The Association between the Use of Proton Pump Inhibitors and the Risk of Hypomagnesemia: A Systematic Review and Meta-Analysis

Abstract

BackgroundAlthough 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.MethodsWe 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 I 2 statistics.ResultsNine 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, I 2 = 98.0%).ConclusionsPPI use may increase the risk of hypomagnesemia. However, significant heterogeneity among the included studies prevented us from reaching a definitive conclusion.

Proton pump inhibitors and risk of hypomagnesemia

“…Unlike other studies [9,10] we found that PPI risk factors for hypomagnesemia were higher among patients taking PPI for less than one year, although severe hypomagnesemia was recorded among patients taking them for longer. Future prospective studies analyzing serum magnesium before PPI therapy are needed to clarify the causal relationship better between PPI and hypomagnesemia.…”

“…The prevalence of hypomagnesemia among the patients taking PPI in our study was similar to that reported in a recent review and metaanalysis [9]. Unlike other studies [9,10] we found that PPI risk factors for hypomagnesemia were higher among patients taking PPI for less than one year, although severe hypomagnesemia was recorded among patients taking them for longer.…”

Serum magnesium and risk of new onset heart failure in men: the Kuopio Ischemic Heart Disease Study

“…systolic versus diastolic HF and HF with preserved versus reduced ejection fractions), because of the absence of such data. Though we adjusted for several confounders, there was a possibility of residual confounding due to other unmeasured confounders (such as proton pump inhibitors and other medications that affect serum magnesium levels (47) and are associated with risk of CVD (48)), which could in part explain the association between serum magnesium and HF. The study included only male Caucasians and cannot necessarily be extrapolated to women and other ethnicities.…”

An Unusual Case of Hypercalcaemia Whilst Severely Hypomagnesaemic

“…The association between PPI use and magnesium levels varies by whether patients concurrently use diuretics. In patients taking diuretics, concurrent use of PPIs was associated with lower adjusted serum magnesium compared to patient not taking diuretics (1)(2)(3)(4). By contrast the occurrence of hypercalcaemia in the context of hypomagnesaemia is unusual.…”