Effects of Vitamin E on Susceptibility of Low-Density Lipoprotein and Low-Density Lipoprotein Subfractions to Oxidation and on Protein Glycation in NIDDM

Peter D Reaven; David A Herold; Joellen Barnett; Steve Edelman

doi:10.2337/diacare.18.6.807

Original Articles

Effects of Vitamin E on Susceptibility of Low-Density Lipoprotein and Low-Density Lipoprotein Subfractions to Oxidation and on Protein Glycation in NIDDM

Peter D Reaven, MD,
David A Herold, MD,
Joellen Barnett, MS and
Steve Edelman, MD

Division of Endocrinology and Metabolism, Department of Medicine University of California San Diego, La Jolla, California
Division of Pathology, Department of Medicine, University of California San Diego, La Jolla, California

Address correspondence and reprint requests to Peter Reaven, MD, Department of Medicine 0682, University of California, San Diego, 9500 Gilman Dr., BSB 1080, La Jolla, CA 92093-0682.

Diabetes Care 1995 Jun; 18(6): 807-816. https://doi.org/10.2337/diacare.18.6.807

Abstract

OBJECTIVE To evaluate the effect of vitamin E supplementation on the susceptibility of low-density lipoprotein (LDL) and LDL subfractions to oxidation and on protein glycation in non-insulin-dependent diabetes mellitus (NIDDM).

RESEARCH DESIGN AND METHODS Twenty-one men with NIDDM (HbA_1c = 6-10%), ages 50–70, were randomly assigned to either 1,600 IU/day of vitamin E or placebo for 10 weeks after a 4-week placebo period. LDL and LDL subfractions were isolated after 4 weeks of placebo and after 6 and 10 weeks of therapy. Susceptibility of LDL to copper-mediated oxidation was measured by conjugated diene formation (lag time) and formation of thiobarbituric acid-reactive substances (TBARS). Fasting serum glucose, mean weekly blood glucose, HbA_1c, and glycated plasma protein concentrations were also determined at these time points.

RESULTS Vitamin E content in plasma and LDL increased 4.0- and 3.7-fold, respectively, in the vitamin E-treated group. Vitamin E decreased the susceptibility of LDL to oxidation in comparison with placebo (lag time, 243 ± 46 vs. 151 ± 22 min, P < 0.01; 3 h TBARS, 24 ± 12 vs. 66 ± 18 nmol malondialdehyde/mg LDL, P < 0.05). Vitamin E content also increased significantly in both buoyant and dense LDL subfractions, and their oxidation was dramatically reduced. The lag time of LDL oxidation correlated well with the content of vitamin E in both LDL and its subfractions (r = 0.69–0.92). Glycemic indexes did not change significantly in either group during the study. Protein glycation, including glycated hemoglobin, glycated albumin, glycated total plasma proteins, and glycated LDL were unchanged in the vitamin E group.

CONCLUSIONS Supplementation of vitamin E in NIDDM leads to enrichment of LDL and LDL subfractions and reduced susceptibility to oxidation. Despite a greater percentage increase in vitamin E content in small dense LDL, it remained substantially more susceptible to oxidation than was buoyant LDL. This suggests that dense, LDL may gain less protection against oxidation from antioxidant supplementation than does larger, more buoyant LDL. In contrast to previous reports, vitamin E supplementation did not reduce glycation of intracellular or plasma proteins.