The effect of quality and amount of dietary fat on the susceptibility of low density lipoprotein to oxidation in subjects with impaired glucose tolerance US Schwab 1,2 , ES Sarkkinen 1 , AH Lichtenstein 2 , Z Li 2 , JM Ordovas 2 , EJ Schaefer 2 and MIJ Uusitupa 1 1 Department of Clinical Nutrition, University of Kuopio, PO Box 1627, 70211 Kuopio, Finland; and 2 Lipid Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, USA Objectives: We examined the effects of a high fat diet rich in monounsaturated fat (MUFA-diet) and a moderate fat diet rich in polyunsaturated fat (PUFA-diet) on the susceptibility of LDL to oxidation. Subjects: 29 subjects with impaired glucose tolerance. Methods: After consuming a run-in diet [37% of energy (E%) fat, 18 E% saturated fat] for three weeks, subjects were randomly assigned either to a MUFA-diet (40 E% fat, 19 E% monounsaturated fatty acids) or a PUFA-diet (34 E% fat, 10 E% polyunsaturated fat) for eight weeks. The susceptibility of LDL to oxidation was measured by challenging LDL with hemin and H 2 O 2 and measuring the time for the reaction to reach maximum velocity. Results are expressed as lag time to oxidation in minutes. Results: In the PUFA-diet group (n  15) lag time tended to decrease during the experimental diet (97  28 vs 90  25 min, mean  s.d., P  0.073), whereas in the MUFA-diet group (n  14) there was no significant change (lag time 96  24 vs 100  16 min, P  0.408). The mean change in lag time was 77  14 min (77.2%) in the PUFA-diet group and  4  16 min (  4.0%) in the MUFA-diet group (P  0.029, PUFA-diet group vs MUFA- diet group). The a-tocopherol concentration in LDL increased significantly (P < 0.01) in both diet groups relative to the run-in diet period, but LDL particle score did not change in either of the diet groups during the dietary intervention. Conclusions: In subjects with impaired glucose tolerance a PUFA-rich diet with a moderate amount of fat tended to increase the susceptibility of LDL to oxidation as compared to a higher fat diet rich in MUFA. Furthermore, the negative mean change in lag time to oxidation found in the PUFA-diet group differed significantly from the slightly positive mean change found in the MUFA-diet group. Sponsorship: Supported by the Foundation for Nutrition Research, Helsinki, Finland; the Council for Health Sciences, Academy of Finland, and the Ministry of Education, Finland, and the Van den Bergh Foods and Valio Ltd, Finland, for supplying the fat products for the study Descriptors: diet; impaired glucose tolerance; LDL; oxidation; saturated fat; monounsaturated fat; polyun- saturated fat; cholesterol Introduction Low density lipoprotein (LDL) is considered to be an atherogenic particle and oxidative modification seems to further increase the atherogenicity of this particle (Ester- bauer et al, 1990; Steinberg et al, 1989). There is strong evidence that oxidative modification of LDL occurs in vivo (Palinski et al, 1989; Yla¨-Herttuala et al, 1989). Oxidized LDL is not recognized by LDL receptors, but it is taken up by scavenger receptors on macrophages (Parthasarathy, 1987; Rohrer et al, 1990; Sparrow et al, 1989). This leads to foam cell formation due to the inability of intracellular cholesterol to downregulate the activity of the scavenger receptors (Brown & Goldstein, 1983; Stein- berg et al, 1989). In addition, oxidized LDL has been shown to be cytotoxic, chemotactic for monocytes, and alters vascular tone and gene expression in arterial wall cells (Cathcart et al, 1989; Cushing et al, 1990; Liao et al, 1991; Quinn et al, 1987). Factors that have been demonstrated to affect the sus- ceptibility of LDL to oxidation include the fatty acid composition and antioxidant content of the particle, particle size and the degree of glycosylation of the particle. LDL particles seem to be more susceptible to oxidation after consumption of a polyunsaturated fat enriched diet than after consumption of a monounsaturated fat enriched diet both in normocholesterolemic and hypercholesterolemic subjects (Abbey et al, 1993; Berry et al, 1991; Bonanome et al, 1992; Reaven et al, 1991, 1993, 1994). Furthermore, small dense particles have been found to be more suscep- tible to oxidation than large buoyant particles (Reaven et al, 1994; DeGraaf et al, 1991; Tribble et al, 1992; Chait et al, 1993; Dejager et al, 1993). Increasing the a-tocopherol content of LDL via supplementation has been reported to decrease the susceptibility of LDL to oxidation (Esterbauer et al, 1991; Reaven & Witztum, 1993; Jialal & Grundy, 1992; Jialal et al, 1995; Princen et al, 1995). However, variations due to naturally occurring a-tocopherol in the diet has not (Babiy et al, 1990; Esterbauer et al, 1991; Esterbauer et al, 1992; Jessup et al, 1990). Glycosylation of LDL has been shown to increase the susceptibility of this particle to oxidation. This has been considered as one possible mechanism for the increased incidence of athero- sclerosis in diabetic patients (Bowie et al, 1993; Campbell et al, 1994; Kawamura et al, 1994; Kimura et al, 1995; Sobenin et al, 1993), especially those patients that are not Correspondence: Dr US Schwab. Received 7 October 1997; revised 4 March 1998; accepted 12 March 1998 European Journal of Clinical Nutrition (1998) 52, 452– 458 ß 1998 Stockton Press. All rights reserved 0954–3007/98 $12.00 http://www.stockton-press.co.uk/ejcn