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Part 3 (continued):

Impaired antioxidant production provides a common rationale for many disparate features of autistic disorders

The identification of reduced antioxidant capacity as a common impairment in autistic children is an important breakthrough that should guide research into the autism epidemic. It strongly suggests that glutathione is a factor that mediates the relationship between environmental chemicals and autism, and for the first time provides a plausible biological link between several trademark features of the disorder that have baffled researchers searching for a single gene or chemical exposure that is triggering autism.

For example, scientists have failed to explain why autism rates are much higher in males, why autism manifests in some children after a period of healthy development, and why autistic children develop intestinal and autoimmune disorders at high rates. Antioxidant imbalance, particularly glutathione deficit, may be the unifying factor that links these apparently disparate symptoms and provides a clue to interventions that could treat autism. Each of these seemingly disconnected features of autism are strongly associated with glutathione capacity.

Autism rates higher, Glutathione levels lower in males

Males make up 70 percent of all autism cases, as well as the majority of children diagnosed with learning disabilities and attention deficit disorder. New research attributes weaker antioxidant capacity in young males with greater vulnerability in their brain and nervous systems, potentially effecting vulnerability to mercury and autism. Women and girls, in contrast, have lower levels of inactive antioxidant chemicals (Rush 2003). Estrogen is a powerful antioxidant that confers substantial benefits against free-radical mediated damage in aging. Male rats have four times higher rate of oxidative damage to mitochondrial DNA, which the authors pose as a reason for female's longer lifespan in many species including humans (Borrás 2003).

The difference in antioxidant capacity between males and females is most pronounced in newborns. Studies using tissue samples from newborn infants reveal significantly higher glutathione levels, glutathione production, and cell survival in response to oxidative stress in cells from girls compared to boys (Lavoie 1997). Studies of brain injury in newborns have found that inherently stronger glutathione capacity in females protects their brain cells from damage after a traumatic injury. Glutathione concentrations remain constant in females but they drop by as much as 80 percent in males after a brain injury (Du 2004). Similar studies found increased brain damage to children younger than four years old when their antioxidant systems are immature and glutathione levels are lower (Fan 2003).

Glutathione deficit may be responsible for intestinal disorders in autistic children

The reduced concentrations of glutathione Dr. James measured in study children may explain common intestinal ailments noted in autistic children. Glutathione is vital to proper functioning of the intestines. Deficits in glutathione cause degeneration of the jejunum and colon (Martensson 1990). Research suggests that oral administration of glutathione protects intestines against toxicity associated with inflammatory diseases, oxidative damage, and other toxins (Martensson 1990). Rodent studies highlight the role of glutathione in preventing positively charged substances—like metals—from passing through the gut (Samiec 2000). Laboratory studies have also demonstrated that treatment with glutathione precursors can protect the gut from different types of free-radical-mediated injury (Jefferies 2003).

Autistic children commonly suffer from intestinal disorders. In these 'leaky gut' disorders undigested proteins pass through the gut and cause oxidative damage to the brain and nervous system (White 2003). This is similar to PKU, a metabolic disorder in which the toxic accumulation of undigested phenylalanine causes oxidative damage leading to autistic-like symptoms. PKU can be averted in laboratory animals by antioxidant supplementation (Martinez-Cruz 2002). Many parents find that their autistic children's behavior and cognition improve when they eliminate milk and wheat from their diets, indicating that their inflamed intestines my be allowing the passage of undigested proteins that exacerbate their oxidative stress.

Glutathione's role in autism and auto-immunity

Autoimmune diseases are conditions in which the immune system targets the body itself instead of bacteria or other foreign objects. Autoimmunity can be triggered when genetically susceptible people are exposed to an environmental chemical or virus. Oxidative stress also plays an important role in autoimmunity by disrupting cell signaling. T lymphocytes are made less active or hypo-responsive when they are exposed to oxygen radicals. T lymphocytes regain normal responsiveness when the antioxidants N-acetyl cysteine (Cemerski 2002) and other glutathione precursors are added to the system (Hehner 2000).

A recent investigation reported chronic inflammation in the brains of autistic patients, resulting from an over-active immune system, a sign of autoimmunity (Vargas 2004). The inflammation indicates that the brain is responding to a process that is stressing or damaging brain cells, a process which might include oxygen radicals.

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