A low-fat diet is recommended for hyperlipidemia. However, low-density lipoprotein (LDL) responses depend on the type of hyperlipidemia (ie, simple hypercholesterolemia or combined hyperlipidemia). In combined hyperlipidemia, which is typical of patients with metabolic syndrome, LDL levels are only one third as responsive to fat and cholesterol as simple hypercholesterolemia. The diminished dietary sensitivity of combined hyperlipidemia is explained by diminished intestinal absorption of cholesterol, a feature of metabolic syndrome. In turn, combined hyperlipidemia is caused by heightened lipid secretion by the liver. A moderate-fat, moderate-carbohydrate diet employing allowable fats has the promise of reducing endogenous lipoprotein production in combined hyperlipidemia. Triglyceride, LDL, and small-dense LDL should be lower, and high-density lipoprotein, apoprotein A-I, and buoyant LDL should be higher. A test of this dietary strategy on lipoproteins and downstream benefits on inflammatory mediators, oxidative stress, and vascular reactivity is now underway.