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Background: Dietary composition is one of the factors influencing the acid–base balance of the body by providing acid or base precursors. One of the methods for assessing the acid-forming potential of a diet is to calculate its potential renal acid load (PRAL). The aim of this study was to identify the sociodemographic, lifestyle, and health factors related to the PRAL. Methods: Dietary intake was assessed among 133 individuals aged 70+ years using the three-day record method. Results: The average PRAL value was 15.7 mEq/day (range from −42.4 to +101.7). The diets of a majority of the participants (71.4%) had acid-forming potential (PRAL > 0). From a univariate analysis, the acid-forming potential of the diets was linked mainly to women (65.3% in PRAL > 0 group vs. 10.5% in PRAL < 0 group), people using dietary supplements, those who consumed alcohol, those who assessed their health as being at least good, people with osteoporosis, those hospitalized during the previous year, and those with rather lower physical activity. Conclusions: From a multivariate analysis, gender was the strongest predictor of an acid-forming diet, but the following also contributed: an average self-rated health status (compared to good), a good health status (compared to poor), alcohol drinking, hospitalization, lack of nutritional knowledge, and, to a lesser extent, non-frail status (compared to pre-frail). Therefore, more extensive nutritional education in the identified groups is required. [ABSTRACT FROM AUTHOR]

Background: Children's rapid growth requires adequate nutrient intake, with breakfast, especially when incorporating dairy, playing an important role. This study examined associations between dairy consumption at breakfast and energy and nutrient intake among children in Southeast Asia. Methods: Utilizing the cross-sectional South East Asian Nutrition Surveys II dataset, using a 24 h dietary recall and questionnaires distributed among 10,286 children aged 2 to 12 years from Malaysia, Thailand, Indonesia, and Vietnam, we investigated the impact of dairy consumption at breakfast on nutrient intake and examined associations between breakfast consumption and the prevalence of stunting and overweight/obesity among 10,135 children. Results: Although most of the children consumed breakfast, only 37%, 27%, 16%, and 18% in Malaysia, Thailand, Indonesia, and Vietnam, respectively, included dairy in this meal, with younger children being significantly more likely to consume dairy at breakfast (p < 0.001). Dairy consumers had significantly higher intakes of vitamins A, B12, and D and calcium both at breakfast and throughout the day (p < 0.001). Breakfast skippers had a 29% increased risk of being overweight/obese. Conclusions: Dairy consumption at breakfast was associated with enhanced nutrient intake and overall diet quality among Southeast Asian children. The association between breakfast habits and anthropometric outcomes highlights the need to address nutritional deficiencies and promote healthy growth and development. [ABSTRACT FROM AUTHOR]

Ischemia-modified albumin (IMA) has emerged as a pivotal biomarker for the early detection of ischemic conditions, particularly myocardial ischemia, where timely diagnosis is crucial for effective intervention. This review provides an overview of the analytical methods for assessment of IMA, including Albumin Cobalt Binding (ACB), Albumin Copper Binding (ACuB), Enzyme-Linked Immunosorbent Assay (ELISA), new techniques such as liquid crystal biosensors (LCB), quantum dot coupled X-ray fluorescence spectroscopy (Q-XRF), mass spectrometry (MS), and electron paramagnetic resonance (EPR) spectroscopy. Each method was thoroughly examined for its analytical performance in terms of sensitivity, specificity, and feasibility. The ACB assay is the most readily implementable method in clinical laboratories for its cost-effectiveness and operational simplicity. On the other hand, the ACuB assay exhibits enhanced sensitivity and specificity, driven by the superior binding affinity of copper to IMA. Furthermore, nanoparticle-enhanced immunoassays and liquid crystal biosensors, while more resource-intensive, significantly improve the analytical sensitivity and specificity of IMA detection, enabling earlier and more accurate identification of ischemic events. Additionally, different biological matrices, such as serum, saliva, and urine, were reviewed to identify the most suitable for accurate measurements in clinical application. Although serum was considered the gold standard, non-invasive matrices such as saliva and urine are becoming increasingly feasible due to advances in technology. This review underscores the role of IMA in clinical diagnostics and suggests how advanced analytical techniques have the potential to significantly enhance patient outcomes in ischemic disease management. [ABSTRACT FROM AUTHOR]

Objective(s): Prior research has indicated that hydroxycitric acid (HCA) can impede the formation of calcium oxalate (CaOx) crystals, yet the specific mechanisms underlying its therapeutic effects remain unclear. In this study, we delved into the protective effects of HCA against glyoxylate-induced renal stones in rats and sought to elucidate the underlying metabolic pathways. Materials and Methods: Forty rats were randomly assigned to five groups: control group, model group, L-HCA-treated group, M-HCA-treated group, and H-HCA-treated group. Von Kossa staining was conducted on renal sections, and blood urea nitrogen and serum creatinine were determined by biochemical analysis. Meanwhile, body weight and urine volume were also measured. We subjected urine samples from the rats to analysis using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Next, we employed a metabolomic approach to scrutinize the metabolic profiles of each group. Results: HCA significantly reduced blood urea nitrogen and serum creatinine, and increased body weight and urine volume. It also reduced CaOx crystal deposition. A total of 24 metabolites, exhibiting a significant reversal pattern following HCA administration, were identified as urine biomarkers indicative of HCA’s preventive effects against CaOx crystal-induced renal injury. These metabolites are primarily associated with glycine, serine, and threonine metabolism; phenylalanine metabolism; tricarboxylic acid cycle; taurine and hypotaurine metabolism; and tryptophan metabolism. Conclusion: It was demonstrated that HCA has a protective effect against CaOx crystal-induced kidney injury in rats by modulating various metabolic pathways. Additionally, results suggest that HCA holds promise as a potential clinical therapeutic drug for both the prevention and treatment of renal stones. [ABSTRACT FROM AUTHOR]

During high-intensity (HI) exercise, metabolic acidosis significantly impairs exercise performance. Increasing the body's buffering capacity through training and exogenous intake of alkalizing supplements may improve highintensity performance. Manipulating water and diet intake may influence the acid-base balance. The aim of this study was to determine the effects of mineral water rich in bicarbonate ions (STY) or placebo water (PLA) on circulating biomarkers and anaerobic performance and to verify whether alkalizing (ALK) or acidizing (ACI) diet would modulate these effects. Twenty-four athletes, assigned either to ALK (n = 12) or ACI (n = 12) diet for four weeks, completed a 1-min rowing Wingate Test in a double-blind and randomized trial after one week of daily hydration (1.5 to 2L/d) with either STY or PLA. Blood samples were taken before and after each test, and urine samples were collected each week. Chronic consumption of bicarbonate-rich water significantly impacted resting urinary pH irrespective of alkalizing or acidizing dietary intake. STY induced a significant increase in blood pH, lactate, and HCO3- ion concentration postexercise compared to PLA. Similar changes were observed when STY was associated with the ALK diet. In contrast, STY combined with the ACI diet only significantly affected urine pH and peak blood lactate compared to PLA (p < 0.05). No effect of bicarbonate-rich water was reported on anaerobic performance (p > 0.05). Our results suggest that consumption of bicarbonate-rich water alters acid-base balance during a warm-up and after HI exercise, could potentiate beneficial effects of an alkalizing diet on the acid-base balance after HI exercise, and reduces the acid load induced by an acidifying diet. [ABSTRACT FROM AUTHOR]

Inconsistent swimming performances are often observed following sodium bicarbonate (NaHCO3) ingestion, possibly because the time taken to reach peak blood buffering capacity is highly variable between individuals. Personalising NaHCO3 ingestion based on time-to-peak blood bicarbonate (HCO3−) could be a solution; however, this strategy is yet to be explored in swimming, or adequately compared to standardised NaHCO3 approaches. Therefore, six highly trained female swimmers ingested 0.3 g·kg BM−1 NaHCO3 in capsules to pre-determine their individual time-to-peak blood HCO3−. They then participated in three experimental trials, consisting of a 6 × 75 m repeated sprint swimming test, followed by a 200 m maximal time trial effort after 30 min active recovery. These experiments were conducted consuming a supplement at three different timings: individualised NaHCO3 (IND: 105–195 min pre-exercise); standardised NaHCO3 (STND: 150 min pre-exercise); and placebo (PLA: 90 min pre-exercise). Both NaHCO3 strategies produced similar increases in blood HCO3− prior to exercise (IND: +6.8 vs. STND: +6.1 mmol·L−1, p < 0.05 vs. PLA) and fully recovered blood HCO3− during active recovery (IND: +6.0 vs. STND: +6.3 mmol·L−1 vs. PLA, p < 0.05). However, there were no improvements in the mean 75 m swimming time (IND: 48.2 ± 4.8 vs. STND: 48.9 ± 5.8 vs. PLA: 49.1 ± 5.1 s, p = 0.302) nor 200 m maximal swimming (IND: 133.6 ± 5.0 vs. STND: 133.6 ± 4.7 vs. PLA: 133.3 ± 4.4 s, p = 0.746). Regardless of the ingestion strategy, NaHCO3 does not appear to improve exercise performance in highly trained female swimmers. [ABSTRACT FROM AUTHOR]

Background: Puberty is a life milestone that marks the transition from childhood to adulthood. An ambispective Chongqing Pubertal Timing (CQPT) cohort was started in 2014 to understand pubertal timing and identify environmental risk factors. Methods: A total of 1429 children and adolescents were recruited and have been followed up once every 6 months for 8 years in a district of Chongqing, China. Data were collected via questionnaires for social and family environment, health conditions, gestational and maternal information, and in-person physical examinations by trained medical school graduate students in follow-ups. Environmental exposures of polycyclic aromatic hydrocarbons (PAHs), neonicotinoids, and heavy metals in urine samples were measured at different time points. Results: The mean ages at pubertal onset were 10.20 for thelarche, 11.62 for pubic hair development, and 11.84 for menarche in girls, and 11.16 for genital development, 11.66 for testicular enlargement, and 12.71 for first spermatorrhea in boys. Four OH-PAHs were associated with delayed timing of menarche, thelarche, pubic hair, and axillary hair development in girls, and thiacloprid was found to potentially impact genital stages in boys and axillary hair development in girls. Conclusions: We built a cohort to provide evidence of regional pubertal timing of boys and girls and the significant environmental factors. Further health outcomes, especially mental health and women's health and its long-term health implications, will be followed. [ABSTRACT FROM AUTHOR]

Purpose: This paper aims to outline the role that serendipity can play in providing a complementary and previously unrepresented vector in deliberate and emergent strategies within organizations. Design/methodology/approach: The paper is conceptual in nature and draws upon the serendipity pattern in sociological theory and serendipitous relations in developmental sciences to provide a framework for executives to consider when examining the process of strategy formation. Two case vignettes are used to illustrate the difference between luck and serendipity and the paper also traces key micro foundations of serendipity by returning to the original serendipity fable and a famed science experiment producing "floppy-eared" rabbits. Findings: The notion of chance favoring the "prepared firm" is espoused where the prepared organizational mind is positioned as an antecedent of serendipitous strategy formation. This is based on Louis Pasteur's famous aphorism, "chance favors the prepared mind." Components of the prepared firm include deep domain knowledge, anticipatory mindset, noticing, abductive reasoning, elaboration and relations development. Research limitations/implications: The paper is a conceptual articulation of a novel concept that now requires deeper empirical case development and ultimately statistical validation. The paper suggests linkages between serendipity and theories of absorptive capacity and the attention-based view of the firm. Practical implications: Several mindsets, capabilities and relations for architecting organizational serendipity are suggested for executives using a stylized framework. Originality/value: From a strategy process perspective, the Mintzberg and Waters seminal article "Of strategies deliberate and emergent" is complemented by considering "floppy-eared" strategy characterized by unexpected, anomalous and strategic datum. [ABSTRACT FROM AUTHOR]

Assessing bone growth trajectories in mammals is crucial for understanding life history dynamics, but the quantification of bone growth in natural settings can be challenging. Bone resorption markers that can be measured in urine, such as C‐telopeptide of type I collagen (CTX‐I), offer a non‐invasive solution to assess bone growth. Although measurement of urinary CTX‐I levels has been applied extensively in human studies, its use in other species is so far limited to a few clinical studies. To validate urinary CTX‐I as a bone resorption marker under less controlled conditions, we investigated within‐individual day‐to‐day variation, diurnal patterns, and sex and age‐specific variation in zoo‐housed bonobos (Pan paniscus). We then also correlated urinary CTX‐I levels with forearm growth velocity measures. We found a day‐to‐day variability in urinary CTX‐I levels of around 25%, comparable to human variation. Diurnally, CTX‐I levels decreased, aligning with observations in humans and other species. Both sexes showed an age‐related decline in urinary CTX‐I levels, with a steady decrease after the age of 10 years. Additionally, we found a positive correlation between forearm growth velocity and urinary CTX‐I levels across age in female, but not in male, bonobos. Our results demonstrate that urinary CTX‐I levels are a meaningful measure of bone growth and highlight its potential to examine bone growth trajectories also in wild populations to investigate life history dynamics. [ABSTRACT FROM AUTHOR]

Lifestyle behaviors, defined as a combination of dietary behavior, physical activity (PA), screen time (ST), and sleep duration indicators, are strongly associated with blood pressure (BP) in students. Our aim was to characterize the joint trajectories of lifestyle behaviors among middle school students and evaluate their association with BP. Data were obtained from the monitoring dataset on common diseases and health factors among students in Jiading District, Shanghai, China, conducted from 2019 to 2023. Lifestyle behavior data were collected annually from middle school students aged 12–18 years through questionnaires covering dietary behavior score, PA, ST, and sleep duration. Students' BP was measured in 2023. Joint trajectories of lifestyle behaviors were determined using group-based multi-trajectory modeling. Associations between lifestyle trajectories and students' BP were examined using multiple linear regression and modified Poisson regression. A total of 1378 middle school students (759 [58.98%] boys, median age 14.36 years [IQR: 13·30–13.28]) with lifestyle behaviors data assessed at least three times were included, and they were categorized into four joint lifestyle trajectories as follows: "remain unhealthy with low PA and increasing ST" (n = 141, 10.46%), "remain unhealthy with only low PA" (n = 305, 22.63%), "change towards unhealthy with decreasing sleep duration" (n = 776, 57.57%), and "relatively healthy" (n = 126, 9.35%). After adjusting for important confounders, the "remain unhealthy with low PA and increasing ST" group was associated with higher diastolic BP (DBP) [β: 3.49, 95% CI: 0.55–6.44] and higher mean arterial pressure (MAP) [β: 3.19, 95% CI: 0.37–6.01] in students compared with the "relatively healthy" group. Additionally, compared with the "relatively healthy" group, students in the "remain unhealthy with low PA and increasing ST" group had a 1.12-fold increase in the risk of hypertension (risk ratios: 1.12, 95% CI: 1.03–1.24). All trend p values in DBP, MAP, and hypertension from the "relatively healthy" group to the "remain unhealthy with low PA and increasing ST" group were less than 0.05. Four distinct lifestyle trajectories were identified among middle school students. Students who remained in the "unhealthy with low PA and increasing ST" lifestyle trajectory were associated with later elevations in BP. [ABSTRACT FROM AUTHOR]

Dietary factors may be implicated in the formation of kidney stones and should be closely monitored. To achieve this aim, patients are routinely assessed by means of generic dietary recall, a tool widely used by authors in a range of extensive patient populations to record food intake; the findings obtained, however, may be skewed due to dietary variations and underestimation of the effect of food additives. Fifty Frequent Kidney Stone Formers (FKSFs, mean age: 54.3 ± 13.9 years) with normal kidney function, absence of comorbidities, and reliable compliance were selected from a total of 68 patients' resident in Sardinia, an Italian island where genetic admixtures have been relatively rare for generations. The study, conducted from 1 January 2020 to 31 December 2023, was aimed at assessing nutritional values based on the meticulous recording of food quantities, quality, and potential modifications related to food preparation. Patients were selected during an initial clinical check-up and all efforts made to ensure they were capable of reliably recording all food and drinks consumed. A seven-day food diary was provided in which food and drink intake and their impact on 24 h urine output was recorded. The following parameters were measured in both foods and urine output: citrates, oxalates, calcium, phosphorous, uric acid, proteins and nitrogen compounds, magnesium, sulfates, potassium, carbohydrates, free fatty acids. Study outcomes established the presence of hypocitraturia, hyperoxaluria, hypercalciuria, and moderately high levels of nitrogen compounds. Univariate analysis followed by multivariate analysis for further confirmation were performed and the following observations made. Citrate intake correlated with citraturia but did not promote oxaluria; calcium intake promoted onset of sulfaturia, azoturia, and ammoniuria, whilst magnesium correlated with magnesiuria but not with oxaluria, calciuria, phosphaturia, and azoturia; sulfate intake elicited onset of azoturia but not kaliuresis; potassium intake promoted oxaluria and protein intake resulted in onset of ammoniuria and azoturia. (A) The chemical composition of urine based on dietary intake is hard to predict without taking into account the presence of dietary and urinary interferents; (B) the geographic isolation of patients studied underlines the importance of epigenetics in maintaining a traditional dietary heritage. (C) Moreover, the widespread use of food additives should consistently be taken into account to ensure a correct diagnosis of FKSF and set up a valid treatment plan. [ABSTRACT FROM AUTHOR]

Background: Bariatric surgery (BS) is effective for achieving significant weight loss. However, weight regain (WR) is an emerging problem. Objective: To assess the prognostic value of morning serum cortisol, a 1 mg dexamethasone suppression test (DST), 24 h urinary free cortisol (UFC) and late-night salivary cortisol (LNSC) in a cohort of patients with severe obesity (pwSO) undergoing BS in terms of weight loss and WR. Methods: Patients scheduled for BS underwent the following procedures at baseline, 12 months and 24 months after BS: medical history, anthropometric data, blood analysis and cortisol tests. We evaluated total weight loss (TWL) ≥ 30% at 1 year and WR after 2 years as an increase of ≥10% of the maximum weight lost. Results: In total, 142 subjects were included; 101 (71.1%) were females and the mean age was 45.9 ± 9.2 years. Up to 76.8% of subjects achieved ≥30% TWL, without statistically significant differences in DST results or morning serum cortisol, UFC or LNSC levels. However, a higher pre-surgery morning serum cortisol level was a significant predictor of a WR ≥ 10% (cortisol 17.8 [IQR 13.1–18.5] vs. 12.0 [IQR 8.8–15.8] μg/dL; p < 0.01); OR of 1.216 (95% CI 1.069–1.384); AUC [0.761, CI: (0.616–0.906); p < 0.01]. A cut-off value of cortisol > 13.0 μg/dL was predictive of a WR ≥ 10% (sensitivity 0.71; specificity 0.63). Conclusions: No cortisol test was useful in predicting weight loss; however, the pre-surgery morning serum cortisol level was able to predict a WR ≥ 10% in a cohort of pwSO 2 years after BS. A cut-off value of cortisol > 13 μg/dL might be an easy tool to identify patients at higher risk of WR, enabling healthcare providers to implement tailored, long-term strategies to minimize this outcome. [ABSTRACT FROM AUTHOR]

Despite the benefits of exercise on mental and physical health, excessive training loads can lead to health problems in the long term, including a wide spectrum of menstrual dysfunction (MD). This narrative review aims to analyze the relationship between physical exercise and MD in adolescent female athletes to support regular menstrual health monitoring and promote educational programs on reproductive risks. When dealing with MD in young athletes, several factors entangled with maturation of the hypothalamus–pituitary–ovarian axis should be considered. Firstly, some disciplines seem to have a higher prevalence of MD due to the high loads of training regimes and the early introduction of athletes to a competitive career. Moreover, low energy intake and a low body mass index appear to exacerbate existing MD. Lastly, disordered eating behaviors and psychological stress can contribute to MD in female athletes. The type of sport, influencing the intensity and duration of exercise, as well as individual psycho-physiological and environmental factors, may influence the role of physical activity in the manifestation of MD. Early recognition and management of MD, along with collaboration between sports organizations and health professionals, are crucial to minimize risks, ensure proper nutrition, and balance training with recovery. Keeping an open discussion on the topic may prospectively improve awareness, early diagnosis, and treatment strategies, as well as reduce injury risk and enhance sports performance. [ABSTRACT FROM AUTHOR]

Chronic low-grade inflammation represents a likely intermediary in the relation between carbohydrate nutrition and both type 2 diabetes and cardiovascular disease. This study assessed the prospective association between carbohydrate quantity and quality [dietary glycemic index (GI), glycemic load (GL), and added sugar, fiber, and whole-grain intake] during puberty, a potentially critical period for later disease, and low-grade inflammation in younger adulthood. The analysis was based on 205 participants (113 girls and 92 boys) from the DONALD (Dortmund Nutritional and Anthropometric Longitudinally Designed) study with at least 2 3-d weighed dietary records during puberty (girls: 9-14 y, boys: 10-15 y) and blood samples in younger adulthood (18-36 y). Multivariable linear regression models were used to analyze the associations between carbohydrate nutrition and circulating concentrations of pro- and anti-inflammatory immune mediators [high-sensitivity C-reactive protein (hs-CRP), interleukin (IL) 6, IL-18, and adiponectin]. A higher intake of carbohydrates during puberty (P-trend = 0.005), particularly from higher-GI food sources (P-trend = 0.01), was prospectively related to higher concentrations of IL-6 in younger adulthood, independently of baseline BMI and early life, socioeconomic, and other nutritional factors. Furthermore, a higher dietary GL (P-trend = 0.002) and a lower intake of whole grains (P-trend = 0.01) were independently associated with higher IL-6 concentrations in adults. Dietary GI and added sugar and fiber intakes were not independently associated with IL-6 (P-trend ≥ 0.09). Carbohydrate nutrition during puberty was not independently related to hs-CRP, IL-18, and adiponectin concentrations (all P-trend > 0.1). During puberty, a higher intake of carbohydrates from higher-GI food sources and lower whole-grain consumption prospectively predict greater IL-6 concentrations in young adulthood. These data support the hypothesis that diet during puberty influences later inflammation and metabolic dysfunction., (© 2014 American Society for Nutrition.)

Nutritive and bioactive components of human milk could be involved in programming metabolic systems that affect bone growth throughout the life course. Bone properties in childhood and adolescence might differ, depending on breastfeeding duration. Thus, breastfeeding could be a relevant factor in the context of primary osteoporosis prevention. The prospective association between breastfeeding duration and bone properties was investigated using the data of 284 participants of the Dortmund Nutritional and Anthropometric Longitudinally Designed Study. Breastfeeding duration was assessed during infancy. Bone properties were measured by peripheral quantitative computed tomography (pQCT) at ages 5-23 years. Cortical volumetric bone mineral density, cortical bone mineral content, strength strain index, total cross-sectional area of the bone and cross-sectional area of the cortical bone were determined at the 65% site of the radius. Linear regression analyses were performed to check for differences in pQCT parameters of subjects who had not or shortly been breastfed (0-16 weeks) and subjects who had been breastfed for a long duration (≥17 weeks). Multivariable models adjusted for age, gender, forearm length, muscle cross-sectional area, body mass index standard deviation score (SDS), height SDS and socio-economic status did not yield associations between breastfeeding duration and pQCT parameters. These findings suggest neither protective nor adverse effects of prolonged breastfeeding on bone health in childhood and adolescence. Influences of early nutrition on bone growth might be overridden by current effects of mechanical loads on bone physiology., (© 2012 John Wiley & Sons Ltd.)

Background: Worldwide, iodine prophylaxis measures have improved iodine status in populations. Several studies have reported an increase in thyrotropin (TSH) levels coinciding with this prophylaxis. Whether this implies an increased risk for hypothyroidism or simply reflects a physiologic TSH adaptation mechanism is not clear., Methods: Data on iodine and thyroid status of 6-17 year old children and adolescents (n=9175), collected between 2003 and 2006 in the German-wide Health Interview and Examination Survey for Children and Adolescents (KiGGS) Study, provided the basis for the analyses of mutual relationships of urinary iodine status (assessed by iodine/creatinine ratio in spot urines), serum TSH levels, and thyroid volume (determined by ultrasound). For data analyses (multivariable linear regression analysis), only those children were included for whom none of the available parameters (including free triiodothyronine [fT3], free thyroxine [fT4], and thyroperoxidase antibody [TPO-Ab] measurements) indicated a potential pathophysiologic thyroid status (n=6101)., Results: In this population-based sample of thyroid-healthy children, higher urinary iodine excretion was associated with higher TSH levels (p<0.05), adjusted for sex, age, body surface area, body mass index, fT3/fT4 ratio, and time of blood sampling. Higher TSH levels were not associated with a higher prevalence of TPO-Ab but with lower thyroid volume (p<0.001, fully adjusted). For the present study sample, one-time spot measurements of urinary iodine excretion were not related to thyroid volume, the long-term marker of iodine status., Conclusion: Our findings show for the first time in thyroid-healthy children that smaller thyroid volume is associated with higher normal TSH levels. A decreased thyroid cell mass and cell amount, as induced by an improved iodine status, does presumably require a higher TSH signal to maintain a constant thyroid hormone production, suggesting an underlying physiologic adaptation. Correspondingly, an increased TSH level should not be used as the single criterion to evaluate the prevalence of hypothyroidism, and the repeatedly observed parallel increases of iodine supply and TSH levels should not readily be interpreted as evidence for an increased hypothyroidism risk. These insights, contradicting conventional interpretations, may contribute to dispel uncertainties about the safety of iodine prophylaxis measures.

Low salt intake and high fruit and vegetable intake (FVI) have been shown to reduce blood pressure (BP) in adults. Longitudinal data on the independent effect of both FVI and salt intake on BP in healthy normotensive children are not available yet. In the present study, we aimed to characterise the concomitant influence of salt intake and FVI on BP development throughout childhood and adolescence. We examined 435 healthy subjects, for whom at least three repeated measurements of BP had been taken and who had provided 24 h urine samples and 3 d weighed dietary records between 4 and 18 years of age. BP was measured using a mercury sphygmomanometer (Mercuro 300, WelchAllyn) and salt intake was determined based on 24 h Na excretion. The intra-individual change in salt intake was almost significantly associated with the change in systolic BP (SBP, P= 0·06) and marginally (P= 0·09) with that in diastolic BP (DBP) in puberty, but not in pre-puberty. A 1 g/d increase in salt intake was associated with a 0·2 mmHg increase in SBP. In pre-puberty, but not in puberty, differences in FVI between children predicted between-person variations in SBP and DBP (P= 0·03). Corresponding findings were obtained for 24 h K excretion (a urinary indicator for FVI). A 100 g/d lower FVI was related to a 0·4 mmHg higher BP value. In conclusion, in healthy children and adolescents with BP in the low-normal range, both salt intake and FVI may already start to influence BP, although at a small magnitude. The potential importance of establishing healthy eating habits in childhood for later BP development emphasises the role of higher FVI and lower salt intake in the prevention of hypertension in the long run.

Urinary free cortisol and urinary free cortisone are decisive markers for the diagnosis of syndromes related to the dysfunction of the adrenal gland or to evaluate certain enzymatic disorders. Here, we present a new method, designed for routine laboratory use, which enables quick determination of these analytes with minor sample workup. Turbulent flow chromatography shortens sample preparation, and connection to a fused-core particle-packed column (rugged amide-embedded C18 phase) permits a rapid and effective separation of the analytes, as well as additional separation from other related and isobaric compounds present in urine. Urinary isobaric compounds were successfully identified. The method requires only 100 μl of urine supernatant per sample. The total time between injections is 9.5 min. The solvents used for both turbulent and analytical chromatography are water and methanol, and the relatively low flows needed during the method resulted in an extended life of the columns. Linearity showed a R (2) > 0.994. Limit of detection and limit of quantification are 0.5 and 1.0 ng/ml for cortisone and 1.0 and 2.0 ng/ml for cortisol. Recoveries ranged from 99.7 to 109.1 % for cortisone and from 98.7 to 102.9 % for cortisol. Accuracy values (relative errors) for intra- and inter-assay experiments were always below 8 %, whereas precision (percent CV) ranged from 3.7 to 10.7 %. No matrix effects were detected during the validation process. The reproducibility for each analyte's retention time was excellent, with a coefficient of variation always below 0.2 %. The final validation step included the study of urine samples from healthy children and from children previously diagnosed with corticoidal disorders. The high selectivity achieved enables quick data handling.

A variety of genetic, mechano-response-related, endocrine-metabolic, and nutritional determinants impact bone health. Among the nutritional influences, protein intake and dietary acid load are two of the factors most controversially discussed. Although in the past high protein intake was often assumed to exert a primarily detrimental impact on bone mass and skeletal health, the majority of recent studies indicates the opposite and suggests a bone-anabolic influence. Studies examining the influence of alkalizing diets or alkalizing supplement provision on skeletal outcomes are less consistent, which raises doubts about the role of acid-base status in bone health. The present review critically evaluates relevant key issues such as acid-base terminology, influencing factors of intestinal calcium absorption, calcium balance, the endocrine-metabolic milieu related to metabolic acidosis, and some methodological aspects of dietary exposure and bone outcome examinations. It becomes apparent that for an adequate identification and characterization of either dietary acid load's or protein's impact on bone, the combined assessment of both nutritional influences is necessary.

Diets high in sulfur-rich protein and low in fruits and vegetables affect human acid-base balance adversely. Corresponding subclinical forms of metabolic acidosis have been linked to hypertension in adults. We longitudinally examined relations of dietary acid load with blood pressure in 257 healthy prepuberty children with 3 or more parallel 3-day weighed dietary records, 24-h urine, and blood pressure measurements. Urinary net acid excretion and the potential renal acid load (PRAL), determined as the difference of major urinary nonbicarbonate anions and mineral cations, were used to predict dietary acid load. PRAL was also calculated from dietary data. In repeated-measures regression analyses, adjusted for body size and dietary fiber, an intraindividual increase of 10 mEq above the 'usual' net acid excretion or urine PRAL were each significantly related to a 0.6-0.7 mm Hg increased systolic blood pressure. Differences in urine PRAL among the children also significantly predicted between-person differences in systolic blood pressure. A higher individual net acid excretion or urine PRAL and intraindividual increase in urine PRAL were significantly related to higher diastolic blood pressure. Blood pressure associations were nonsignificant for dietary PRAL and urinary sodium. Thus, in healthy children, renal biomarker analyses reveal an association of proton load with higher blood pressure. Especially for systolic blood pressure, a more alkalizing nutrition may be beneficial for blood pressure development within a given individual. Experimental confirmation of a causal acid load-blood pressure link is required.

Purpose: Iodine deficiency increases the risk of cognitive impairment and delayed physical development in children. It is also associated with cognitive impairment in adults. Cognitive abilities are among the most inheritable behavioural traits. However, little is known about the consequences of insufficient postnatal iodine intake and whether the individual genetic disposition modifies the association between iodine intake and fluid intelligence in children and young adults., Methods: The cultural fair intelligence test was used to assess fluid intelligence in the participants of the DONALD study (n = 238; mean age, 16.5 [SD = 7.7] years). Urinary iodine excretion, a surrogate iodine intake marker, was measured in 24-h urine. Individual genetic disposition (n = 162) was assessed using a polygenic score, associated with general cognitive function. Linear regression analyses were conducted to determine whether Urinary iodine excretion was associated with fluid intelligence and whether this association was modified by individual genetic disposition., Results: Urinary iodine excretion above the age-specific estimated average requirement was associated with a five-point higher fluid intelligence score than that below the estimated average requirement (P = 0.02). The polygenic score was positively associated with the fluid intelligence score (β = 2.3; P = 0.03). Participants with a higher polygenic score had a higher fluid intelligence score., Conclusion: Urinary iodine excretion above the estimated average requirement in childhood and adolescence is beneficial for fluid intelligence. In adults, fluid intelligence was positively associated with a polygenic score for general cognitive function. No evidence showed that the individual genetic disposition modifies the association between Urinary iodine excretion and fluid intelligence., (© 2023. The Author(s).)

Background: Breastfeeding may lower chronic disease risk by long-term effects on hormonal status and adiposity, but the relations remain uncertain., Objective: To prospectively investigate the association of breastfeeding with the growth hormone- (GH) insulin-like growth factor- (IGF) axis, insulin sensitivity, body composition and body fat distribution in younger adulthood (18-37 years)., Design: Data from 233 (54% female) participants of a German cohort, the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study, with prospective data on infant feeding were analyzed. Multivariable linear as well as quantile regression were performed with full breastfeeding (not: ≤ 2, short: 3-17, long: >17 weeks) as exposure and adult IGF-I, IGF binding proteins (IGFBP) -1, -2, -3, homeostasis model assessment of insulin resistance (HOMA-IR), fat mass index, fat-free mass index, and waist circumference as outcomes., Results: After adjustment for early life and socio-economic factors, women who had been breastfed longer displayed higher adult IGFBP-2 (p(trend) = 0.02) and lower values of HOMA-IR (p(trend) = 0.004). Furthermore, in women breastfeeding duration was associated with a lower mean fat mass index (p(trend) = 0.01), fat-free mass index (p(trend) = 0.02) and waist circumference (p(trend) = 0.004) in young adulthood. However, there was no relation to IGF-I, IGFBP-1 and IGFBP-3 (all p(trend) > 0.05). Associations for IGFBP-2 and fat mass index were more pronounced at higher, for waist circumference at very low or high percentiles of the distribution. In men, there was no consistent relation of breastfeeding with any outcome., Conclusions: Our data suggest that breastfeeding may have long-term, favorable effects on extremes of adiposity and insulin metabolism in women, but not in men. In both sexes, breastfeeding does not seem to induce programming of the GH-IGF-axis.

Background: The specific effects of fruit and vegetable (F&V) intake on water balance and consequently on 24-h hydration status (HS) are unknown., Objectives: In a large observational cohort of German children, we examined whether a higher F&V intake per se is associated with improved HS and attempted to quantify the influence of greater consumption of F&Vs on HS., Design: A total of 1286 complete 3-d weighed dietary records and 24-h urine samples for 442 children (4- to 10-y-olds) collected in 2000-2010 in the Dortmund Nutritional and Anthropometric Longitudinally Designed Study were analyzed. Free water reserve [FWR; urine volume (mL/24 h) minus obligatory urine volume (mL/24 h)] served as an HS biomarker. Median FWR and water balance variables were analyzed in different categories of solid-F&V intakes. Repeated-measures regression models (PROC MIXED; SAS Institute), adjusted for all other dietary water sources, were used to quantify the separate effects of solid-F&V and F&V-juice consumption on FWR., Results: Negative FWR values, which indicated risk of hypohydration, were observed in 22% of children. FWR was significantly higher in solid-F&V consumers with high intakes than in those with low intakes (P < 0.0001). PROC MIXED models predicted an increase of 46 mL in FWR (average in boys and girls) when increasing solid-F&V intake by 100 g. Similar results were observed for F&V juice (β = 43, P < 0.0001). Drinking water and milk were the other significant dietary predictors of FWR. Solid F&Vs and F&V juices contributed 12% and 10%, respectively, to total water intake., Conclusions: These data confirm that regular intake of F&Vs may relevantly improve HS in children. Dietary interventions to increase F&V intake may be a promising strategy to achieve positive water balance in this 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.

Objective: Carbohydrate nutrition during periods of physiological insulin resistance such as puberty may affect future risk of type 2 diabetes. This study examined whether the amount or the quality (dietary glycemic index [GI], glycemic load [GL], and added sugar, fiber, and whole-grain intake) of carbohydrates during puberty is associated with risk markers of type 2 diabetes in younger adulthood., Research Design and Methods: The analysis was based on 226 participants (121 girls and 105 boys) from the Dortmund Nutritional and Anthropometric Longitudinally Designed Study (DONALD) with an average of five 3-day weighed dietary records (range 2-6) during puberty (girls, age 9-14 years; boys, age 10-15 years) and fasting blood samples in younger adulthood (age 18-36 years) (average duration of follow-up 12.6 years). Multivariable linear regression was used to analyze the associations between carbohydrate nutrition and homeostasis model assessment-insulin resistance (HOMA-IR) as well as the liver enzymes alanine aminotransferase (ALT) and γ-glutamyltransferase (GGT) (n = 214)., Results: A higher dietary GI was prospectively related to greater values of HOMA-IR (P(trend) = 0.03), ALT (P(trend) = 0.02), and GGT (P(trend) = 0.04). After adjustment for sex, adult age, baseline BMI, and early life and socioeconomic factors as well as protein and fiber intake, predicted mean HOMA-IR values in energy-adjusted tertiles of GI were 2.37 (95% CI 2.16-2.60), 2.47 (2.26-2.71), and 2.59 (2.35-2.85). The amount of carbohydrates, GL, and added sugar, fiber, and whole-grain intake were not related to the analyzed markers., Conclusions: Our data indicate that a habitually higher dietary GI during puberty may adversely affect risk markers of type 2 diabetes in younger adulthood.

Recent studies provide evidence that insulin-like-growth-factor I (IGF-I) and its binding proteins (IGFBP) IGFBP-2 and IGFBP-3 are related to the risk of several common cancers. It remains to be clarified whether their concentrations can be programmed by protein intake from different sources during growth. This study addressed the hypothesis that animal protein intakes during infancy, mid-childhood, and adolescence differ in their relevance for the growth-hormone (GH)-IGF-I axis in young adulthood. Data from the Dortmund Nutritional and Anthropometric Longitudinally Designed Study participants with at least 2 plausible 3-d weighed dietary records during adolescence (age: girls, 9-14 y; boys, 10-15 y; n = 213), around the adiposity rebound (age 4-6 y; n = 179) or early life (age 0.5-2 y; n = 130), and one blood sample in young adulthood were included in the study. Mean serum concentrations of IGF-I, IGFBP-1, IGFBP-2, and IGFBP-3 were compared between tertiles of habitual animal protein intake using multivariable regression analysis. Habitually higher animal protein intakes in females during puberty were related to higher IGF-I (P-trend = 0.005) and IGFBP-3 (P-trend = 0.01) and lower IGFBP-2 (P-trend = 0.04), but not to IGFBP-1 in young adulthood. In turn, IGF-I concentrations in young adulthood were inversely related to animal protein intakes in early life among males only (P-trend = 0.03), but not to animal protein intake around adiposity rebound (P-trend > 0.5). Our data suggest that, among females, a habitually higher animal protein intake during puberty may precipitate an upregulation of the GH-IGF-I axis, which is still discernible in young adulthood. By contrast, among males, higher animal protein intakes in early life may exert a long-term programming of the GH-IGF-I axis.

Background: The reduced activity of 11β hydroxysteroid dehydrogenase type 2 (11βHSD2) contributes to elevated blood pressure (BP) in clinical syndromes, but its effect on BP in the physiologic range is unclear., Objectives: We examined the association of 11βHSD2 activity with BP in healthy children independent of known BP-related dietary and other factors and determined whether the diet-dependent acid load may constitute a dietary factor related to BP., Design: We conducted a cross-sectional analysis in 267 healthy children (age range: 4-14 y) who provided a 24-h urine sample, a parallel 3-d weighed dietary record, and 1-3 BP measurements ±1.5 y around the urine collection. The ratio of urinary free cortisone to cortisol measured by using a radioimmunoassay was used as an index for 11βHSD2. Urinary net acid excretion and the urinary and dietary potential renal acid load (PRAL) were used to predict the diet-dependent acid load. The PRAL was calculated as the sum of major mineral nonbicarbonate anions minus the sum of mineral cations. Sex-, age- and height-independent SD scores (SDSs) of systolic and diastolic BP were used as outcomes in linear regression analyses., Results: 11βHSD2 was inversely associated with systolic BP SDSs in basic models and in analyses adjusted for body size, maternal BP, breastfeeding, and dietary intakes of total energy, salt, and fruit and vegetables (P = 0.03). In models that included indexes of dietary acid load instead of fruit and vegetables, all 3 acid-load biomarkers were significantly (P = 0.006-0.02) directly related to systolic BP., Conclusion: A lower 11βHSD2 activity and higher dietary acid load may independently contribute to higher systolic BP in healthy children.

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. [ABSTRACT FROM AUTHOR]

High sodium chloride (NaCl) intake can induce low-grade metabolic acidosis (LGMA) and may thus influence bone and protein metabolism. We hypothesized that oral potassium bicarbonate (KHCO(3)) supplementation may compensate for NaCl-induced, LGMA-associated bone resorption and protein losses. Eight healthy male subjects participated in a randomized trial with a crossover design. Each of two study campaigns consisted of 5 d of dietary and environmental adaptation followed by 10 d of intervention and 1.5 d of recovery. In one study campaign, 90 mmol KHCO(3)/d were supplemented to counteract NaCl-induced LGMA, whereas the other campaign served as a control with only high NaCl intake. When KHCO(3) was ingested during high NaCl intake, postprandial buffer capacity ([HCO(3)(-)]) increased (P = 0.002). Concomitantly, urinary excretion of free potentially bioactive glucocorticoids [urinary free cortisol (UFF) and urinary free cortisone (UFE)] was reduced by 14% [∑(UFF,UFE); P = 0.024]. Urinary excretion of calcium and bone resorption marker N-terminal telopeptide of type I collagen was reduced by 12 and 8%, respectively (calcium, P = 0.047; N-terminal bone collagen telopeptide, P = 0.044). There was a trend of declining net protein catabolism when high NaCl was combined with KHCO(3) (P = 0.052). We conclude that during high salt intake, the KHCO(3)-induced postprandial shift to a more alkaline state reduces metabolic stress. This leads to decreased bone resorption and protein degradation, which in turn might initiate an anticatabolic state for the musculoskeletal system in the long run.

Objective: The 'backdoor' pathway provides an efficient route from 17α-hydroxyprogesterone (17-OHP) to dihydrotestosterone (DHT) in patients with 21-hydroxylase deficiency (21-OHD). 17-OHP is a good substrate for 5α-reductase leading to 17α-hydroxyallopregnanolone, which is an excellent substrate for the 17,20-lyase activity of CYP17A1. 5α-Reductase and CYP17A1 are therefore two crucial enzymes in the backdoor route. The 17,20-lyase activity of CYP17A1 additionally promotes the conversion of 17-OHP and 17α-hydroxypregnenolone to androgens in the classical Δ(4) and Δ(5) pathways. Thus, we hypothesised that the activities of 5α-reductase and 17,20-lyase should determine the flux through the androgen synthesis pathways in patients with 21-OHD., Design and Methods: We compared retrospectively urinary steroid hormone profiles determined by gas chromatography-mass spectrometry of 142 untreated 21-OHD patients (age range: 1 day to 25.4 years; 51 males) with 138 control subjects., Results: The relative activities of the backdoor pathway and 5α-reductase correlated significantly (p<0.0001). Neonates with 21-OHD demonstrated a moderate activity of the 5α-reductase leading to moderate 17α-hydroxyallopregnanolone generation in the backdoor pathway. Due to substantial 17,20-lyase activity, 17α-hydroxyallopregnanolone is converted rapidly to androsterone. During infancy, the activity of 5α-reductase is very high leading to a high activity of the backdoor pathway until the generation of 17α-hydroxyallopregnanolone. Only a moderate androsterone production is the result of low 17,20-lyase activity. Children show a low 5α-reductase and a high 17,20-lyase activity leading to a low androsterone generation via the backdoor pathway., Conclusion: The 5α-reductase is the gatekeeper of the backdoor pathway, whereas the 17,20-lyase activity of CYP17A1 is the regulator of the flux through the androgen pathways., (Copyright © 2012 Elsevier Inc. All rights reserved.)

An objective noninvasive biomarker for fruit and vegetable (FV) consumption would help to more reliably characterize the relationship between FV intake and health status in observational studies. Because increases in urinary hippuric acid (HA) were observed after consumption of several FV varieties, we aimed to investigate whether 24-h urinary HA may represent a potential biomarker for FV consumption in children and adolescents. The association of FV and juice (FVJ) intake calculated from 3-d weighed dietary records with 24-h urinary HA excretion was analyzed in 240 healthy children and adolescents and compared with associations of the established biomarkers urinary nitrogen (uN) and urinary potassium (uK) with protein and potassium intake, respectively. Spearman correlation coefficients (r) and cross-classifications were calculated for all diet-biomarker associations. Potential confounders for the HA-FVJ association were examined in linear regression models. In children, correlations of HA with FVJ (r = 0.62), uN with protein (r = 0.64), and potassium intake with uK (r = 0.65) were comparable. In adolescents, the HA-FVJ association was weaker (r = 0.41) compared with the biomarkers uN (r = 0.60) and uK (r = 0.58) (all P < 0.0001). Cross-classification into the same/adjacent quartile by dietary and urinary data were >85% for all analyzed comparisons except for a 75% classification agreement between HA and FVJ in adolescents. Unadjusted and adjusted linear regression models indicated significant (P < 0.0001) HA-FVJ associations in both age groups. FVJ explained more of the variability in HA excretion in children (R(2) = 0.38) than in adolescents (R(2) = 0.22). Our findings in children showing HA-FVJ associations comparable to those for well-established biomarkers with their respective dietary intakes suggest that HA may represent a useful biomarker for FVJ.

The DONALD study has been conducted in Dortmund, Germany since 1985 to examine the complex relations between nutritional intake, metabolism and growth from infancy to adulthood. Every year, approximately 40 infants are newly recruited into the open cohort study. Examinations conducted at ages 3, 6, 9, 12, 18, 24 months and then annually until young adulthood, comprise anthropometry, a 3 day weighed dietary record, a 24 h urine sample (from age 3-4 years onwards), medical examinations and parental interviews. Since 2005, participants are invited for follow-up visits during adulthood (including fasting blood samples). Approximately 1,400 children have been recruited into the study up to 2010. Recent findings revealed e.g. (i) the relevance of early life factors for subsequent development of body composition and puberty timing, (ii) the relation between pubertal hormonal status and puberty onset, (iii) age and time trends in iodine status and modern dietary habits and (iv) potential furan and benzol exposition by commercial weaning foods. Future analyses will provide insight into the extent to which health in young adulthood is receptive to diet, anthropometric pattern and hormonal status in distinct potentially critical periods during childhood.

Mild dehydration, defined as a 1-2% loss in body mass caused by fluid deficit, is associated with risks of functional impairments and chronic diseases. Whether water requirements change with increasing age remains unclear. Therefore, the aim of the present investigation is to quantify hydration status and its complex determining factors from young to old adulthood to analyse age-related alterations and to provide a reliable database for the derivation of dietary recommendations. Urine samples collected over a 24 h period and dietary records from 1528 German adults (18-88 years; sub-sample of the first National Food Consumption Survey) were used to calculate water intake (beverages, food and metabolic water) and water excretion parameters (non-renal water losses (NRWL), urine volume, obligatory urine volume) and to estimate hydration status (free-water-reserve) and 'adequate intake (AI)'. Median total water intake (2483 and 2054ml/d, for men and women, respectively (P<0·0001)), decreased with increasing age only in males (P=0·001). Obligatory urine volume increased in both sexes (P<0·0001) due to decreased renal concentration capacity. The latter was balanced by a decrease of NRWL (P<0·05), leaving the free-water-reserve and therefore hydration status almost unchanged. Calculated 'AI' of total water was the same for young (18-24 years) and elderly (≥65 years) adults (2910 and 2265ml/d, for men and women, respectively). The present study is the first population-based examination showing that total water requirements do not change with age although ageing affects several parameters of water metabolism. Reduced sweat loss with increasing age appears to be primarily responsible for this observation.

Reduced bone mineral density (BMD) and bone mass have been observed in children with idiopathic hypercalciuria. Whether urinary calcium excretion at the higher end of the normal physiologic range can influence bone health in healthy children independent of dietary intake is unknown. Urinary calcium was quantified in 603 24-h urine samples from 154 healthy children and adolescents who had ≥3 urine collections and parallel 3-day weighed dietary records during the 4years preceding proximal forearm bone analyses by peripheral quantitative computed tomography (pQCT). Urinary potential renal acid load (uPRAL) was determined according to urine ionogram by subtracting measured quantitatively important mineral cations from nonbicarbonate anions. Urinary calcium excretion was significantly associated with volumetric (v)BMD (P=0.04), almost significantly with cortical bone mineral content (BMC) (P=0.05), but not with cortical cross-sectional area (CSA) (P=0.09), total CSA (P=0.3), or Strength-Strain Index (P=0.8) in the total population sample. Stratified analyses based on the median split of uPRAL showed that calcium excretion was negatively associated with vBMD (P=0.007), cortical BMC (P=0.001), and cortical CSA (P=0.004) in those children with higher uPRALs, but not in those with low uPRALs (P>0.3). In conclusion, long-term higher calciuria within the physiological range predicts reduced diaphyseal bone mass and bone density particularly in healthy children and adolescents with long-term unfavorable higher dietary acid load, i.e., with lower fruit and vegetable intake., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: 17-Hydroxyprogesterone (17-OHP) can be converted to dihydrotestosterone (DHT) via an alternative "backdoor" route that bypasses the conventional intermediates androstenedione and testosterone. In this backdoor pathway, 17-OHP is converted to 5α-pregnane-3α,17α-diol-20-one (pdiol), which is an excellent substrate for the 17,20 lyase activity of CYP17A1 to produce androsterone. OBJECTIVE AND HYPOTHESES: The objective of this study was to obtain evidence for the presence of the backdoor pathway in patients with 21-hydroxylase deficiency (21-OHD)., Methods: We compared urinary steroid hormone profiles determined by gas chromatography-mass spectrometry of 142 untreated 21-OHD patients (age range, 1 d to 25.4 yr; 51 males) with 138 control subjects. The activity of the backdoor pathway was assessed using the ratios of the urinary concentrations of pdiol to those of the metabolites of the classic Δ4 and Δ5 pathways. In contrast to etiocholanolone, which originates almost exclusively from the classic pathways, androsterone may be derived additionally from the backdoor pathway. Therefore, the androsterone to etiocholanolone ratio can be used as an indicator for the presence of the backdoor pathway., Results: Untreated 21-OHD subjects showed increased urinary ratios of pdiol to the Δ4 and Δ5 pathway metabolites and a higher androsterone to etiocholanolone ratio., Conclusions: The elevated ratios of pdiol to the Δ4 and Δ5 pathway metabolites as well as the higher androsterone to etiocholanolone ratio in patients with 21-OHD indicate postnatal activity of the backdoor pathway with maximum activity during early infancy. Our data provide new insights into the pathophysiology of androgen biosynthesis of 21-OHD.

Early onset of puberty may confer adverse health consequences. Thus, modifiable factors influencing the timing of puberty are of public health interest. Childhood overweight as a factor in the earlier onset of menarche has been supported by prospective evidence; nonetheless, its overall contribution may have been overemphasized, since secular trends toward a younger age at menarche have not been a universal finding during the recent obesity epidemic. Current observational studies suggest notable associations between dietary intakes and pubertal timing beyond contributions to an energy imbalance: children with the highest intakes of vegetable protein or animal protein experience pubertal onset up to 7 months later or 7 months earlier, respectively. Furthermore, girls with high isoflavone intakes may experience the onset of breast development and peak height velocity approximately 7-8 months later. These effect sizes are on the order of those observed for potentially neuroactive steroid hormones. Thus, dietary patterns characterized by higher intakes of vegetable protein and isoflavones and lower intakes of animal protein may contribute to a lower risk of breast cancer or a lower total mortality., (© 2012 International Life Sciences Institute.)

Nonalcoholic fatty liver disease (NAFLD), frequently already present in young subjects, has been linked to reduced growth hormone levels and signaling. Similar hormonal changes occur during metabolic acidosis (MA), which may thus contribute to an increased NAFLD risk. Because subclinical MA can be diet induced, we aimed to examine whether a higher diet-dependent acid load during adolescence is prospectively associated with several currently used NAFLD surrogates in young adulthood. Dietary acidity during adolescence (boys:10-15 y, girls: 9-14 y) was calculated as potential renal acid load (PRAL) from at least three 3-d weighed dietary records according to a published algorithm considering dietary protein and minerals in 145 healthy participants. Routine measurements derived from blood analysis and anthropometric data in participants' young adulthood (18-25 y) were used to determine the NAFLD surrogates alanine-aminotransferase (ALT), hepatic steatosis index (HSI), and fatty liver index (FLI). Sex-stratified linear regression models, adjusted for dietary fiber, saturated fat, protein, and adolescent BMI SD scores, were run with PRAL as the independent variable. Dietary PRAL during puberty was positively associated with ALT (P = 0.02), HSI (P = 0.002), and FLI (P = 0.005) in adult females but not males. Females with an adolescent dietary acid load in the highest tertile had 3.5, 4.4, and 4.5 higher values of ALT, HSI, and FLI as adults, respectively, compared to females with the lowest PRAL. The present findings suggest that higher dietary acidity in adolescence may be prospectively associated with hepatic lipid accumulation in females. Whether this relationship is due to the higher proton load or rather represents an unhealthy dietary pattern requires further investigation.

Cow's milk is one of the most important iodine providers in the human diet. The milk iodine content (MIC) is significantly determined by cattle feeding. The aim of the study was to investigate the longitudinal development of the MIC of German cow's milk during the last years and to assess the current contribution of milk consumption to the population's iodine supply. MIC was analysed by a Cer-Arsenit method after alkaline wet washing in 112 milk samples from nationwide available trademarks (eight samples each were purchased in June and December from 2004 onward to 2010 in the same food markets in the greater Dortmund area). We found an increasing trend of MIC until 2010 (p < 0.005).The mean MIC in 2004/05 was 97 +/- 32 microg/I, in 2009/10 it was 110 +/- 36 microg/l. This increase was only observable for conventionally (p = 0.0003), and not for organically produced milk (p = 0.6). The MIC of summer milk was about 22 microg/l lower than that of winter milk (p < 0.0001), however, seasonal variation was especially pronounced in organically produced milk. MIC of organically produced milk was in average about 54 microg/l lower than that of conventionally produced milk (p < 0.0001). Thus, the moderate increase of MIC to 110 microg/l on average contributes to the maintainence of the population's iodine supply, whereas the analysed maximum iodine contents of around 160 microg/l do not give reason to expect an excessive iodine intake, even in case of a high milk consumption. An appropriate iodine supplementation in foodstuff can be assumed.

Worldwide, the iodisation of salt has clearly improved iodine status. In industrialised countries, iodised salt added to processed food contributes most to iodine supply. Yet it is unclear as to what extent changes in the latter may affect the iodine status of populations. Between 2004 and 2009, 24-h urinary iodine excretions (UIE) were repeatedly measured in 278 German children (6 to 12 years old) of the Dortmund Nutritional and Anthropometric Longitudinally Designed Study (n 707). Na excretion measurements and simultaneously collected 3-d weighed dietary records provided data on intakes of the most important dietary sources of iodine in the children's diet. Actual trends of UIE (2004-9) and contributions of relevant food groups were analysed by mixed linear regression models. Longitudinal regression analysis showed a plateau of UIE in 2004-6; afterwards, UIE significantly decreased till 2009 (P = 0·01; median 24-h UIE in 2004-6: 85·6 μg/d; 2009: 80·4 μg/d). Median urinary iodine concentration fell below the WHO criteria for iodine sufficiency of 100 μg/l in 2007-9. Salt, milk, fish and egg intake (g/d) were significant predictors of UIE (P < 0·005); and the main sources of iodine were salt and milk (48 and 38 %, respectively). The present data hint at a beginning deterioration in the iodine status of German schoolchildren. A decreased use of iodised salt in industrially produced foods may be one possible reason for this development. Because of the generally known risks for cognitive impairment due to even mild iodine deficits in children, a more widespread use of iodised salt, especially in industrially processed foods, has to be promoted.

Background & Aims: Short sleep duration in early childhood may increase the risk for chronic diseases in later life. Strategies to improve sleep duration are thus of interest. We investigated whether the nutritional composition of the evening meal is associated with children's sleep duration in the 2nd year of life., Methods: Multivariable regression models included 594 participants of the DONALD Study with 3-days weighed dietary records and average daily sleep duration at age 1.5 and 2 years., Results: Higher energy intakes with the evening meal were associated with a longer sleep duration (1 min/10 kcal, p = 0,01). With respect to absolute intakes, carbohydrates (0.8 min/g, p < 0.0001), especially from high GI foods (1.3 min/g, p < 0.01), and a higher GL (1.5 min/g GL, p < 0.01) were accompanied by longer sleeping time. A qualitative exchange of energy from protein by energy from carbohydrates from high GI foods was only associated with increased sleep duration in toddlers without (1.9 min/%E, p < 0.05), but not with nightly eating occasions (p > 0.4)., Conclusions: The observed associations are in line with suggested sleep-improving effects of carbohydrates. Effect sizes suggest that the clinical relevance of nutritional composition for sleep duration is limited in healthy young toddlers. These observations and their possible importance for more vulnerable groups need to be confirmed in clinical trials., (Copyright © 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: It has not been investigated whether there are associations between urinary iodine (UI) excretion measurements some years apart, nor whether such an association remains after adjustment for nutritional habits. The aim of the present study was to investigate the relation between iodine-creatinine ratio (ICR) at two measuring points 5 years apart., Methods: Data from 2,659 individuals from the Study of Health in Pomerania were analyzed. Analysis of covariance and Poisson regressions were used to associate baseline with follow-up ICR., Results: Baseline ICR was associated with follow-up ICR. Particularly, baseline ICR >300 μg/g was related to an ICR >300 μg/g at follow-up (relative risk, RR: 2.20; p < 0.001). The association was stronger in males (RR: 2.64; p < 0.001) than in females (RR: 1.64; p = 0.007). In contrast, baseline ICR <100 μg/g was only associated with an ICR <100 μg/g at follow-up in males when considering unadjusted ICR., Conclusions: We detected only a weak correlation with respect to low ICR. Studies assessing iodine status in a population should take into account that an individual with a low UI excretion in one measurement is not necessarily permanently iodine deficient. On the other hand, current high ICR could have been predicted by high ICR 5 years ago., (Copyright © 2011 S. Karger AG, Basel.)