NO - Besoin d'assistance

Mechanisms and Biomarkers (WG 4) page 53
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had no effect in the study by Abbey et al. (1993). Supplements as low as 100 mg α-tocopheryl
acetate/day were able to increase the resistance of LDL to oxidation when administered
together with 15 g fish oil to 48 postmenopausal women both using and not using hormone-
replacement therapy (Wander et al., 1996).
Few attempts have been done to ascertain the minimum dose of α-tocopherol that would
decrease the susceptibility of LDL to oxidation. Dieber-Rotheneder et al. (1991) were the
first, giving daily dosages of 150, 225, 800, or 1200 IU α-tocopherol for 21 days to 8 subjects
(plus 4 placebo). They found that the oxidation resistance of LDL was higher during vitamin
E supplementation, but they used only 2 subjects in each group and could not undertake
statistical analyses. Jialal et al. (1995) made a dose-response study and evaluated the effect of
the supplementation of healthy volunteers with 60, 200, 400, 800 and 1200 IU/day for 8 wk
on copper-catalysed LDL oxidation, measuring the formation of conjugated dienes and lipid
peroxides by TBARS. All doses resulted in significant increases in plasma and LDL
concentrations of α-tocopherol, however the susceptibility of LDL to oxidation decreased
only at doses > 400 IU/day. Princen et al. (1995) evaluated the effect of 25, 50, 100, 200, 400
and 800 IU/day α-tocopherol acetate in 20 healthy volunteers during six 2-week periods, and
found that the resistance of LDL to oxidation was elevated dose-dependently (+28% after the
last period) and differed significantly from the baseline resistance time even after ingestion of
only 25 IU/day. However the progression of lipid peroxidation in LDL was reduced only after
intake of 400 or 800 IU/day. The authors suggested that only at high dosages α-tocopherol
becomes incorporated into the interior of the LDL particle in sufficiently amounts to retard
the autocatalytic chain reaction of the propagation phase.
In many of the papers reported, a correlation was found between oxidative resistance and
LDL-α-tocopherol concentration, however the correlation becomes weaker in
unsupplemented subjects (Frei and Gaziano, 1993; Dieber-Rotheneder, 1991).
From these data it seems that the interest in the role of α-tocopherol in protecting LDL from
oxidation is well documented. However, the examination of all data reported in literature, and
in particular of data regarding the profile of lipid hydroperoxide (LOOH) accumulation in
LDL oxidation, reveals that α-tocopherol can also be prooxidative. For example, it has been
shown that supplementation of LDL with α-tocopherol increases the initial rate of lipid
peroxidation; the rate of lipid peroxidation is higher in the presence of α-tocopherol than
immediately after its depletion; the maximal rate of lipid peroxidation in the presence of the
vitamin is independent from the rate of initiation of lipid peroxidation (Bowry and Stocker,