Effects of a high-protein diet on regulation of phosphorus homeostasis.

High-protein diets, which are popular for weight loss, contain large quantities of phosphorus. Phosphorus excess and consequent changes in phosphorus regulatory hormones are implicated in vascular calcification and cardiovascular disease. We tested the hypothesis that a moderate increase in dietary phosphorus during a high-protein diet leads to changes in phosphorus-responsive hormones. We conducted a post hoc analysis of a sequential dietary modification trial in 19 healthy volunteers in the general community. Participants received 2 weeks of a weight-maintaining, low-protein (15%) diet, followed by 2 weeks of an isocaloric, high-protein (30%) diet, followed by 12 weeks of an ad libitum high-protein (30%) diet. Using previously collected samples, plasma concentrations of fibroblast growth factor-23 (FGF-23), PTH, 1,25-dihydroxyvitamin D, and 24,25-dihydroxyvitamin D were measured at 8 time points to assess 24-hour variability and in 24-hour pooled samples to delineate changes at the end of each diet period. Mean dietary phosphorus intake during each study period was 1556, 2071, and 1622 mg/d, respectively. Plasma concentrations of FGF-23 and vitamin D metabolites varied in a diurnal pattern; plasma PTH concentrations varied in a bimodal pattern. After changing from a low- to high-protein isocaloric diet, plasma FGF-23 concentrations decreased slightly (mean -4.48 pg/mL, 95% confidence interval 1.88-7.07). There were no other statistically significant changes in phosphorus regulatory hormones in response to diet modifications. Among healthy people, an approximate 33% increase in dietary phosphorus after institution of a high-protein diet does not cause large changes in measured concentrations of phosphorus regulatory hormones.