Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:190-198
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© 1995 American Heart Association, Inc.
Articles |
The Effect of 
-Tocopherol Supplementation on LDL Oxidation
A Dose-Response Study
From the Center for Human Nutrition (I.J., C.J.F.), Laboratory of Molecular Pathology (I.J.), and the General Clinical Research Center (B.A.H.), Departments of Internal Medicine (I.J.) and Pathology (I.J.), University of Texas Southwestern Medical Center, Dallas.
Abstract Because much data have accrued to support the
concept that oxidatively modified LDL (Ox-LDL) can promote
atherogenesis, the role of antioxidants in decreasing LDL oxidation has
assumed great importance. High-dose 
-tocopherol
supplementation in humans decreases the susceptibility of LDL to
oxidation. Hence, the aim of the present study was to ascertain the
minimum dose of -tocopherol that would decrease the susceptibility
of LDL to oxidation. The effect of -tocopherol in doses of 60, 200,
400, 800, and 1200 IU/d on copper-catalyzed LDL oxidation was tested in
a randomized placebo-controlled study over 8 weeks. There were eight
subjects in each group. Oxidation of LDL was monitored by measuring the
formation of conjugated dienes and lipid peroxides by the
thiobarbituric acid–reacting substances (TBARS) assay over an 8-hour
time course at baseline and after 8 weeks of supplementation. Neither
placebo nor any of the doses of -tocopherol resulted in any side
effects or exerted an adverse effect on the plasma lipoprotein profile.
However, there was a dose-dependent increase in plasma and
lipid-standardized -tocopherol levels with increasing doses of
-tocopherol supplementation. LDL -tocopherol appeared to follow a
similar trend. When the time-course curves of LDL oxidation and the
kinetics of LDL oxidation were examined, there was no significant
effect at 8 weeks compared with baseline in the groups that received
placebo or -tocopherol 60 or 200 IU/d. However, in the groups that
received at least 400 IU/d -tocopherol, there was a
decreased susceptibility of LDL to oxidation, as shown by the mean
levels in the time-course curves, prolongation in the lag phase, and a
decrease in the oxidation rate. Furthermore, both plasma and LDL
-tocopherol correlated significantly with the lag phase of
oxidation and inversely with the oxidation rate. The results of the
present study show that the minimum dose of -tocopherol needed
to significantly decrease the susceptibility of LDL to oxidation is 400
IU/d.
Key Words: lipid peroxidation • -tocopherol • LDL oxidation • atherosclerosis • antioxidants
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