Interlaboratory variability of urinary iodine measurements.

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

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

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

Iodine status in preschool children and evaluation of major dietary iodine sources: a German experience.

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.

Long-term dietary potential renal acid load during adolescence is prospectively associated with indices of nonalcoholic fatty liver disease in young women.

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.

Water balance throughout the adult life span in a German population.

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.

Current trends of 24-h urinary iodine excretion in German schoolchildren and the importance of iodised salt in processed foods.

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.

Urinary Citrate, an Index of Acid-Base Status, Predicts Bone Strength in Youths and Fracture Risk in Adult Females.

CONTEXT: Diet can impact on bone strength via metabolic shifts in acid-base status. In contrast to the strongly diet-dependent biomarker urinary potential renal acid load (uPRAL), the amount of renally excreted citrate integrates nutritional and systemic influences on acid-base homeostasis with high citrate indicating prevailing alkalization. OBJECTIVE: To examine the association between urinary citrate excretion and bone strength as well as long-term fracture risk. DESIGN AND PARTICIPANTS: Prospective cross-sectional analysis; 231 healthy children (6-18 y) of the Dortmund Nutritional and Anthropometric Longitudinally Designed Study were included, with at least 2 urine collections available during the 4 years preceding peripheral quantitative computed tomography (pQCT) of the nondominant proximal forearm. uPRAL, urinary citrate, and urinary nitrogen excretion were quantified in 857 24-hour urine samples. Data on overall fracture incidence were collected within a 15-year follow-up after pQCT measurement. MAIN OUTCOME MEASURES: Parameters of bone quality and geometry (pQCT) as well as long-term fracture incidence. RESULTS: After controlling for confounders, especially forearm length, muscle area, and urinary nitrogen (biomarker of protein intake), urinary citrate excretion was positively associated with various parameters of bone quality and geometry (P < .05). Fracture risk in adult females, but not in males, was inversely associated with urinary citrate and positively with uPRAL (P < .05). CONCLUSIONS: Although urinary citrate has to be confirmed as an integrated noninvasive biomarker of systemic acid-base status in further studies, our results substantiate dietary and metabolic acidity as potentially adverse for bone health in the long run from childhood onward.

Iodine status assessment in children: spot urine iodine concentration reasonably reflects true twenty-four-hour iodine excretion only when scaled to creatinine.

BACKGROUND: Currently, the measurement of urinary iodine concentration (UIC, µg/L) is the recommended parameter to assess iodine status, however, the dependency of UIC on urine volume may limit its use as an accurate parameter for monitoring iodine status in populations. Therefore, our objective was to compare two approaches for the assessment of urinary iodine excretion in spot urine samples: UIC (µg/L) and a creatinine-scaled estimate of 24-hour iodine excretion (est24h-UIEcrea [µg/d]) against actually measured 24-hour urinary iodine excretion rates (24h-UIE, µg/d). METHODS: Urinary iodine and creatinine were measured both in 24-hour urine samples and parallel collected spot urine samples from 180 healthy participants of the DONALD Study, aged 6-18 years. 24h-UIE was used as quasi-reference for actual iodine status. Published 24-hour creatinine reference values served to calculate est24h-UIEcrea. Correlation analysis, cross-classifications, and Bland-Altman plots were used to evaluate agreement between the different assessment approaches. RESULTS: Correlation coefficients of 24h-UIE with UIC (r=0.12, r=0.22; p=n.s.) were substantially weaker than with est24h-UIEcrea (r=0.41, r=0.47; p<0.001) in the 6-12 year old and 13-18 year old groups, respectively. Cross-classification into opposite quartiles by UIC was 7% (6-12 year old group) and 15% (13-18 year old group) versus 5% and 3% by est24h-UIEcrea, respectively. Bland-Altman plots indicated greater deviation from 24h-UIE for the UIC versus the est24h-UIEcrea approach. CONCLUSION: Our findings in children and adolescents clearly show a better comparability of real 24h-UIE with est24h-UIEcrea than with UIC. Whenever highest possible validity is required for iodine status assessment from spot urine sampling, the determination of est24h-UIEcrea appears to be the more accurate monitoring approach.

Interrelations between thyrotropin levels and iodine status in thyroid-healthy children.

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.

Contribution of fruit and vegetable intake to hydration status in schoolchildren.

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 (ß = 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.

[Time trends and seasonal variation of iodine content in German cow's milk--investigations from Northrhine-Westfalia]. / Aktuelle Untersuchungen zeitlicher Trends und saisonaler Effekte des Jodgehaltes in Kuhmilch--Untersuchungen aus Nordrhein Westfalen.

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.

Higher urine volume results in additional renal iodine loss.

BACKGROUND: For some endocrine and nutritional biomarkers, for example, cortisol and vitamin B(12), significant associations between 24-hour renal analyte excretion and the respective 24-hour urine volume (U-Vol) have been reported. Therefore, our objective was to investigate whether 24-hour U-Vol (a marker of fluid intake) is also a relevant influencing factor of absolute daily iodine excretion. METHODS: Urinary iodine excretion rates were measured in repeatedly collected 24-hour urine samples of (i) 9 healthy women participating in a controlled diet experiment with constant iodine intake and (ii) 204 healthy free-living adolescents (aged 13-18 years) who performed the respective urine collection during 2003-2008. Associations between U-Vol (L) and renal iodine excretion (µg/24 h) were investigated cross sectionally (multiple linear regression model, PROC GLM) and longitudinally (repeated-measures regression models, PROC MIXED). The major iodine sources in the adolescent's diet (iodized salt, milk, fish, eggs, and meat) were controlled for. RESULTS: Urinary iodine excretion was significantly associated with 24-hour U-Vol in all performed fully adjusted regression models. A 1-L increase of U-Vol predicted an additional 15.0 µg/day (adolescents, 95% confidence interval: [9.8, 20.0], p < 0.0001) and 16.5 µg/day (women, 95% confidence interval: [9.2, 23.7], p = 0.0002) increase in iodine excretion. The longitudinal analysis in adolescents revealed a stronger relation of iodine excretion with U-Vol in girls than in boys (ß = 17.1 vs. ß = 10.5). CONCLUSION: A high fluid consumption, and thus a high U-Vol, could lead to an additional renal iodine loss that obviously cannot be compensated by the iodine contents of non-milk-based beverages, reported to amount to ∼4 µg/L, on average. For specific research questions using the biomarker 24-hour urinary iodine excretion, U-Vol should therefore be considered as a potential confounder.