Estimates of renal net acid excretion and their relationships with serum uric acid and hyperuricemia in a representative German population sample.

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

Renal biomarkers of acid excretion capacity: relationships with body fatness and blood pressure.

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

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

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

Increased body fatness adversely relates to 24-hour urine pH during childhood and adolescence: evidence of an adipo-renal axis.

BACKGROUND: Reduced net acid excretion (NAE) capacity indicates a decrease in renal function. This reduction manifests as a disproportionally low 24-h urine pH in relation to the sum of actually excreted ammonium and titratable acidity by the kidney. OBJECTIVE: The aim of this study was to test the hypothesis that higher body fatness is one determinant of kidney function impairment with a lowered urine pH even at a young age. METHODS: NAE, pH, urea, and creatinine were measured in 24-h urine samples from 524 healthy children and adolescents (aged 6-17 y) participating in the DOrtmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study. Body fatness was assessed anthropometrically by body mass index-standard deviation score (BMI-SDS), fat mass index (FMI), body fat % (BF%), and waist circumference (WC). Multivariable linear and mixed linear regressions were used to examine cross-sectionally (n = 524 urine samples; age groups: 6-8, 9-11, 12-14, 15-17 y) and longitudinally (n = 1999 urine samples) the associations of body fatness with 24-h urine pH as the outcome variable, respectively. RESULTS: After adjusting for the kidneys' total net acid load (24-h urinary NAE) and further relevant covariates, FMI showed significant inverse relations with urinary pH in all 4 age groups, and BMI-SDS, BF%, and WC each in 3 out of these 4 groups (P ≤ 0.02). Longitudinal results substantiated these interindividual relations and further showed intraindividual increases in body fatness to be paralleled by urine pH decreases (P ≤ 0.0002). CONCLUSIONS: Independent of underlying acid load, an early increase in body fatness is associated with increased free proton excretion, and thus with a decline in the kidney's acid excretion function, which could potentiate the risk of renal nephrolithiasis.

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

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

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

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

Dietary Acid Load and Potassium Intake Associate with Blood Pressure and Hypertension Prevalence in a Representative Sample of the German Adult Population.

Diets rich in fruits and vegetables, like the Dietary Approaches to Stop Hypertension (DASH)-diet, are usually characterized by high potassium intake and reduced dietary acid load, and have been shown to reduce blood pressure (BP). However, the relevance of potential renal acid load (PRAL) for BP has not been compared with the relevance to BP of urinary biomarker (K-urine)- and dietary food frequency questionnaire (K-FFQ)-based estimates of potassium intake in a general adult population sample. For 6788 participants (aged 18-79 years) of the representative German Health-Interview and Examination Survey for Adults (DEGS1), associations of PRAL, K-urine, and K-FFQ with BP and hypertension prevalence were cross-sectionally examined in multivariable linear and logistic regression models. PRAL was significantly associated with higher systolic BP (p = 0.0002) and higher hypertension prevalence (Odds ratio [OR] high vs. low PRAL = 1.45, p = 0.0004) in models adjusted for age, sex, body mass index (BMI), estimated sodium intake, kidney function, relevant medication, and further important covariates. Higher estimates of K-FFQ and K-urine were related to lower systolic BP (p = 0.04 and p < 0.0001) and lower hypertension prevalence (OR = 0.82, p = 0.04 and OR = 0.77, p = 0.02) as well as a lower diastolic BP (p = 0.03 and p = 0.0003). Our results show, for the first time in a comparative analysis of a large representative population sample, significant relationships of BP and hypertension prevalence with questionnaire- and biomarker-based estimates of potassium intake and with an estimate of dietary acid load.

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

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

Diet-independent relevance of serum uric acid for blood pressure in a representative population sample.

A direct relationship between serum uric acid and blood pressure (BP) has been reported, but the possible confounding impact of diet on this association is unclear. The authors performed a cross-sectional analysis in the representative German Health Interview and Examination Survey for Adults (n=6788, aged 18-79 years). In adjusted regression models considering dietary factors, each 1-mg/dL higher uric acid value was associated with a 1.10-mm Hg (P=.0002) and a 0.60-mm Hg (P=.04) higher systolic BP among participants younger than 50 years and participants 50 years and older, respectively. For diastolic BP, uric acid was a significant predictor (ß=0.71 mm Hg, P=.0001) among participants younger than 50 years and for participants 50 years and older without antihypertensive treatment. Adjusted odds ratios of hypertension for participants with hyperuricemia were broadly similar in younger (odds ratio, 1.71; P=.02) and older (odds ratio, 1.81; P=.0003) participants. Uric acid is a significant predictor of systolic BP and hypertension prevalence in the general adult population in Germany independently of several known dietary BP influences.

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

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

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

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

Early Diet and Later Cancer Risk: Prospective Associations of Dietary Patterns During Critical Periods of Childhood with the GH-IGF Axis, Insulin Resistance and Body Fatness in Younger Adulthood.

Early life, adiposity rebound, and puberty represent critical growth periods when food choices could have long-term relevance for cancer risk. We aimed to relate dietary patterns during these periods to the growth hormone-insulin-like-growth-factor (GH-IGF) axis, insulin resistance, and body fatness in adulthood. Data from the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study participants with outcome data at 18-37 years, and ≥2 dietary records during early life (1-2 yr; n = 128), adiposity rebound (4-6 years, n = 179), or puberty (girls 9-14, boys 10-15 yr; n = 213) were used. Dietary patterns at these ages were derived by 1) reduced rank regression (RRR) to explain variation in adult IGF-I, IGF-binding protein-3 (IGFBP-3), homoeostasis model assessment for insulin resistance (HOMA-IR) and fat-mass index; 2) principal component analysis (PCA). Regarding RRR, the patterns "cake/canned fruit/cheese & eggs" (early life), "sweets & dairy" (adiposity rebound) and "high-fat foods" (pubertal boys) were independently associated with higher adult HOMA-IR. Furthermore, the patterns "favorable carbohydrate sources" (early life), "snack & convenience foods" (adiposity rebound), and "traditional & convenience carbohydrates" (pubertal boys) were related to adult IGFBP-3 (P trend < 0.01). PCA identified "healthy" patterns for all periods, but none was associated with the outcomes (P trend > 0.1). In conclusion, dietary patterns during sensitive growth periods may be of long-term relevance for adult insulin resistance and IGFBP-3.

Prospective relevance of fruit and vegetable consumption and salt intake during adolescence for blood pressure in young adulthood.

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

Dietary protein's and dietary acid load's influence on bone health.

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.

Longitudinal relationships between diet-dependent renal acid load and blood pressure development in healthy children.

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.

Salt, fruit and vegetable consumption and blood pressure development: a longitudinal investigation in healthy children.

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.

Animal protein intakes during early life and adolescence differ in their relation to the growth hormone-insulin-like-growth-factor axis in young 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.

11ß Hydroxysteroid dehydrogenase type 2 and dietary acid load are independently associated with blood pressure in healthy children and adolescents.

BACKGROUND: The reduced activity of 11ß hydroxysteroid dehydrogenase type 2 (11ßHSD2) 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 11ßHSD2 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 11ßHSD2. 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: 11ßHSD2 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 11ßHSD2 activity and higher dietary acid load may independently contribute to higher systolic BP in healthy children.