Over the past 20 years, the medical research community has become increasingly aware of the effect of oxidative stress and the thiol / disulfide redox state in the pathogenesis of a diverse group of more than a hundred human diseases and aging disorders (Cross 1987) and (Djordjevic 2004). An organism is considered to be under oxidative stress when its production of oxidants (free radicals and other reactive oxidative species) is greater than its antioxidant protection capacity.
The recognition of glutathione as the "Master Antioxidant" and most abundant thiol in all animal cells has led to numerous clinical studies, which have investigated glutathione metabolism in human populations and its correlation with health, disease and longevity. Over the last decade, comprehensive reviews on the significance of glutathione in human disease have been regularly published in peer reviewed medical journals, (White 1994), (Lomaestro 1995), (Harding 1996), (Sen 1997), (Kidd 1997), (Exner 2000), (Lang 2001), (Reid 2001), (Droge 2002), (Townsend 2003), (Jefferies 2003) and (Wu 2004).
Indisputable cause and effect links have been demonstrated between glutathione metabolism and diseases, such as diabetes, cystic fibrosis, cancer, neurodegenerative diseases, HIV and aging. A variety of explanations as to why the depletion of glutathione is linked to oxidative stress in these disease states have been proposed. However, the general consensus of the reviewers is that the major determinant of the rate of glutathione synthesis is the availability of the precursor cysteine, with the undersupply of cysteine being the foremost cause of glutathione deficiency.
The need to replenish glutathione levels has been identified as a potential key treatment strategy in numerous diseases and disorders. Strategies for increasing glutathione are confounded by the fact that the two most obvious methods i.e. increasing dietary intake of either glutathione and/or cysteine, are generally ineffective in increasing cellular glutathione content. Due to the extreme concentration gradient between the intracellular glutathione content (1-10 mM) compared with the extracellular concentration (plasma 2-10 M), passive transport of glutathione either across the cell membrane, or from the intestinal contents is thermodynamically unfavourable. This means that orally or intravenously administered glutathione is not effectively transported into cells and is ultimately degraded into its component amino acids extracellularly. Administration of cysteine is also ineffective as it is reportedly toxic and rapidly oxidizes to the poorly soluble cysteine.