Another mechanism that could explain the influence of PPIs on vitamin D homeostasis is through hypomagnesemia because several steps in vitamin D metabolism depend on magnesium as a cofactor, such as vitamin D binding to vitamin D binding protein, 25(OH)D synthesis, 1,25 (OH)2D synthesis, 25-hydroxylase synthesis and vitamin D receptor expression for cellular effects [23]. This evidence concerns the gene VDR and familial primary hypomagnesemia.