© 1997 American Heart Association, Inc.
Articles |
Dose-Response Comparison of RRR-
-Tocopherol and All-Racemic -Tocopherol on LDL Oxidation
From the Center for Human Nutrition (C.J.F., I.J.) and Departments of Internal Medicine (B.A-H., I.J.) and Pathology (S.D., I.J.), University of Texas Southwestern Medical Center, Dallas, Tex.
Correspondence to I. Jialal, MD, PhD, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75235-9072. E-mail jialal.i{at}pathology.swmed.edu
Abstract Much data have accrued in support of the concept
that oxidation of LDL is a key early step in atherogenesis. The most
consistent data with respect to micronutrient antioxidants and
atherosclerosis appear to relate to
-tocopherol (AT), the predominant lipid-soluble
antioxidant in LDL. There are scant data on the direct comparison of
RRR-AT and all-racemic (rac)-AT on LDL
oxidizability. Hence, the aim of the present study was to examine
the relative effects of RRR-AT and all-rac-AT on
plasma antioxidant levels and LDL oxidation in healthy persons in a
dose-response study. The effect of RRR-AT and
all-rac-AT at doses of 100, 200, 400, and 800 IU/d on plasma
and LDL AT levels and LDL oxidation was tested in a randomized,
placebo-controlled study of 79 healthy subjects. Copper-catalyzed
oxidation of LDL was monitored by measuring the formation of conjugated
dienes and lipid peroxides over an 8-hour time course at baseline and
again after 8 weeks. Plasma AT, lipid-standardized AT, and LDL AT
levels rose in a dose-dependent fashion in both the RRR-AT
and all-rac-AT groups compared with baseline. There were no
significant differences in plasma, lipid-standardized, and LDL AT
levels between RRR-AT and all-rac-AT
supplementation at any dose comparison. The lag phases of oxidation
were significantly prolonged with doses 
400 IU/d of RRR-AT
and all-rac-AT, as measured by conjugated-dienes assay and
at 400 IU/d of RRR-AT and 800 IU/d of both forms of AT by
lipid peroxide assay. Again, there were no significant differences in
the lag phase of oxidation at each dose for RRR-AT when
compared with all-rac-AT. Also, there were no significant
differences in LDL oxidation after in vitro enrichment of LDL with
RRR-AT and all-rac-AT. Thus, supplementation with
either RRR-AT or all-rac-AT resulted in similar
increases in plasma and LDL AT levels at equivalent IU doses, and the
degree of protection against copper-catalyzed LDL oxidation was only
evident at doses 400 IU/d for both forms.
Key Words: RRR--tocopherol • all-racemic -tocopherol • LDL oxidation • -tocopherol
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