'Lemonade Legs': Why do Some Patients Get Profound Hypomagnesaemia on Proton-Pump Inhibitors?

Abstract

Proton pump inhibitors (PPIs) are widely used though an association with hypomagnesaemia and hypocalcaemia has only been described since 2006. Patients typically present after years of stable dosing with musculoskeletal, neurological or cardiac arrhythmic symptoms, but it is likely that many cases are under-recognised. Magnesium levels resolve rapidly on discontinuation of PPI therapy and hypomagnesaemia recurs rapidly on rechallenge with any agent in the class. The cellular mechanisms of magnesium homeostasis are increasingly being understood, including both passive paracellular absorption through claudins and active transcellular transporters, including the transient receptor potential channels (TRPM6) identified in the intestine and nephron. PPIs may alter luminal pH by modulating pancreatic secretions, affecting non-gastric H+K+ATPase secretion, altering transporter transcription or channel function. A small reduction in intestinal absorption appears pivotal in causing cumulative deficiency. Risk factors have been associated to help identify patients at risk of this effect but clinical vigilance remains necessary for diagnosis.

Impact of Long-Term Proton Pump Inhibitor Therapy on Gut Microbiota in F344 Rats: Pilot Study

“…This prolonged use may feature side effects or complications of PPI therapy, such as bone metabolism, fracture, hypomagnesaemia, vitamin B 12 deficiency, iron deficiency anemia, and pneumonia 3–5. In addition, an increasing number of studies have evaluated whether the long-term use of PPI causes small intestinal bacterial overgrowth (SIBO) or Clostridium difficile infection.…”

Long Term Use of Proton Pump Inhibitors: Where to Draw the Line

“…The first case of PPI-induced hypomagnesemia and hypocalcemia was reported in 2006 [119]. Thereafter a good number of publications reported the similar suggestions [120,121]. The mechanism of PPI induced hypomagnesemia has yet to be elucidated, but impaired intestinal absorption through PPI inhibition of paracellular claudin-mediated divalent cation channels or transcellular active transporter channels, appears to be associated with the condition [120].…”

“…Thereafter a good number of publications reported the similar suggestions [120,121]. The mechanism of PPI induced hypomagnesemia has yet to be elucidated, but impaired intestinal absorption through PPI inhibition of paracellular claudin-mediated divalent cation channels or transcellular active transporter channels, appears to be associated with the condition [120]. Recently in a publication the authors recommended monitoring of magnesium, calcium and potassium levels in patients on PPIs for long-term, especially the elderly patient [122].…”

Atrial fibrillation and gastrooesophageal reflux disease: association mechanisms, treatment approaches

“…Хотя большинство перорального магния абсорбируется пассивно через парацеллюлярные пути между энтероцитами, ИПП влияют на работу второй транспортной системы магния -трансклеточных катионных каналов, которые позволяют адаптироваться к низкому потреблению магния путем увеличения фракционного поглощения магния. Считается, что хроническое использование ИПП ухудшает этот адаптивный кишечный ответ на низкое потребление магния с пищей [41][42][43][44].…”