Proton Pump Inhibitors and Severe Hypomagnesaemia

Tim Cundy; Jonathan Mackay


Curr Opin Gastroenterol. 2011;27(2):180-185. 

In This Article

Clinical Features

The clinical features of the patients described in the current literature are shown in Table 1. The median age at diagnosis was 70 (range 51–82) and there were more women than men. Common symptoms reported include fatigue, unsteadiness, paraesthesiae, tetany, seizures, ataxia and delirium. Bowel symptoms were also reported. The most severe symptoms are associated with the lowest plasma magnesium and calcium concentrations. There is no evidence that these patients have generalized malabsorption. Small bowel and colonic biopsies have shown no histological abnormalities.[7,17•]

A long duration of treatment is common: of the 28 cases in Table 1, 17 (61%) had been on PPI therapy for at least 5 years, and eight of them (29%) for at least 10 years, but hypomagnesaemia occurring after only 1 year of PPI treatment has also been described.[14,15] One report has emphasized a high degree of adherence to treatment as an important factor.[10] No single indication for PPI use is particularly associated with hypomagnesaemia. There is no clear relation to drug dose, but there are suggestions that higher doses are more likely to precipitate hypomagnesaemia: a woman with Zollinger–Ellison syndrome who had taken pantoprazole 160 mg daily for 2 years without apparent ill effect, developed severe hypomagnesaemia 2 months into a clinical trial with high-dose esomeprazole (240 mg daily).[8]

Some patients were taking diuretics, in addition to PPIs, which could have contributed to the development of hypomagnesaemia.[10,13,17•] Similarly, some patients had conditions that could have contributed to the development of hypomagnesaemia, such as bacterial gastroenteritis, intestinal lymphangiectasia or previous bowel surgery, but in all patients, plasma magnesium concentrations returned to normal only after withdrawal of PPI treatment.