Circulation, Vol 88, 2780-2786, Copyright © 1993 by American Heart Association
I Jialal and SM Grundy
BACKGROUND. Data continue to accumulate supporting a proatherogenic role
for oxidized low-density lipoprotein (Ox-LDL). Antioxidant micronutrients
such as ascorbate, alpha-tocopherol, and beta carotene, levels of which can
be favorably manipulated by dietary measures without side effects, could be
a safe approach in inhibiting LDL oxidation. In fact, in vitro studies have
shown that all three antioxidants can inhibit LDL oxidation. The present
study was undertaken to ascertain both the safety and antioxidant effect of
combined supplementation with alpha-tocopherol, ascorbate, and beta
carotene on LDL oxidation. METHODS AND RESULTS. The effect of combined
supplementation with alpha-tocopherol (800 IU/d) plus ascorbate (1.0 g/d)
and beta carotene (30 mg/d) on copper-catalyzed LDL oxidation was tested in
a randomized, placebo-controlled study in two groups of 12 male subjects
over a 3-month period. Blood samples for the lipoprotein profile,
antioxidant levels, and LDL isolation were obtained at baseline and at 3
months. Neither placebo nor combined antioxidant therapy resulted in any
side effects or exerted an adverse effect on the plasma lipoprotein
profile. Compared with placebo, combined antioxidant therapy resulted in a
significant increase in plasma ascorbate and lipid standardized
alpha-tocopherol and beta carotene levels (2.6-, 4.1-, and 16.3-fold,
respectively). At baseline, there were no significant differences in the
time course curves and kinetics of LDL oxidation as evidenced by the
thiobarbituric acid reacting substances (TBARS) assay and the formation of
conjugated dienes. However, at 3 months, combined supplementation resulted
in a twofold prolongation of the lag phase and a 40% decrease in the
oxidation rate. The combined antioxidant group was also compared with a
group that received 800 IU of alpha-tocopherol only. Although the combined
antioxidant group had significantly higher ascorbate and beta carotene
levels than the group supplemented with alpha-tocopherol alone, there were
no significant differences between the two groups with respect to LDL
oxidation kinetics. CONCLUSIONS. Combined supplementation with ascorbate,
beta carotene, and alpha-tocopherol is not superior to high- dose
alpha-tocopherol alone in inhibiting LDL oxidation. Hence, alpha-
tocopherol therapy should be favored in future coronary prevention trials
involving antioxidants.
ARTICLES
Effect of combined supplementation with alpha-tocopherol, ascorbate, and beta carotene on low-density lipoprotein oxidation
Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas 75235-9052.
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