Biomarker-based nutritional phosphorus status in children and adolescents and its long-term association with the endocrine phosphate regulatory and adrenal medullary system

This thesis investigates biomarker-based the long-term physiological implications of higher phosphorus intake during childhood and adolescence, with a focus on how a habitually phosphorus-rich nutrition during growth shapes the phosphate metabolism-related endocrine and the sympathetic nervous system. Using longitudinal data from the DONALD (DOrtmund Nutritional and Anthropometric Longitudinally Designed) Study, the research integrates biomarker-based assessments of nutrient intake with 24h urine and blood measurements in young adulthood to examine in three studies implications and consequences of long-term phosphorus ingestion relevantly exceeding dietary recommendations. Study I examined trends in phosphorus intake (P-In) among German children and adolescents over a 30-year period (1985–2015), using 24-hour urinary phosphate excretion (PO4-Ex) as a biomarker. Despite considerable changes in the food environment, PO4-Ex remained stable over time. However, intake levels consistently exceeded recommended dietary allowances (RDAs), pointing to chronic overexposure in around half of the participants examined. PO4-Ex was significantly associated with protein and sodium intake, net acid excretion, and inversely with fruit and vegetable intake all biomarker-based assessed, indicating that phosphate metabolism is shaped not only by absolute intake, but also by overall dietary quality and acid–base balance. Study II extended these findings by linking habitual P-In and dietary acid load during growth with endocrine markers of phosphate regulation—namely fibroblast growth factor 23 (FGF23) and α-klotho—in young adulthood. A positive association was observed between early P-In and circulating FGF23 levels, indicating that high phosphorus exposure during critical developmental periods may alter long-term endocrine regulation. This suggests that dietary phosphorus exerts a long-lasting regulatory influence on the endocrine pathways governing phosphate metabolism with adversly altering the constellation of FGF23 and α-klotho in a way that is usually seen along with kidney decline. In Study III the link between urinary catecholamine excretion in young adulthood and preceding P-In in children and adolescents had been investigated. The results revealed a significant, sex-specific association between early phosphorus intake and increased excretion of epinephrine and norepinephrine in females—suggesting that phosphorus may play a role in modulating sympathetic nervous system activity in the long-term. These findings introduce the possibility that habitual phosphate exposure during growth could influence neuroendocrine stress responses later in life, potentially through adrenally involved phosphate-sensitive pathways. Overall, the studies provide support for the concept that chronic dietary phosphorus excess, particularly from various probably well available sources, acts through multiple regulatory axes—including endocrine, renal, and sympathoadrenal pathways—to potentially unfavorable influence long-term metabolic and physiological health.