**Susceptibility factors in mercury toxicity: immune reactivity,
detoxification system function, enzymatic blockages, synergistic
exposures. B. Windham(Ed.)**

It is well documented in the medical literature that the major factors
in mercury toxicity effects in addition to dose are susceptibility
factors like immune reactivity(1,2), degree of other toxic exposures and
synergisms(3,15), systemic detoxification ability based on blood allele
type(4,15) or metallothionein function(5), sulfur detoxification
deficiencies(6), or other inhibited enzymatic processes related to
detoxification(7-10) . It has been shown that such susceptibility
factors can play a larger role in effects than dose among a population
with significant exposure to mercury and at extremely low levels of
exposure.

Those with the genetic allele ApoE4 protein in the blood have been found
to detox metals poorly and to be much more genetically susceptible to
chronic neurological conditions than those with types ApoE2 or
E3(4,11,15). Researchers have shown that genetic carriers of the brain
protein APO E2 are protected against Alzheimer\'s disease (AD) whereas
genetic carriers of the APO E4 genotype are at enhanced risk factor for
developing AD. APO E proteins are synthesized in the brain with the
assigned physiological task of carrying waste material from the brain to
the cerebrospinal fluid, across the blood brain barrier into the plasma
where the material is cleared by the liver. The biochemical difference
between APO E2 and APO E4 is that APO E2 has two additional thiol
groups, capable of binding and removing mercury (and ethyl mercury) that
APO E4 does not have. The second highest concentration of APO E proteins
is in the cerebrospinal fluid. Therefore, the protective effects of APO
E2 is due to its ability to protect the brain from exposure to oxidants
like mercury and ethyl mercury by binding these toxicants in the
cerebrospinal fluid and keeping them from entering the brain.

Recent studies found that prenatal mercury exposures from mother's
amalgams and other sources along with susceptibility factors such as
ability to excrete mercury appear to be major factors in those with
chronic neurological conditions like autism(11,15,20). Infants whose
mothers received prenatal Rho D immunoglobulin injections containing
mercury thimerosal for RH factor or whose mother's had high levels of
amalgam fillings had a much higher incidence of autism. While the hair
test levels of mercury of infants without chronic health conditions like
autism were positively correlated with the number of the mother's
amalgam fillings, vaccination thimerosal exposure, and mercury from
fish, the hair test levels of those with chronic neurological conditions
such as autism were much lower than the levels of controls and those
with the most severe effects had the lowest hair test levels, even
though they had high body mercury levels. This is consistent with past
experience of those treating children with autism and other chronic
neurological conditions(12).

Large studies of U.S. dentists and dental assistants have found that
mercury level in urine is significantly associated with neurological
dysfunction using several different measures, but that those with a
polymorphism in blood heme (CPOX4) or to a polymorphism in neurofactor
(BDNF) were more susceptible to neurological effects(19).

Studies have documented that prenatal mercury exposure causes lasting
effects that causes increased susceptibility to future toxic exposures.
The effects of chronic, low-dose fetal and lactational organic (MeHgCl)
and inorganic (HgCl2) mercury intoxication on epilepsy/seizures were
investigated and compared in rats and were found to have significant
correlations between seizure susceptibility and cortical mercury
level(16) Inorganic mercury exposure facilitated the duration of seizure
discharges in younger animals and appeared to be more permanent than
methyl mercury exposure. Another researcher had similar findings for
infants(17). A study of children of mothers consuming a marine diet
which exposes them to mercury, found that there are significant
cardiovascular effects as birth mercury blood level increases from 1
microgram per liter to 10 ug/L(a), as well as effects on ability to
respond to sensory stimuli in exposed children later in life(18).
Children with lower birth weights experienced blood pressure increases
about 50% higher than normal birth weight children having similar
mercury levels. At seven years of age, clear dose-response relationships
were observed for deficits in attention, language, and memory(b). Thus a
levels of exposure below current Government health safety limits,
mercury is documented to have significant cardiovascular effects and the
recommended limit for mercury has been decreased from the former limit
of 10 ug/L in blood.

The mechanisms by which low level chronic mercury exposure causes over
30 chronic health conditions such as those looked at in this review are
well documented in the literature; and the fact that those treated for
mercury toxicity usually recover after treatment is also well documented
by many dozens of medical studies in the literature and thousands of
clinical cases(13). Some of the autoimmune conditions commonly caused by
immune reactivity to mercury include chronic fatigue
syndrome([CFS](http://www.home.earthlink.net/~berniew1/cfsfm.html)),
[fibromyalgia](http://www.home.earthlink.net/~berniew1/cfsfm.html),
[lupus](http://www.home.earthlink.net/~berniew1/ms.html), rheumatoid
arthritis,
[Parkinson's](http://www.home.earthlink.net/~berniew1/parkins.html),
multiple sclerosis
([MS](http://www.home.earthlink.net/~berniew1/ms.html)), amyotropic
lateral
sclerosis([ALS](http://www.home.earthlink.net/~berniew1/als.html)),
[depression](http://www.home.earthlink.net/~berniew1/depress.html),
[autism](http://fclv.com/kidshg.html),
[ADHD](http://fclv.com/tmlbn.html),
[eczema](http://www.home.earthlink.net/~berniew1/immunere.html),
[asthma](http://www.home.earthlink.net/~berniew1/inflamhg.html), etc.
(14,1,2,hyperlinks).

References

\(1\) MELISA blood lymphocyte immune reactivity test, MELISA medical
labs, [www.melisa.org](http://www.melisa.org/); autoimmune autism caused
by thimerosal: <http://www.melisa.org/autism.php>

V.D.M.Stejskal, Dept. Of Clinical Chemistry, Karolinska Institute,
Stockholm, Sweden LYMPHOCYTE IMMUNO‑STIMULATION ASSAY ‑MELISA" , VDM
Stejskal et al, \"MELISA: tool for the study of metal allergy\",
Toxicology in Vitro, 8(5):991-1000, 1994; & "Mercury-specific
Lymphocytes: an indication of mercury allergy in man", J. Of Clinical
Immunology, 1996, Vol 16(1);31-40; & Stejskal J, Stejskal V. The role of
metals in autoimmune diseases and the link to neuroendocrinology
Neuroendocrinology Letters, 20:345‑358, 1999.
[www.melisa.org/knowledge/education14.html](http://www.melisa.org/knowledge/education14.html)

\(2\) Sterzl I, Prochazkova J, Stejaskal VDM et al, Mercury and nickel
allergy: risk factors in fatigue and autoimmunity. Neuroendocrinology
Letters 1999; 20:221-228; & Sterzl I, Hrda P, Prochazkova J, Bartova J,
Reactions to metals in patients with chronic fatigue and autoimmune
endocrinopathy. Vnitr Lek 1999 Sep;45(9):527‑31; & P.W. Mathieson,
"Mercury: god of TH2 cells",1995, Clinical Exp Immunol

\(3\) Schubert J, Riley EJ, Tyler SA. Combined effects in toxicology. A
rapid systematic testing procedure: cadmium, mercury, and lead. Toxicol
Environ Health 1978;4(5/6):763-776.

\(4\) American College of Medical Genetics Working Group findings on
ApoE4 strong connection to Alzheimer's, JAMA, 1995,274:1627-29. ; & Duke
Univ. Medical Center, www.genomics.duke.edu/pdf/Alzheimer.pdf & Godfrey
ME, Wojcik DP, Krone CA. Apolipoprotein E genotyping as a potential
biomarker for mercury neurotoxicity. J Alzheimers Dis. 2003
Jun;5(3):189-95.

\(5\) Walsh WJ, Pfeiffer Treatment Center, Metal‑Metabolism and Human
Functioning, 2000, www.hriptc.org/mhfres.htm; & Walsh, WJ, Health
Research Institute, Autism and Metal
Metabolism,www.hriptc.org/autism.htm, Oct 20, 2000; & **(MT) and Toxic
Metal Sensitivity, Pfeiffer Treatment Clinic, Dr. W. Walsh et al,
[www.flcv.com/ptcmt.html](http://www.flcv.com/ptcmt.html)**

\(6\) Mc Fadden SA, Phenotypic variation in xenobiotic metabolism and
adverse environmental response: focus on sulfur-dependent detoxification
pathways. Toxicology, 1996, 111(1-3):43-65; & 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; & 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; &
T.L. Perry et al, "Hallevorden-Spatz Disease: cysteine accumulation and
cysteine dioxygenase defieciency", Ann Neural, 1985, 18(4):482-489.

\(7\) Mondal MS, Mitra S. Inhibition of bovine xanthine oxidase activity
by Hg2+ and other metal ions. J Inorg Biochem 1996; 62(4): 271-9; &

\(8\) Sastry KV, Gupta PK. In vitro inhibition of digestive enzymes by
heavy metals and their reversal by chelating agents: Part 1, mercuric
chloride intoxication. Bull Environ Contam Toxicol 1978; 20(6): 729-35;
& W.Y.Boadi et al, Dept. Of Food Engineering and Biotechnology, T-I Inst
of Tech., Haifa, Israel, "In vitro effect of mercury on enzyme
activities", Environ Res, 1992, 57(1):96-106;

\(9\) J.R. Cade et al, Autism and schizophrenia linked to malfunctioning
enzyme for milk protein digestion. Autism, Mar 1999.
http://www.hsc.ufl.edu/post/post0399/post03_19/1.html; & Reichelt KL et
al, Biologically active peptide-containing fractions in schizophrenia
and childhood autism. Adv Biochem Psychopharmocol 1981; 28: 627-43; &
Shibuya-Saruta H, Kasahara Y, Hashimoto Y. Human serum dipeptidyl
peptidase IV (DPPIV) and its unique properties. J Clin Lab Anal.
1996;10(6):435-40; & Blais A, Morvan-Baleynaud J, Friedlander G, Le
Grimellec C. Primary culture of rabbit proximal tubules as a cellular
model to study nephrotoxicity of xenobiotics. Kidney Int. 1993
Jul;44(1):13-8; & Puschel G, Mentlein R, Heymann E, \'Isolation and
characterization of dipeptidyl peptidase IV from human placenta\', *Eur
J Biochem* 1982 Aug;126(2):359-65; & Kar NC, Pearson CM. Dipeptyl
Peptidases in human muscle disease. Clin Chim Acta 1978; 82(1-2):
185-92.

\(10\) Edelson SB, Cantor DS. Autism: xenobiotic influences. Toxicol Ind
Health 1998; 14(4): 553-63; & Liska, DJ. The detoxification enzyme
systems. Altern Med Rev 1998. 3(3):187-98;

\(11\) A.S. Holmes, M.F. Blaxill and B.E. Haley, *Reduced Levels of
Mercury in First Baby Haircuts of Autistic Children;* International
Journal of Toxicology, 2003, & Baby hair, mercury toxicity and autism.
Int J Toxicol. 2004 Jul-Aug;23(4):275-6. Grether J, Croen L, Theis C,
Blaxill M, Haley B, Holmes A.

[www.ncbi.nlm.nih.gov/pubmed/12933322?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum](http://www.ncbi.nlm.nih.gov/pubmed/12933322?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum)

\(12\) Dr. A Holmes, Autism Treatment Center,Baton Rouge, La,
[http://healing‑arts.org/children/holmes.htm](); &
[www.flcv.com/autismc.html](http://www.flcv.com/autismc.html) ; &
L.Redwood, Mercury and Autism, Vitamin Research News, May 2001,
15(5):1-12; & Jaquelyn McCandless, M.D., Autism Spectrum Treatment
Center, Woodland Hills, CA,& Jaquelyn McCandless, M.D, Children with
Starving Brains, A Medical Treatment Guide for Autism Spectrum Disorder,
2003 ;
[www.autism‑rxguidebook.com/DesktopDefault.aspx?tabindex=11&tabid=15]()
; & Andrew H. Cutler, PhD, PE; [Amalgam Illness:*Diagnosis and
Treatment*]{.underline}; 1996 ,
[www.noamalgam.com/](http://www.noamalgam.com/)

\(13\) B. Windham, Review: Mechanisms by which mercury causes over 40
chronic health conditions and clinical cases involving recovery from
these conditions after amalgam replacement (over 60,000 clincial cases)

[www.flcv.com/indexa.html](http://www.flcv.com/indexa.html) &
[www.flcv.com/hgremove.html](http://www.flcv.com/hgremove.html)

\(14\) B. Windham, Review:The Mercury Connection to Allergies and Immune
Reactive Conditions: allergies, asthma, eczema, diabetes, autism, etc.
in children and chronic fatigue, Fibromyalgia, lupus, psoriasis, oral
lichen planus, multiple sclerosis in adults.
[www.www.flcv.com/damspr14.html](http://www.www.flcv.com/damspr14.html)

\(15\) B.E. Haley/Medical Veritas 2 (2005) 535û542 535 Mercury toxicity:
Genetic susceptibility and synergistic effects; & **Mutter J**,
**Naumann J**, **Sadaghiani C**, **Schneider R**, **Walach H**.
Alzheimer disease: mercury as pathogenetic factor and apolipoprotein E
as a moderator. Neuro Endocrinol Lett. 2004 Oct;25(5):331-9.

\(16\) Effects of continuous low-dose exposure to organic and inorganic
mercury during development on epileptogenicity in rats. Szasz A, Barna
B, et al,

Neurotoxicology. 2002 Jul;23(2):197-206.\
(17) D.Klinghardt(MD), "Migraines, Seizures, and Mercury Toxicity",
Future Medicine Publishing, 1997

\(18\) (a) More evidence of mercury effects in children; Environ Health
Perspect. 1999 Nov;107(11):A554-5; & Epidemiology   July
1999;10:370-375; & (b) \[Environmental epidemiology research leads to a
decrease of the exposure limit for mercury\] \[Article in Danish\] Weihe
P, Debes F, White RF, Sorensen N, Budtz-Jorgensen E, Keiding N,
Grandjean P. Ugeskr Laeger. 2003 Jan 6;165(2):107-11.

\(19\) Echeverria D, Woods JS, et al, Chronic low-level mercury
exposure, BDNF polymorphism, and associations with cognitive and motor
function. Neurotoxicol Teratol. 2005 Nov-Dec;27(6):781-96: & The
association between a genetic polymorphism of coproporphyrinogen
oxidase, dental mercury exposure and neurobehavioral response in humans.
Neurotoxicol Teratol. 2006 Jan-Feb;28(1):39-48. Epub 2005 Dec 15;
Echeverria D, Woods JS,

\(20\) Mercury and autism: accelerating evidence? Mutter J, Naumann J,
Schneider R, Walach H, Haley B. Neuro Endocrinol Lett. 2005
Oct;26(5):439-46