Background:The fatty acid content and saturation degree of the diet can modulate HDL composition and cholesterol efflux. Objective: We studied the modifications in plasma lipoprotein particles and serum capacity to stimulate cholesterol efflux induced by different fatty acids. Design: Seventeen women and 24 men followed in the same sequence 4 diets containing 35% of total energy as fat. The saturated fat diet contained 17% palm oil; the monounsaturated fat diet, 20.9% olive oil; the nϪ6 polyunsaturated fat diet, 12.5% sunflower oil; and the nϪ3 polyunsaturated fat diet, sunflower oil supplemented with 4-4.5 g fish oil/d. Each phase lasted 4-5 wk. Results: In both sexes, apolipoprotein (apo) A-I concentrations were significantly lower with unsaturated fat diets than with the saturated fat diet, but concentrations of lipoproteins containing only apo A-I (Lp A-I) were lower only in the men. Concentrations of lipoproteins containing both apo A-I and apo A-II (Lp A-I:A-II) were lower with both polyunsaturated fat diets in the women but significantly higher in the men. Lp E concentrations were significantly higher with the 2 polyunsaturated fat diets. Lp E non-B particle concentrations were not modified in the men but were significantly higher in the women in both polyunsaturated fat phases. Lp C-III concentrations were higher with the saturated fat diet only in the men. The serum samples taken after the nϪ3 polyunsaturated fat phase were the most efficient for extracting cellular cholesterol in both sexes. Conclusions: The monounsaturated and polyunsaturated fat diets were healthier, producing a better lipid profile. The nϪ3 polyunsaturated fat diet increased the capacity of serum to promote the efflux of cholesterol from cells in culture.Am J Clin Nutr 2002;75:484-91. KEY WORDSDiet, fatty acid, lipid, lipoprotein particle, cholesterol efflux, reverse cholesterol transport, HDL, LDL, saturated fat, polyunsaturated fat, monounsaturated fat INTRODUCTIONThe incidence of cardiovascular disease (CVD), the main cause of death and morbidity in developed countries (1), is closely related to diet, mainly to fat composition. The type of fat in the diet can modify the lipid profile, which is directly related to the growth of atheroma plaque (2, 3). In Spain, the mortality rate due to this disease is relatively low compared with that in other developed countries (4,5). This finding could be explained by 2 facts: the Spanish diet is rich in vegetables, fruit, fish, and oils containing monounsaturated fatty acids (MUFAs), a regimen considered favorable for cardiovascular health (6), and Spaniards have elevated plasma concentrations of HDL (7).However, in the dietetic studies performed until now, the results regarding changes in HDL with the administration of monounsaturated fats are controversial (2,8,9). Several epidemiologic studies showed an inverse correlation between serum concentrations of HDL cholesterol and the risk of CVD (10). This favorable role of HDL is mainly due to its participation in metabolic reverse cho...