Research: Mercury, Inflammation and Immunity
I. Increasing incidence of inflammatory and immune reactive conditions
The incidence of allergic and immune reactive conditions such as allergies, asthma, lupus and allergic contact disease (such as eczema and psoriasis) have been increasing rapidly in the United States over the last decade. The prevalence of asthma doubled over the last decade to approximately 31 million, 11.5% of the total population. At least 50 million have allergies (19%), and the largest increase has been in infants, with approximately 10% of infants – approximately 15 million in the U.S. with systemic eczema. Approximately 12% have had chronic sinusitis.
Inflammation has been found to be a major factor in many chronic health conditions such as cardiovascular problems; diabetes; arthritis; depression; osteoporosis; periodontal disease; joint stiffness; chronic fatigue; fibromyalgia and age-related immune dysfunction. 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, eg: amalgam (mercury, copper, tin, silver), gold alloys (gold, palladium), nickel or stainless steel crowns (nickel, cobalt) causes galvanic electrical currents, and much higher mercury vapour levels in oral air and metal levels in oral tissues.
Government agencies and medical studies have found that the largest source of mercury exposure in most people is from dental amalgam fillings. For those with amalgam dental fillings, exposure from fillings amounts to from 50 to 90% of exposure, with the average being about 75% of total exposure. Mercury is an unusual metal commonly a liquid at room temperature and vaporising to a gas from its liquid or solid states. The studies found that mercury amalgams are unstable due to mercury's vaporisation and galvanic action, leaking mercury vapour continuously into the lungs and saliva at levels exceeding government health standards. Dental amalgam is also a major source of methyl mercury exposure for many since oral and intestinal mercury is methylised by oral bacteria and other methyl donors. The other most common sources of mercury exposure are methyl mercury from fish or mercury thimerasol from vaccines, which is a major source of exposure mostly for infants or those frequently receiving flu vaccinations.
The amount of mercury released into saliva has been found by large studies to be about 1.5 to 1.9 micrograms per litre for each additional amalgam filling, resulting in an increase of about 1 microgram per litre in urine and even higher levels excreted in faeces.
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. 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. 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 the 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. 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.
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. Most usually improve from these conditions after removal of amalgam fillings and/or the amalgam tattoos by surgery. 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. 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 (sulphhydryl) in sulphur 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 recognising them as appropriate nutrients and attacking them with chronic exposure resulting in autoimmunity. Such binding and autoimmune damage has also been documented in collagen. 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.
Mercury and other toxic metals cause release of inflammatory cytokines such as Tumor Necrosis Factor-alpha (TNFa), Interleukin-8, Interleukin-4. These will be documented to be factors in the chronic inflammatory conditions discussed here, including asthma, lupus, rheumatoid arthritis, Scleroderma, coeliac and Crohn’s disease. Studies have demonstrated low concentrations of mercury (HgCl2), significantly enhanced chemi-luminescence, as well as stimulated H2O2 production by polymorphonuclear leukocytes).
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. 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 to increase effects of factors in cardiovascular disease and neurological disease. Melatonin, vitamin E, and vitamin C have been found to counter these adverse effects. Theaflavins from black tea, EGCG from green tea, and curcumin have also been found effective at inhibiting inflammatory effects.
HgCl2 induces a protein kinase C-dependent Ca2+ influx through L-type calcium channels. 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.
Mercury from amalgam fillings has also been documented to cause proliferation of the inflammatory cytokine IL-8. IL-8 is responsible for much of the acute inflammation in inflammatory conditions such as asthma, gum disease, and inflammatory bowel disease (IBS). 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 such as asthma, gum disease, IBS, strokes, pancreatitis, colitis, cancer and cardiovascular disease. 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.
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 and influenza.
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. Studies have found that in asthma, lupus, rheumatoid arthritis, Scleroderma, coeliac disease, Crohn’s, disease, 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.
The activity of some free-radical scavenging enzymes and 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.
Nickel, chromium & cobalt
A study found that 39% of a group of Crohn’s disease patients tested were immune reactive to nickel. Nickel is the most common cause of ACD, approximately 20% of total Nickel (Ni), chromium (Cr) and cobalt (Co) as ions and compounds, are well recognised skin sensitisers. Cobalt-positive reactions are associated with nickel sulphate and/or potassium dichromate sensitivity. In 2,594 subjects, cobalt sensitivity was seen in association with positive reactions to nickel and chromium in 95.2% of cases. Patients tested to cobalt, chromium and nickel, sensitised to any one of the metals had significantly higher odds of sensitisation to an additional metal.
Gold was found to be the sixth most frequent cause of positive patch test reactions in the U.S. 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 thiosulphate (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 gold.
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. 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. A study by Bruze et al reported that a large percentage of the patch tests were long lasting, and 35% developed late reactions. 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.
Gold salt therapy, restorative materials in dentistry, orthopaedic appliances and jewellery are the most accepted causes for gold ACD. Medical practitioners have long recognised the adverse effects, including ACD, in the risk-benefit balance of the usage of gold 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 gold was seen in more than 50% of patients so treated, as indicated by patch testing with GSTM. Patients developed dermatitis, stomatitis, and eosinophilia, and less commonly immune complex glomerulonephritis, lymphadenopathy, antinuclear antibody, increased serum IgE and other blood disorders.
Gold-based dental restoration appeared to be an important risk factor for gold ACD. Several authors have found that a positive patch test to gold is significantly correlated with gold dental restorations. The saliva may slowly dissolve gold and transport it through the mucous membranes into the bloodstream and the amount of dental gold has been found to be correlated qualitatively and quantitatively to the blood level of gold. Oral lichenoid mucositis, clinically and histologically similar to oral lichen planus, were observed at sites directly adjacent to gold 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 sensitised only to gold showed marked clinical improvement with removal of their dental gold restorations. Hypersensitivity to gold 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 thiosulphatoaurate. Moreover, implanting a gold-plated stent seemed to represent a risk of sensitising the patients to gold. In the stent group, 45.5% of patients had a contact dermatitis to gold while in the control group, 20.0% of subjects reacted and this difference was significant. Lymphocyte proliferation in vitro shows good correlation to allergic epicutaneous test reactions to gold.
There are several reports on palladium (Pd) sensitivity associated with exposure to palladium containing dental restorations. 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 palladium-free (or metal-free) constructions. Another aspect of Pd2+ sensitization is its frequent specific cross-sensitisation with nickel. During a 10-year period, the trend of sensitisation to palladium 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-sensitised patients, 40.5% complained of hand dermatitis, 47.4% complained of body dermatitis, and 1.7% complained of burning mouth syndrome.
The similarities in chemistry of Ni2+ and Pd2+ support the idea of a similar mechanism involving common protein binding sites and conformational alterations. 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. There are also reports of allergic reactions from non-dermatological causes such as glasses frames ... (continued - see below)