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Mechanisms and Biomarkers (WG 4) page 21
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cell-mediated LDL oxidation (Frei, 1999). Work done by Frei et al. clearly demonstrated that
plasma antioxidants (mainly vitamin C) are able to protect LDL oxidation induced by many
different oxidising conditions and that vitamin C is also able to protect isolated LDL particles
against metal ion-dependent and -independent oxidative modification. These in vitro studies
agreed well with epidemiological studies showing a negative correlation between the presence
of antioxidants in the plasma and the incidence of coronary heart diseases (Gey et al., 1993);
other data from ongoing studies suggest that protective effect of vitamin E could be effective
only in users of supplements. Data on EURAMIC study (Kardinaal et al., 1993) however,
showed that low adipose tissue ß-carotene concentrations were associated with significantly
increased risk of myocardial infarction. Interestingly, in that study myocardial infarction was
mainly confined to smokers and similar data were also obtained on the protective effect of ßcarotene
in health professional studies and showing 22 % reduction of coronary risk in the
individuals from the top fifth of ß-carotene intake. Concerning the low incidence of
cardiovascular disease in individuals consuming the « Mediterranean diet » antioxidants,
polyphenolic substances but also mono unsaturated fatty acids may contribute to protective
effects. Concerning flavonoids, a recent paper reviewed the data obtained on flavonoids from
different foods on coronary heart disease (Lairon and Amiot, 1999). Based on
epidemiological studies on protective effect of red wine and tea consumption, many
intervention studies were designed to confirm the effect of flavonoids on cardiovascular risk
in humans. Altogether, some of these studies on tea and onion or parsley failed to show any
protective effect, whereas others using red grape juice, red wine and beer effectively showed
LDL protection against oxidation, tendency to increase HDL cholesterol, rise of plasma
antioxidant capacity and plasma vitamin E levels. The authors proposed that such a
discrepancy may result from factors such as the initial physiological state on the volunteers,
the composition and the amount of foodstuffs ingested during supplementation period or the
duration of the experimental period. Other factors are the lack of knowledge on the
bioavailability and metabolism of flavonoids contained in the foods tested.
Ageing
As mentioned above, oxidised by-products are always found in the circulation and thus non
specific oxidative damage may be at the origin of ageing processes as stated by Harman
(1956) some 40 years ago. Whether oxidative stress is a marker or causal agent in ageing is a
question recently addressed by Fukagawa (1999) and the following will be based mainly on
what he developed in that review. Undoubtedly physiological functions decline inevitably
with age, these adverse changes finally leading to death. Ageing is also associated with