The association between the use of proton pump inhibitors and the risk of hypomagnesemia: a systematic review and meta-analysis.
BACKGROUND
Although many case reports have described patients with proton pump inhibitor (PPI)-induced hypomagnesemia, the impact of PPI use on hypomagnesemia has not been fully clarified through comparative studies. We aimed to evaluate the association between the use of PPI and the risk of developing hypomagnesemia by conducting a systematic review with meta-analysis.


METHODS
We conducted a systematic search of MEDLINE, EMBASE, and the Cochrane Library using the primary keywords "proton pump," "dexlansoprazole," "esomeprazole," "ilaprazole," "lansoprazole," "omeprazole," "pantoprazole," "rabeprazole," "hypomagnesemia," "hypomagnesaemia," and "magnesium." Studies were included if they evaluated the association between PPI use and hypomagnesemia and reported relative risks or odds ratios or provided data for their estimation. Pooled odds ratios with 95% confidence intervals were calculated using the random effects model. Statistical heterogeneity was assessed with Cochran's Q test and I2 statistics.


RESULTS
Nine studies including 115,455 patients were analyzed. The median Newcastle-Ottawa quality score for the included studies was seven (range, 6-9). Among patients taking PPIs, the median proportion of patients with hypomagnesemia was 27.1% (range, 11.3-55.2%) across all included studies. Among patients not taking PPIs, the median proportion of patients with hypomagnesemia was 18.4% (range, 4.3-52.7%). On meta-analysis, pooled odds ratio for PPI use was found to be 1.775 (95% confidence interval 1.077-2.924). Significant heterogeneity was identified using Cochran's Q test (df = 7, P<0.001, I2 = 98.0%).


CONCLUSIONS
PPI use may increase the risk of hypomagnesemia. However, significant heterogeneity among the included studies prevented us from reaching a definitive conclusion.
Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.
Chan Hyuk
CH
Park
Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.
Eun Hye
EH
Kim
Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, Korea.
Yun Ho
YH
Roh
Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, Korea.
Ha Yan
HY
Kim
Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.
Sang Kil
SK
Lee
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000009:adverse effects; D064748:Dexlansoprazole / Q000009:adverse effects; D064098:Esomeprazole / Q000009:adverse effects; D006801:Humans; D064747:Lansoprazole / Q000009:adverse effects; D008274:Magnesium / Q000097:blood*; D016017:Odds Ratio; D009853:Omeprazole / Q000009:adverse effects; D000077402:Pantoprazole; D054328:Proton Pump Inhibitors / Q000009:adverse effects*; D064750:Rabeprazole / Q000009:adverse effects; D012307:Risk Factors; D016896:Treatment Outcome
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D054328:Proton Pump Inhibitors; D064747:Lansoprazole; D064750:Rabeprazole; C119615:ilaprazole; D000077402:Pantoprazole; D008274:Magnesium; D009853:Omeprazole; D064098:Esomeprazole; D064748:Dexlansoprazole