Abstract
Increased dietary inorganic phosphate (Pi) intake stimulates renal Pi excretion, in part, by parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23) or dopamine. High dietary Pi 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 Pi intake over shorter periods are unknown. We studied the effects of a low or high Pi 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 Pi diet) or phosphate capsules (750 mg phosphorus, high Pi diet) in a randomized cross-over trial for 5 days with a 7-day washout between diets. High Pi intake increased plasma Pi levels and 24-h excretion and decreased urinary calcium excretion. High Pi 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 Pi excretion and reducing calcitriol in healthy young men during steady-state high dietary Pi intake. High dietary Pi intake elevated blood Pi levels in healthy young subjects with normal renal function and may therefore be a health risk, as higher serum Pi levels are associated with cardiovascular risk in the general population.