Glutathione (GSH) is a central player in the antioxidant defense system. It is a tripeptide (3-amino-acid protein) made from glutamate, cysteine and glycine. The active site on the glutathione molecule is the sulfhydryl (SH) group on the cysteine part of the glutathione (which is where the “SH” comes from in the ’GSH’ abbreviation for glutathione). The sulfhydryl group (sometimes called a thiol group) interacts with a free radical to form a glutathione radical, which dimerizes (pairs up with another glutathione radical) to form oxidized glutathione (GSSG). Oxidized glutathione is then recycled (reduced) back to glutathione for reuse.

The maintenance of reduced glutathione appears to be especially critical for overall health maintenance; children with Down syndrome appear to be more susceptible to infection when glutathione levels are low, even when other deficiencies are milder than expected [MacLeod, 1996]. Down's syndrome children with high glutathione levels appear to be more healthy, even if they are suffering from additional deficiencies that are more severe than usual.

Although glutathione levels do tend to increase when other antioxidant deficiencies are corrected, they generally do not fully normalize. We do not know why. Given that cysteine is a component of glutathione, it is somewhat paradoxical that Down's syndrome is characterized by abundant cysteine and deficient glutathione. The dynamics of this relationship are not yet fully understood, but it may be wholly or partly the direct result of oxidative stress.

Glutathione Peroxidase


Glutathione peroxidase (GSHpx) is a endogenous antioxidant enzyme that detoxifies hydrogen peroxide (HOOH) and fatty acid hydroperoxides (fatty-OOH). It is constructed from four identical subunits, each of which contains one atom of selenium (Se). Glutathione peroxidase uses reduced glutathione to detoxify peroxides, releasing oxidized glutathione in the process. Oxidized glutathione is recycled by glutathione reductase back to reduced glutathione  using riboflavin (vitamin B2) as a cofactor and NADPH as a reducing agent (an anti-oxidizing substance).

The central role of selenium in glutathione peroxidase activity provides a possible focus for intervention. Selenium supplementation may be able to up-regulate glutathione peroxidase activity to restore some degree of balance with the overexpressed SOD. In areas of the world where selenium deficiency is severe (i.e., New Zealand and China), selenium supplementation has been found to readily reverse selenium-deficiency diseases in animals (e.g., white-muscle disease in sheep) and man (Keshan's disease).

Food sources of selenium can be problematic. Selenium is not an essential nutrient in plants as it is in animals. Wheat grown in selenium-rich soil (i.e., South Dakota) contains respectable levels of selenium, but wheat grown in selenium-poor soil (i.e., Oregon) does not. Does anybody really know where their wheat was grown?

In one trial of Down's syndrome individuals, selenium supplementation was found to increase the levels of glutathione peroxidase. Thus, selenium supplementation appears to be a viable strategy for compensating for SOD overexpression.

Source: Antioxidant Intervention in Down’s Syndrome

Note: Selenium should only be supplemented individually under careful guidence of a practitioner, it must be carefully dosed.  Selenium can be found in carefully selected doses in both Nutrivene and MSB, which are both Down syndrome specific multivitamins.   Food sources of selenium can be found here.


There is only one form of oral glutathione supplement that I have seen recommended, it is Setria Glutathione  Glutathione can also be given transdermally via a cream, the Neurobiologix cream I have seen recommended quite a few times.

B12,   Vitamin C, Folinic Acid and Vitamin E have all been mentioned as useful in raising glutathione levels.  Food sources can be found by following this link.

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