Mechanism of increase in steatorrhea with calcium and magnesium in exocrine pancreatic insufficiency: an animal model

We used a rat model to investigate the phenomenon of increased steatorrhea associated with administration of calcium or magnesium containing antacids in humans with pancreatic insufficiency. Adult male rats with bile and pancreatic duct ligation were fed test meals containing 56 mumol [14C]triolein (0.5 ml), synthetic human bile (1.0 ml, 100 mumol bile salts, 75% glycine and 25% taurine conjugates, and 14.5 mumol lecithin), pancreatic enzymes (0.5 ml), and antacids (1.0 ml). The percent lipid malabsorbed when antacids were fed in addition to the test meal was: control 19.3 +/- 1%, NaHCO3 15.3 +/- 1% (P less than 0.05 vs. control), Al(OH)3 18.3 +/- 2%, Mg(OH)2 38.2 +/- 2% (p less than 0.001 vs. control), and CaCO3 42.4 +/- 1% (p less than 0.001 vs control). With NaCl, Al(OH)3, and NaHCO3 the malabsorbed fat was primarily triolein, whereas with Ca++ or Mg++ the majority of the lipid recovered was oleic acid. Calcium or magnesium administration was associated with precipitation of glycine-, but not taurine-, conjugated bile salts in the small intestine. When calcium was administered to animals in which the bile consisted entirely of glycine-conjugated bile salts, the lipid recovered (64.0 +/- 3% malabsorption) was almost entirely triolein suggesting reduced lipolysis. These studies suggest that these divalent cations exert their deleterious effect on replacement enzyme therapy by formation of poorly soluble calcium or magnesium soaps and precipitation of glycine conjugated bile salts.