The Human Response to Acute Enteral and Parenteral Phosphate Loads
Open accessAbstract
The human response to acute phosphate (PO4) loading is poorly characterized, and it is unknown whether an intestinal phosphate sensor mechanism exists. Here, we characterized the human mineral and endocrine response to parenteral and duodenal acute phosphate loads. Healthy human participants underwent 36 hours of intravenous (IV; 1.15 [low dose] and 2.30 [high dose] mmol of PO4/kg per 24 hours) or duodenal (1.53 mmol of PO4/kg per 24 hours) neutral sodium PO4 loading. Control experiments used equimolar NaCl loads. Maximum PO4 urinary excretory responses occurred between 12 and 24 hours and were similar for low-dose IV and duodenal infusion. Hyperphosphatemic responses were also temporally and quantitatively similar for low-dose IV and duodenal PO4 infusion. Fractional renal PO4 clearance increased approximately 6-fold (high-dose IV group) and 4-fold (low-dose IV and duodenal groups), and significant reductions in plasma PO4 concentrations relative to peak values occurred by 36 hours, despite persistent PO4 loading. After cessation of loading, frank hypophosphatemia occurred. The earliest phosphaturic response occurred after plasma PO4 and parathyroid hormone concentrations increased. Plasma fibroblast growth factor-23 concentration increased after the onset of phosphaturia, followed by a decrease in plasma 1,25(OH)2D levels; α-Klotho levels did not change. Contrary to results in rodents, we found no evidence for intestinal-specific phosphaturic control mechanisms in humans. Complete urinary phosphate recovery in the IV loading groups provides evidence against any important extrarenal response to acute PO4 loads.
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Acute increases in dietary Pi intake as well as enteral or i.v. Pi loading cause a rapid increase in PTH and calcitriol, and timely delayed elevation of iFGF23.
“Acute increases in dietary Pi intake as well as enteral or i.v. Pi loading cause a rapid increase in PTH and calcitriol, and timely delayed elevation of iFGF23 [44, 50, 59].”
From Controlled dietary phosphate loading in healthy young men elevates plasma phosphate and FGF23 levels (2025) · cites this paper as [50]
The Results report that PTH rose after phosphate loading and FGF-23 rose later, as claimed. But 1,25(OH)2D (calcitriol) decreased significantly only after 36 hours in the IV groups and 48 hours in the intestinal group—the opposite of the claimed rapid increase. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredControlled experiments in healthy humans examined periods of either a few hours or several weeks, and often varied dietary calcium intake.
“controlled experiments in healthy humans examined periods of either a few hours or several weeks, and often varied dietary calcium intake.”
From Controlled dietary phosphate loading in healthy young men elevates plasma phosphate and FGF23 levels (2025) · cites this paper as [50]
The Discussion (page unavailable) describes controlled experiments in healthy volunteers who spent three weeks in the study unit, with phosphate loading for 36 hours and observations over five days. It also says their diet, including calcium intake, was constant throughout the study, so this source does not support the claim that dietary calcium intake was varied. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn mixed sex, intermediate-term studies, oral, enteral, or intravenous Pi loading increased iFGF23 and urinary Pi excretion.
“In mixed sex, intermediate-term studies, oral, enteral, or intravenous Pi loading increased iFGF23 and urinary Pi excretion, while enteral and intravenous Pi loading additionally increased serum Pi, and PTH, and decreased calcitriol [2, 20, 25, 50, 58].”
From Controlled dietary phosphate loading in healthy young men elevates plasma phosphate and FGF23 levels (2025) · cites this paper as [50]
The Discussion reports that intravenous and intestinal phosphate loading increased FGF-23 and produced similar increases in urinary phosphate excretion; the study included men and women and used 36-hour loading protocols. However, it administered phosphate intravenously or into the duodenum, not orally, and the Analysis section specifies a C-terminal FGF-23 assay rather than an intact FGF-23 assay (page numbers unavailable). (LLM, conf=0.89)
Experimental — accuracy not yet measuredIn mixed sex, intermediate-term studies, enteral and intravenous Pi loading increased serum Pi and PTH and decreased calcitriol.
“In mixed sex, intermediate-term studies, oral, enteral, or intravenous Pi loading increased iFGF23 and urinary Pi excretion, while enteral and intravenous Pi loading additionally increased serum Pi, and PTH, and decreased calcitriol [2, 20, 25, 50, 58].”
From Controlled dietary phosphate loading in healthy young men elevates plasma phosphate and FGF23 levels (2025) · cites this paper as [50]
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Tiong, M. K., Cai, M. M. X., Toussaint, N. D., Tan, S.-J., Pasch, A., & Smith, E. R. (2022) · Scientific Reports · doi:10.1038/s41598-022-11065-3 · Cited by 38 · see citing works
Controlled dietary phosphate loading in healthy young men elevates plasma phosphate and FGF23 levels
Gerber, J. S., Arroyo, E. M. P., Pastor, J., Correia, M., Rudloff, S., Moe, O. W., Egli-Spichtig, D., Mohebbi, N., & Wagner, C. A. (2025) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-024-03046-4 · Cited by 15 · see citing works
- Authors
- Scanni, R., vonRotz, M., Jehle, S., Hulter, H. N., & Krapf, R.
- Affiliations
- University of Basel (CH)
- University of California, San Francisco (US)
- Corresponding author
- Scanni, Roberto
- Jehle, Sigrid
- Krapf, Reto
- Venue
- Journal of the American Society of Nephrology
- Published
- 2014-12
- Volume
- 25
- Issue
- 12
- Pages
- 2730-2739
- ISSN
- 1046-6673 (ISSN-L)
- PMC
- PMC4243350
- OpenAlex
- W2117621745
- Cited by
- 118
- References
- 41
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 11 · 2023: 7 · 2022: 10 · 2021: 9 · 2020: 13 · 2019: 10 · 2018: 16 · 2017: 16 · 2016: 12 · 2015: 5 · 2014: 1 · 2012: 1
- FWCI
- 8.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of the American Society of Nephrology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
- Health Sciences › Medicine › Nephrology › Renal function and acid-base balance
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Alkaline Phosphatase Research Studies
- Keywords
- urinary phosphate excretion, hyperphosphatemia, hypophosphatemia, parathyroid hormone, fibroblast growth factor 23, 1,25-dihydroxyvitamin D, alpha-klotho, mineral metabolism
- MeSH terms
- Fibroblast Growth Factor-23, Klotho Proteins, Adult, Duodenum, Electrolytes, Endocrine System, Female, Fibroblast Growth Factors, Glomerular Filtration Rate, Glucuronidase, Humans, Hypocalcemia, Hypophosphatemia, Familial, Infusions, Intravenous, Male, Parathyroid Hormone, Phosphates, Time Factors, Hypophosphatemia, Young Adult, Administration, Intravenous
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