More Than Heartburn: A Case of PPI-Induced Hypomagnesemia

Abstract Background Proton pump inhibitors (PPIs) are widely used for the treatment of acid-related gastrointestinal conditions. Although generally well-tolerated, long-term PPI use has been associated with hypomagnesemia, a potentially life-threatening electrolyte disturbance. We report a case of severe hypomagnesemia secondary to prolonged PPI therapy, highlighting the clinical presentation, diagnostic workup, and the pathophysiological mechanisms involved. Methods A 70-year-old male presented with generalized fatigue, muscle cramps, and recurrent episodes of palpitations. Laboratory investigations revealed a serum magnesium level of 0.3 mmol/L (reference range: 0.7–1.0 mmol/L), with associated hypocalcaemia and mild hypokalaemia. The patient had been taking pantoprazole 40 mg daily for over four years for gastroesophageal reflux disease. Potential alternative causes, including gastrointestinal losses, renal magnesium wasting, and the use of diuretics or other hypomagnesemia-associated medications, were systematically excluded. Magnesium supplementation resulted in only transient improvements until the PPI was discontinued. Upon cessation of pantoprazole, serum magnesium normalised after 5 weeks without further supplementation, confirming PPI-induced hypomagnesemia. Results The pathogenesis of PPI-induced hypomagnesemia is not entirely understood, but evidence suggests impaired active and passive intestinal magnesium absorption via the transient receptor potential melastatin 6 and 7 (TRPM6/7) ion channels. Prolonged PPI use may interfere with luminal pH, reducing TRPM6/7 function. The condition may go unrecognized until significant symptoms develop and can recur with re-challenge. Conclusion Clinicians should be aware of the risk of hypomagnesemia in patients on long-term PPI therapy, especially those presenting with neuromuscular or cardiac symptoms. Routine monitoring of serum magnesium should be considered in at-risk individuals, and alternative acid suppression therapies should be evaluated when appropriate. Early identification and discontinuation of the causative agent can lead to resolution of the deficiency and reduce the risk of further complications.