What causes cholelithiasis (gallstones)?

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From the Guidelines

Gallstones are primarily caused by imbalances in the substances that make up bile, specifically an excess of cholesterol or bilirubin, or a deficiency in bile salts. When considering the formation of gallstones, it's crucial to understand the role of bile composition and its impact on morbidity, mortality, and quality of life. The most common type of gallstones are cholesterol stones, which form when the liver produces bile with excessive cholesterol that cannot remain dissolved 1.

Key Factors Contributing to Gallstone Formation

  • Obesity
  • Rapid weight loss
  • High-fat and low-fiber diets
  • Female gender, especially during pregnancy or when taking hormonal medications
  • Age over 40
  • Family history
  • Certain medical conditions like diabetes or Crohn's disease
  • The gallbladder's decreased efficiency in emptying bile, leading to more concentrated bile

Prevention Strategies

  • Maintaining a healthy weight
  • Eating regular meals with adequate fiber
  • Avoiding rapid weight loss programs It's essential to recognize that while these factors contribute to the formation of gallstones, the primary cause is the imbalance in bile composition, which can be influenced by these factors. Understanding the causes and risk factors for gallstone formation is critical for developing effective prevention and treatment strategies that prioritize reducing morbidity, mortality, and improving quality of life.

From the Research

Causes of Gallstones

  • Cholesterol gallstones are the most common type of gallstone and are formed when the amount of cholesterol in gallbladder bile exceeds the maximum concentration that is soluble at the given concentration of bile salts and phospholipids 2
  • Bilirubin gallstones form if the ion product of unconjugated bilirubin and calcium in gallbladder bile exceeds the solubilisation capacities of mixed micelles and vesicles 2
  • The individual risk of gallstone formation is determined by interactions of lithogenic alleles of gallstone susceptibility genes and multiple environmental factors 2
  • Dietary factors that may increase the risk of developing cholesterol gallstones include:
    • Cholesterol
    • Saturated fat
    • Trans fatty acids
    • Refined sugar
    • Possibly legumes 3
  • Obesity is also a risk factor for gallstones 3, 4
  • Other risk factors for developing gallstone disease include:
    • Female sex
    • Older age
    • Certain medications
    • Having type 2 diabetes mellitus, nonalcoholic fatty liver disease, rapid weight loss, or hemolytic anemia 4

Pathogenesis of Gallstones

  • Cholesterol gallstone formation is very likely based upon supersaturated bile formation 5
  • Defects of hepatic metabolism of lipids and organic anions lead to biliary stones 5
  • Nutritional factors, especially lipid compounds, are seemingly crucial in the pathogenesis of biliary diseases 5
  • Lysophosphatidylcholine (lysoPC) and phospholipase A2 have been reported to be increased in bile of pancreaticobiliary maljunction and are considered to be the major risk factor for biliary tract cancers 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Hereditary liver disease: gallstones.

Best practice & research. Clinical gastroenterology, 2010

Research

Nutritional approaches to prevention and treatment of gallstones.

Alternative medicine review : a journal of clinical therapeutic, 2009

Research

Gallstone Disease: Common Questions and Answers.

American family physician, 2024

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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