Controlled dietary phosphate loading in healthy young men elevates plasma phosphate and FGF23 levels

• Published in: Pflügers Archiv Vol. 477; no. 3; pp. 495 - 508
• Main Authors: Gerber, Jennifer Scotti, Arroyo, Eva Maria Pastor, Pastor, Johanne, Correia, Miguel, Rudloff, Stefan, Moe, Orson W., Egli-Spichtig, Daniela, Mohebbi, Nilufar, Wagner, Carsten A.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.03.2025; Springer Nature B.V
• Subjects: Adult; Aldosterone; Biomedical and Life Sciences; Biomedicine; Blood levels; Calcitriol; Calcitriol - blood; Calcium (dietary); Calcium (urinary); Calcium - urine; Calcium metabolism; Cardiovascular diseases; Cell Biology; Cross-Over Studies; Diet; Dietary intake; Dopamine; Excretion; Fibroblast Growth Factor-23; Fibroblast Growth Factors - blood; Glucuronidase - blood; Human Physiology; Humans; Klotho protein; Klotho Proteins; Male; Molecular Medicine; Neurosciences; Norepinephrine; Nutrient deficiency; Parathyroid hormone; Parathyroid Hormone - blood; Phosphate; Phosphates - administration & dosage; Phosphates - blood; Phosphorus; Phosphorus, Dietary - administration & dosage; Physiology; Receptors; Renal function; Young Adult; Human trial; Diet; FGF23; Phosphate; Health risk
• ISSN: 0031-6768; 1432-2013; 1432-2013
• DOI: 10.1007/s00424-024-03046-4

Increased dietary inorganic phosphate (P i ) intake stimulates renal P i excretion, in part, by parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23) or dopamine. High dietary P i may also stimulate sympathetic outflow. Rodent studies provided evidence for these regulatory loops, while controlled experiments in healthy humans examined periods of either a few hours or several weeks, and often varied dietary calcium intake. The effects of controlled, isolated changes in dietary P i intake over shorter periods are unknown. We studied the effects of a low or high P i diet on parameters of mineral metabolism in 10 healthy young men. Participants received a standardized diet (1000 mg phosphorus equivalent/day) supplemented with either a phosphate binder (low P i diet) or phosphate capsules (750 mg phosphorus, high P i diet) in a randomized cross-over trial for 5 days with a 7-day washout between diets. High P i intake increased plasma P i levels and 24-h excretion and decreased urinary calcium excretion. High P i intake increased intact FGF23 (iFGF23) and suppressed plasma Klotho without affecting cFGF23, PTH, calcidiol, calcitriol, Fetuin-A, dopamine, epinephrine, norepinephrine, metanephrine, or aldosterone. Higher iFGF23 correlated with lower calcitriol and higher PTH. These data support a role for iFGF23 in increasing renal P i excretion and reducing calcitriol in healthy young men during steady-state high dietary P i intake. High dietary P i intake elevated blood P i levels in healthy young subjects with normal renal function and may therefore be a health risk, as higher serum P i levels are associated with cardiovascular risk in the general population.