Common Heavy Metals: Sources and Specific Effects

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Mercury

Heavy metals have no function in the body and can be highly toxic. Introduction Aluminum Arsenic Cadmium Lead Nickel Antimony Barium Uranium Mercury

Mark S. Hulet, D.D.S., who conducts research on amalgam fillings, wrote a pamphlet for his patients, in which he cites five categories of pathological reaction to mercury fillings, as identified by dentists, doctors, and toxicologists. The categories are:

• Neurological: emotional manifestations (depression, suicidal impulses, irritability, inability to cope) and motor symptoms (muscle spasms, facial tics, seizures, multiple sclerosis)
• Cardiovascular problems: nonspecific chest pain, accelerated heart beat o Collagen diseases: arthritis, bursitis, scleroderma, systemic lupus erythematosis
• Immune system diseases: compromised immunity
• Allergies: Airborne allergies, food allergies, and "universal" reactors. One of the keys to mercury's effects on health may be its ability to block the functioning of manganese, a key mineral required for physiological reactions in all five categories, notes Dr. Hulet.

Discussion

Mercury Exposure And Toxicity Is A Prevalent And Significant Public Health Threat

Chronic mercury exposure from occupational, environmental, dental amalgam, and contaminated food exposure is a significant threat to public health.¹

Those with amalgam fillings exceed all occupational exposure allowances of mercury exposure of all European and North American countries. Adults with four or more amalgams run a significant risk from the amalgam, while in children as few as two amalgams will contribute to health problems.² In most children, the largest source of mercury is that received from immunizations ^{3 4 5 6} or that transferred to them in utero from their mother.^{7 8}

Dental Amalgams Are A Major Source Of Mercury Toxicity

A single dental amalgam filling with a surface area of only 0.4 sq.cm is estimated to release as much as 15 micrograms of mercury per day primarily through mechanical wear and evaporation.1 ^{9 10 11}

The average individual has eight amalgam fillings and could absorb up to 120 micrograms of mercury per day from their amalgams. These levels are consistent with reports of 60 micrograms of mercury per day collected in human feces.¹² By way of contrast, estimates of the daily absorption of all forms of mercury from fish and seafood is 2.3 micrograms and from all other foods, air and water is 0.3 micrograms per day. ¹³ Currently, Germany, Sweden and Denmark severely restrict the use of amalgams.¹

A “silver” filling, or dental amalgam, is not a true alloy. Amalgams are made up of 50% mercury. The amalgam also consists of 35% silver, 9% tin, 6% copper and a trace of zinc.⁶ More than 100 million mercury fillings are placed each year in the U.S. as over 90% of dentists use them for restoring posterior teeth.¹⁴

The mercury vapor from the amalgams is lipid soluble and passes readily through cell membranes and across the blood brain barrier. ¹⁵ The vapor serves as the primary route of mercury from amalgams into the body. It is clear that amalgam mercury transfers to human tissues, accumulates with time, and presents a potential health threat. The mercury escapes continuously during the entire life of the filling primarily in the form of vapor, ions but also abraded particles.^{16 17} Chewing, brushing, and the intake of hot fluids stimulates this release.^{18 19 20}

Statements made by dental authorities which claim that the amount of mercury exposure encountered by patients from dental amalgams is too small to be harmful, are contradicted by the literature.²¹

Animal studies show that radioactively labeled mercury released from ideally placed amalgam fillings appear quickly in the kidneys²², brain and wall of the intestines.²³ The fact that mercury amalgam fillings are banned in some European countries is strong evidence of the clinical toxicity of this material.

Any metal tooth restoration placed in the mouth will also produce electrogalvanic effects. When dissimilar metals are placed in the oral cavity they exert a battery-like effect because of the electroconductivity of the saliva. The electrical current causes metal ions go into solution at a much higher rate, thereby increasing the exposure to mercury vapor and mercury ions manyfold. Gold placed in the vicinity of an amalgam restoration produces a 10-fold increase in the release of mercury.²⁴

Hal Huggins, D.D.S., a specialist in the effect of mercury amalgams on health, reports that 90% of the 7,000 patients he tested showed immune system reactivity from exposure to low levels of mercury. In 1984, the American Dental Association (ADA), without providing scientific evidence, claimed that only 5% of the U.S. population is reactive to mercury exposure, and that this figure is insignificant. Meanwhile, the ADA mandates that dentists alert all dental personnel to the potential hazards of inhaling mercury vapors. The Environmental Protection Agency (EPA) goes further, instructing dentists to treat mercury amalgam as a toxic material while handling before insertion, and as toxic waste after removal.

Mercury's Long Half-Life In The Central Nervous System

Mercury in the central nervous system (CNS) causes psychological, neurological, and immunological problems in humans.^{25 26 27} Mercury bonds very firmly to structures in the CNS through its affinity for sulfhydryl-groups on amino acids. Other studies have shown that mercury is taken up in the periphery by all nerve endings and rapidly transported inside the axon of the nerves (axonal transport) to the spinal cord and brainstem.^{28 29 30} Unless actively removed, mercury has an extremely long half-life of somewhere between 15 and 30 years in the CNS.^{1 31}

Mercury Toxicity Symptoms

The overt clinical effects resulting from toxic exposure to mercury have been clearly described.^{32 33} The scientific literature shows that amalgam fillings have been associated with a variety of problems such as Alzheimer's Disease,^{34 35} autoimmunity,^{36 37 38} kidney dysfunction,³⁹ infertility,^{40 41 42} polycystic ovary syndrome, ⁴³ neurotransmitter imbalances,⁴⁴ food allergies,⁴⁵ multiple sclerosis,⁴⁶ thyroid problems,⁴⁷ and an impaired immune system.⁴⁸

Patients with many amalgam fillings will also have an increase in the prevalence of antibiotic resistant bacteria.⁴⁹ Subclinical neuropsychological and motor control effects were also observed in dentists who had documented high mercury exposure levels.^{50 51} Amalgam use may also be related to fatigue, poor memory and certain psychological disorders.⁵²

There has been a recent epidemic of autism in the US^{53 54} and many investigators believe that this may be partially related to the increased exposure infants have had to mercury through the preservative thimerosal that was included in nearly all vaccines until recently.⁵⁵

The nervous system is more sensitive to mercury toxicity than any other organ in the body. Mercury has recently been documented to be associated with arrhythmias and cardiomyopathies as hair analysis showed mercury levels to be 20,000 higher in those with these cardiac abnormalities.⁵⁶ Mercury exposure has also been associated with other neurological problems such as tremors,⁵⁷ insomnia, polyneuropathy, paresthesias, emotional lability, irritability, personality changes, headaches, weakness, blurred vision, dysarthria, slowed mental response and unsteady gait.^{1 58 59}

Systemic Mercury Elimination

There are a number of agents that have been demonstrated to have clinical utility in facilitating the removal of mercury with someone who has demonstrated clinical signs and symptoms of mercury toxicity. The urine and feces are the main excretory pathways of metallic and inorganic mercury in humans.^{1 60}

The most important part of systemic elimination is to remove the source of mercury.

For most this involves amalgam removal. Individuals should seek a dentist who is specially trained in this area as improperly removed amalgam may result in unnecessarily high exposure to mercury.⁶¹ The following is a summary of the most effective agents that have been documented in the peer-reviewed literature.

DMPS

DMPS (Sodium 2,3-dimercaptopropane-1-sulfonate) is an acid-molecule with two free sulfhydryl groups that forms complexes with heavy metals such as zinc, copper, arsenic, mercury, cadmium, lead, silver, and tin. DMPS was developed in the 1950s in the former Soviet Union and has been used to effectively treat metal intoxication since the 1960s there.⁶² It is a water-soluble complexing agent.

Because it had potential use as an antidote for the chemical warfare agent, Lewisite, it was not available outside of the Soviet Union until 1978, at which time Heyl, a small pharmaceutical company in Berlin, Germany started to produce it. It has an abundance of international research data and an excellent safety record in removing mercury from the body⁶³ and has been used safely in Europe as Dimaval for many years.^{64 65 66 67}

DMPS is registered in Germany with the BGA (their FDA) for the treatment of mercury poisoning but is still an investigational drug in the United States.⁶⁸

The best and only brand of DMPS that should be used is Heyl from Germany. Great care should also be exercised in making certain the DMPS is compounded properly from the pharmacist. If the DMPS contacts metal during it will be oxidized, so the compounding pharmacist must use nonmetal needles must be used in preparing the product.

DMPS Can Be Used To Eliminate Mercury Systemically

The use of DMPS to treat mercury toxicity is well established and accepted. ^{69 70 71} DMPS has clearly demonstrated elimination effects on the connective tissue.^{72 73} The DMPS dose is 3-5 mg /kg of body weight once a month which is injected slowly intravenously over five minutes. DMPS-stimulated excretion of all heavy metals reaches a maximum 2-3 hours after infusion and decreases thereafter to return to baseline levels after 8 hours.⁷⁴

DMPS Safety

DMPS is not mutagenic, teratogenic or carcinogenic.⁷⁵ Ideally intravenous DMPS should never be used in patients that still have amalgam fillings in place, although investigators have done this as diagnostically, as a one-time dose, without complications.⁷⁶ DMPS appears in the saliva and may mobilize significant amounts of mercury from the surface of the fillings and precipitate seizures, cardiac arrhythmias, or severe fatigue.

One should use DMPS with great caution and NEVER use it in patients with amalgam fillings. Ideally DMPS should be administered after 25 grams of ascorbic acid administered intravenously. This will minimize any potential toxicity from the DMPS.

Even though DMPS has a high affinity for mercury, the highest affinity appears to be for copper and zinc⁷⁷ and supplementation needs to be used to not avoid depleting these beneficial minerals. Zinc is particularly important when undergoing mercury chelation.⁷⁸ DMPS is administered over a five-minute period since hypotensive effects are possible when given intravenously as a bolus.^{79 80} Other possible side effects include allergic reactions and skin rashes.

DMSA

DMSA (meso-2, 3-dimercaptosucccinic acid) is another mercury chelating agent. It is the only chelating agent other than cilantro and d-penicillamine⁸¹ that penetrates brain cells. DMSA removes mercury both via the kidneys and via the bile.⁸² The sulfhydryl groups in both DMPS and DMSA bind very tightly to mercury.

DMSA has three distinct disadvantages relative to DMPS.

First, DMPS appears to remain in the body for a longer time than DMSA.⁸³

Secondly, DMPS acts more quickly than DMSA, probably because its distribution is both intracellular and extracellular.⁸⁴

Thirdly, preparations of DMPS are available for intravenous or intramuscular use, while DMSA is available only in oral form.⁸⁵ Since succinic acid is used in the citric acid cycle inside the cell, DMSA has been suspected for displacing mercury towards the inside of the cell⁸⁶ after binding mercury somewhere on its way from the intestine to the succinic acid deficient cell.

We propose therefore that DMSA be used late in the mercury elimination process, after the connective tissue mercury load has been reduced with DMPS. The standard dose of DMSA is 5-10 mg/kg twice a day for two weeks. The DMSA is then stopped for two weeks and then the cycle is repeated.

Chlorella

Algae and other aquatic plants possess the capacity to take up toxic trace metals from their environment, resulting in an internal concentration greater than those of the surrounding waters.⁸⁷ This property has been exploited as a means for treating industrial effluent containing metals before they are discharged, and to recover the bioavailable fraction of the metal.⁸⁸

Chlorella has been shown to develop resistance to cadmium contaminated waters by synthesizing metal-binding proteins.⁸⁹ A book written for the mining industry, Biosorption of Heavy Metals,⁹⁰ details how miners use these organisms to increase the yield of precious metals in old mines. The mucopolysaccharides in chlorella's cell wall absorb rather large amounts of toxic metals similar to an ion exchange resin.

Chlorella also enhances mobilization of mercury compartmentalized in non-neurologic structures such as the gut wall,⁹¹ muscles, ligaments, connective tissue, and bone.

High doses of chlorella have been found to be very effective in Germany for mercury elimination.⁹²

Chlorella is an important part of the systemic mercury elimination program, as approximately 90% of the mercury is eliminated through the stool. Using large doses of chlorella facilitates fecal mercury excretion. After the intestinal mercury burden is lowered, mercury will more readily migrate into the intestine from other body tissues from where chlorella will effectively remove it.

Chlorella is not tolerated by about one-third of people due to gastrointestinal distress. Chitosan can be effectively used as an alternative in these individuals. Chitosan makes up most of the hull of insects shellfish and also bind metals like mercury from the lumen of the intestines.^{93 94 95}

Cilantro

Omura determined that cilantro could mobilize mercury and other toxic metals rapidly from the CNS.^{96 97}

Cilantro mobilizes mercury, aluminum, lead and tin stored in the brain and in the spinal cord and moves it into the connective tissues. The mobilized mercury appears to be either excreted via the stool, the urine, or translocated into more peripheral tissues.

The mechanism of action is unknown. Cilantro alone often does not remove mercury from the body; it often only displaces the metals form intracellularly or from deeper body stores to more superficial structures, from where it can be easier removed with the previously described agents. The use of cilantro with DMSA or DMPS has produced an increase in motor nerve function.⁹⁸

Potentiating Agents

Adequate sulfur stores are necessary to facilitate mercury's binding to sulfhydryl groups.

Many individual's sulfur stores are greatly depleted which impairs sulfur containing chelating or complexing agents, such as DMPS or DMSA, effectiveness as they are metabolized and utilized as a source of sulfur. Sulfur containing natural substances, like garlic^{99 100} and MSM (methylsulfonylmethane) may also serve as an effective agent to supply organic sulfur for detoxification.¹⁰¹ Fresh garlic is preferred as it has many other recently documented benefits.^{102 103 104} The garlic is consumed just below the threshold of social unacceptability, which is typically 1-2 cloves per day.

Antioxidants

Vitamin E doses of 400 I.U per day have been shown to have a protective effect when the brain is exposed to methyl-mercury.^{68 105} Selenium, 200-400 mcg daily,^{106 107 108 109} is a particularly important trace mineral in mercury elimination and should be used for most patients.

Selenium facilitates the function of glutathione, which is also important in mercury detoxification.^{110 111 112} Some clinicians find repetitive high dose intravenous glutathione useful, especially in neurologically compromised patients.

There is a suggestion in a rat model that lipoic acid may also be useful,¹¹³ but some clinicians are concerned about the potential of lipoic acid to bring mercury into the brain early in the stages of chelation, similar to DMSA and N-acetylcysteine (NAC), which has also been used in mercury chelation.¹¹⁴ Doses larger than 50-100 mg per day should be used with caution.

Vitamin C is also a helpful supplement for mercury elimination as it will tend to mobilize mercury from intracellular stores.^{115 116 117 118 119 120}

Some clinicians will use it intravenously in doses of 25-100 grams IV in preference to DMPS and DMSA.

Hyaluronic acid (HA) is a major carbohydrate component of the extracellular matrix and can be found in the skin, joints, eyes and most other organs and tissues.¹²¹ HA is utilized in many chemotherapy protocols as a potentiating agent.¹²² HA is also being utilized for many novel applications in medicine.^{123 124} Personal experience has shown that the addition of 2 ml with the DMPS tends to improve the excretion of mercury by two to four fold with virtually no toxicity.

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References

1 Toxicological Profile For Mercury. U.S.Department Of Health & Human Services, Agency for Toxic Substances and Disease Registry, March 1999 Published by Division of Toxicology/Toxicology Information Branch, 1600 Clifton Road NE, E-29, Atlanta, Georgia 3033

2 Richardson GM. Assessment of mercury exposure and risks from dental amalgam. Medical Devices Bureau, Environmental Health Directorate, 1995 Health Canada.

3 Stajich GV, Lopez GP, Harry SW, et al. Iatrogenic exposure to mercury after hepatitis B vaccination in preterm infants. J Pediatr. 2000 May;136(5):679-81.

4 Pless R, Risher JF. Mercury, infant neurodevelopment, and vaccination. J Pediatr. Mercury, infant neurodevelopment, and vaccination. 2000 May;136(5):571-3.

5 Offit PA. Preventing harm from thimerosal in vaccines. JAMA. 2000 Apr 26;283(16):2104.

6 No authors listed. From the Centers for Disease Control and Prevention. Recommendations regarding the use of vaccines that contain thimerosal as a preservative. JAMA. 1999 Dec 8;282(22):2114-5.

7 Inouye M, Murakami U. Placental transfer of methylmercury and mercuric mercury in mice. Environ Med 1990;34:160-172.

8 Kuntz WD, Pitkin RM, Bonstrom AW, et al. Maternal and cord blood background levels. A longitudinal surveillance. Am J Obstet Gynecol 1982;143:440-443.

9. Harrison IA; Some electromchemical features of the in vivo corrosion of dental amalgams. J Appl Electrochem 1989;19: 301-310

10 Marek M. Dissolution of mercury vapor in simulated oral environments. Dent Mater 1997 Sep;13(5):312-5.

11 WHO. Inorganic Mercury. Geneva, Switzerland: World Health Organization, International Programme on Chemical Safety. 1991 Vol 118.

12. Skare I, Engqvist A., Human exposure to mercury and silver released from dental amalgam restorations. Arch Environ Hlth 1994;49:384-394

13. World Health Organization. Environmental Health Criteria. 118, Inorganic Mercury (Friber I, ed) WHO Geneva 1991.

14. Berry TC, Nicholson J, Torendle K.; Almost two centuries with amalgam. Where are we today? J Am Dent Assn 1994;120:394-395

15. Lorschider, F, Vimy MJ, Summers, AO: Mercury exposure from "silver" tooth fillings: Emerging evidence questions a traditional dental paradigm. FASEB J 1995; 9:504-508

16. Lorscheider F, Vimy MJ: Evaluation of the safety issue of mercury release from dental fillings. FASEB J 1993;7:1432-1433

17 Bjorkman L, Sandborgh-Englund G, Ekstrand J. Mercury in salvia and feces after removal of amalgam fillings. Toxicol Apply Pharmacol 1997;144:156-162.

18. Svare CW, Peterson LC, Reinhardt JW, Boyer DB, et.al; The effects of dental amalgams on mercury levels in expired air. J Dent Res 1981;60:1668-1671

19. Vimy MJ, Lorscheider F; Intra-oral air mercury released from dental amalgam. J Dent Res 1985;64:10069-1071

20. Aronsson AM; Lind B, Nylander M, Nordberg M; Dental amalgam and mercury. Biol Metals 1989; 2:25-30

21. Hanson M, Pleva J: The dental amalgam issue. A review. J Experentia. 1991;47:479-22

22 Zalups RK. Molecular interactions with mercury in the kidney. Pharmacol Rev 2000 Mar;52(1):113-43.

23. Hahn LJ, Kloiber R, Leininzer RW, Vimy MJ, Lorscheider FI; Whole-body imaging of the distribution of mercury released from dental fillings into monkey tissues. FASEB J 1990;4:3256-3260

24 Zahnaerztl, Knappwost et al. Abgabe von Quecksilberdampf aus Dentalamalgamen unter Mundbedingungen. Welt/Reform 1985;94, 131-138

25. Nierenberg DW, Nordgren RE, Chang MB, et al. Delayed cerebellar disease and death after accidental exposure to dimethylmercury. N Engl J Med. 1998;338(23): 1672-1676

26. Clarkson TW; Mercury - an element of mystery. N Engl J Med. 1990;323:1137-1139

27. The toxicological profile of mercury. 1994 publication by the US Department of Health and Human Services (Agency for Toxic Substances and Disease Registry, Division of Toxicology; 1600 Clifton Road NE E-29, Atlanta, GA 30333).

28. Eggleston DW, Nylander M.; Correlation of dental amalgam with mercury in the brain. J Prost Dent 1987;58:704-707

29. Retrograde Axonal Transport of Mercury; Bjoern Arvidson Experimental Neurology 1987;98, 198-203

30 Inorganic Mercury is Transported from Muscular Nerve Terminals to Spinal and Brainstem Motorneurons: Bjoern Arvidson Muscle and Nerve 1992;15:1089-1094

31 Handbuch der Amalgamvergifung, Max Daunderer, Ecomed Verlag, Muenchen(1996)

32 Clarkson TW, Hursh IB, Sager PR, Sverson TLM: Mercury. In Biological Monitoring of Toxic Metals (Clarkson TW, Friberg L, Nordberg CF,, and Sager PR, eds) pp 199-246. Plenum, New York 1988.

33 Klassen CD. Heavy metals and heavy-metal antagonists. In: The Pharmacological Basis of Theraputics, 8th edition(Gilman AC, Rall TW, Niew AS, Taylor P, eds) pp. 1598-1602. Pergamon Press, New York 1990.

34 Pendergrass JC, Haley BE, Vimy MJ, et al. Mercury vapor inhalation inhibits binding of GTP to tubulin in rat brain: similarity to a molecular lesion in Alzheimer diseased brain. Neurotoxicology. 1997;18(2):315-24.

35 Pendergrass JC, Haley BE. Inhibition of brain tubulin-guanosine 5'-triphosphate interactions by mercury: similarity to observations in Alzheimer's diseased brain. Met Ions Biol Syst. 1997;34:461-78.

36 Hirsch F, Kuhn J, Ventura M, Vial MC, Fournie G, Druet P; Production of monoclonal antibodies. J Immunol 1986;136:3272-3276

37 Hultman P, Johansson U, Turley Sj, Lindh U, Enestrom S, Pollard KM; Adverse immunological effects and autoimmunity induced by dental amalgam and alloy in mice. FASEB J 1994;8:1183-1190

38 Biagazzi M, Pierlguigi E; Autoimmunity and heavy metals. Lupus 1994;3:449-453.

39 Nylander M, Frierg I, Lind B; Mercury concentrations in the human brain and kidneys in relation to exposure from dental amalgam fillings. Swed Dent J 1987;11:179-187

40 Dondero F, Lenzi A, Lombardo F, Gandini L; Therapy of immunologic infertiilty. Acta Eur Fertil 1991;22:139-145

41 Rowlands AS, Baird DD, Weinberg CP, Shore DL, Shy CM, Wilcos AJ. The effect of occupational exposure to mercury vapor on the fertility of female dental assistants. Occup Environ Med 1994;51:28-34.

42 Gerhard I, Monga B, Waldbrenner A, Runnebaum B Heavy metals and fertility. J Toxicol Environ Health 1998;21;54(8):593-611

43 Gerhard I, Frick A, Monga B: Diagnosis of mercury body burden. Clin Lab 1997;43:637-647

44 Duhr E, Pendergrasss C, Kasarskis E, Slevin J Haley B; Mercury induces GTP-tubulin interactions in rat brain similar to those observed in Alzheimer's disease. FASEB J 1991; 5:456.

45 Hultman P, Johansson U, Turle S,J, et al: Adverse immunological effects and autoimmunity induced by dental amalgam and alloy in mice. FASEB J 1994;8:1183-1190

46 Siblered TL, Kienholz E. Evidence that mercury from silver dental fillings may be an etiological factor in reduced nerve conduction velocity in multiple sclerosis patients. Journal of Orthomolecular Medicine 1997;12(3):169-172.

47 Barregard L, Lindtedt G, Shutz A, et al. Endocrine function in mercury exposed chloralkali owkers. Occup Environ Med 1994, 51 (8)536-540.

48 Moszczynski P, Lisiewica J, Bartus R, et al. Lymphocytes T and NK cells in men occupationally exposed to mercury vapors. Int J Occup Med Environ Health 1995 8(1):49-56.

49 Summers AO, Wireman J, Vimy MI, Lorscheider FI, Marshall B, Levy SB, et al; Mercury released from dental Asilver@ fillings provokes an increase in mercury and antibiotic-resistant bacteria in oral and intestinal floras of primates. Antimicrob Agents and Chemother 1993;37:825-834

50 Escheverria D, Hever N, Martin MD, Naleway CA, Woods JS Bittner AC; Behavioral effects of low level exposure to mercury among dentists. Neurotxicol Teratol 1995;17:161-168

51 Ngim CH: Chronic neurobiological effects of elemental mercury in dentists. Br J Indust Med 1992;49:782-790

52 Siblerud RL; The relationship between mercury from dental amalgam and mental health. Am J Psychotherapy 1989;18:575-587

53 Powell JE, Edwards A, Edwards M, et al. Changes in the incidence of childhood autism and other autistic spectrum disorders in preschool children from two areas of the West Midlands, UK. Dev Med Child Neurol. 2000 Sep;42(9):624-8.

54 Tanguay PE. Pervasive developmental disorders: a 10-year review. J Am Acad Child Adolesc Psychiatry. 2000 Sep;39(9):1079-95.

55 Rice D, Barone S Jr. Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models. Environ Health Perspect. 2000 Jun;108 Suppl 3:511-33.

56 Frustaci A, Magnavita N, Chimenti C, et. al; Marked elevation of myocardial trace elements in idiopathic dilated cardiomyopathy. J Am Coll Cardiology 1999;33:1578-83

57 Chang YC, Yeh C, Wang JD. Subclinical neurotoxicity of merucyr vapor revcelaed by a multimodality evoked potential study of chloralkali workers. Amer J Ind Med 1995;27(2):271-279.

58 Yang Y-J, Huang C-C, Shih T-S, et al . Chronic elemental mercury intoxication:clinical and field studies in lampsocked manufacturers. 1994;Occup Environ Med 57(1):245-247.

59 Bluhm RE, Bobbitt RG, Wlech LW, et al. Elemental mercury vapour toxicity, treatment and prognosis after acute intensive exposure in chloraklali plant workers. Part 1I. History, neuropsychological findings and chelator effects. Hum Exp Toxicol 1992 11(3):201-210.

60 Clarkson TW. Mercury. 1989; J Am Coll Toxicol 8(7):1291-1296.

61 Eley BM The future of dental amalgam: A review of the literature. Part 2: Mercury exposure in dental practice. Br Dent J 1997;182(8):293-7.

62 Petrunkin VE: Synthesis and properties of demercapto derivatives of alkylsulfonic acids. Toksikol mosc 1958;21: 53-59

63 Torres-Alanis O, Garza-Ocanas L, Pineyro-Lopez A. Evaluation of urinary mercury excretion after administration of 2,3-dimercapto-1-propane sulfonic acid to occupationally exposed men. J Toxicol Clin Toxicol 1995;33(6):717-720

64 Aaseth J, Jacobsen D, Andersen O, Wickstrom E. Treatment of mercury and lead poisonings with dimercaptosuccinic acid and sodium dimercaptopropanesulfonate. 1995;120(3):853-854

65 Aposhian HV, Maiorino RM, Rivera M, et al Human studies with the chelating agents, DMPS and DMSA. J Toxicol Clin Toxicol 1992;30(4):505-528

66 Aposhian HV, Aposhia MM. Meso-2,3 dimercaptosuccinic acid: chemical, pharmacological and toxicological properties of an orally effective metal chelating agent. Annu Rev Toxicol 1990;30:279-306

67 Lorscheider FL, Vimy MJ. Evaluation of the saftey issue of mercury release from dental fillings. FASEB J 1993;7:432-1433

68 Aposhian VK: Mobilization of Mercury and Arsenic in Humans by Sodium 2,3 Dimercapto-1-propane Sulfonate (DMPS). Environ Health Perspect 1998;106(Suppl 4):1017-1025

69 Crinnion WJ. Environmental medicine, part three: long-term effects of chronic low-dose mercury exposure Altern Med Rev 2000 Jun;5(3):209-23

70 Schiele R, Schaller KH, Welte D: Mobilization of mercury reserves in the organism by means of DMPS. Occup Med Soc Med Prevent Med 1989;24: 249-251

71 Kidd RF Results of dental amalgam removal and mercury detoxification using DMPS and neural therapy. Altern Ther Health Med 2000 Jul;6(4):49-55

72 Belles M, Sanchez DJ, Gomez M, Domingo JL, Jones MM, Singh PK Assessment of the protective activity of monisoamyl meso-2,3-dimercaptosuccinate against methylmercury-induced maternal and embryo/fetal toxicity in mice. Toxicology 1996;106(1-3):93-97

73 Kostial K, Restek-Samarzija N, Blanusa M, Piasek M, Prester L, Jones MM, Singh PK Racemic-2,3-dimercaptosuccinic acid for inorganic mercury mobilization in rats. J Appl Toxicol 1997;17(1):71-74

74 Gerhard I; Runnebaum B: Schadstoffe und Fertiliatatsstorungen Schwermetalle und Mineralstoffe. Geburtshilfe Frauenheillkd 1992;52:383-396, 509-515

75 Baum CR Treatment of mercury intoxication. Curr Opin Pediatr 1999 Jun;11(3):265-8

76 Vamnes JS, Eide R, Isrenn R, Hol PJ et al. Diagnostic value of a chelating agent in patients with symptoms allegedly caused by amalgam fillings.J Dent Res 2000 Mar;79(3):868-74

77 Sallsten G, Barregard L, Schutz A Clearance half life of mercury in urine after the cessation of long term occupational exposure: influence of a chelating agent (DMPS) on excretion of mercury in urine. Occup Environ Med 1994;51(5):337-342

78 Afonne OJ, Orisakwe OE, Ndubuka GI, et al. Zinc protection of mercury-induced hepatic toxicity in mice. Biol Pharm Bull 2000 Mar;23(3):305-8

79 Aposhian HV, Maiorino RM, Gonzalez-Ramirez D, et al. Mobilization of heavy metals by newer, therapeutically useful chelating agents. Toxicology 1995;31;97(1-3):23-38

80 Gonzalez-Ramirez D, Maiorino RM, Zuniga-Charles M, et al Sodium 2,3-dimercaptopropane-1-sulfonate challenge test for mercury in humans: II. Urinary mercury, porphyrins and neurobehavioral changes of dental workers in Monterrey, Mexico. J Pharmacol Exp Ther 1995;272(1):264-274

81 Kostial K, Restek-Samarzija N, Blanusa M, Piasek M, Jones MM, Singh PK Combined oral treatment with racemic and meso-2,3-dimercaptosuccinic acid for removal of mercury in rats. Pharmacol Toxicol 1997;81(5):242-244

82 Miller AL. Dimercaptosuccinic acid (DMSA), a non-toxic, water-soluble treatment for heavy metal toxicity. Altern Med Rev. 1998;3(3): 199-207

83 Hurlbut KM, Maiorino RM, Mayersohn M, Dart RC, Bruce DC, Aposhian HV Determination and metabolism of dithiol chelating agents. XVI: Pharmacokinetics of 2,3-dimercapto-1-propanesulfonate after intravenous administration to human volunteers. J Pharmacol Exp Ther 1994;268(2):662-668

84 Zheng W, Maiorino RM, Brendel K, Aposhia HV. Determination and metabolism of dithiol chelating agents. Fundam Appl Toxicol 1990;14:598-607

85 Aposhian HV. Mobilization of mercury and arsenic in humans by sodium 2,3-dimercapto-1-propane sulfonate. Environ Health Perspect 1998;106 Suppl 4:1017-1025

86 Research data presented at the annual meeting of the Australasian Society of Oral medicine and Toxicology in Sydney, Australia, Sept.1998

87 H.B.Xue, W.Stumm, L.Sigg: The binding of Heavy Metals to Algal Surfaces, Water Res 1988;22, 917

88 Ahner, AB, Kong KS, Morell MM, Phytochelatin production in marine algea: An interspecies comparison. Limnol Oceanograph 1995;40: 649-657

89 Carr HP, et al. Characterization of the cadmium-binding capacity of Chlorella vulgaris. Bull Environ Contam Toxicol. 1998;60(3): 433-440

90 M. Tsezos: Biosorption of Radioactive Species, in: Biosorption of Heavy Metals, pp 45-50 editied by B.Volesky, CRC Press(1990)

91 M.Kraft: Bindungsverhalten von Arsen, Cadmium, Chrom, Quecksilber, Nickel und Blei an schwerverdauliche Lebensmittel und Lebensmittelkomponenten in kuenstlichem Magen-Darm-Saft. PhD Thesis. Institut fuer Hygiene, Sozial-und umweltmedizin der Ruhr-Universitaet Bochum, Germany, (1998)

92 Klinghardt, D: Amalgam/Mercury Detox as a Treatment for Chronic Viral, Bacterial, and Fungal Illnesses Explore! Volume 1997;8, No 3

93 R.Muzzarelli, O.Tubertini: Chitin and chitosan on chromatographic supports and adsorbents for collection of metal ions from organic and aqueous solutions and sea water, Talanta, 1969;16, 1571 ff

94 Y.Subramanian, T.Yoshinar: Studies on the formation of chitin-metal complexes, Rep.No 27, Marine Sciences Center, Mc Gill Univ, Montreal (1974)

95 J.W.Park, M.O. Park: Mechanism of metal ion binding to chitosan in solution, cooperative inter- and intramolecular chelations. Bull.Korean Chem.Soc. 1984;5(3), 108

96 Omura Y, Beckman SL Role of mercury (Hg) in resistant infections & effective treatment of Chlamydia trachomatis and Herpes family viral infections (and potential treatment for cancer) by removing localized Hg deposits with Chinese parsley and delivering effective antibiotics using various drug uptake enhancement methods. Acupunct Electrother Res. 1995;20(3-4): 195-229

97 Omura Y, Shimotsuura Y, Fukuoka A, Fukuoka H, Nomoto T. Significant mercury deposits in internal organs following the removal of dental amalgam, & development of pre-cancer on the gingiva and the sides of the tongue and their represented organs as a result of inadvertent exposure to strong curing light (used to solidify synthetic dental filling material) & effective treatment: a clinical case report, along with organ representation areas for each tooth. Acupunct Electrother Res. 1996 ;21(2): 133-160.

98 Ewan KB, Pamphlett R Increased inorganic mercury in spinal motor neurons following chelating agents. Neurotoxicology 1996;17(2):343-349

99 Cha CW A study on the effect of garlic to the heavy metal poisoning of rat. J Korean Med Sci 1987;2(4):213-224

100 Lee JH, Kang HS, Roh Protective effects of garlic juice against embryotoxicity of methylmercuric chloride administered to pregnant Fischer 344 rats. J Yonsei Med J 1999 Oct;40(5):483-9

101 The Miracle of MSM The Natural Solution for Pain. Jacob, S., Lawrence, RM, Zucker, M. Penguin Putnam, New York, NY 1999.

102 Stjernberg L, Berglund J. Garlic as an insect repellent. JAMA. 2000 Aug 16;284(7):831.

103 Fleischauer AT, Poole C, Arab L. Garlic consumption and cancer prevention: meta-analyses of colorectal and stomach cancers. Am J Clin Nutr. 2000 Oct;72(4):1047-52.

104 Morelli V, Zoorob RJ. Alternative therapies: Part II. Congestive heart failure and hypercholesterolemia. Am Fam Physician. 2000 Sep 15;62(6):1325-30.

105 Chang, L.W , Gilbert,M and Sprecher,J: Modification of methylmercury neurotoxicity by vitamin E, Environ.Res. 1978;17:356-366

106 Yoneda S, Suzuki KT Detoxification of mercury by selenium by binding of equimolar Hg-Se complex to a specific plasma protein. Toxicol Appl Pharmacol 1997;143(2):274-280

107 Akesson I, Ingrid B; Status of mercury and selenium in dental personnel: Impact of amalgam work and own fillings. Arch Environ Health 1991;46(2):103-109

108 Johansson E: Selenium and its protection against the effects of mercury and silver. J Trace Elements 1991;5:273-274

109 Gailer J; George GN; Pickering IJ, et al. Structural Basis of the Antagonism between Inorganic Mercury and Selenium in Mammals. Chem Res Toxicol 2000 Nov 20;13(11):1135-1142

110 Hultberg B, Andersson A, Isaksson A Thiol and redox reactive agents exert different effects on glutathione metabolism in HeLa cell cultures.Clin Chim Acta 1999 May;283(1-2):21-32

111 Westphal GA; Schnuch A; Schulz TG, et al. Homozygous gene deletions of the glutathione S-transferases M1 and T1 are associated with thimerosal sensitization. Int Arch Occup Environ Health 2000 Aug;73(6):384-8.

112 Schurz(1) F; Sabater-Vilar M; Fink-Gremmels J. Mutagenicity of mercury chloride and mechanisms of cellular defence: the role of metal-binding proteins. Mutagenesis 2000 Nov;15(6):525-530

113 Anuradha B, Varalakshmi P Protective role of DL-alpha-lipoic acid against mercury-induced neural lipid peroxidation. Pharmacol Res 1999 Jan;39(1):67-80

114 Ballatori N, Lieberman MW, Wang W N-acetylcysteine as an antidote in methylmercury poisoning. Environ Health Perspect 1998 May;106(5):267-71

115 Dirks M, Marvin J; Mercury excretion and intravenous ascorbic acid. Arch Environ Health 1994;49(1):49-52

116 Hill, CH. Interactions of vitamin C with lead and mercury. Ann N Y Acad Sci 1980;355:262-6

117 Yamini B, Sleight SD. Effects of ascorbic acid deficiency on methyl mercury dicyandiamide toxicosis in guinea pigs J Environ Pathol Toxicol Oncol 1984 Jul;5(4-5):139-50

118 Zorn NE, Smith JT A relationship between vitamin B12, folic acid, ascorbic acid, and mercury uptake and methylation.Life Sci 1990;47(2):167-73

119 Sorg O, Schilter B, Honegger P, et. al. Increased vulnerability of neurones and glial cells to low concentrations of methylmercury in a prooxidant situation. Acta Neuropathol (Berl) 1998 Dec;96(6):621-7

120 Iyengar GV; Nair PP. Global outlook on nutrition and the environment: meeting the challenges of the next millennium. Sci Total Environ 2000 Apr 17;249(1-3):331-46.

121 Chen WY, Abatangelo G.Functions of hyaluronan in wound repair. Wound Repair Regen 1999;7(2):79-89

122 Delpech B, Girard N, Bertrand P, Courel MN, Chauzy C, Delpech Hyaluronan: fundamental principles and applications in cancer. J Intern Med 1997;242(1):41-8

123 Sutherland IW. Novel and established applications of microbial polysaccharides. Trends Biotechnol 1998;16(1):41-6

124 Knudson CB, Nofal GA, Pamintuan L, Aguiar DJ: The chondrocyte pericellular matrix: a model for hyaluronan-mediated cell-matrix interactions. Biochem Soc Trans 1999;27(2):142-7