Rise and Falls of Dietary Antioxidants for Oxidative Stress Prevention: Magic Bullets
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RISE AND FALLS OF DIETARY ANTIOXIDANTS FOR OXIDATIVE STRESS PREVENTION: MAGIC BULLETS, FASLE MITH OR SCARCE KNOWLEDGE?
Serafini M Antioxidant Research Laboratory at the Unit of Human Nutrition, National Institute for Food and Nutrition Research, Rome, Italy
Oxidative stress can be defined as the imbalance between Free Radical Species (FRS) production and antioxidant defense inside human organism. A non physiological FRS production originates either by exogenous agents, such as pollution and cigarette smoking, or by endogenous sources, such as inflammation and the respiratory burst [1]. Clinical, genetic and epidemiological studies have shown that oxidative stress is a risk factor playing a significant pathogenetic role for cardiovascular diseases [2,3], cancer [4,5], diabetes [6], neuro-degenerative diseases [7], as well as chronic inflammatory diseases [8]. Human body has developed a sophisticated and co-operative array of antioxidant defenses to protect cellular district from the widely damaging FRS. Despite the high grade of complexity and efficiency of endogenous antioxidant defenses, the mechanism is not infallible and it is well agreed among experts that there is a need to optimize the redox defenses with dietary antioxidant molecules [9]. Several studies indicate that diets rich in plant foods might reduce oxidative stress- related disease development. The hypothesis that dietary consumption of antioxidant-rich foods may lower the risk of degenerative diseases has been supported by biochemical and epidemiological findings [10-14]. However, contrasting results from clinical trials have raised strong concerns about the importance of antioxidants on human health. A vulnerable point of the research on antioxidants is the lack of information on the effect of the whole array of dietary antioxidants in disease prevention, as so far mainly single galenic molecules have been investigated. Antioxidant molecules do not act in isolation and synergistic interactions, in part involving antioxidant regeneration, need to be taken into account in order to properly assess antioxidant status in vivo. Total Antioxidant Capacity (TAC), defined as the moles of oxidants neutralized by one litre of plasma [15], represents a biomarker measuring the antioxidant potential, including redox synergistic interactions, of body fluids, single compounds and food extracts [15]. Due to the fact that TAC does not take into account antioxidant protection afforded by endogenous redox enzymes, in this work we replaced the term Total with Non Enzymatic, Antioxidant Capacity (NEAC), better describing the dietary and endogenous battery of antioxidant molecules. Despite many food items rich in antioxidants such as chocolate, wine, olive oils, fruit and vegetables have been accredited of an antioxidant action in vivo, the extent to which plant foods are able to tune oxidative stress in human is unclear and it represents a fundamental matter of debate. Dietary intervention studies have shown that consumption of plant foods is able to modulate plasma NEAC in human subjects [15]. However, mainly due to the wide number of phytochemicals potentially involved, the identification of the exogenous molecules able to tuning antioxidant defences is far to be obtained. In recent years, epidemiological and experimental evidence has mounted on previously unrecognized properties of a large group of phytochemicals, such as PolyPhenols (PP) [16-18]. PP are non-nutrient compounds widely present in the vegetable kingdom, endowed with different chemical structures and bioactivity [19]. Extensive studies have provided a wealth of information on the different modality of action of these molecules, including antimicrobial, antiviral and anti-inflammatory activities, regulation of detoxification enzymes, stimulation of immune function, inhibition of platelet aggregation, modulation of hormone and cholesterol metabolism [20]. PP are able to scavenge oxygen and nitrogen derived free radicals [21], modulating antioxidant enzymes and cellular redox transcription factors such as Nuclear Factor kB (NFkB) [22]. However, evidences of an antioxidant in vivo action of these molecules are contrasting and a lack of correlation between changes of plasma endogenous antioxidant defenses and circulating levels of dietary PP has been reported [23-25]. Indeed, the low degree of absorption, the extensive metabolism within the body and a clear discrepancy between PP concentration in body fluids and the extent of increase of plasma TAC has raised questions about their contribution to the in vivo antioxidant network [21,25]. The first systematic review of dietary intervention studies with plant foods on markers of antioxidant function and oxidative stress will be presented and the association between dietary and endogenous antioxidant defences in vivo will be discussed. The “weight” of variables such as food association and homeostatic control of antioxidant defences will be discussed in order to obtain a realistic portrait of the complex interactions at the basis of the postulated protective effect of antioxidants molecules. There is a strong need of increasing the existing knowledge on the real efficacy of antioxidants in vivo in order to clarify if redox molecules represent a scientific-based strategy for disease prevention or just ancillary ingredients of fruit and vegetables. REFERENCES
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