Brenda C T Kieboom1, Jessica C Kiefte-de Jong2, Mark Eijgelsheim3, Oscar H Franco4, Ernst J Kuipers5, Albert Hofman4, Robert Zietse5, Bruno H Stricker6, Ewout J Hoorn5. 1. Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands; Inspectorate of Health Care, Utrecht, the Netherlands. 2. Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands; Leiden University College, The Hague, the Netherlands. 3. Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands. 4. Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands. 5. Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands. 6. Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands; Inspectorate of Health Care, Utrecht, the Netherlands. Electronic address: b.stricker@erasmusmc.nl.
Abstract
BACKGROUND: Proton pump inhibitor (PPI) use has been associated with hypomagnesemia in case reports and hospital-based cohort studies. Our objective was to determine whether PPI use is associated with hypomagnesemia in the general population and whether this is also found in histamine 2 receptor antagonist (H2RA) users. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 9,818 individuals from the general population (Rotterdam Study). PREDICTOR: PPI use and H2RA use compared to no use. OUTCOMES & MEASUREMENTS: Serum magnesium and hypomagnesemia (serum magnesium ≤ 1.44 mEq/L). Analyses were adjusted for age, sex, body mass index, kidney function, comorbid conditions, and alcohol and diuretic use. RESULTS: Serum magnesium level was 0.022 mEq/L lower in PPI users (n=724; 95% CI, -0.032 to -0.014 mEq/L) versus those with no use. PPI use was associated with increased risk of hypomagnesemia (n=36; OR, 2.00; 95% CI, 1.36-2.93) compared to no use. Effect modification was found between the use of PPIs and loop diuretics; in participants using loop diuretics (n=270), PPI use was associated with a further increased risk of hypomagnesemia (n=5; OR, 7.22; 95% CI, 1.69-30.83) compared to no use. The increased risk with PPIs was only seen after prolonged use (range, 182-2,618 days; OR, 2.99; 95% CI, 1.73-5.15). Including dietary magnesium intake into the model did not alter results (available for 2,504 participants, including 231 PPI users). H2RA users (n=250) also had a lower serum magnesium level (-0.016 [95% CI, -0.032 to -0.002] mEq/L) and increased risk of hypomagnesemia (n=12; OR, 2.00; 95% CI, 1.08-3.72) compared to those with no use, but no interaction with loop diuretics. LIMITATIONS: Cross-sectional analysis with single serum magnesium measurement. CONCLUSIONS: PPI use is associated with hypomagnesemia in the general population. Prolonged PPI use and concomitant loop diuretic use are associated with a stronger risk increase. Similar but weaker associations were found in H2RA users, except for interaction with loop diuretics.
BACKGROUND:Proton pump inhibitor (PPI) use has been associated with hypomagnesemia in case reports and hospital-based cohort studies. Our objective was to determine whether PPI use is associated with hypomagnesemia in the general population and whether this is also found in histamine 2 receptor antagonist (H2RA) users. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 9,818 individuals from the general population (Rotterdam Study). PREDICTOR: PPI use and H2RA use compared to no use. OUTCOMES & MEASUREMENTS: Serum magnesium and hypomagnesemia (serum magnesium ≤ 1.44 mEq/L). Analyses were adjusted for age, sex, body mass index, kidney function, comorbid conditions, and alcohol and diuretic use. RESULTS: Serum magnesium level was 0.022 mEq/L lower in PPI users (n=724; 95% CI, -0.032 to -0.014 mEq/L) versus those with no use. PPI use was associated with increased risk of hypomagnesemia (n=36; OR, 2.00; 95% CI, 1.36-2.93) compared to no use. Effect modification was found between the use of PPIs and loop diuretics; in participants using loop diuretics (n=270), PPI use was associated with a further increased risk of hypomagnesemia (n=5; OR, 7.22; 95% CI, 1.69-30.83) compared to no use. The increased risk with PPIs was only seen after prolonged use (range, 182-2,618 days; OR, 2.99; 95% CI, 1.73-5.15). Including dietary magnesium intake into the model did not alter results (available for 2,504 participants, including 231 PPI users). H2RA users (n=250) also had a lower serum magnesium level (-0.016 [95% CI, -0.032 to -0.002] mEq/L) and increased risk of hypomagnesemia (n=12; OR, 2.00; 95% CI, 1.08-3.72) compared to those with no use, but no interaction with loop diuretics. LIMITATIONS: Cross-sectional analysis with single serum magnesium measurement. CONCLUSIONS: PPI use is associated with hypomagnesemia in the general population. Prolonged PPI use and concomitant loop diuretic use are associated with a stronger risk increase. Similar but weaker associations were found in H2RA users, except for interaction with loop diuretics.
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