Association of bowel movement frequency and use of laxatives with the occurrence of symptomatic gallstone disease in a prospective study of women

OBJECTIVES: The authors prospectively examined the association between bowel movement frequency (used as a proxy for intestinal transit), laxative use, and the risk of symptomatic gallstone disease. METHODS: A total of 79,829 women, aged 36–61 yr, without a history of symptomatic gallstone disease and free of cancer, responded to a mailed questionnaire in 1982 that assessed bowel movement frequency and use of laxatives. Between 1984 and 1996, 4,443 incident cases of symptomatic gallstone disease were documented. Relative risks (RRs) of symptomatic gallstone disease and 95% confidence intervals (CIs) were calculated using logistic regression. RESULTS: After controlling for age and established risk factors, the multivariate RRs were, compared to women with daily bowel movements, 0.97 (95% CI 0.86–1.08) for women with bowel movements every third day or less, and 1.00 (95% CI 0.91–1.11) for women with bowel movement more than once daily. No trend was evident. As compared to women who never used laxatives in 1982, a significant modest inverse association was seen for monthly laxative use, with a multivariate RR of 0.84 (95% CI 0.72–0.98), and weekly to daily laxative use was associated with a RR of 0.88 (95% CI 0.78–1.02). CONCLUSIONS: These findings do not support an association between infrequent bowel movements and risk of symptomatic gallstone disease in women, and indicate that simple questions directed at bowel movement frequency are unlikely to enhance our ability to predict risk of symptomatic gallstone disease. The slightly inverse association between use of laxatives and risk of symptomatic gallstone disease may be due to a mechanism that is not related to bowel movement frequency.

Farnesoid X receptor agonism - a new approach to the treatment of cholesterol gallstone disease

Gallstone disease is very common among native Americans and Hispanics, and similar to 20 million patients are treated for this disease annually in the US. The nuclear farnesoid X receptor (FXR) is the receptor for bile acids, and GW4064 is a synthetic agonist at the FXR. FXR-/- mice fed a lithogenic diet (high fat, cholesterol and cholic acid) are more susceptible to gallstone disease than wild-type mice with the same mixed background, thus establishing that the ablation of FXR is associated with this disease. The C57L mouse is susceptible to gallstone formation. When C57L mice are fed a lithogenic diet for a week, the bile contains large aggregates of cholesterol precipitates, and two of five C57L mice had macroscopic cholesterol crystals. in contrast, when C57L mice were fed the lithogenic diet and administered GW4064 100 mg/kg/day by oral gavage, there was no precipitation of cholesterol. Treatment with this agent also increased bile salt and phospholipid concentration, and prevented gallbladder epithelium damage. As FXR agonism with GW4064 has been shown to be useful in a mouse model of cholesterol gallstone disease, it should undergo further development for the treatment of this condition.