Cholecystokinin increases bile acid synthesis with total parenteral nutrition but does not prevent stone formation

Total parenteral nutrition (TPN) is associated with cholestasis and gallstones. Gallbladder stasis may be important in the development of gallstones, and cholecystokinin (CCK) to stimulate gallbladder contraction has been proposed as a treatment to prevent this complication. We studied in vivo bile acid synthesis and bile acid output in miniswine on TPN to test whether daily CCK improves bile acid output and normalizes bile acid profiles with TPN. Nine miniswine were nutritionally maintained with TPN for 4 weeks; four pigs received CCK (0.1 mg/kg) iv daily. In vivo bile acid synthesis was measured with injection of 7 alpha-tritiated cholesterol. An increase in tritiated water reflects the activity of 7 alpha-hydroxylation, the rate-limiting step in bile acid synthesis. At the end of 4 weeks, bile was collected and bile acid output and bile salt profiles were determined. One of five animals on TPN developed gallstones while two of four receiving daily CCK developed stones. In vivo bile acid synthesis decreased with TPN (controls, 63 +/- 9 mg/24 hr versus TPN, 13 +/- 4 mg/24 hr) and increased in TPN animals with CCK treatment (TPN-CCK, 105 +/- 35 mg/24 hr). Bile acid profiles are changed with TPN with more secondary bile acids, this was not improved with CCK. CCK improved bile acid synthesis and bile acid output but failed to prevent gallstone formation or normalize bile salt profiles. In addition to promoting gallbladder contraction, CCK may have a stimulatory effect on bile acid synthesis. CCK alone did not prevent gallstone formation.