Characterisation of the effect of polyphenol fortified red grape juice on markers of oxidative stress and redox potential in healthy human subjects.
Background Information
Oxidative stress caused by free radicals is considered a primary contributor to the aging process. As we age, increasingly unchecked free radical activity results in accelerated damage to cell proteins and lipids and an accumulation of damage to genomic and mitochondrial nucleotides (DNA/RNA).1 Production of reactive oxygen and nitrogen radicals form part of normal cellular respiration and metabolism. In healthy tissue the potential for damage by these free radicals is kept in check by the cells antioxidant defence systems. This system includes endogenous enzymes such as catalase, superoxide dismutase and glutathione peroxidise, and smaller molecular species such as, tocopherols (vitamin E), ascorbate (vitamin C) and Retinol (Vitamin A).2
Free radical 'stress' occurs when the rate of production of free radicals outstrips the capacity of the bodies antioxidant defence systems to detoxify these reactive chemicals.
The body's antioxidant defence potential can be enhanced in two important ways; 1) cellular adaptive response and 2) ingestion of foods containing natural antioxidants (e.g. fruits and vegetables).
In relation to food derived antioxidants, the class of molecules called 'polyphenols' which are derived from red grapes and other dark fruits has attracted considerable attention in recent years owing to the observation that persons who consume regular amounts of these molecules in their diet have a considerably reduced risk of a range of lifestyle related diseases.3-4
One theory to explain this phenomenon centres on the ability of the grape-mix of polyphenols (including Resveratrol) to both reduce free radical damage and, in the case of resveratrol, stimulate sirtuin activity.5 Sirtuins are a class of enzymes involved in the regulation of transcription, apoptosis and stress resistance as well as cellular defence mechanisms. A popular hypothesis is that sirtuins, through the regulation of these metabolic processes, may play a key role in extending the lifespan of mammals.6
While the mechanism behind the anti-aging effects of these grape polyphenols likely involves antioxidant activity, the process has not been well characterised and may involve other pathways. Recent work in our own laboratory has demonstrated significant acceleration in DNA repair and altered redox potential in cultured primary human cells treated with selected polyphenols (Grant et al. 2008, Unpublished data). It is important to note that changes in redox potential are also associated with reduced oxidative stress and increased lifespan.
Study Aims
- To test the hypothesis that polyphenol fortified grape juice will: a) reduce serum oxidative stress markers and b) increase the redox potential in human blood.
References
1. Dröge W. Oxidative stress and aging. Adv Exp Med Biol. 2003; 543:191-200.
2. Ames BN, Shigenaga MK, Hagen TM. Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci. 1993; 90(17):7915-22.
3. Kopp P. Resveratrol, a phytoestrogen found in red wine. A possible explanation for the conundrum of the 'French paradox. Eur J Endocrinol. 1998;138(6):619-20.
4. Orallo F, Trans-resveratrol: a magical elixir of eternal youth? Curr Med Chem. 2008;15(19):1887-98.
5. Ghosh HS. The anti-aging, metabolism potential of SIRT1. Curr Opin Investig Drugs. 2008;9(10):1095-102.
