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

I. Increasing Incidence of Inflammatory, Immune Reactive Conditions

The incidence of allergic and immune reactive conditions such as allergies, asthma, lupus, and allergic contact disease (eczema, psoriasis, etc.) increased 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).

Inflammation has been found to be a major factor in many chronic health conditions, including cardiovascular problems, diabetes, arthritis, depression, osteoporosis, periodontal disease, joint stiffness, chronic fatigue, fibromyalgia, age-related immune dysfunction, etc. (186,188) 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

Exposure to metals has been found to be one of the most common causes of allergic contact diseases (ACD) and other allergic and immune reactive conditions.  One of the largest sources 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. (101-110,184,185).    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). EMF and wi-fi exposure increase mercury vapor emissions from amalgam, increasing toxic effects.

 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, burning mouth, discomfort, tooth pain, gingivitis, oral lichen planus, and orofacial granulomatosis (102-107,111,15,16,39-43,140,146-148).  Most usually improve from these conditions after removal of amalgam fillings and/or the amalgam tattoos by surgery (102,106,107,109,73b, 126,127,15,16,39-43,147).  The high levels of accumulated mercury also are dispersed to other parts of the body.   Studies have also found persons with chronic exposure to electromagnetic fields (EMF) or wi-fi 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), Interleukin-8, Interleukin-4, (47, 35a,41a,186), 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  leukocytefunctions 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(95af).  Theaflavins from black tea, EGCG from green tea, and curcumin have also been found effective at inhibiting inflammatory effects(186).

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. Studies also indicate that mercury suppresses NO synthesis by inhibition of the NF-kappaB pathway and modulates cytokine expression by p38 MAPK activation in J774A.1 macrophage cells(47). NF-κB is found in almost all animal cell types and is involved in cellular responses to stimuli such as stress, cytokines, free radicals, heavy metals, ultraviolet irradiation, oxidized LDL, and bacterial or viral antigens.^{[1][2][3][4][5]} NF-κB plays a key role in regulating the immune response to infection. Incorrect regulation of NF-κB has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development. Nitric Oxide(NO) is required for key physiological functions within our body.

 Mercury from amalgam fillings has also been documented to cause proliferation of the inflammatory cytokine IL-8 (35a,41a,47).  IL-8 is responsible for much of the acute inflammation in inflammatory conditions such as asthma, gum disease, inflammatory bowel disease (IBS), etc. (186).  Theaflavins from black tea have been found to block such effects of IL-8 and C-reactive protein (CFP), and to have beneficial effects for many inflammatory conditions, including asthma, gum disease, IBS, strokes, pancreatitis, colitis, cancer, cardiovascular disease, etc.   Supplemented patients also show significantly reduced levels of the inflammation-generating transcription factor NFkB, the cytokine-generating enzyme COX-2, and the adhesion molecule ICAM-1(186).  Digestive problems are common and increase with aging, as generation of enzymes necessary for proper digestion decline and proliferation of pathogenic biological agents in the intestines increases.  Such problems often decrease absorption of minerals and nutrients and cause increases in inflammatory processes. Supplementing with digestive enzymes and enteric coated probiotics such as bacillus coagulans have been found to offer significant improvement in inflammatory conditions such as rheumatoid arthritis, IBS, Crohn�s Disease, influenza, etc. (186) 

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.) Also that they have synergistic effects.

 A study found that 39% of a group of crohn�s disease patients tested were immune reactive to nickel (100,19). Nickel is the most common cause of ACD, approx. 20% of total. Mercury (hg), chromium (Cr) and cobalt (Co)

as ions and compounds, are well recognized skin sensitizers. Cobalt positive reactions are associated with nickel sulfate and/or potassium dichromate sensitivity [184,185]. In 2594 subjects, Co sensitivity was seen in association with positive reactions to Ni and Cr in 95.2% of cases [185]. Patients tested to Co, Cr and Ni, sensitized to any one of the metals had significantly higher odds of sensitization to an additional metal [184].

Gold was found to be the sixth most frequent cause of positive patch test reactions in the U.S. [151]. Similar prevalence was observed in Europe and Japan. In a large Swedish study, 8.6% of 832 patients with suspected contact allergy on routine patch testing gave a positive response with gold sodium thiosulfate (GST). Other patients with contact allergy to GST also gave positive reactions to potassium dicyanoaurate, but were negative to gold sodium thiomalate (GSTM) and metallic Au [152]. These findings were confirmed by another group of investigators, who found that 4.6% of 278 patients in United Kingdom had positive reactions to GST on routine testing [153]. All of these patients were females, with a mean age of 37 years and the most frequent site of eczema was the head and neck. In Japan, 8.4% of 653 patients tested from 1990 to 2001 showed a positive reaction to gold chloride, and also in this work significantly more women (10.2%) than men (0.8%) reacted [154]. A study by Bruze et al. reported that a large percentage of the patch tests was long lasting, and 35% developed late reactions [155]. In a number of cases, positive test sites were seen to remain negative after 3 days, but to turn positive by day 7. These findings emphasize the necessity of a second patch test reading at a distance of 1 week, at least [156, 157].

Gold salt therapy, restorative materials in dentistry, orthopedic appliances and jewellery are the most accepted causes for Au ACD. Medical  practitioners have long recognized the adverse effects, including ACD, in the risk-benefit

balance of the usage of Au in anti-inflammatory therapy. In particular, an increasing incidence of delayed skin reactions has been noted since the introduction of GST and GSTM in the treatment of rheumatoid arthritis. Allergy to Au was seen in more than 50% of patients so treated, as indicated by patch testing with GSTM [158]. Patients developed dermatitis, stomatitis, and eosinophilia, and less commonly immunecomplex glomerulonephritis, lymphadenopathy, antinuclear antibody, increased serum IgE and other blood disorders.

Gold-based dental restoration appeared to be an important risk factor for Au ACD. Several Authors have found that a positive patch test to Au is significantly correlated with Au dental restorations [160,161,19]. The saliva may slowly dissolve Au and transport it through the mucous membranes into the bloodstream [159] and the amount of dental Au has been found to be correlated qualitatively and quantitatively to the blood level of Au [162,163]. Oral lichenoid mucositis, clinically and histologically similar to oral lichen planus, were observed at sites directly adjacent to Au dental restorations.

A study of Yiannias et al. retrospectively reviewed 46 patients with oral lichenoid lesions who had also been patch tested; 2 patients who were sensitized only to Au showed marked clinical improvement with removal of their dental Au restorations [164]. Hypersensitivity to Au has been reported in students involved in the manufacture of prosthetic materials in a, dental clinic in Japan, and 3 of 12 individuals tested had positive reactions to sodium thiosulfatoaurate [165]. Moreover, implanting a Au-plated stent seemed to represent a risk of sensitizing the patients to Au. In the stent group, 45.5% of patients had a contact dermatitis to Au while in the control group, 20.0% of subjects reacted and this difference was significant [166].

]. Lymphocyte proliferation in vitro shows good correlation to allergic

epicutaneous test reactions to Au [167, 168,19].

There are several reports on palladium (Pd) sensitivity associated with exposure to Pd containing dental restorations [171-175,19]. Symptoms observed included signs of contact dermatitis, stomatitis, mucositis, and oral lichen planus. General symptoms like swelling of the lips and cheeks, dizziness, asthma, chronic urticaria, and other symptoms have also been reported. In some case reports, complaints disappeared after replacement with Pd-free (or metal-free) constructions. Another aspect of Pd2+ sensitization is its frequent specific cross-sensitization with nickel [176-178]. During a 10-year period, the trend of sensitization to Pd in a clinic population increased to a maximum of 9.7% in the year 2000, with a higher percentage in females than in males. Of Pd-sensitized patients, 40.5% complained of hand dermatitis, 47.4% complained of body dermatitis, and 1.7% complained of burning mouth syndrome [169]. The similarities in chemistry of Ni2+ and Pd2+ support the idea of a similar mechanism involving common protein binding sites and conformational alterations [179]. A study with 10,000 participants tested with about 25 allergens, confirmed that of all patients 5.4% reacted to palladium dichloride alone, whereas all other patients also had a positive reaction to nickel sulphate [180].  There are also reports of allergic reactions from nondermatological causes such as glasses frames (181-183).

        Titanium has also been found to be a common immune sensitizer (19), especially in those with amalgam fillings. It has been proposed that the optimized version of LLT, i.e., MELISA (16-19), had a greater potentiality in diagnosing hypersensitivity to Ti. In a recent study, 56 patients chronically exposed to Ti via dental or endoprosthetic implants presented clinical symptoms and were subjected to the MELISA test against 10 metals including Ti. Of the 56 patients tested, 21 (37.5%) were positive to Ti. On the contrary, when patients were patch-tested, all resulted to be negative to Ti. Following removal of the implants, patients showed remarkable clinical improvement [145]. Thousands of patients have been documented to have recovered or significantly improved after amalgam and/or metals replacement (16-19).

   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 effect 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 (93,187).  Inorganic mercury was found to be a cause of systemic eczema and digestive problems by a Japanese study (15).  Hg exposure was significantly associated with metabolic syndrome and their components such as obesity and increased fasting glucose.  Blood Hg is associated with metabolic syndrome, in which Hg exposure plays a role as a risk factor for cardiovascular disease(15b).

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. 

The 1998-2000 North American Contact Dermatitis Group (NACDG) data base reported thiomersal to have a definite or probable relevance in 2.9% of the patients with a positive patch test. Thiomersal may be found in topical medications, especially ophthalmic and nasal preparations, cosmetics, and as a preservative in vaccines and contains organic Hg and thiosalicylate [149]. Positive patch test reactions to one or both the constituents of thiomersal have been frequently encountered. Thiomersal resulted to be the fifth most common allergen in patients [149].  The main target of autoantibodies is the ribonucleoprotein fibrillarin, which may also be a target in scleroderma patients [150]. Mercuric chloride causes antifibrillarin antibodies and immune complex glomerulonephritis in susceptible mouse strains. Antifibrillarin antibodies occur in a subset of scleroderma patients and preliminary evidence suggests that mercury levels may be higher in this group of individuals(87).

 Positive responses to phenylmercury, a bactericidal agent in root fillings and in pharmaceutical preparations, were also noted in the oral lichen group but not in the control groups. Thus, low-grade chronic exposure to Hg may induce a state of systemic sensitization as verified by Hg-specific lymphocyte reactivity in vitro [16].

W�hrl et al. suggested that a high percentage (15.2%) of children sensitized to copper (Cu) was due to the increased use of this metal in dental amalgam [141,139]. In the same way, a woman developed Cu ACD of the oral mucosa caused by the long-term exposure to Cu enriched dental amalgam fillings [142]. Houger et al. observed a relationship between intraoral metal ACD (i.e., mucositis) and pathogenesis of squamous cell carcinoma. Because of this high prevalence, Cu was considered an additional risk factor in the evolution of cancer [143]. Additionally, a case of a woman with lesions of oral lichen planus due to the Cu contained in her prosthesis has been reported. The change of the prosthesis made the lesions improved [144].   In light of the possible Cu-Ni cross-sensitization, it is unsafe to suggest to cover nickel goods with a layer of Cu to protect individuals allergic to Ni [141]. In 30 patients known to be contact sensitive to Ni but patch-test negative to Cu, the severity of patch test reaction to a Cu/Ni mixture was greater (p <0.001) than to Ni alone, suggesting that ions enhanced the sensitivity reaction to Ni.

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, copper, chromium, cobalt, and palladium (5-13,18,19, 60,91,141).  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). Mercury from dental amalgam and from mercury exposed gold miners also increases production of TNFa and INFy (interferon gamma) (49m). IFNγ is an important activator of macrophages and inducer of Class II major histocompatibility complex (MHC) molecule expression. Aberrant IFNγ expression is associated with a number of autoinflammatory and autoimmune diseases. These studies provides further evidence that mercury exposure may lead to autoimmune dysfunction and systemic inflammation in affected populations(49m).

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.

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 (17,18). 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, 50d). 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,27,33,70,71,187,31,18), allergies(22,31,32,43,48,49,52,53,66-74,99),  chronic multiple chemical sensitivities (32,52,70,71,73,75-77,187, 17,31), Oral lichen planus (15,16,39-43),   CFS (17,31,33,52-54,66,70,71, 75,84,85,187) and muscular/joint pain/fibromyalgia (17,31,53,72,84,187)  MS(16b,31,99,187). Mercury has been found to accumulate in connective tissue, resulting in lupus or scleroderma (187,87, etc.).    

     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.***

IV. Arthritis   - toxic metal and pathogen factors in Arthritis

        Osteoarthritis is characterized by degeneration of the articular cartilage or synovial membrane and bone next to the cartilage of knees, hips, and spine, or hand).  Cracking or thinning of cartilage leads to loss of shock absorption ability and resulting thickening of bone and development of bone spurs, and inflammatory reactions.  The result in stiffness and pain.

        Rheumatoid arthritis is an autoimmune condition, characterized by chronic inflammation and thickening of the synovial lining and cartilage destruction. The majority with RA have positive rheumatoid factor in serum. (186) Copper deficiency can be a factor in RA and supplementation can be helpful in such circumstances. Pathogens such as lyme disease, parvovirus, andchlamydea  have also been found to be factors in rheumatoid arthritis, especially in patients with immune systems weakened by toxic exposures such as mercury(188,186).  

Treatment of Arthritis

        Arthritis is chronic inflammation of joints, characterized by high levels in the joints of archidonicacid products, which are metabolized along 2 enzymatic pathways- PGE-2 & LTB4. The destruction of bone and cartilage in both osteoarthritis(OA) and rheumatoid arthritis(RA) is related to pro-inflammatory cytokines such as TNFa, Interleukin-1 and IL6.  It has been found that there is an excess of TNFa in both OA and RA, and some treatments attempt to inhibit TNFa.  While NSAIDs relieve symptoms they do not alleviate the underlying problems and usually result in more damage to joints in the long run (186).  Celebrex and Vioux are COX-2 inhibitors but do not block inflammation and damage through the LTB4 pathway, plus have significant adverse health effects.  Embrel is an expensive TNFa blocker, but can also block useful purposes of TNFa such as for fighting infections and does not suppress other inflammatory cytokines. Other natural options are more effective and safer.  DHA from fish oil is an effective anti-inflammatory with no adverse effects.  For those for whom this is not sufficient, the drug pentoxifylline(PTX) (Trental) is often helpful (186).  [Rifampin is known to attenuate chlamydial gene transcription, including the heat shock proteins that prepare infected cells for apoptosis.  "Combining this effect with antibiotics that block chlamydial protein synthesis (e.g., doxycycline or azithromycin) may allow for successful eradication of the cell harboring persistently infecting intracellular organisms, such as chlamydia"](188c). 

                        As has been seen, toxic metals like mercury cause pro-inflammatory cytokines and inflammation, so reductions in exposure and body burden such as amalgam replacement, avoidance, and detoxification have been found to be effective at reducing such inflammation. Mercury accumulation in areas of sensory ganglia and the Autonomic Nervous System has been found to commonly be a cause of such pain and fatigue (187).

Several natural supplements have been found to be beneficial in reducing arthritis pain and damage by reducing inflammatory cytokines and. Inflammation.  These include nettle leaf, SAMe, ginger, glucosamine and chondroitin sulfate, willow bark (pain relief), EFAs, antioxidants, Gamma-Linolenic Acid (GLA), MSM, and curcumin  (186). Inflacin is a topically applied compound that has been found to relieve arthritic pains. Nexrutine is a natural anti-inflammatory that inhibits COX-2 and has been found to be helpful, while 5-Loxin (Boswellic Acid) inhibits the 5-LOX pathway.  Both can be beneficial in extreme cases. 

        Food allergens that can increase inflammation include grain gluten, nightshades, corn, dairy products (casein), and red meats. Fish is a preferred protein. Generally vegetarian diets with probiotics are often helpful for arthritis relief (186). Uncooked vegen diets rich in berries, fruits, vegetable, nuts, and seeds often benefit arthritis sufferers. 

V. Asthma

Asthma is a chronic inflammatory disorder of the airways, characterized by wheezing, shortness of breath, chest tightness, mucus production, etc. At least 7.2% of the adult population has asthma and asthma in children has become much more prevalent. (186)  Asthma is closely tied to immune system reactions of the humoral system, as controlled by cell signaling cytokines. Allergic antigens bind to immune mast cells and basophils, and when these come into contact with IgE antibody, a hypersensitivity response of the immune system occurs leading to inflammation and bronchoconstriction.  

        Current pharmaceutical treatments are bronchodilators or anti-inflammatory compounds. As previously seen, toxic metal exposures increase inflammatory cytokines and inflammation, so reductions in toxic exposures can significantly improve such conditions.   Natural supplements that have been found effective in reducing asthma effects include essential fatty acids (DHA,EPA, GLA), curcumin, flavinoids such as silybin, lycopene, pycogenol, quercetin, Ginkgo extracts, licorice(coughs & congestion), Yerba mate, bee pollen (186). 

        Breastfeeding for at least 6 months and low levels of cereals has been found to be protective against asthma and allergies, Probiotics for the breastfeeding mother has also been found to be a preventive factor. (186)  Food allergies often related to asthma include cereal grains.  Other foods that produce common allergies are milk, nuts, chocolate, eggs, MSG, aspirin.  High intake of red meat and fats also are related to asthma.  Anti-inflammatories like vit C, E, and NAC are usually beneficial in asthma prevention. The minerals selenium and magnesium are protective against asthma. (186)

VI. Chronic Digestive Problems (Crohn’s Disease, Colitis, IBS, Leaky gut ,etc.)

Crohn’s Disease: gastrointestinional tract becomes inflamed and weak.  Toxic exposures such as mercury or other substances cause activation of inflammatory cytokines and/or autoimmune condition where immune system attacks intestine areas.  Reduce toxic exposures and treat inflammation. Elimination diet and avoid food allergens(dairy, gluten,eggs, nuts, fruit, nightshades, corn, red meat, refined carbohydrates).  Treat candida as necessary. Good multivit/min.  Lots of probiotics/ FOS, consider colonics probiotics.    Repair intestinal damage: glutamine, B5, zinc, tructoseoligosaccharides, vit C, fish oil.   DHEA lowers inflammation. Butyrate enemas are beneficial usually.   

Ulcerative colitis is where the large intestine becomes inflamed and ulcerated. Caused by inflammation, inflammatory cytokines.  Treat inflammation - Beneficial treatments: fish oil, butyrate enemas, glutamine, yeast RNA, DHEA, vit K, curcumin, etc. 

Irritable Bowel Syndrome (IBS): chronic or reoccurring bowel disease (abdominal fullness, bloating, flatulence, diarrhea alternating with constipation, cramps, etc.) Often patient also has depression or anxiety. 

Treatment of cramps [Regiment (Peppermint & Carraway Oil)], Treatment of Leaky gut.

Elimination diet and avoid food allergens (dairy, gluten, eggs, nuts, fruit, nightshades, corn, red meat, refined carbohydrates).  Treat Candida as necessary and consider candida diet. 

Probiotics, digestive enzymes, artichoke-black radish tablets, avoid sugar.  

Treat inflammation: antioxidants, DHEA, etc. 

Leaky gut

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