What causes gallstones?

Scientists believe cholesterol stones form when bile contains too much cholesterol, too much bilirubin, or not enough bile salts, or when the gallbladder does not empty completely or often enough. The reason these imbalances occur is not known.

The cause of pigment stones is not fully understood. The stones tend to develop in people who have liver cirrhosis, biliary tract infections, or hereditary blood disorders—such as sickle cell anemia—in which the liver makes too much bilirubin.

The mere presence of gallstones may cause more gallstones to develop. Other factors that contribute to the formation of gallstones, particularly cholesterol stones, include

• Sex. Women are twice as likely as men to develop gallstones. Excess estrogen from pregnancy, hormone replacement therapy, and birth control pills appears to increase cholesterol levels in bile and decrease gallbladder movement, which can lead to gallstones.
• Family history. Gallstones often run in families, pointing to a possible genetic link.
• Weight. A large clinical study showed that being even moderately overweight increases the risk for developing gallstones. The most likely reason is that the amount of bile salts in bile is reduced, resulting in more cholesterol. Increased cholesterol reduces gallbladder emptying. Obesity is a major risk factor for gallstones, especially in women.
• Diet. Diets high in fat and cholesterol and low in fiber increase the risk of gallstones due to increased cholesterol in the bile and reduced gallbladder emptying.
• Rapid weight loss. As the body metabolizes fat during prolonged fasting and rapid weight loss—such as “crash diets”—the liver secretes extra cholesterol into bile, which can cause gallstones. In addition, the gallbladder does not empty properly.
• Age. People older than age 60 are more likely to develop gallstones than younger people. As people age, the body tends to secrete more cholesterol into bile.
• Ethnicity. American Indians have a genetic predisposition to secrete high levels of cholesterol in bile. In fact, they have the highest rate of gallstones in the United States. The majority of American Indian men have gallstones by age 60. Among the Pima Indians of Arizona, 70 percent of women have gallstones by age 30. Mexican American men and women of all ages also have high rates of gallstones.
• Cholesterol-lowering drugs. Drugs that lower cholesterol levels in the blood actually increase the amount of cholesterol secreted into bile. In turn, the risk of gallstones increases.
• Diabetes. People with diabetes generally have high levels of fatty acids called triglycerides. These fatty acids may increase the risk of gallstones.