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), fibromyalgia, lupus, rheumatoid arthritis, Parkinson’s, multiple sclerosis (MS),  amyotropic lateral sclerosis(ALS), depression, autism, ADHD, eczema, asthma, etc. (14,1,2,hyperlinks). 

                            

  References

 

(1) MELISA blood lymphocyte immune reactivity  test, MELISA medical labs, 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

(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

(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

 

(12) Dr. A Holmes, Autism Treatment Center,Baton Rouge, La, http://healing‑arts.org/children/holmes.htm; & 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; 1996 , 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     &   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

(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