Immune Reactive Conditions: The mercury connection to inflammatory and immune reactive conditions (asthma, eczema, lupus, Scleroderma, celiac, chron’s, allergies,etc.)

I. Increasing Incidence of Inflammatory, Immune Reactive Conditions

The incidence of allergic and immune reactive conditions such as allergies, asthma, eczema, lupus, psoriasis, etc. have been increasing rapidly in the United States over the last decade(1-4). The prevalence of asthma doubled over the last decade(4) to approximately 31 million, 11.5% of the total population(2). At least 50 million have allergies(19%)(3), and the largest increase has been in infants(1-4), with approximately 10 % of infants- approximately 15 million in the U.S. with systemic eczema(1). Approximately 12% have had chronic sinusitis(3c). Many studies have found exposure to mercury and other heavy metals to be common causes of such conditions as will be shown in this paper.

II. Oral Metal Exposures from Dental Materials and Oral Effects

The largest source of exposure to the metals that will be shown to commonly cause inflammatory, immune reactive conditions is from dental metals. Having dissimilar metals in the teeth, e.g.- amalgam(mercury,copper,tin,silver), gold alloys(gold,palladium), nickel or stainless steel crowns(nickel,cobalt) causes galvanic electrical currents, and much higher mercury vapor levels in oral air and metal levels in oral tissues. (101-110). Government agencies and medical studies have found that the largest source of mercury exposure in most people is from dental amalgam fillings(122-130). For those with amalgam dental fillings, exposure from fillings amounts to from 50 to 90 percent of exposure, with the average being about 75 % of total exposure (123,125‑130). Mercury is an unusual metal commonly a liquid at room temperature and vaporizing to a gas from its liquid or solid states. The studies found that mercury amalgams are unstable due to mercury's vaporization and galvanic action(101-110), leaking mercury vapor continuously into the lungs and saliva at levels exceeding government health standards(110,122,124,126). Dental amalgam is also a major source of methyl mercury exposure for many since oral and intestinal mercury is methylized by oral bacteria and other methyl donars(121,130). The other most common sources of mercury exposure are methyl mercury from fish or mercury thimerosal from vaccines, which is a major source of exposure mostly for infants or those frequently receiving flu shots(113).

The amount of mercury released into saliva has been found by large studies to be about 1.5 to 1.9 micrograms per liter for each additional amalgam filling (116), resulting in an increase of about 1 microgram per liter in urine(125) and even higher levels excreted in feces(128). Average mercury levels in gum tissue near amalgam fillings are over 100 ppm, and are the result of flow of mercury into the mucous membrane because of galvanic currents with the mucous membrane serving as cathode and amalgam metals as anode(101,104,105,114). Concentrations of mercury in oral mucosa for a population of patients with 6 or more amalgam fillings taken during oral surgery were 20 times the level of controls(114). Amalgam also releases significant amounts of silver, tin, and copper which also have toxic effects, with organic tin compounds formed in the body being even more neurotoxic than organic mercury.

Mercury and other metals accumulate in the oral cavity in fibroblasts, macrophages, and multinuclear giant cells of connective tissue, in blood vessel walls, along nerve sheath fibres, in basement-membranes of mucosal epithelium, striated muscle fibres, along collagen bundles and elastic tissue, in acini of salivary glands, and in tooth roots and jaw bones(104,105). Such mercury including that in the commonly formed amalgam tattoos moves to other parts of the body over time in significant amounts and more rapidly than the other metals. Macrophages remove mercury by phagocytosis and the mercury moves to other parts of the body through the blood and along nerves. Oral galvanism, where electric currents caused by mixed metals in the mouth take the metals into the gums and oral mucosa, results in accumulating mercury and other dental metals at the base of teeth with large amalgam fillings or metal crowns over amalgam base(101-111). Such metals are documented to cause local and systemic lesions and health effects such as inflamed tissues, metal mouth, discomfort, tooth pain, gingivitis, and oral lichen planus(102-107,111,15,16,39-43). Most usually improve from these conditions after removal of amalgam fillings and/or the amalgam tattoos by surgery(102,106,107,109,73b,126,127,15,16,39-43). The high levels of accumulated mercury also are dispersed to other parts of the body. Some studies have also found persons with chronic exposure to electromagnetic fields(EMF) to have higher levels of mercury exposure and excretion(117,118). Such fields are known to induce current in metals and would increase the effects of galvanism..

III. Mechanisms by Which Mercury and Heavy Metals Cause Chronic Inflammatory Conditions

Metals like mercury bind to SH-groups(sulfhydryl) in sulfur compounds like amino acids

and proteins, changing the structure of the compound that it is attached to. This often results in suppression of the immune system and in the immune systems T-cells not recognizing them as appropriate nutrients and attacking them(78,18) with chronic exposure resulting in autoimmunity. Such binding and autoimmune damage has also been documented in collagen(18). Metals by binding to SH radicals in proteins and other such groups can cause autoimmunity by modifying proteins which via T-cells activate B-cells that target the altered proteins inducing autoimmunity as well as causing aberrant MHC II expression on altered target cells(81de).

Mercury and other toxic metals cause release of inflammatory cytokines such as Tumor Necrosis Factor-alpha(TNFa) and Interleukin-4 (47), which will be documented to be factors in the chronic inflammatory conditions discussed here, including asthma, lupus, rheumatoid arthritis, Scleroderma, celiac and chron’s disease, etc. Studies have demonstrated that low concentrations of mercury(HgCl2,ie, 10(-9)-10(-15) M) significantly enhanced chemiluminescence, as well as stimulated H2O2 production by polymorphonuclear leukocytes(137). These studies clearly demonstrate the ability of extremely low levels of HgCl2 not only to suppress various PMN leukocyte functions involved in host defense, but also to stimulate reactive oxygen metabolism(137,95). In vivo, these HgCl2 effects would not only compromise host defense but also promote tissue injury via the local production of reactive oxygen metabolites. This has been demonstrated increase effects of factors in cardiovascular disease and neurological disease. Melatonin, vitamin E, and vitamin C have been found to counter these adverse effects(95a).

HgCl2 induces a protein kinase C-dependent Ca2+ influx through L-type calcium channels(65acd). The calcium/calcineurin-dependent pathway and protein kinase C activation are both implicated in HgCl2-induced IL-4 gene expression; and HgCl2 can activate directly protein kinase C, which is one of the main intracellular targets for HgCl2. Inorganic mercury exposure results in T cell polyclonal activation and the expansion of pathogenic autoreactive anti-class II Th2 cells . These cells produce interleukin (IL)-4 and induce a B cell polyclonal activation that is responsible for autoimmune disease. These effects of HgCl2 appear to be independent of antigen-specific recognition.

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, nickel, aluminum, and other toxic metals are documented to inhibit Na(+),K(+)-ATPase function at very low levels of exposure(94,97,65). Studies have found that in asthma, lupus, rheumatoid arthritis, Scleroderma, celiac/chron’s/IBS, and eczema cases there was a reduction in serum magnesium and red blood cell(RBC) membrane Na(+)-K+ ATPase activity and an elevation in plasma serum digoxin (87-90,65). The activity of some free-radical scavenging enzymes, concentration of glutathione decreased significantly, 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 that mercury and toxic metals are common causes of these conditions (22,30,29,47-50,65,87-90,95,96,98,28,etc.) A study found that 39% of a group of chron’s disease patients tested were immune reactive to nickel (100).

Studies have also found mercury and lead cause autoantibodies to neuronal proteins and neurofilaments, (18,79ag,80,82). The thymus gland plays a significant part in the establishment of the immune system and lymphatic system from the 12^th week of gestation until puberty. Inhibition of thymus function can thus affect proper development of the immune and lymphatic systems. Lymphocyte differentiation, maturation and peripheral functions are affected by the thymic protein hormone thymulin. Mercury at very low concentrations has been seen to impair some lymphocytic functions causing subclinical manifestations in exposed workers. Animal studies have shown mercury significantly inhibits thymulin production at very low micromolar levels of exposure(131). The metal allergens mercuric chloride and nickel sulfate were found to stimulate DNA synthesis of both immature and mature thymocytes at low levels of exposure, so chronic exposure can have long term effects(132). Nickel in stainless steel braces and crowns is a source of reactivity and autoimmunity along with gold and palladium in crowns(32bc,16-18) Also, micromolar levels of mercuric ions specifically blocked synthesis of ribosomal RNA, causing fibrillarin relocation from the nucleolus to the nucleoplasm in epithelial cells as a consequence of the blockade of ribosomal RNA synthesis(133,81e). This appears to be a factor in deregulation of basic cellular events and in autoimmunity caused by mercury. There were specific immunotoxic and biochemical alterations in lymphoid organs of mice treated at the lower doses of mercury. The immunological defects were consistent with altered T-cell function as evidenced by decreases in both T-cell mitogen and mixed leukocyte responses. Mercury caused increased immunoreactivity for glial fibrillary protein at 1 nanamole (0.2 ppb) concentration, and microglial response at even lower levels(134). There was a particular association between the T-cell defects and inhibition of thymic pyruvate kinase, the rate-limiting enzyme for glycolysis(135). Pyruvate and glycolysis problems are often seen in mercury toxic children being treated for autism(136).

One mechanism of mercury’s affect on contact sensitivities is the inhibition of glutathione S- transferase(92), which is a modulator of inflamation. Mercury also causes intestinal damage and leaky gut, causing metabolic damage and increasing food sensitivities(93). Inorganic mercury was found to be a cause of systemic eczema and digestive problems by a Japanese study(15).

Many studies including patch tests and immune reactivity tests have been carried out to assess the level of mercury sensitivity in different populations. They have found that there is a significant portion of the population that are reactive and sensitive to mercury and such have significant effects. In a group of medical students tested by patch test, 13 % were sensitive to mercury(20). The mercury sensitized students were found to have more than average number of amalgam fillings, higher hair mercury than non-sensitized students, and more allergic reactions to other things such as cosmetics, soaps, shampoos, etc. Many other studies have found similar levels of sensitization in recent years, with those populations with higher exposures such as those with many fillings or dental staff tending to have higher levels of sensitization(17-19) and more adverse health effects. In a group of 8 with contact eczema patch tested for mercury in Spain, all were positive for mercurochrome, six to inorganic mercury, and some to thimerosal(21). This study like several others noted the danger in patch tests for mercury as 2 of the patients suffered anaphylactic shock after the patch test due to the extreme immune reactivity of some to mercury.

Allergic contact eczema is the most frequent occupational disease (1,91), and the most common cause of contact eczema is exposure to metals(1, 5-14). The metals most commonly causing allergic immune reactivity are nickel, mercury, chromium, cobalt, and palladium(5-13,18, 60,91). The highest level of sensitization is to Infants, who are most reactive to thimerosal, a form of mercury that has been used as a preservative in vaccines and eye drops(14).

Antigen specific LST-test was performed on a large number of patients with atopic eczema(33), using T-cells of peripheral blood. 87% showed LST positive reactions to Hg, 87% to Ni, 38% to Au and 40% to Pd They removed LST positive dental metals from the oral cavities of patients. Improvement of symptoms was obtained in 82% (160/196) of the patients within 1-10 months. Similar results have been obtained at other clinics(34-38).***

Dental staff have been found to have significantly higher prevalence of eye problems, conjunctivitis, atopic dermatitis, and contact urticaria(91c). Finnish dental staff have the highest occupational risk of contact dermatitis with 71% affected over time(91b) with plastics, rubber, and mercury the most common causes of sensitization. Korean dental technicians have a high incidence of contact dermatitis, with dental metals the most common sensitizers. Over 25% had contact dermatitis with over 10% sensitive to 5 metals, chromium, mercury, nickel, cobalt, and palladium(91a). 16.3% were immune reactive to mercury.

In asthma allergen related T-lymphocytes cause release of inflammatory mediators from mast cells, esinophils, and lymphocytes, along with inflammatory cytokins such as Interleulin-4(Il-4), TNF-alpha, histamine, and increased IgE(49i). It has also been documented that the majority of cases have decreased serum magnesium levels, decreased NA+K+ATPase levels, and increased digoxin levels(an inhibitor of NA+K+ATPase)(49d). Mercury exposure has been documented to cause an increase in inflammatory cytokines such as TNF-alpha and IL-4(47,49b,49e,65a,81abc). TNFA-alpha has been found to increase the Ca(2+) sensitivity of agonist-stimulated phosphorylation and contractility in airway smooth muscle (ASM) and increase airway hyper-responsiveness(49a). TNFa levels have also been found to be significantly correlated to levels of the inflammatory cytokines Il-4, Il-8, Il-13 released from histamine-containing basophils which results in histamine releases and increased IgE levels, as well as airway reactivity, and asthmatic attacks(49acfkl). The release of these inflammatory cytokines has also been shown to be a factor in mercury’s inducement of autoimmunity that is involved in the development of airway inflammation(49g).

Asthmatic patients are especially susceptible to air pollution. Upon contact with an allergen, sensitized mast cells release highly active proinflammatory mediators. Allergen-mediated mast cell activation is an important mechanism in the pathogenesis of atopic asthma. Epidemiologic studies found a positive correlation between severity of symptoms among asthmatic patients and the level of particulate matter (PM) in the air. Among the constituents of PM are metals and transition metals. A Polish study(49b) observed that several metal and transition metal ions activated mast cells and enhanced allergen-mediated mast cell activation.

Metal and transition metal ions also induced significant secretion of interleukin (IL)-4 and increased antigen-mediated IL-4 secretion in mast cells. These effects of metal and transition metal ions on mast cells were observed at concentrations that do not result in direct cytotoxicity.

Genetic characteristics have been found that affect the susceptibility

Many clinics and studies involving thousands of patients have found that patients with allergic reactive conditions such as oral lichen planus, eczema, chronic allergies etc. usually recover or have significant improvements after amalgam replacement. Of a group of 86 patients with CFS symptoms, 78% reported significant health improvements after replacement of amalgam fillings within a relatively short period, and MELISA test found significant reduction in lymphocyte reactivity compared to pre removal tests(17). The improvement in symptoms and lymphocyte reactivity imply that most of the Hg-induced lymphocyte reactivity is allergenic in nature. Patients with other systemic neurological or immune symptoms such as arthritis, myalgia, OLP, MCS, MS, etc. also often recover after amalgam replacement(15-18). Cases of documented clinical cases with recovery after amalgam replacement include:

eczema and contact dermatitis(22,33,34,52-54,16b,99), psoriasis(33-36, 99), asthma(50,52,72,99),

lupus(16b,27,33,70,71,31,18),allergies(22,31,32,43,48,49,52,53,66-74,99), chronic multiple chemical sensitivities (32,52,70,71,73,75-77,17,31),

Oral lichen planus (15,16,39-43), CFS (17,31,33,52-54,66,70,71,75,84,85)

and muscular/joint pain/fibromyalgia (17,31,53,72,84) MS(16b,31,99) ***

As an example of experience of those with allergic conditions after amalgam replacement, a German study(52) followed a large group of patients. Over 50% followed indicated they experienced significant improvement after amalgam replacement for 5 chronic conditions followed: asthma, chronic bronchitis, polymyosis, eczema, contact allergy and food allergy. The study showed that skin allergy(patch) test apparently is not a reliable indicator of those with mercury related health problems. Patch test was positive in only 13.1 % of patients, whereas more than 50% of patients had significant health improvement for most conditions followed.***

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(50) (a)Katsunuma et al, “Anaphylaxis improvement after removal of amalgam fillings”, Annals of Allergy, 1990, 64(5):472-75; & (b)Yoshida S, Mikami H, Nakagawa H, Amayasu H. Amalgam allergy associatiated with exacerbation of aspirin-intolerant asthma. Clin Exp Allergy 1999; 29(10): 1412-4; & (c) M.Drouet et al, “Is mercury a respiratory tract allergen?”, Allerg Immunol(Paris),1990; 22(3):81.

(52) B.A.Weber, “The Marburg Amalgam Study”, Arzt und Umwelt, Apr, 1995; (266 cases)

& (b) B.A. Weber, “Amalgam and Allergy”, Institute for Naturopathic Medicine, 1994; &

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(53) S.Zinecker, “Amalgam: Quecksilberdamfe bis ins Gehirn”, der Kassenarzt, 1992, 32(4):23; “Praxiproblem Amalgam”, Der Allgermeinarzt, 1995,17(11):1215-1221. (1800 patients)

(54) A.Tosti et al, “Contact stomatitis”, Semin Cutan Med Surg, 1997, 16(4):314-9;

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& (b) D.B.Veprintsev, 1996, Russian Academy of Sciences, Pb2+ and Hg2+ binding to alpha‑lactalbumin”.Biochem Mol Biol Int 1996 ; 39(6): 1255‑65;

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(66)Melchart D, Wuhr E, Weidenhammer W, Kremers L. A multicenter survey of amalgam fillings and subjective complaints in non-selected patients in the dental practice. Eur J Oral Sci 1998; 106:770-77 (6,744 patients in 34 clinics)

(67)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;

(68) Daunderer M, 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”,Niedersachsiscles Umweltministerium, 1991; & “Amalgam”, Ecomed-Verlag, Landsberg, 1995; & “Amalgamtest”, Forum Prakt.Allgen.Arzt, 1990, 29(8): 213-4; & “Besserung von Nerven- und Immunschaden nach Amalgamsanierung”,Dtsch.Aschr. F. Biologische Zahnmedzin, 1990, 6(4):152-7. ( amalgam removal & DMPS,over 3,000 cases)

(69) 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)

(70) M.Davis,editor, Defense Against Mystery Syndromes”, Chek Printing Co., March, 1994 (case histories)

(71) Sven Langworth et al,”Amalgamnews and Amalgamkadefonden, 1997 and Svenska Dogbladet,1997 (286 cases); & F.Berglund,Bjerner/Helm,Klock,Ripa,Lindforss,Mornstad,Ostlin), “Improved Health after Removal of dental amalgam fillings”, Swedish Assoc. Of Dental Mercury Patients, 1998. (www.tf.nu) (over 1000 cases) (Sweden Gov’t maintains health records on all citizens) ; & Heavy Metal Bulletin, No.3,1996 and No.1, 1999, p7,8;

& Klock B, Blomgren J, Ripa U, Andrup B, "Effekt av amalgamavlägsnande på patienter som misstänker att de lider eller har lidit av amalgamförgiftning", Tandläkartidn 81(23):1297-1302 (1989) .

(72) P.Engel, “Beobachtungen uber die gesundheit vor und nach amalgamentfernug”,Separatdruck aus Schweiz. Monatsschr Zahnm. 1998, vol 108(8).(75 cases amalgam removal) http://soho.globalpoint.ch/paul‑engel (89% sigificant improvement)

(73) Lichtenberg, HJ "Elimination of symptoms by removal of dental amalgam from mercury poisoned patients", J Orthomol Med 8:145-148, 1993;

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& K.H.Friese, ”Homoopathische Behandlung der Amalgamvergiftung”, Allg. Homoopathische Z, 241(5); 184-187, &Erfahrungsheikunde, 1996, (4): 251-253;

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(75)Adolph Coors Foundation, “Coors Amalgam Study: Effects of placement and removal of amalgam fillings”, 1995. (www) & Internations DAMS Newsletter, p17, Vol VII, Issue 2, Spring 1997. (31 cases)

(76)G.Hall, V-TOX, Mercury levels excreted after Vit C IV as chelator‑ by number of fillings Int Symposium "Status Quo and Perspectives of Amalgam and Other Dental Materials" European Academy, Ostzenhausen/Germany. April 29 ‑ May 1, 1994; & Heavy Metal Bulletin, Apr 1996,Vol.3,Issue 1, p6-8 (200 cured or significantly improved)

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