Primary and secondary prevention of gallstone disease: implications for patient management and research priorities

Am J Surg. 1993 Apr;165(4):541-8. doi: 10.1016/s0002-9610(05)80958-4.


Primary prevention is defined as the prevention of gallstone formation; secondary prevention is defined as the prevention of clinical manifestations of gallstones--symptoms or more severe complications. For primary prevention, general "wellness" measures can be recommended from a theoretic standpoint. These include elimination of obesity (to decrease excessive cholesterol biosynthesis or mobilization of tissue cholesterol during rapid weight loss); a high-fiber, high-calcium diet (to diminish input of deoxycholic acid); ingestion of meals at regular intervals (to diminish gallbladder storage and interruption of the enterohepatic circulation of bile acids); and vigorous exercise (to permit frequent meals without excessive caloric intake). In addition, based on animal studies, intake of low saturated fatty acids may diminish the nucleation of supersaturated bile. Secondary prevention is recommended only when gallstones become symptomatic because of the benign natural history of asymptomatic gallstones, the intrinsic limitations of medical therapy, and the absence of predictors that would enable selection of asymptomatic patients at high risk for becoming symptomatic. Secondary prevention involves nonsurgical approaches (dissolution with ursodiol, extracorporeal shock-wave lithotripsy plus adjuvant bile acids, and, rarely, contact dissolution with organic solvents). For patients with symptomatic gallstones, nonsurgical therapy will be used by those patients who cannot or will not have surgery, as well as those patients who wish to explore a trial of nonsurgical therapy before having surgery. Because of the intrinsic limitations of nonsurgical therapy in comparison to the efficacy and safety of surgery, most patients will undergo surgery. Future research priorities include elucidation of factors responsible for: (1) bile that is supersaturated in cholesterol; (2) elevated biliary deoxycholic acid levels in patients with cholesterol gallstones; (3) rapid nucleation in patients with multiple cholesterol gallstones; (4) precipitation of calcium bilirubinate; and (5) impaired gallbladder motility in gallbladder stone disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Bile Acids and Salts / therapeutic use
  • Calcium / analysis
  • Calcium, Dietary / administration & dosage
  • Cholecystectomy
  • Cholelithiasis / chemistry
  • Cholelithiasis / complications
  • Cholelithiasis / etiology
  • Cholelithiasis / prevention & control*
  • Cholelithiasis / therapy
  • Cholesterol / analysis
  • Diet, Reducing
  • Dietary Fiber / administration & dosage
  • Humans
  • Lithotripsy
  • Primary Prevention
  • Research Design
  • Risk Factors
  • United States


  • Bile Acids and Salts
  • Calcium, Dietary
  • Dietary Fiber
  • Cholesterol
  • Calcium