Oral Phosphorus Supplementation Secondarily Increases Circulating Fibroblast Growth Factor 23 Levels at Least Partially via Stimulation of Parathyroid Hormone Secretion

Abstract

Phosphorus is an essential nutrient for many biological functions, including cellular signal transduction, mineral metabolism, and energy exchange. On the other hand, a relatively high serum phosphorus level is reportedly a risk factor for cardiovascular disease (1, 2) because inorganic phosphates have been shown to stimulate differentiation of vascular smooth muscle cells into calcifying vascular cells (3). Therefore, serum phosphorus regulation may help to prevent cardiovascular diseases.Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that plays a regulatory role in phosphorus homeostasis. FGF23 has been shown to reduce serum phosphorus levels by inhibition of proximal tubular phosphorus reabsorption through decreased expression of types 2a and 2c sodium-phosphate cotransporters and by decreasing intestinal phosphorus absorption through inhibiting calcitriol synthesis in the kidney (4). Moreover, FGF23-null mice were shown to exhibit severe vascular calcification with concomitant hyperphosphatemia (5). These facts suggest that FGF23 may have a protective effect on vascular calcification by hyperphosphatemia suppression. In contrast, several hemodialysis studies reported that elevated FGF23 levels were associated with aortic calcification (6) and mortality (7, 8) independent of serum phosphorus levels. Elevated serum FGF23 levels, even within the normal range, are reportedly associated with increased left ventricular mass index and increased risk for the presence of left ventricular hypertrophy in elderly subjects (9). Furthermore, a recent study suggested that elevated FGF23 levels contributed directly to high rates of left ventricular hypertrophy and mortality in individuals with chronic kidney diseases (10). Thus, FGF23 regulation may also play a clinically significant role in the prevention of cardiovascular diseases.Oral phosphorus supplementation is known to stimulate FGF23 secretion, although the underlying mechanism has not been clarified. In our preliminary study, we found that plasma FGF23 levels in rats increased after oral phosphorus administration at a physiological dose; however, this increase slowly began around the time that plasma phosphorus levels had decreased (unpublished data). Based on these findings, we reasoned that oral phosphorus supplementation may secondarily increase FGF23 secretion. Parathyroid hormone (PTH) is also secreted in response to phosphorus administration (11) and subsequently increases urinary phosphorus excre- Note Oral Phosphorus Supplementation Secondarily Increases Circulating Fibroblast Growth Factor 23 Levels at Least Partially via Stimulation of Parathyroid Hormone SecretionSatoshi Takasugi, Miho Akutsu and Masashi Nagata Food Science Research Laboratories, Division of Research and Development, Meiji Co., Ltd., 540 Naruda, Odawara, Kanagawa 250-0862, Japan (Received August 20, 2013) Summary Oral phosphorus supplementation stimulates fibroblast growth factor 23 (FGF23) secretion; however, the underlying mechanism remains unclear. The aim of this ...

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