Effect of Phosphorus Additives on the Metabolome in Healthy Adults

Phosphorus is an essential micronutrient involved in a number of key biological processes. Excess phosphorus intake is linked to hypertension, heart failure, and disorders of bone and mineral metabolism. This has critical implications for public health in that dietary phosphorus consumption in the US far exceeds current recommendations for daily intake.

Most studies that examined the adverse effects of excess phosphorus intake have focused on single tissue or cell specific processes. However, a full understanding of the systemic impact of nutritional phosphorus intake requires a more integrated biologic approach. The human metabolome represents the final end-product of the omics cascade, which can serve as an integrated measure of the total biological response to dietary exposures. Few studies have examined the impact of nutritional phosphorus intake on the human metabolome. Expanding the understanding of the effect of diet phosphorus on the metabolome has the potential to identify novel phosphorus-responsive pathways that may be therapeutic targets for reducing the development of hypertension, cardiovascular and kidney disease. The investigators will test the following hypothesis: consumption of a high phosphorus diet will result in significant changes in circulating metabolites associated with cardiometabolic health.

This hypothesis is supported by published and preliminary studies showing that high phosphorus intake alters metabolic pathways with a wide variety of pathophysiologic effects. In the current application, the investigators propose to build on this work by investigating the effect of phosphorus consumption on the human metabolome using an untargeted approach. The investigators will do so by conducting a cross-over study in healthy adults consuming a study diet (normal diet supplemented by neutral sodium phosphorus, 1 gram/day) for seven days and a control diet (normal diet supplemented by sodium and potassium chloride only) for seven days with a 28 day wash-out period.

Inclusion criteria

• healthy volunteers, aged 18 - 45 years with normal kidney function (estimated glomerular filtration rate > 60 ml/min/1.73m2).

Exclusion criteria

• abnormal urinalysis-presence of hematuria, proteinuria, or leukocyturia. pregnancy or breast-feeding
• Medical conditions impacting phosphate metabolism-primary hyperparathyroidism; gastrointestinal malabsorption disorders such as Crohn's Disease, ulcerative colitis, celiac disease, or liver dysfunction; hyper- or hypothyroidism; irregular menses for female subjects.
• Medications known to affect phosphorus metabolism- current use of phosphorus supplements, high-dose or activated vitamin D compounds, regular antacid or laxative use, anticonvulsants.
• Hyper- or hypophosphatemia (≥ 4.6 mg/dl or ≤ 2.5 mg/dl respectively), hyper- or hypocalcemia (≥ 10.6 or ≤ 8.5 mg/dl respectively), or severe anemia (hemoglobin < 8 g/dl for women and < 9 g/dl for men), hyperkalemia (potassium > 5.0 mmol/L).