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

Abstract

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.