Phosphorus

The metabolically active and perpetually remodeling calcium phosphate-based endoskeleton in terrestrial vertebrates sets the demands on whole-organism calcium and phosphate homeostasis that involves multiple organs in terms of mineral flux and endocrine cross talk. The fibroblast growth factor (FGF)-Klotho endocrine networks epitomize the complexity of systems biology, and specifically, the FGF23-αKlotho axis highlights the concept of the skeleton holding the master switch of homeostasis rather than a passive target organ as hitherto conceived. Other than serving as a coreceptor for FGF23, αKlotho circulates as an endocrine substance with a multitude of effects. This review covers recent data on the physiological regulation and function of the complex FGF23-αKlotho network. Chronic kidney disease is a common pathophysiological state in which FGF23-αKlotho, a multiorgan endocrine network, is deranged in a self-amplifying vortex resulting in organ dysfunction of the utmost severity that contributes to its morbidity and mortality.

This review explores the potential adverse impact of the increasing phosphorus content in the American diet on renal, cardiovascular, and bone health of the general population. Increasingly, studies show that phosphorus intakes in excess of the nutrient needs of a healthy population may significantly disrupt the hormonal regulation of phosphate, calcium, and vitamin D, which contributes to disordered mineral metabolism, vascular calcification, impaired kidney function, and bone loss. Moreover, large epidemiologic studies suggest that mild elevations of serum phosphate within the normal range are associated with cardiovascular disease (CVD) risk in healthy populations without evidence of kidney disease. However, few studies linked high dietary phosphorus intake to mild changes in serum phosphate because of the nature of the study design and inaccuracies in the nutrient composition databases. Although phosphorus is an essential nutrient, in excess it could be linked to tissue damage by a variety of mechanisms involved in the endocrine regulation of extracellular phosphate, specifically the secretion and action of fibroblast growth factor 23 and parathyroid hormone. Disordered regulation of these hormones by high dietary phosphorus may be key factors contributing to renal failure, CVD, and osteoporosis. Although systematically underestimated in national surveys, phosphorus intake seemingly continues to increase as a result of the growing consumption of highly processed foods, especially restaurant meals, fast foods, and convenience foods. The increased cumulative use of ingredients containing phosphorus in food processing merits further study given what is now being shown about the potential toxicity of phosphorus intake when it exceeds nutrient needs.

The Western dietary pattern of intake common to many Americans is high in fat, refined carbohydrates, sodium, and phosphorus, all of which are associated with processed food consumption and higher risk of life-threatening chronic diseases. In this review, we focus on the available information on current phosphorus intake with this Western dietary pattern, and new knowledge of how the disruption of phosphorus homeostasis can occur when intake of phosphorus far exceeds nutrient needs and calcium intake is limited. Elevation of extracellular phosphorus, even when phosphorus intake is seemingly modest, but excessive relative to need and calcium intake, may disrupt the endocrine regulation of phosphorus balance in healthy individuals, as it is known to do in renal disease. This elevation in serum phosphate, whether episodic or chronically sustained, may trigger the secretion of regulatory hormones, whose actions can damage tissue, leading to the development of cardiovascular disease, renal impairment, and bone loss. Therefore, we assessed the health impact of excess phosphorus intake in the context of specific issues that reflect changes over time in the U.S. food supply and patterns of intake. Important issues include food processing and food preferences, the need to evaluate phosphorus intake in relation to calcium intake and phosphorus bioavailability, the accuracy of various approaches used to assess phosphorus intake, and the difficulties encountered in evaluating the relations of phosphorus intake to chronic disease markers or incident disease.