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

Hess MW, de Baaij JH, Gommers LM, Hoenderop JG, Bindels RJ - PLoS ONE (2015)

Bottom Line: Treatment with omeprazole significantly reduced serum Mg2+ and Ca2+ levels.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+.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Effects of the combinatory application of omeprazole and 10% inulin enriched diets on electrolytes.Serum Ca2+ concentration (A), 24 h urinary Ca2+ excretion (B), 24 h fecal Ca2+ excretion, serum K+ concentration (D) and serum Na+ concentration (E). Significant differences compared to control are indicated by * with P < 0.05, significant differences between the omeprazole-treated groups are annotated by # with P < 0.05. Bars represent means ± SEM, with n = 10 mice per group.
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pone.0138881.g003: Effects of the combinatory application of omeprazole and 10% inulin enriched diets on electrolytes.Serum Ca2+ concentration (A), 24 h urinary Ca2+ excretion (B), 24 h fecal Ca2+ excretion, serum K+ concentration (D) and serum Na+ concentration (E). Significant differences compared to control are indicated by * with P < 0.05, significant differences between the omeprazole-treated groups are annotated by # with P < 0.05. Bars represent means ± SEM, with n = 10 mice per group.

Mentions: Serum Ca2+ of the omeprazole-treated mice was slightly, but, significantly reduced compared to the vehicle-treated control group (2.19 ± 0.01 mmol/L and 2.27 ± 0.01 mmol/L, respectively, P < 0.05, Fig 3A). Importantly, application of the inulin diet during omeprazole treatment resulted in a correction of serum Ca2+ to the level of control mice and inulin-only treated mice. This is reflected in the 24 h urinary Ca2+ excretion; omeprazole treated mice displayed a reduced urinary Ca2+ excretion compared to the mice on the inulin diet 2.7 ± 0.3 μmol/24 h and 4.3 ± 0.5 μmol/24 h, respectively, P < 0.05 Fig 3B). The fecal excretion of Ca2+ in all groups was significantly lower compared to control mice (for inulin 0.55 ± 0.03 mmol/24 h, for omeprazole 0.48 ± 0.03 mmol/24 h, for inulin-omeprazole 0.55 ± 0.03 mmol/24 h vs. control 0.93 ± 0.07 mmol/24 h, Fig 3C).


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

Hess MW, de Baaij JH, Gommers LM, Hoenderop JG, Bindels RJ - PLoS ONE (2015)

Effects of the combinatory application of omeprazole and 10% inulin enriched diets on electrolytes.Serum Ca2+ concentration (A), 24 h urinary Ca2+ excretion (B), 24 h fecal Ca2+ excretion, serum K+ concentration (D) and serum Na+ concentration (E). Significant differences compared to control are indicated by * with P < 0.05, significant differences between the omeprazole-treated groups are annotated by # with P < 0.05. Bars represent means ± SEM, with n = 10 mice per group.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4580428&req=5

pone.0138881.g003: Effects of the combinatory application of omeprazole and 10% inulin enriched diets on electrolytes.Serum Ca2+ concentration (A), 24 h urinary Ca2+ excretion (B), 24 h fecal Ca2+ excretion, serum K+ concentration (D) and serum Na+ concentration (E). Significant differences compared to control are indicated by * with P < 0.05, significant differences between the omeprazole-treated groups are annotated by # with P < 0.05. Bars represent means ± SEM, with n = 10 mice per group.
Mentions: Serum Ca2+ of the omeprazole-treated mice was slightly, but, significantly reduced compared to the vehicle-treated control group (2.19 ± 0.01 mmol/L and 2.27 ± 0.01 mmol/L, respectively, P < 0.05, Fig 3A). Importantly, application of the inulin diet during omeprazole treatment resulted in a correction of serum Ca2+ to the level of control mice and inulin-only treated mice. This is reflected in the 24 h urinary Ca2+ excretion; omeprazole treated mice displayed a reduced urinary Ca2+ excretion compared to the mice on the inulin diet 2.7 ± 0.3 μmol/24 h and 4.3 ± 0.5 μmol/24 h, respectively, P < 0.05 Fig 3B). The fecal excretion of Ca2+ in all groups was significantly lower compared to control mice (for inulin 0.55 ± 0.03 mmol/24 h, for omeprazole 0.48 ± 0.03 mmol/24 h, for inulin-omeprazole 0.55 ± 0.03 mmol/24 h vs. control 0.93 ± 0.07 mmol/24 h, Fig 3C).

Bottom Line: Treatment with omeprazole significantly reduced serum Mg2+ and Ca2+ levels.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+.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus