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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).)

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).)

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: 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.

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 (β = 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.

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 (P trend  = 0.03), but not among males. Both FlavFV-intake and uHA-excretion were inversely associated with HSI (P trend  < 0.0001 and P trend  = 0.02, respectively) and the pro-inflammatory score (P trend  = 0.02 and P trend  = 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.

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.

Purpose: Preliminary iodine concentration (UIC) measurements in spot urines of the representative German adult study DEGS indicated a severe worsening of iodine status compared to previous results in German children (KiGGS study). Therefore, we aimed to evaluate adult iodine status in detail and to investigate the impact of hydration status on UIC., Methods: UIC and creatinine concentrations were measured in 6978 spot urines from the German nationwide DEGS study (2008-2011). Twenty-four-hour iodine excretions (24-h UIE) were estimated by relating iodine/creatinine ratios to age- and sex-specific 24-h creatinine reference values. Urine osmolality was measured in two subsamples of spot urines (n = 100 each) to determine the impact of hydration status on UIC., Results: In DEGS, median UIC was 69 µg/L in men and 54 µg/L in women, lying clearly below the WHO cutoff for iodine sufficiency (100 µg/L). Estimated median 24-h UIE was 113 µg/day, accompanied by 32 % of DEGS adults, lying below the estimated average requirement (EAR) for iodine. Comparative analysis with the KiGGS data (>14,000 spot urines of children; median UIC 117 µg/L) revealed a comparable percentage

Purpose: Fruit and vegetable (FV) consumption and salt intake are known dietary influences on blood pressure (BP) in adults, but data on their long-term relevance during growth for later BP are rare. We aimed to examine the independent and concomitant influences of adolescent FV and salt intakes on BP in young adulthood., Methods: In total, 206 participants (108 males) provided a plausible BP measurement in young adulthood (18-25 years) as well as three repeated 3-day weighed dietary records, 24-h urine samples and BP measurements during adolescence (11-16 years). FV intake was assessed based on dietary records and its urinary biomarkers such as potassium, oxalate and hippuric acid. Urinary sodium chloride (NaCl) was used to estimate salt intake. Prospective associations of adolescent FV and salt intake with adult BP were examined in sex-stratified linear regression models., Results: In multivariable models, a 100 g higher FV intake during adolescence was prospectively related to 0.9 mmHg lower systolic BP in young adult females (P = 0.02), but not in males (P = 0.8). Biomarkers supported the findings for FV regarding systolic BP. Concurrently, a 1 g higher salt intake was related to 1.7 mmHg higher systolic BP in young men only (P = 0.01). For diastolic BP, results were inconsistent., Conclusions: Our findings suggest that in adolescent healthy girls, a higher FV intake may be more relevant for BP than a reduced salt intake and the opposite appears to apply for boys. The physiological implications of the observed sex-specific diet-BP relationships need deeper examination.

Purpose: A high dietary salt intake is a serious risk factor for the development of hypertension. Daily salt intake in most of the European countries substantially exceeds the current recommendations of salt intake. For Germany, so far, no valid biomarker-based data on current daily salt intake are available., Methods: Data basis for this biomarker-based estimation of salt intake in the German population was the representative DEGS Study (German Health Interview and Examination Survey for Adults) conducted 2008-2011 in 18-79 old adults living in Germany. Daily salt intake was estimated from 6,962 sodium and creatinine measurements in spot urine samples., Results: Median estimated daily salt intake of the 18-79 olds was 10.0 g in men and 8.4 g in women. More than 75% of men and about 70% of women exceeded the current recommendation of a maximum salt intake of 6 g/day. Fifty percentage of men and more than 35% of the women had a daily salt intake >10 g., Conclusion: Daily salt intake of the German population considerably exceeds the current recommendation to eat no more than 6 g salt per day. A general reduction of salt content in processed foods-which are currently the main source of salt intake-offers a promising and cost-effective potential for the improvement of all salt intake-dependent health outcomes in the population.

Purpose: Even mild iodine deficiency may negatively affect cognitive performance, especially at a young age. Our aim was to investigate iodine status in very young children and to assess the importance of iodized salt in processed foods of which the use has decreased during the last years in Germany., Methods: Twenty-four hours urinary iodine excretion (UIE) as a marker of iodine intake was measured in 378 24 h urine samples collected 2003-2010 by 221 3 to <6 years old participants of the DONALD Study. Parallel 3-d weighed dietary records and measurements of urinary sodium excretion provided data on the daily consumption of the most important iodine sources in the children's diet (iodized salt, milk, fish, meat and eggs). Time trends of UIE (2003-2010) and contributions of the different food groups were analyzed by using linear mixed-effects regression models., Results: Median UIE of 71 μg/d in boys and 65 μg/d in girls (P = 0.03), corresponding to an iodine intake of 82 and 75 μg/d, respectively (assumption: 15% non-renal iodine losses), was below the recommended dietary allowance (RDA) of 90 μg/d. Milk, salt and egg intake were significant predictors of UIE; milk and salt together accounted for >80% of iodine supply. Between 2003 and 2010, UIE decreased significantly by approximately 1 μg/d per year. The contribution of salt intake to UIE decreased from 2003-2006 to 2007-2010., Conclusion: In countries where salt is a major iodine source, already modest decreases in the iodized proportion of salt used in processed foods may relevantly impair iodine status even in preschool children.

Nutrition during childhood and adolescence is an important determinant of development and health, both for the child and the later adult. In industrialised countries as well as in many countries of economic transition, emphasis has moved from combating nutrient deficiencies to research on the effects of overnutrition and food selection. Prevention of chronic diseases including obesity have become a major focus in research. However, the complex relation between infant growth and its related endocrine and metabolic changes on the one hand and the influence of nutrition and nutritional status on the other hand still need to be understood in detail. Studies aiming to elucidate this have to follow children and adolescents during their growth period. The following pages display the features of the German DONALD Study ( DOrtmund Nutritional and Anthropometric Longitudinally Designed Study) which was specifically designed to address these complex research questions. Finally, comparisons to other studies are made and the specific strength and weaknesses of this study are discussed. As the DONALD study offers unique research opportunities and due to its long follow-up an abundance of data, collaborative research is encouraged.

Background: Nutrition has long been known to strongly influence acid-base balance. Recently, we have shown that it is possible to appropriately estimate the renal net acid excretion (NAE) of healthy subjects from the composition of their diets., Aim of the Study: 1) To briefly present a physiologically based calculation model that allows a reasonable estimation of the analytically determined urinary NAE, 2) to summarize the underlying metabolic mechanisms and 3) to study the specific effect of protein on ammoniagenesis which may counteract, to a small degree, the primary acid load-increasing potential of protein., Methods: The calculation model and the algorithm for predicting the dietary acid load are summarized, major metabolic (and intestinal) pathways of acid and base equivalents are explained, and urinary excretion rates of ammonium and NAE were specifically examined with special regard to the respective protein intake levels. For the latter examinations, data from diet experiments in adults and epidemiological data from children (protein intake; NAE, pH, and ammonium excretion in 24-h urine samples) were analyzed., Results: The paper shows that the diet-induced generation of acidity and alkalinity is not only determined by the metabolism (oxidation) of sulfur-containing amino acids and organic acid anions of alkali salts, respectively. The intestine is also directly involved in the generation of food-derived acid or alkali loads which is due to the considerably different intestinal absorption rates of relevant food components, i. e., protein and minerals. Further analyses of the interrelation between diet and acid-base status revealed that increasing protein intake (despite its potential to increase NAE) also significantly improves the capacity for renal net acid excretion by stimulating urinary ammonium excretion., Conclusion: An adequate concept to estimate renal NAE and potential renal acid loads from dietary intakes must consider the specific bioavailability of the individual nutrients. Furthermore, an increased protein intake does not necessarily result in an accordingly increased use of endogenous acid excretion capacity for two reasons: 1) additional alkali loads in an appropriately composed diet can compensate for the protein-related raised acid production and 2) protein itself moderately improves the renal capacity to excrete net acid by increasing the endogenous supply of ammonia which is the major urinary hydrogen ion acceptor.