Effects of Ursodeoxycholic Acid and Aspirin on the Formation of Lithogenic Bile and Gallstones during Loss of Weight

Abstract

We attempted to determine whether the administration of aspirin or ursodeoxycholic acid during loss of weight could prevent the development of lithogenic changes in bile and the formation of gallstones. Sixty-eight obese subjects without gallstones who were entered in a program (520 kcal per day) to lose weight were randomly assigned to receive ursodeoxycholic acid (1200 mg per day), aspirin (1300 mg per day), or placebo in double-blind fashion for up to 16 weeks. At entry, at four weeks of treatment, and at three weeks after the completion of treatment, the subjects underwent ultrasonography to detect gallstones and duodenal drainage of bile to detect cholesterol crystals and to determine the bile saturation index and glycoprotein concentration. No gallstones or cholesterol crystals formed in the patients treated with ursodeoxycholic acid. Among the patients given placebo, gallstones formed in five (P less than 0.05 vs. ursodeoxycholic acid) and cholesterol crystals in six (P less than 0.001 vs. ursodeoxycholic acid); among those given aspirin, gallstones formed in two and cholesterol crystals in one (no significant difference from ursodeoxycholic acid treatment). By the fourth week, the bile saturation index increased in the placebo group (from 1.07 +/- 0.26 to 1.29 +/- 0.27; P less than 0.001), decreased in the ursodeoxycholic acid group (from 1.11 +/- 0.34 to 0.91 +/- 0.24; P less than 0.001), and did not change significantly in the aspirin group. The concentration of glycoprotein in bile increased in the placebo group (27.9 +/- 14.5 percent; P less than 0.001) but did not change significantly in the groups treated with ursodeoxycholic acid or aspirin. We conclude that ursodeoxycholic acid prevents lithogenic changes in bile and the formation of gallstones in obese subjects during loss of weight.

Estimation of the cost savings resulting from the use of ursodiol for the prevention of gallstones in obese patients undergoing rapid weight reduction

“…Other studies published in the medical literature reported a range of 20±40% for the incidence of gallstone formation in morbidly obese patients undergoing rapid weight loss, 13,14,22 right in line with the results obtained in the placebo arms of the two trials being investigated. Two of these studies also relied on abdominal ultrasonography to detect gallstones.…”

“…There were numerous sporadic reports in the literature regarding the percentage of gallstones requiring surgical removal. Broom®eld et al, 13 reported that 5.2% of their patient cohort required surgery within one year. Kamrath et al, 24 reported that 5.5% of their cohort needed surgery, while Shiffman et al 22 and Worobetz et al 14 reported 11% and 14%, respectively.…”

“…It has been used as a gallstone dissolution agent 10±12 and approved by the Food and Drug Administration (FDA) for that indication. Previous studies have indicated that ursodeoxycholic acid could reduce the incidence of gallstone formation in patients undergoing rapid weight reduction, by either very-low-calorie diet 13 or bariatric surgery. 14 These observations led to two multicenter, placebo-controlled, randomized, double-blind trials to determine the optimal dosage of ursodiol to prevent gallstone formation in patients undergoing either gastricbypass-induced 12 rapid weight loss (b300 patients) or very-low-calorie-diet 11 weight loss (b1000 patients).…”

Ref: Gallstone formation in obese subjects undergoing a weight reduction diet

“…Especially so, since half of the subjects were administered ursodeoxycholic acid which has been demonstrated to reduce the rate of gallstone formation during weight loss. 6 Also puzzling is their report of a mean 6 kg weight loss over an 8 week period with a de®cit of only 500 kcal/day. Assuming an energy value of approximately 7000 kcal per kg of weight lost, the expected mean weight loss is only about 4 kg which suggests that subjects may have restricted their energy intake beyond what was prescribed by the investigators.…”

Risk Factors for Gallstone Formation in Young Saudi Women: A Case Control Study

“…It is believed that the mechanism of gallstone formation in obese people is probably a combination of excess cholesterol saturation of bile [35,36] and reduced gallbladder motor function [37]. It has been found that paradoxically weight reducing is held responsible for induction of gallstone formation [38][39][40][41] and the use of drugs such as chenodeoxycholic acid, uricodeoxycholic acid, terpenes or aspirin, may prevent this in patients on reducing diets [42][43][44][45]. Diabetes mellitus had been reported, though inconclusively, to be associated with gallstones [46] and was found in 22% of females and 19% of males in a series of cholecystectomies reported from Riyadh [4].…”