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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 [less than or equal to] 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., Author(s): Danika Krupp [sup.1], Yifan Hua [sup.1], Jonas Esche [sup.1], Thomas Remer [sup.1] Author Affiliations: (1) DOrtmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study Center, Department of Nutritional Epidemiology, Institute [...]

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 (eNAE.sub.PRAL+OA) and the other based on FFQ-derived protein and potassium intake ratios (eNAE.sub.Prot/K). The associations of eNAE.sub.PRAL+OA and eNAE.sub.Prot/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, eNAE.sub.PRAL+OA (p = 0.0048) and eNAE.sub.Prot/K (p = 0.0023) were positively associated with SUA. In addition, participants with a higher eNAE.sub.PRAL+OA or eNAE.sub.Prot/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., Author(s): Jonas Esche [sup.1], Danika Krupp [sup.1], Gert BM Mensink [sup.2], Thomas Remer [sup.1] Author Affiliations: (1) DONALD Study Center Dortmund, IEL - Nutritional Epidemiology, University of Bonn, Dortmund, Germany [...]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM PUBLISHER]

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. [ABSTRACT FROM PUBLISHER]