by Bernard Windham

I. Mechanisms of Developmental Damage by Toxic Metals.

The human brain forms and develops over a long period of time compared to other
organs, with neuron proliferation and migration continuing in the postnatal period. The
blood-brain barrier is not fully developed until the middle of the first year of life.
Similarly there is postnatal activity in the development of neuronal receptors and
transmitter systems, as well as in the production of myelin. The fetus has been found to
get significant exposure to toxic substances through maternal blood and across the
placenta, with fetal levels of toxic metals often being higher than that of maternal
blood(30-32,41-43). Likewise infants have been found to get significant exposure to
toxics, such as mercury that their mother is exposed to, through breast-feeding(26,43).

Studies have found that heavy metals such as mercury, cadmium, lead, and tin affect
chemical synaptic transmission in the brain and the peripheral and central nervous
system(
24a,37-40,43,57). They also have been found to disrupt brain and cellular calcium
levels that significantly affect many body functions: such as (a) calcium levels in the
brain affecting cognitive development and degenerative CNS diseases(5,28,43,74) (b)
calcium-dependent neurotransmitter release which results in depressed levels of
serotonin, norepinephrine, and acetylcholine(5,28,44-47,43) – related to mood and
motivation; (c)cellular calcium-sodium ATP pump processes affecting cellular nutrition
and energy production processes(5,28,43); (d) calcium levels in bones causing skeletal
osteodystery(5,74). Toxic metals have also been found to affect cellular transfer and
levels of other important minerals and nutrients that have significant neurological and
health effects such as magnesium, lithium, zinc, iron, Vitamins B-6 & B1-12
(5,27,43,46,75). Based on thousands of hair tests, at least 20 % of Americans are
deficient in magnesium and lithium(5,68,76), with zinc deficiencies also common. The
resulting deficiency of such essential nutrients has been shown to increase toxic metal
neurological damage(5,43,74,75).

Lithium protects brain cells against excess glutamate and calcium, and low levels cause
abnormal brain cell balance and neurological disturbances (75). Lithium also is important
in Vit-B12 transport and distribution, and studies have found low lithium levels common
in learning disabled children, incarcerated violent criminals, and people with heart
disease(76).

In one study a group including violent offenders and family abusers were divided into 2
groups. Half got lithium supplements and half a placebo. The group getting lithium had
significantly increased scores for mood, happiness, friendliness, and energy, while the
other group did not(77). In a large Texas study, incidence of suicide, homicide, rape,
robbery, burglary, theft, and drug use were significantly higher in counties with low
lithium levels in drinking water(78). In a placebo controlled study on prisoners with a
history of impulsive/aggressive behavior, the group taking lithium supplements had a
significant reduction in aggressive behavior and infractions involving violence(79). The
authors suggest that for those areas with low lithium levels in water, water systems
should add lithium; and those with deficiencies in lithium or displaying aggressive or
impulsive behavior would likely benefit from lithium supplements(78,79).

Studies have also found heavy metals to deplete glutathione and protein-bound sulfhydryl
SH groups, resulting in inhibiting SH-containing enzymes and production of reactive
oxygen species such as superoxide ion, hydrogen peroxide, and hydroxyl
radical(39,43,45-47). This has been found to be a major factor in neurological and
immune damage caused by the heavy metals, including damage to mitochondria and
DNA(37-40,43) , as well as chronic autoimmune conditions and diseases(29). High lead
levels have been found to be associated with Attention deficit hyperactivity
disorder(ADHD), impulsivity, and inability to inhibit inappropriate responding(20a).
High aluminum levels have been found to be related to encephalopathies and
dementia(49). Some individuals have been found to be more sensitive to toxic metals
depending on genetic sensitivity and past exposure to toxic substances(28,29). Nickel
exposure is common and nickel exposure has been found to be significantly related to
perinatal unthriftiness and mortality in animal studies and large numbers of people
affected by allergic conditions such as eczema and psoriasis vulgaris(59) and serious
autoimmune conditions such as lupus and CFS(28).

Other agents including mercury are known to accumulate in endocrine system organs
such as the pituitary gland, thyroid, and hypothallamous and to alter hormone levels and
endocrine system development during crucial periods of development(33,37,43,27). Such
effects are usually permanent and affect the individual throughout their life. Some of the
documented effects of exposure to toxic metals include significant learning and
behavioral disabilities, mental retardation, autism, etc. But even some of the relatively
subtle effects that have been found to occur such as small decreases in IQ, attention span,
and connections to delinquency and violence, if they occur in relatively large numbers
over a lifetime can have potentially serious consequences for individuals as well as for
society(26,37,41,42). The incidence of neurological conditions in children such as autism
has increased over 200% in the last decade(80), and mercury has been found to be a
factor in most of those tested(81).

II. Extent of Exposure of Children to Toxic Metals

The U.S. Center for Disease Control ranks toxic metals as the number one environmental
health threat to children, adversely affecting large numbers of children in the U.S. each
year and thousands in Florida(1-4). According to an EPA/ATSDR assessment, the toxic
metals lead, mercury, and arsenic are the top 3 toxics having the most adverse health
effects on the public based on toxicity and current exposure levels in the U.S.(1), with
cadmium, chromium and nickel also highly listed. Large numbers of people have been
found to have allergic conditions and immune reactive autoimmune conditions due to the
toxic metals, especially inorganic mercury and nickel(28,29).

The heavy metals(lead,mercury,cadmium,nickel) tend to concentrate in the air and in the
food chain along with other toxic metals like arsenic and aluminum, facilitating metal
poisoning which is the most widespread environmental disorder in the U.S. Mercury and
cadmium from combustion emissions are also accumulating in coastal estuaries and
inland water body sediments, and are widespread in shellfish and other organisms (34-
36). Mercury and cadmium are extremely toxic at very low levels and have serious
impacts on the organisms in water bodies that accumulate them(34,2). These heavy
metals have also been found to be endocrine system disrupting chemicals and have been
found to be having effects on the endocrine and reproductive systems of fish, animals,
and people similar to the organochlorine chemicals (33,43). Estrogenic chemicals like
mercury have been found in Florida wildlife at levels that feminized males to the extent
of not being able to reproduce, and also had adverse effects on the female reproductive
systems(33,36). Similar effects have also been documented in humans (33,37,43).

III. Developmental Effects of Toxic Metals on Cognitive Ability and Behavior.

According to studies reviewed, over 20% of the children in the U.S. have had their health
or learning significantly adversely affected by toxic metals such as mercury, lead, and
cadmium; and over 50% of children in some urban areas have been adversely affected.
Significant behavioral effects were also documented. Such effects similarly affect
adults(43). Many epidemiologists believe the evidence demonstrates that over 50% of all
U.S. children have had their learning ability or mental state significantly adversely
affected by prenatal and/or postnatal exposure to toxics substances. The toxic metals have
been documented to be reproductive and developmental toxins, causing birth defects and
damaging fetal development, as well as neurological effects, developmental delays,
learning disabilities, depression, and behavioral abnormalities in many otherwise normalappearing
children(5-33,37-43).

Prenatal exposure to 7 heavy metals was measured in a population of pregnant women at
approximately 17 weeks gestation(9). Follow-up tests on the infants at 3 years of age
found that the combined prenatal toxic exposure score was negatively related to
performance on the McCarthy Scales of Children’s Abilities and positively related to the
number of childhood illnesses reported. Many similar studies measuring child hair levels
of the toxic metals aluminum, arsenic, cadmium, lead, and mercury have found that these
toxic metals have significant effects on learning ability and cognitive performance,
explaining as much as 20 % of cognitive differences among randomly tested children
who have low levels of exposure not exceeding health guidelines for exposure to any of
these metals(8,9,12,13,17). These toxic metals have been found to have synergistic
negative effects on childhood development and cognitive ability(8,13-15,19.).

Among those more significantly affected by neurological deficits or problems, the affects
appear even more significant. Comparison of groups of children who are mentally
retarded or significantly learning disabled to normal controls found significantly higher
levels of toxic metals in the affected groups(7,11,17,18,21), with the level of the toxic
metals and minerals known to be affected by them correctly identifying those with
significant disabilities in from 90 to 98% of cases in the studies. A study of rural children
with subtoxic exposure levels found significantly higher levels of lead and cadmium in a
group of mildly retarded/borderline intelligence(IQ 55-84) than controls(11). 76% of the
study group had one of 5 toxic metals exceeding the lab’s upper safety limit. A large
study found that hair cadmium level is highly correlated with and predictive of very
significant learning disability or mental retardation(18). Over 90 % of those with hair
cadmium levels of 0.4 parts per million or more were found to have significant
disabilities and over 95% of those with levels above 0.7 were mentally retarded. In a
group of students with normal range IQS who failed one subject area on a standardized
test (paradiagatic LD), the groups cadmium and lead hair levels were significantly higher
than controls; and hair metal levels with lithium levels included correctly separated the
groups with 95% accuracy(7). Average hair cadmium levels in the group with learning
disabilities was 1.7 ppm. Similar findings regarding toxic metal exposure levels were
found for dyslexic children(10) and autistic children(16). A study of dyslexic children
with normal IQS found the dyslexic group had a cadmium hair level average of 2.6 ppm,
25 times that of the control group(10) and exceeding the maximum of the normal
acceptable range. The dyslexic group also had somewhat higher aluminum and copper
levels. Studies of groups with schizophrenia have found increased levels of copper and
mercury and reduced levels of zinc, magnesium and calcium, which are known to be
inhibited by heavy metals and affect neurotransmitter levels(48,49).

These toxic metals have also been found similarly to have significant behavioral and
emotional effects on children and adults(6-8,11,14-16,43). One group of students were
scored by their classroom teacher on the Walker Problem Behavior Identification
Checklist(WPBIC). A combined hair level score for mercury, lead, arsenic, cadmium and
aluminum was found to be significantly related to increased scores on the WPBIC
subscales measuring acting-out, disturbed peer relations, immaturity, and the total
score(6) among a population of students with no known acute exposures. The combined
metals score explained 23 % of the difference of the total WPBIC score, and 16 to 29%
of the differences on the subscales for withdrawal, acting out, disturbed peer relations,
distractibility, and immaturity(6). Similar results were found in the other studies, and
have been found to have implications not only in the classroom but on relations at home,
on driving habits, and on job performance. Studies have found evidence that abnormal
metal and trace elements affected by metal exposure appear to be a factor associated with
aggressive or violent behavior(37,60-62), and that hair trace metal analyses may be a
useful tool for identifying those prone to such behavior. Similar tests in the California
juvenile justice system have found significant relations to classroom achievement,
juvenile delinquency, and criminality. Three studies in the California prison system found
those in prison for violent activity had significantly higher levels of hair manganese than
controls(61,37). Like several other studies they found higher levels of such toxic metals
in blacks than in Caucasian populations. Studies of an area in Australia with much higher
levels of violence as well as autopsies of several mass murderers also found high levels
of manganese to be a common factor(37). Such violent behavior has long been known in
those with high manganese exposure.

Studies have previously found that low levels of lead exposure is significantly related to
hyperactivity and attention deficit(20a), school cognitive performance(20a,23,50,60a),
behavioral problems(21,22), mental disorders(24), allergies(60), growth(54), gestational
age(54), and spontaneous abortions(60). In one study children’s umbilical cord blood at
birth was recorded and a teacher assessment of learning/behavioral characteristics
completed at the end of the school year at age 8 (20a). Girls with higher than average(>
10 ug/dL) chord blood level were found to be more likely to be dependent, inpersistant,
and have an inflexible approach to tasks. (10 ug/dL blood approx. 8 ppm hair, #52) Boys
with higher than average chord blood level were found to be more likely to have
problems following simple directions or sequences of directions. A follow up study to the
Cincinnati lead study measured blood lead levels and compared to standardized IQ test
scores at approximately 6.5 years of age(50). The study found blood lead levels were
significantly inversely related to both full-scale and performance IQ, and that blood lead
levels over 20 ug/dL were related to an average deficit in IQ of 7 points on performance
IQ as compared to those with below 10 ug/dL blood lead levels. Another study in
Australia measured IQ at approximately 12 years of age and compared to blood lead
levels measured from 1 to 7 years of age(51). Total , verbal, and performance IQ were all
significantly inversely related with blood lead levels measured during the first 7 years of
life. Two studies found average hair lead levels in groups of learning disabled children
over 20 ppm(7,12), compared to 4 ppm in controls.

However other studies have pointed out that these studies generally did not investigate or
consider the effects and synergistic interactions of the other toxic metals(6,11,20,28), and
the fact that lead and cadmium levels tend to have positive correlations with each other.
A study of rural school children without acute exposures and with IQS in the normal
range found highly significant relations between lead and cadmium with intelligence
scores and school achievement tests(12). Lead and cadmium explained 29 % of the variance
in IQ. These two metals have been found to have different mechanisms of CNS damage,
with cadmium affecting verbal ability more and lead affecting performance measures
more. The author of another study(28) of 9 year olds living in an area near an incinerator
in Ohio concluded that part of the developmental effects attributed to lead in many past
studies was mostly due to cadmium effects, with lead serving as a marker for cadmium
effects due to their common origins and cadmium’s effect of increasing lead
accumulation. The findings of this study were generally consistent with a previous
study(12) regarding higher levels of cadmium and lower levels of zinc in children with
cognitive deficits.

However this study found zinc level, though significantly affected, can be increased in
some depending on other factors. Cadmium as previously noted as well as mercury have
anti metabolite effects that significantly affect calcium, zinc, and phosphate levels in the
body(74,28,43). The reduction in zinc levels causes increased absorption of lead, and
cadmium’s affect on the pyrimdine-5-nucleotidase enzyme inhibits phosphorylation in
the energy/respiratory ATP function(28). This study found the level of hair phosphorous,
as affected by cadmium exposure, was the best indicator of cognitive function and
disfunction. Lead was found to have a lesser effect on phosphorous level and ATP
function. The entire group of learning disabled boys had low hair phosphorous levels
compared to those without learning disabilities. The main factors appearing to affect
those with high cadmium levels and low phosphorous hair levels were living within 2
miles of the incinerator, exposure to passive cigarette smoke, and living in a rural area
that may have had high cadmium levels in wells. Another study found heavy smokers
have cadmium levels in body tissues about 2 times that of non smokers, and hair
cadmium levels in newborns of smokers were twice as great as in newborns of non
smokers(53).

Other studies have found that cadmium causes significant decreases in birth weight
through its antimetabolite actions(53,54) and significant increases in blood pressure(55).
Newborn hair cadmium levels have been found to be significantly correlated to maternal
hair levels and mothers exposed occupationally to heavy metals to have hair levels twice
as high as controls(54). Likewise adults with higher than average cadmium levels
performed less well on measures of attention, Psychomotor speed, and memory(56).

These toxic metals have also been found to have significant effects on motor-visual
ability and performance(6a,8,20,43), as measured by the Bender Visual-Motor Gestalt
Test score. Arsenic, lead, and cadmium levels had the highest correlation with cognitive
scores, while aluminum had a significant relation mostly with motor-visual performance
and mercury had lesser but highly significant correlations to both.

Studies have also found evidence of a connection between low levels of zinc and two
other common childhood diseases, childhood-onset diabetes(72) and epilepsy(73). Zinc is
an antagonist to toxic metals like cadmium and mercury, and adequate levels are required
to balance the adverse effects of these toxic metals on cellular calcium and other
enzymatic processes(28,74)

It should be noted that both blood and hair mercury level have been found to not be
highly correlated to exposure from mercury vapor, which is the most common exposure
from mercury, because of special properties of mercury(43). Mercury vapor has an
extremely short half life in blood, and rapidly crosses cell membranes in body organs
where it is oxidized to inorganic mercury, accumulating in the brain, heart, kidneys, and
other locations. Thus although elemental mercury exposures are typically greater than
organic exposures, most mercury in the blood is organic. Likewise hair mercury has been
shown to be more highly correlated with organic mercury exposure than with
inorganic(43). Hair test are affected by external mercury exposure in occupational
exposures such as dental offices which typically have fairly high levels of mercury. Other
measures of mercury such as stool, saliva, and urine have been found to be better
measures of mercury for such cases. Urine contains mostly inorganic mercury, but
becomes less reliable with long term chronic exposure due to cumulative damage to the
urinary detox system. Urinary fractionated porphyrin test is a good test of metabolic
damage that has occurred due to mercury of other toxics. The level and distribution of the
6 porphyrins measured indicates extent of damage as well as likely source of damage(43).

Hair levels have been found to be generally reliable indicators of recent environmental
metal exposures other than mercury(28,52,54,58). Similarly, blood levels have been
found to not reflect chronic or historic cadmium exposure(52,53,58) since metals such as
cadmium and mercury have extremely short half life in the blood but long half life in the
body.. Air measurements of cadmium or mercury tend to be very unreliable due to the
small particle size, dispersion variation, and other factors. Measure of accumulation in
area plants is one reasonably reliable method; areas with cadmium levels over 0.5 ppm
indicate significant air pollution.

IV. Sources of exposure to Toxic Metals

The studies reviewed suggest that exposure to toxic metals may account for as many as
20% of learning disabilities, 20% of all strokes and heart attacks, and in some areas be a
factor in over 40% of all birth defects(43). The U.S. Center for Disease Control has found
that primary exposure to lead is from paint chips, drinking water, fertilizer, food, auto and
industrial emissions, and dust. High levels of cadmium are found in regions with high
emissions from incinerators, coal plants, or cars(28), as well as in shellfish(36) and
cigarette smoke(28). Other common sources include rural drinking water wells(28),
processed food, fertilizer, and old paint. Common exposures to aluminum include
aluminum cookware, antiperspirants, cheese and other processed food. Nickel, which is
highly toxic and commonly causes immune reactions, is commonly seen in dental crowns
and braces, along with jewelry, etc.(nickel and inorganic mercury commonly produce
allergic type autoimmune problems,29). Manganese and other metal exposure can come
through welding or metal work. Cadmium, mercury, arsenic, chromium, silver, copper,
and are other metals to which Floridians and others are commonly exposed in drinking
water, food, or dental materials (34-36).

The most common significant exposure for most people is to mercury vapor from
amalgam fillings(43). Most people with several amalgam fillings have daily exposure
exceeding the U.S. government health guideline for mercury(4,43). Likewise a major
exposure source of infants and young children is from placental transfer from their
mother’s amalgam fillings and breast feeding(43). Another major exposure source to
infants is from thimerosal used in vaccinations as a preservative. The majority of infants
get exposure above Government health guidelines for mercury and large numbers of
infants with related neurological problems such as autism and ADD have been
documented(81). A major source of phenyl mercury is from mercury in paint, where
many have been exposed to dangerous levels(82). The major source of exposure to
organic(methyl) mercury is from fish and shellfish, but inorganic mercury has also been
found to be methylated in the body by bacteria, yeast, etc.(43). Significant levels of
various forms of organic mercury have also been documented from dental work such as
root canals and gold crowns over amalgam base(43,29). Mercury vapor is the form that
most readily crosses cellular membranes including the blood-brain barrier and placenta of
pregnant women, and results in the highest levels in the major organs such as the brain,
heart, and kidneys for a given level of exposure. But the average half-life of vapor in the
blood is only 3 seconds so blood tests are not a good measure of such exposure. For
similar reasons hair mercury is a less accurate measure of body inorganic mercury burden
than for the other metals. Both mercury vapor and organic mercury have been found to be
highly toxic and to have independent and synergistic effects at very low levels(43).
However developmental effects have been found at comparable or lower levels from
mercury vapor than from organic or inorganic exposure(43), and it has been well
established that the primary exposure for most people and children is from mercury
vapor.

V. Measures to Reduce or Alleviate Toxic Metal Toxicity

The most important measure to alleviate effects of toxic metals is avoidance of exposure
or reducing current exposures. Current exposure levels of most common metals can be
tested by a stool test kit from a lab such as Doctors Data, and recent exposures can be
tested somewhat easier and cheaper by hair tests(see 66).

As noted previously, the majority of those with amalgam fillings have significant daily
exposures often exceeding government health standards for mercury. Daily inorganic
mercury exposure can be assessed by stool or saliva test or mouth oral air measurement,
but since many have been tested, several studies have developed analytical equations to
estimate daily exposure based on number of amalgam surfaces in the mouth, which give
reasonable estimates. The main way to reduce mercury exposure to elemental mercury is
to avoid amalgam fillings and/or replace amalgam fillings by other materials. Other
materials are available that perform as well as amalgam.

Seafood and fish have often been found to have high levels of organic mercury,
cadmium, and arsenic. For those eating significant amounts of such, the levels in the diet
can be monitored by direct food testing or stool test for current exposure levels, or by hair
or blood test.. Fish and seafood from areas known to contain high levels of toxic metals
should be eaten only occasionally if at all, depending on levels. Those who eat a lot of
freshwater fish or seafood often have levels of mercury or some other metal exceeding
government guidelines. Hair tests offer a reasonable reliable low cost method of
assessing the level of many toxic metals in one test. Aluminum exposures can be reduced
by avoiding aluminum antiperspirants, food cooked in aluminum cookware, and foods
such as processed cheese that have high levels of aluminum.

As previously noted one of the main mechanisms of toxic effects is generation of free
radicals and oxidative damage(66). This can be partially alleviated by eating foods high
in antioxidants or supplementation of Vit A, C, E, along with such as grapeseed extract,
pinebark extract, bilberry, etc. Bioflavinoids like bilberry and other fruits have been
found to improve the function of the blood brain barrier. Vit C provides prtection against
toxicity of inorganic mercury by reducing the more toxic Hg2+ form to the less toxic
Hg+ form of mercury. Vit B complex is also important to alleviate neurological effects.
Most toxic metals also have mineral antagonist known to counteract toxic effects.

For example selenium and zinc are antagonists of mercury, while zinc and iron are
antagonists of cadmium.(5,64,65,74). Iron and zinc deficiencies, which can be caused by
exposure to toxic metals, increase metal toxicities and supplementation can reduce
toxicities, but they can also be toxic if levels are too high. Likewise calcium and
magnesium deficiencies and imbalances have been seen to be caused by toxic metals, and
proper supplementation can reduce toxicities and reverse conditions caused by these
deficiencies or imbalances. Several studies have found that most children with ADHD
have deficiencies of certain minerals that are commonly depleted by exposure to toxic
metals, such as magnesium and zinc, and most show significant improvement after
supplementation with these minerals(67-71). Magnesium is the most common significant
mineral deficiency among ADHD children(67-69), but zinc is commonly deficient among
children with ADHD and disruptive behavior disorder(68). One study found the level of
free fatty acids also significantly lower in children with ADHD(70), and some
practitioners recommend supplementation of essential fatty acids as well in treatment of
ADHD.

Whey protein and N-acetylcysteine(NAC) can increase levels of glutathione which is
necessary for detoxification and is depleted by toxic metals as previously noted(66).
However care must also be exercised regarding proper level if these are supplemented,
starting with low levels. Chelation with chemical chelators such as DMSA and EDTA
can also greatly reduce metal body burden, but should only be considered for those with
serious toxicities and with advice of a knowledgeable physician. DMSA and EDTA are
mainly used for lead detoxification, but DMSA is also effective for mercury and other
toxic metals. Studies have found that use of EDTA by patients with high levels of
mercury can cause serious side effects, so EDTA should be used only when mercury
levels have been found to be low(43).

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