Comparison of an oleic acid enriched-diet vs NCEP-I diet on LDL susceptibility to oxidative modi®cations P Castro 1 , J Lo Âpez Miranda 1 , P Go Âmez 1 , DM Escalante 1 , F Lo Âpez Segura 1 , A Martõ Ân 2 , F Fuentes 1 , A Â Blanco 1 , JM Ordova Âs 2 and FP Jime Ânez 1 * 1 Lipids Research Unit, Hospital University Reina So®a, Medical School, University of Co Ârdoba, Spain; and 2 The Lipid Metabolism Laboratory, USDA, Human Nutrition Research Center on Aging at Tufts University, Boston, USA Objective: The objective of this trial was to compare the effect on the susceptibility of plasma Low Density Lipoprotein (LDL) to oxidative modi®cations of consumption of two oleic rich diets, prepared with two different plant oils, virgin olive oil (OL) 1 and re®ned high monounsaturated fatty acids (MUFA sun¯ower oil (SU)), with the susceptibility of plasma LDL to oxidation after an National Cholesterol Education Program step 1 (NCEP-I) phase diet. Design: A randomized crossover design. Subjects and interventions: Twenty-two healthy normolipidemic young males consumed an NCEP-I diet for a 4-week period. Subjects were then assigned to two diets each of 4-weeks duration. Group one was placed on an olive oil enriched diet (40% fat, 22% MUFA) followed by a 4-week period of a MUFA diet enriched in sun¯ower oil (40% fat, 22% MUFA). In group two, the order of the diets was reversed. Results: Both MUFA diets induced a decrease in saturated (14 : 0, 16 : 0, and 18 : 0) and an increase in monounsaturated and polyunsaturated n-6 (18 : 2, 20 : 3, and 20 : 5) plasma LDL-phospholipid fatty acids, compared to the NCEP-I diet (P < 0.01). No signi®cant differences in lag times were observed between the olive oil and the NCEP-I diet periods. However there was a greater inhibition time (P < 0.001) when subjects consumed the MUFA rich sun¯ower oil diet compared to the NCEP-I diet. These differences were probably related to the relative enrichment of plasma LDL particles in a-tocopherol due to the high vitamin E content of the MUFA-rich sun¯ower oil. Indeed, the a-tocopherol content was positively correlated with lag time (r  0.338; P < 0.008). Conclusion: Our ®ndings suggest that changes in plasma LDL a-tocopherol content with practical solid-food diets can decrease its susceptibility to oxidation. Sponsorship: This work has been supported by grants from the Investigaciones de la Seguridad Social (FIS 92=0182, to Francisco Pe Ârez Jime Ânez); and from Koype Co, Andu Âjar, Jae Ân, Spain. Descriptors: oxidized low density lipoproteins; a-tocopherol; phospholipid; monounsaturated fatty acids; low fat diets; fatty acids European Journal of Clinical Nutrition (2000) 54, 61±67 Introduction Coronary heart disease (CHD) due to atherosclerosis remains the most prevalent cause of death and disability in Europe and North America. The dramatic geographic differences in the incidence of this disease and the marked shifts in CHD rates observed in migrant populations emphasize the importance of environmental factors in the development of CHD. Growing evidence suggests that oxidative modi®cation of plasma low density lipoproteins (LDL) enhances their atherogenic properties (Berliner & Heinecke, 1996; Grundy 1995; Jialal & Devaraj 1996a, Luck & Fruchart, 1991; Penn & Chisolm, 1994; Rosenfeld, 1991; Steinberg et al, 1989; Williams & Tabas, 1995). Oxidized LDL could promote atherosclerosis in several ways: by its cytotoxicity (Hughes et al, 1994; Thorne et al, 1996), its chemotactic effect on monocytes (Cushing et al, 1990), its inhibitory effect on macrophage motility, its effects on the vascular tone (Chin et al, 1992); Liao et al, 1995), its thrombogenic effects (Drake et al, 1991; Latron et al, 1991) and its uptake by the macrophage scavenger receptor mechanism, the later lead- ing to stimulation of cholesterol esteri®cation and foam cell formation (Maor et al, 1995). Furthermore, several lines of evidence support the in vivo existence of oxidized LDL (Bui et al, 1996; Hammer et al, 1995, Itabe et al, 1994; Yla È-Herttuala et al, 1994). The ®rst target of peroxidation are the polyunsaturated fatty acids within the LDL (Esterbauer et al, 1987). This process is inhibited by chain-breaking antioxidants such as vitamin E commonly present within plasma LDL particles (Bays & Dujovne, 1993). Hence lowering the content of antioxidant and=or increasing the amount of polyunsatu- rated fatty acids in plasma LDL should render these lipoproteins more prone to oxidative modi®cations (Este- bauer et al, 1987; Jialal & Devaraj, 1996b). Studies in *Correspondence: Francisco Pe Ârez Jime Ânez. Departamento de Medicina, Avda, Mene Ândez Pidal s=n, Facultad de Medicina, 14004, Co Ârdoba, Spain. Guarantor: FP Jime Ânez Contributors: P Go Âmez and MD Escalante, in vitro experiments of oxidation of LDL. A Martin and F Lo Âpez Segura the determination of a- tocoferol. J Lo Âpez Miranda, selection of the populations, the control of the adherence of the diets and different biochemical determinations. A Blanco and F Fuentes the determinations of fatty acid composition and the control of the adherence of the diets. JM Ordovas provided advice during all the stages of the work and participated actively in data analysis and manuscript preparation. F Perez-Jimenez is the group leader and contributed to the experimental design and data analysis. P Castro contributed to the experimental design, the control of adherence of the diets, data analysis and prearation of the manuscript. Received 18 March 1998; revised 18 March 1999; accepted 30 March 1999 European Journal of Clinical Nutrition (2000) 54, 61±67 ß 2000 Macmillan Publishers Ltd. All rights reserved 0954±3007/00 $15.00 www.nature.com/ejcn