UCSF

Background Despite epidemiologic evidence for increased cardiovascular morbidity and mortality associated with both high dietary and serum phosphate in humans with normal renal function, no controlled phosphate intervention studies of systemic hemodynamics have been reported. Higher serum 25(OH) vitamin D levels are associated with better cardiovascular outcomes, but vitamin D increases intestinal phosphate absorption.Methods We conducted a prospective outpatient study with blinded assessment in 20 young adults with normal renal function randomized to high phosphate (regular diet plus 1 mmol/kg body wt per day of Na as neutral sodium phosphate) or low phosphate (regular diet plus lanthanum, 750 mg thrice/day, plus 0.7 mmol/kg body wt per day of Na as NaCl) for 11 weeks. After 6 weeks, all subjects received vitamin D₃ (600,000 U) by intramuscular injection. Outcome parameters were 24-hour ambulatory systolic and diastolic BP (SBP and DBP), pulse rate (PR), biomarkers, and measures of endothelial and arterial function.Results Compared with the low-phosphate diet group, the high-phosphate diet group had a significant increase in mean±SEM fasting plasma phosphate concentration (0.23±0.11 mmol/L); 24-hour SBP and DBP (+4.1; 95% confidence interval [95% CI], 2.1 to 6.1; and +3.2; 95% CI, 1.2 to 5.2 mm Hg, respectively); mean 24-hour PR (+4.0; 95% CI, 2.0 to 6.0 beats/min); and urinary metanephrine and normetanephrine excretion (54; 95% CI, 50 to 70; and 122; 95% CI, 85 to 159 µg/24 hr, respectively). Vitamin D had no effect on any of these parameters. Neither high- nor low-phosphate diet nor vitamin D affected endothelial function or arterial elasticity.Conclusions Increased phosphate intake (controlled for sodium) significantly increases SBP, DBP, and PR in humans with normal renal function, in part, by increasing sympathoadrenergic activity.