A chronic high phosphate intake in mice is detrimental for bone health without major renal alterations

Abstract

Background Phosphate intake has increased in the last decades due to a higher consumption of processed foods. This higher intake is detrimental for patients with chronic kidney disease, increasing mortality and cardiovascular disease risk and accelerating kidney dysfunction. Whether a chronic high phosphate diet is also detrimental for the healthy population is still under debate. Methods We fed healthy mature adult mice over a period of one year with either a high (1.2% w/w) or a standard (0.6% w/w) phosphate diet, and investigated the impact of a high phosphate diet on mineral homeostasis, kidney function and bone health. Results The high phosphate diet increased plasma phosphate, parathyroid hormone (PTH) and calcitriol levels, with no change in fibroblast growth factor 23 levels. Urinary phosphate, calcium and ammonium excretion were increased. Measured glomerular filtration rate was apparently unaffected, while blood urea was lower and urea clearance was higher in animals fed the high phosphate diet. No change was observed in plasma creatinine levels. Blood and urinary pH were more acidic paralleled by higher bone resorption observed in animals fed a high phosphate diet. Total and cortical bone mineral density was lower in animals fed a high phosphate diet and this effect is independent of the higher PTH levels observed. Conclusions A chronic high phosphate intake did not cause major renal alterations, but affected negatively bone health, increasing bone resorption and decreasing bone mineral density.

Hyperphosphatemia increases inflammation to exacerbate anemia and skeletal muscle wasting independently of FGF23-FGFR4 signaling

“…We employed a graded Pi diet to study the effects of excess Pi on the liver ( Figure 2 ). Studies show conflicting results toward renal and liver health, following supplementation of a high Pi diet ( Baquerizo et al, 2003 ; Haut et al, 1980 ; Ugrica et al, 2021 ). In our study, no significant changes in macroscopic parameters were observed following dietary Pi overload ( Table 2 ).…”

The Complexities of Organ Crosstalk in Phosphate Homeostasis: Time to Put Phosphate Sensing Back in the Limelight

“…Ingestion of these food types, where significant amounts of highly bioavailable phosphate-based preservatives are added to improve taste and increase shelf life, has led to an ongoing debate as to whether these preservatives impact human health outcomes [ 10 , 11 ]. While evidence for phosphate toxicity in humans might not be conclusive, a high dietary phosphate burden has been reported to induce significant changes in vascular calcification [ 8 ] and bone health in rodent models [ 12 ]. Recent rodent studies have also provided unexpected insights into the short- and long-term hormonal adaptions that occur in response to dietary phosphate load [ 12 ], which may change our understanding and perception of human disease outcomes.…”

“…While evidence for phosphate toxicity in humans might not be conclusive, a high dietary phosphate burden has been reported to induce significant changes in vascular calcification [ 8 ] and bone health in rodent models [ 12 ]. Recent rodent studies have also provided unexpected insights into the short- and long-term hormonal adaptions that occur in response to dietary phosphate load [ 12 ], which may change our understanding and perception of human disease outcomes.…”

Distinct Effects of High-Fat and High-Phosphate Diet on Glucose Metabolism and the Response to Voluntary Exercise in Male Mice

“…Fast food and soda also contain high levels of phosphate additives [ 9 , 11 ]. A high-phosphate diet (HPD) detrimentally affects bone health [ 12 ], is a risk factor in cardiorenal syndrome [ 13 ], and is correlated with a higher all-cause mortality [ 14 ]. However, the effects of HPD on metabolic function, and specifically on white adipose tissue, remain largely understudied [ 15 ].…”