Diets containing inorganic phosphate additives are unbalanced with respect to calcium and these diets have been linked to the development of altered bone metabolism. Using two randomized cross-over studies in healthy humans, we (1) characterized the hormonal and urinary response to two meals with the same reported phosphorus amount (562-572 mg), where one was manufactured with inorganic phosphate additives and a comparatively lower Ca:P molar ratio (0.26 vs. 0.48), and (2) assessed how acute homeostatic mechanisms adapt following 5-day exposure to recommended dietary phosphorus amount (~700 mg P/day) compared to a diet enriched with inorganic phosphate additives (~1100 mg P/day). Participants were then challenged with 500 mg of oral phosphorus in the form of inorganic phosphate after an overnight fast following each diet condition. Measurements included serum calcium, phosphate, PTH, and FGF-23, vitamin D metabolites, and urine calcium and phosphate excretion. Following the meal containing inorganic phosphate additives with a low Ca:P ratio, serum phosphate was higher and more phosphate was excreted in the urine compared to the low additive meal. Although the Ca:P and calcium content was lower in the high additive meal, the same amount of calcium was excreted into the urine. Subsequently increasing only dietary phosphate through additives resulted in lower 24-hour excretion of calcium. The oral phosphate challenge promoted urinary calcium excretion, despite no consumption of calcium, which was attenuated when pre-acclimated to a high phosphate diet. These data suggest that ingestion of inorganic phosphate promotes calcium excretion, but homeostatic mechanisms may exist to reduce calcium excretion that are responsive to dietary intake of phosphate. Future studies are required to evaluate potential implication of diets enriched with inorganic phosphate additives on bone health.
