High-phytate/low-calcium diet is a risk factor for crystal nephropathies, renal phosphate wasting, and bone loss

Abstract

Phosphate overload contributes to mineral bone disorders that are associated with crystal nephropathies. Phytate, the major form of phosphorus in plant seeds, is known as an indigestible and of negligible nutritional value in humans. However, the mechanism and adverse effects of high-phytate intake on Ca2+ and phosphate absorption and homeostasis are unknown. Here, we show that excessive intake of phytate along with a low-Ca2+ diet fed to rats contributed to the development of crystal nephropathies, renal phosphate wasting, and bone loss through tubular dysfunction secondary to dysregulation of intestinal calcium and phosphate absorption. Moreover, Ca2+ supplementation alleviated the detrimental effects of excess dietary phytate on bone and kidney through excretion of undigested Ca2+-phytate, which prevented a vicious cycle of intestinal phosphate overload and renal phosphate wasting while improving intestinal Ca2+ bioavailability. Thus, we demonstrate that phytate is digestible without a high-Ca2+ diet and is a risk factor for phosphate overloading and for the development of crystal nephropathies and bone disease.

Importance of Dietary Phosphorus for Bone Metabolism and Healthy Aging

“…Phytate, which is the major form of phosphorus in the seeds of plants, is a compound that can form indigestible mineral phytate salts in humans (who lack the enzyme phytase that can release P i from phytate) [ 113 ]. At physiological pH, phytate binds calcium with high affinity [ 114 ].…”

“…At physiological pH, phytate binds calcium with high affinity [ 114 ]. If the calcium concentration is high, phytate forms indigestible, multiple calcium phytate salts [ 113 ]. However, phytate becomes digestible at low calcium concentrations due to reduced calcium binding [ 113 ].…”

“…If the calcium concentration is high, phytate forms indigestible, multiple calcium phytate salts [ 113 ]. However, phytate becomes digestible at low calcium concentrations due to reduced calcium binding [ 113 ]. Kim et al demonstrated that high phytate/low calcium diets increase intestinal P i absorption in rats following intestinal phytate hydrolysis that makes P i bioaccesible [ 113 ].…”

“…However, phytate becomes digestible at low calcium concentrations due to reduced calcium binding [ 113 ]. Kim et al demonstrated that high phytate/low calcium diets increase intestinal P i absorption in rats following intestinal phytate hydrolysis that makes P i bioaccesible [ 113 ]. This P i load results in secondary hyperparathyroidism and renal P i wasting, which appears to be independent of FGF23 [ 113 ].…”

“…Kim et al demonstrated that high phytate/low calcium diets increase intestinal P i absorption in rats following intestinal phytate hydrolysis that makes P i bioaccesible [ 113 ]. This P i load results in secondary hyperparathyroidism and renal P i wasting, which appears to be independent of FGF23 [ 113 ]. Calcium supplementation alleviates this effect [ 113 ].…”