based self-administered 24-h dietary recall myfood24-Germany: comparison with a weighed dietary record and biomarkers.

PURPOSE: We aimed to validate myfood24-Germany, a web-based 24-h dietary recall (24HDR), by comparing its performance with a weighed dietary record (WDR) and biomarkers. METHODS: 97 adults (77% female) completed a 3-day WDR with a 24-h urine collection on day 3, followed by at least one 24HDR with myfood24-Germany (corresponding to day 3 of the WDR). Intake of energy and 32 nutrients assessed by myfood24-Germany and the WDR for the same day were compared (method comparison). Intakes of protein and potassium assessed by myfood24-Germany/WDR were compared with intake estimated from urinary biomarkers for protein and potassium (biomarker comparison). RESULTS: In the method comparison, significant correlations were found for energy and all tested nutrients (range 0.45-0.87). There was no significant difference between both methods in the assessed mean energy and macronutrient intake. However, myfood24-Germany underestimated mean intake of 15 nutrients. In the biomarker comparison, protein intake reported by myfood24-Germany/WDR was on average 10%/8% lower than estimated by biomarker. There was no significant difference in mean potassium intake assessed by myfood24-Germany/WDR and biomarker. However, a shared bias in the assessment of potassium intake was observed for both instruments. Concordance correlation coefficients (pc) and weighted Kappa coefficients (κ) confirmed good agreement with the biomarker estimates for myfood24-Germany/WDR in case of protein (pc = 0.58/0.66, κ = 0.51/0.53) and moderate agreement in case of potassium (pc = 0.44/0.51; κ = 0.30/0.33). CONCLUSION: Our results suggest that myfood24-Germany is of comparable validity to traditional dietary assessment methods.

Relevance of fructose intake in adolescence for fatty liver indices in young adulthood.

PURPOSE: To examine the association between fructose intake in adolescence and fatty liver indices (hepatic steatosis index (HSI), fatty liver index (FLI)) in young adulthood. METHODS: Overall, 246 participants of the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study who had a fasting blood sample in adulthood (18-36 years), at least two 3-day weighed dietary records for calculating fructose intakes and other fructose-containing sugars (total (TS), free (FS), added sugar (AS)) as well as two complete 24-h urine samples for calculating sugar excretion (fructose excretion (FE), fructose + sucrose excretion (FE + SE)) in adolescence (males: 9.5-16.5 years; females: 8.5-15.5 years) were analysed using multivariable linear regression analyses. RESULTS: On the level of dietary intake, no prospective associations were observed between adolescent fructose intake and both adult fatty liver indices, whereas higher FS intakes were associated with lower levels of HSI (Ptrend = 0.02) and FLI (Ptrend = 0.03). On the urinary excretion level, however, a higher FE (Ptrend = 0.03) and FE + SE (Ptrend = 0.01) in adolescence were prospectively related to higher adult FLI values. No associations were observed between adolescent sugar excretion and adult HSI. CONCLUSION: The present study does not provide unambiguous support for a detrimental impact of adolescent fructose intake on adult liver health. Nonetheless, further examinations estimating exposure by means of urinary excretion as well as dietary intake levels appear warranted.