Title

The role of gastric pH and bicarbonate secretion in intestinal absorption of calcium from supplements

Date of Completion

January 2008

Keywords

Health Sciences, Pharmacology

Degree

Ph.D.

Abstract

Calcium supplements, used for prevention and treatment of osteoporosis, must remain soluble for absorption from the gastrointestinal tract into systemic circulation. Unfortunately, intestinal calcium absorption from a typical dose averages only 25% with a highly variable range. The hypothesis investigated here is that a key barrier to calcium absorption is the intestinal precipitation of calcium carbonate due to the secretion of bicarbonate to increase intestinal pH. The solubility of many calcium salts are pH-dependent and may be soluble at low gastric pH but have limited solubility, and therefore bioavailability, in the more neutral pH of the small intestine, the major site of absorption. An in vitro system was developed to determine the extent of calcium carbonate precipitation after dissolution and neutralization, simulating the in vivo gastrointestinal environment. The effects of bicarbonate secretion rate, neutralizing solution, calcium dose, calcium salt, and the presence of bile components or amino acids on the concentration of calcium remaining in solution were determined. Total soluble calcium significantly decreased at supplemental doses of calcium citrate and calcium chloride with neutralization using bicarbonate. Using relationships at equilibrium, the concentration of each calcium species was calculated, and the presence of soluble calcium ion pairs did affect the calcium precipitation profiles. Less precipitation occurred in the presence of bile components and amino acids. To investigate the importance of calcium bicarbonate, a soluble ion, on intestinal absorption, calcium transport was evaluated through Caco-2 cell monolayers under different pH and PCO2 environments. No differences in calcium transport or apparent permeability were observed, indicating that calcium absorption is not affected by the bicarbonate ion. Finally, calcium bioavailability was analyzed in healthy adults, who were pretreated with lansoprazole to increase gastric pH or placebo, in a double blind, crossover study. The data were inconclusive due to the administration of water that affected gastric pH and buffering effect of the calcium salt. The in vitro data support the hypothesis and give a scientific basis to suggest novel formulation strategies for calcium supplementation, especially targeted to the growing population administered medication to increase gastric pH, and who may potentially be at higher risk for osteoporosis. ^