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Submitted on January 5, 2006
Accepted on May 22, 2006
Division of Endocrinology, Department of Medicine, University of California, San Francisco, California, USA; Pharmaceutical Research Laboratory, Kirin Brewery Co. Ltd., Takasaki, Japan; Division of Pediatric Nephrology, Department of Pediatrics, University of California, San Francisco, California, USA
* To whom correspondence should be addressed. E-mail: aportale{at}peds.ucsf.edu.
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(OH)2D concentrations. Conversely, states of absent or biologically inactive circulating FGF-23 are associated with increased serum phosphorus and 1,25(OH)2D concentrations. Restriction of the dietary intake of phosphorus increases renal phosphate reabsorption and 1,25(OH)2D 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)2D to changes in dietary phosphorus.
Design, Setting and Participants: We studied 13 healthy men as inpatients during a 4-week 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 days: 1) control =1,500 mg/day; 2) supplemented =2,300 mg/day; 3) restricted =625 mg/day. Intakes of calcium, sodium, potassium, magnesium and energy were constant.
Main Outcome Measure: Serum FGF-23, 1,25(OH)2D, phosphorus and calcium concentrations.
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)2D concentrations increased significantly from 29 ± 10 pg/ml (75 ± 26 pmol/L) during phosphorus supplementation to 40 ± 16 pg/ml (104 ± 42 pmol/L) during phosphorus restriction (P < 0.001). Serum 1,25(OH)2D 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 physiologic range of intakes regulate serum FGF-23 concentrations, and suggest that dietary phosphorus regulation of 1,25(OH)2D production is mediated, at least in part, by changes in circulating FGF-23.
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