How do PPIs Induce Hypomagnesemia?

- Whereas passive paracellular Mg2+ absorption remains intact, the active transport via TRPM6/7 channels is disrupted.

- It appears that a PPI-induced decrease in intestine luminal pH of 0.5 (a 3.5-fold increase in protons) alters TRPM6/7channel affinity for Mg2+.

- PPIs reduce the ionized/un-ionized ratio for ionized carboxyl side chains of both glutamic and aspartic acid residues , which decreases channel affinity for Mg2+ and reduces absorption.

Ref: Perazella M. Kidney International. 2013;83:553–556