What causes cholesterol gallstones (cholelithiasis)?

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Last updated: April 22, 2025 • View editorial policy

From the FDA Drug Label

The 7-dehydroxylation reaction appears to be alpha-specific, i. e. chenodiol is more efficiently 7-dehydroxylated than ursodiol and, for equimolar doses of ursodiol and chenodiol, levels of lithocholic acid appearing in bile are lower with the former. Lithocholic acid is formed by 7-dehydroxylation of the dihydroxy bile acids (ursodiol and chenodiol) in the gut lumen. The cause of bile gallstones is not directly stated in the provided drug labels, but it can be inferred that lithocholic acid, a metabolite of ursodiol and chenodiol, may play a role in the formation of gallstones. However, the exact cause of bile gallstones is not explicitly stated. 1

From the Research

Bile gallstones are primarily caused by imbalances in the chemical composition of bile in the gallbladder, with the most common type being cholesterol gallstones, which form when there's too much cholesterol in the bile, as stated in the most recent study 2. The formation of gallstones is a complex process that involves multiple factors, including:

  • An imbalance in the composition of bile, resulting in precipitation of one or more of its components 2
  • Excessive secretion of cholesterol or bilirubin conjugates, and/or deficient secretion of bile salt and lecithin, which are the solubilizers of these otherwise insoluble lipids 3
  • Risk factors such as being female, over 40, obese, rapid weight loss, pregnancy, certain medications, and genetic predisposition 2
  • Diabetes, metabolic syndrome, and a diet high in fats and low in fiber can also increase the risk of developing gallstones 4 The gallbladder's reduced contractions during fasting periods can concentrate bile, further promoting stone formation, and prevention strategies include maintaining a healthy weight, eating regular meals, consuming adequate fiber, and avoiding rapid weight loss programs. It is essential to note that the liver produces more cholesterol than the bile can dissolve, or when the gallbladder doesn't empty properly, which can lead to the formation of cholesterol gallstones, as mentioned in the study 2. Pigment gallstones, another type, develop when there's excess bilirubin in the bile, often due to conditions like liver disease or blood disorders, and the chemical compositions of brown and black pigment stones are different, as stated in the study 3.

References

Research

Pathogenesis of gallstones.

Recenti progressi in medicina, 1992

Research

Physical and metabolic factors in gallstone pathogenesis.

Gastroenterology clinics of North America, 1999

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