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Down Syndrome Abstract
of the Month: Jan 1999

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Biomarkers of oxidative stress are significantly elevated in Down syndrome

Jovanovic SV, Clements D, MacLeod K
Free Radic Biol Med. 1998 Dec;25(9):1044-8.

International Center for Metabolic Testing, Ottawa, Ontario, Canada

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There is convincing epidemiological and in vitro evidence of chronic oxidative stress in individuals with Down syndrome (DS). These individuals develop Alzheimer like changes in the brain in their 30s and 40s. The incidence of autoimmune diseases and cataracts is significantly increased, and the overall ageing process is accelerated. In vitro studies show that impaired viability of DS neurons may be amended by simple chemical antioxidants, such as vitamin E, BHT and propyl gallate, clearly indicative of oxyl radical involvement. However, because of the lack of in vivo experiments, the role of oxidative stress in DS remains controversial. We report here on the results of the chemical analyses of urine samples of 166 individuals, where DS subjects were matched by their siblings. The levels of 8-hydroxy-2'-deoxyguanosine, a biomarker of oxidative damage to DNA, and malondialdehyde, a biomarker of lipid peroxidation, are significantly elevated in individuals with DS. Dietary influences failed to show any significant correlation with the oxidative stress biomarkers. These results provide direct evidence for increased oxidative stress in individuals with DS.

My comments:

This article comes from the research arm of Nutrichem Labs, which manufactures a nutritional supplement for children with Down syndrome. One of the ongoing debates surrounding the use of this and other supplements has been the possible need for oral antioxidants. This article is an attempt to show a possible need for antioxidants in Down syndrome.

Specifically, one of the genes found on the 21st chromosome makes the enzyme SuperOxide Dismutase (SOD). This enzyme helps convert the oxygen radicals produced by normal metabolic processes to hydrogen peroxide; two other enzymes convert the hydrogen peroxide to oxygen and water. In mouse models of trisomy 21, an overabundance of hydrogen peroxide is therefore produced and causes oxidative damage to the cells of the body. This has been theorized as a possible cause for premature aging and neuronal death in people with Down syndrome. However, to date the studies that implicate this as a problem have been only on mice or human cells in a culture dish in a lab. This is the first attempt to try to identify if there is evidence of oxidative damage in living people with Down syndrome.

In the patients studied, the results show that the children with Down syndrome definitely had more urinary markers of increased oxidative metabolism, consistent with the overabundance of SOD. This is a well done study and should provide the impetus for even more research on this topic. The drawback to the study is that there is still no correlation with increased oxidative activity and disease process in the living person with Down syndrome. Also, it still does not answer the question of whether there is a use for oral antioxidants in Down syndrome, since it is not known if oral antioxidants would be able to counteract the SOD overactivity specific to Down syndrome.

Addendum, Jan 2005: To date, no more research has been done on this specific topic. The primary investigator left Nutricehm Labs shortly after this study was completed.
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