Exploration of intestinal calcium precipitation as a barrier to absorption at high calcium doses.
Pharm Res. 2008 Dec;25(12):2760-8. Epub 2008 Jun 17. PMID: 18560997
School of Pharmacy, U-3092, University of Connecticut, Storrs, CT 06269, USA.
PURPOSE: To investigate the hypothesis that intestinal bicarbonate secretions precipitate calcium as the carbonate salt, thereby resulting in poor absorption (20-40%) from calcium supplements. METHODS: The in vitro effect of calcium dose and bicarbonate secretion rate on soluble calcium was determined by neutralizing elemental Ca(2+)(250, 475, and 630 mg) in 0.1 N HCl to pH 7 with a bicarbonate secretion rate of 0.12 or 1.2 mEq/min. P (CO2) and pH of the solutions were monitored. Soluble calcium was analyzed using atomic absorption spectrometry. Additionally, the transport of calcium across Caco-2 cell monolayers was determined. RESULTS: Calcium from a 250 mg dose remained soluble during bicarbonate secretion, regardless of rate. Once the dose increased, the calcium remaining in solution decreased during neutralization with bicarbonate. The Ca(2+)/CaHCO(3) (+) ratio had no effect on calcium permeation across Caco-2 cell monolayers. CONCLUSIONS: The physicochemical mechanism of intestinal calcium precipitation supports published clinical data by suggesting that once the solubility product of calcium carbonate is reached, increasing the calcium dose results in significant precipitation at intestinal pH values.