Melatonin’s anti-inflammatory and antioxidant effects in gallstone disease: A narrative review

Gallstone disease (cholelithiasis) is a common gastrointestinal (GI) disorder characterized by the accumulation of hardened bile constituents, often leading to complications such as cholecystitis, cholangitis, and pancreatitis. Most gallstones are cholesterol-based and form due to bile supersaturation, gallbladder dysmotility, and inflammation. Current treatment options-such as ursodeoxycholic acid, laparoscopic cholecystectomy, and dietary modifications-have limitations including invasiveness, prolonged duration, side effects, and recurrence risk. Melatonin, a hormone secreted by the pineal gland, has gained attention for its antioxidant and anti-inflammatory properties, as well as its regulatory effects on lipid metabolism and gallbladder motility. Experimental studies suggest that melatonin reduces biliary cholesterol, suppresses oxidative stress, and restores gallbladder muscle function, thereby preventing gallstone formation. It is also present in bile and shown to enhance cholesterol conversion into bile acids and inhibit intestinal cholesterol absorption. Beyond gallstone prevention, melatonin demonstrates protective effects against GI malignancies, including hepatocellular carcinoma and cholangiocarcinoma, by regulating mitochondrial function, inhibiting glycolysis, and modulating apoptosis. With a strong safety profile and minimal side effects, melatonin may serve as a promising adjunct or alternative for gallstone management, particularly in patients unfit for surgery. Further clinical research is warranted to validate its therapeutic role.