Nucleation time: a key factor in the pathogenesis of cholesterol gallstone disease.

In earlier studies, we concluded that biliary cholesterol supersaturation may be a necessary but not sufficient cause for gallstone formation. In the present studies, we calculated cholesterol saturation indices (CSI) for 120 bile specimens of cholesterol gallstone patients and controls, using the solubility boundaries of Carey and Small (J Clin Invest 61:998-1026, 1978) for artificial biles. The mean CSI + SD was 1.42 +/- 0.68 for controls and 1.80 +/- 1.02 for cholesterol gallstone patients. Of the control bile samples, 68% were supersaturated. Since the two groups could not be sharply distinguished by saturation index, we studied another property of bile samples: nucleation time for cholesterol crystal formation. The mean nucleation time for 16 control bile samples was 15 days, and a strong correlation (r = 0.84) was found between CSI and nucleation time. Twelve bile samples of cholesterol gallstone patients had a mean nucleation time of 3 days and no correlation between CSI and nucleation time. A discriminant analysis of the data, which took into account both the CSI and the nucleation time for each sample, allowed a sharp distinction between bile samples of cholesterol gallstone patients and controls. This distinction could not have been drawn from studies with artificial biles, since these differ only in their CSI.

Effect of oral administration of 'essential' phospholipid, beta-glycerophosphate, and linoleic acid on biliary lipids in patients with cholelithiasis.

6 patients with radiolucent cholelithiasis underwent randomized successive 3-week trials on each of the following medications: beta-glycerophosphate, linoleic acid, or purified soybean lecithin. Bile-rich duodenal fluid was obtained prior to the study and following each treatment period. Soybean lecithin feeding effected a qualitative change in biliary lecithin with increased fatty acid unsaturation, but no significant improvement in biliary cholesterol saturation or lipid composition changes including a proportionate increase in biliary phospholipids resulted from any treatment program. A 6-month therapeutic trial with soybean lecithin plus cholic acid failed to show a therapeutic response indicative of gallstone dissolution in the 6 patients.