Proton Pump Inhibitors and Severe Hypomagnesaemia

Tim Cundy; Jonathan Mackay


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

In This Article

Biochemical Findings

The plasma magnesium concentrations reported in patients with symptomatic PPI-associated hypomagnesaemia range from 0.05 to 0.35 mmol/l. Values this low are rarely recorded in adults other than those who are critically ill with severe sepsis, after major gastrointestinal surgery or having platinum-based chemotherapy.[10] The red cell magnesium concentration was low (1.32 mmol/l, normal 2.1–2.5) in one patient in whom this was measured.[11]

In addition to hypomagnesaemia, patients commonly have severe hypokalaemia and hypocalcaemia (Table 1). Plasma PTH is usually detectable, but very low considering the prevailing hypocalcaemia. As discussed above, these are known consequences of severe hypomagnesaemia and probably the main cause of symptoms.

Urinary magnesium concentrations are uniformly low, unsurprisingly in view of the very low filtered magnesium load. Studies reporting fractional magnesium clearance (CMg/Ccreatinine) also show values on PPIs of less than 1.5%, suggesting that renal retention of magnesium is appropriate.[10,14–16] It increases when PPIs are withdrawn.[16] Two studies have estimated TmMg in hypomagnesaemic patients while still taking PPI treatment. In two patients,[10] it was normal (0.7–0.8 mmol/l), suggesting there was no renal tubular leak of magnesium. In the third patient,[16] it was below normal (0.45 mmol/l), but a TmMg at this level should sustain a plasma concentration of approximately 0.65 mmol/l – not low enough to cause symptomatic hypomagnesaemia. PPI-associated hypomagnesaemia can occur even in advanced chronic renal failure, which is usually characterized by hypermagnesaemia.[15]

One study reported that less than 30% of an infused magnesium load appeared in the urine of two hypomagnesaemic patients still taking their PPI, suggesting that there was severe whole body magnesium depletion.[10] This finding does not, however, exclude the possibility that there were significant losses of the infused load into the intestine.