Effect of Phosphorus Additives on the Metabolome in Healthy Adults
Study Details
Study Description
Brief Summary
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.
Condition or Disease | Intervention/Treatment | Phase |
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N/A |
Detailed Description
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Placebo Comparator: Control diet 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. |
Other: Control Diet
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
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Experimental: Phosphorus-supplemented study diet 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. |
Other: Phosphorus-supplemented study diet
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.
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Outcome Measures
Primary Outcome Measures
- Untargeted Metabolomics [7 days]
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.
Secondary Outcome Measures
- Fibroblast growth factor 23 (FGF23) [7 days]
FGF23 concentrations will be measured at the end of each dietary period
Eligibility Criteria
Criteria
Inclusion Criteria:
- healthy volunteers, aged 18 - 45 years with normal kidney function (estimated glomerular filtration rate > 60 ml/min/1.73m2).
Exclusion Criteria:
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abnormal urinalysis-presence of hematuria, proteinuria, or leukocyturia. pregnancy or breast-feeding
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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.
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Medications known to affect phosphorus metabolism- current use of phosphorus supplements, high-dose or activated vitamin D compounds, regular antacid or laxative use, anticonvulsants.
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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).
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | University of Alabama | Birmingham | Alabama | United States | 35294 |
Sponsors and Collaborators
- University of Alabama at Birmingham
Investigators
- Principal Investigator: Orlando Gutierrez, M.D., University of Alabama at Birmingham
Study Documents (Full-Text)
None provided.More Information
Publications
- Adeney KL, Siscovick DS, Ix JH, Seliger SL, Shlipak MG, Jenny NS, Kestenbaum BR. Association of serum phosphate with vascular and valvular calcification in moderate CKD. J Am Soc Nephrol. 2009 Feb;20(2):381-7. doi: 10.1681/ASN.2008040349. Epub 2008 Dec 10.
- Block GA, Klassen PS, Lazarus JM, Ofsthun N, Lowrie EG, Chertow GM. Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol. 2004 Aug;15(8):2208-18.
- Dhingra R, Sullivan LM, Fox CS, Wang TJ, D'Agostino RB Sr, Gaziano JM, Vasan RS. Relations of serum phosphorus and calcium levels to the incidence of cardiovascular disease in the community. Arch Intern Med. 2007 May 14;167(9):879-85.
- Foley RN, Collins AJ, Herzog CA, Ishani A, Kalra PA. Serum phosphate and left ventricular hypertrophy in young adults: the coronary artery risk development in young adults study. Kidney Blood Press Res. 2009;32(1):37-44. doi: 10.1159/000203348. Epub 2009 Feb 20.
- Gutiérrez OM, Luzuriaga-McPherson A, Lin Y, Gilbert LC, Ha SW, Beck GR Jr. Impact of Phosphorus-Based Food Additives on Bone and Mineral Metabolism. J Clin Endocrinol Metab. 2015 Nov;100(11):4264-71. doi: 10.1210/jc.2015-2279. Epub 2015 Aug 31.
- Gutiérrez OM. Fibroblast growth factor 23 and disordered vitamin D metabolism in chronic kidney disease: updating the "trade-off" hypothesis. Clin J Am Soc Nephrol. 2010 Sep;5(9):1710-6. doi: 10.2215/CJN.02640310. Epub 2010 May 27. Review.
- Ix JH, De Boer IH, Peralta CA, Adeney KL, Duprez DA, Jenny NS, Siscovick DS, Kestenbaum BR. Serum phosphorus concentrations and arterial stiffness among individuals with normal kidney function to moderate kidney disease in MESA. Clin J Am Soc Nephrol. 2009 Mar;4(3):609-15. doi: 10.2215/CJN.04100808. Epub 2009 Feb 11.
- Kestenbaum B, Sampson JN, Rudser KD, Patterson DJ, Seliger SL, Young B, Sherrard DJ, Andress DL. Serum phosphate levels and mortality risk among people with chronic kidney disease. J Am Soc Nephrol. 2005 Feb;16(2):520-8. Epub 2004 Dec 22.
- Mathew S, Tustison KS, Sugatani T, Chaudhary LR, Rifas L, Hruska KA. The mechanism of phosphorus as a cardiovascular risk factor in CKD. J Am Soc Nephrol. 2008 Jun;19(6):1092-105. doi: 10.1681/ASN.2007070760. Epub 2008 Apr 16.
- Saab G, Whooley MA, Schiller NB, Ix JH. Association of serum phosphorus with left ventricular mass in men and women with stable cardiovascular disease: data from the Heart and Soul Study. Am J Kidney Dis. 2010 Sep;56(3):496-505. doi: 10.1053/j.ajkd.2010.03.030. Epub 2010 Jun 26.
- Shuto E, Taketani Y, Tanaka R, Harada N, Isshiki M, Sato M, Nashiki K, Amo K, Yamamoto H, Higashi Y, Nakaya Y, Takeda E. Dietary phosphorus acutely impairs endothelial function. J Am Soc Nephrol. 2009 Jul;20(7):1504-12. doi: 10.1681/ASN.2008101106. Epub 2009 Apr 30.
- Tonelli M, Sacks F, Pfeffer M, Gao Z, Curhan G; Cholesterol And Recurrent Events Trial Investigators. Relation between serum phosphate level and cardiovascular event rate in people with coronary disease. Circulation. 2005 Oct 25;112(17):2627-33. Erratum in: Circulation. 2007 Dec 4;116(23):e556.
- Uribarri J, Calvo MS. Hidden sources of phosphorus in the typical American diet: does it matter in nephrology? Semin Dial. 2003 May-Jun;16(3):186-8.
- Uribarri J. Phosphorus homeostasis in normal health and in chronic kidney disease patients with special emphasis on dietary phosphorus intake. Semin Dial. 2007 Jul-Aug;20(4):295-301. Review.
- IRB-300002442