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the Division of Endocrinology and Metabolism, Department of Medicine, University of CaliforniaSan Diego, La Jolla, Calif.
Correspondence to Peter Reaven, Department of Medicine, 0682, University of CaliforniaSan Diego, 9500 Gilman Dr, La Jolla, CA 92093-0682.
Previous studies have demonstrated that compared with more buoyant LDL, dense LDL (D-LDL) is more susceptible to oxidation and less readily protected from oxidation by antioxidant enrichment. However, diets enriched in monounsaturated fatty acids (MUFAs) appear particularly effective in protecting D-LDL from oxidation. We therefore evaluated in 12 noninsulin-dependent diabetes mellitus subjects the effects of supplementation with
-tocopherol (1600 IU/d) and probucol (1 g/d) alone and in combination with an MUFA-enriched diet on LDL and LDL subfraction susceptibility to oxidation and monocyte release of superoxide anion. Subjects received either
-tocopherol or probucol for 4 months, and during the fourth month both groups also received an MUFA-enriched diet.
-Tocopherol levels were significantly increased in LDL and LDL subfractions (P<.05) after 3 months of supplementation. MUFA-enriched diets led to further increases in
-tocopherol in LDL fractions in the
-tocopherol group as well as in those receiving probucol. In the
-tocopherolsupplemented group, lag times were increased significantly (1.6- to 2.0-fold) for all LDL fractions, although the absolute increase was least for D-LDL. Although probucol supplementation increased lag times of LDL and LDL subfractions three- to fourfold, D-LDL was still more readily oxidized. In both the
-tocopherol and probucol-supplemented groups the benefit of adding MUFA-enriched diets was greatest for D-LDL, with further increases in lag time of 26% and 18%, respectively. Neither antioxidant supplementation nor the addition of an MUFA-enriched diet reduced unstimulated or phorbol esterstimulated monocyte superoxide anion production. These data demonstrate the markedly different effects that antioxidants and diet may have on different LDL subfractions, which may be particularly important in individuals with noninsulin-dependent diabetes mellitus, who frequently have increased amounts of D-LDL.
Key Words: lipid peroxidation monocyte dense LDL probucol monounsaturated fatty acids
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