Simulation of the defect of bile acid metabolism associated with cholesterol cholelithiasis by sorbitol ingestion in man

I tested the possibility that shortening small bowel transit time by administration of the nonabsorbable alcohol sorbitol might reproduce the defect of bile acid metabolism associated with cholesterol gallstone disease. Nine normal volunteers were studied by isotope dilution techniques after a 2-week control period on a metabolic ward and again after 2 to 3 weeks of sorbitol ingestion. Sorbitol dose was low enough to preclude diarrhea but sufficient to reduce mean small bowel transit time from 86 to 44 min. Sorbitol ingestion lowered the total bile acid pool in all nine subjects with an average reduction of 27% for the group as a whole (p < 0.005). This reduction in total pool included significant reductions in the pools of all three bile acids, cholic, chenodeoxycholic, and deoxycholic, without disproportionate reductions for any of the three. Reductions in primary bile acid pools were a result of both an increase in fractional turnover (cholic only) and a small decrease in synthesis (both primary bile acids). These changes in bile acid metabolism, which approximate those found in subjects with cholesterol gallstone disease, were accompanied by a significant increase in the relative cholesterol content of bile from 6.99 to 7.81 molar percent (p < 0.01). In addition to providing a model for the defect of bile acid metabolism associated with cholesterol cholelithiasis, these data may have practical implications for a group such as the American Indians of the Southwest whose high prevalence of cholesterol gallstones may be aggravated by ingestion of nonabsorbable carbohydrates known to be present in unusually large amounts in these Indians' diet.