Dietary fish oil inhibits cholesterol monohydrate crystal nucleation and gallstone formation in the prairie dog

Abstract

Epidemiologic studies suggest that populations consuming a diet rich in fish oil have lower rates of both atherosclerotic heart disease and gallstones. The mechanisms underlying this inhibitory effect on cholesterol gallstone formation remain unclear. We therefore studied the effect of dietary fish oil on bile composition and cholesterol precipitation in an animal model of gallstone disease. Adult male prairie dogs were fed a standard control diet (n = 12) or a lithogenic 1.2% cholesterol diet (n = 16). One half of the animals in each group had their diet supplemented with concentrated fish oil. After 14 days animals receiving the cholesterol diet all developed biliary cholesterol monohydrate crystals and gallstones. When fish oil was added to this high cholesterol diet, solid cholesterol crystal precipitation and gallstone formation were completely inhibited. This inhibition of gallstone formation was accompanied by a significant decrease in biliary calcium and total protein concentration. Microscopic cholesterol liquid crystals were evident in the bile of all of the animals fed the cholesterol plus fish oil diet. Dietary fish oil also significantly prolonged cholesterol monohydrate crystal observation time in animals receiving the lithogenic diet. These data suggest that dietary fish oil exerts a potent antilithogenic effect on cholesterol gallstone disease and may induce a stable liquid crystalline phase retarding nucleation.