REVIEWCan oxidative damage be treated nutritionally?
Introduction
The last 50 years have been characterised by the understanding of the impact of nutrition and dietary patterns on health.1 Oxidation of lipids, nucleic acids or proteins has been suggested to be involved in the aetiology of several chronic diseases including cancer, cardiovascular disease, cataract, age-related macular degeneration and aging in general. The “free radical theory of aging” proposed in 1957 by Harman2 has fostered a important body of research investigating the potential role of antioxidant nutrients in therapeutic or preventive strategies.3 In the critically ill patients, free radical-mediated damage has also generated a large body of research, and various antioxidant strategies have been proposed.
Until very recently, the only mean of prolonging life span in laboratory animals was to restrict their calorie intake. A trial published in 2004 using nutritional antioxidants challenges this evidence: the life span of mice-fed diets enriched with a metabolite of curcuma vs. standard diets was prolonged 11.7% (84 days) by the supplementation: similarly in another series of mice-fed standard diets, the addition of green tea extracts to drinking water resulted in a 6.4% (52 days) prolongation of life span.4 Both antioxidant agents are know for their atherosclerosis preventing properties, pathology which is irrelevant in wild-type rodents, but is a killer in humans: supplementation with these agents can therefore be expected to be even more effective in humans. Beyond these specific results, these animal data demonstrate that AOX intervention strategies have a significant impact on a series of biological variables and on survival—is this form of supplementation to be considered as prevention or as a therapy?
Individuals in the Mediterranean area have been shown to present with a lower risk of several important chronic diseases, including coronary heart disease and a number of types of cancer associated with nutritional traditions, such as breast, colon, and prostate cancer. The use of large amounts of vegetables and fruits in general and cooked tomatoes, together with olive oil, appears to account for this lower risk.5 Among the nutrients that have “disease preventive” properties, vitamins and trace elements have been shown to be the most active components. Beyond micronutrients, other nutrients such glutamine may also be considered as antioxidant especially in selected critically ill patients. Overall many substances can be considered antioxidant, including some drugs, but are beyond the scope of the present review which will concentrate on vitamins and trace elements, and consider their potential “therapeutic” value in treating oxidative damage.
Section snippets
Free radicals, inflammatory response and oxidative stress
Free radicals and their deleterious effects have been extensively reviewed.6, 7, 8 Briefly, free radicals are atoms or molecules containing one or more unpaired electrons: they are unstable and strive to restore parity. The oxygen-centred radicals which are produced under normal aerobic metabolism, are also called reactive oxygen species (ROS); they are mainly produced by leukocytes and by the respiratory mitochondrial chain; they are essential for cell signalling, and for bacterial defence.
Antioxidants
Antioxidants (AOX) are substances, which inhibit or delay oxidation of a substrate while present in minute amounts.17 Endogenous AOX defences are both non-enzymatic (e.g. uric acid, glutathione, bilirubin, thiols, albumin, and nutritional factors, including vitamins and phenols) and enzymatic (e.g. the superoxide dismutases, the glutathione peroxidases=GSHPx, and catalase). In the normal subject the endogenous antioxidant defences balance the ROS production, but for the above-mentioned 1% daily
Status of the general population
An important part of the population is exposed to the risk of trace element and vitamin deficiency for multiple reasons including the changes in eating habits in Western countries, but also the lower food concentration of micronutrients caused by intensive agricultural techniques, compared to standards determined in the 1950s. Children, young women and elderly aged 65 years and up are most exposed.25 Indeed, more than 10 years ago, a French study showed of large-scale deficit in micronutrients
Intervention trials
Efforts to fight nutrient deficiencies have centred on supplemental nutrient administration and on addition of selected nutrients to the food chain in the form of food fortification.1 Supplementation and fortification has been proposed in healthy individuals, with the aim of reducing their risk of future diseases such as cardiovascular diseases, diabetes, and cancer. Nevertheless, with our increasing understanding of the genetic heterogeneity of human nutrient requirements, it is likely that
Discussion and conclusion
For all the above-mentioned reasons my answer to the question « can oxidative damage be treated nutritionally? » is yes. If one considers the cellular mechanisms, current knowledge clearly supports the role of AOX nutrients in the intracellular prevention AOX-related damage and of proximity damage propagation. AOX also appear to have defined pathology targets: some examples of AOX modulable conditions are ischemia-reperfusion, burns, renal failure, age-related ocular diseases, and some cancers.
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