Higher Renal Net Acid Excretion, but Not Higher Phosphate Excretion, during Childhood and Adolescence Associates with the Circulating Renal Tubular Injury Marker Interleukin-18 in Adulthood.

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.

Protein intake and risk of urolithiasis and kidney diseases: an umbrella review of systematic reviews for the evidence-based guideline of the German Nutrition Society.

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.

The DONALD study as a longitudinal sensor of nutritional developments: iodine and salt intake over more than 30 years in German children.

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.

Dietary protein intake and health-related outcomes: a methodological protocol for the evidence evaluation and the outline of an evidence to decision framework underlying the evidence-based guideline of the German Nutrition Society.

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.

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.

Early life factors and their relevance for markers of cardiometabolic risk in early adulthood.

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.

Inflammatory mediators in the adipo-renal axis: leptin, adiponectin, and soluble ICAM-1.

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.

Sugar intake among German adolescents: trends from 1990 to 2016 based on biomarker excretion in 24-h urine samples.

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.

Contribution of iodized salt to total iodine and total salt intake in Germany.

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.

Flavonoid intake from fruit and vegetables during adolescence is prospectively associated with a favourable risk factor profile for type 2 diabetes in early adulthood.

PURPOSE: Flavonoid consumption during adolescence could contribute to preventing adult onset of type 2 diabetes mellitus. We investigated the prospective association between habitual intake of flavonoids from fruit and vegetables (FlavFV) during adolescence and risk markers of type 2 diabetes in early adulthood. METHODS: This analysis included participants of the DONALD Study, who had provided a fasting blood sample in adulthood (18-39 years), data on FlavFV-intake during adolescence (females: 9-15 years, males: 10-16 years) and relevant covariates. Habitual FlavFV-intake was either estimated using repeated 3-day weighed dietary records (n = 268), or the validated biomarker hippuric acid (uHA)-excretion in repeated 24-h urine samples (n = 241). Multivariable linear regressions were performed to analyse the prospective associations of FlavFV or uHA with homeostasis model assessment insulin sensitivity (HOMA2-%S), hepatic steatosis index (HSI), fatty liver index (FLI) and a pro-inflammatory score. RESULTS: Higher FlavFV-intake was independently related to higher HOMA2-%S among females (Ptrend = 0.03), but not among males. Both FlavFV-intake and uHA-excretion were inversely associated with HSI (Ptrend < 0.0001 and Ptrend = 0.02, respectively) and the pro-inflammatory score (Ptrend = 0.02 and Ptrend = 0.008, respectively), but not with FLI. CONCLUSIONS: Our data indicate that flavonoid consumption from fruit and vegetables during adolescence is associated with a favourable risk factor profile for type 2 diabetes in early adulthood.

Median urinary iodine concentration reflected sufficient iodine supply in neonates from Northeast Germany in 2005-2006.

PURPOSE: Data from recent adult studies suggest a decline of median urinary iodine concentrations (UIC) in Germany, but since 1996 no German study investigated UIC in neonates. The aim of our study was to investigate UIC and serum thyroid-stimulating hormone (TSH) levels in neonates from Germany. METHODS: We used data from 399 neonates, which were born between April 2005 and November 2006 in the Northeast of Germany. UIC were evaluated by a photometric procedure with Sandell and Kolthoff reaction and afterwards corrected to be comparable with an ICP-MS method. TSH was determined from capillary blood, which was taken within 5 days after birth, by DELFIA. RESULTS: Median UIC were 150 µg/L (25th percentile: 104 µg/L; 75th percentile: 196 µg/L) and differed between boys (153.3 µg/L) and girls (131.5 µg/L; p = 0.012). The prevalence of serum TSH levels > 5 mIU/L was 14%. Neonates from mothers with intake of iodine supplementation (150 µg/L) had significantly higher median UIC than neonates from mothers without iodine supplementation (132 µg/L; p = 0.011). Multivariable linear regression adjusted for sex and iodine supplementation of the mother revealed a significant association between UIC and log-transformed serum TSH levels (ß = 0.003: 95% confidence interval (CI) = 0.0001-0.005; p = 0.028). CONCLUSIONS: Neonates in Northeast Germany did show a sufficient supply of iodine. This points towards the possibility of a sufficient iodine supply of neonates also in other regions of Germany, even though recent studies in adults may indicate mild iodine deficiency.

Prospective relation of adolescent citrate excretion and net acid excretion capacity with blood pressure in young adulthood.

Experimental data and observational studies in adults suggest that even subtle changes in acid-base balance, indicative of a higher systemic proton load, are related to higher blood pressure (BP) levels and an increased hypertension risk. However, these associations have not been investigated during growth. The kidney is the central organ in regulating excretion of nonvolatile acids, and renal citrate excretion has been shown to be a sensitive, noninvasive marker of changes in systemic acid balance. We thus analyzed the prospective relation of 24-h citrate excretion, as well as net acid excretion capacity (NAEC; a noninvasive indicator of the renal ability to excrete protons), during adolescence (boys: 10-15 yr; girls: 9-14 yr) with BP levels in young adulthood (18-30 yr) in 374 healthy participants of the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study. In linear-regression analyses adjusted for age, sex, 24-h urinary excretions of sodium and potassium, as well as further relevant confounders, a 1-mmol/1.73 m2/day higher adolescent citrate excretion was related to 1.2 mmHg lower systolic BP ( P = 0.02) but not to diastolic BP ( P = 0.6). A 10-mEq higher NAEC during adolescence was related to 1.7 mmHg lower systolic BP in young men, but this association was statistically nonsignificant ( P = 0.07) after multivariable adjustment. Additional adjustment for adult body mass index did not alter these findings. To conclude, subtle changes in systemic acid-base balance during adolescence are already indicative for later BP. Potential sex differences in these associations should be investigated in further studies.

Dietary Potential Renal Acid Load Is Positively Associated with Serum Uric Acid and Odds of Hyperuricemia in the German Adult Population.

Background: Initial interventional data indicate that a reduction in dietary acid load (e.g., by an increased consumption of alkalizing fruit and vegetables) can increase renal uric acid excretion and decrease serum uric acid (SUA). Objective: Against this background, we examined the association between dietary potential renal acid load (PRAL) and SUA in a representative population sample. Methods: Cross-sectional analyses were performed in 6894 participants (aged 18-79 y) of the German Health Interview and Examination Survey for Adults (DEGS1). Dietary intake was assessed with a food-frequency questionnaire. Nutritive acid load and the intake of uric acid equivalents (UAEs) were characterized by assigning PRAL and UAE values to reported food consumption. In multiple linear regression models, the associations of PRAL, UAEs, and relevant food groups with SUA were analyzed. Multiple logistic regressions were used to calculate ORs for hyperuricemia comparing lower and upper tertiles of the predictors. Results: After adjustment for relevant confounders, PRAL (P = 0.003), alcohol (P < 0.0001), and UAE (P = 0.03) intakes were positively associated with SUA, whereas the intake of dairy products and fruit and vegetables was inversely associated (both P < 0.0001). Subgroup analyses among participants without interacting medication use confirmed these results. In addition, participants with lower PRAL had lower odds for hyperuricemia (OR: 0.60; 95% CI: 0.43, 0.83). Conclusions: Apart from observing known dietary influences on SUA, we found in this population-based, cross-sectional study in adults that low PRAL may represent a potentially SUA-reducing dietary pattern. This highlights dietary alkalization as a possible nonpharmacologic option to influence elevated SUA concentrations.

Interlaboratory variability of urinary iodine measurements.

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.

13C-Mixed Triglyceride Breath Test and Fecal Elastase as an Indirect Pancreatic Function Test in Cystic Fibrosis Infants.

BACKGROUND: The 'gold standard' test for the indirect determination of pancreatic function status in infants with cystic fibrosis (CF), the 72-hour fecal fat excretion test, is likely to become obsolete in the near future. Alternative indirect pancreatic function tests with sufficient sensitivity and specificity to determine pancreatic phenotype need further evaluation in CF infants. OBJECTIVE: Evaluation of the clinical utility of both the noninvasive, nonradioactive C-mixed triglyceride (MTG) breath test and fecal elastase-1 (FE1) in comparison with the 72-hour fecal fat assessment in infants with CF. METHODS: C-MTG breath test and the monoclonal and polyclonal FE1 assessment in stool was compared with the 72-hour fecal fat assessment in 24 infants with CF. Oral pancreatic enzyme substitution (PERT; if already commenced) was stopped before the tests. RESULTS: Sensitivity rates between 82% and 100% for CF patients with pancreatic insufficiency assessed by both the C-MTG breath test and the FE1 tests proved to be high and promising. The C-MTG breath test (31%-38%) as well as both FE1 tests assessed by the monoclonal (46%-54%) and the polyclonal (45%) ELISA kits, however, showed unacceptably low-sensitivity rates for the detection of pancreatic-sufficient CF patients in the present study. CONCLUSIONS: The C-MTG breath test with nondispersive infrared spectroscopy (NDIRS) technique, as well as both FE1 tests, are not alternatives to the fecal fat balance test for the evaluation of pancreatic function in CF infants during the first year of life.

Relative validation of 24-h urinary hippuric acid excretion as a biomarker for dietary flavonoid intake from fruit and vegetables in healthy adolescents.

PURPOSE: A biomarker for dietary flavonoid intake from fruit and vegetables (FlavFV) is needed to elucidate the relevance of flavonoids from these sources for the prevention of chronic diseases. Urinary hippuric acid (HA)-a major metabolite of flavonoids-is promising in this respect as it was shown to satisfyingly indicate fruit and vegetable consumption in different age groups. Therefore, we validated urinary HA as a biomarker for intake of FlavFV. METHODS: Analyses included data from 287 healthy adolescents of the DONALD Study (aged 9-16 years) for whom a minimum of two pairs of HA measurements from 24-h urine samples (test method) and FlavFV intake estimated from 3-day weighed dietary records (reference method) existed. Agreement between both methods was assessed by Spearman correlation and cross-classification analyses. Possible confounders of the association were identified by linear regression models. Analyses were performed using a split-sample approach allowing for consecutive exploration (n = 192) and confirmation (n = 95) of results. RESULTS: Agreement between urinary HA excretion and FlavFV intake was moderate according to correlation analysis in the exploratory sample (r unadjusted = 0.47, P < 0.0001). Yet, 79 % of the subjects were classified into same/adjacent quartiles, and only 5 % were misclassified into opposite quartiles. These findings were corroborated by analyses in the confirmatory sample (r unadjusted = 0.64; 88 % in same/adjacent vs. 4 % in opposite quartiles). Body surface area (BSA) was the only relevant covariate in the exploratory sample, and its adjustment improved cross-classification estimates in both subsamples. CONCLUSIONS: BSA-adjusted 24-h urinary HA excretion represents a suitable biomarker of habitual FlavFV intake in healthy adolescents.

Higher diet-dependent renal acid load associates with higher glucocorticoid secretion and potentially bioactive free glucocorticoids in healthy children.

Metabolic acidosis induces elevated glucocorticoid (GC) levels. However, the influence of less strong daily acid loads on GCs is largely unexplored. To investigate this, we studied whether higher acid loads in children, fully within the normal range of habitual diets, associate with endogenous GCs. In a specific quasi-experimental design, we examined 200 6- to 10-year-old healthy participants of the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study equally divided to either high or low 24-hour renal net acid excretion. Major urinary GC metabolites were analyzed by gas chromatography-mass spectrometry to assess daily adrenal GC secretion and metabolites of tissue cortisol catabolism (6ß-hydroxycortisol and 20α-dihydrocortisol). Liquid chromatography-mass spectrometry was used to quantify urinary free cortisol and cortisone. After confounder adjustment, significant positive associations were unmasked for urinary potential renal acid load and net acid excretion with adrenal GC secretion, free cortisone, free cortisone plus cortisol, 6ß-hydroxycortisol, and 20α-dihydrocortisol. An inverse association emerged for an enzymatic marker (5ß-reductase) of irreversible GC inactivation. Our data suggest that existing moderate elevations in diet-dependent acid loads suffice to raise GCs and affect cortisol metabolism. Thus, potential detrimental effects of high acid loading appear to be mediated, in part, by increased GC activity via increased GC secretion and/or reduced GC inactivation. Higher cortisone levels, directly available for intracrine activation to cortisol may play a special role.

Relevance of fruits, vegetables and flavonoids from fruits and vegetables during early life, mid-childhood and adolescence for levels of insulin-like growth factor (IGF-1) and its binding proteins IGFBP-2 and IGFBP-3 in young adulthood.

The growth hormone (GH) insulin-like growth factor (IGF) axis has been linked to insulin metabolism and cancer risk. Experimental evidence indicates that the GH-IGF axis itself can be influenced by dietary flavonoids. As fruit and vegetable (FV) intake is a major source of flavonoid consumption, FV's beneficial health effects may be explained via flavonoids' influence on the GH-IGF axis, but observational evidence is currently rare. We used data from Dortmund Nutritional and Anthropometric Longitudinally Designed Study participants to analyse prospective associations between FV, fruit intake and flavonoid intake from FV (FlavFV) with IGF-1 and its binding proteins IGFBP-2 and IGFBP-3. Subjects needed to provide a fasting blood sample in adulthood (18-39 years) and at least two 3-d weighed dietary records in early life (0·5-2 years, n 191), mid-childhood (3-7 years, n 265) or adolescence (girls: 9-15 years, boys: 10-16 years, n 261). Additional analyses were conducted among those providing at least three 24-h urine samples in adolescence (n 236) to address the predictor urinary hippuric acid (HA), a biomarker of polyphenol intake. Higher fruit intake in mid-childhood and adolescence was related to higher IGFBP-2 in adulthood (P=0·03 and P=0·045). Comparable trends (P=0·045-0·09) were discernable for FV intake (but not FlavFV) in all three time windows. Similarly, higher adolescent HA excretion tended to be related (P=0·06) to higher adult IGFBP-2 levels. Regarding IGFBP-3, a marginal (P=0·08) positive association was observed with FlavFV in mid-childhood only. None of the investigated dietary factors was related to IGF-1. In conclusion, higher fruit and FV intakes during growth may be relevant for adult IGFBP-2, but probably not for IGFBP-3 or IGF-1.

Dietary ratio of animal:plant protein is associated with 24-h urinary iodine excretion in healthy school children.

UNLABELLED: Adequate dietary iodine intake in children is essential for optimal physical and neurological development. Whether lower dietary animal food and salt intake may adversely affect iodine status is under discussion. We examined the association between dietary animal:plant protein ratio with 24-h urinary iodine excretion (24-h UI, µg/d), and whether this is modified by salt intake. A 24-h UI was measured in 1959 24-h urine samples from 516 6- to 12-year-old participants of the Dortmund Nutritional and Anthropometric Longitudinally Designed Study. Parallel 3 d weighed food records were used to estimate dietary intakes. Protein sources were classified as dairy, animal and plant. A repeated-measures regression model (PROC MIXED) was used to analyse the effect of animal:plant protein ratios on 24-h UI. ANIMAL: plant protein ratios ranged from 0.5 (95 % CI 0.4, 0.6) to 1.6 (95 % CI 1.4, 1.9) (lowest and highest quartile). After adjustment for total energy intake, main dietary iodine sources (dairy and salt intake), and further covariates, the inter-individual variation in animal:plant protein ratio was significantly associated with variation in 24-h UI. One unit higher animal:plant protein ratio predicted 6 µg/d higher 24-h UI (P= 0.002) in boys and 5 µg/d (P= 0.03) in girls. This relationship was partially mediated by a higher salt intake at higher animal:plant protein ratios. These results suggest that lower consumption of animal protein is associated with a small decline in iodine excretion, partially mediated by decreased salt intake. Because limited salt and increased intake of plant-based foods are part of a preferable healthy food pattern, effective nutrition political strategies will be required in the future to ensure appropriate iodine nutrition in adherent populations.