From the Guidelines
Cholesterol stones are primarily caused by the supersaturation of bile with cholesterol, which is influenced by factors such as female gender, obesity, rapid weight loss, and advancing age, as reported in the 2017 WSES and SICG guidelines on acute calcolous cholecystitis in elderly population 1. The etiology of cholesterol stones is multifactorial, involving the interplay of various risk factors that contribute to the supersaturation of bile with cholesterol.
- Key factors include:
- Female gender, especially during reproductive years
- Obesity
- Rapid weight loss
- Pregnancy
- Certain medications, such as estrogen therapy and some lipid-lowering drugs
- Genetic predisposition
- Advancing age, with the prevalence of gallstones increasing to 15% and 24% at 70 years of age, and 24% and 35% at 90 years of age for males and females, respectively, as shown in the MICOL study cited in the guidelines 1
- Metabolic conditions, such as diabetes and insulin resistance, also increase the risk of developing cholesterol stones.
- Gallbladder hypomotility, which allows cholesterol crystals to remain in the gallbladder longer, promoting stone formation, is another contributing factor.
- Certain ethnic groups, particularly Native Americans and Hispanic populations, have a higher genetic susceptibility to developing cholesterol stones.
- Dietary factors, such as high-calorie, high-cholesterol diets, may also play a role, although their significance is less than that of metabolic and genetic factors. The understanding of these mechanisms is crucial in explaining why cholesterol stones account for approximately 80% of all gallstones in Western populations, highlighting the importance of addressing these risk factors in the prevention and management of gallstone disease.
From the Research
Cholesterol Stones Etiology
- Cholesterol gallstones are formed when bile is supersaturated with cholesterol 2, 3, 4
- The supersaturation of bile with cholesterol is due to excessive secretion of cholesterol into the bile 3
- Dietary factors such as high intake of cholesterol, saturated fat, trans fatty acids, and refined sugar may increase the risk of developing cholesterol gallstones 5
- On the other hand, dietary factors like polyunsaturated fat, monounsaturated fat, fiber, and caffeine may help prevent the development of gallstones 5
- Obesity is also a risk factor for gallstones, and identification and avoidance of allergenic foods may relieve symptoms of gallbladder disease 5
- Certain biochemical defects and dyslipidaemia may also contribute to the formation of cholesterol gallstones 3, 6
Pathogenesis of Cholesterol Gallstones
- The pathogenesis of cholesterol gallstones involves a physical-chemical event that results from alterations in the lipid composition of gallbladder bile 3
- Cholesterol crystal formation requires the presence of one or more of the following: cholesterol supersaturation, accelerated nucleation, or gallbladder hypomotility/bile stasis 4
- Risk factors for cholesterol stones include age, gender, genetics, obesity, rapid weight loss, and ileal disease 4
Prevention and Treatment
- Medical therapy with oral bile acids, such as ursodiol and chenodiol, may be effective in dissolving small cholesterol stones and preventing recurrence 2, 5
- Statins and ezetimibe, used to treat dyslipidaemia, may also have a beneficial effect on bile composition and cholesterol gallstone formation 6
- Nutritional supplements like vitamin C, soy lecithin, and iron, as well as a mixture of plant terpenes (Rowachol), may help prevent gallstones 5