AUTISM AND GLUTATHIONE
NOTHING SHORT OF EXCITING..................
Autism effects many parts of the body
not only the brain development but also
intestinal and immune dysregulation
NOTHING SHORT OF EXCITING..................
Autism effects many parts of the body
not only the brain development but also
intestinal and immune dysregulation
Report Release Date: 13 December 2004 Mercury Primer Summary
Scientists have identified a signature metabolic impairment or "biomarker" in autistic children that strongly
suggests that these children would be susceptible to the harmful effects of mercury and other toxic chemical
exposures (James 2004a).
This impairment manifests as a severe imbalance in the ratio of active to inactive GLUTATHIONE, the body's
most important tool for detoxifying and excreting metals. GLUTATHIONE works as an antioxidant, keeping in
check the potentially destructive process of oxidative stress caused both by normal metabolism and
environmental contaminants. Autistic children showed a significant impairment in every one of five
measurements of the body's ability to maintain a healthy GLUTATHIONE defense.
These findings raise serious concerns about children's overall exposure to environmental contaminants.
Mercury is of particular concern, however, because of its proven toxicity to the developing brain and nervous
system, and documented high exposures from a variety of sources.
One of every six pregnancies is exposed to methyl mercury above EPA's safe level from maternal
consumption of contaminated seafood (CDC 2002, Mahaffey 2004). Thimerosal, a preservative in vaccines that is
49 percent ethyl mercury, was a major source of mercury exposure from 1988 through 2002 when it was
removed from childhood immunizations at the urging of the Public Health Service and the American Academy
of Pediatrics. Elemental mercury from dental amalgams is another potentially important source, but its
contribution to overall mercury exposure is less well studied.
The incidence of autism increased 10-fold from 6 in 10,000 in the 1980s (Blaxill 2004), to about 60 in 10,000 today
(Autism Alarm, PDF file). These new findings significantly strengthen the possibility that mercury could cause
or contribute to autism and other neurodevelopmental disorders by identifying a metabolic imbalance common
to nearly all autistic children that would make these children poorly equipped to mount a defense against a
number of neurotoxic compounds, including mercury.
Finally, these findings raise serious concerns about the studies that have allegedly proven the safety of
mercury in vaccines. The epidemiologic studies used to dismiss a causal relationship between autism and
thimerosal have assumed that all children have the same resistance to chemical exposure. To properly
investigate the potential harm from mercury-containing shots researchers would have to compare autism rates
in children with the same type of vulnerability.
Background
In 1988, the Centers for Disease Control (CDC) recommended important new additions to the nation's infant
immunization program, including three Hepatitis B immunizations (one injected at birth), and three Haemophilis
B shots—all delivered by six months of age. Drug companies responded with vaccinations supplied in multiple
dose containers preserved with the mercury-based antibacterial thimerosal. Neither the CDC, nor the Food and
Drug Administration (FDA), which monitors the safety of vaccinations, expressed concerns at that time about
the relatively high doses of mercury that newborn babies and infants would be exposed to through these shots.
A dramatic nationwide increase in autism followed directly on the heels of the abrupt rise in thimerosal
exposure (Blaxill 2001). Rates rose from 6 in 10,000 children in the 1980s to 60 in 10,000 today (Blaxill 2004a,
American Academy of Pediatrics 2004). In 2003, the Autism Society of America estimated the cost of treating
and caring for 1.5 million autistic children at $90 billion per year (Autism Society of America 2003).
To better understand whether or not the dramatic increase in autism was related to the abrupt nationwide
increase in exposure to mercury in vaccinations, the CDC conducted its own epidemiologic study, and then
convened a panel of the Institute of Medicine (IOM) of the National Academy of Sciences to review the issue
independently. On May 17, 2004, the IOM published its final report on the possible link between thimerosal and
autism. The IOM rejected "a causal relationship" between the two, and then took the unusual step of
recommending the termination of additional research into the subject, stating clearly that, "Further research to
find the cause of autism should be directed toward other lines of inquiry" (IOM press release 2004a). Or as put
by the chair of the IOM committee, "Available funding for autism research should be channeled to the most
promising areas, of which the link with vaccines does not appear to be one" (Barclay 2004). The chief of the
national immunization program at the Centers for Disease Control went even further, declaring that only "junk
scientists and charlatans" support research into the potential link between thimerosal exposure and autism
(Levin 2004).
The IOM's recommendation that research into the potential link between mercury and autism be abandoned is
highly unusual coming from an institution built on the notion of free scientific inquiry. Not surprisingly, the
statement was cause for concern in some scientific quarters. In spite of these and other concerns, however, the
committee's findings remain, on balance, an accurate reflection of the published epidemiologic studies at the
time of its release.
What is more important, but largely overlooked, was the committee's own admission that it did not adequately
address the leading theory among independent scientists — that autism could be triggered by environmental
exposures, including mercury in vaccines, in a subset of vulnerable children. As the IOM panel stated in its final
report:
"...the committee cannot rule out, based on the epidemiological evidence, the possibility that vaccines
contribute to autism in some small subset or very unusual circumstances" (IOM 2004b).
Or as put by the Chair of the IOM committee, Dr. Marie McCormick, of the Harvard School of Public Health:
"Some children could be particularly vulnerable or susceptible to mercury exposure because of genetic or
other differences" (McCormick 2001).
Findings
An eighteen-month investigation by Environmental Working Group concludes that scientists have identified a
signature metabolic profile or "biomarker" in autistic children that may indeed characterize a "small subset" of
susceptible children. These findings represent a potential milestone in our understanding of individual
vulnerability to toxic substances, including, but not limited to, mercury. This science turns on its head the IOM's
judgment that research into the thimerosal/autism link be abandoned, and instead strengthens significantly the
case for additional research in this area.
We found that:
Newly published research and follow-up testing by former FDA senior research scientist Dr. Jill James, now of
the University of Arkansas for Medical Sciences, has uncovered a unique and consistent metabolic imbalance in
autistic children when compared to normal healthy children (James 2004a, 2004b). This impairment manifests
as a severe deficit in the body's most important antioxidant and metals detoxifier, GLUTATHIONE. When
compared to normal health children, autistic children showed a significant impairment in every one of five
measurements of the body's ability to maintain a healthy GLUTATHIONE defense.
These findings are strong evidence that if these children were exposed to a potentially toxic dose of mercury or
other compound they would be much less able to mount an effective defense.
Source: James 2004b
- The finding of a significant GLUTATHIONE deficit in autistic children provides a biological basis for integrating
many facets of autism that have baffled researchers attempting to pin the autism epidemic on a single gene or
chemical exposure.
- The implications of these findings extend well beyond thimerosal and autism. Reduced antioxidant defense
may characterize a group of individuals who are demonstrably more sensitive to the effects of a range of toxic
chemical exposures, and shed light on increasing rates of related learning and behavioral disorders.
- These findings raise serious concerns about the studies that have allegedly proven the safety of mercury in
vaccines. While Dr. James' results do not prove that mercury causes autism, they significantly strengthen this
possibility. The epidemiologic studies used to dismiss a causal relationship between mercury and autism
assumed that all children have the same resistance to chemical exposure. Given James' finding that autistic
children would be much more sensitive to certain chemical contaminants, studies that do not acknowledge
these vulnerabilities cannot be used to dismiss the relationship between environmental chemicals, including
mercury, and the disease.
- When James' results are considered together with the existing body of science, including other recently
published research, the weight of the evidence now strongly supports increased research into the relationship
between thimerosal and autism as well as other neurodevelopmental and neurodegenerative disorders.
Mercury Primer
Mercury, a potent toxic metal that targets the developing brain and nervous system, is challenging lead as the
number one environmental health threat to American children. According to the EPA's top mercury scientist,
one out of every six children born in the United States is exposed to levels of methyl mercury during
pregnancy that exceed what the Agency considers safe (Mahaffey 2004). The principal source of high fetal
methyl mercury exposure is maternal consumption of contaminated seafood, primarily canned tuna. Pregnant
women who eat significant quantities of large ocean-going fish could expose their babies to amounts of
mercury that are well above the government's recommended safe levels.
In March, 2004, the Food and Drug Administration revised their mercury seafood advisory to include a specific
warning about consumption of canned albacore tuna. Pregnant women and children are advised to eat no more
than one six ounce can of albacore tuna per week. The advisory, however, provides no consumption advice for
a number of fish where high mercury levels are a concern, including tuna steaks, sea bass, halibut, and many
others. The Environmental Working Group has filed a legal challenge to the FDA mercury seafood advisory,
charging that it is not based on the best available science on seafood contamination and mercury risk levels to
the developing fetus.
But contaminated seafood is not the only source of mercury exposure for the developing fetus or infant.
Mercury amalgam dental fillings are a potentially significant source of fetal mercury exposure, although precise
amounts are not well characterized. And from 1988 through about 2002, children were exposed to significant
doses of mercury from birth through six months of age in the form of a mercury-based preservative,
thimerosal, used in routine childhood immunizations. Children born to Rh negative mothers were also exposed
to mercury in-utero when their mothers received a mercury-containing RhoGAM shot. The flu shot is another
source of fetal and infant mercury exposure. The health impact of mercury exposure through vaccinations has
been the source of intense debate because of significant changes in the vaccination regimen from 1988 through
1991 that increased neonatal and infant exposure to mercury.
Drug companies were similarly silent on the matter, although internal company documents show that they were
aware of the potent neurotoxic effects of mercury as early as the 1940s. Notably, the FDA banned the sale of
topically applied thimerosal antibiotics in the 1980s due to severe, even crippling, adverse skin reactions in
sensitive individuals.
The amount of mercury in the standard battery of childhood immunizations more than doubled between 1988
and 1991 when these additional shots were added to the early childhood vaccination regimen. Throughout the
1990s, children received nine mercury-containing vaccinations within their first six months of life, including the
unprecedented injection of a mercury-containing vaccine at birth, and up to three shots given in a single day at
2-, 4-, and 6-months. The average two-month old baby vaccinated with thimerosal-containing shots in the 1990s
received a single day dose of mercury that was between 100 and 125 times the government's long-term safe
exposure level.
Drug companies used thimerosal as a vaccine preservative to allow multiple injections to be shipped and
stored in single containers. Thimerosal is 49 percent ethyl mercury, a widely recognized and potent neurotoxin.
After more than a decade of nationwide, high childhood exposures, it was removed from childhood
vaccinations between 1999 and 2002, at the urging of the Public Health Service and the American Academy of
Pediatrics, but is still present in most flu vaccines. California and Iowa have banned mercury-containing
thimerosal from all vaccinations, and Missouri and Nebraska have legislation in progress.
Part 1:
Environmental triggers are a neglected component of autism research
There is no doubt that an environmental factor has contributed to the dramatic increase in the incidence of
autism over the past 15 years. Genetic factors are a component in the condition—concurrent rates of autism in
identical twins approach 90 percent—but rates of inherited genetic diseases do not change abruptly in one
generation, whereas autism rates skyrocketed during the 1990s. Rates of autism in the United States increased
from fewer than 6 cases per 10,000 children in the 1980s to more than 60 per 10,000 children today (Blaxill
2004a). The American Academy of Pediatrics and the Centers for Disease Control (CDC) currently estimate that
autism affects one in every 166 children (AAP 2004). Improved diagnosis does not adequately account for this
increase (Blaxill 2004a, Croen 2003).
Autism is a complex neurological disorder characterized by severely impaired social interaction and language
skills.
There has been little progress in identifying pre- and post-natal environmental exposures that might trigger the
severe impacts to brain development, intestinal and immune dysregulation that characterize autism disorders
(London 2000). Hundreds of studies have explored the genetic roots of the autism epidemic, but none has
uncovered a single gene or vulnerability to account for more than a fraction of cases.
Children's exposure to mercury in immunizations has been a long-standing concern of autism advocates—and
for good reason. Mercury is highly toxic to brain cells and other body systems impacted by autism. Several
classic features of autism—speech loss and loss of social and communication skills—are signature traits of
mercury poisoning. Many parents report children slipping into autism shortly after receiving multiple mercury-
containing vaccinations.
The findings discussed here, that autistic children share a common deficit in antioxidant protection, call into
question the conclusion that mercury in vaccines is uniformly safe for all children, and underscores the need
for a broader look at the role of environmental chemicals in the autism epidemic.
Important New Finding offers clues to autism prevention and treatment
In an exciting breakthrough, Dr. Jill James of the University of Arkansas School of Medicine has documented a
unique metabolic profile in 95 autistic children with regressive autism. (James 2004a, 2004b) Regressive autism
is a form of the disease in which children develop normally for a certain period before losing previously
acquired language or behaviors and being diagnosed with autism.
The metabolic profile in the James study children manifests as a severe imbalance in the ratio of active to
inactive GLUTATHIONE in autistic children, compared to a group of healthy control children (James 2004a,
2004b). GLUTATHIONE, a potent antioxidant, is the body's most important tool for detoxifying and excreting
metals.
Autistic children have significant differences in every measure of antioxidant capacity and oxidative stress
The James study shows that children with regressive autism have consistently elevated levels of oxidative
stress as compared to normal healthy children. Individuals with reduced GLUTATHIONE antioxidant capacity
will be under chronic oxidative stress and will be more vulnerable to toxic compounds that act primarily
through oxidative damage, including mercury (James 2004). Oxidative stress plays a key role in several
important degenerative diseases of the brain and nervous system, including Alzheimer's, Parkinson's,
Huntington's disease, and schizophrenia (Shulz 2000, Granot 2004).
Scientists have identified a signature metabolic impairment or "biomarker" in autistic children that strongly
suggests that these children would be susceptible to the harmful effects of mercury and other toxic chemical
exposures (James 2004a).
This impairment manifests as a severe imbalance in the ratio of active to inactive GLUTATHIONE, the body's
most important tool for detoxifying and excreting metals. GLUTATHIONE works as an antioxidant, keeping in
check the potentially destructive process of oxidative stress caused both by normal metabolism and
environmental contaminants. Autistic children showed a significant impairment in every one of five
measurements of the body's ability to maintain a healthy GLUTATHIONE defense.
These findings raise serious concerns about children's overall exposure to environmental contaminants.
Mercury is of particular concern, however, because of its proven toxicity to the developing brain and nervous
system, and documented high exposures from a variety of sources.
One of every six pregnancies is exposed to methyl mercury above EPA's safe level from maternal
consumption of contaminated seafood (CDC 2002, Mahaffey 2004). Thimerosal, a preservative in vaccines that is
49 percent ethyl mercury, was a major source of mercury exposure from 1988 through 2002 when it was
removed from childhood immunizations at the urging of the Public Health Service and the American Academy
of Pediatrics. Elemental mercury from dental amalgams is another potentially important source, but its
contribution to overall mercury exposure is less well studied.
The incidence of autism increased 10-fold from 6 in 10,000 in the 1980s (Blaxill 2004), to about 60 in 10,000 today
(Autism Alarm, PDF file). These new findings significantly strengthen the possibility that mercury could cause
or contribute to autism and other neurodevelopmental disorders by identifying a metabolic imbalance common
to nearly all autistic children that would make these children poorly equipped to mount a defense against a
number of neurotoxic compounds, including mercury.
Finally, these findings raise serious concerns about the studies that have allegedly proven the safety of
mercury in vaccines. The epidemiologic studies used to dismiss a causal relationship between autism and
thimerosal have assumed that all children have the same resistance to chemical exposure. To properly
investigate the potential harm from mercury-containing shots researchers would have to compare autism rates
in children with the same type of vulnerability.
Background
In 1988, the Centers for Disease Control (CDC) recommended important new additions to the nation's infant
immunization program, including three Hepatitis B immunizations (one injected at birth), and three Haemophilis
B shots—all delivered by six months of age. Drug companies responded with vaccinations supplied in multiple
dose containers preserved with the mercury-based antibacterial thimerosal. Neither the CDC, nor the Food and
Drug Administration (FDA), which monitors the safety of vaccinations, expressed concerns at that time about
the relatively high doses of mercury that newborn babies and infants would be exposed to through these shots.
A dramatic nationwide increase in autism followed directly on the heels of the abrupt rise in thimerosal
exposure (Blaxill 2001). Rates rose from 6 in 10,000 children in the 1980s to 60 in 10,000 today (Blaxill 2004a,
American Academy of Pediatrics 2004). In 2003, the Autism Society of America estimated the cost of treating
and caring for 1.5 million autistic children at $90 billion per year (Autism Society of America 2003).
To better understand whether or not the dramatic increase in autism was related to the abrupt nationwide
increase in exposure to mercury in vaccinations, the CDC conducted its own epidemiologic study, and then
convened a panel of the Institute of Medicine (IOM) of the National Academy of Sciences to review the issue
independently. On May 17, 2004, the IOM published its final report on the possible link between thimerosal and
autism. The IOM rejected "a causal relationship" between the two, and then took the unusual step of
recommending the termination of additional research into the subject, stating clearly that, "Further research to
find the cause of autism should be directed toward other lines of inquiry" (IOM press release 2004a). Or as put
by the chair of the IOM committee, "Available funding for autism research should be channeled to the most
promising areas, of which the link with vaccines does not appear to be one" (Barclay 2004). The chief of the
national immunization program at the Centers for Disease Control went even further, declaring that only "junk
scientists and charlatans" support research into the potential link between thimerosal exposure and autism
(Levin 2004).
The IOM's recommendation that research into the potential link between mercury and autism be abandoned is
highly unusual coming from an institution built on the notion of free scientific inquiry. Not surprisingly, the
statement was cause for concern in some scientific quarters. In spite of these and other concerns, however, the
committee's findings remain, on balance, an accurate reflection of the published epidemiologic studies at the
time of its release.
What is more important, but largely overlooked, was the committee's own admission that it did not adequately
address the leading theory among independent scientists — that autism could be triggered by environmental
exposures, including mercury in vaccines, in a subset of vulnerable children. As the IOM panel stated in its final
report:
"...the committee cannot rule out, based on the epidemiological evidence, the possibility that vaccines
contribute to autism in some small subset or very unusual circumstances" (IOM 2004b).
Or as put by the Chair of the IOM committee, Dr. Marie McCormick, of the Harvard School of Public Health:
"Some children could be particularly vulnerable or susceptible to mercury exposure because of genetic or
other differences" (McCormick 2001).
Findings
An eighteen-month investigation by Environmental Working Group concludes that scientists have identified a
signature metabolic profile or "biomarker" in autistic children that may indeed characterize a "small subset" of
susceptible children. These findings represent a potential milestone in our understanding of individual
vulnerability to toxic substances, including, but not limited to, mercury. This science turns on its head the IOM's
judgment that research into the thimerosal/autism link be abandoned, and instead strengthens significantly the
case for additional research in this area.
We found that:
Newly published research and follow-up testing by former FDA senior research scientist Dr. Jill James, now of
the University of Arkansas for Medical Sciences, has uncovered a unique and consistent metabolic imbalance in
autistic children when compared to normal healthy children (James 2004a, 2004b). This impairment manifests
as a severe deficit in the body's most important antioxidant and metals detoxifier, GLUTATHIONE. When
compared to normal health children, autistic children showed a significant impairment in every one of five
measurements of the body's ability to maintain a healthy GLUTATHIONE defense.
These findings are strong evidence that if these children were exposed to a potentially toxic dose of mercury or
other compound they would be much less able to mount an effective defense.
Source: James 2004b
- The finding of a significant GLUTATHIONE deficit in autistic children provides a biological basis for integrating
many facets of autism that have baffled researchers attempting to pin the autism epidemic on a single gene or
chemical exposure.
- The implications of these findings extend well beyond thimerosal and autism. Reduced antioxidant defense
may characterize a group of individuals who are demonstrably more sensitive to the effects of a range of toxic
chemical exposures, and shed light on increasing rates of related learning and behavioral disorders.
- These findings raise serious concerns about the studies that have allegedly proven the safety of mercury in
vaccines. While Dr. James' results do not prove that mercury causes autism, they significantly strengthen this
possibility. The epidemiologic studies used to dismiss a causal relationship between mercury and autism
assumed that all children have the same resistance to chemical exposure. Given James' finding that autistic
children would be much more sensitive to certain chemical contaminants, studies that do not acknowledge
these vulnerabilities cannot be used to dismiss the relationship between environmental chemicals, including
mercury, and the disease.
- When James' results are considered together with the existing body of science, including other recently
published research, the weight of the evidence now strongly supports increased research into the relationship
between thimerosal and autism as well as other neurodevelopmental and neurodegenerative disorders.
Mercury Primer
Mercury, a potent toxic metal that targets the developing brain and nervous system, is challenging lead as the
number one environmental health threat to American children. According to the EPA's top mercury scientist,
one out of every six children born in the United States is exposed to levels of methyl mercury during
pregnancy that exceed what the Agency considers safe (Mahaffey 2004). The principal source of high fetal
methyl mercury exposure is maternal consumption of contaminated seafood, primarily canned tuna. Pregnant
women who eat significant quantities of large ocean-going fish could expose their babies to amounts of
mercury that are well above the government's recommended safe levels.
In March, 2004, the Food and Drug Administration revised their mercury seafood advisory to include a specific
warning about consumption of canned albacore tuna. Pregnant women and children are advised to eat no more
than one six ounce can of albacore tuna per week. The advisory, however, provides no consumption advice for
a number of fish where high mercury levels are a concern, including tuna steaks, sea bass, halibut, and many
others. The Environmental Working Group has filed a legal challenge to the FDA mercury seafood advisory,
charging that it is not based on the best available science on seafood contamination and mercury risk levels to
the developing fetus.
But contaminated seafood is not the only source of mercury exposure for the developing fetus or infant.
Mercury amalgam dental fillings are a potentially significant source of fetal mercury exposure, although precise
amounts are not well characterized. And from 1988 through about 2002, children were exposed to significant
doses of mercury from birth through six months of age in the form of a mercury-based preservative,
thimerosal, used in routine childhood immunizations. Children born to Rh negative mothers were also exposed
to mercury in-utero when their mothers received a mercury-containing RhoGAM shot. The flu shot is another
source of fetal and infant mercury exposure. The health impact of mercury exposure through vaccinations has
been the source of intense debate because of significant changes in the vaccination regimen from 1988 through
1991 that increased neonatal and infant exposure to mercury.
Drug companies were similarly silent on the matter, although internal company documents show that they were
aware of the potent neurotoxic effects of mercury as early as the 1940s. Notably, the FDA banned the sale of
topically applied thimerosal antibiotics in the 1980s due to severe, even crippling, adverse skin reactions in
sensitive individuals.
The amount of mercury in the standard battery of childhood immunizations more than doubled between 1988
and 1991 when these additional shots were added to the early childhood vaccination regimen. Throughout the
1990s, children received nine mercury-containing vaccinations within their first six months of life, including the
unprecedented injection of a mercury-containing vaccine at birth, and up to three shots given in a single day at
2-, 4-, and 6-months. The average two-month old baby vaccinated with thimerosal-containing shots in the 1990s
received a single day dose of mercury that was between 100 and 125 times the government's long-term safe
exposure level.
Drug companies used thimerosal as a vaccine preservative to allow multiple injections to be shipped and
stored in single containers. Thimerosal is 49 percent ethyl mercury, a widely recognized and potent neurotoxin.
After more than a decade of nationwide, high childhood exposures, it was removed from childhood
vaccinations between 1999 and 2002, at the urging of the Public Health Service and the American Academy of
Pediatrics, but is still present in most flu vaccines. California and Iowa have banned mercury-containing
thimerosal from all vaccinations, and Missouri and Nebraska have legislation in progress.
Part 1:
Environmental triggers are a neglected component of autism research
There is no doubt that an environmental factor has contributed to the dramatic increase in the incidence of
autism over the past 15 years. Genetic factors are a component in the condition—concurrent rates of autism in
identical twins approach 90 percent—but rates of inherited genetic diseases do not change abruptly in one
generation, whereas autism rates skyrocketed during the 1990s. Rates of autism in the United States increased
from fewer than 6 cases per 10,000 children in the 1980s to more than 60 per 10,000 children today (Blaxill
2004a). The American Academy of Pediatrics and the Centers for Disease Control (CDC) currently estimate that
autism affects one in every 166 children (AAP 2004). Improved diagnosis does not adequately account for this
increase (Blaxill 2004a, Croen 2003).
Autism is a complex neurological disorder characterized by severely impaired social interaction and language
skills.
There has been little progress in identifying pre- and post-natal environmental exposures that might trigger the
severe impacts to brain development, intestinal and immune dysregulation that characterize autism disorders
(London 2000). Hundreds of studies have explored the genetic roots of the autism epidemic, but none has
uncovered a single gene or vulnerability to account for more than a fraction of cases.
Children's exposure to mercury in immunizations has been a long-standing concern of autism advocates—and
for good reason. Mercury is highly toxic to brain cells and other body systems impacted by autism. Several
classic features of autism—speech loss and loss of social and communication skills—are signature traits of
mercury poisoning. Many parents report children slipping into autism shortly after receiving multiple mercury-
containing vaccinations.
The findings discussed here, that autistic children share a common deficit in antioxidant protection, call into
question the conclusion that mercury in vaccines is uniformly safe for all children, and underscores the need
for a broader look at the role of environmental chemicals in the autism epidemic.
Important New Finding offers clues to autism prevention and treatment
In an exciting breakthrough, Dr. Jill James of the University of Arkansas School of Medicine has documented a
unique metabolic profile in 95 autistic children with regressive autism. (James 2004a, 2004b) Regressive autism
is a form of the disease in which children develop normally for a certain period before losing previously
acquired language or behaviors and being diagnosed with autism.
The metabolic profile in the James study children manifests as a severe imbalance in the ratio of active to
inactive GLUTATHIONE in autistic children, compared to a group of healthy control children (James 2004a,
2004b). GLUTATHIONE, a potent antioxidant, is the body's most important tool for detoxifying and excreting
metals.
Autistic children have significant differences in every measure of antioxidant capacity and oxidative stress
The James study shows that children with regressive autism have consistently elevated levels of oxidative
stress as compared to normal healthy children. Individuals with reduced GLUTATHIONE antioxidant capacity
will be under chronic oxidative stress and will be more vulnerable to toxic compounds that act primarily
through oxidative damage, including mercury (James 2004). Oxidative stress plays a key role in several
important degenerative diseases of the brain and nervous system, including Alzheimer's, Parkinson's,
Huntington's disease, and schizophrenia (Shulz 2000, Granot 2004).
Metabolite Number of Average in Average in Difference in p-value
Healthy Controls Autistic Children Healthy Children autistic group
Homocysteine 75 5.5 5.9 7% less 0.05
(umol/L)
Cysteine 75 161 205 22% less than 0.0001
(umol/L)
ACTIVE GLUTATHIONE
Total: tGSH 75 5.1 7.5 31% less than 0.0001
(umol/L)
Free: fGSH 49 1.5 2.1 30% less than 0.0001
(umol/L)
Inactive GLUTATHIONE: 49 0.41 0.31 34% more
00.0015
GSSG (nmol/L)
GLUTATHIONE ratio
(unitless)
tGSH/GSSG 49 16.7 27.6 40% less <0.0001
fGSH/GSSG 49 5.0 7.1 30% less <0.0001
Healthy Controls Autistic Children Healthy Children autistic group
Homocysteine 75 5.5 5.9 7% less 0.05
(umol/L)
Cysteine 75 161 205 22% less than 0.0001
(umol/L)
ACTIVE GLUTATHIONE
Total: tGSH 75 5.1 7.5 31% less than 0.0001
(umol/L)
Free: fGSH 49 1.5 2.1 30% less than 0.0001
(umol/L)
Inactive GLUTATHIONE: 49 0.41 0.31 34% more
00.0015
GSSG (nmol/L)
GLUTATHIONE ratio
(unitless)
tGSH/GSSG 49 16.7 27.6 40% less <0.0001
fGSH/GSSG 49 5.0 7.1 30% less <0.0001
Oxygen radicals damage the brain and nervous system
Autistic children's inability to combat oxidative stress can lead to many health problems. Oxidative stress is
caused by oxygen radicals — highly unstable chemicals that react with and destroy healthy cells. These free
oxygen radicals are produced by the body in manageable amounts as byproducts of normal body metabolism,
but their prevalence can be exacerbated by exposure to environmental chemicals. Oxygen radicals damage
cells by reacting with proteins, DNA, carbohydrates, and fats, setting off chain reactions that can only be
stopped by a cell's antioxidant defense system. In the process they disrupt cell functions and interfere with
signals sent between cells in the body, which can lead to auto-immunity (Klein 2003).
Oxidative damage is counteracted by the body's antioxidant systems, which convert oxygen radicals into
harmless byproducts. Oxidative stress occurs when oxygen radicals overwhelm the capacity of the body's
antioxidant systems. Oxidative stress affects many body systems. It damages cell membrane structure
(lipids), the cell machinery that performs the essential work of the cells (proteins), and the body's ability to
regulate cell growth and protein synthesis (DNA and RNA). Oxidative stress is associated with premature aging
of cells, and can lead to tissue inflammation, damaged cell membranes, autoimmunity and cell death (Klein
2003). GLUTATHIONE is the most important antioxidant for metals detoxification and excretion.
The brain and nervous system are particularly vulnerable to oxidative stress due to limited antioxidant
capacity. The brain makes up about two percent of a person's mass but consumes 20 percent of their
metabolic oxygen. The vast majority of this energy is used by the neurons (Shulman 2004). Some brain cells,
like neurons, cannot make GLUTATHIONE, but instead rely on surrounding astrocyte cells to provide useable
GLUTATHIONE precursors. Because the brain has limited access to the bulk of antioxidants produced by the
body, neurons are the first cells to be affected by a shortage of antioxidants, and are most susceptible to
oxidative stress. Researchers studying antioxidant protection of neurons are finding short windows during
development of high vulnerability to oxidative stress (Perry 2004).
Children are more vulnerable than adults to oxidative stress due to their naturally low GLUTATHIONE levels
from conception through infancy (Erden-Inal 2003, Ono 2001). Risks created by this natural deficit in
detoxification capacity in infants are compounded by the fact that mercury and other environmental chemicals
that invoke oxidative stress are found at higher concentrations in the developing infant than in their mothers
and appear to accumulate in the placenta.
In addition to this natural variability in antioxidant status with age, a person's genes play a strong role in their
ability to make antioxidants in response to oxidative stress. A host of genes determine the speed and
responsiveness of antioxidant production and recycling. Some genes common in one quarter to one half of the
U.S. population reduce GLUTATHIONE activity and are linked with increased odds of several cancers (Hallier
1994, Engel 2002). People with gene deletions for two types of GLUTATHIONE genes (GST M1 and T1) are more
likely to have allergic reactions to the mercury-based preservative thimerosal (Westphal 2000).
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 bodies 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.
The weight of the evidence supports a fresh look at the mercury-autism hypothesis
Both autism and mercury exposure are characterized by
functional impairment to speech, language and behavior
(Bernard 2001, Blaxill 2004b). Recent studies also suggest
that the same key regions of the brain are affected in both
cases (Limke 2004, Kates 2004). At the same time, episodes
of severe mercury exposure reveal that there is no single
manifestation of mercury poisoning. In fact, children
exposed to high levels of mercury during gestation and
infancy have suffered from strikingly different diseases.
Minamata disease resulted from in-utero exposure to
mercury-contaminated fish. Children with Minamata disease
had symptoms indistinguishable from mental retardation or
cerebral palsy (Kondo 2000). Acrodynia resulted from mercury
in infant teething powders in the early 1900s. Children with
Acrodynia suffered peeling and reddened skin on their hands
and feet, and heightened sensitivity to light (Warkany 1966).
Individual susceptibility played an important role in both disorders.
Although thousands of children were treated with mercury-containing teething powders, only one in 500 to one
in 1,000 children who were exposed developed Acrodynia (Warkany 1966). The role of individual sensitivity
made it extremely difficult to link mercury exposure with what was, at the time, a new and bizarre disease.
Similarly, when children have been exposed to high levels of mercury in foods, only a small group develop
severe mercury poisoning while thousands are apparently unharmed (Jalili 1961, Kondo 2000).
Dr. James' findings clearly reveal a mechanism by which autistic children would be predisposed to mercury-
related oxidative damage to their developing brain and nervous system. Several additional pieces of evidence
strengthen the potential link between mercury exposure and autism in children with abnormal antioxidant
capacity. These include:
- The indisputable toxicity of mercury to the brain, particularly the developing brain (Limke 2004, Clarkson
2002, Mahaffey 1999).
- Peer-reviewed reports showing that autistic children are extremely poor at ridding their bodies of mercury
as measured by mercury hair levels (Holmes 2003).
- The recent finding that autism-like symptoms are triggered by thimerosal in mice with a predisposition to
autoimmunity (Hornig 2004).
- The fact that the prevalence of autism in boys is four times that in girls, and that boys have elevated
incidence of damage from mercury exposure in epidemiologic studies (Vahter 2002).
Mercury targets brain cells
Pre-natal and early life mercury exposures cause multiple impacts to basic brain development by disrupting
the division and migration of neuronal cells (Mahaffey 1999). Mercury creates oxidative stress that directly kills
brain cells. Human beings accumulate more mercury in the brain than in blood or other organs. Organic
mercury actively transported through the blood—brain barrier accumulates in the highest concentrations in the
cerebellum, especially the neuronal cells (Limke 2004). The cerebellum is the brain region associated with
movement and cognition, and a key region targeted by toxic chemicals (Fonnum 2000), and a region of
impairment in autistic patients (McAlonan 2004).
Dr. James investigated the effect of thimerosal on human brain astrocyte and neuron cells. She found that
astrocytes have higher levels of GLUTATHIONE compared to neurons and were more resistant to the cytotoxic
effects of thimerosal (James 2005). Mercury was less toxic to human brain cells pretreated with GLUTATHIONE
or a GLUTATHIONE precursor N-acetyl cysteine, which is used as a treatment for mercury intoxication and it is
thought to speed mercury excretion from the body (Ballatori 1998). Similar studies have documented oxidative
damages of mercury and GLUTATHIONE protection to T cells, astrocytes, neurons and fibroblasts (Makani
2002, Shanker 2003).
Immune symptoms
In the summer of 2004, researchers at Columbia's Mailman School of Public Health reported symptoms similar
to autism in thimerosal-exposed mice. Thimerosal was administered to three strains of laboratory mice at
exposures that replicated infant exposure in the 1990s. Only the mouse strain with a predisposition to
autoimmunity was affected by thimerosal exposure. These mice had significant growth delay, reduced
locomotion, exaggerated response to novelty, and changes in the brain and nervous system that were
suggestive of autism (Hornig 2004).
Metal metabolism and regression
Unlike most substances that are toxic to the brain, there is a significant lag time between exposure to either
mercury or thimerosal, and the emergence of the symptoms of mercury poisoning. The length of the lag
period depends on the severity of exposures. The delay between first exposure and on-set of symptoms of
mercury poisoning has been attributed to the gradual depletion of the brain's compensatory responses, chiefly
GLUTATHIONE and other antioxidants (Weiss 2002).
Autism often is diagnosed after a period of seemingly healthy development. Regressive children lose
previously acquired skills such as speech and mobility, or fail to progress in their development. The role that
oxidative stress and environmental chemicals play in regressive autism is unknown, but studies finding
reduced metal excretion in autistic children point to different dynamics in regressive autism.
A recent publication by physician Amy Holmes reported that autistic children had significantly lower levels of
mercury in their hair relative to non-autistic children, suggesting greater accumulation of mercury in the body
due to reduced excretion capabilities (Holmes 2003). Hair samples were analyzed from 94 autistic children and
45 non-autistic children between one and two years of age and the autistic children had significantly lower
levels of mercury in their hair samples (0.47 vs. 3.63 ppm).
For non-autistic children the level of mercury in the hair sample was strongly correlated with the mother's
exposure to mercury in dental fillings, fish consumption and mercury-containing RhoGAM vaccinations during
pregnancy. In autistic children there was no correlation, hair levels were always low, even in cases where
elevated maternal mercury exposure was reported.
Regressive cases had higher concentrations of mercury in hair indicating less impaired mercury metabolism.
This indicates that children least able to excrete mercury might experience autistic symptoms immediately
while regressive cases of those with some capacity to detoxify and get rid of mercury would at first appear
normal, but would then build up mercury to a critical point before their excretion capacity was overwhelmed
and autistic symptoms surfaced.
Autistic children's inability to combat oxidative stress can lead to many health problems. Oxidative stress is
caused by oxygen radicals — highly unstable chemicals that react with and destroy healthy cells. These free
oxygen radicals are produced by the body in manageable amounts as byproducts of normal body metabolism,
but their prevalence can be exacerbated by exposure to environmental chemicals. Oxygen radicals damage
cells by reacting with proteins, DNA, carbohydrates, and fats, setting off chain reactions that can only be
stopped by a cell's antioxidant defense system. In the process they disrupt cell functions and interfere with
signals sent between cells in the body, which can lead to auto-immunity (Klein 2003).
Oxidative damage is counteracted by the body's antioxidant systems, which convert oxygen radicals into
harmless byproducts. Oxidative stress occurs when oxygen radicals overwhelm the capacity of the body's
antioxidant systems. Oxidative stress affects many body systems. It damages cell membrane structure
(lipids), the cell machinery that performs the essential work of the cells (proteins), and the body's ability to
regulate cell growth and protein synthesis (DNA and RNA). Oxidative stress is associated with premature aging
of cells, and can lead to tissue inflammation, damaged cell membranes, autoimmunity and cell death (Klein
2003). GLUTATHIONE is the most important antioxidant for metals detoxification and excretion.
The brain and nervous system are particularly vulnerable to oxidative stress due to limited antioxidant
capacity. The brain makes up about two percent of a person's mass but consumes 20 percent of their
metabolic oxygen. The vast majority of this energy is used by the neurons (Shulman 2004). Some brain cells,
like neurons, cannot make GLUTATHIONE, but instead rely on surrounding astrocyte cells to provide useable
GLUTATHIONE precursors. Because the brain has limited access to the bulk of antioxidants produced by the
body, neurons are the first cells to be affected by a shortage of antioxidants, and are most susceptible to
oxidative stress. Researchers studying antioxidant protection of neurons are finding short windows during
development of high vulnerability to oxidative stress (Perry 2004).
Children are more vulnerable than adults to oxidative stress due to their naturally low GLUTATHIONE levels
from conception through infancy (Erden-Inal 2003, Ono 2001). Risks created by this natural deficit in
detoxification capacity in infants are compounded by the fact that mercury and other environmental chemicals
that invoke oxidative stress are found at higher concentrations in the developing infant than in their mothers
and appear to accumulate in the placenta.
In addition to this natural variability in antioxidant status with age, a person's genes play a strong role in their
ability to make antioxidants in response to oxidative stress. A host of genes determine the speed and
responsiveness of antioxidant production and recycling. Some genes common in one quarter to one half of the
U.S. population reduce GLUTATHIONE activity and are linked with increased odds of several cancers (Hallier
1994, Engel 2002). People with gene deletions for two types of GLUTATHIONE genes (GST M1 and T1) are more
likely to have allergic reactions to the mercury-based preservative thimerosal (Westphal 2000).
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 bodies 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.
The weight of the evidence supports a fresh look at the mercury-autism hypothesis
Both autism and mercury exposure are characterized by
functional impairment to speech, language and behavior
(Bernard 2001, Blaxill 2004b). Recent studies also suggest
that the same key regions of the brain are affected in both
cases (Limke 2004, Kates 2004). At the same time, episodes
of severe mercury exposure reveal that there is no single
manifestation of mercury poisoning. In fact, children
exposed to high levels of mercury during gestation and
infancy have suffered from strikingly different diseases.
Minamata disease resulted from in-utero exposure to
mercury-contaminated fish. Children with Minamata disease
had symptoms indistinguishable from mental retardation or
cerebral palsy (Kondo 2000). Acrodynia resulted from mercury
in infant teething powders in the early 1900s. Children with
Acrodynia suffered peeling and reddened skin on their hands
and feet, and heightened sensitivity to light (Warkany 1966).
Individual susceptibility played an important role in both disorders.
Although thousands of children were treated with mercury-containing teething powders, only one in 500 to one
in 1,000 children who were exposed developed Acrodynia (Warkany 1966). The role of individual sensitivity
made it extremely difficult to link mercury exposure with what was, at the time, a new and bizarre disease.
Similarly, when children have been exposed to high levels of mercury in foods, only a small group develop
severe mercury poisoning while thousands are apparently unharmed (Jalili 1961, Kondo 2000).
Dr. James' findings clearly reveal a mechanism by which autistic children would be predisposed to mercury-
related oxidative damage to their developing brain and nervous system. Several additional pieces of evidence
strengthen the potential link between mercury exposure and autism in children with abnormal antioxidant
capacity. These include:
- The indisputable toxicity of mercury to the brain, particularly the developing brain (Limke 2004, Clarkson
2002, Mahaffey 1999).
- Peer-reviewed reports showing that autistic children are extremely poor at ridding their bodies of mercury
as measured by mercury hair levels (Holmes 2003).
- The recent finding that autism-like symptoms are triggered by thimerosal in mice with a predisposition to
autoimmunity (Hornig 2004).
- The fact that the prevalence of autism in boys is four times that in girls, and that boys have elevated
incidence of damage from mercury exposure in epidemiologic studies (Vahter 2002).
Mercury targets brain cells
Pre-natal and early life mercury exposures cause multiple impacts to basic brain development by disrupting
the division and migration of neuronal cells (Mahaffey 1999). Mercury creates oxidative stress that directly kills
brain cells. Human beings accumulate more mercury in the brain than in blood or other organs. Organic
mercury actively transported through the blood—brain barrier accumulates in the highest concentrations in the
cerebellum, especially the neuronal cells (Limke 2004). The cerebellum is the brain region associated with
movement and cognition, and a key region targeted by toxic chemicals (Fonnum 2000), and a region of
impairment in autistic patients (McAlonan 2004).
Dr. James investigated the effect of thimerosal on human brain astrocyte and neuron cells. She found that
astrocytes have higher levels of GLUTATHIONE compared to neurons and were more resistant to the cytotoxic
effects of thimerosal (James 2005). Mercury was less toxic to human brain cells pretreated with GLUTATHIONE
or a GLUTATHIONE precursor N-acetyl cysteine, which is used as a treatment for mercury intoxication and it is
thought to speed mercury excretion from the body (Ballatori 1998). Similar studies have documented oxidative
damages of mercury and GLUTATHIONE protection to T cells, astrocytes, neurons and fibroblasts (Makani
2002, Shanker 2003).
Immune symptoms
In the summer of 2004, researchers at Columbia's Mailman School of Public Health reported symptoms similar
to autism in thimerosal-exposed mice. Thimerosal was administered to three strains of laboratory mice at
exposures that replicated infant exposure in the 1990s. Only the mouse strain with a predisposition to
autoimmunity was affected by thimerosal exposure. These mice had significant growth delay, reduced
locomotion, exaggerated response to novelty, and changes in the brain and nervous system that were
suggestive of autism (Hornig 2004).
Metal metabolism and regression
Unlike most substances that are toxic to the brain, there is a significant lag time between exposure to either
mercury or thimerosal, and the emergence of the symptoms of mercury poisoning. The length of the lag
period depends on the severity of exposures. The delay between first exposure and on-set of symptoms of
mercury poisoning has been attributed to the gradual depletion of the brain's compensatory responses, chiefly
GLUTATHIONE and other antioxidants (Weiss 2002).
Autism often is diagnosed after a period of seemingly healthy development. Regressive children lose
previously acquired skills such as speech and mobility, or fail to progress in their development. The role that
oxidative stress and environmental chemicals play in regressive autism is unknown, but studies finding
reduced metal excretion in autistic children point to different dynamics in regressive autism.
A recent publication by physician Amy Holmes reported that autistic children had significantly lower levels of
mercury in their hair relative to non-autistic children, suggesting greater accumulation of mercury in the body
due to reduced excretion capabilities (Holmes 2003). Hair samples were analyzed from 94 autistic children and
45 non-autistic children between one and two years of age and the autistic children had significantly lower
levels of mercury in their hair samples (0.47 vs. 3.63 ppm).
For non-autistic children the level of mercury in the hair sample was strongly correlated with the mother's
exposure to mercury in dental fillings, fish consumption and mercury-containing RhoGAM vaccinations during
pregnancy. In autistic children there was no correlation, hair levels were always low, even in cases where
elevated maternal mercury exposure was reported.
Regressive cases had higher concentrations of mercury in hair indicating less impaired mercury metabolism.
This indicates that children least able to excrete mercury might experience autistic symptoms immediately
while regressive cases of those with some capacity to detoxify and get rid of mercury would at first appear
normal, but would then build up mercury to a critical point before their excretion capacity was overwhelmed
and autistic symptoms surfaced.
GLUTATHIONE and antioxidant precursors have
been examined as treatments for metabolic
conditions like PKU that create long-term
oxidative stress (Baielli 2003). A small pilot
study found that GLUTATHIONE supplements
caused a 42 percent decline in disability for
patients with Parkinson's disease (Sechi 1996).
Antioxidants are also proposed to treat metal
toxicity, particularly arsenic (Flora 1999),
borate (Banner 1986), cadmium (Tandon 2003),
chromate (Banner 1986), copper
(Henderson 1985), lead (Tandon 2003),
and mercury (Ballatori 1998).
Oxidative damage to brain cells during pregnancy
and early life can lead to permanent changes to
brain structure and functioning, resulting in
autism. In order to fully protect brain cells,
GLUTATHIONE and antioxidant precursors must
be administered in advance of environmental
exposures that stress or kill brain cells.
Nonetheless, bolstering GLUTATHIONE recycling in
children already diagnosed with autism could
ameliorate many downstream effects of
GLUTATHIONE depletion including intestinal
function, auto-immunity, and cellular inflammation.
Dr. James is hopeful that the success of the intervention "implies that certain aspects of autism may be
treatable" (James 2004a).
Please note here that the studies involved in this report are at the bottom of this page for viewing and
verification..........
been examined as treatments for metabolic
conditions like PKU that create long-term
oxidative stress (Baielli 2003). A small pilot
study found that GLUTATHIONE supplements
caused a 42 percent decline in disability for
patients with Parkinson's disease (Sechi 1996).
Antioxidants are also proposed to treat metal
toxicity, particularly arsenic (Flora 1999),
borate (Banner 1986), cadmium (Tandon 2003),
chromate (Banner 1986), copper
(Henderson 1985), lead (Tandon 2003),
and mercury (Ballatori 1998).
Oxidative damage to brain cells during pregnancy
and early life can lead to permanent changes to
brain structure and functioning, resulting in
autism. In order to fully protect brain cells,
GLUTATHIONE and antioxidant precursors must
be administered in advance of environmental
exposures that stress or kill brain cells.
Nonetheless, bolstering GLUTATHIONE recycling in
children already diagnosed with autism could
ameliorate many downstream effects of
GLUTATHIONE depletion including intestinal
function, auto-immunity, and cellular inflammation.
Dr. James is hopeful that the success of the intervention "implies that certain aspects of autism may be
treatable" (James 2004a).
Please note here that the studies involved in this report are at the bottom of this page for viewing and
verification..........
References for the James Study at the upper section.......
American Academy of Pediatrics, Center for Disease Control's National Center on Birth Defects and Developmental
Disabilities. 2004. Autism A.L.A.R.M. http://www.medicalhomeinfo.org
Autism Society of America. 2003. Autism Cost to Economy in Billions. Available at: http://www.autism-society.org/site/
News2?JServSessionIdr008=qsr4rlqyt1.app26a&page=NewsArticle&id=5828
Baieli S, Pavone L, Meli C, Fiumara A, Coleman M. 2003. Autism and phenylketonuria. J Autism Dev Disord. 33(2):201-4.
Ballatori N, Lieberman MW, Wang W. 1998. N-acetylcysteine as an antidote in methylmercury poisoning. Environ Health
Perspect. 106(5):267-71.
Banner W Jr, Koch M, Capin DM, Hopf SB, Chang S, Tong TG. 1986. Experimental chelation therapy in chromium, lead, and
boron intoxication with N-acetylcysteine and other compounds. Toxicol Appl Pharmacol. 83(1):142-7.
Barclay L. 2004. Mercury Linked to Autism-Like Damage in Mice: Institute of Medicine Says Study Does Not Support Link
Between Mercury, Autism in Humans. WebMD Medical News. June 9, 2004. Available at:
http://my.webmd.com/content/Article/88/99936.htm
Barlow BK 2004. A fetal risk factor for Parkinson's disease. Dev Neurosci. 26(1):11-23.
Barlow BK, Lee DW, Cory-Slechta DA, Opanashuk LA. 2005. Modulation of antioxidant defense systems by the environmental
pesticide maneb in dopaminergic cells. Neurotoxicology. 26(1):63-75.
Baskin DS, Ngo H, Didenko VV. 2003. Thimerosal induces DNA breaks, caspase-3 activation, membrane damage, and cell
death in cultured human neurons and fibroblasts. Tox Sci 74(2):361-8.
Bernard S. 2001. Autism: a novel form of mercury poisoning. Medical Hypotheses 56(4):462-471.
Blaxill M. 2001. Presentation to Immunization Safety Review Committee. Rising Incidence of Autism: Association with
Thimerosal. Cambridge, Massachusetts. July 16, 2001. Available at: www.iom.edu/includes/DBFile.asp?id=7505
Blaxill M. 2004a. What's Going On? The Question of Time Trends in Autism. Public Health Reports. (119)536-551.
Blaxill M, Redwood L, Bernard S. 2004b. Thimerosal and autism? A plausible hypothesis that should not be dismissed. Medical
Hypotheses. (62)788-94.
Borras C, Sastre J, Garcia Sala D, Lloret A, Pallardo FV, Vina J. 2003. Mitochondria from females exhibit higher antioxidant
gene expression and lower oxidative damage than males. Free Radical Biology & Medicine. 34(5):546-52.
Cemerski S. 2002. Reactive Oxygen Species Differentially Affect T Cell Receptor-signaling Pathways. Journal of Biological
Chemistry. 227(22):19585-92.
Centers for Disease Control. 1995. Recommended Childhood Immunization Schedule -- United States, 1995.
http://www.cdc.gov/mmwr/preview/mmwrhtml/00038256.htm Last reviewed May 2001.
Centers for Disease Control. 2004. Questions & Answers: Thimerosal-Containing Influenza Vaccine.
http://www.cdc.gov/flu/about/qa/thimerosal.htm Updated October 26, 2004.
Chrysochoou C. 2003. An 11-month-old boy with psychomotor regression and auto-aggressive behaviour. Eur J Pediatr.
(162):559-561.
Clarkson TW. 2002. Three modern faces of mercury. Environmental Health Perspectives. 110(Suppl 1):11-23.
Croen LA, Grether JK. 2003. A Response to Blaxill, Baskin, and Spitzer on Croen et al. (2002), 'The Changing Prevalence of
Autism in California.' Journal of Autism and Developmental Disorders, 33(2):227-9.
Desole MS, Esposito G, Migheli R, Sircana S, Delogu MR, Fresu L, Miele M, de Natale G, Miele E. 1997. Glutathione deficiency
potentiates manganese toxicity in rat striatum and brainstem and in PC12 cells. Pharmacol Res. 36(4):285-92.
Du L, Bayir H, Lai Y, Zhang X, Kochanek PM, Watkins SC, Graham SH, Clark RS. 2004. Innate gender-based proclivity in
response to cytotoxicity and programmed cell death pathway. J Biol Chem. 279(37):38563-70.
Engel LS. 2002. Pooled analysis and meta-analysis of Glutathione S-Transferase M1 and Bladder Cancer: a HuGE review. Am J
Epidemiol (156):95-109.
Erden-Inal M, Sunal E, Kanbak G. 2002. Age-related changes in the glutathione redox system. Cell Biochem Funct. 20(1):61-6.
Fan P, Yamauchi T, Noble LJ, Ferriero DM. 2003. Age-Dependent Differences in Glutathione Peroxidase Activity After Traumatic
Brain Injury. Journal of Neurotrauma. 20(5):437-445.
Flora SJ. 1999. Arsenic-induced oxidative stress and its reversibility following combined administration of N-acetylcysteine
and meso 2,3-dimercaptosuccinic acid in rats. Clin Exp Pharmacol Physiol. 26(11):865-9.
Fonnum F, Lock EA. 2000. Cerebellum as a target for toxic substances. Toxicol Lett. (112-113):9-16.
Food and Drug Administration, Center for Biologics Evaluation and Research. 2004a. Mercury in Plasma-Derived Products.
http://www.fda.gov/cber/blood/mercplasma.htm Updated September 9, 2004
FDA Center for Biologics Evaluation and Research. 2004b. Mercury in Vaccines
http://www.fda.gov/cber/vaccine/thimerosal.htm Updated September 28, 2004.
Gimenez-Llort L, Ahlbom E, Dare E, Vahter M, Ogren S, Ceccatelli S. 2001. Prenatal exposure to methylmercury changes
dopamine-modulated motor activity during early ontogeny: age and gender-dependent effects. Environ. Toxicol. Pharmacol.
9(3):61-70.
Granot E, Kohen R. 2004. Oxidative stress in childhood health and disease states. Clinical Nutrition 23(1):3-11.
Hallier E, Schroder KR, Asmuth K, Dommermuth A, Aust B, Goergens HW. 1994. Metabolism of dichloromethane (methylene
chloride) to formaldehyde in human erythrocytes: influence of polymorphism of glutathione transferase theta (GST T1-1). Arch
Toxicol. 68(7):423-7.
Hehner SP. 2000. Enhancement of T cell receptor signaling by a mild oxidative shift in the intracellular thiol pool. J. Immunol.
165(8):4319-4328.
Henderson P, Hale TW, Shum S, Habersang RW. 1985. N-Acetylcysteine therapy of acute heavy metal poisoning in mice.Vet
Hum Toxicol. 27(6):522-5.
Holmes AS, Blaxill MF, Haley BE. 2003. Reduced Levels of Mercury in First Baby Haircuts of Autistic Children. International
Journal of Toxicology, (22):277-285.
Hornig M, Chian D, Lipkin WI. 2004. Neurotoxic effects of postnatal thimerosal are mouse strain dependent. Mol Psychiatry.
9(9):833-45.
Institute of Medicine. 2004a. Press Release: MMR Vaccine and Thimerosal-Containing Vaccines Are Not Associated With
Autism, IOM Report Says. May 18, 2004. http://www4.nationalacademies.org/news.nsf/isbn/030909237X?OpenDocument
Institute of Medicine. 2004b. Immunization Safety Review: Vaccines and Autism. National Academies Press. Available at:
http://books.nap.edu/catalog/10997.html
Jalili MA, Abbasi AH. 1961. Poisoning by ethyl mercury toluene sulphonanilide. Br J Ind Med. (18):303-8.
James SJ, Cutler P, Melnyk S, Hernigan S, Janak L, Gaylor DW, Neubrander JA. 2004a. Metabolic biomarkers of increased
oxidative stress and methylation capacity in children with autism. American Journal of Clinical Nutrition. 80(6):1611-1617.
[Advanced copy available at http://www.ajcn.org/cgi/content/full/80/6/1611]
James SJ, et al. 2004b. Unpublished results follow-up testing of 75 autistic children and 42 controls. Personal communication
with EWG.
James SJ, Slikker W 3rd, Melnyk S, New E, Pogribna M, Jernigan S. 2005. Thimerosal Neurotoxicity is Associated with
Glutathione Depletion: Protection with Glutathione Precursors. Neurotoxicology. 26(1):1-8.
Jefferies H. 2003. The role of glutathione in intestinal dysfunction. J Invest Surg. 16(6):315-23.
Kates WR, Burnette CP, Eliez S, Strunge LA, Kaplan D, Landa R, Reiss AL, Pearlson GD. 2004. Neuroanatomic variation in
monozygotic twin pairs discordant for the narrow phenotype for autism. Am J Psychiatry. 161(3):539-46.
Klein JA, Ackerman SL. 2003. Oxidative stress, cell cycle, and neurodegeneration. In Redox Signaling in Biology and Disease,
Roy J. Soberman, Series Editor J. Clin. Invest. (111):785-793.
Kondo K. 2000. Congenital Minamata disease: warning from Japan's experience. J Child Neurol. 15(7):458-64.
Lavoie JC, Chessex P. 1997. Gender and maturation affect glutathione statues in human neonatal tissues. Free Radical
Biology & Medicine. 23(4)648-57.
Lee DW, Opanashuk LA. 2004. Polychlorinated biphenyl mixture aroclor 1254-induced oxidative stress plays a role in
dopaminergic cell injury. Neurotoxicology. 25(6):925-39.
Levin. 2004. 'Taking It to Vaccine Court; Parents say mercury in shots caused their children's autism, and they want drug firms
to pay. The industry calls its defense rock-solid.' Los Angeles Times, August 7, 2004. Foreign Desk; Part A; Pg. 1.
Li N, Kim S, Wang M, Froines J, Sioutas C, Nel A. 2002. Use of a stratified oxidative stress model to study the biological effects
of ambient concentrated and diesel exhaust particulate matter. Inhal Toxicol. 14(5):459-86.
Limke TL, Heidemann SF, Atchison WD. 2004. Disruption of intraneuronal divalent cation regulation by methylmercury: are
specific targets involved in altered neuronoal development and cytotoxicity in methylmercury poisoning? NeruroToxicology.
(25):741-60.
London E, Etzel RA. 2000. The environment as an etiologic factor in autism: A new direction for research. Environmental
Health Perspectives. (108)S3.
Mahaffey KR. 1999. Methylmercury: A new look at the risks. Public Health Reports. 114(5):402-13.
Mahaffey KR. 2004. Methylmercury: Epidemiology Update. Slide presentation given at the National Forum on Contaminants in
Fish. San Diego, CA. January 26, 2004. http://www.epa.gov/waterscience/fish/forum/2004/
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American Academy of Pediatrics, Center for Disease Control's National Center on Birth Defects and Developmental
Disabilities. 2004. Autism A.L.A.R.M. http://www.medicalhomeinfo.org
Autism Society of America. 2003. Autism Cost to Economy in Billions. Available at: http://www.autism-society.org/site/
News2?JServSessionIdr008=qsr4rlqyt1.app26a&page=NewsArticle&id=5828
Baieli S, Pavone L, Meli C, Fiumara A, Coleman M. 2003. Autism and phenylketonuria. J Autism Dev Disord. 33(2):201-4.
Ballatori N, Lieberman MW, Wang W. 1998. N-acetylcysteine as an antidote in methylmercury poisoning. Environ Health
Perspect. 106(5):267-71.
Banner W Jr, Koch M, Capin DM, Hopf SB, Chang S, Tong TG. 1986. Experimental chelation therapy in chromium, lead, and
boron intoxication with N-acetylcysteine and other compounds. Toxicol Appl Pharmacol. 83(1):142-7.
Barclay L. 2004. Mercury Linked to Autism-Like Damage in Mice: Institute of Medicine Says Study Does Not Support Link
Between Mercury, Autism in Humans. WebMD Medical News. June 9, 2004. Available at:
http://my.webmd.com/content/Article/88/99936.htm
Barlow BK 2004. A fetal risk factor for Parkinson's disease. Dev Neurosci. 26(1):11-23.
Barlow BK, Lee DW, Cory-Slechta DA, Opanashuk LA. 2005. Modulation of antioxidant defense systems by the environmental
pesticide maneb in dopaminergic cells. Neurotoxicology. 26(1):63-75.
Baskin DS, Ngo H, Didenko VV. 2003. Thimerosal induces DNA breaks, caspase-3 activation, membrane damage, and cell
death in cultured human neurons and fibroblasts. Tox Sci 74(2):361-8.
Bernard S. 2001. Autism: a novel form of mercury poisoning. Medical Hypotheses 56(4):462-471.
Blaxill M. 2001. Presentation to Immunization Safety Review Committee. Rising Incidence of Autism: Association with
Thimerosal. Cambridge, Massachusetts. July 16, 2001. Available at: www.iom.edu/includes/DBFile.asp?id=7505
Blaxill M. 2004a. What's Going On? The Question of Time Trends in Autism. Public Health Reports. (119)536-551.
Blaxill M, Redwood L, Bernard S. 2004b. Thimerosal and autism? A plausible hypothesis that should not be dismissed. Medical
Hypotheses. (62)788-94.
Borras C, Sastre J, Garcia Sala D, Lloret A, Pallardo FV, Vina J. 2003. Mitochondria from females exhibit higher antioxidant
gene expression and lower oxidative damage than males. Free Radical Biology & Medicine. 34(5):546-52.
Cemerski S. 2002. Reactive Oxygen Species Differentially Affect T Cell Receptor-signaling Pathways. Journal of Biological
Chemistry. 227(22):19585-92.
Centers for Disease Control. 1995. Recommended Childhood Immunization Schedule -- United States, 1995.
http://www.cdc.gov/mmwr/preview/mmwrhtml/00038256.htm Last reviewed May 2001.
Centers for Disease Control. 2004. Questions & Answers: Thimerosal-Containing Influenza Vaccine.
http://www.cdc.gov/flu/about/qa/thimerosal.htm Updated October 26, 2004.
Chrysochoou C. 2003. An 11-month-old boy with psychomotor regression and auto-aggressive behaviour. Eur J Pediatr.
(162):559-561.
Clarkson TW. 2002. Three modern faces of mercury. Environmental Health Perspectives. 110(Suppl 1):11-23.
Croen LA, Grether JK. 2003. A Response to Blaxill, Baskin, and Spitzer on Croen et al. (2002), 'The Changing Prevalence of
Autism in California.' Journal of Autism and Developmental Disorders, 33(2):227-9.
Desole MS, Esposito G, Migheli R, Sircana S, Delogu MR, Fresu L, Miele M, de Natale G, Miele E. 1997. Glutathione deficiency
potentiates manganese toxicity in rat striatum and brainstem and in PC12 cells. Pharmacol Res. 36(4):285-92.
Du L, Bayir H, Lai Y, Zhang X, Kochanek PM, Watkins SC, Graham SH, Clark RS. 2004. Innate gender-based proclivity in
response to cytotoxicity and programmed cell death pathway. J Biol Chem. 279(37):38563-70.
Engel LS. 2002. Pooled analysis and meta-analysis of Glutathione S-Transferase M1 and Bladder Cancer: a HuGE review. Am J
Epidemiol (156):95-109.
Erden-Inal M, Sunal E, Kanbak G. 2002. Age-related changes in the glutathione redox system. Cell Biochem Funct. 20(1):61-6.
Fan P, Yamauchi T, Noble LJ, Ferriero DM. 2003. Age-Dependent Differences in Glutathione Peroxidase Activity After Traumatic
Brain Injury. Journal of Neurotrauma. 20(5):437-445.
Flora SJ. 1999. Arsenic-induced oxidative stress and its reversibility following combined administration of N-acetylcysteine
and meso 2,3-dimercaptosuccinic acid in rats. Clin Exp Pharmacol Physiol. 26(11):865-9.
Fonnum F, Lock EA. 2000. Cerebellum as a target for toxic substances. Toxicol Lett. (112-113):9-16.
Food and Drug Administration, Center for Biologics Evaluation and Research. 2004a. Mercury in Plasma-Derived Products.
http://www.fda.gov/cber/blood/mercplasma.htm Updated September 9, 2004
FDA Center for Biologics Evaluation and Research. 2004b. Mercury in Vaccines
http://www.fda.gov/cber/vaccine/thimerosal.htm Updated September 28, 2004.
Gimenez-Llort L, Ahlbom E, Dare E, Vahter M, Ogren S, Ceccatelli S. 2001. Prenatal exposure to methylmercury changes
dopamine-modulated motor activity during early ontogeny: age and gender-dependent effects. Environ. Toxicol. Pharmacol.
9(3):61-70.
Granot E, Kohen R. 2004. Oxidative stress in childhood health and disease states. Clinical Nutrition 23(1):3-11.
Hallier E, Schroder KR, Asmuth K, Dommermuth A, Aust B, Goergens HW. 1994. Metabolism of dichloromethane (methylene
chloride) to formaldehyde in human erythrocytes: influence of polymorphism of glutathione transferase theta (GST T1-1). Arch
Toxicol. 68(7):423-7.
Hehner SP. 2000. Enhancement of T cell receptor signaling by a mild oxidative shift in the intracellular thiol pool. J. Immunol.
165(8):4319-4328.
Henderson P, Hale TW, Shum S, Habersang RW. 1985. N-Acetylcysteine therapy of acute heavy metal poisoning in mice.Vet
Hum Toxicol. 27(6):522-5.
Holmes AS, Blaxill MF, Haley BE. 2003. Reduced Levels of Mercury in First Baby Haircuts of Autistic Children. International
Journal of Toxicology, (22):277-285.
Hornig M, Chian D, Lipkin WI. 2004. Neurotoxic effects of postnatal thimerosal are mouse strain dependent. Mol Psychiatry.
9(9):833-45.
Institute of Medicine. 2004a. Press Release: MMR Vaccine and Thimerosal-Containing Vaccines Are Not Associated With
Autism, IOM Report Says. May 18, 2004. http://www4.nationalacademies.org/news.nsf/isbn/030909237X?OpenDocument
Institute of Medicine. 2004b. Immunization Safety Review: Vaccines and Autism. National Academies Press. Available at:
http://books.nap.edu/catalog/10997.html
Jalili MA, Abbasi AH. 1961. Poisoning by ethyl mercury toluene sulphonanilide. Br J Ind Med. (18):303-8.
James SJ, Cutler P, Melnyk S, Hernigan S, Janak L, Gaylor DW, Neubrander JA. 2004a. Metabolic biomarkers of increased
oxidative stress and methylation capacity in children with autism. American Journal of Clinical Nutrition. 80(6):1611-1617.
[Advanced copy available at http://www.ajcn.org/cgi/content/full/80/6/1611]
James SJ, et al. 2004b. Unpublished results follow-up testing of 75 autistic children and 42 controls. Personal communication
with EWG.
James SJ, Slikker W 3rd, Melnyk S, New E, Pogribna M, Jernigan S. 2005. Thimerosal Neurotoxicity is Associated with
Glutathione Depletion: Protection with Glutathione Precursors. Neurotoxicology. 26(1):1-8.
Jefferies H. 2003. The role of glutathione in intestinal dysfunction. J Invest Surg. 16(6):315-23.
Kates WR, Burnette CP, Eliez S, Strunge LA, Kaplan D, Landa R, Reiss AL, Pearlson GD. 2004. Neuroanatomic variation in
monozygotic twin pairs discordant for the narrow phenotype for autism. Am J Psychiatry. 161(3):539-46.
Klein JA, Ackerman SL. 2003. Oxidative stress, cell cycle, and neurodegeneration. In Redox Signaling in Biology and Disease,
Roy J. Soberman, Series Editor J. Clin. Invest. (111):785-793.
Kondo K. 2000. Congenital Minamata disease: warning from Japan's experience. J Child Neurol. 15(7):458-64.
Lavoie JC, Chessex P. 1997. Gender and maturation affect glutathione statues in human neonatal tissues. Free Radical
Biology & Medicine. 23(4)648-57.
Lee DW, Opanashuk LA. 2004. Polychlorinated biphenyl mixture aroclor 1254-induced oxidative stress plays a role in
dopaminergic cell injury. Neurotoxicology. 25(6):925-39.
Levin. 2004. 'Taking It to Vaccine Court; Parents say mercury in shots caused their children's autism, and they want drug firms
to pay. The industry calls its defense rock-solid.' Los Angeles Times, August 7, 2004. Foreign Desk; Part A; Pg. 1.
Li N, Kim S, Wang M, Froines J, Sioutas C, Nel A. 2002. Use of a stratified oxidative stress model to study the biological effects
of ambient concentrated and diesel exhaust particulate matter. Inhal Toxicol. 14(5):459-86.
Limke TL, Heidemann SF, Atchison WD. 2004. Disruption of intraneuronal divalent cation regulation by methylmercury: are
specific targets involved in altered neuronoal development and cytotoxicity in methylmercury poisoning? NeruroToxicology.
(25):741-60.
London E, Etzel RA. 2000. The environment as an etiologic factor in autism: A new direction for research. Environmental
Health Perspectives. (108)S3.
Mahaffey KR. 1999. Methylmercury: A new look at the risks. Public Health Reports. 114(5):402-13.
Mahaffey KR. 2004. Methylmercury: Epidemiology Update. Slide presentation given at the National Forum on Contaminants in
Fish. San Diego, CA. January 26, 2004. http://www.epa.gov/waterscience/fish/forum/2004/
presentations/monday/mahaffey.pdf Accessed November 29, 2004.
Makani S. 2002. Biochemical and molecular basis of thimerosal-induced apoptosis in T cells: a major role of mitochondrial
pathway. Genes and Immunity 3(5)270-278.
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McAlonan GM, Cheung V, Cheung C, Suckling J, Lam GY, Tai KS, Yip L, Murphy DG, Chua SE. 2004. Mapping the brain in
autism. A voxel-based MRI study of volumetric differences and intercorrelations in autism. Brain. (0):3321.
McCormick MC. 2001. Opening Statement, Institute of Medicine News Conference on the Institute of Medicine Report on
Thimerosal and Neurodevelopmental Outcomes, October 2001. Available at:
http://www.cdc.gov/nip/news/iom-thim-stmt-10-1-01.htm
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Mahaffey KR. 2004. Hair mercury levels in U.S. children and women of childbearing age: reference range data from NHANES
1999-2000. Environ Health Perspect. 112(11):1165-7.
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Perry SW, Norman JP, Litzburg A, Gelbard HA. 2004. Antioxidants are required during the early critical period, but not later, for
neuronal survival. J Neurosci Res. 78(4):485-92.
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containing thiomersal: a descriptive study. Lancet. 360(9347):1737-41.
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109(10):1011-7.
MORE SCIENCE.........
SCIENTIFIC STUDIES FROM WWW.RECENTMEDICALFINDINGS.COM
- autism / GLUTATHIONE levels in brain = 12 studies, latest ones from 2011
- low levels of GLUTATHIONE connected to brain development - 1 study
Seth CS, Remans T, Keunen E, Jozefczak M, Gielen H, Opdenakker K, Weyens N, Vangronsveld J, Cuypers A:
Phytoextraction of toxic metals: a central role for GLUTATHIONE. Plant Cell Environ; 2012 Feb;35(2):334-46
■[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
■[Title] Phytoextraction of toxic metals: a central role for GLUTATHIONE.
■ Special attention is paid to the central role of GLUTATHIONE (GSH) in this process.
■ Because of the high affinity of metals to thiols and as a precursor for phytochelatins (PCs), GSH is an
essential metal chelator.
■ Being an important antioxidant, a direct link between metal detoxification and the oxidative challenge in
plants growing on contaminated soils is observed, where GSH could be a key player.
■ In addition, as redox couple, oxidized and reduced GSH transmits specific information, in this way tuning
cellular signalling pathways under environmental stress conditions.
- autism / glutathione 1 out of about 72 publishings
- 80% Adams JB, Baral M, Geis E, Mitchell J, Ingram J, Hensley A, Zappia I, Newmark S, Gehn E, Rubin RA,
Mitchell K, Bradstreet J, El-Dahr JM: The severity of autism is associated with toxic metal body burden and red
blood cell glutathione levels. J Toxicol; 2009;2009:532640
■[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
■[Title] The severity of autism is associated with toxic metal body burden and red blood cell glutathione levels.
■This study investigated the relationship of children's autism symptoms with their toxic metal body burden and
red blood cell (RBC) glutathione levels.
■ In children ages 3-8 years, the severity of autism was assessed using four tools: ADOS, PDD-BI, ATEC, and
SAS.
■ Multiple positive correlations were found between the severity of autism and the urinary excretion of toxic
metals.
■ Variations in the severity of autism measurements could be explained, in part, by regression analyses of
urinary excretion of toxic metals before and after DMSA and the level of RBC glutathione (adjusted R(2) of 0.22-
0.45, P < .005 in all cases).
■ This study demonstrates a significant positive association between the severity of autism and the relative
body burden of toxic metals.
one more study in this section......
69% Vojdani A, Mumper E, Granpeesheh D, Mielke L, Traver D, Bock K, Hirani K, Neubrander J, Woeller KN,
O'Hara N, Usman A, Schneider C, Hebroni F, Berookhim J, McCandless J: Low natural killer cell cytotoxic
activity in autism: the role of glutathione, IL-2 and IL-15. J Neuroimmunol; 2008 Dec 15;205(1-2):148-54
■[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
■[Title] Low natural killer cell cytotoxic activity in autism: the role of glutathione, IL-2 and IL-15.
■Although many articles have reported immune abnormalities in autism, NK cell activity has only been
examined in one study of 31 patients, of whom 12 were found to have reduced NK activity.
■ For this reason, we explored the measurement of NK cell activity in 1027 blood samples from autistic children
obtained from ten clinics and compared the results to 113 healthy controls.
■ This counting of NK cells and the measurement of their lytic activity enabled us to express the NK cell
activity/100 cells.
■ Overall, after this correction factor, 45% of the children with autism still exhibited low NK cell activity,
correlating with the intracellular level of glutathione.
■ Finally, we cultured lymphocytes of patients with low or high NK cell activity/cell with or without glutathione,
IL-2 and IL-15.
■ The induction of NK cell activity by IL-2, IL-15 and glutathione was more pronounced in a subgroup with very
low NK cell activity.
■ We conclude that that 45% of a subgroup of children with autism suffers from low NK cell activity, and that
low intracellular levels of glutathione, IL-2 and IL-15 may be responsible.
■[MeSH-major] Autistic Disorder / immunology. Cytotoxicity, Immunologic / physiology. Glutathione /
physiology. Interleukin-15 / physiology. Interleukin-2 / physiology. Killer Cells, Natural / immunology
■[MeSH-minor] Adolescent. Analysis of Variance. Case-Control Studies. Cell Count. Child. Child, Preschool.
Female. Humans. Male
You can further explore science publishings on www.recentmedicalfindings.com - useing the bottom search
engine is best.
Hope this gives you more insight into the importance of GSH replenishing in the body on the AS.
SHORT VERSION INFORMATION.......
IMPORTANT TO UNDERSTAND.........
Understanding autism spectrum disorders
- Autism is not a single disorder, but a spectrum of closely-related disorders with a shared core of symptoms.
- Every individual on the autistm spectrum has problems to some degree with social skills, empathy,
communication, and flexible behavior.
- But the level of disability and the combination of symptoms varies tremendously from person to person. In
fact, two kids with the same diagnosis may look very different when it comes to their behaviors and abilities.
- If you’re a parent dealing with a child on the autism spectrum, you may hear many different terms including
high-functioning autism, atypical autism, autism spectrum disorder, and pervasive developmental disorder.
These terms can be confusing, not only because there are so many, but because doctors, therapists, and other
parents may use them in dissimilar ways.
- But no matter what doctors, teachers, and other specialists call the autism
spectrum disorder, it’s your child’s unique needs that are truly important. No
diagnostic label can tell you exactly what problems your child will have. Finding
treatment that addresses your child’s needs, rather than focusing on what to call the
problem, is the most helpful thing you can do. You don’t need a diagnosis to start
getting help for your child’s symptoms.
I hope the information that you gain from this page will show you just how important
getting to the "true health root" of your loved one is. This information is pure
science, benefits are seen in most bodies, one must remember that
TTT Things Take Time
each body is unique in how quickly it will respond to the ability of replenishing its
GLUTATHIONE. Some might see benefits in first couple of wks however some
might see benefits within 3 mths. One thing - once you read this information you
will realize that your loved one is lacking sadly in GLUTATHIONE and once it is
replenished
THE SKY can be the limit for recovery and normalcy.
Short version information:
- AUTISTIC SPECTRUM bodies have dysfunction in the BRAIN, DIGESTIVE SYSTEM AND IMMUNE SYSTEM
- GLUTATHIONE is a natural molecule we are born with, with adequate we live healthy lives / with inadequate
we become sick
- Jobs of GLUTATHIONE ( GSH ) : MASTER ANTIOXIDANT
IMMUNE SYSTEM BALANCE ANS STRENGTHEN
DETOXIFICATION in organs and total body
- Science has proven that the brain of the person on the AS is deficit in GLUTATHIONE / replenishing the GSH in
the body allows for improved Detoxification of the Brain from pollution ( heavy metals etc )
- adequate GSH is absolutely necessary for an intact high functioning Digestive system, giving the body the
ability to replenish GSH builds a strong high functioning INTACT Digestive system
- adequate GSH is required in the body to maintain a strong and balanced Immune System able to ward off
virus / bacteria, giving the body the ability to replenish GSH gives the Immune System the ability to function to
its optimum.
- the body must make its own GSH in order to have it utilized to the optimum
- science states that in order for the body to replenish its own GSH it requires Cysteine
- Cysteine is extremely fragile, heat sensitive, stomach acid sensitive; in order for the body to be given
Cysteine you must give it in the Whey of natural milk, this whey must not be heated in any way or the
Cysteine is disturbed and is not absorbed to allow for GSH replenishing
- in order to attain a natural whey you must consume a PRIMARY WHEY PRODUCT, the Primary Whey product
undergoes no heating allowing for the total benefits the cow puts in her milk to help our bodies
- GSH-IMMUNITY is a Primary Whey Product, it allows for the Cysteine and Immune system components to be
absorbed into the small intestine for replenishing of GSH + other natural Immune System components such as
Lactoferrin and Immunoglobulins.
You may contact me directly - Peggy Maki 250 - 422 - 3163 MTN time or via email :
peggymaki@hotmail.com to discuss GSH and your loved one,
if you require specific scientific information please read on!!!!!
I do have clients on the AS doing well, I do not place testimonials on my site, I need to make sure that the
science of GSH is understood then it is a decision that is made with knowledge that this will aid the body with
no question.
IMPORTANT TO UNDERSTAND.........
Understanding autism spectrum disorders
- Autism is not a single disorder, but a spectrum of closely-related disorders with a shared core of symptoms.
- Every individual on the autistm spectrum has problems to some degree with social skills, empathy,
communication, and flexible behavior.
- But the level of disability and the combination of symptoms varies tremendously from person to person. In
fact, two kids with the same diagnosis may look very different when it comes to their behaviors and abilities.
- If you’re a parent dealing with a child on the autism spectrum, you may hear many different terms including
high-functioning autism, atypical autism, autism spectrum disorder, and pervasive developmental disorder.
These terms can be confusing, not only because there are so many, but because doctors, therapists, and other
parents may use them in dissimilar ways.
- But no matter what doctors, teachers, and other specialists call the autism
spectrum disorder, it’s your child’s unique needs that are truly important. No
diagnostic label can tell you exactly what problems your child will have. Finding
treatment that addresses your child’s needs, rather than focusing on what to call the
problem, is the most helpful thing you can do. You don’t need a diagnosis to start
getting help for your child’s symptoms.
I hope the information that you gain from this page will show you just how important
getting to the "true health root" of your loved one is. This information is pure
science, benefits are seen in most bodies, one must remember that
TTT Things Take Time
each body is unique in how quickly it will respond to the ability of replenishing its
GLUTATHIONE. Some might see benefits in first couple of wks however some
might see benefits within 3 mths. One thing - once you read this information you
will realize that your loved one is lacking sadly in GLUTATHIONE and once it is
replenished
THE SKY can be the limit for recovery and normalcy.
Short version information:
- AUTISTIC SPECTRUM bodies have dysfunction in the BRAIN, DIGESTIVE SYSTEM AND IMMUNE SYSTEM
- GLUTATHIONE is a natural molecule we are born with, with adequate we live healthy lives / with inadequate
we become sick
- Jobs of GLUTATHIONE ( GSH ) : MASTER ANTIOXIDANT
IMMUNE SYSTEM BALANCE ANS STRENGTHEN
DETOXIFICATION in organs and total body
- Science has proven that the brain of the person on the AS is deficit in GLUTATHIONE / replenishing the GSH in
the body allows for improved Detoxification of the Brain from pollution ( heavy metals etc )
- adequate GSH is absolutely necessary for an intact high functioning Digestive system, giving the body the
ability to replenish GSH builds a strong high functioning INTACT Digestive system
- adequate GSH is required in the body to maintain a strong and balanced Immune System able to ward off
virus / bacteria, giving the body the ability to replenish GSH gives the Immune System the ability to function to
its optimum.
- the body must make its own GSH in order to have it utilized to the optimum
- science states that in order for the body to replenish its own GSH it requires Cysteine
- Cysteine is extremely fragile, heat sensitive, stomach acid sensitive; in order for the body to be given
Cysteine you must give it in the Whey of natural milk, this whey must not be heated in any way or the
Cysteine is disturbed and is not absorbed to allow for GSH replenishing
- in order to attain a natural whey you must consume a PRIMARY WHEY PRODUCT, the Primary Whey product
undergoes no heating allowing for the total benefits the cow puts in her milk to help our bodies
- GSH-IMMUNITY is a Primary Whey Product, it allows for the Cysteine and Immune system components to be
absorbed into the small intestine for replenishing of GSH + other natural Immune System components such as
Lactoferrin and Immunoglobulins.
You may contact me directly - Peggy Maki 250 - 422 - 3163 MTN time or via email :
peggymaki@hotmail.com to discuss GSH and your loved one,
if you require specific scientific information please read on!!!!!
I do have clients on the AS doing well, I do not place testimonials on my site, I need to make sure that the
science of GSH is understood then it is a decision that is made with knowledge that this will aid the body with
no question.
FURTHER SCIENTIFIC INFORMATION FOR YOUR KNOWLEDGE
