Effect of proton pump inhibitors on magnesium balance: is there a link to cardiovascular risk?

Magnesium (Mg(2+)) is the second most copious element inside human cells and the fourth most abundant positively charged ion in the human body. It is of central importance for a broad variety of physiological processes, including intracellular signaling, neuronal excitability, muscle contraction, bone formation and enzyme activation. Its overall balance is tightly regulated by the concerted actions of the intestine, bones and kidneys. Disturbance of this balance can have serious consequences. Symptoms of hypomagnesaemia include tetany, seizures and cardiac arrhythmias, whereas hypermagnesaemia may cause cardiovascular and neuromuscular abnormalities. Drugs can interfere with Mg(2+) homoeostasis in several ways, and proton-pump inhibitors (PPIs) have been associated with hypomagnesaemia. A better understanding of the molecular mechanisms underlying the adverse effects of these medications on Mg(2+) balance will isuggest ideas for prevention and treatment, and might provide greater insight into Mg(2+) homoeostasis. This review gives an overview of the influence of PPIs on Mg(2+) homoeostasis and provides some understanding of the underlying physiological mechanisms. Moreover, we will discuss the potential link between PPI-induced changes in Mg(2+) homeostasis, and the reported cardiovascular risk observed in long-term PPI users.