Proton-pump inhibitor-induced hypomagnesemia: Current research and proposed mechanisms

Figure 1 Under conditions of magnesium deficiency, proton-pump inhibitors may inhibit magnesium absorption by increasing the pH of the intestinal lumen, through both gastric and non-gastric antagonism of the H⁺-K⁺ ATPase pump (“proton pump”). TRPM6/7 affinity for magnesium decreases in a higher pH environment. While this may trigger mRNA transcription of TRPM6 channels in most individuals, hypomagnesemia may develop when this compensation is incomplete or the individual has additional risk factors. TRPM: Transient receptor potential melastatin; cHK-α: Colonic hydrogen-potassium ATPase; CNNM4: Cyclin M4; PPI: Proton-pump inhibitor.