http://www.flcv.com/als.html
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.)
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 (56bc, 416).
Mitochondrial DNA mutations or dysfunction is fairly common, found in
at least 1 in every 200 people(275), 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 ALS, Parkinson's
disease, autism, etc. (33,56,416,442).
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).
See Also: http://www.flcv.com/damspr15.html