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

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 Mg(2+) and Ca(2+). 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, Mg(2+) and Ca(2+) 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 Mg(2+) and Ca(2+) levels. However, concomitant addition of dietary inulin fibers normalized serum Ca(2+) but not serum Mg(2+) 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 Ca(2+) absorption upon PPI treatment. In contrast, inulin did not increase intestinal absorption of Mg(2+) sufficiently to recover serum Mg(2+). The clinical potential of dietary inulin treatment should be the subject of future studies.