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Mechanisms and Biomarkers (WG 4) page 63
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Conclusion
Cumulative evidence from this review appears to support the requirement for a balanced
supply of dietary-derived antioxidant and protective molecules. The natural stoichiometry of
these components in tomatoes and other plant foods, allows an orderly detoxication and
removal of deleterious products from the body without the build up of potentially toxic
intermediates. Studies with megadoses of purified/synthetic antioxidants have not revealed
the ‘magic bullet’ and serve to reinforce the argument for dietary modulation.
Overall Recommendations
Since the inception of this Network in 1997 there have been major changes in the perception
of how we should investigate the role of phytochemicals with putative antioxidant properties
in healthy diets. Salutory lessons have been learnt from major intervention studies and
emphasis has moved from the study of high doses of purified compounds, to the more
physiologically relevant investigation of delivery of these compounds as crucial components
in the food matrix.
The function of WG4 has been to research the notion that oxidative stress is involved in many
diseases and may result in tissue injury, and that dietary modification may ameliorate these
conditions.
A study of the chemical properties of biological oxidants and their respective antioxidants
leads us to predict the mechanisms by which they will interact in biological systems. Despite
the innate complexities of even the most simple cellular systems, studies with animal models
and cell culture systems have largely supported the basic mechanistic proposals for the mode
of action of RS and free radicals in oxidative stress, and the protection conferred against this
damage by exogenous and endogenous antioxidant systems. What has been less successful
was the extrapolation of animal and cell culture data to design large scale human intervention
studies such as the ATBC and CARET trials.
False inferences have been made based on major components in certain complex diets,
leading to simplistic designs for the intervention trials. More recent mechanistic studies have
revealed beneficial synergistic relationships which will have important bearing on the design
of future intervention trials.
The overall message from this Network is to support the need for additional research on
dietary intervention using whole foods to better define what is a basic healthy diet, and to