Impact of Phosphorus-Based Food Additives on Bone and Mineral Metabolism
Open accessAbstract
CONTEXT: Phosphorus-based food additives can substantially increase total phosphorus intake per day, but the effect of these additives on endocrine factors regulating bone and mineral metabolism is unclear. OBJECTIVE: This study aimed to examine the effect of phosphorus additives on markers of bone and mineral metabolism. Design and Setting, and Participants: This was a feeding study of 10 healthy individuals fed a diet providing ∼1000 mg of phosphorus/d using foods known to be free of phosphorus additives for 1 week (low-additive diet), immediately followed by a diet containing identical food items; however, the foods contained phosphorus additives (additive-enhanced diet). Parallel studies were conducted in animals fed low- (0.2%) and high- (1.8%) phosphorus diets for 5 or 15 weeks. MAIN OUTCOME MEASURES: The changes in markers of mineral metabolism after each diet period were measured. RESULTS: Participants were 32 ± 8 years old, 30% male, and 70% black. The measured phosphorus content of the additive-enhanced diet was 606 ± 125 mg higher than the low-additive diet (P < .001). After 1 week of the low-additive diet, consuming the additive-enhanced diet for 1 week significantly increased circulating fibroblast growth factor 23 (FGF23), osteopontin, and osteocalcin concentrations by 23, 10, and 11%, respectively, and decreased mean sclerostin concentrations (P < .05 for all). Similarly, high-phosphorus diets in mice significantly increased blood FGF23, osteopontin and osteocalcin, lowered sclerostin, and decreased bone mineral density (P < .05 for all). CONCLUSIONS: The enhanced phosphorus content of processed foods can disturb bone and mineral metabolism in humans. The results of the animal studies suggest that this may compromise bone health.
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Two to five days of high dietary Pi intake increases iFGF23 but not cFGF23.
“Two to five days of high dietary Pi intake increases iFGF23 but not cFGF23 [20, 25, 34, 58].”
From Controlled dietary phosphate loading in healthy young men elevates plasma phosphate and FGF23 levels (2025) · cites this paper as [25]
The Human studies section reports a 23% increase in plasma FGF23 after one week of an additive-enhanced diet compared with the preceding low-additive week. It does not establish an increase after two to five days or report that intact FGF23 increased while C-terminal FGF23 did not; the Data collection section refers only to FGF23 measurement. Page numbers are unavailable in our copy. (LLM, conf=0.87)
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 [25]
The Human studies and Study protocol sections describe a controlled two-week dietary intervention in healthy volunteers, supporting the several-weeks part of the claim. Our copy does not describe a human experiment lasting only a few hours, and the Human studies section says calcium content did not differ significantly between the two study diets—not that 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 [25]
The Human studies section reports that a one-week phosphorus-additive diet increased FGF23 in participants of both sexes; urinary phosphorus excretion rose from its low-additive-diet level back to baseline. The Study protocol describes dietary loading, not enteral or intravenous loading, and the cited passages do not establish that the measured FGF23 was intact FGF23 (iFGF23). No page numbers are available in our copy. (LLM, conf=0.87)
Experimental — accuracy not yet measuredFurther association studies suggest that higher blood Pi levels are associated with higher all-cause and cardiovascular mortality and with lower bone mass.
“further association studies suggest that higher blood Pi levels are associated with higher all-cause and cardiovascular mortality and with lower bone mass [9, 15, 16, 25, 55].”
From Controlled dietary phosphate loading in healthy young men elevates plasma phosphate and FGF23 levels (2025) · cites this paper as [25]
The Animal studies section reports lower bone mineral density in mice fed a high-phosphorus diet, providing limited support for the bone-mass portion. It does not establish an association between higher blood phosphate and lower bone mass, and the passages found do not report associations with all-cause or cardiovascular mortality (page numbers unavailable). (LLM, conf=0.78)
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 [25]
The Study protocol (page unavailable) describes a two-week food-additive intervention, not enteral or intravenous phosphate loading. The Human studies section (page unavailable) reports no statistically significant change in circulating phosphorus or PTH during that dietary intervention; the copy does not report a calcitriol result. Searches for enteral or intravenous loading and calcitriol found no passage addressing the claimed studies. (LLM, conf=0.76)
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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
- Gutiérrez, O. M., Luzuriaga-McPherson, A., Lin, Y., Gilbert, L. C., Ha, S.-W., & Beck, G. R.
- Affiliations
- Emory University (US)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2015-11
- Volume
- 100
- Issue
- 11
- Pages
- 4264-4271
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC4702463
- OpenAlex
- W2110435733
- Cited by
- 82
- References
- 36
- Citations by year
- 2026: 9 · 2025: 4 · 2024: 11 · 2023: 7 · 2022: 11 · 2021: 5 · 2020: 10 · 2019: 5 · 2018: 5 · 2017: 9 · 2016: 5 · 2015: 1
- FWCI
- 5.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs (I01 BX002363)
- Emory University
- National Institutes of Health (UL1TR000165, UL1TR001417)
- School of Medicine, Emory University
- National Cancer Institute (R01CA136716)
- National Institute of Diabetes and Digestive and Kidney Diseases (R03DK095005, P30DK056336, P30DK079626)
- National Institute of Neurological Disorders and Stroke (R01NS080850)
- National Center for Advancing Translational Sciences (UL1-TR-00165)
- Topics
- Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Alkaline Phosphatase Research Studies
- Keywords
- bone mineral metabolism, high-phosphate diet, fibroblast growth factor 23, sclerostin, osteocalcin, osteopontin, bone mineral density, processed foods, dietary phosphorus intake, bone health
- MeSH terms
- Fibroblast Growth Factor-23, Adult, Animals, Bone and Bones, Diet, Feeding Behavior, Female, Fibroblast Growth Factors, Food Additives, Genetic Markers, Humans, Male, Mice, Inbred C57BL, Middle Aged, Minerals, Biomarkers, Bone Density, Osteocalcin, Phosphorus Compounds, Bone Morphogenetic Proteins, Adaptor Proteins, Signal Transducing, Mice, Osteopontin, Young Adult
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