Amyotrophic Lateral Sclerosis(ALS): the Mercury
Connection
Bernie Windham(Ed.)
I. Introduction.
ALS
is a systemic motor neuron disease that affects the corticospinal and
corticobulbar tracts, ventral horn motor neurons, and motor cranial nerve
nuclei(405). Approximately 10 percent of ALS cases are of the familial type
that has been linked to a mutation of the copper/zinc super oxide dismustase
gene(Cu/Zn SOD). The majority of ALS cases
are of the sporadic type. Based on
studies of groups of monozygous twins, animal studies, and ALS patient case
studies, the majority of ALS cases do not appear to be genetic but rather have
primarily environmental related causes often affecting genetically susceptible
individuals (405,416,423,471,520,93,94,97,200,303,35,etc.). Some of the mechanisms of neural damage found
in ALS include increased free radical generation/oxidative damage, impaired
electron transport, disrupted calcium channel function, neurotoxicity,
oxidative damage to mitochondrial DNA/ inhibition of the mitochondrial
respiratory chain, and generalized disruption of metabolism of neuroexciotoxic
amino acids like glutamate, aspartate, NAAG.
The mechanisms by which exposure to mercury and other neurotoxic
substances cause all of this will be documented.
The
main factors determining whether chronic conditions are induced by metals
appear to be exposure and genetic susceptibility, which determines individuals
immune sensitivity and ability to detoxify metals(405,342,60,181,303,314,330,464). Very low levels of exposure have been found
to seriously affect relatively large groups of individuals who are immune
sensitive to toxic metals, or have an inability to detoxify metals due to
such as deficient sulfoxidation or metallothionein function or other
inhibited enzymatic processes related to detoxification or excretion of
metals. Those with the genetic allele
ApoE4 protein in the blood have been found to detox metals poorly and to be much
more susceptible to chronic neurological conditions than those with types ApoE2
or E3(437,577).
Some
of the toxic exposures which have been found to be a factor in ALS other than
mercury include lead(94a),
pyretherins(93), agricultural chemicals(94b), Lyme disease(471), failed
root canaled teeth(35,200,437), and smoking(94c). All have been demonstrated to cause some of the mechanisms of damage listed above
seen in ALS and since such exposures are common as is exposure to mercury, such
exposures appear to synergistically cause the types of damage seen in ALS. This paper will demonstrate that mercury is
the most common of toxic substances which are documented to accumulate through
chronic exposure in the neurons affected
by ALS and which have been documented to cause all of the conditions and
symptoms seen in ALS. It will also be
noted that chronic infections such as mycoplasma,echo-7 enterovirus, and
candida albicans also usually affect those with chronic immune deficiencies
such as ALS patients and need to be dealt with in treatment. Some studies have also found persons with
chronic exposure to electromagnetic fields(EMF) to have higher levels of
mercury exposure and excretion(28) and higher likelihood of getting chronic
conditions like ALS(526).
II. Documentation of High
Common Exposures and Accumulation of Mercury in Motor Neurons
Amalgam
fillings are the largest source of mercury in most people with daily exposures
documented to commonly be above government health guidelines(49,79,183,506,600).
This is due to continuous vaporization
of mercury from amalgam in the mouth, along with galvanic currents from mixed
metals in the mouth that deposit the mercury in the gums and oral cavity(600). Mercury has been found in autopsy studies
to accumulate in the brain of those with chronic exposures, and levels are
directly proportional to the number of amalgam filling surfaces(85,270). Due to the high daily mercury exposure and
excretion into home and business sewers of those with amalgam, dental amalgam
is also the largest source of the high levels of mercury found in all sewers
and sewer sludge, and thus according to government studies a significant source
of mercury in rivers, lakes, bays, fish, and crops(603). People also get significant exposure from
vaccinations, fish, and dental office vapor(600).
When
amalgam was placed into teeth of monkeys and rats, within one year mercury was
found to have accumulated in the brain, trigeminal ganglia, spinal ganglia,
kidneys, liver, lungs, hormone glands, and lymph glands(20). People also commonly get exposures to mercury and other toxic metals
such as lead, arsenic, nickel, and aluminum from food, water, and other
sources(601). All of these are highly
neurotoxic and are documented to cause
neurological damage which can result in chronic neurological conditions
over time.
Mercury has been found to accumulate
preferentially in the primary motor function related areas involved in ALS-
such as the brain stem, cerebellum, rhombencephalon, dorsal root ganglia, and
anterior horn motor neurons, which enervate the skeletal
muscles(20,291,327,329,442,48).
Mercury, with exposure
either to vapor or organic mercury tends to accumulate in the glial cells in a
similar pattern, and the pattern of deposition is the same as that seen from
morphological changes(327g,287,305).
Though mercury vapor and organic mercury readily cross the blood-brain
barrier, mercury has been found to be taken up into neurons of the brain and
CNS without having to cross the blood-brain barrier, since mercury has been
found to be taken up and transported along nerve axons as well through calcium
and sodium channels and along the olfactory path(329, 288,333,34). Exposure to inorganic mercury has significant
effects on blood parameters and liver function. Studies have found that in a
dose dependent manner, mercury exposure causes reductions in oxygen consumption
and availability, perfusion flow, biliary secretion, hepatic ATP
concentration, and cytochrome P450 liver
content(260), while increasing blood hemolysis products and tissue calcium
content and inducing heme oxygenase, porphyria, platelet aggregation through
interfering with the sodium pump.
III. Effects of Exposure to Mercury and Toxic
Metals
A direct mechanism involving mercury’s inhibition
of cellular enzymatic processes by binding with the hydroxyl radical(SH) in
amino acids appears to be a major part of the connection to allergic/immune
reactive/ conditions such as eczema, psoriasis, rheumatoid arthritis, Lupus,
Scleroderma, allergies, autism, schizophrenia, (114c,181,303,330,331,411,412,152b,
439,602,601), as well as to autoimmune conditions such as ALS, Alzheimer’s(AD), Chronic Fatigue(CFS), Fibromyalgia(FM), etc.(405,342,60,181,303,314b,513,etc.)
. For example mercury has been found to
strongly inhibit the activity of dipeptyl peptidase (DPP IV) which is required
in the digestion of the milk protein casein(411,412) as well as of xanthine
oxidase(439) Additional cellular level enzymatic effects of mercury’s
binding with proteins include blockage of sulfur oxidation processes
(33,114c,194,330,331,412), enzymatic processes involving vitamins B6(417) and
B12(418), effects on the cytochrome-C energy processes (43,84,232,338c,35),
along with mercury’s adverse effects on cellular mineral levels of calcium,
magnesium, copper, zinc, and lithium (43b,96,198,333,
338,386,427,430,432,461,489,507). And
along with these blockages of cellular enzymatic processes, mercury has been
found to cause additional neurological and immune system effects in many by
causing immune/ autoimmune reactions (60,152c,181,288c,314,342,405,513). A
recent study gives a comprehensive review of studies finding a connection
between ALS, toxic metals, and autoimmunity(405).
Oxidative stress and reactive oxygen
species(ROS) have been implicated as major factors in neurological disorders
including ALS, motor neuron disease(MND), CFS, FM, Parkinson’s(PD), Multiple
Sclerosis(MS), and Alzheimer’s(AD) (13,43,56,84,145,169,207b,424,442-444,453,
462,496,577). Mercury forms conjugates
with thiol compounds such as glutathione and cysteine and causes depletion of
glutathione(56), which is necessary to mitigate reactive damage. One study found that insertion of amalgam
fillings or nickel dental materials causes a suppression of the number of
T-lymphocytes(270), and impairs the T-4/T-8 ratio. Low T4/T8 ratio has been found to be a factor
in autoimmune conditions. Mercury induced lipid
peroxidation has been found to be a major factor in mercury’s
neurotoxicity, along with leading to decreased levels of glutathione
peroxidation and superoxide dismustase(SOD)(13,254,490,494-496). Only a few micrograms of mercury severely
disturb cellular function and inhibits nerve growth (305,147,175,226,255). Metalloprotein(MT) have a major role in
regulation of cellular copper and zinc metabolism, metals transport and
detoxification, free radical scavenging, and protection against inflammation
(114,442,464,602). Mercury inhibits
sulfur ligands in MT and in the case of intestinal cell membranes inactivates
MT that normally bind cuprous ions(477,114), thus allowing buildup of copper to
toxic levels in many and malfunction of the Zn/Cu SOD function (495,13a, 443).
Mercury also causes displacement of zinc in MT and SOD, which has been shown to
be a factor in neurotoxicity and neuronal diseases(405,495,517). Exposure to mercury results in changes in
metalloprotein compounds that have genetic effects, having both structural and
catalytic effects on gene expression(114,241,296,442,464,477,495,517). Some of the processes affected by such MT
control of genes include cellular respiration, metabolism, enzymatic processes,
metal-specific homeostasis, and adrenal stress response systems. Significant
physiological changes occur when metal ion concentrations exceed threshold
levels. Such MT formation also appears
to have a relation to autoimmune reactions in significant numbers of people
(114,60, 342,369, 442,464). Of a population of over 3000 tested by the immune
lymphocyte reactivity test(MELISA,60,342), 22% tested positive for inorganic
mercury and 8% for methyl mercury, but much higher percentages tested positive
among autoimmune condition patients. In
the MELISA laboratory, 12 out of 13 ALS patients tested showed positive immune
reactivity lymphocyte responses to metals in vitro [60c], indicating metals
reactivity a likely major factor in their condition. A recent study assessed the possible causes
of high ALS rates in Guam and similar areas and the recent decline in this
conditions. One of the studies conclusions was that a likely major factor for
the high ALS rates in Guam and similar areas in the past was chronic dietary
deficiency since birth in Ca, Mg and Zn induced excessive absorption of divalent
metal cations such as mercury which accelerates oxidant-mediated neuronal
degenerations in a genetically susceptible population(466).
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 inducement of the inflammatory cytokine Tumor Necrosis
Factor-alpha(TNFa) (126), reactive oxygen species and oxidative stress(13,43a,56a,296b,495),
reduced glutathione levels(56,126a,111a), liver enzyme effects and inhibition
of protein kinase C and cytochrome P450(43,84,260), nitric oxide and
peroxynitrite toxicity (43a,521,524), excitotoxicity and lipid
peroxidation(490,496), excess free cysteine levels (56d,111a,33,330),excess
glutamate toxicity(13b, 416), excess dopamine toxicity (56d,13a), beta-amyloid
generation(462,56a), increased calcium influx toxicity
(296b,333,416,432,462c,507) and DNA fragmentation(296,42,114,142) and mitochondrial
membrane dysfunction (56de, 416).
Chronic
neurological conditions such as ALS appear to be primarily caused by chronic or
acute brain inflammation. The brain is very sensitive to inflammation. Disturbances in metabolic networks:
e.g., immuno-inflammatory processes,
insulin-glucose homeostasis, adipokine
synthesis and secretion, intra-cellular signaling cascades, and mitochondrial
respiration have been shown to be major factors in chronic neurological conditions (592,593,598,
etc.). Inflammatory chemicals such as mercury, aluminum, and other toxic metals
as well as other excitotoxins including MSG and aspartame cause high levels of
free radicals, lipid peroxidation, inflammatory cytokines, and oxidative stress
in the brain and cardiovascular systems(13,595-598,etc.)
Mercury and other toxic metals inhibit
astrocyte function in the brain and CNS(119), causing increased glutamate and
calcium related neurotoxicity (119,333,416,496). Mercury and increased
glutamate activate free radical forming processes like xanthine oxidase which
produce oxygen radicals and oxidative neurological damage(142,13). Nitric oxide related toxicty caused by
peroxynitrite formed by the reaction of NO with superoxide anions, which
results in nitration of tyrosine residues in neurofilaments and manganese
Superoxide Dimustase(SOD) has been found to cause inhibition of the
mitochondrial respiratory chain, inhibition of the glutamate transporter, and
glutamate-induced neurotoxicity involved in ALS(524,521).
These inflammatory
processes damage cell structures including DNA, mitochondria, and cell
membranes. They also activate microglia
cells in the brain, which control brain inflammation and immunity. Once activated, the microglia secrete large
amounts of neurotoxic substances such as glutamate, an excitotoxin, which adds
to inflammation and stimulates the area of the brain associated with
anxiety(598). Inflammation also disrupts brain neurotransmitters resulting in
reduced levels of serotonin, dopamine, and norepinephrine. Some of the main causes of such disturbances
that have been documented include
vaccines, mercury, aluminum, other toxic metals, MSG, aspartame, etc.
(593,598,600,etc.)
Reduced levels of magnesium and zinc are related to
metabolic syndrome, insulin resistance, and brain inflammation and are
protective against these conditions(595,43).
Mercury and cadmium inhibiting magnesium and zinc levels as well as
inhibiting glucose transfer are other mechanisms by which mercury and toxic
metals are factors in metabolic syndrome and insulin resistance/diabetes
(43,196,338,597).
TNFa(tumor necrosis factor-alpha) is a cytokine
that controls a wide range of immune cell
response in mammals, including cell death(apoptosis). This process is involved in inflammatory and
degenerative neurological conditions like ALS, MS, Parkinson’s, rheumatoid
arthritis, etc. Cell signaling
mechanisms like sphingolipids are part of the control mechanism for the TNFa
apoptosis mechanism(126a). glutathione
is an amino acid that is a normal
cellular mechanism for controlling apoptosis.
When glutathione is depleted in the brain, reactive oxidative species
increased, and CNS and cell signaling mechanisms are disrupted by toxic
exposures such as mercury, neuronal cell apoptosis results and neurological
damage. Mercury has been shown to induce TNFa,
deplete glutathione, and increase
glutamate, dopamine, and calcium related toxicity, causing inflammatory effects and cellular
apoptosis in neuronal and immune cells(126b,126c). Mercury’s biochemical damage at the cellular
level include DNA damage, inhibition of DNA and RNA synthesis
(42,114,142,197,296,392); alteration of
protein structure (33,111,114,194,252,442);
alteration of the transport and signaling functions of calcium(333,43b,254,416d,462,507);
inhibitation of glucose transport(338,254), and of enzyme function and
transport of other essential nutrients (96,198,254,263,264,33,330,331,339,347,
441,442); induction of free radical formation
(13a,43b,54,405,424), depletion of cellular glutathione (necessary for
detoxification processes) (56,111,126,424), inhibition of glutathione
peroxidase enzyme(13a,442), inhibits glutamate uptake(119,416), induces
peroxynitrite and lipid peroxidation damage(521b), causes abnormal migration of
neurons in the cerebral cortex(149),
immune system damage (111,194, 226,252,272,316,325,355); inducement of inflammatory
cytokines(126,152,181) and autoimmunity(226,272,369,405,etc.)
Exposure
to mercury vapor and methyl mercury is well documented to commonly
cause conditions
involving tremor, with populations exposed to mercury experiencing
tremor levels on
average proportional to exposure level (250,565). Mercury exposure
causes high levels of
oxidative stress/reactive oxygen species(ROS)(13), which has
been found to be a
major factor in apoptosis and neurological disease
(56,250,441,442,443,13)
including dopamine or glutamate related apoptosis(288c).
Mercury and quinones
form conjugates with thiol compounds such as glutathione and
cysteine and cause
depletion of glutathione, which is necessary to mitigate reactive
damage. Such conjugates are found to be highest in
the brain substantia nigra with
similar conjugates
formed with L-Dopa and dopamine in Parkinson’s disease(56).
Mercury depletion of
GSH and damage to cellular mitochondria and the increased lipid
peroxidation in protein
and DNA oxidation in the brain appear to be a major factor in
Parkinson’s
disease(33,56,442) and a factor in
other neurological conditions.
Mercury blocks the immune function of magnesium and zinc (198,427,38), whose
deficiencies are known to cause significant neurological
effects(461,463,430,601). The low Zn levels result in deficient CuZnSuperoxide dismustase (CuZnSOD), which in
turn leads to increased levels of superoxide due to toxic metal exposure. This is in addition to mercury’s effect on
metallothionein and copper homeostasis as previously discussed(477). Copper is an essential trace metal which
plays a fundamental role in the biochemistry of the nervous system
(477,489,495,463,464). Several chronic
neurological conditions involving copper metabolic disorders are well
documented like Wilson’s Disease and Menkes Disease. Mutations in the copper/zinc enzyme
superoxide dismustase(SOD) have been shown to be a major factor in the motor
neuron degeneration in conditions like familial ALS. Exposures to toxic metals such as mercury and
cadmium have been found to cause such effects(13a,495,517,etc.) and similar effects on Cu/Zn SOD have been
found to be a factor in other conditions such as autism, Alzheimer’s,
Parkinson’s, and non-familial ALS (489,490,495,464,469,111). This condition can result in zinc deficient
SOD and oxidative damage involving
nitric oxide, peroxynitrite, and lipid
peroxidation(490,495,496,489,521,524), which have been found to affect
glutamate mediated excitability and apoptosis of nerve cells and effects on
mitochondria (119c,412,416,495,496,502,519,524). These effects can be reduced by zinc
supplementation (464,495,517,430), as well as supplementation with antioxidants
and nitric oxide-suppressing agents and peroxynitrite scavengers such as Vit C,
Vit E, lipoic acid, Coenzyme Q10, carnosine, gingko biloba, N-acetyl
cysteine,melatonin, etc.(444,464,494,495,469,470,521,524,572). Ceruloplasmin in
plasma can be similarly affected by
copper metabolism dysfunction, like SOD function, and is often a factor in
neurodegeneration(489).
Motor neuron dysfunction and loss in amyotrophic
lateral sclerosis (ALS) have been attributed to several different mechanisms,
including increased intracellular calcium (333,496,507), glutamate
dysregulation and excitotoxicity(119c,412,416,496,502), oxidative stress and
free radical damage(13,43,56,442,490), nitric oxide related toxicity caused by
peroxynitrite(524,521), mitochondrial damage/dysfunction(519), neurofilament aggregation and dysfunction of
transport mechanisms(507), and autoimmunity(313,314,369,405,513). These
alterations and effects are not mutually exclusive but rather are synergistic,
and increased calcium and altered calcium homeostasis appears to be a common
denominator. Mercury forms strong bonds with the-SH groups
of proteins causing alteration of the transport of calcium
(333,43,96,254,329,432,496) and causes
mitochondrial release of calcium (21,35,43,329,333,432,496,519). This results in a rapid and sustained
elevation in intracellular levels of calcium (333,496). Calcium plays a major role in the extreme
neurotoxicity of mercury and methyl mercury. Both inhibit cellular calcium
ATPase and calcium uptake by brain microsomes at very low levels of exposure
(270,288,329,333,432,56,). Protein Kinase C (PKC) regulates intracellular and
extra cellular signals across neuronal membranes, and both forms of mercury
inhibit PKC at micro molar levels, as well as inhibiting phorbal ester
binding(43,432). They also block or inhibit calcium L-channel currents in the
brain in an irreversible and concentration dependent manner. Mercury vapor or inorganic mercury exposure
affects the posterior cingulate cortex and causes major neurological effects
with sufficient exposure (428,453).
Metallic mercury is much more potent than methyl mercury in such
actions, with 50 % inhibition in animal studies at 13 ppb(333,329). Mercury is seen to be a factor in all of
these known mechanisms of neural degeneration seen n ALS and other motor neuron
conditions.
Spatial and temporal changes in
intracellular calcium concentrations are critical for controlling gene
expression and neurotransmitter release in neurons(432,496,43,114). Mercury alters calcium homeostasis and
calcium levels in the brain and affects gene expression and neurotransmitter
release through its effects on calcium, etc.
Mercury inhibits sodium and potassium (N,K)ATPase in dose dependent
manner and inhibits dopamine and noreprenephrine uptake by synaptosomes and
nerve impulse transfer(288,270,56,43,35).
Mercury also interrupts the cytochrome oxidase system, blocking the ATP
energy function (35,43,84), lowering immune growth factor IGF-I levels
and impairing astrocyte function(119,152,416d,497). Astrocytes are common cells in the CNS
involved in the feeding and detox of nerve cells. Increases in inflammatory cytokines such as
caused by toxic metals trigger increased free radical activity and damage to
astrocyte and astrocyte function(152,416d).
IGF-I protects against brain and neuronal pathologies like ALS, MS, and
Fibromyalgia by protecting the astrocytes from this destructive process.
Na(+),K(+)-ATPase is a transmembrane protein that
transports sodium and potassium ions across cell membranes during an activity
cycle that uses the energy released by ATP hydrolysis. Mercury is documented to inhibit
Na(+),K(+)-ATPase function at very low levels of exposure(288ab). Studies have
found that in ALS cases there was a reduction in serum magnesium and RBC
membrane Na(+)-K+ ATPase activity and an
elevation in plasma serum digoxin(263,260d).
The activity of all serum free-radical scavenging enzymes, concentration
of glutathione, alpha tocopherol, iron binding capacity, and ceruloplasmin
decreased significantly in ALS, while the concentration of serum lipid
peroxidation products and nitric oxide increased. The inhibition of Na+-K+ ATPase can
contribute to increase in intracellular calcium and decrease in magnesium,
which can result in 1) defective neurotransmitter transport mechanism, 2)
neuronal degeneration and apoptosis, 3) mitochondrial dysfunction, 4) defective
golgi body function and protein processing dysfunction. It is documented in this paper that mercury
is a cause of most of these conditions seen in ALS
(13a,111,288,442,521b,43,56,263etc.)
Mercury exposure also degrades the immune
system resulting in more susceptibility to viral, bacterial, or parasitic
effects along with candida albicans which are often present in those with
chronic conditions and require treatment (404,468,470,485,600). Four such commonly found in ALS patients are
mycoplasma AND echo-7 enterovirus(468,470), candida albicans (404), and
parasites(485). One clinic found that
over 85% of patients with ALS tested have mycoplasma infection, often M.
Pneumoniae(470), but in Gulf War veterans mostly a manmade variety used in
bioterrorism agents- M. fermentans.
Mercury from amalgam interferes with production of cytokines that
activate macrophage and neutrophils, disabling early control of viruses or
other pathogens and leading to enhanced infection(131). While the others are also being commonly
found, mycoplasma has been found in 85% of ALS patients by clinics treating
such conditions(470). Mycoplasma
appears to be a cofactor with mercury in the majority of cases and shifts the
immune T cell balance toward inflammatory cytokines(470b). Treatment of these chronic infections are
required and documented to cause improvement in such patients(470).
Mercury
lymphocyte reactivity and effects on amino acids such as glutamate in the CNS
induce CFS type symptoms including profound tiredness, musculoskeletal pain,
sleep disturbances, gastrointestinal and neurological problems along with other
CFS symptoms and Fibromyalgia (346,342,369,416,496,513,119b,152,314). Mercury
has been found to be a common cause of
Fibromyalgia (293,346,369) , which based on a Swedish survey occurs in about 12% of women
over 35 and 5.5% of men(342). ALS patients have been found to have a
generalized deficiency in metabolism of the neuroexcitotoxic amino acids like
glutamate, aspartate, NAAG, etc.(416).
Glutamate is the most abundant amino acid in the body and in the CNS
acts as excitory neurotransmitter (346,412,416,438,496,119c), which also causes
inflow of calcium. Astrocytes, a type
of cell in the brain and CNS with the task of keeping clean the area around
nerve cells, have a function of neutralizing excess glutamate by transforming
it to glutamic acid. If astrocytes are
not able to rapidly neutralize excess glutamate, then a buildup of glutamate
and calcium occurs, causing swelling and
neurotoxic effects (119,152,333,416,496, 524).
Mercury and other toxic metals inhibit astrocyte function in the brain
and CNS (119,152,416), causing increased glutamate and calcium related
neurotoxicity (119,152,333, 226a,496) which are responsible for much of the
Fibromyalgia symptoms and a factor in neural degeneration in MS and ALS. This is also a factor in conditions such as CFS,
Parkinson’s, and ALS(346,416,496,524,600).
Animal studies have confirmed that increased levels of glutamate(or
aspartate, another amino acid excitory neurotransmitter) cause increased
sensitivity to pain , as well as higher body temperature- both found in
CFS/Fibromyalgia. Mercury and increased
glutamate activate free radicals forming processes like xanthine oxidase which
produce oxygen radicals and oxidative neurological damage(346,142,13). Nitric oxide related toxicty caused by
peroxynitrite formed by the reaction of NO with superoxide anions, which
results in nitration of tyrosine residues in neurofilaments and manganese
Superoxide Dimustase(SOD) has been found to cause inhibition of the
mitochondrial respiratory chain, inhibition of the glutamate transporter, and
glutamate-induced neurotoxicity involved in ALS(524,521).
In addition to the documentation showing
the mechanisms by which mercury causes the conditions and symptoms seen in ALS
and other neurodegenerative diseases, many studies of patients with major
neurological or degenerative diseases have found direct evidence mercury and
amalgam fillings play a major role in development of conditions such as such as ALS
(92,97,207,229b,305,325,327,416,423,442,468,470,520,35). Such supplements including
N-acetylcysteine(NAC), Vitamins E and C, zinc, and creatinine have been found to offer significant
protection against cell apoptosis and neurodegeneration in neurological
conditions such as ALS(13c,56a,517,524,564,494).
Medical studies and doctors treating
chronic conditions like Fibromyalgia have found that supplements which cause a
decrease in glutamate or protect against its effects have a positive effect on
Fibromyalgia and other chronic neurologic conditions. Some that have been found to be effective
include CoQ10(444), ginkgo biloba and pycnogenol(494a), NAC(54,494a), Vit B6, methyl cobalamine(B12), L-carnitine,
choline, ginseng, vitamins C and E, nicotine, and omega 3 fatty acids(fish and
flaxseed oil)(417,495e).
In a study of the brains of persons dying
of ALS, spherical and crescent-shaped introneuronal inclusions(SCI) were
distributed in association with each other among the parahippocampal gyrus,
dentate gyrus of the hippocampus and amygdala, but not any non-motor-associated
brain regions(522). The occurrence of SCI in both the second and third layers
of the parahippocampal gyrus and amygdala was significantly correlated to the
presence of dementia in ALS cases. Mercury has been found to accumulate in
these areas of the brain and to cause adverse behavioral effects in animal
studies and humans(66,287,305).
Another neurological effect of mercury that
occurs at very low levels is inhibition of nerve growth factors, for which
deficiencies result in nerve degeneration.
Only a few micrograms of mercury severely disturb cellular function and
inhibits nerve growth (175,147,226,255,305,149). Prenatal or neonatal exposures have been
found to have life long effects on nerve function and susceptibility to toxic
effects. Prenatal mercury vapor exposure
that results in levels of only 4 parts per billion in newborn rat brains was
found to cause decreases in nerve growth factor and other effects(305). This is a level that is common in the
population with several amalgam fillings or other exposures(600). There is also evidence that fetal or infant
exposure causes delayed neurotoxicity evidenced in serious effect at middle
age(255). Insulin-like-growth factor I
(IGF-I) are positively correlated with growth hormone levels and have been
found to be the best easily measured marker for levels of growth hormone, but
males have been found more responsive to this factor than women(497). IGF-I controls the survival of spinal motor
neurons affected in ALS during development as well as later in
life(497,498). IGF-I and insulin levels
have been found to be reduced in ALS patients with evidence this is a factor in
ALS(497,498). Several clinical trials
have found IGF-I treatment is effective at reducing the damage and slowing the
progression of ALS and Alzheimer’s with no medically important adverse
effects(498). It has also been found
that in chronically ill patients the levels of pituitary and thyroid hormones
that control many bodily processes are low, and that supplementing both
thyrotropin-releasing hormone and growth control hormone is more effective at
increasing all of these hormone levels in the patient(499).
Tick-borne encephalitis, such as Lyme
Disease, has been found to cause ALS in
a significant portion of untreated acute cases(471). Lyme disease is widespread in the U.S.
Large numbers of patients diagnosed with ALS
have been found to have treatable tick-borne encephalitis, and many have
recovered after treatment.
Extremely toxic anaerobic bacteria from
root canals or cavitations formed at incompletely healed tooth extraction
sites have also been found to be common
factors in Fibromyalgia and other chronic neurological conditions such as
Parkinson’s and ALS, with condensing osteitis which must be removed with a
surgical burr along with 1 mm of bone around it(35,200, 437, 600). Cavitations have been found in 80% of sites
from wisdom tooth extractions tested and 50% of molar extraction sites
tested(35,200,437). The incidence is
likely somewhat less in the general population. Medical studies and doctors treating
Fibromyalgia have found that supplements which cause a decrease in glutamate or
protect against its effects have a positive effect on Fibromyalgia and other
chronic neurologic conditions like ALS.
Some that have been found to be effective include Vit B6, methyl
cobalamine(B12), L-carnitine, choline, ginseng, Ginkgo biloba, vitamins C and
E, CoQ10, nicotine, and omega 3 fatty acids(fish and flaxseed oil)(417,468).
Clinical tests of patients with ALS, MND,
Parkinson’s, Alzheimer’s, Lupus(SLE), and rheumatoid arthritis have found that
the patients generally have elevated plasma cysteine to sulphate ratios, with
the average being 500% higher than controls(330,331,56,84), and in general
being poor sulphur oxidizers. This means
that these patients have blocked enzymatic processes for converting the basic
cellular fuel cysteine to sulfates and glutathione, and thus insufficient sulfates available to carry out
necessary bodily processes. Mercury has
been shown to diminish and block sulphur oxidation and thus reducing
glutathione levels which is the part of this process involved in detoxifying
and excretion of toxics like mercury(33). Glutathione is produced through the
sulphur oxidation side of this process. Low levels of available glutathione
have been shown to increase mercury retention and increase toxic effects(111),
while high levels of free cysteine have been demonstrated to make toxicity due
to inorganic mercury more severe(333,194,56,33b). The deficiency in conjugation and
detoxification of sulfur based toxins in the liver results in toxic metabolites
and progressive nerve damage over time (331).
Mercury has also been found to play a part in inducing intolerance and
neuronal problems through blockage of the P-450 enzymatic process(84,33b).
Patients with some of these conditions have found that bathing in Epsom Salts
(magnesium sulfate) offers temporary relief for some of their symptoms by providing
sulfates that avoid the blocked metabolic pathway. A test that some doctors treating conditions
like ALS usually prescribe to measure the cysteine to sulfate ratio and other
information useful in diagnosis and treatment is the Great Smokies Diagnostic
Labs comprehensive liver detox test(386). The test results come with some
recommendations for treatment. A hair
test for toxic metals is also usually ordered to determine toxic exposures that
might be involved(386). A more
definitive test such as MELISA for immune reactivity to toxics is available by
sending blood to a European lab(87).
Other labs also have other useful tests such as Immune Reactivity
Biocompatability Tests(445), ELISA or organic acid panels or amino acid
panels(386). Treatment using IV
glutathione, vitaminC, and minerals has been found to be very effective in the
stabilizing and amelioration of some of these chronic neurological conditions
by neurologist such as Perlmutter in Florida(469).
In
one subtype of ALS, damaged, blocked, or
faulty enzymatic superoxide dimustase (SOD) processes appear to be a major
factor in cell apoptosis involved in the condition (443,495). Mercury is known to damage or inhibit SOD
activity(13,33,111).
Total
dental revision(TDR) which includes replacing amalgam fillings, extracting root
canaled teeth, and treating cavitations has been found to offer significant
health improvements to many with ALS and other autoimmune
conditions(35,200,293,437). Root canals and cavitations have been found to harbor
anaerobic bacteria which give off toxins of extreme toxicity which block
enzymatic processes at the cellular level causing degenerative processes
according to the medical labs that do the tests(437,200,35), similar to
mercury’s effects but in some cases even more toxic . IGF-1 treatments have also been found to
alleviate some of the symptoms of ALS(424).
Medical studies and doctors treating Fibromyalgia have found that
supplements which cause a decrease in glutamate or protect against its effects
have a positive effect on Fibromyalgia.
Some that have been found to be effective in treating metals related
autoimmune conditions include Vit B6, CoenzymeQ10, methyl cobalamine(B12), L-carnitine, choline,
ginseng, Ginkgo biloba, vitamins C and E, nicotine, and omega 3 fatty
acids(fish and flaxseed oil)(417,444,468).
One dentist with severe symptoms similar
to ALS improved after treatment for mercury poisoning(246), and others treated
for mercury poisoning or using TDR have also recovered or significantly
improved (97,229,405,406,437,468-470,485,35).The Edelson Clinic in Atlanta
which treats ALS patients reports similar experience(406), and the Perlmutter
Clinic has also had some success with treatment of ALS and other degenerative
neurological conditions(469).
While there are many studies
documenting effectiveness of chemical chelators like DMSA and DMPS at reducing
metals levels and alleviating adverse effects for most conditions, and many
thousands of clinical case results(600,601); there is also some evidence from
animal studies that these chelators can result in higher levels of mercury in
the motor neurons in the short term which might be a problem for ALS
patients(600). Thus other detox options
might be preferable for ALS patients until enough clinical evidence is
available treating ALS patients with them with mercury toxicity. Another chelator used for clogged arteries,
EDTA, forms toxic compounds with mercury and can damage brain function(307). Use of EDTA may need to be restricted in
those with high Hg levels. N-acetyl
cysteine(NAC) has been found to be effective at increasing cellular glutathione
levels and chelating mercury(54).
Experienced doctors have also found additional zinc to be useful when
chelating mercury(222) as well as counteracting mercury’s oxidative damage(43).
Zinc induces metallothionein which protects against oxidative damage and
increases protective enzyme activities and glutathione which tend to inhibit
lipid peroxidation and suppress mercury toxicity(430,464). Also lipoic acid,LA, has been found to dramatically increase
excretion of inorganic mercury(over 12 fold), but to cause decreased excretion
of organic mercury(572d) and copper.
Lipoic acid has a protective effect regarding lead or inorganic mercury
toxicity through its antioxidant properties(572), but should not be used with
high copper until copper levels are reduced.
LA and NAC (N-acetyl cysteine)
also increase glutathione levels and protect against superoxide radical/
peroxynitrite damage, so thus have an additional neuroprotective
effect(494ab,521,572c,54). Zinc is a
mercury and copper antagonist and can be used to lower copper levels and
protect against mercury damage. Lipoic
acid has been found to have protective effects against cerebral
ischemic-reperfusion, excitotoxic amino acid(glutamate) brain injury,
mitochondrial dysfunction, diabetic neuropathy(494). Other antioxidants such as carnosine(495a),
Coenzyme Q10,Vitamins C & E, gingko biloba, and pycnogenol have also been
found protective against degenerative neurological conditions(494,495e,
444).
Two
other supplements that appears useful in conditions involving muscle function
degeneration are creatine(502)and
lithium(590). In the motor cortex of the ALS group the N-acetylaspartate
(NAA)/creatine (Cr(t)) metabolite ratio was lower than in our control group,
indicating NAA loss. Upon creatine supplementation we observed in the that
creatine supplementation causes an increase in the diminished NAA levels in ALS
motor cortex as well as an increase of choline levels in both ALS and control
motor cortices. This indicates an improvement in function of the pathological
ALS skeletal muscles related to changes of mitochondrial respiratory chain
which appears to affect motor neuron survival.
In another study by the NAS, lithium carbonate at 150 mg twice daily
significantly reduced the degeneration of ALS patients(590).
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