Susceptibility
factors in mercury toxicity: immune reactivity, detoxification system function,
enzymatic blockages, synergistic exposures. B. Windham(Ed.)
It
is well documented in the medical literature that the major factors in mercury
toxicity effects, in addition to dose, are
susceptibility factors like immune reactivity(1,2), degree of other
toxic exposures and synergisms(3,15,27), systemic detoxification ability based on
blood allele type(4,15,27) or metallothionein function(5), sulfur
detoxification deficiencies(6), or other inhibited enzymatic processes related
to detoxification (7-10,27) or methylation (27,28). It has been shown that such
susceptibility factors can play a larger role in effects than dose among a
population with significant exposure to mercury and at extremely low levels of
exposure.
Inherited
defects or differences in the body’s ability to detoxify can contribute to
heavy metal accumulation (27,4,11,15,etc.). Deficiencies of certain minerals, vitamins, and amino acids reduce
the body’s ability to excrete toxins following exposure (27). Those
with the genetic allele ApoE4 protein in the blood have been found to detoxify
metals poorly and to be much more genetically susceptible to chronic
neurological conditions than those with types ApoE2 or E3(4,11,15). Researchers have shown that genetic
carriers of the brain protein APO E2 are protected against Alzheimer's disease
(AD) whereas genetic carriers of the APO E4 genotype are at enhanced risk
factor for developing AD and other degenerative neurological conditions. APO E
proteins are synthesized in the brain with the assigned physiological task of
carrying waste material from the brain to the cerebrospinal fluid, across the
blood brain barrier into the plasma where the material is cleared by the liver.
The biochemical difference between APO E2 and APO E4 is that APO E2 has two
additional thiol groups, capable of binding and removing mercury (and ethyl
mercury) that APO E4 does not have. The second highest concentration of APO E
proteins is in the cerebrospinal fluid. Therefore, the protective effects of
APO E2 is due to its ability to protect the brain from exposure to oxidants
like mercury and ethyl mercury by binding these toxicants in the cerebrospinal
fluid and keeping them from entering the brain.
Another study found that polymorphisms
in glutamyl-cysteine ligase and glutathione S-tranferases genes modify mercury
retention in humans exposed to elemental mercury vapor. Genotypes with
decreased GSH availability for mercury conjugation affect the metabolism of
inorganic mercury, increasing mercury retention (26).
Recent studies found that prenatal
mercury exposures from mother’s amalgams and other sources along with
susceptibility factors such as ability to excrete mercury appear to be major
factors in those with chronic neurological conditions like autism and ADHD(11,15,20,27).
Infants whose mothers received prenatal Rho D immunoglobulin injections
containing mercury thimerosal for RH factor or whose mother’s had high levels
of amalgam fillings had a much higher incidence of autism. While the hair test levels of mercury of
infants without chronic health conditions like autism were positively
correlated with the number of the mother’s amalgam fillings, vaccination
thimerosal exposure, and mercury from fish, the hair test levels of those with
chronic neurological conditions such as autism were much lower than the levels of
controls and those with the most severe effects had the lowest hair test
levels, even though they had high body mercury levels. This is consistent with past experience of
those treating children with autism and other chronic neurological conditions(12). Exposure to toxics such as mercury
have been found to inhibit enzymes needed to digest wheat gluten and milk
casein, resulting in symptoms of autism,
ADHD, diabetes, etc. after chronic exposure to gluten or casein. These
conditions commonly significantly improve after avoidance of gluten and
casein. Some cases of hypothyroidism are driven by immune
reactions to gluten in celiac disease (27) Genetic or toxic exposure related impairments
in methylation function ,
detoxification, clearance
of catecholamines, or in the clearance of adrenalin may contribute to symptoms
in autism or ADD/ADHD for those subjected to stress or inadequate nutrition to
overcome impairments(27). Prenatal and neonatal toxic exposures also can cause
leaky gut in infants; ‘Leaky gut’ in autism can promote toxic burden in the body, as well
as the development of food allergies(27) which have been found to often be factors in autism symptoms.
Studies have documented that
prenatal mercury exposure causes lasting effects that causes increased
susceptibility to future toxic exposures. The effects of chronic, low-dose
fetal and lactational organic (MeHgCl) and inorganic (HgCl2) mercury
intoxication on epilepsy/seizures
were investigated and compared in rats and were found to have significant
correlations between seizure susceptibility and cortical mercury level(16) Inorganic mercury exposure facilitated the
duration of seizure discharges in younger animals and appeared to be more
permanent than methyl mercury exposure.
Another researcher had similar findings for infants(17).
A
study of children of mothers consuming a marine diet which exposes them to
mercury, found that there are significant cardiovascular effects as birth
mercury blood level increases from 1 microgram per liter to 10 ug/L(a), as well as effects on ability to respond to sensory
stimuli in exposed children later in life(18). Children with lower birth
weights experienced blood pressure increases about 50% higher than normal birth
weight children having similar mercury levels. At seven years of age, clear dose-response
relationships were observed for deficits in attention, language, and memory(b). Thus a levels of
exposure below current Government health safety limits, mercury is documented
to have significant cardiovascular effects and the recommended limit for
mercury has been decreased from the former limit of 10 ug/L in blood.
Large
studies of U.S. dentists and dental assistants have found that mercury level in
urine is significantly associated with neurological dysfunction using several
different measures, but that among a population with low level mercury exposure
those with a polymorphism in blood heme
(CPOX4) or to a polymorphism in neurofactor (BDNF) or to a functional
single nucleotide polymorphism (Val158Met) in the gene encoding the
catecholamine catabolic enzyme catechol O-methyltransferase
(COMT) were more susceptible to neurological effects or deficits(19). An
association in a population with low level mercury exposure between such
polymorphisms and mood disorders was found only for female dental assistants. The associations between a
polymorphism of the serotonin transporter gene (5-HTTLPR), dental mercury
exposure, and self-reported symptoms were evaluated among 157 male dentists and
84 female dental assistants. The
findings suggest that within this restricted population of mercury exposed
workers, increased symptoms of depression, anxiety, and memory are associated
with the 5-HTTLPR polymorphism among both males and females(19d).
Inherited impairments in methylation or toxic
related inhibition of functional methylation by toxics such as mercury can have
a dramatic effect on mood regulation and depression (27,28).
Genetic related or toxic exposure
related hormone imbalances
are documented to make people more susceptible to depression and anxiety disorders(27)
. Many patients with depression suffer from thyroid hormone imbalances that may
make them more treatment-resistant, or imbalances of DHEA or cortisol(27),
which can be related to genetic susceptibility or toxic exposures to toxics such as
mercury. Thyroid imbalances can
strain the adrenal glands; or adrenal imbalances can also disrupt normal
thyroid function; either making an individual more susceptible to depression or anxiety disorders(27).
Malabsorption
in genetically or toxic related celiac
disease can interfere with mood regulating neurotransmitters and nutrients
such as vitamin B12(27).
Inherited
defects in detoxification of environmental chemicals (as previously documented)
may promote toxicity and fatigue in
CFS, and inherited tendencies toward inflammation and methylation defects
can exacerbate the chronic pain of fibromyalgia(27). Exposures
to heavy metal toxins can impair energy production and further burden the
detoxification system. Stress can over
time cause hormonal imbalances and deficiencies and leaky gut and malabsorption
of essential nutrients either genetic or related to toxic exposures can result
in inability to detoxify harmful substances and waste products(27),
enabling chronic conditions.
Chronic exposure
to toxic substances such as mercury can facilitate overgrowths of pathogenic
bacteria, viruses, and yeast(27), leading to chronic
conditions. Thyroid imbalances related
to genetic susceptibility or toxic exposures can strain the adrenal glands; or adrenal
imbalances in similar regards can disrupt normal thyroid function(27).
Genetic
factors or toxic exposures that weaken the immune system can
result in increased
susceptibility to allergies and biological pathogens.
Inherited impairments in detoxification
function can also interact with environmental factors to promote multiple
chemical sensitivity(MCS) (27). Defects in the body’s
ability to neutralize environmental chemicals lead directly to the accumulation
of toxins, and the body’s ability to neutralize and excrete environmental
toxins depends on the availability of key nutrients(27).
Some cases of MCS may be secondary to ‘leaky
gut’ and the passage of toxins or food particles into the system. Arthritis
is an inflammatory condition also often secondary to ‘leaky gut’,which can be caused by toxic exposures, and to the related
passage of toxins or undigested food particles into the system(27). Individuals
with asthma often have an inherited predisposition to produce excessive
inflammatory mediators(27) or increased inflammatory cytokines
related to either prenatal or
later toxic exposures to toxics such as mercury.
Inherited defects in methylation or control of inflammation in the
body or similar toxic related
effects can influence the course of heart disease(27)
Inherited
risks associated with cardiovascular disease, obesity, or estrogen metabolism
may exacerbate Metabolic Syndrome, for which toxic exposures are also significant
factors. Metabolic Syndrome increases cardiovascular risk by
promoting hyperlipidemia, clot formation, inflammation, and hypertension.
Imbalances or deficiencies in key nutrients can exacerbate metabolic imbalances
in Metabolic Syndrome and prevent healing(27). High insulin
levels in Metabolic Syndrome contribute to oxidative stress by unstable free
radicals in the body(27). As men age, declining
testosterone may trigger metabolic imbalances that promote insulin resistance
with significant differences depending on genetic factors and cumulative toxic exposures.
Programmed cell death (apoptosis) is documented to
be a major factor in degenerative neurological conditions like ALS,
Alzheimer’s, MS, Parkinson’s, etc. Some
of the factors documented to be involved in apoptosis of neurons and immune cells
include mitochondrial membrane dysfunction (22bc, 24).
Mitochondrial DNA mutations or dysfunction is fairly common, found in at
least 1 in every 200 people(23), and toxicity effects
affect this population more than those with less susceptibility to
mitochondrial dysfunction. Mercury
depletion of GSH and damage to cellular mitochrondria and the increased lipid
peroxidation in protein and DNA oxidation in the brain appear to be a major
factor in conditions such as autism, Parkinson’s disease, etc. (21-25).
The mechanisms by which low level
chronic mercury exposure causes over 30
chronic health conditions such as those looked at in this review are well
documented in the literature and differences in susceptibilities are documented
in all of these; and the fact that those treated for mercury toxicity usually recover after treatment
is also well documented by many dozens of medical studies in the literature and
thousands of clinical cases(13). Some
of the autoimmune conditions commonly
caused by immune reactivity to mercury include chronic fatigue syndrome(CFS), fibromyalgia, lupus, rheumatoid
arthritis, Parkinson’s,
multiple sclerosis (MS), amyotropic lateral sclerosis(ALS), depression, autism, ADHD, eczema, asthma, etc.
(14,1,2,hyperlinks). People are
documented to vary significantly in immune reactivity to toxic substances and
susceptibility to these conditions(see hyperlinks).
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note: underlined or
shaded statements have hyperlinks to additional documentation that can be
reached by clicking on the link.