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.

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.

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, P¼0·06) and marginally (P¼ 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 (P¼ 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.Key words: Blood pressure: Salt: fruit and vegetable: Children: Potassium CVD and cerebrovascular diseases are two leading causes of death (1) and hypertension is a main risk factor for the occurrence of CHD and stroke (2) . The evidence for a causal relationship between chronic high salt intake and high blood pressure (BP) in adults is strong (3,4) . Apart from salt intake, the potential of a higher fruit and vegetable intake (FVI) to decrease BP has been documented in well-conducted intervention studies (5,6) . In one well-controlled trial, the Dietary Approaches to Stop Hypertension (DASH) Study, it has been shown that a reduction of salt intake together with the consumption of a FV-rich diet leads to the greatest reduction of BP (7) .Concern exists about the rising prevalence of hypertension in childhood and adolescence (8) and the existing tracking pattern of BP (9) . Therefore, it is important that modifiable risk factors be identified and preventive nutritional measures be started early in childhood. A meta-analysis of ten controlled trials (10) with a median duration of 4 weeks has provided evidence that dietary salt intake during growth plays a role in the regulation of BP in children. Longitudinal or intervention studies on the influence of FVI on BP are rare, especially in normotensive children. So far, a small longitudina...

Metabolic acidosis induces elevated glucocorticoid (GC) levels. However, the influence of less strong daily acid loads on GCs is largely unexplored. To investigate this, we studied whether higher acid loads in children, fully within the normal range of habitual diets, associate with endogenous GCs. In a specific quasi-experimental design, we examined 200 6- to 10-year-old healthy participants of the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study equally divided to either high or low 24-hour renal net acid excretion. Major urinary GC metabolites were analyzed by gas chromatography-mass spectrometry to assess daily adrenal GC secretion and metabolites of tissue cortisol catabolism (6β-hydroxycortisol and 20α-dihydrocortisol). Liquid chromatography-mass spectrometry was used to quantify urinary free cortisol and cortisone. After confounder adjustment, significant positive associations were unmasked for urinary potential renal acid load and net acid excretion with adrenal GC secretion, free cortisone, free cortisone plus cortisol, 6β-hydroxycortisol, and 20α-dihydrocortisol. An inverse association emerged for an enzymatic marker (5β-reductase) of irreversible GC inactivation. Our data suggest that existing moderate elevations in diet-dependent acid loads suffice to raise GCs and affect cortisol metabolism. Thus, potential detrimental effects of high acid loading appear to be mediated, in part, by increased GC activity via increased GC secretion and/or reduced GC inactivation. Higher cortisone levels, directly available for intracrine activation to cortisol may play a special role.

A higher animal protein intake may be involved in an earlier attainment of ATO and APHV, whereas a more intensive adrenarchal process may precipitate a shorter pubertal growth spurt and a notably earlier onset of breast and genital development in girls and boys, respectively.

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.

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.

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