Effects of linoleate-enriched and oleate-enriched diets in combination with alpha-tocopherol on the susceptibility of LDL and LDL subfractions to oxidative modification in humans.

This report describes the effects of feeding linoleate- or oleate-enriched diets to subjects who were concurrently taking 1200 mg/d of alpha-tocopherol on the susceptibility of low-density lipoprotein (LDL) and buoyant and dense LDL subfractions to oxidation. LDL isolated from subjects who consumed linoleate-enriched diets was more susceptible to copper-mediated oxidation, as measured by formation of conjugated dienes and lipid peroxides and loss of unsaturated fatty acids, compared with LDL isolated from subjects who consumed their usual or oleate-enriched diets. In all subjects, buoyant LDL had a higher content of alpha-tocopherol per particle and a lower 18:2 to 18:1 ratio and was considerably more resistant to oxidation than dense LDL. Although dense LDL from all groups had comparable alpha-tocopherol levels, dense LDL from the linoleate group was most susceptible to oxidation, followed by that from the standard diet, whereas dense LDL isolated from the oleate diet group was most resistant. In summary, high dosages of alpha-tocopherol did not prevent enhanced susceptibility to oxidation of LDL isolated from subjects fed linoleate-enriched diets. Furthermore, dense LDL was more susceptible to oxidation than was buoyant LDL, and this effect was greatly exaggerated in the dense LDL isolated from subjects fed linoleate-enriched diets. Conversely, dense LDL isolated from subjects fed oleate-enriched diets was the most protected. If oxidation of LDL is important in the pathogenesis of atherosclerosis, then these data suggest that in people with increased amounts of small, dense LDL, dietary enrichment in oleic acid may decrease the susceptibility of their LDL to oxidation.

Effects of oleate-rich and linoleate-rich diets on the susceptibility of low density lipoprotein to oxidative modification in mildly hypercholesterolemic subjects.

We report the results of feeding oleate- or linoleate-enriched diets for 8 wk to mildly hypercholesterolemic subjects and the resulting alterations in composition and functional properties of their plasma LDL and HDL. LDL isolated from subjects on oleate-enriched diets was less susceptible to copper-mediated oxidation, as measured by conjugated diene and lipid peroxide formation, and less susceptible to LDL-protein modification, as evidenced by reduced LDL macrophage degradation after copper- or endothelial cell-induced oxidation. For all subjects, the percentage of 18:2 in LDL correlated strongly with the extent of conjugated diene formation (r = 0.89, P < 0.01) and macrophage degradation (r = 0.71, P < 0.01). Oxidation of LDL led to initial rapid depletion of unsaturated fatty acids in phospholipids followed by extensive loss of unsaturated fatty acids in cholesteryl esters and triglycerides. Changes in HDL fatty acid composition also occurred. However, HDL from both dietary groups retained its ability to inhibit oxidative modification of LDL. This study demonstrates that alterations in dietary fatty acid composition can effectively alter the fatty acid distribution of LDL and HDL in hypercholesterolemic subjects and that susceptibility to LDL oxidation is altered by these changes. Substitution of monounsaturated (rather than polyunsaturated) fatty acids for saturated fatty acids in the diet might be preferable for the prevention of atherosclerosis.

Feasibility of using an oleate-rich diet to reduce the susceptibility of low-density lipoprotein to oxidative modification in humans.

Oxidized low-density lipoprotein (LDL) is more atherogenic than native LDL. The initial step in the oxidation is the peroxidation of polyunsaturated fatty acids. Thus, decreasing the concentration of polyunsaturated fatty acids should reduce the susceptibility of LDL to oxidation. Therefore, we tested the possibility that diets enriched in oleate might result in LDL that is less susceptible to oxidative modification. LDL isolated from subjects consuming an oleate-enriched diet, compared with LDL from subjects on a linoleate-enriched diet, contained significantly more oleate (28.7% vs 11.5%) and less linoleate (31.9% vs 50.9%). Generation of conjugated dienes was significantly lower in the LDL from the oleate group. Most important, after incubation with endothelial cells, LDL from the oleate group underwent less degradation by macrophages. These studies demonstrate the feasibility of altering the diet in a way that will not raise LDL cholesterol concentrations and yet will decrease the susceptibility of LDL to oxidative modification.

Assessment of dietary intake of lysine and arginine in patients with herpes simplex.

In this study, dietary intake of the amino acids lysine and arginine did not differ significantly between normal controls and patients with herpes virus. Both groups of subjects consumed significantly more lysine than arginine on a daily basis. Those results are not surprising given the American population's preference for high lysine foods, such as meat and dairy products, as opposed to foods high in arginine, such as legumes, whole grains, and nuts. The mean daily intakes of lysine and arginine for the 16 subjects studied were 8.11 gm +/- 2.28 and 6.32 gm +/- 1.74, respectively. The standard deviations of the mean intakes indicate that there is a large variability in the intake of both amino acids and the ratios of the two amino acids in individual diets. This information is important, considering the conflicting results obtained previously by researchers investigating the efficacy of lysine therapy for herpes infections. The extent of the variability in total amino acid intake or ratio of lysine to arginine in the diet cannot be determined from previous studies. More important, the possible effects of these ranges on the interpretation of study results remain unknown. In order for future studies to accurately determine the effects of supplemental lysine in the treatment of herpes infections, close monitoring of dietary intake is essential.