Environmental Chemicals & Autism
Overloaded?: Environmental Chemicals & Autism
Environmental chemicals that provoke oxidative stress could contribute to autism or other health problems
During a typical day children and pregnant women are exposed to many different types of environmental chemicals that cause oxidative stress. These exposures add up, creating special concerns for infants and small children due to age-related sensitivity that derives from naturally low glutathione levels. This natural age-related vulnerability is exacerbated in individuals with impaired glutathione ratios. If these children were exposed to a high dose of any compound that produced significant oxidative stress, they would be less able to detoxify and excrete the compound.
Pervasive environmental contaminants like air pollutants from power plants and auto exhaust, pesticides, heavy metals and food additives all produce some degree of oxidative stress. Fine particulate matter and diesel exhaust both provoke tremendous oxidative stress and deplete glutathione (Li 2002). Oxygen radicals wreak havoc in the lungs of asthmatic children. The pain reliever acetaminophen and alcohol both provoke oxidative stress, but their combined effects are much more potent than either chemical alone.
Exposure to the pesticides maneb and paraquat can push neuron cells already under oxidative stress over a threshold of toxicity and "act as an additional insult to the system and prevent the normal recovery of [antioxidant] defenses" (Barlow 2005). Researchers have concluded that maneb disruptions to cells might cause neurodegeneration "especially with concurrent exposures to other environmentally relevant oxidative stressors, such as paraquat" (Barlow 2005). When they dosed pregnant mice with these pesticides the male offspring showed permanent alterations to neurological systems and enhanced susceptibility as an adult to paraquat (Barlow 2004).
PCBs induce a concentration-dependent increase in oxygen radicals. Cells with low levels of available glutathione are more sensitive to PCBs while cells pre-treated with antioxidants had reduced radical production and less cell death (Lee 2004).
Heavy metals-mercury, cadmium, chromium, cobalt, lead, antimony, nickel and others-are a major source of oxidative stress that are commonly detected in air, soil, water and food. Arsenic and chromium in pressure-treated wood, mercury in fish and vaccines, lead in paint, and metals in soil or drinking water are chronic if not daily sources of oxidative stress in the child's environment.
Glutathione is one of the bodys most important mechanism of heavy metal detoxification and excretion. Some metals-copper, chromium, iron and vanadium-directly provoke oxygen radical formation. Glutathione binds with these compounds as well as other metals—cadmium, lead, mercury, and nickel (Stohs 1995). The resulting, water-soluble chemical is more easily filtered out of the body. People with less 'active glutathione' will not be able to excrete metals as quickly. For example, cells treated with chemicals to inhibit glutathione recycling are much more sensitive to manganese toxicity (Desole 1997). People chronically exposed to arsenic in drinking water have increased oxidative damage and decreased antioxidant potential (Wu 2001).
Numerous studies link thimerosal with oxidative stress to the brain and neurological system at concentrations similar to those that were experienced by children vaccinated in the 1990s. Researchers measured mercury concentrations between 10 and 30 nanomoles per liter (nM) in premature infants given a single Hepatitis B shot at birth (Stajich 2000). Mercury concentrations ranging from 4 to 21 nM are reported in young children when measurements were collected 3 to 20 days after vaccination (Pichichero 2002). Four recent studies of thimerosal toxicity to human brain cells report oxidative damage, interruption of methylation, and decreased cell energy resulting from thimerosal exposure in the range of exposure overlapping with those for vaccinated children in the 1990s (Waly 2004, Baskin 2003, Ueha-Ishibashi 2004, Makani 2002). Several studies documented the protective benefits of antioxidants, especially glutathione, which attenuate the damages caused by thimerosal (Makani 2004, James 2005, Shanker 2003).
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.