Effect of Phosphorus Additives on the Metabolome in Healthy Adults

This study evaluates the effect of phosphorus supplementation on the human metabolome. 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 in between. Untargeted metabolomic analyses will be done in serum samples obtained at the end of each diet period.

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.

Eligible subjects will consume a phosphorus supplemented diet (study diet) and a sodium and potassium chloride supplemented diet (control diet), with cross-over to the other diet following a 24-day wash-out period. The order in which the diets are consumed will be randomly assigned.

Participants will be asked to consume a normal diet supplemented with sodium chloride (sodium chloride tablets, USP, 1 gram; 3 tablets per day) and potassium chloride (Klor-Con, 8 mEq; 0.5 tablets per day) for 1 week.

Participants will be instructed to consume a normal diet with supplemental phosphorus (K-Phos Neutral tablets, 250 mg; 4 tablets a day) for 1 week.

Participants will be instructed to consume a normal diet and will take a total of 1,000 mg of supplemental phosphorus per day in the form of neutral sodium phosphorus (K-Phos neutral®) for 1 week.

Participants will be asked to consume a normal diet supplemented with sodium and potassium chloride tablets commensurate with the extra sodium and potassium content consumed during the study diet period for 1 week

Untargeted metabolomics will be the primary endpoint and will be performed on serum samples obtained for all participants at the end of each dietary 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).

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