Journal of Nutritional & Environmental Medicine (2001) 11, 53 62

REVIEW

Mercury Toxicity and Systemic Elimination Agents

JOSEPH MERCOLA DO1
1 2

AND

DIETRICH KLINGHARDT MD PHD2

Optimal Wellness Center, 1443 W. Schaumburg, Schaumburg, IL 60194, USA; American Academy of Neural Therapy, 2802 E. Madison#147, Seattle, WA 98112, USA

Abstract This paper reviews the published evidence supporting amalgam toxicity and clinical techniques that facilitate mercury elimination. A literature review is provided which documents effective mercury elimination strategies to improve mercury toxicity syndromes. Considering the weight of evidence supporting mercury toxicity, it would seem prudent to select alternative dental restoration materials and consider effective mercury elimination strategies if mercury toxicity is present.
Keywords: amalgam and mercury toxicity, DMPS, DMSA, chlorella, cilantro.

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 signi cant threat to public health [1]. Those with amalgam llings exceed all occupational exposure allowances of mercury exposure of all European and North American countries. Adults with four or more amalgams run a signi cant risk from them, 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 6] or that transferred to them in utero from their mothers [7, 8]. DENTAL AMALGAMS ARE A MAJOR SOURCE OF MERCURY TOXICITY A single dental amalgam lling with a surface area of only 0.4 cm 2 2 is estimated to release as much as 15 l g Hg day 2 1 primarily through mechanical wear and evaporation [1, 9 11]. The average individual has eight amalgam llings and could absorb up to 120 l g Hg day 2 1 from their amalgams. These levels are consistent with reports of 60 l g Hg day 2 1 collected in human feces [12]. By way of contrast, estimates of the daily absorption of all forms of mercury from sh and seafood is 2.3 l g and from all other foods, air and water is 0.3 l g per day [13]. Currently, Germany, Sweden and Denmark severely restrict the use of amalgams [1]. A silver lling, 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 llings are placed each year in the US 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
ISSN 1359-0847 print/ISSN 1364-6907 online/01/010053-10 DOI: 10.1080/13590840020030267 Taylor & Francis Ltd

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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 lling primarily in the form of vapor, ions and abraded particles [16, 17]. Chewing, brushing, and the intake of hot uids stimulate this release [18 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 llings appears quickly in the kidneys [22], brain and wall of the intestines [23]. 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 to 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].

MERCURYS LONG HALF-LIFE IN THE CENTRAL NERVOUS SYSTEM Mercury in the central nervous system (CNS) causes psychological, neurological, and immunological problems in humans [25 27]. Mercury bonds very rmly to structures in the CNS through its af nity 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 30]. 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 scienti c literature shows that amalgam llings have been associated with a variety of problems such as Alzheimers disease [34, 35], autoimmunity [36 38], kidney dysfunction [39], infertility [40 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 llings 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 USA [53, 54] and many investigators believe that this may be partially related to the increased exposure that infants have had to mercury through the preservative thimerosal that was included in nearly all vaccines until recently [55]. Although the Centers for Disease Control (CDC) have asked that the mercury be removed, thimerosal-free vaccines are still not universally available, nor is it likely that all vaccines will be thimerosal-free in the near future. The nervous system is more sensitive to mercury toxicity than any other system 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].

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TABLE 1. Systemic mercury elimination agents Agent DMPS DMSA Dose 3 5 mg kg IV

2 1

Cautions Do NOT give if amalgams present Some clinicians believe will facilitate mercury into the brain so it is added late in the treatment regimen None None 30% are hypersensitive and can not tolerate 10 20% are hypersensitive and can not tolerate

Frequency Monthly Twice daily for two weeks; 81 86 stop for two weeks; then repeat cycle

References 62 80

5 10 mg kg 2 orally

Glutathione IV Vitamin C Chlorella

4 mg kg 2

IV

350 1500 mg kg 2 1 5 10 mg kg 2 1 orally 5 10 mg kg 2 orally

1

Once to three times weekly Once to three times weekly Once to twice daily Once daily

110 114 117 122 87 95

Cilantro

96 98

SYSTEMIC MERCURY ELIMINATION There are a number of agents that have been demonstrated to have clinical utility in facilitating the removal of mercury in 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 (see Table 1).

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, and silver. DMPS was developed in the 1950s in the former Soviet Union and has been used to effectively treat metal intoxication since the 1960s [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 body [63] and has been used safely in Europe as Dimaval for many years [64 67]. DMPS is registered in Germany with the BGA (the German equivalent of the US FDA) for the treatment of mercury poisoning but is still an investigational drug in the USA [68]. DMPS Can Be Used To Eliminate Mercury Systemically. The use of DMPS to treat mercury toxicity is well established and accepted [69 71]. DMPS has clearly demonstrated

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elimination effects on the connective tissue [72, 73]. The DMPS dose is 3 5 mg kg 2 1 body weight once a month which is injected slowly intravenously over ve minutes. DMPS-stimulated excretion of all heavy metals reaches a maximum 2 3 h after infusion and decreases thereafter to return to baseline levels after 8 h [74]. DMPS Safety. DMPS is not mutagenic, teratogenic or carcinogenic [75]. Ideally intravenous DMPS should never be used in patients who still have amalgam llings in place, although investigators have done this diagnostically, as a one-time dose, without complications [76]. DMPS appears in the saliva and may mobilize signi cant amounts of mercury from the surface of the llings and precipitate seizures, cardiac arrhythmias, or severe fatigue. Even though DMPS has a high af nity for mercury, the highest af nity appears to be for copper and zinc [77] and supplementation needs to be used to avoid depleting these bene cial minerals. Zinc is particularly important when undergoing mercury chelation [78]. DMPS is administered over a ve-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-penicillamine [81] 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 of displacing mercury towards the inside of the cell [86] after binding mercury somewhere on its way from the intestine to the succinic acid de cient 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 2 1 twice a day for two weeks. The DMSA is then stopped for two weeks and 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 ef uent 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 chlorellas 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

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due to gastrointestinal distress. Chitosan can be effectively used as an alternative in these individuals. Chitosan makes up most of the hull of insects and shell sh and also bind metals like mercury from the lumen of the intestines [93 95]. Cilantro Omura determined that cilantro could mobilize mercury and other toxic metals rapidly from the CNS [96, 97]. Cilantro mobilizes mercury, aluminum, and lead 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 super cial structures, from where it can be more easily 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 mercurys binding to sulfhydryl groups. Many individuals sulfur stores are greatly depleted which impairs the effectiveness of sulfur containing chelating or complexing agents, such as DMPS or DMSA, 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 effective agents to supply organic sulfur for detoxi cation [101]. Fresh garlic is preferred as it has many other recently documented bene ts [102 104]. 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 IU day 2 1 have been shown to have a protective effect when the brain is exposed to methyl-mercury [68, 105]. Selenium, 200 400 l g day 2 1 [106 109], 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 detoxi cation [110 114]. Some clinicians nd 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 [115], 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 [116]. Vitamin C is also a helpful supplement for mercury elimination [117 122]. Some clinicians will use it intravenously in doses of 25 100 g 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 [123]. HA is utilized in many chemotherapy protocols as a potentiating agent [124]. HA is also being utilized for many novel applications in medicine [125, 126]. Personal experience has shown that the addition of 2 ml with the DMPS tends to improve the excretion of mercury by two to fourfold with virtually no toxicity. CONCLUSION We have described the signi cant toxicities associated with mercury amalgams and treatment agents that both authors have used successfully over the past two decades to

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eliminate mercury and resolve many chronic health complaints. Considering the weight of evidence supporting amalgam toxicity it would seem prudent to select alternative dental restoration materials.

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