The antioxidant vitamins C and E

liver F 2α -isoprostanes, markers of in vivolipid peroxidation, were increased in vitamin
C–deficient guinea pigs loaded with iron, but reduced by vitamin C supplementation
(74). In the latter study, hepatic vitamin C levels, in contrast to iron levels, were
inversely associated with hepatic F 2α -isoprostane levels (74). Another recent study
using rats showed an antioxidant effect of vitamin C when given before a paraquat
challenge, but a prooxidant effect when given after the challenge, as determined by
expiratory ethane (75). The prooxidant effect was attributed to the paraquat-mediated
release of metal ions from damaged cells. That study (75), therefore, suggests that vitamin
C may have different effects depending on when it is added to the system under
study, as has been observed previously with copper-dependent lipid peroxidation in
LDL (76,77). Another recent study (78) found that large doses of intravenous ascorbate
increased the levels of loosely bound iron and in vitro oxidation of serum
obtained from iron-loaded guinea pigs, but not control animals (Table 3.2).
Susceptibility of LDL to ex vivo oxidation increased after vitamin C injection in the
control group, but there was no further increase in the iron-loaded group.
Human Supplementation Studies
A study carried out in humans to assess the effects of simultaneous iron and vitamin C
supplementation yielded mixed results with respect to formation of various types of
oxidized DNA bases in leukocytes (Table 3.2). Reanalysis of the data from that study
(79) shows an inverse association between the plasma concentration of vitamin C and
total DNA base damage. In addition, there was a positive correlation between the concentration
of plasma vitamin C and the percentage of transferrin saturation, possibly
due to a vitamin C–dependent increase in iron bioavailability (59), but no correlation
was observed between the percentage of transferrin saturation and total base damage.
These correlations are analogous to those observed in the above study using guinea
pigs and suggest that vitamin C acts as an antioxidant, rather than a prooxidant, in vivo
in the presence of iron.
Decreased levels of serum vitamin C and increased levels of lipid and protein
oxidation products have been detected in hemochromatosis and β-thalassemia
patients (60,61), which was attributed to the iron overload condition. However, these
conclusions are not supported by a study in preterm infants, who often have excess
iron in their plasma (66). In that study, plasma levels of F2α-isoprostanes and protein
carbonyls were not correlated with levels of bleomycin-detectable iron, even in the
presence of high concentrations of vitamin C (Table 3.2). It was found recently (80)
that supplementation of either vitamin C or vitamin C plus iron did not cause a rise in
total oxidative DNA damage measured by gas chromatography-mass spectrometry.
However, a significant decrease was observed in the levels of the purine base oxidation
product, 8-oxoguanine, after ascorbate supplementation. 5-Hydroxymethyl
uracil levels were also decreased by either ascorbate or ascorbate plus iron supplementation,
relative to the presupplemental levels, but not relative to the placebo
group. In addition, levels of 5-hydroxymethyl hydantoin and 5-hydroxy cytosine
increased significantly by ascorbate plus iron supplementation relative to the presup-
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