Further, PPI users with cirrhosis had significantly lower serum magnesium levels than non-users with cirrhosis and than patients without cirrhosis, regardless of PPI use (physique 2). patients with cirrhosis were NAV3 significantly lower in PPI users than non-users (1.780.22 vs 1.870.22?mg/dL, p=0.03). Conclusions Outpatients receiving long-term PPI treatment had significantly lower serum magnesium concentrations than those not treated with PPI. To the best of our knowledge, this study is the first to show hypomagnesaemia in Japanese patients with cirrhosis receiving long-term PPI treatment. strong class=”kwd-title” Keywords: PROTON PUMP INHIBITION, LIVER CIRRHOSIS, SMALL INTESTINE Summary box What is already known about this subject? ?? Hypomagnesaemia may result from diarrhoea or malabsorption or it can be induced by medications such as cisplatin preparations.?? The US Food and Drug Administration issued an alert stating that the long-term use of proton pump inhibitors (PPIs) may result in hypomagnesaemia.?? Statistically significant relations were observed between lower serum magnesium concentrations and PPI treatment in US inpatients. What are the new findings? ?? Statistically significant relations were observed between lower serum magnesium concentrations and PPI treatment in Japanese outpatients.?? Serum magnesium levels did not differ among the groups of patients taking the three types of PPIs.?? PPI users with cirrhosis had significantly lower serum magnesium levels than non-users with cirrhosis and than patients without cirrhosis, regardless of PPI use. How might it impact on clinical practice in the foreseeable future? ?? PPIs are frequently used Clindamycin palmitate HCl in everyday medical practice. Although PPI-induced hypomagnesaemia is extremely rare, it may be life threatening in some patients. Introduction Proton pump inhibitors (PPIs) are widely used to treat gastrointestinal disorders, such as gastric ulcers, duodenal ulcers and reflux oesophagitis.1 Because these drugs are well tolerated, increased numbers of patients receive long-term PPI treatment. However, PPI-associated hypomagnesaemia has been reported in several patients in the USA and Europe. 2 Magnesium is the fourth most common cation in the body. Although found primarily in the muscles and bones and a constituent of numerous body structures, magnesium is also essential for enzymes involved in generating ATP, thus playing a key role in regulating numerous physiological functions. 3 Hypomagnesaemia may result from diarrhoea or malabsorption or it can be induced by medications such as cisplatin preparations. 4 Although hypomagnesaemia may cause Clindamycin palmitate HCl serious conditions, such as tetany, spasms and arrhythmias, some patients are asymptomatic. Thus, the specific incidence of hypomagnesaemia associated with PPIs remains unknown. In May 2011, the US Food and Drug Administration issued an alert stating that the long-term use of PPIs may result in hypomagnesaemia.5 Serum magnesium concentrations were found to be significantly lower in the western inpatients and outpatients who received long-term PPI treatment compared with those who did not.6 7 Serum magnesium concentrations of patients receiving PPIs have only been rarely investigated in Japan, and there is only one case report.8 We therefore examined the effect of long-term use of PPIs on serum magnesium concentrations in Japanese outpatients. Methods We studied 1742 individuals treated as outpatients at the Ishikawa Prefectural Central Hospital between October and November 2011. Our general hospital has a focus on digestive diseases. The study participants were 481 outpatients who met the inclusion criteria as follows: age 20?years and no history of hospitalisation within 1?week of blood sampling. Exclusion criteria were as Clindamycin palmitate HCl follows: dialysis patients and patients who were administered magnesium oxide, diuretics or cisplatin preparations that may have affected serum magnesium. Cirrhosis was defined by clinical findings, blood examination data and image diagnosis (CT or ultrasound). Outpatients underwent blood sampling in the morning after at least a 12?h overnight fast. We measured serum magnesium levels in units of 0.1?mg/dL. Patient records were retrospectively reviewed to determine their underlying diseases (hypertension, diabetes, cirrhosis and dyslipidaemia), possibility of ingestion, oral medications used, long-term use of PPIs and serum magnesium concentrations. Patients administered a PPI for 1?year were regarded as PPI users, whereas those administered a PPI for 1?year or not at all were considered PPI non-users. At the time this study was conducted, only three PPIs were approved for clinical use in Japan: omeprazole, lansoprazole and rabeprazole. The dose of each drug was omeprazole 20?mg, lansoprazole 15 or 30?mg and rabeprazole 10?mg. Further, during this study, none of the patients were hospitalised for hypomagnesaemia. The protocol and consent form for this study were approved by the Institutional Review Board of Ishikawa Prefectural Central Hospital, and all patients provided written informed consent. Statistical analysis Mean, SD and percentage with frequency were used to report continuous and discrete variables. 2 test.