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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., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background/objectivesFormulas developed to estimate diet-dependent net acid excretion (NAE) generally agree with measured values for typical Western diets. Whether they can also appropriately predict NAE for 'Paleolithic-type' (Paleo) diets-which contain very high amounts of fruits and vegetables (F&V) and concurrent high amounts of protein is unknown. Here, we compare measured NAEs with established NAE estimates in subjects with Type 2 diabetes (T2D).Subjects/methodsThirteen subjects with well-controlled T2D were randomized to either a Paleo or American Diabetes Association (ADA) diet for 14 days. Twenty-four hour urine collections were performed at baseline and end of the diet period, and analyzed for titratable acid, bicarbonate and ammonium to calculate measured NAE. Three formulas for estimating NAE from dietary intake were used; two (NAE_diet R or L) that include dietary mineral intake and sulfate- and organic acid (OA) production, and one that is empirically derived (NAE_diet F) only considering potassium and protein intake.ResultsMeasured NAE on the Paleo diet was significantly lower than on the ADA-diet (+31±22 vs 112±52 mEq/day, P=0.002). Although all formula estimates showed similar and reasonable correlations (r=0.52-0.76) with measured NAE, each one underestimated measured values. The formula with the best correlation did not contain an estimate of dietary OA production.ConclusionsPaleo-diets are lower in NAE than typical Western diets. However, commonly used formulas clearly underestimate NAE, especially for diets with very high F&V (as the Paleo diet), and in subjects with T2D. This may be due to an inappropriate estimation of proton loads stemming from OAs, underlining the necessity for improved measures of OA-related proton sources.

High dietary phosphorus intake (P-In) and high acid loads may adversely affect kidney function. In animal models, excessive phosphorus intake causes renal injury, which, in humans, is also inducible by chronic metabolic acidosis. We thus examined whether habitually high P-In and endogenous acid production during childhood and adolescence may be early indicators of incipient renal inflammatory processes later in adulthood. P-In and acid-base status were longitudinally and exclusively determined by biomarker-based assessment in 277 healthy children, utilizing phosphate and net acid excretion (NAE) measurements in 24 h urine samples repeatedly collected between the ages of 3 and 17 years. Standard deviation scores (by sex and age) were calculated for anthropometric data and for the urinary biomarkers available within age range 3-17 years. Multivariable linear regression was used to analyze the relations of phosphate excretion and NAE with the adulthood outcome circulating interleukin-18 (IL-18), a marker of inflammation and kidney dysfunction. After adjusting for growth- and adulthood-related covariates and pro-inflammatory biomarkers to rule out confounding by non-renal inflammatory processes, regression models revealed a significant positive relationship of long-term NAE ( p = 0.01), but not of long-term phosphate excretion with adult serum IL-18. Similar significant positive regression results were obtained after replacing NAE with 24 h urinary ammonium excretion as the exposition variable. Our results suggest that even moderate elevations in renal ammonia production, as caused by habitually higher acid loading during growth, may affect the intrarenal pro-inflammatory system in the long-term, known to be boosted by acidosis-induced raised ammoniagenesis.

BACKGROUND/OBJECTIVES: The [sup.13]C mixed triglyceride (MTG) breath test has been proposed for the non-invasive assessment of fat digestion and absorption. To evaluate whether reference values for the adequacy of fat absorption, set in the non-dispersive infrared spectrometry (NDIRS) system software proposed for healthy children and adults using the [sup.13]C MTG breath test, are also applicable to infants of < 5 months of age. SUBJECTS/METHODS: [sup.13]C MTG breath testing with the NDIRS technique was performed in 54 healthy infants < 5 months of age (38 breast-fed, 16 formula-fed) and six infants diagnosed with cystic fibrosis (CF) using two NDIRS devices, IRIS and FANci2. RESULTS: The IRIS results were slightly higher compared with those assessed by the FANci2 device. The minimum cutoff value for pancreatic sufficiency (PS) is set as a cumulative percentage dose of [sup.13]C recovered (cPDR) after 5 h of 13.0%. Pancreatic function status of six CF infants, three with PS and three with pancreatic insufficiency (PI), according to the 72 h-faecal fat balance test could be correctly determined with the [sup.13]C MTG breath test using two NDIRS techniques. However, if these reference values had been used to determine pancreatic function status in healthy infants, 26 out of 54 infants would have been misclassified as pancreatic insufficient. CONCLUSIONS: Although the [sup.13]C MTG breath test with the MS technique has the potential to be a suitable assessment of fat absorption in infants, the technique of NDIRS appears too insensitive in an infant population group. European Journal of Clinical Nutrition (2016) 70, 959-962; doi:10.1038/ejcn.2015.228; published online 13 January 2016, INTRODUCTION Stable isotope breath tests are designed to offer a safe, simple, repeatable and non-invasive way for the clinical investigation of fat malabsorption due to impaired digestion or mucosal absorption. [...]

BACKGROUND/OBJECTIVES: The assessment of urinary excretion of specific nutrients (e.g. iodine, sodium) is frequently used to monitor a population's nutrient status. However, when only spot urines are available, always a risk of hydration-status-dependent dilution effects and related misinterpretations exists. The aim of the present study was to establish mean values of 24-h creatinine excretion widely applicable for an appropriate estimation of 24-h excretion rates of analytes from spot urines in adults. SUBJECTS/METHODS: Twenty-four-hour creatinine excretion from the formerly representative cross-sectional German VERA Study (n = 1463, 20-79 years old) was analysed. Linear regression analysis was performed to identify the most important influencing factors of creatinine excretion. In a subsample of the German DONALD Study (n = 176, 20-29 years old), the applicability of the 24-h creatinine excretion values of VERA for the estimation of 24-h sodium and iodine excretion from urinary concentration measurements was tested. RESULTS: In the VERA Study, mean 24-h creatinine excretion was 15.4 mmol per day in men and 11.1 mmol per day in women, significantly dependent on sex, age, body weight and body mass index. Based on the established 24-h creatinine excretion values, mean 24-h iodine and sodium excretions could be estimated from respective analyte/creatinine concentrations, with average deviations < 10% compared with the actual 24-h means. CONCLUSIONS: The present mean values of 24-h creatinine excretion are suggested as a useful tool to derive realistic hydrationstatus-independent average 24-h excretion rates from urinary analyte/creatinine ratios. We propose to apply these creatinine reference means routinely in biomarker-based studies aiming at characterizing the nutrient or metabolite status of adult populations by simply measuring metabolite/creatinine ratios in spot urines. European Journal of Clinical Nutrition (2015) 69, 1336-1343; doi: 10.1038/ejcn.2015.121; published online 29 July 2015, INTRODUCTION Epidemiological population-based studies frequently aim to estimate dietary intakes of nutrients or dietary components. Regarding this, the classic dietary assessment methods such as dietary records, food frequency questionnaires or [...]

Purpose: Changes in dietary protein intake metabolically affect kidney functions. However, knowledge on potential adverse consequences of long-term higher protein intake (HPI) for kidney health is lacking. To summarise and evaluate the available evidence for a relation between HPI and kidney diseases, an umbrella review of systematic reviews (SR) was conducted., Methods: PubMed, Embase and Cochrane Database of SRs published until 12/2022 were searched for the respective SRs with and without meta-analyses (MA) of randomised controlled trials or cohort studies. For assessments of methodological quality and of outcome-specific certainty of evidence, a modified version of AMSTAR 2 and the NutriGrade scoring tool were used, respectively. The overall certainty of evidence was assessed according to predefined criteria., Results: Six SRs with MA and three SRs without MA on various kidney-related outcomes were identified. Outcomes were chronic kidney disease, kidney stones and kidney function-related parameters: albuminuria, glomerular filtration rate, serum urea, urinary pH and urinary calcium excretion. Overall certainty of evidence was graded as 'possible' for stone risk not to be associated with HPI and albuminuria not to be elevated through HPI (above recommendations (> 0.8 g/kg body weight/day)) and graded as 'probable' or 'possible' for most other kidney function-related parameters to be physiologically increased with HPI., Conclusion: Changes of the assessed outcomes may have reflected mostly physiological (regulatory), but not pathometabolic responses to higher protein loads. For none of the outcomes, evidence was found that HPI does specifically trigger kidney stones or diseases. However, for potential recommendations long-term data, also over decades, are required., (© 2023. The Author(s).)

Background: Salt reduction campaigns without a parallel increase of iodine fortification will lead to a worsened iodine status in countries with a relevant salt iodization. A decline in iodine supply bears the risk of higher prevalences of goiter, thyroid nodules, and cognitive delay in children. Against this background, we analyzed the contribution of iodized salt to total iodine and salt intake in Germany and compared the results with data from Switzerland., Methods: Analyses were performed with data of the representative German Health-Interview and Examination-Survey for Adults (DEGS1, 2008-2011) using spot urine measurements of creatinine, iodine, and sodium (n = 6738). Median daily iodine and salt intakes were calculated by estimating 24-h iodine and sodium excretions from urinary analyte/creatinine ratios. Linear regressions were used to deduce iodine intake that originates from iodine containing foods (i.e., salt-independent iodine). From this, ingested iodine originating from salt and the proportion of iodized salt to total salt intake were calculated. Data from Switzerland were obtained from the literature., Results: In Germany, only 42% (52.2 µg/d) of the predicted median total iodine intake (126.2 µg/d), i.e., 12% less than in Switzerland, were found to originate from salt, whereas 73.7 µg/d came from iodine containing foods. 28% (2.6 g/d) of the median salt intake (9.3 g/d) of the German population was calculated to represent iodized salt against 43% in Switzerland., Conclusions: Along with an almost identical inherent iodine intake in Germany and Switzerland, the average total iodine intake, the contribution of iodized salt to total iodine intake, and the proportion of iodized salt to total salt are higher in Switzerland than in Germany. Despite this, iodine fortification of table salt has recently been increased in Switzerland from 20 to 25 mg/kg to ensure iodine sufficiency in the population, whereas in Germany fortification still remains at a mean level of 20 mg/kg implying a growing risk of increasing iodine deficiency rates if general salt intake drops.

Background: Overweight and higher BMI are known to be related to increased blood pressure (BP) and additionally associate with lowered urine pH values even at comparable total daily acid loading. Since a reduced urine pH level at a given total acid load indicates an impaired renal net acid excretion capacity (NAEC) and renal function also relates to BP, we hypothesized that NAEC may be one mediator of the body fat-BP association., Methods: Ammonium, titratable acid, pH, creatinine, and urea were measured in 24-h urine samples among 9-15-year-old adolescents of the DONALD Study. NAEC was determined as residual of the body surface area-corrected net acid excretion on urine pH (NAEC1) or body surface area-corrected ammonium excretion on urine pH (NAEC2). Markers of body fatness were determined anthropometrically and systolic and diastolic BP sphygmomanometrically. Multilinear regressions were used to examine cross-sectionally the body fat-NAEC and prospectively the NAEC1-BP associations., Results: All body fat parameters were inversely associated with both NAEC1 and NAEC2 among youth (P ≤ 0.01). In a separate prospective analyses, to check for possible mediation, higher adolescent NAEC1 was significantly associated with lower systolic BP in male adults only (P = 0.04), but this association was attenuated to a trend (P = 0.07) in multivariable-adjusted models., Conclusions: Independent of systemic acid load, NAEC, i.e., the kidney's function to eliminate acids is reduced with higher body fatness, and may also contribute as a mediator in the body fatness-BP relation.

Background/objective: Preliminary interventional data suggest that a reduction of dietary acid load raises renal uric acid excretion and decreases serum uric acid (SUA). In line with this, in a recent cross-sectional analysis of a representative adult population sample, a higher potential renal acid load (PRAL) was found to associate with higher SUA levels. Against this background, we re-examined the relationship of the body's acid load with SUA and hyperuricemia using nutrition-derived estimates of renal net acid excretion (NAE)., Subjects/methods: Cross-sectional analyses were performed in n = 6894 participants (18-79 y) of the German Health Interview and Examination Survey for Adults (DEGS1). Two different approaches were used to estimate NAE, one based on the sum of food frequency questionnaire (FFQ)-derived PRAL and body-surface area-derived organic acids (eNAE PRAL+OA ) and the other based on FFQ-derived protein and potassium intake ratios (eNAE Prot/K ). The associations of eNAE PRAL+OA and eNAE Prot/K with SUA were analyzed in multiple linear regression models. Multiple logistic regressions were used to calculate odds ratios (OR) for hyperuricemia comparing higher (T3) and lower (T1) tertiles of the NAE estimates., Results: After adjusting for relevant confounders, eNAE PRAL+OA (p = 0.0048) and eNAE Prot/K (p = 0.0023) were positively associated with SUA. In addition, participants with a higher eNAE PRAL+OA or eNAE Prot/K had higher ORs for having hyperuricemia (OR: 1.73, 95% CI: 1.24-2.40, OR: 1.51, 95% CI: 1.10-2.08, respectively)., Conclusion: The results substantiate findings of a previous analysis that dietary acid load is a potential influencing factor on SUA. This implicates that a lower dietary acid load may have beneficial effects on SUA.

Discovered about 50 years ago, the four C 21 steroidal acids (α-)cortolic acid, β-cortolic acid, (α‑)cortolonic acid and β-cortolonic acid present the oxidative end products of cortisol metabolism. Undergoing renal elimination, these cortoic acids have been assumed to constitute up to 25 % of total urinary cortisol metabolites. However, their analysis has been difficult, only few data has been published in adults, and this class of steroids has become practically forgotten. Since data in children are lacking and nothing is known about their metabolism during human development, we aimed at establishing a more practical analytical method and determined their urinary concentrations in a high number of healthy subjects. In our method, 5-mL-aliquots of 24-hour urine samples were subjected to solid phase extraction (C18 cartridges), followed by strong anion exchange chromatography, and formation of 2-propylester-trimethylsilylether derivatives (2-PR/TMS). The cortoic acids were quantified by targeted gas chromatography-mass spectrometry (GC-MS) using a nonpolar GC column and selected ion monitoring (SIM). Baseline separation of all cortoic acids was achieved. Calibration graphs were linear (R 2 > 0.98). Variations in precision and accuracy were less than 15 %, respectively. The detection limit was 100 pg (injected) with a signal-to-noise ratio of 3. 240 specimens from 24-hour urine collections from healthy children (120 boys, 120 girls, aged 3-18 years; DONALD study) were analyzed for cortoic acids and neutral cortisol metabolites to create first reference ranges. The profile of cortoic acids was dominated by α-cortolonic acid with excretion rates up to 70 µg/d. Absolute excretion rates of cortoic acids increased with age, their total excretion rates ranged between 11.0 and 127.3 µg/d (median 45.7 µg/d), but did not show any sexual dimorphism. Since cortoic acids make up only about 1 % of total urinary cortisol metabolites, determination of neutral urinary steroids reliably allows assessment of cortisol production. However, cortoic acids might present potential biomarkers of the body's redox state., (Copyright © 2022. Published by Elsevier Ltd.)

Both veganism and high dietary acid load are linked to unfavorable bone health. However, the specific role of dietary alkali or acid load for the bone health of vegans is so far unknown. Thus, the renal biomarker for dietary acid or alkali load, i.e., urinary potential renal acid load (uPRAL), was measured in 24 h urine samples of 34 vegans and 35 omnivores (50.7% males). Bone health was assessed via calcaneal quantitative ultrasound. Associations between uPRAL and bone health indices were examined using multivariable general linear models. Compared to omnivores, vegans had a significantly lower uPRAL (mean difference = −34.5 mEq/24 h, p < 0.0001), a lower 24 h urinary phosphate excretion (p = 0.0004), a lower 24 h urinary sulfate excretion (p = 0.01), and a higher urine pH value (p < 0.0001). Broadband ultrasound attenuation (BUA) was lower among vegans versus omnivores (p = 0.037), yet it was not associated with uPRAL irrespective of adjustments. This study confirms different acid-base profiles of vegans and omnivores, with a pronounced alkaline excess among vegans and a rather low acid load among a group of omnivores with moderate protein intake. Within this spectrum of alkaline to low acid load, no association with bone health was found.

Eating a net acid-producing diet can produce an "acid stress" of severity proportional to the diet net acid load, as indexed by the steady-state renal net acid excretion rate. Depending on how much acid or base is ingested or produced from endogenous metabolic processes and how well our homeostatic mechanisms can buffer or eliminate the additional acids or bases, we can alter our systemic acid-base balance. With increasing age, the kidney's ability to excrete daily net acid loads declines (a condition similar to that of mild CKD), invoking increased utilization of potential base stores (eg, bone, skeletal muscle) on a daily basis to mitigate the acid accumulation, thereby contributing to development of osteoporosis, loss of muscle mass, and age-related renal insufficiency. Patients suffering from more advanced CKD often present with more severe acid stress or metabolic acidosis, as the kidney can no longer excrete the entire acid load. Alkaline diets based on fruits and vegetables may have a positive effect on long-term preservation of renal function while maintaining nutritional status. This chapter discusses the biochemistry of dietary precursors that affect acid or base production., (Copyright © 2022 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Context: Varying protein intake is known to influence human height growth. However, whether a habitually higher protein intake consistently above dietary recommendations during childhood and adolescence affects adult stature is not known., Objective: To examine whether protein intake in excess of recommendations from childhood onward may exert an anabolic effect on adult stature., Methods: We examined habitual protein intake based on 3-day weighed dietary records and 24-hour urinary biomarker excretions in a longitudinal cohort of 189 healthy individuals aged between 3 and 17 years (analyzing 11 diet recordings and 11 24-urine samples per child on average). Urinary urea nitrogen (uN) excretion was used as a biomarker for protein intake. Multilinear regressions were applied to examine the prospective associations of average total and average animal protein intake during growth with the outcome adult height (AH) after adjusting for parental heights, energy intake, dietary potential renal acid load (PRAL), and pubertal, early-life, and socioeconomic factors., Results: Mean SD scores of total (P = .001) and animal (P < .0001) protein intake as well as uN (P = .01) were prospectively and independently related to adult height in girls, but not in boys. Also for girls only, the fully adjusted regression for renal biomarkers (R2total = 0.79) indicated an inverse relationship between AH and the urinary biomarker for dietary acidity PRAL (P = .06)., Conclusion: Our prospective, biomarker-confirmed findings on habitual protein intake during the pediatric period provide evidence that protein ingestion above dietary recommendation contributes to an enhanced AH in girls. This enhancement, in turn, may be weakened by an insufficient alkalizing potential through PRAL-raising fruit- and vegetable-poor nutrition., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Mild-to-moderate iodine deficiency was present in large parts of Germany up to the beginning 1990s and improved from then on. Current epidemiological data on spot urine iodine measurements in German children strongly suggest the re-occurrence of an impaired iodine status. We thus examined whether this re-occurrence is identifiable in more detail, through iodine analyses of 24-h urine samples of a well-characterized cohort of German children in whom samples have been systematically collected from 1985 onward. As iodized salt is a major source for iodine supply, urinary sodium excretion was additionally studied., Methods: Daily iodine and sodium excretions were measured in 2600 24-h urine samples collected between 1985 and 2018 by 677 healthy children aged 6-12 years (participants of the DONALD study). These data were compared with 24-h iodine and sodium excretion estimates obtained from spot urine samples collected in the representative German Health Interview and Examination Surveys for Children and Adolescents KiGGS-baseline (2003-2006) and KiGGS-wave-2 (2014-2017)., Results: Between 1985 and1992, DONALD participants started with a median daily iodine excretion level of 40.1 µg/d. Then, during 1993-2003, iodine excretions mounted up to an approximate plateau (~ 84.8 µg/d). This plateau lasted until 2012. Thereafter, iodine concentrations started to decrease again resulting in a median iodine excretion of only 58.9 µg/d in 2018. Sodium excretion, however, had increased. The marked decrease in iodine status along with an abundant sodium excretion corresponded closely with nationwide KiGGS data., Conclusions: As exemplified for the clearly worsening iodine status in German children, longitudinal cohort studies collecting detailed biomarker-based prospective data have the potential to reliably capture health-relevant nutritional changes and trends, applicable on a more comprehensive and even representative population level., (© 2022. The Author(s).)

Purpose: The present work aimed to delineate (i) a revised protocol according to recent methodological developments in evidence generation, to (ii) describe its interpretation, the assessment of the overall certainty of evidence and to (iii) outline an Evidence to Decision framework for deriving an evidence-based guideline on quantitative and qualitative aspects of dietary protein intake., Methods: A methodological protocol to systematically investigate the association between dietary protein intake and several health outcomes and for deriving dietary protein intake recommendations for the primary prevention of various non-communicable diseases in the general adult population was developed., Results: The developed methodological protocol relies on umbrella reviews including systematic reviews with or without meta-analyses. Systematic literature searches in three databases will be performed for each health-related outcome. The methodological quality of all selected systematic reviews will be evaluated using a modified version of AMSTAR 2, and the outcome-specific certainty of evidence for systematic reviews with or without meta-analysis will be assessed with NutriGrade. The general outline of the Evidence to Decision framework foresees that recommendations in the derived guideline will be given based on the overall certainty of evidence as well as on additional criteria such as sustainability., Conclusion: The methodological protocol permits a systematic evaluation of published systematic reviews on dietary protein intake and its association with selected health-related outcomes. An Evidence to Decision framework will be the basis for the overall conclusions and the resulting recommendations for dietary protein intake., (© 2022. The Author(s).)

Background: The iodine status of populations is usually assessed by median urinary iodine concentrations (UIC) in population-based studies, but it is unclear to which extent UIC are comparable across different laboratories. The aim of our study was to investigate the variability of UIC measurements across three well-established German laboratories with long-term clinical-chemical expertise in iodine measurements and to compare these results to the gold standard inductively coupled plasma mass spectrometry (ICP-MS)., Methods: UIC levels were measured from 303 urine samples derived from the "Dortmund Nutritional and Anthropometric Longitudinally Designed Study" and from volunteers of the University Medicine Greifswald at four different German laboratories. Three of these laboratories used Sandell-Kolthoff reaction with different digestion methods for UIC measurement (Lab1-Lab3), whereas one laboratory used ICP-MS as gold standard., Results: Median UIC levels were significantly different across the four laboratories (ICP-MS: 77 μg/L; Lab1: 69 μg/L; Lab2: 73 μg/L; Lab3: 111 μg/L). Linear regressions associating UIC levels of Lab1-Lab3 with UIC levels of ICP-MS showed intercepts significantly different from 0 and slopes significantly different from 1. Intraclass correlations (ICC) in comparison to ICP-MS were 0.91 for Lab1, 0.98 for Lab2, and 0.69 for Lab3. Using the digestion method of Lab2 in Lab3 improved the comparison of UIC levels of Lab3 with those from the ICP-MS (ICC=0.89)., Conclusions: We have demonstrated larger interlaboratory variations across high-quality laboratories with long-lasting experience in iodine measurements indicating a relevant non-comparability of UIC measurements in iodine monitoring studies. Therefore, standardization of UIC measurements has to be expedited.

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 (P trend  = 0.02) and FLI (P trend  = 0.03). On the urinary excretion level, however, a higher FE (P trend  = 0.03) and FE + SE (P trend  = 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., (© 2021. The Author(s).)

Background and Aims: Early life exposures could be pertinent risk factors of cardiometabolic diseases in adulthood. We assessed the prospective associations of early life factors with markers of cardiometabolic risk among healthy German adults., Methods and Results: We examined 348 term-born DONALD Study participants with measurement of fasting blood at the age of 18-24 years to assess metabolic indices: fatty liver index (FLI), hepatic steatosis index (HSI), pro-inflammatory score and insulin sensitivity (HOMA2-%S). Early life factors (maternal weight in early pregnancy, maternal early pregnancy BMI, gestational weight gain (GWG), maternal age, birth weight and full breastfeeding (>17 weeks)) were assessed at enrolment of the offspring into the study. Multivariable linear regression models were used to analyze associations between early life factors and markers of cardiometabolic risk in early adulthood with adjustment for potential confounders. A higher early pregnancy BMI was related to notably higher levels of offspring FLI, HSI, pro-inflammatory score and a lower HOMA2-%S (all p < 0.0001). Similarly, a higher gestational weight gain was associated with a higher FLI (p = 0.044), HSI (p = 0.016), pro-inflammatory score (p = 0.032) and a lower HOMA2-%S among females (p = 0.034). Full breastfeeding was associated with a lower adult FLI (p = 0.037). A casual mediation analysis showed that these associations were mediated by offspring adult waist circumference (WC)., Conclusion: This study suggests that early pregnancy BMI, gestational weight gain, and full breastfeeding are relevant for offspring markers of cardiometabolic risk which seems to be mediated by body composition in young adulthood., Competing Interests: Declaration of competing interest A.E.B. is a member of the International Carbohydrate Quality Consortium. All other authors declare no conflicts of interest., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Purpose: To examine the prospective relevance of dietary sugar intake (based on dietary data as well as urinary excretion data) in adolescent years for insulin sensitivity and biomarkers of inflammation in young adulthood. Methods: Overall 254 participants of the DONALD study who had at least two 3-day weighed dietary records for calculating intakes of fructose, glucose, sucrose, total, free, added sugars, total sugars from sugar-sweetened beverages (SSB), juice, and sweets/sugar or at least two complete 24 h urine samples ( n = 221) for calculating sugar excretion (urinary fructose and urinary fructose + sucrose) in adolescence (females: 9-15 years, males: 10-16 years) and a fasting blood sample in adulthood (18-36 years), were included in multivariable linear regression analyses assessing their prospective associations with adult homeostasis model assessment insulin sensitivity (HOMA2-%S) and a pro-inflammatory score (based on CRP, IL-6, IL-18, leptin, chemerin, adiponectin). Results: On the dietary intake level, no prospective associations were observed between adolescent fructose, sucrose, glucose, added, free, total sugar, or total sugar from SSB, juice or sweets/sugar intake and adult HOMA2-%S ( p > 0.01). On the urinary level, however, higher excreted fructose levels were associated with improved adult HOMA2-%S ( p = 0.008) among females only. No associations were observed between dietary or urinary sugars and the adult pro-inflammatory score ( p > 0.01). Conclusion: The present study did not provide support that dietary sugar consumed in adolescence is associated with adult insulin sensitivity. The one potential exception was the moderate dietary consumption of fructose, which showed a beneficial association with adult fasting insulin and insulin sensitivity., Competing Interests: AB is a member of the International Carbohydrate Quality Consortium (ICQC) and a member of the Carbohydrate Task Force, ILSI Europe. GK received a funding from Mars, Inc. for unrelated research on flavan-3-ols. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Della Corte, Penczynski, Kuhnle, Perrar, Herder, Roden, Wudy, Remer, Alexy and Buyken.)

A lower 24-h urine pH (24h-pH), i.e., a higher renal excretion of free protons, at a given acid load to the body, denotes a reduction in the kidney's capacity for net acid excretion (NAE). There is increasing evidence, not only for patients with type 2 diabetes but also for healthy individuals, that higher body fatness or waist circumference (WC) has a negative impact on renal function to excrete acids (NAE). We hypothesized that adiposity-related inflammation molecules might mediate this relation between adiposity and renal acid excretion function. Twelve biomarkers of inflammation were measured in fasting blood samples from 162 adult participants (18-25 yr old) of the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study who had undergone anthropometric measurements and collected 24-h urine samples. Both Baron and Kenny's (B&K's) steps to test mediation and causal mediation analysis were conducted to examine the potential mediatory roles of biomarkers of inflammation in the WC-24-h pH relationship after strictly controlling for laboratory-measured NAE. In B&K's mediation analysis, leptin, soluble intercellular adhesion molecule 1 (sICAM-1), and adiponectin significantly associated with the outcome 24-h pH and attenuated the WC-pH relation. In agreement herewith, causal mediation analysis estimated the "natural indirect effects" of WC on 24-h pH via leptin ( P = 0.01) and adiponectin ( P = 0.03) to be significant, with a trend for sICAM-1 ( P = 0.09). The calculated proportions mediated by leptin, adiponectin, and sICAM-1 were 64%, 23%, and 12%, respectively. Both mediation analyses identified an inflammatory cytokine (leptin) and an anti-inflammatory cytokine (adiponectin) along with sICAM-1 as being potentially involved in mediating adiposity-related influences on renal acid excretion capacity.

Trend analyses based on dietary records suggest decreases in the intakes of total sugar (TS), added and free sugar since 2005 among children and adolescents in Germany. In terms of age trends, TS intake decreased with increasing age. However, self-reported sugar intake in epidemiological studies is criticised, as it may be prone to bias due to selective underreporting. Furthermore, adolescents are more susceptible to underreporting than children. We thus analysed time and age trends in urinary fructose excretion (FE), sucrose excretion (SE) and the sum of both (FE + SE) as biomarkers for sugar intake among 8·5-16·5-year-old adolescents. Urinary sugar excretion was measured by UPLC-MS/MS in 997 24-h urine samples collected from 239 boys and 253 girls participating in the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study cohort between 1990 and 2016. Time and age trends of log-transformed FE, SE and FE + SE were analysed using polynomial mixed-effects regression models. Between 1990 and 2016, FE as well as FE + SE decreased (linear time trend: P = 0·0272 and P < 0·0001, respectively). A minor increase in excretion during adolescence was confined to FE (linear age trend: P = 0·0017). The present 24-h excretion measurements support a previously reported dietary record-based decline in sugar intake since 2005. However, the previously seen dietary record-based decrease in TS from childhood to late adolescence was not confirmed by our biomarker analysis, suggesting a constant sugar intake for the period of adolescence.

Background: Early life factors may predispose an offspring to cardiovascular disease in later life; relevance of these associations may extend to ‟healthy" people in Western populations. We examined the prospective associations between early life factors and adult carotid intima-media thickness (IMT), a surrogate marker of atherosclerosis, in a healthy German population., Methods: We studied term participants (n = 265) of the DONALD Study, with bilateral sonographic measurements of IMT (4-8 measurements on both left and right carotid artery) at age 18-40 years and prospectively collected data on early life factors (maternal and paternal age at child birth, birth weight, gestational weight gain and full breastfeeding (>17weeks). Mean IMT values were averaged from mean values of both sides. Associations between early life factors and adult IMT were analyzed using multivariable linear regression models with adjustment for potential confounders., Results: Adult mean IMT was 0.56mm, SD 0.03, (range: 0.41 mm-0.78 mm). Maternal age at child birth was of relevance for adult IMT, which was sex specific: Advanced maternal age at child birth was associated with an increased adult IMT among female offspring only (β 0.03, SE 0.009 mm/decade, P = 0.003), this was not affected by adult waist circumference, BMI or blood pressure. Other early life factors were not relevant for IMT levels in males and females., Conclusion: This study suggests that advanced maternal age at child birth is of prospective relevance for adult IMT levels in a healthy German population and this association may be of adverse relevance for females only., Competing Interests: The authors have declared that no competing interests exist.

Background: In patients with Cushing disease, renal citrate excretion is reduced. A low urinary citrate concentration is a risk factor for nephrolithiasis. Since higher acid loading is one major determinant of reduced citrate excretion, we aimed to examine whether glucocorticoids still within the physiological range may already impact on urinary citrate excretion independently of acid-base status., Methods: Overall, 132 healthy prepubertal participants of the DOrtmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study who had collected two successive 24-h urine samples (at 1 and 2 years) before the start of their pubertal growth spurt were included in the study. Net acid excretion capacity (NAEC), urinary potential renal acid load (PRAL), creatinine, calcium, and various cortisol metabolites were measured in all samples. Glucocorticoid quantification was done by GC-MS and radioimmunoassay., Results: In regression models multivariable-adjusted for 24-h urinary PRAL, NAEC, creatinine and calcium, urinary free cortisol (UFF), 6β-hydroxycortisol, and 20α-dihydrocortisol showed significant inverse relationships (P ≤ 0.02) with 24-h renal citrate output. By contrast, the estimate of renal 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), i.e., the ratio of urinary free cortisone/UFF, associated positively with urinary citrate (P = 0.04)., Conclusions: In line with studies in hypercortisolic state, even moderately high cortisol levels in healthy children, still within the physiological range, may negatively impact on the kidney's citrate excretion. Besides, a higher 11β-HSD2 activity, favoring cortisol inactivation, is paralleled by an increased citrate excretion.

Minimal data exist on whether the acid-base balance of the diet is linked to muscle strength. The aim of this study was to determine if dietary acid load is associated with grip strength in a nationally representative sample of middle- to older-age adults. We examined the cross-sectional association of grip strength with dietary acid load quantified through potential renal acid load (PRAL) and net endogenous acid production (NEAP) in 4,059 adults aged 50 years and older in the 2011-2014 NHANES survey cycles. PRAL and NEAP were estimated from two 24-h recalls and categorized into sex-specific quartiles. Grip strength was measured on a dynamometer. Multiple linear regression models were used to determine the associations of PRAL and NEAP (as quartiles) with grip strength for men and women separately, adjusting for total energy, age, race/ethnicity, weight, physical activity, smoking, serum 25-hydroxyvitamin D, and estimated glomerular filtration rate. Mean grip strength was 26.8 ± 0.2 kg in women and 43.0 ± 0.4 kg in men. Adjusted grip strength was inversely associated with quartiles of PRAL (p trend  = 0.049) and NEAP (p trend  = 0.034) in women with quartile 4 vs 1 differences of - 1.21 and - 1.08 kg (both p < 0.05), respectively. Adjusted grip strength was not associated with PRAL or NEAP in men. Overall, we found inverse associations between dietary acid load and grip strength in middle- and older-age women, suggesting that an alkaline diet may be important in maintaining muscle strength in this population. There was no association between dietary acid load and grip strength in men., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)