International Scene

NEL Vol.23 No.5/6, Oct-Dec 2002      ORIGINAL ARTICLE

 

Dental amalgam removal improves health

2002; 23:459-482  pii: NEL235602A12  PMID: 12500173

NEUROENDOCRINOLOGY LETTERS

including Psychoneuroimmunology, Neuropsychopharmacology,
Reproductive Medicine, Chronobiology and Human Ethology, ISSN 0172-780X

Key words: amalgam, metal exposure, mercury, chronic fatigue,
removal, antioxidants, plasma, questionnaire, quality of life
 

Removal of dental amalgam and other metal alloys supported by antioxidant
therapy alleviates symptoms and improves quality of life in patients with
amalgam-associated ill health

 

by Ulf Lindh, Romuald Hudecek, Antero Danersund, Sture Eriksson & Anders Lindvall

 

Submitted: July 29, 2002 Accepted: August 1, 2002

SETTING AND DESIGN: We included 796 patients in a retrospective study using a questionnaire about symptom changes, changes in quality of life as a consequence of treatment and assessment of care taking.

METHODS: Treatment of the patients by removal of offending dental metals and concomitant antioxidant therapy was implemented according to the Uppsala model based on a close co-operation between physicians and dentists.

RESULTS: More than 70% of the responders, remaining after exclusion of those who had not begun or completed removal, reported substantial recovery and increased quality of life. Comparison with similar studies showed accordance of the main results. Plasma concentrations of mercury before and after treatment supported the metal exposure to be causative for the ill health.

MAIN FINDINGS: Treatment according to the Uppsala model proved to be adequate for more than 70% of the patients. Patients with a high probability to respond successfully to current therapy might be detected by symptom profiles before treatment.

CONCLUSIONS: The hypothesis that metal exposure from dental amalgam can cause ill health in a susceptible part of the exposed population was supported. Further research is warranted to develop laboratory tests to support identification of the group of patients responding to current therapy as well as to find out causes of problems in the group with no or negative results

 

 

Introduction

Dental amalgam was used very early in China. "Silver paste" is mentioned in the materia medica of Su Kung in 659 A.D. The name used is probably the historical reason why this material in some countries is called "silver amalgam" although its main ingredient always has been mercury. French chemists and dentists experimenting with various mixtures of metals in the end of the 18th century initiated the use of amalgam in the western world. Introduction of dental amalgam is usually ascribed to the French brothers Crawcour in 1831. They used a mixture of mercury and filings of French silver coins. Two years later the Crawcour brothers introduced the filling material in New York and they falsely pretended to be dentists.

Discussions about the rationale in using mercury as the main component in dental amalgams have been going on more than 160 years. In fact, the debate started immediately after the introduction of the material in the U.S.A. American medical-dentists at that time started a merciless crusade against their foreign rivals. They declared that not only was silver amalgam a lousy filling material but it also caused mercury poisoning. This had among other things the consequence that professional dentists started a dental association (The American Society of Dental Surgeons) in New York in 1840 to "increase the standing of the profession and to counteract charlatanry". The first amalgam war had begun.

Almost ignored were the results of studies in which warnings were issued for negative health effects associated with exposure to mercury from dental amalgams [1, 2]. Later during the 1920s, the German chemist Alfred Stock warned about the danger with mercury vapor [3, 4]. As late as in 1939 he issued enhanced warnings [5]. The latest phase in these amalgam wars started in the late 1970s and has been especially intense in Scandinavia but also in the U.S.A. and Germany. Various attempts to estimate risks from dental amalgams have been published advancing conclusions of increased risk of disease [6] as well as no correlation between amalgams and health problems [7]. The latter study, however, demonstrated negligence of combinations of gold and amalgam causing increased corrosion and mercury vapor emission. Richardson [8-10] concludes that a significant portion of all age groups exceeds the proposed reference dose for mercury exposure (0.98 mg Hg/day - tolerable daily intake) more than fives times due to dental amalgam. He also concludes that data suggest that approximately 19 to 20% of the general population may experience sub-clinical central nervous system and/or kidney function impairment as a result of the presence of amalgam fillings. Berlin [11] arrives at the conclusion that the prevalence of side effects from mercury in amalgam on the nervous system, immune system and kidneys should fall in the interval 0.1-10% with the highest probability of 1%. This makes the probable side effects from amalgams a significant health problem.

Documented effects of amalgam removal appeared already in 1842 [1]. However, probably the first comprehensive study was published in 1928 as a consequence of Stock's warnings [15]. Seven patients with a completed treatment reported substantially improved health or complete health. Fleischmann [15] interpreted the symptoms as an expression of "hypersensitivity" and recommended dentistry to abandon copper amalgam of that time immediately and silver amalgam when equivalent materials were available. Several contemporary studies have been published dealing with implications, both in general health, oral pathology and laboratory medicine, of removal of dental amalgam [16-35]. A drawback of most of these studies is, however, that there are few indications of the treatment quality.

The rationale for highlighting clinical effects of chronic low-dose mercury exposure is the advancement of modern research in the behavior of mercury in tissues. This metal has a lot of potentially toxic effects on various levels in a living organism. Mercury exposure decreases the DNA content and increases collagenase-resistant protein formation in synovial tissues. This leads to an increased risk for reduced joint function and decreased ability to repair joint damage [36] partly explaining the joint problems in the patient group.

Decreased amounts of available selenium are also a consequence of exposure to heavy metals, in particular mercury, which compounds the oxidative burden on the body [37]. Mercury also decreases levels of glutathione (GSH) in the body [38]. Mercury binds irreversibly to GSH causing the loss of up to two GSH molecules per mercury ion. The GSH-Hg-GSH complex is excreted via the bile into the feces. Part of the irreversible loss of GSH is due to the inhibition of GSH reductase by mercury, which is used to recycle oxidized glutathione and return GSH to the pool of available antioxidants [39]. At the same time, mercury also inhibits GSH synthetase, so a lesser amount of new GSH is created. Since mercury promotes formation of hydrogen peroxide, lipid peroxides and hydroxyl radicals, it is evident that mercury sets up a scenario for a serious imbalance in the oxidant/antioxidant ratio of the body [40].

Central nervous affection by exposure to mercury may in part be explained by that Hg0 and Hg2+ are accumulated in motor neurons and Purkinje cells in the brain [41]. Important intracellular effects of mercury are intimately connected to enzymes. All enzymes with sulfur amino acids as well as selenocysteine are open for attack by Hg2+ with a probable outcome of impairment of function. Cells presented with Hg0 will not be able to stop penetration through membranes due to the lipophilicity of uncharged mercury atoms. This opens for a multitude of possible symptoms from various organs in the body. First order thiol binding constant of Hg2+ is 1030-40, which demonstrates the extreme affinity of mercury for thiol groups [42]. Additionally, the ligand exchange rate constant of Hg2+ among thiol groups is among the highest known (109 s-1), again showing the extreme properties of the mercuric ion [43].

Exposure of workers to 0.0058 mg m-3 mercury vapor (0.007-0.021 mg m-3) affected the chemotaxis of polymorphonuclear leukocytes significantly [44]. This exposure is in good agreement to what could be expected from a "normal" set of amalgam fillings [45]. A sensitive subgroup of the population, therefore, has to be expected to suffer from impairment of circulating blood cells. Furthermore, neutrophil activity has been shown to be inhibited by mercury [46]. Even damages to DNA has been attributed to mercury exposure [47]. Mercury interacts with the GABAA receptor by way of alkylation of thiol groups of cysteinyl residues found in GABAA receptor subunit sequences [48]. This has the consequence that the binding site of benzodiazepine is modulated.

Structural alteration of the mitochondrial inner membrane with consequent dissipation of membrane potential and disruption of oxidative phosphorylation is another cellular effect of mercuric ions [49-51]. The intracellular calcium homeostasis is altered by mercury inducing mitochondrial release of calcium [51, 52]. Cellular influx of calcium also seems to be a consequence of human exposure to mercury and other metals from dental amalgam [13]. Mercury-induced stress may transform innocuous astrocytes into potentially lethal sources of cytotoxic oxygen free radicals [53].

Low levels of mercuric ions alter the normal pattern of protein tyrosine phosphorylation in B-lymphocytes during antigen receptor-stimulated signal transduction, suggesting that low levels of mercuric ions interfere with signal transduction pathways that are mediated by receptor-associated tyrosine kinases [54]. Additionally, Mattingly et al. [55] showed that low concentrations of mercuric ions interfere with the normal activation of Ras and MAP kinase during antigen receptor-mediated signal transduction in T lymphocytes. The regulation of cell growth is interfered by low and non-toxic levels of ionic mercury [56]. Mercury-induced apoptosis seems to be species dependent in human lymphoid cells in a comparison between the effects of methylmercuric chloride and mercuric chloride [57]. Each of the mercurial species trigger the apoptotic cascade, however, there are profound differences in the mechanism of action at the mitochondrial level. This disparity of mode of action may be linked to differential effects on the anti-death gene, bcl-2. Low-dose exposure to silver, copper, mercury and nickel ions alters the metabolism of human monocytes [58]. These authors conclude that the levels of metals released from dental alloys may be significant to monocytic function.

Mercury as well as cadmium binds iron regulatory protein 1 (IRP-1) with high affinity, compared with iron. These metals may cause the disruption of iron metabolism by inhibiting posttranscriptional regulation of iron-related proteins, such as ferritin and transferrin receptor. The effects of these toxic metals on inactivation of IRP-1/IRE binding and activation of aconitase may explain part of the cell toxicity [59]. Even ion channels may be adversely affected by mercury exposure. Divalent mercury blocked human skeletal Na+ channels (hSkM1) in a stable dose-dependent manner in the absence of reducing agent. Dithiothreitol (DTT) significantly prevented Hg2+ block of hSkM1 and Hg2+ block was also readily reversed by DTT [60].

Mercury is additionally well known to have adverse effects on the immune system with increased IgE in blood and deposits of immune complexes in the renal mesangium [61, 62]. Immunomodulation is but one of the facets of mercury exposure. Experimental animal studies and observations in humans indicate that immunomodulatory properties of metals such as mercury are heterogeneous and are not restricted to contact allergy [63]. Mercury causes induction of oligoclonal T cell responses skewed toward type-2 reactions [64]. There are numerous studies showing the induction of autoimmunity by mercury exposure [65-69]. Even neurological diseases have been hypothesized to be, at least partly, due to induction by exposure to heavy metals such as mercury [70-72].

During the last twenty years an increasing number of patients have sought dental and/or medical care for problems possibly associated with dental amalgam. These patients have observed a relationship in time between odontological treatment and occurrence or increase of their symptoms. The metal syndrome was conceived by our group as a collective term describing such patients with a series of symptoms for which no other etiologic diagnosis could be found in spite of thorough examination and laboratory tests [12]. Most other possible causes, except for metal exposure from amalgams, for the disease of these patients have been excluded by meticulous investigations performed by several specialist physicians. A differential diagnostic procedure had thus been thoroughly implemented. These patients suffered from several general, neurological, psychiatric and oral symptoms.

Soon additional laboratory tests were included in these studies. Nuclear microscopy of single isolated blood cells revealed that patients, in contrast to healthy controls, displayed distorted profiles of trace elements in blood cells [13]. In addition, changes of trace elements in blood plasma assessed by X-ray fluorescence were observed.

Hypersensitivity or allergy to metals comprising dental alloys was suspected rather early. To avoid potential side effects of traditional patch testing, an in vitro test was applied. This test being called MELISA® (MEmory Lymphocyte Immuno Stimulation Assay) is a development of the common lymphocyte transformation test. MELISA® applied to 3000 patients with suspected side effects from metals in dental restorative materials in three analytical centers demonstrated a reasonable degree of conformity [14].

The aim of the present study was to evaluate the treatment of patients at the former Department of Clinical Metal Biology at the University Hospital in Uppsala, Sweden. A questionnaire comprising questions about symptoms, quality of life as well as care-taking assessment was constructed and sent to patients. The study design was, therefore, a before-after design in which patients constituted their own controls and was undertaken in retrospect and longitudinally. This design has the attractive advantage of setting aside genetic differences between cases and controls. Even if the study had been prospective, it would not have been possible to adopt a double-blind placebo-controlled design for obvious reasons.