Last review and update: December 10, 2022.
Post type: A Short Communication.
Subject: Endocrine regulation of phosphate (Pi) and calcium metabolism.
Physiological Literacy: Vitamin D is both phosphate and calcium regulator. High phosphate is toxic to nephrons, other tissues. This makes phosphate a major pro-aging factor. High protein diets mean high phosphate. High phosphate is challenging for aging kidney. High vitamin D, in particular, through supplementation, may be problematic in the context of disturbed phosphate and calcium metabolism.
The cited literature: A quality work by people who can think.
Re-reading+++
Ming Chang Hu, Makoto Kuro-o, et al., 2013:
“Endocrine regulation of phosphate (Pi) and calcium metabolism. (a) Multiple negative feedback loops between the principal regulators of mineral metabolism: parathyroid hormone (PTH), fibroblast growth factor (FGF) 23, Klotho, and vitamin D. The kidney is a major contributor to circulating blood Klotho. Klotho is postulated to suppress FGF23 production from bone. Klotho functions as a coreceptor ofFGFR allowing FGF23 to suppress PTH. PTH increases plasma levels of FGF23 and vitamin D. Increased vitamin further stimulates FGF23 and directly and indirectly suppresses PTH. Increased vitamin D also stimulates Klotho production in the kidney. Through several negative or positive feedback loops, Klotho functions as both a Pi-regulatory hormone and a calciumregulatory hormone. (b) A change in one parameter triggers a cascade of events starting with hypocalcemia. Ionized calcium usually inhibits PTH secretion (1). When plasma-ionized calcium levels are low, PTH is stimulated, which promotes synthesis of active vitamin D (2), which in turn increases intestinal absorption of calcium and Pi (3). PTH also leads to renal calcium retention (4)and increased bone turnover (5). These act in concert (3–5) to restore plasma ionized calcium. When blood Pi levels and/or Pi intake is increased, FGF23 is increased (6). FGF23 suppresses vitamin D directly (7) and indirectly by suppressing PTH (2, 8)inaKlothodependent manner. Together with its phosphaturic activity (9), FGF23 induces negative Pi balance. FGF23 is also increased by vitamin D(10) and PTH (11), thereby closing negative feedback loops between FGF23, PTH, and vitamin D.”
Figure: Endocrine regulation of phosphate (Pi) and calcium metabolism. Source: Ming Chang Hu, Makoto Kuro-o, et al., 2013.
