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

Ok Hee Kim ,Hyeonjin Kim,Cheolsoo Choi,Sun Wook Cho,Kyong Soo Park,June Hur,Hyung Jin Choi,Han Seok Choi,Joong-Hyuck Auh,Jinwook Lee,Young Jae Lee,Cheol Soon Lee,Yun Jae Jung,Young Joo Park,Woo Jin Jung,Dong Hoon Lee ,Yun Shin Jung ,Jiwon Kang ,Ji Young ,Jun Young Yang ,Young–Bum Kim ,Carmen J Booth ,Seung Soon Im ,Jung Wan Kim ,Byung‐Chul Oh

doi:10.7554/elife.52709

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.

Highlights

Phytate (Myo-inositol hexaphosphate) is the main phosphorus storage system in plant seeds such as those of cereal grains, nuts, oilseeds, and legumes (Raboy, 2000; Reddy et al, 1982), accounting for up to 80% of total phosphorous
We found that dietary phytate led to the inhibition of intestinal absorption of essential minerals such as Ca2+, Mg2+, and Fe2+ in a concentration-dependent manner (Figure 1G– H, Figure 1—figure supplement 1A)
Parathyroid hormone (PTH) levels markedly increased (5.4–11.7-fold) in the high-phytate groups by week 5 (Figure 1, Figure 1—figure supplement 1B) and remained elevated (2.8–6.4-fold) to week 12 (Figure 1L) in all phytate-fed rats because of sustained inhibition of intestinal Ca2+ absorption. These results suggest that PTH plays a role in the development of hypophosphatemia in high-phytate-fed rats

Summary

Introduction

Phytate (Myo-inositol hexaphosphate) is the main phosphorus storage system in plant seeds such as those of cereal grains, nuts, oilseeds, and legumes (Raboy, 2000; Reddy et al, 1982), accounting for up to 80% of total phosphorous. Plant seeds or high-fiber vegetable proteins represent a poor or negligible source of bioavailable phosphate for intestinal absorption compared with animal proteins (Moe et al, 2011; Vervloet et al, 2017). They are not considered to affect intestinal phosphate absorption adversely in humans eating diets that are mainly comprised of plant-based, cereal-rich diets (Reddy and Sathe, 2002). There are insufficient data indicating the amount of phytate phosphorus that is bioavailable for intestinal absorption and whether specific conditions can modulate the bioavailability and digestibility of phytate

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Results