Vitamin D and Phosphate Interactions in Health and Disease

Vitamin D plays an essential role in calcium and inorganic phosphate (Pi) homeostasis, maintaining their optimal levels to assure adequate bone mineralization. Vitamin D, as calcitriol (1,25(OH)₂D), not only increases intestinal calcium and phosphate absorption but also facilitates their renal reabsorption, leading to elevated serum calcium and phosphate levels. The interaction of 1,25(OH)₂D with its receptor (VDR) increases the efficiency of intestinal absorption of calcium to 30-40% and phosphate to nearly 80%. Serum phosphate levels can also influence 1,25(OH)₂D and fibroblast growth factor 23 (FGF23) levels, i.e., higher phosphate concentrations suppress vitamin D activation and stimulate parathyroid hormone (PTH) release, while a high FGF23 serum level leads to reduced vitamin D synthesis. In the vitamin D-deficient state, the intestinal calcium absorption decreases and the secretion of PTH increases, which in turn causes the stimulation of 1,25(OH)₂D production, resulting in excessive urinary phosphate loss. Maintenance of phosphate homeostasis is essential as hyperphosphatemia is a risk factor of cardiovascular calcification, chronic kidney diseases (CKD), and premature aging, while hypophosphatemia is usually associated with rickets and osteomalacia. This chapter elaborates on the possible interactions between vitamin D and phosphate in health and disease.