Dietary fats rich in saturated fatty acids (12∶0, 14∶0, and 16∶0) enhance gallstone formation relative to monounsaturated fat (18∶1) in cholesterol‐fed hamsters

To test the possibility that dietary palmitic acid (16∶0) may be lithogenic, different fats were blended to exchange 18∶1 in olive oil with either 16∶0 in palm stearin, 12∶0+14∶0 in coconut oil, or 14∶0+16∶0 in butterfat. Dietary 18∶2 was held constant at 1.2% energy (en) (with extra safflower oil as needed) in these four purified diets containing low fat (11% of total energy) and 0.4% cholesterol. A fifth, high‐fat diet provided 40% of the total energy as the 16∶0‐rich blend. All hamsters fed the low‐fat, 16∶0‐rich blend for six weeks developed cholesterol gallstones (8/8). Although the gallstone incidence was lower for the 12∶0+14∶0‐rich diet (5/8), the severity of stone formation in affected hamsters was equal to that in the low‐fat, 16∶0‐rich group. Mucin accumulation in gallbladder bile was often associated with cholesterol gallstones in diets containing 16∶0, but was minimal in 18∶1‐rich and 12∶0+14∶0‐rich groups. Neither the lithogenic index (all>1.0), plasma lipids, nor liver cholesterol was a selective predictor of stone formation. The high‐fat, 16∶0‐rich diet actually decreased cholesterol stone incidence (3/8) and severity, but yielded a high incidence of pigment stones (5/8). Thus, saturated fat and 16∶0 per se were not responsible for the exaggerated lithogenesis. Because the antilithogenic 18∶1‐rich diet also normalized the 18∶2 intake (1.2% en) relative to previous butter diets (0.3% en), the potential importance of essential fatty acids (EFA) deficiency in the model was tested in a second study by feeding graded amounts of 18∶2 (0.3, 0.6, 0.9, and 1.2% en) as safflower oil in four low‐fat, butter‐rich diets (11% en as fat) without alleviating gallstone incidence or severity. These studies indicate that substitution of 18∶1 for saturated fatty acids in low‐fat diets reduces gallstone formation without affecting the lithogenic index. Furthermore, intake of 18∶2 at or below the EFA requirement does not appear to be a major factor in this model.