Dietary Inulin Fibers Prevent Proton-Pump Inhibitor (PPI)-Induced Hypocalcemia in Mice

PLoS One. 2015 Sep 23;10(9):e0138881. doi: 10.1371/journal.pone.0138881. eCollection 2015.


Background: Proton-pump inhibitor-induced hypomagnesemia (PPIH) is the most recognized side effect of proton-pump inhibitors (PPIs). Additionally, PPIH is associated with hypocalcemia and hypokalemia. It is hypothesized that PPIs reduce epithelial proton secretion and thereby increase the pH in the colon, which may explain the reduced absorption of and Mg2+ and Ca2+. Fermentation of dietary oligofructose-enriched inulin fibers by the microflora leads to acidification of the intestinal lumen and by this enhances mineral uptake. This study aimed, therefore, to improve mineral absorption by application of dietary inulin to counteract PPIH.

Methods: Here, C57BL/J6 mice were supplemented with omeprazole and/or inulin. Subsequently, Mg2+ and Ca2+ homeostasis was assessed by means of serum, urine and fecal electrolyte measurements. Moreover, the mRNA levels of magnesiotropic and calciotropic genes were examined in the large intestine and kidney by real-time PCR.

Results: Treatment with omeprazole significantly reduced serum Mg2+ and Ca2+ levels. However, concomitant addition of dietary inulin fibers normalized serum Ca2+ but not serum Mg2+ concentrations. Inulin abolished enhanced expression of Trpv6 and S100g in the colon by omeprazole. Additionally, intestinal and renal mRNA levels of the Trpm6 gene were reduced after inulin intake.

Conclusions: This study suggests that dietary inulin counteracts reduced intestinal Ca2+ absorption upon PPI treatment. In contrast, inulin did not increase intestinal absorption of Mg2+ sufficiently to recover serum Mg2+. The clinical potential of dietary inulin treatment should be the subject of future studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / blood
  • Dietary Fiber / administration & dosage*
  • Drug Evaluation, Preclinical
  • Fatty Acids / biosynthesis
  • Hypocalcemia / blood
  • Hypocalcemia / chemically induced
  • Hypocalcemia / prevention & control*
  • Intestinal Absorption / drug effects
  • Inulin / administration & dosage*
  • Magnesium / blood
  • Male
  • Mice, Inbred C57BL
  • Omeprazole / adverse effects*
  • Proton Pump Inhibitors / adverse effects*
  • S100 Calcium Binding Protein G / metabolism


  • Dietary Fiber
  • Fatty Acids
  • Proton Pump Inhibitors
  • S100 Calcium Binding Protein G
  • S100g protein, mouse
  • Inulin
  • Magnesium
  • Omeprazole
  • Calcium

Grants and funding

This study was funded through a grant of the Institute of Genetic Metabolic Diseases of the Radboud university medical center Nijmegen. This work was supported by grants from the Netherlands Organization for Scientific Research (ZonMw 9120.8026, NWO ALW 818.02.001, VICI 016.130.668, Rubicon 825.14.021), the Dutch Kidney Foundation (Kolff 14OKG17), and the EURenOmics project from the European Union seventh Framework Programme (FP7/2007–2013, agreement no. 305608). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.