Dietary Phosphorus Regulates Serum Fibroblast Growth Factor-23 Concentrations in Healthy Men

CONTEXT: Fibroblast growth factor 23 (FGF-23) is important in the regulation of phosphorus and vitamin D metabolism. States of excess circulating FGF-23 are associated with renal phosphate wasting and inappropriately low serum 1,25-dihydroxyvitamin D 1,25(OH)(2)D concentrations. Conversely, states of absent or biologically inactive circulating FGF-23 are associated with increased serum phosphorus and 1,25(OH)(2)D concentrations. Restriction of the dietary intake of phosphorus increases renal phosphate reabsorption and 1,25(OH)(2)D production, whereas the opposite occurs when dietary phosphorus is supplemented. OBJECTIVE: We sought to determine whether serum FGF-23 concentration is regulated by dietary phosphorus and thereby mediates the physiological response of serum 1,25(OH)(2)D to changes in dietary phosphorus. DESIGN, SETTING, AND PARTICIPANTS: We studied 13 healthy men as inpatients during a 4-wk dietary phosphorus intervention study. INTERVENTION: Subjects consumed a constant diet that provided 500 mg of phosphorus per day, which was supplemented to achieve three phosphorus intakes, each of 9 d: 1) control = 1500 mg/d; 2) supplemented = 2300 mg/d; 3) restricted = 625 mg/d. Intakes of calcium, sodium, potassium, magnesium, and energy were constant. MAIN OUTCOME MEASURE: Serum FGF-23, 1,25(OH)(2)D, phosphorus, and calcium concentrations were measured. RESULTS: Serum FGF-23 concentrations decreased significantly from 30.7 +/- 8.7 pg/ml during phosphorus supplementation to 19.6 +/- 7.0 pg/ml during phosphorus restriction. Serum 1,25(OH)(2)D concentrations increased significantly from 29 +/- 10 pg/ml (75 +/- 26 pmol/liter) during phosphorus supplementation to 40 +/- 16 pg/ml (104 +/- 42 pmol/liter) during phosphorus restriction (P < 0.001). Serum 1,25(OH)(2)D concentrations varied inversely with those of serum FGF-23 (r = -0.67, P < 0.001). CONCLUSIONS: We conclude that in healthy men, changes in dietary phosphorus within the physiological range of intakes regulate serum FGF-23 concentrations and suggest that dietary phosphorus regulation of 1,25(OH)(2)D production is mediated, at least in part, by changes in circulating FGF-23.