Toxic Exposures and
Parkinson’s: the Mercury and Other Toxicity Connections
Bernard Windham (Ed.)
I. Introduction.
There
has been a huge increase in the incidence of degenerative neurological
conditions in virtually all Western countries over the last 2 decades(574). The increase in Parkinson’s and other motor
neuron disease has been over 50%. The primary
cause appears to be increased exposures to toxic pollutants(574).
Amalgam
fillings are the largest source of mercury in most people with daily exposures
documented to commonly be above government health guidelines (49,79,183,199,506,600,217). 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(605). 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, as well as ADHD, mood, and behavioral disorders
(601,602). A study found that those with
occupational exposure to lead, arsenic, or copper have more than double the
incidence of Parkinson’s than normal(560).
Mercury is one of the most toxic substances
in existence and is known to bioaccumulate in the body of people and animals
that have chronic exposure(600). Mercury exposure is cumulative and comes
primarily from 4 main sources: silver(mercury) dental
fillings, food(mainly fish), vaccinations, and occupational exposure. Whereas
mercury exposure from fish is primarily methyl mercury and mercury from
vaccinations is thimerosal(ethyl mercury), mercury from occupational exposure and dental
fillings is primarily from elemental mercury vapor. Developmental and
neurological conditions occur at lower levels of exposure from mercury vapor
than from inorganic mercury or methyl mercury(606). Mercury in amalgam fillings, because of its high vapor pressure and
galvanic action with other metals in the mouth, has been found to be
continuously vaporized and released into
the body, and has been found to be the
directly correlated to the number of
amalgam surfaces and the largest source of mercury in the majority of people
(49,183,199,209,79,99,600), typically between 60 and 90% of the total. The level of daily exposure of those with
several amalgam fillings commonly exceeds the U.S. EPA health guideline for
daily mercury exposure of
0.1 ug/kg body weight/day, and the oral mercury level commonly
exceeds the mercury MRL of the U.S.ATSDR
of 0.2 ug/ cubic meter of air(217,600).
When amalgam fillings are replaced, levels of mercury in the blood,
urine, saliva, and feces typically rise temporarily but decline between 60 to
90% within 6 to 9 months (79,600.).
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). 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
II. Mechanisms by which
mercury causes neurological conditions found in Parkinson’s and
neurodegenerative diseases.
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 inflamatory 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), increased calcium influx toxicity (296b,333,416,432,462c,507)
and DNA fragmentation(296,42,114,142) and mitochondrial membrane dysfunction
(56de, 416). The mechanisms by which mercury causes(often synergistically along with other toxic
exposures) all of these conditions and neuronal apoptosis will be
documented.
TNFa(tumor necrosis
factor-alpha) is a cytokine that controls a wide range of immune cell response
in mammals, including cell death(apoptosis) in neuronal and immune cells. This process is involved in inflamatory and
degenerative neurological conditions like ALS, MS, Parkinson’s, rheumatoid
arthritis, etc. Cell signaling
mechanisms like sphingolipids are part of the control mechansim for the TNFa
apoptosis mechanism(126a). Gluthathione 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 mechinsisms are disrupted by toxic
exposures such as mercury, neuronal cell apoptosis results and neurological
damage. Mercury has been
shown to induce TNFa and deplete glutathione, causing inflamatory effects and cellular
apoptosis in neuronal and immune cells(126b,126c).
Mercury’s biochemical damage at the
cellular level include
Oxidative
stress and reactive oxygen species(ROS) have been implicated as major factors
in neurological disorders including stroke, Parkinson’s Disease(PD),
Alzheimer’s, ALS, etc.(13,424,442). 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)
(13,441,443). Only a few micrograms of
mercury severely disturb cellular function and inhibit nerve growth
(147,149,226,255, 305,442). Exposure to
mercury results in metalloprotein compounds that have genetic effects, having
both structural and catalytic effects on gene expression (114,241,296,442).
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).
Some of the processes affected by such metalloprotein control of genes
include cellular respiration, metabolism, enzymatic processes, metal-specific
homeostasis, and adrenal stress response systems. Significant psysiological changes occur when
metal ion concentrations exceed threshold levels. Such metalloprotein formation also appears to
have a relation to autoimmune reactions in significant numbers of people (114,60,313,342,368,369,405, 442). Increased formation of reactive oxygen species(ROS) has also been found to increase formation of
advanced glycation end products(AGEs) that have been found to cause activation
of glial cells to produce superoxide and nitric oxide, they can be considered
part of a vicious cycle, which finally leads to neuronal cell death in the
substantia nigra in PD(424).
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
congugates are found to be highest in the brain substantia nigra with similar
congugates formed with L-Dopa and dopamine in Parkinson’s disease(56). Mercury depletion of GSH and damage to cellular
mitochrondria and the increased lipid perxodation in protein and DNA oxidation
in the brain appear to be a major factor in Parkinson’s disease(33,56,442).
Exposure to mercury vapor and methyl mercury is well documented to commonly
cause conditions involving tremor, with populations exposed to mercury
experiencing tremor on average proportional to exposure level (250,565,98). One study
found higher than average levels of mercury in the blood, urine, and hair of
Parkinson’s disease patients(363). Another study(169)
found blood and urine mercury levels to be very strongly related to Parkinson’s
with odds ratios of approx. 20 at high levels of Hg exposure. Other studies (145) that reviewed
occupational exposure data found that occupational exposure to manganese and
copper have high odds rations for relation to PD, as well as multiple exposures
to these and lead, but one study noted that this effect was only seen for
exposure of over 20 years. Occupational exposure to mercury has been found to
cause Parkinson’s(98). One study found the EDTA
chelation was effective in reducing some of the effects(145b).
Glutamate is the most abundant amino acid in the
body and in the CNS acts as excitory neurotransmitter(346,386),
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(119,333).
Mercury and other toxic metals inhibit astrocyte function in the brain
and CNS(119), causing increased glutamate and calcium
related neurotoxicity(119,333,226) which are responsible for much of the
fibromylgia symptoms. This is also a factor in
conditions such as CFS, Parkinson’s, and ALS(346,416).
Parkinson's disease involves the aggregation of
alpha-synuclein to form fibrils, which are the major constituent of
intracellular protein inclusions (Lewy bodies and Lewy neurites) in
dopaminergic neurons of the substantia nigra(564).
Occupational exposure to specific metals, especially manganese, copper, lead,
iron, mercury, zinc, aluminum, appears to be a risk factor for Parkinson's
disease based on epidemiological studies(98,145,564). Elevated levels of
several of these metals have also been reported in the substantia nigra of
Parkinson's disease subjects (564).
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 Parkinson’s cases there was an
elevation in plasma serum digoxin and a reduction in serum magnesium, RBC
membrane Na(+)-K+ ATPase activity (263).
The activity of all serum free-radical scavenging enzymes, concentration
of glutathione, alpha tocopherol, iron binding capacity, and ceruloplasmin
decreased significantly in PD, 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
Parkinson’s (13a,111,288,442,521b,43,56,etc.)
Many
studies of patients with major neurological or degenerative diseases have found
evidence amalgam fillings may play a major role in development of conditions such as such as Alzheimers
(66,67,158,166,204, 207,221,242,244,257,295,300), ALS(92,97,325,442),
MS(102,163,170,184,212,213,285,291,302,324,326), Parkinson’s(98,145,169,248,250,256,258,
363,405,56,84), etc. Mercury exposure
causes high levels of oxidative stress/reactive oxygen species(ROS)(13),
which has been found to be a major factor in neurological disease(56). 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 congugates are found to be highest in
the brain substantia nigra with similar congugates formed with L-Dopa and
dopamine in Parkinson’s disease(56,442). Mercury depletion of GSH and damage to
cellular mitochrondria and the increased lipid perxodation in protein and
An EKM system for evaluating nerve and
muscle function ability using a set of 5 measures (precision, imprecision, tremor, Fitts'
constant, and irregularity) and tested on a group of Cree Indians with mercury
exposure from fish eating(565). Ninety-six participants, including 30
controls subjects, 36 Cree subjects exposed to mercury, 21 subjects with
Parkinson disease, 6 with presumed cerebellar deficit, and 3 with essential
tremor, participated in the study. An
ANOVA on the three largest groups generated significant results for tremor,
Fitts' constant, and irregularity between the Cree and the control subjects and
on Fitts' constant and irregularity between the subjects with Parkinson's
disease and the control subjects. Three
subgroups of the same mean age composed of six subjects each were selected. One
was composed of Cree subjects with the highest level of mercury exposure,
another with Cree subjects having a low level of mercury exposure, and a third
with control subjects. An ANOVA on
these three groups revealed a significant difference between both groups of Cree
subjects and the control group for Fitts' constant and irregularity. These
preliminary results suggest that the EKM system is able to discriminate the
performance of different groups of subjects and found significant evidence that
mercury exposure is related to nerve and muscle function conditions such as
tremor and Parkinson’s(565).
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, and
platelet aggregation through interfering with the sodium pump.
Mercury has been found to accumulate
preferentially in the primary motor function related areas 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). There is considerable indication this may be
a factor in development of ALS and other neurodegenerative conditions(48,325,405,442). Mercury penetrates and damages the blood
brain barrier allowing penetration of the barrier by other substances that are
neurotoxic (20,38,85,105,301,311/262). Such damage to the blood brain barrier’s
function has been found to be a major factor in chronic neurological diseases
such as MS(286,289,291,302, 324,326). MS patients have been found to have much
higher levels of mercury in cerebrospinal fluid compared to controls (163,35,139). Large German studies
including studies at German universities have found that MS patients usually
have high levels of mercury body burden, with one study finding 300% higher
than controls(271).
Most recovered after mercury detox(369), with
some requiring additional treatment for viruses and intestinal dysbiosis. Studies have found mercury related mental
effects to be indistinguishable from those of MS
(207,212,222,244,271,289,291,302,183,184,213,324,326). 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 neurologists
such as Perlmutter in
Low levels of toxic metals have been found
to inhibit dihydroteridine reductase, which affects the neural system function
by inhibiting brain transmitters through its effect on phenylalanine, tyrosine
and tryptophan transport into neurons(122,257,258,289,372). This was found to cause severe impaired
amine synthesis and hypokinesis. Tetrahydro-biopterin, which is essential in
production of
nerurotransmitters, is significantly decreased in patients with
Alzheimer’s, Parkinson’s, and MS. Such patients have abnormal inhibition of
neurotransmitter production(432).(supplements which
inhibit breach of the blood brain barrier such as bioflavonoids have been found
to slow such neurological damage).
Clinical tests of patients with
MND,ALS, 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), and in
general being poor sulphur oxidizers.
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(33,442).
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). Mercury has also
been found to play a part in neuronal problems through blockage of the P-450
enzymatic process(84).
Other toxic metals and toxics such as pesticides have also been found to
cause the types of damage seen in Parkinson’s and to exposure to have positive
correlation to Parkinson’s (400,98,145). Another exposure that affects somes appears
to be hexane(505).
There are
synergistic effects of various toxics that result in conditions
like Parkinson’s(524b,13c).
Determination of one’s factors by history assessment and tests is a
first step in improving the condition.
One genetic difference found in animals
and humans is cellular retention differences for metals related to the ability
to excrete mercury(426). For example it has been found that individuals
with genetic blood factor type APOE-4 do not excrete mercury readily and
bioaccumulate mercury, resulting in susceptibility to chronic autoimmune
conditions such as Alzheimer’s, Parkinsons, etc. as early as age 40, whereas
those with type APOE-2 readily excrete mercury and are less susceptible. Those with type APOE-3 are intermediate to
the other 2 types(437,35).
The Huggins Clinic(35) using total dental
revision(TDR) has successfully treated over a thousand patients with chronic
autoimmune conditions like MS, Parkinson’s,Lupus, ALS, AD, diabetes, etc.(35),
including himself with the population of over 600(approx. 85%) who experienced
significant improvement in MS. Jaw bone
cavitations were found to be common significant factors in some of these
conditions such as Parkinson’s.
Huggins Total Dental
Revision Protocol(35):
(a) history
questionnaire and panel of tests.
(b) replace
amalgam fillings starting with filling with highest negative current or highest
negative quadrant, with supportive vitamin/mineral
supplements.
© extract all root canaled
teeth using proper finish protocol.
(d) test
and treat cavitations and amalgam tattoos where relevant
(e) supportive
supplementation, periodic monitoring tests, evaluate need for further
treatment(not usually needed).
(f) avoid acute
exposures/challenges to the immune system on a weekly
Tests suggested by Huggins/Levy(35)
for evaluation and treatment of mercury toxicity:
(a) hair
element test(386) (low hair mercury
level does not indicate low body level)(more than 3 essential minerals out of normal range indicates likely metals
toxicity)
(b) CBC blood test with
differential and platelet count
© blood
serum profile
(d) urinary mercury (for
person with average exposure with amalgam fillings, average mercury level is 3
to 4 ppm; lower test level than this
likely means person is poor excretor and accumulating mercury, often mercury
toxic(35)
(e) fractionated
porphyrin urine test(note test results sensitive to light, temperature,
shaking)
(f) individual
tooth electric currents(replace high negative current teeth first)
(g) patient
questionnaire on exposure and symptom history
(h) specific
gravity of urine(test for pituitary function, s.g>1.022 normal; s.g.<
1.008 consistent with depression
and suicidal tendencies(35)}
Note: during initial exposure to mercury
the body marshalls immune system and other measures to try to deal with the challenge, so many test indicators will be
high; after prolonged exposure the body and immune system inevitably lose the
battle and measures to combat the challenge decrease- so some test indicator
scores decline. Chronic conditions are
common during this phase. Also high
mercury exposures with low hair mercury or urine mercury level usually indicates body
is retaining mercury and likely toxicity problem(35). In such cases where (calcium> 1100 or < 300 ppm) and low
test mercury,manganese,zinc,potassium; mercury
toxicity likely and hard to treat since
retaining mercury.
Test results indicating mercury/metals toxicity(35):
(a) white
blood cell count >7500 or < 4500
(b) hemocrit
> 50% or < 40%
© lymphocyte count
> 2800 or < 1800
(d) blood
protein level > 7.5 gm/100 ml
(e) triglycerides
> 150 mg %ml
(f) BUN > 18 or < 12
(g) hair
mercury > 1.5 ppm or < .4 ppm
(h) oxyhemoglobin
level < 55% saturated
(I) carboxyhemoglubin >
2.5% saturated
(j) T lymphocyte count
< 2000
(k)
(l)
(m) hair
aluminum > 10 ppm
(n) hair
nickel > 1.5 ppm
(o) hair
manganese > 0.3 ppm
(p) immune
reactive to mercury, nickel, aluminum, etc.
(q) high
hemoglobin and hemocrit and high alkaline phosphatase(alk phos) and lactic
dehydrogenese(LDA) during initial phases
of exposure; with low/marginal
hemoglobin and hemocrit plus low oxyhemoglobin during long term chronic fatigue phase.
note: after treatment of many cases of
chronic autoimmune conditions such as MS, ALS, Parkinson’s, Alzheimer’s, CFS,
Lupus, Rheumatoid Arthritis, etc., it has been observed that often mercury
along with root canal toxicity or cavitation toxicity are major factors in
these conditions, and most with these conditions improve after TDR if protocol
is followed carefully(35).
There are extensive documented cases (many
thousands) where removal of amalgam fillings led to cure of serious health
problems such as MS(94,95,102,170,212,213,222,271,291,302,34 ,35,229,405),
ALS(229,325,405,35), Parkinson’s/ muscle tremor (222,248,229,271,212,94,98,35),
Alzheimer’s(204,35), muscular/joint pain/fibromyalgia (222,293,317,303,322,369,35,94), anxiety & mental confusion
(94,212,222,229,233,271,317,320,322,57), Chronic Fatigue Syndrome
(60,212,293,229,222, 232,233,271,293,313, 317,320, 368,369,376), memory disorders(94,222,35,303)
Medical
studies and doctors treating fibromylagia 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
including 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),
tumeric, lipoic acid, proteolytic enzymes,(417,444). Reduced glutathione(GSH)
and N-acetyl cysteine(NAC) have been found to be protective against cellular
apoptosis seen in Parkinson’s and other neurodegenerative conditions(
56ab,462c, 149b). Vitamins C and E along
with zinc(517) have also been found protective against
oxidative stresss and some effects of mercury toxicity(4163,462c,56a). IGF-1
treatments have also been found to alleviate some of the symptoms of ALS(424).
Some clinics have found root canals, cavitations,
and amalgam tattoos to also be a factor in such autoimmune conditions and that
treatment of them improves prognosis in recovery from these conditions(35,437).
Studies have also found mercury and lead cause
autoantibodies to neuronal proteins, neurofilaments, and myelin basic protein(
References
(13)(a) S.Hussain et
al, “Mercuric chloride‑induced reactive oxygen species and its effect on
antioxidant enzymes in different regions of rat brain”,J
Environ Sci Health B 1997 May;32(3):395‑409; & P.Bulat, “Activity of Gpx and SOD in
workers occupationally exposed to mercury”, Arch Occup Environ Health, 1998,
Sept, 71 Suppl:S37-9; & Stohs SJ, Bagchi D. Oxidative mechanisms in the
toxicity of metal ions. Free
Radic Biol Med 1995; 18(2): 321-36 ; & D.Jay,
“Glutathione inhibits SOD activity of Hg”, Arch Inst cardiol Mex, 1998,68(6):457-61; &
El-Demerdash FM. Effects of selenium and mercury on the enzymatic
activities and lipid peroxidation in brain, liver, and blood of rats. J
Environ Sci Health B. 2001 Jul;36(4):489-99. &(b) S.Tan et al, “Oxidative stress induces programmed
cell death in neuronal cells”, J Neurochem, 1998, 71(1):95-105; & Matsuda T, Takuma K, Lee E, et
al. Apoptosis of astroglial cells [Article in Japanese] Nippon Yakurigaku
Zasshi. 1998 Oct;112 Suppl 1:24P-; &
Lee YW, Ha MS, Kim YK.. Role of reactive oxygen
species and glutathione in inorganic mercury-induced injury in human glioma
cells. Neurochem Res. 2001 Nov;26(11):1187-93; & (c)Ho PI, Ortiz D,
(20) M.J.Vimy,Takahashi,Y,
(33) (a)Markovich et al, "Heavy metals (Hg,Cd) inhibit the
activity of the liver and kidney sulfate transporter Sat‑1",
Toxicol Appl Pharmacol, 1999,154(2):181‑7;
& (b)2S.A.McFadden, “Xenobiotic
metabolism and adverse environmental response: sulfur-dependent detox pathways”,Toxicology, 1996, 111(1-3):43-65; &
(c) S.C. Langley-Evans et al, “SO2:
a potent glutathion depleting agent”, Comp Biochem Physiol Pharmocol
Toxicol Endocrinol, 114(2):89-98; &(d)Alberti A, Pirrone P, Elia M, Waring
RH, Romano C. Sulphation
deficit in “low-functioning” autistic children. Biol Psychiatry 1999, 46(3):420-4.
(34) PatrickStörtebecker,Associate
Professor of Neurology, Karolinska Institute,
(35) Huggins HA, Levy,TE, Uniformed Consent: the
hidden dangers in dental care, 1999, Hampton Roads Publishing Company Inc;
(Parkinson’s, cavitations, p133)
& Hal Huggins, Its All in
Your Head, 1993; & Center for Progressive Medicine, 1999, other autoimmune conditions (arthritis,
diabetes, Lupus, Parkinson’s, Alzheimer’s, Leukemia, etc. ) http://www.hugginsappliedhealing.com/story3.php
(42) Rodgers JS, Hocker JR, et al, Mercuric ion inhibition of eukaryotic
transcription factor binding to DNA. Biochem Pharmacol. 2001 Jun 15;61(12):1543-50; & Babich et al ., The mediation of mutagenicity
and clastogenicity of heavy metals by
physiochemical factors. Environ Res.,
1985:37;253‑286; & K.Hansen et al A survey of metal induced
mutagenicity in vitro and in vivo, J
Amer Coll Toxicol , 1984:3;381‑430.
(43)(a)Knapp LT; Klann E.
Superoxide‑induced stimulation of protein kinase C via thiol
modification and modulation of zinc content. J Biol Chem 2000 May 22; &
P.Jenner,“Oxidative mechanisms in PD”, Mov Disord, 1998; 13(Supp1):24-34;&(b) Rajanna B et al, “Modulation of protein kinase C by
heavy metals”,
Toxicol Lett, 1995, 81(2-3):197-203: & Badou A et al, “HgCl2-induced IL-4 gene expression in
T cells involves a protein kinase C-dependent calcium influx through L-type
calcium channels”J
Biol Chem. 1997 Dec 19;272(51):32411-8., & D.B.Veprintsev, 1996, Institute
for Biological Instrumentation, Russian Academy of Sciences, Pb2+ and Hg2+ binding to alpha‑lactalbumin”.Biochem Mol Biol Int 1996 ;39(6):
1255‑65; & M. J. McCabe,
University of Rochester School of Medicine & Dentistry, 2002, Mechanisms of
Immunomodulation by Metals, www.envmed.rochester.edu/envmed/TOX/faculty/mccabe.html; & Buzard GS, Kasprzak KS. Possible
roles of nitric oxide and redox cell signaling in metal-induced toxicity and
carcinogenesis: a review. Environ Pathol Toxicol Oncol. 2000;19(3):179-99
(48) K.Arvidson,”Corrosion
studies of dental gold alloy in contact with amalgam”, Swed. Dent. J 68: 135-139,1984.
(49) Kingman A, Albertini T, Brown LJ. National
(54) M.E.
Lund et al, “Treatment of acute MeHg poisoning by NAC”, J Toxicol Clin Toxicol,
1984,
22(1):31-49;
& G.Ferrari et al, Dept. Of Pathology,
RR. Ratan et al, Dept. of Neurology, Johns Hopkins Univ.,
J Neurosci, 1994, 14(7): 4385-92; Z.Gregus et
al, “Effect of lipoic acid on biliary excretion of
glutathione and metals”, Toxicol APPl Pharmacol, 1992,
114(1):88-96; & J.F. Balch et al, Prescription for
Nutritional Healing”,
2nd Ed., 1997.
(56) (a) A.Nicole et al, “Direct evidence for
glutathione as mediator of apoptosis in neuronal cells”, Biomed Pharmacother,
1998; 52(9):349-55; & J.P.Spencer et al, “Cysteine & GSH in PD”,
mechanisms involving ROS”, J Neurochem, 1998, 71(5):2112-22: &
& J.S. Bains et al, “Neurodegenerative disorders in humans and role
of glutathione in oxidative stress mediated neuronal death”, Brain Res Rev,
1997, 25(3):335-58; &
Medina S, Martinez M, Hernanz A, Antioxidants inhibit the human cortical
neuron apoptosis induced by hydrogen peroxide, tumor necrosis factor alpha,
dopamine and beta-amyloid peptide 1-42.
Free Radic Res. 2002 Nov;36(11):1179-84. &(b) D. Offen et
al, “Use of thiols in treatment of PD”, Exp Neurol, 1996,141(1):32-9; & Pocernich CB, et al. Glutathione elevation and its protective role
in acrolein-induced protein damage in synaptosomal membranes: relevance to
brain lipid peroxidation in neurodegenerative disease. Neurochem Int 2001 Aug;39(2):141-9; & (c) Pearce RK, Owen A, Daniel S, Jenner P,
Marsden CD. Alterations in the distribution of glutathione in the
substantia nigra in Parkinson's disease. J Neural Transm. 1997;104(6-7):661-77; & A.D.Owen et al, Ann NY
Acad Sci, 1996, 786:217-33; & JJ Heales et al, Neurochem Res, 1996,
21(1):35-39; & X.M.Shen et al,
Neurobehavioral effects of NAC conjugates of dopamine: possible relevance for
Parkinson’sDisease”, Chem Res Toxicol,
1996, 9(7):1117-26; & Chem Res Toxicol, 1998, 11(7):824-37; & (d) Li
H, Shen XM, Dryhurst G. Brain mitochondria catalyze the oxidation of
7-(2-aminoethyl)-3,4-dihydro-5-hydroxy-2H-1,4-benzothiazine-3-carboxyli
c acid (DHBT-1) to intermediates that irreversibly inhibit complex I and
scavenge glutathione: potential relevance to the pathogenesis of Parkinson's
disease. J Neurochem.
1998 Nov;71(5):2049-62;& (e) Araragi
S, Sato M. et al, Mercuric chloride induces apoptosis via a
mitochondrial-dependent pathway in human leukemia cells. Toxicology.
2003 Feb 14;184(1):1-9.
(57) N.Campbell
& M.Godfrey,“Confirmation of Mercury Retention and
Toxicity using DMPS provocation” ,J of
Advancement in Medicine, 7(1) 1994;(80 cases);
&(b)D.Zander et al, “Mercury
mobilization by DMPS in subjects with and without amalgams”, Zentralbl Hyg Umweltmed, 1992, 192(5):
447-54(12 cases);
(60) V.D.M.Stejskal,
Dept. Of Clinical Chemistry, Karolinska Institute,
IMMUNO‑STIMULATION
ASSAY ‑MELISA”
& VDM Stejskal et al, "MELISA: tool for the study of
metal
allergy", Toxicology in Vitro, 8(5):991-1000, 1994.
(66) “Regional
brain trace‑element studies in Alzheimer's disease”. C.MThompson&W.R.
Markesbery, et al, Univ. Of
(67) A search
for longitudinal variations in trace element levels in nails of Alzheimer's
disease patients. Vance DE Ehmann WD Markesbery WR In: Biol Trace Elem Res
(1990 Jul‑Dec)26‑27:461‑70; & Ehmann et al, 1986,
Neurotoxicology, 7:195-206; & Thompson et al, 1988, Neurotoxicology,
9:1-7.
(84) J.C.Veltman
et al, “Alterations of heme, cytochrome P-450, and steroid metabolism by
mercury in rat adrenal gland”, Arch Biochem Biophys, 1986, 248(2):467-78; &
A.G.Riedl et al, Neurodegenerative Disease Research Center, King’s College,UK,
“P450 and hemeoxygenase enzymes in the basal ganglia and their role’s in
Parkinson’s disease”, Adv Neurol, 1999; 80:271-86.
(85) J.A.Weiner
et al,“The relationship between mercury concentration
in human organs and predictor variables", Sci Tot Environ, 138(1-3):101-115,1993; & "An estimation of the uptake of
mercury from amalgam fillings in Swedish subjects", Science of the Total
Environment, v168,n3, p255-265, 1995.
(92) L. Tandon
et al, "Elemental imbalance studies by INAA on ALS patients", J
Radioanal Nuclear Chem 195(1):13-19,1995; & Y.Mano et al, “Mercury in the hair of ALS patients”, Rinsho Shinkeigaku, 1989, 29(7): 844-848; &
Mano et al, 1990, Rinsho Shinkeigaku
30: 1275-1277; & Khare et al,
1990, “Trace element imbalances in ALS”,
Neurotoxicology, 1990,11:521-532.
(94) F.Berglund,
Case reports spanning 150 years on the adverse effects of dental amalgam, Bio-Probe,
Inc.,Orlando,Fl,1995;ISBN 0-9410011-14-3(245 cured)
(95) H.J.Lichtenberg,
"Elimination of symptoms by removal of dental amalgam from mercury
poisoned patients", J Orthomol Med 8:145-148, 1993; & “Symptoms before and after removal of
amalgam”,J of Orth Med,1996,11(4):195- (119 cases)
(96) A.F.Goldberg et al, “Effect of Amalgam
restorations on whole body potassium and bone mineral content in
older men”,Gen Dent , 1996, 44(3): 246-8; &
K.Schirrmacher,1998, “Effects of lead, mercury, and methyl mercury on gap
junctions and [Ca2+]i in bone cells”, Calcif Tissue Int 1998 Aug;63(2):134‑9.
(97) O. Redhe
et al, "Recovery from ALS after removal of dental amalgam fillings",
Int J Risk & Safety in Med
4:229-236, 1994; & N.Vanacore et al, Dirparimento di Scienze
Neurologiche, Univer. La Sapienza,
Roma, Med Lav (
(98) A.Seidler
et al, Possible environmental factors for Parkinson's disease",Neurology
46(5): 1275- 1284, 1996; &
F.O.Vroom et al, "Mercury
vapor intoxication", 95: 305-318,
1972; & Ohlson et al, “Parkinsons Disease and Occupational Exposure
to Mercury”, Scand J. Of Work
Environment Health, Vol7, No.4: 252-256, 1981; L.G. Golota, “Theraputic
properties of Unitihiol” Farm. Zh. 1980, 1: 18-22; & Miller K, Ochudlo S, Opala G,
Smolicha W, Siuda J. [Parkinsonism in chronic occupational metallic mercury intoxication]
Neurol Neurochir Pol. 2003;37 Suppl
(102)R.L. Siblerud et al,"Evidence that mercury
from silver fillings may be an etiological factor in multiple sclerosis",
Sci Total Environ, 1994,v142,n3, p191- , & “Mental health, amalgam fillings, and MS”, Psychol Rep,1992,
70(3 Pt2), 1139-51; &
T.Engalls,Am J Forensic Med
Pathol, 4(1):1983, Mar, 55-61.
(111) (a) Quig D, Doctors Data Lab,"Cysteine metabolism and metal toxicity", Altern Med Rev, 1998;3:4, p262‑270, & (b) J.de
Ceaurriz et al, Role of gamma‑
glutamyltraspeptidase(GGC) and extracellular glutathione in dissipation of inorganic mercury",J Appl
Toxicol,1994, 14(3): 201‑; &
W.O. Berndt et al, "Renal glutathione
and mercury uptake", Fundam
Appl Toxicol, 1985, 5(5):832‑9;
& Zalups
RK, Barfuss DW. Accumulation and handling of inorganic mercury in the
kidney after coadministration with glutathione, J Toxicol Environ Health, 1995,
44(4): 385-99; & T.W.Clarkson et al, "Billiary secretion
of glutathione‑metal complexes",
Fundam Appl Toxicol, 1985, 5(5):816‑31;
(114) M.Aschner et al, “Metallothionein induction in
fetal rat brain by in utero exposure to elemental mercury vapor”, Brain Research, 1997, dec 5,
778(1):222-32; & Aschner
M, Rising L, Mullaney KJ. Differential sensitivity of neonatal rat astrocyte
cultures to mercuric chloride (MC) and methylmercury (MeHg): studies on K+ and
amino acid transport and metallothionein (MT) induction.
Neurotoxicology. 1996 Spring;17(1):107-16.
& T.V. O’Halloran, “Transition metals
in control of gene expression”, Science, 1993, 261(5122):715-25; & Matts
RL, Schatz JR, Hurst R, Kagen R. Toxic
heavy metal ions inhibit reduction of disulfide bonds. J Biol Chem 1991; 266(19): 12695-702; Boot
JH. Effects of
SH-blocking compounds on the energy metabolism in isolated rat hepatocytes. Cell Struct Funct 1995; 20(3): 233-8; & Baauweegers HG, Troost D. Localization of metallothionein in the
mammilian central nervous system.. Biol Signals 1994, 3:181-7.
(119)(a)
L.Ronnback et al, "Chronic encephalopaties induced by low doses of
mercury or lead", Br J Ind Med 49:
233-240, 1992; & H.Langauer‑Lewowicka,” Changes in the nervous system
due to occupational metallic mercury poisoning” Neurol Neurochir Pol 1997 Sep‑Oct;31(5):905‑13;
&(b) Kim P, Choi BH. “Selective inhibition of glutamate uptake by mercury
in cultured mouse astrocytes”, Yonsei Med J 1995; 36(3): 299-305; & Brookes
N. In vitro evidence for the role of glutatmate in the CNS
toxicity of mercury. Toxicology 1992, 76(3):245-56; & Albrecht J, Matyja
E. Glutamate: a potential mediator of
inorganic mercury toxicity. Metab Brain Dis 1996; 11:175-84.
(122) B.Ono et
al, “Reduced tyrosine uptake in strains sensitive to inorganic mercury”, Genet, 1987,11(5):399-
(126) (a)Singh I, Pahan K, Khan M,
(139) G.Sallsten et al, “Mercury in cerebrospinal fluid in
subjects exposed to mercury vapor”, Environmental Research, 1994; 65:195-206.
(142) Ariza ME; Bijur GN; Williams MV. Lead and
mercury mutagenesis: role of H2O2, superoxide dismustase, and xanthine oxidase. Environ Mol Mutagen 1998;31(4):352‑61; & M.E. Ariza et al, Mercury mutagenesis”, Biochem Mol Toxicol, 1999,
13(2):107-12; & M.E.Ariza et al,
Mutagenic
effect of mercury", InVivo 8(4):559-63,1994;
(145)
Carpenter DO. Effects
of metals on the nervous system of humans and animals.
Int J Occup Med Environ Health.
2001;14(3):209-18; & Vanacore N, Bonifati V, et al,
Epidemiology of multiple system atrophy. ESGAP
Consortium. European Study Group on Atypical
Parkinsonisms. Neurol Sci. 2001 Feb;22(1):97-9; & J.M.Gorell et
al, “Occupational exposure to mercury, manganese, copper, lead, and the risk of
Parkinson’s disease”, Neurotoxicology, 1999, 20(2-3):239-47;
& J.M. Gorell et al,”Occupational exposures to metals as
risk factors for Parkinson's disease”,
Neurology, 1997 Mar, 48:3, 650‑8.; & B.A.Rybicki et
al,”Parkinson's disease mortality and the industrial use of heavy metals in
Michigan”, Mov Disord, 1993, 8:1, 87‑92.; & (b) Chacon Pena JR, Duran
Ferreras E. Parkinsonism probably induced by manganese] [ Spanish] Rev Neurol.
2001 Sep 1;33(5):434-7; & Chun HS, Lee H, Son JH. Manganese induces
endoplasmic reticulum (ER) stress and activates multiple caspases in nigral
dopaminergic neuronal cells, SN4741.
Neurosci Lett. 2001 Dec 4;316(1):5-8;
& Discalzi G, Meliga F et al;
Occupational Mn parkinsonism: magnetic resonance imaging and clinical patterns
following CaNa2-EDTA chelation. Neurotoxicology. 2000
Oct;21(5):863-6.
(147) .M.Wood,"Mechinisms for the
Neurotoxicity of Mercury", in Organotransitional Metal Chemistry, Plenum Publishing Corp,
N.Y, N.Y, 1987.
& R.P. Sharma et al, “Metals and
Neurotoxic Effects”, J of Comp Pathology, Vol 91,
1981.
(148) H.R.Casdorph, Toxic
Metal Syndrome, Avery Publishing Group, 1995.
(149) B.Choi et al, "Abnormal
neuronal migration of human fetal brain", Journal of Neurophalogy, Vol 37,
p719-733, 1978; & F. Monnet-Tschudi et al, “Comparison of the developmental
effects of 2 mercury compounds on glial cells and neurons in the rat
telencephalon”,
Brain Research, 1996, 741: 52-59; & Chang LW, Hartmann HA, “Quantitative cytochemical studies of
RNA in experimental mercury poisoning”, Acta Neruopathol(Berlin), 1973,
23(1):77-83; & L.Larkfors et al,"Methylmercury induced alterations in
the nerve growth factor level in the
developing brain ", Res Dev
Res,62(2),1991,287- ; &(b) Belletti
S, Gatti R. Time
course assessment of methylmercury effects on C6 glioma cells: submicromolar
concentrations induce oxidative DNA damage and apoptosis. J
Neurosci Res. 2002 Dec 1;70(5):703-11.
(158) Wenstrup
et al, “Trace element imbalances in the brains of Alzheimers patients”,
Research, Vol 533,p125-131,1990; & F.L.Lorscheider,B.Haley,et al, “Mercury
vapor inhibits tubulin binding...”, F
(163) Ahlrot et al, Nutrition
Research, 1985 Supplement, & Second Nordic Symposium on Trace Elements
and Human Health, Odense, Denmark,
Aug 1987.
(166) H.Basun et al, J Neural Transm
Park Dis Dement Sect, “Metals
in plasma and cerebrospinal fluid in
normal aging and Alzheimer’s
disease”,1991,3(4):231-58.
(169) C.H.Ngim et al, Neuroepidemiology,”Epidemiologic
study on the association between body burden mercury level and idiopathic
Parkinson’s disease”,
1989, 8(3):128-41.
(170)R.L.Siblerud, “A commparison of mental health of
multiple schlerosis patients with silver
dental fillings and those with fillings removed”, Psychol Rep, 1992, 70(3),Pt2,
1139-51.
(181) P.W. Mathieson, “Mercury: god of TH2 cells”,1995, Clinical Exp Immunol.,102(2):229-30; & (b) Heo Y,
Parsons PJ, Lawrence DA, Lead differentially modifies cytokine production in
vitro and in vivo. Toxicol Appl
Pharmacol, 196; 138:149-57;
(183) World Health Organization(WHO),1991,
Environmental Health criteria 118,
Inorgtanic Mercury, WHO,
(184)T.H.Ingalls, J Forsenic Medicine and
Pathology, Vol 4, No 1, 1953; & Epidemiology, etiology and prevention of MS”,Am J Fors Med & Pathology, 1983, 4:55-61; & “Endemic clustering of MS”, Am J.Fors Med Path, 1986,7:3-8.
(194)
(197) J.Taylor, A Complete Guide to Mercury
Toxicity from Dental Fillings ,Scripps Pullishing;
(198)E.S. West et al, Textbook of Biochemistry, MacMillan Co, 1957,p853;& B.R.G.Danielsson
et al,”Ferotoxicity of inorganic mercury: distribution and effects of nutrient
uptake by placenta and fetus”, Biol Res Preg Perinatal. 5(3):102-109,1984; &
Danielsson et al, Nurotoxicol. Teratol., 18:129-134;
(204)Tom Warren, Beating Alzheimer’s, Avery Publishing Group,
1991.
(207)Boyd Haley, Univ. Of
(212)Ziff, M.F., “Documented
Clinical Side Effects to Dental Amalgams”, ADV. Dent. Res.,1992; 1(6):131-134; & S.Ziff,Dentistry without Mercury, 8th Edition, 1996, Bio-Probe, Inc., ISBN
0-941011-04-6; & Dental Mercury
Detox, Bio-Probe, Inc.
http://www.bioprobe.com. (cases:FDA Patient
Adverse Reaction Reports-762,
Dr.M.Hanson-Swedish patients-519,
Dr. H. Lichtenberg-100 Danish patients,Dr. P.Larose- 80 Canadian
patients, Dr. R.Siblerud, 86
(213)Dr. C. Kousmine, Multiple Scherosis is
Curable, 1995.
(221)R. Golden et al,
(222)M. Daunderer, Handbuch der Amalgamvergiftung, Ecomed Verlag, Landsberg 1998, ISBN 3‑609‑71750‑5 (in German); & “Improvement of Nerve and Immunological Damages after Amalgam Removal”, Amer. J. Of Probiotic Dentistry and Medicine, Jan 1991; & Toxicologische erfahrungen am menchen; Quecksilber in der umwelf-hearing zum amalgamproblem