Environmental Medicine Department
Long-term effects of chronic low dose mercury exposure
Walter J. Crinnion ND
Mercury is ubiquitous in our environment and in our mouths, in the form of “silver” amalgams. Once introduced to the body through food or vapor it is rapidly absorbed and accumulates in several tissues leading to increased oxidative damage, mitochondrial dysfunction and cell death. It primarily affects the neurological tissue leading to numerous neurological symptoms, the kidneys and the immune system. It causes increased production of free radicals and reduces available antioxidants. It also has devastating effects on the Glutathione content of the body giving rise to the possibility of increased retention of other environmental toxins. Fortunately, there are good tests available to get and idea of the mercury burden and sulfur-containing compounds to help reduce the load.
Mercury is ubiquitous in our environment due to the constant off gassing of mercury from the earths crust. This mercury enters the waterways where it is methylated by algae and bacteria. This methylmercury makes its way into fish and shellfish and ultimately into man. Additional mercury is released by industry into the atmosphere that will ultimately become methylmercury in the waterways. Forty states now have warnings in some of their waters because of mercury contamination. Warning have been issued for fish in nearly 15 percent of the nation’s lake acres and 5 percent of river and stream miles. In the Pacific Northwest the most recent finding of high mercury was in the sediment of the Spokane River. The mercury contamination came from its headwaters Lake Coeur d’Alene in Northern Idaho. The contamination of this lake with not only mercury but also zinc, lead, cadmium, arsenic and antimony is believed to have come from more than a century of mining operations in northern Idaho’s Silver Valley. The US Geological Survey has estimated that the bed of Lake Coeur d’Alene contains about 70 million metric tons of contaminated sediment.
In 1999 the Environmental Protection Agency (EPA) finally directed utilities to measure the amount of mercury released by coal-burning power plants. Mercury is also released into the environment by the burning of oil, its use as a fungicide (often applied to seeds), outdoor paint (it was banned in indoor paint in 1990) and processes involving chlorine manufacture and use. Waste mercury is released into the atmosphere by cremations (with estimations that a single crematorium releases 5,453 kg of mercury per year(1). A great amount of elemental mercury is also released into the environment by waste water from dental offices. In King County, Washington, the mercury contaminates the sludge from waste water treatment sites that is often then sold as fertilizer. Gold mining in the Amazon basin uses mercury to capture gold particles as amalgam. This has also resulted in widespread pollution of mercury in the Amazon River and its human and animal inhabitants(2). Fish absorb methylmercury from water as it passes over their gills and as they feed on aquatic organism. This methylmercury accumulates in the fish and passes up the food chain. Methylmercury binds tightly to the proteins in the fish tissue, including muscle. Cooking does not appreciably reduce the methylmercury content of the fish. The half-life of methylmercury in fish is 2 years, which is two to five times the half-life of inorganic mercury. (3)
Nearly all fish contain trace amounts of methyl mercury. Fish living in areas of high pollution, like the Great Lakes, will have much higher levels of mercury as well as other pollutants. Methylmercury levels for most fish range from less that 0.01ppm to 0.5ppm. Usually only the large predator fish such as shark and swordfish are the ones found to have level of methylmercury reaching the Food and Drug Administration (FDA) limit for human consumption of 1 ppm. Certain species of very large tuna that are typically sold as tuna steaks or sushi can also have levels of 1 ppm or greater. Canned tuna is usually composed of smaller species of tuna such as skipjack and albacore and will typically have much lower levels averaging about 0.17 ppm. In the Seychelles Islands in the western Indian Ocean the larger fish, Kingfish, Becune, Carangue Balo and Bonita all exceeded the 1ppm levels. More than half of the Dogtooth tuna recently sampled there also exceeded the FDA limit with two fish reaching levels of 3.3 and 4.4 ppm(4). While the level of methylmercury in the Skipjack tuna from those waters ranged only from 0.02-0.44ppm. The average concentration of methylmercury for most commercial fish is less than 0.3ppm.(5) Whales are also found to have a very high mercury content. Sport fish from the Great Lakes average from a low of 0.11 ppm in Lake Michigan and 0.19 ppm in Lake Huron to between .24 -.58 ppm in Lake Erie and .48-.88 ppm in Lake St. Clair. Perch from Lake St. Clair had the high mark of .88 ppm while those from Lake Erie averaged .24 ppm. In Lake Erie the high mercury-containing fish were Walleye, White bass and Smallmouth bass. (6)
In the FDA Total Diet Survey mercury was found in 100% (16/16) samples of canned tuna (avg. 0.277ppm), frozen cod/haddock fillets (avg. 0.132ppm), canned mushrooms (avg. 0.0298ppm), and shrimp (avg. 0.0281ppm). It was found in 15/16 samples of fish sticks (avg. 0.0254ppm) and crisped rice cereal (avg. 0.0044ppm).  (7)
Methylmercury is efficiently absorbed into the body (more than 95% absorption from food) and crosses both the blood-brain barrier and the placental barrier. It is known to be a potent neurotoxin and terratogen(8). Its biological half-life in humans is about 70 days.(9) It is present in the breast milk of lactating mothers who consume mainly seafood diets. The mercury concentration in the milk of these women has ranged from 2.45 ug/liter in women of the Faroe Islands eating meat and blubber of the pilot whale (10), to 3 ug/liter in Sweden (11) and 7.6 ug/liter in coastal Alaska (where they ate a lot of whale)(12). Major poisoning incidents with methylmercury have occurred in Minamata Bay (1953-1960) and Niigata (1965) in Japan when industrial dumping of mercury led to chronic mercury poisoning in persons whose primary source of food was seafood from those waters(13). A more recent poisoning episode occurred in Iraq in the fall and winter of 1971-1972. In this situation wheat that was treated with alkyl mercury as a fungicide and intended for seed was used instead to be ground into flour for bread. This exposure resulted in over 6,000 persons being hospitalized and 459 deaths(14).
Elemental mercury sources
Silver “amalgam” dental fillings typically weigh between 1.5-2.0g with approximately 50% of the material being elemental mercury. Persons with such fillings on their occlusal surfaces have been found to have levels of mercury vapor in their oral cavity nine times greater than persons without Amalgams
when no chewing has occurred (unstimulated). When chewing stimulation occurs those same individuals had a six-fold increase in elemental mercury levels. This gave those amalgam-bearing individuals 54 times greater levels of mercury vapor in their oral cavities during chewing than persons without amalgams(15). Serial measurements of these individuals found that mercury concentrations remained elevated during 30 minutes of continuous chewing and declined slowly over 90 minutes after cessation of chewing(16). Based upon their small trial (35 subjects) the researchers concluded that persons with one to four occlusal Amalgams
would be exposed to an average daily dose of 8ug elemental mercury. Those with twelve or more occlusal Amalgams
were estimated to receive 29ug per day. They placed the average of all the 35 subjects at 20ug per day. Individual cases have been published showing urinary mercury excretion to be 23-60ug/Hg/day (25-54ug/g creatinine) indicating a daily intake as high as 100ug(17). In these individuals bruxism and gum chewing were noted as the probable causes of the high mercury output, which fell back to “normal” levels with Amalgam
removal. Greater levels of mercury release from dental amalgams have also been found with tooth brushing (18) and after consuming hot drinks(19).
Mercury vapor released in these instances is highly lipid soluble and enters the blood from both the lungs and oral mucus membranes, traverses cell membranes (including the blood brain and placental barriers), rapidly partitions between plasma and red blood cells and becomes widely distributed. Up to 40% of the mercury vapor is excreted through the feces(20). Once in the cells Hg gets oxidized by catalase-hydrogen peroxide and becomes divalent Hg2+, a reactive species. This combines covalently with nearby sulfhydryl groups such as hemoglobin, reduced glutathione and protein cysteine groups. Those with mercury exposure have been found to have lower levels of reduced glutathione(21).
Blood mercury concentrations have been positively correlated with the number and surface area of Amalgam
restorations and are significantly higher in those with amalgams than those without(22). Amalgams are also associated with higher urinary output(23) as well as high levels in breast milk but not hair(24). When examining association with mercury presence in breast milk it was found that total and inorganic mercury levels in blood and milk were correlated with the number of Amalgam
fillings. In this study where seafood was not the main dietary staple there was no association found between dietary methylmercury intake and milk levels. Exposure of the breastfeeding infant to mercury was calculated at a range of up to 0.3ug/kg (one half of the tolerable daily intake for adults recommended by the World Health Organization).
Animal models have demonstrated that mercury from dental amalgams will migrate to and concentrate in the kidney, liver, gastrointestinal tract, and jaw (25,26). The choroid plexus, an important part of the blood brain barrier, acts as a sink for mercury and other heavy metals (27). It has also been shown that mercury is selectively concentrated in human brains in the medial basal nucleus, amygdala and hippocampus regions all of which are involved with memory function, the granule cells in the granular layer of the cerebellum and the sensory neurons of the dorsal root ganglia. It has also been shown to be taken up by the retina(28), the granule cells of layer IV in the visual cortex of the brain and to cause an reversible impairment of color perception(29)
Other mercury exposure sources
Historically mercury was used to treat syphilis and other infective diseases. When Captains Meriwether Lewis and William Rogers Clark set out with their Corps of Discovery in 1804 they brought with then a large store of “Rushes’s Pills”. These were mercury pills provided for the journey by Dr. Benjamin Rush, one of the most famous American Physicians of the time(30). The use of these pills is reflected in the journals of Meriwether Lewis as he recorded their dispensing. The use of mercury for medical treatments by this famous group may yield information on the exact location of Fort Clatsop where the Corps wintered in 1805/06. Archeologists are currently searching for the location of their latrine by taking soil samples and measuring for high concentrations of mercury, which would have followed the fecal route of excretion. Once found it would pinpoint the location of the fort for which only a general location is now known. Mercury is still being used today in some medicines as a preservative. It is present in this form in various vaccinations.
Mercury poisonings have occurred with mercury left in abandoned industrial sites. In Texarkana, Arkansas teenagers found 2 ½ pints of mercury in an abandoned neon sign plant leading to one hospitalization and seven homes being evacuated by the EPA(31). A more serious incident occurred in New Jersey. There, a group of artists and their families converted a five-story factory building used to manufacture mercury vapor lamps in the 1930s, into condominium apartments that were occupied in 1994-1995. When residents reported finding standing pools of mercury on the countertops and floors the local health agencies were contacted. Air mercury levels were found to range from 5 ug/m3 to 888ug/m3 (over visible pools of mercury on the floor), 69% of the residents’ urine samples had levels of mercury greater than 20 ug/l(32). Comparisons of the urine at the time of evacuation from the building and 10 weeks later showed no significant differences(33). Former residents with the highest urine mercury levels exhibited the most errors on a test for fine motor function and reported the greatest elevations in somatic and psychological symptoms. Another residential poisoning was reported in which mercury vapor was spread by the use of the family vacuum. It had previously been used to vacuum up mercury from a broken thermometer. Continued use of the vacuum spread mercury droplets throughout the house. The 2-year-old girl developed nephrotic syndrome and her 3-year-old brother had significant neurological problems(34). Mercury poisoning has also been found in persons living proximal to an inactive mercury mine in California(35), and in individuals from several states using Crema de Belleza-Manning facial cream. This cream was found to contain 6-10% mercury, while the facial cream Nutrapeil Cremaning Plus was found to have 9.7% mercury(36).
Adverse effects on the body
Cellular and nutritional alterations
Mercury has the ability to cause changes on the cellular level including in platelets and erythrocytes. These cells were used as surrogate markers for mercury damage of neurological tissue. It was found that the addition of methylmercury to whole blood caused a dramatic dissolution of microtubules in platelets and red blood cells. This effect was more pronounced in erythrocytes than platelets, which was consistent with the known sequestration of methylmercury in erythrocytes(37). This effect on microtubules has also been found in the brain(38) and results in the disruption of the cell cycle. This disruption has been shown to lead to apoptosis in both neuronal and non-neuronal cells(39).
Mercury has also been found to cause apoptosis in monocytes and to decrease phagocytic activity(40). The percentage of cells undergoing apoptosis was dependent upon the mercury content of the medium, regardless of the form of mercury. Methylmercury chloride was also shown in the same study to cause a decrease in the mitochondrial transmembrane potential within one hour of exposure. Methylmercury has also been shown to cause increased rates of lymphocyte apoptosis. The mechanism for this includes a depletion of glutathione (GSH) content predisposing the cell to oxidative damage while activating death-signaling pathways(41). These researchers also found that mercury led to altered mitochondrial function. When synovial joint tissue was looked at it was found that mercury (as well as cadmium and lead) caused a decrease in DNA content and an increase in collagenase-resistant protein formation(42).
Mercury is bound by selenium in the body, which can actually counteract mercuric chloride and methylmercury toxicity (43,44). While this does not result in a decrease in the amount of mercury, it does result in a decrease in the toxicity of mercury. It does however appear to lead to a reduced amount of available selenium which compounds the oxidative burden on the body. It was previously mentioned that mercury reduces the level of GSH in the body (21), which is accomplished by several mechanisms. Mercury will bind irreversibly to GSH causing the loss up to two GSH molecules through the bile into the feces. Part of the irreversible loss of GSH is due to the inhibition of GSH reductase by mercury(45), which is used to “recycle” oxidized GSH and return GSH to the pool of available antioxidants. At the same time mercury also inhibits GSH synthetase so that less new GSH can be made. This is compounded by the mercury-reduced selenium content that would normally stimulate more GSH production. Since mercury promotes formation of hydrogen peroxide, lipid peroxides and hydroxyl radicals at the same time, it is clear that mercury sets up a scenario for a serious imbalance in the oxidative/antioxidant ratio of the body (46). The heavy oxidative toll on the body by mercury has been postulated to be a cause of increased rates of fatal myocardial infarctions and other forms of cardiovascular disease(47). All of these interactions show the clear need for increased levels of Selenium, and Vitamin E, which has also been shown to reduce methylmercury toxicity(42,48).
Mercury in both organic and inorganic forms is neurotoxic. Methylmercury accumulates in the brain and becomes associated with mitochondria, endoplasmic reticulum, golgi complex, nuclear envelopes, and lysosomes. In nerve fibers methylmercury is localized primarily in myelin sheaths where it leads to demyelination and in the mitochondria(49). Pathologic examination of patients with methylmercury poisoning indicates that the cerebellar cortex is prominently affected with granule cells being more susceptible than Purkinje cells. Typically, glial cells are spared direct damage, although reactive gliosis may occur. Toxicity from mercury probably does not result from action on a single target. Instead, because of its highly reactive nature, a complex series of many unrelated (and some interrelated) effects may occur more or less simultaneously, initiating a sequence of additional events that ultimately lead to cell death. Some of these events include the following.
The adverse affect of mercury on GSH has secondary effects on the levels of Na+, K+ and Mg++ ATPases, all of which are –SH dependant. These enzymes are all found to be reduced by various mercurial compounds(50) and are critical for the proper functioning of nervous and other tissues. Injections of GSH in animals exposed to methylmercury fortunately resulted in the recovery of N+, K+, and Mg++ ATPases(51). In the absence of nutrients to counteract this action, the reduction of these ATPases results in the neurotoxic swelling and destruction of astrocytes(52). Astrocytes are the primary cells responsible for the homeostatic control of synaptic pH, Na/K and glutamate. Mercury is also known to inhibit the uptake of dopamine(53), serotonin(54), and norepinephrine (55) at synaptic sites. For serotonin-binding sites the mercury apparently has a higher binding affinity. Mercury has also been reported to cause an increase in evoked acetylcholine release followed by a sudden and complete blockade(56). Prolonged exposure to methylmercury results in an up-regulation of muscarinic cholinergic receptors in the hippocampus and cerebellum and on circulating lymphocytes(57). It also affects the release of neurotransmitters from presynaptic nerve terminals. This may be due to its ability to change the intracellular concentration of Ca2+ by disrupting regulation of Ca2+ from intracellular pools and increasing the permeability of plasma membranes to Ca2+(58). While there is undoubtedly much more to learn about the specific mechanisms of mercury-neurotoxicity, the symptoms of it are fairly clear.
The widespread pollution of Minamata bay by methylmercury in the 1950s has provided researchers with a clear picture of methylmercury-induced neurotoxicity as a great cost to the inhabitants of the area. Known as Minamata Disease (MD), the neurotoxic signs include ataxia, speech impairment, constriction of visual fields, hypoesthesia, dysarthria, hearing impairment and sensory disturbances. These neurological problems persisted and were found in other areas of Japan as the mercury contamination spread(59). Follow-up studies in the Minamata area almost forty years after the spill and almost thirty years since a fishing ban was enacted for the area showed continued problems. Residents in fishing villages in the area in 1995 reported significantly higher prevalence’s than “town-resident-controls” in males for the following complaints: stiffness, dysesthesia, hand tremor, dizziness, loss of pain sensation, cramping, atrophy of the upper arm musculature, arthralgia, insomnia and lumbago. Female residents of the fishing villages had significantly higher incidents of complaints of leg tremor, tinnitus, loss of touch sensation, leg muscular atrophy and muscular weakness(60). Amazonian children exposed to methylmercury from local gold mining have also been studied for the neurotoxic effect of methylmercury. In the villages studied, more than 80% of the children had hair mercury levels above 10ug/g (a level above which adverse effects on brain development are likely to occur). Neuropsychological tests of motor function, attention, and visuospatial performance in these children showed decrements associated with hair mercury concentrations(61).
Neurotoxicity is not related just to methylmercury as a study of 98 dentists with 54 non-dentist controls revealed. The dentists, with an average of 5.5 years of exposure to amalgams, performed significantly worse on all of the following neurobehavioral tests: motor speed (finger tapping), visual scanning (trail making), visuomotor coordination and concentration (digit symbol), verbal memory, visual memory and visuomotor coordination speed(62). The dentists’ performance on each of these tests diminished as their total exposure increased (amount of daily exposure and years of exposure).
Mercury is also being implicated in Alzheimer’s disease and other chronic neurological complaints. In 1988, it was reported from Alzheimer cadaver studies that mercury was found in much higher levels in the nucleus basalis of Meynert than in controls (40ppb vs. 10ppb)(63). Subsequent studies have showed elevated mercury throughout the brain in persons with Alzheimer’s(64). Further, when rats were exposed to elemental mercury vapor at the same levels as have been documented in the oral cavity of humans with amalgams, lesions similar to those seen in Alzheimer’s disease have occurred(65). The same lesions have been demonstrated when rat brains were exposed to EDTA-mercury complex(66). While ALS has been associated in some instances with possible Cadmium exposure, a published case history revealed a diagnosed case of ALS recovering after amalgam removal. The individual in question had 34 amalgam fillings. After the first removal her ALS symptoms were exacerbated, but noted improvement fairly soon after all were removed. Five months later upon returning to the neurology clinic she was found to have no evidence of motor neuron disorder(67).
Mental health symptoms are also quite common with mercury toxicity. Evidence linking mercury exposure to psychological disorders has been accumulating for the past 60 years. The recognized psychological symptoms of mercury include: irritability, excitability, temper outburst, quarreling, fearfulness, restlessness, Depression
and in some cases insomnia. In a study of individuals with amalgam filling who had them removed the majority noted psychological improvements. The greatest improvements were found in anger outbursts, depression, irritability and fatigue(68). None of these manifestations being too surprising when related to the effect of mercury on reducing serotonin effect. The association of mercury to Depression
has stimulated some interesting questions as to whether mercury toxicity was to blame for Sir Isaac Newton’s health problems of 1692-93(69). One would also wonder if it might have contributed to the Depression
and apparent suicide of Meriwether Lewis.
Kidney injury is a characteristic consequence of acute poisoning from inorganic mercury. Albuminuria is a classic sequelae, and may be of either glomerular or tubular origin. In rabbits, rats and mice multiple exposures to inorganic mercury induce the production of antibodies against the glomerular basement membrane, deposition of immune complexes in the mesangium and glomerular basement membrane, and glomerular nephritis,,,(70,71,72,73). Further studies have shown that mercury induces a nephropathy that at the lowest effective doses is restricted primarily to the S3 segment of the proximal tubule. With greater doses of mercury the lesions move to include the S2 and S1 segments as well(74). This nephropathy is apparently due to a selective induction of apoptosis of the renal proximal tubular cells(75), presumably by the same method of apoptosis previously mentioned regarding other cell lines. Studies in sheep have identified renal tubular reabsorption of inulin to be impaired following amalgam placement(76). In a small human study no increased albuminuria was found in healthy male students with amalgams(77), but a study of natural gas workers exposed to mercury vapor revealed minor kidney changes without the presence of neurological changes(78). Mercury has also been associated in potassium-wasting nephropathy(79); including one case in the author’s own practice(80).
As mentioned earlier, mercury increases apoptosis of both monocytes and lymphocytes and reduces phagocytic ability of the monocytes. It has been demonstrated that workers occupationally exposed to mercury vapor exhibited diminished capacity to produce both TNFalpha and IL-1(81). A number of investigators have reported that mercurials are capable of immune activation leading to autoimmunity while simultaneously reducing the cellular immune response leading to increased infection (70-73, 82,83,84,85),,,, which is the classic appearance of immunotoxicity(86). Simultaneously with the immune alterations are changes in the hypothalamic-pituitary-adrenal axis as exhibited by increased levels of ACTH and corticosterone(87). The increase in corticosterone levels could add to the immunosuppresiveness that is already present. Not only will the mercury cause abherent responses in both the cellular and humoral immune systems but also it may cause bacteria to become resistant to Antibiotics
. Studies done on monkeys has shown that within five weeks of getting amalgam fillings the intestinal bacteria of the primates became resistant to penicillin, streptomycin, kanamycin, chloramphenicol and tetracycline(88).
As previously mentioned in the body of this text several methods for assessing mercury contamination have been used including hair, urine and blood. Methylmercury shows up very well in the hair and has been the primary testing measurement of Amazonian children(61), and persons from around Minamata bay(89). Some methylmercury studies look at a combination of urine and hair, both of which appear as sensitive markers and correlate significantly with each other(90). Elemental mercury (from amalgams) does not show up well in the hair(24), in fact other hair mercury studies have shown that hair mercury levels are 79-94% methylmercury, leaving only 6-21% as elemental mercury(89). With such a low affinity of elemental mercury for the hair, one may have a significant amount of elemental mercury and not exhibit any on the hair test. Since mercury binds tightly to selenium and sulfur it has been suggested that low mercury and high sulfur and/or selenium on the hair test indicates a body burden of elemental mercury(91). Elemental mercury from amalgams shows up best in the plasma and urine(92). While twenty-four hour urine samples are generally used in such studies, in males no diurnal variations are found in mercury excretion and the first morning urine shows strong correlation with the twenty-four hour sample(93). Women did exhibit a diurnal pattern in urinary mercury excretion leaving the twenty-four hour sample as the best way to measure mercury.
While an unprovoked twenty-four hour urine test for mercury can bed very illuminating, a urine test following a provocative challenge with 2,3-Dimercaptosuccinic acid (DMSA) or 2,3-dimercaptopropane-1-sulfonate (DMPS) can reveal even more. This can be especially revealing if the provoked test is done following the unprovoked. The author has found this method to be quite effective at revealing heavy metal (not just mercury) burdens in chronically ill individuals. However, neither provoked nor unprovoked tests may show the whole picture of heavy metal load. In a study of 18 subjects, all of whom previously had amalgam fillings and who exhibited symptoms of mercury overload, the four who still had their fillings showed urine mercury levels within the normal range. Those who had already had amalgam removal showed elevated urine levels. When the four had their amalgams removed, their urine output increased to elevated levels over time. The researchers hypothesized that some persons with amalgams present exhibit a “retention toxicity”(94), where they fail to dump mercury in the urine even while they are mercury burdened. The same researchers hypothesized that a large fraction of the total body burden on mercury may be present in the bone as is found with lead.
Currently there is one laboratory that is also utilizing fecal testing on heavy metals. Since the primary route of excretion for heavy metals is the bowel this form of testing makes sense. It is also a very easy method for testing young children as gathering a sample is fairly easy. The lab has currently reported that a high mercury content in the fecal sample is indicative of a high mercury output on a provocative urine test(91).
To effectively reduce the body burden of mercury the sulfur-containing compounds 2,3-Dimercapatosuccinic acid (DMSA) and 2,3-Dimercapto-1-propanesulfonic acid (DMPS), and N-acetyl Cysteine (NAC) have all been used. DMSA was first proposed as a treatment for heavy metal toxicity in 1965 by Ting(95). It has since demonstrated its effectiveness for successfully mobilizing lead, mercury, cadmium and arsenic (96.97). The optimum dose shown by these researchers was 30mg/kg/day given in 3 divided doses for 5 days at a time. This dose actually showed greater clearing of lead than EDTA given at a dose of 50 mg/kg/day. Both will increase the urinary output of these four heavy metals with no nephrotoxicity being noted. In fact DMPS may be of benefit in reducing the nephrotoxicity of mercuric chloride(98). When all three agents were tested along with potassium citrate (5 g), DMPS (orally given at a dose of 10mg/kg while intravenously it is dosed at 3 mg/kg), DMSA (30 mg/kg) and NAC 30mg/kg) their effects on mercury excretion were reasonably similar(99). When given alone DMSA caused an increase in urinary mercury excretion of 163%, DMPS 135%, NAC 131%, and Potassium citrate 83%. When given with potassium citrate the urinary mercury excretion increased to 163% for both DMPS and NAC.
DMSA and DMPS have similar affinities for the heavy metals although in the authors experience DMSA is more effective at mobilizing lead. DMSA was also found to have no effect on the elimination of iron, calcium or magnesium although both DMSA and DMPS will increase the excretion of copper and zinc(100). In addition these both have affinity for manganese and molybdenum. It may be prudent to provide these nutrients before, during, or after the use of these agents to prevent nutrient depletion. Zinc supplementation may also be warranted for extra protection of the kidneys from mobilized arsenic, cadmium and mercury as it will stimulate the production of metallothionien (see excellent review on this topic by Quig,D, Alt. Med Rev. Aug. 1998). The author has found that although these compounds do not chelate magnesium, their use will increase urinary magnesium excretion that is already elevated in many of the heavy metal-burdened individuals. He has found that supplementation with magnesium is necessary in these persons.
Mercury is ubiquitous in our environment and in our mouths, in the form of “silver” amalgams. It is rapidly absorbed in the body and accumulates in several tissues leading to increased oxidative damage, mitochondrial dysfunction and cell death. It primarily affects the neurological tissue, the kidneys and the immune system. It also has devastating effects on the Glutathione content of the body giving rise to the possibility of increased retention of other environmental toxins. Fortunately, there are good tests available to get and idea of the mercury burden and sulfur-containing compounds to help reduce the load.
 Maloney SR, Phillips CA, Mills A. Mercury in the hair of crematoria workers. Lancet 1998;352:1602
 Lebel J. Mergler D, Lucotte M. Evidence of early nervous system dysfunction in Amazonian populations exposed to low-levels of methylmercury. Neurotoxicol 1996;17:157-167.
 Stopford W, Goldwater LJ. Methylmercury in the environment: a review of current understanding. Environ Health Perspect 1975;12:115-118
 Matthews AD. Mercury content of commercially important fish of the Seychelles, and hair mercury levels of a selected part of the population. Environ Res 1983;30:305-312.
 Mercury in fish: cause for concern? U.S. Food and Drug Administration, FDA Consumer. September 1994, Revised May 1995
 Tollefson L, Cordle F. Methylmercury in fish: a review of residue levels, fish consumption and regulatory action in the United States. Environ Health Perspect 1986;68:203-208.
 Gunderson EL. FDA Total Diet Study, April 1982-April 1986. Dietary intake of pesticides, selected elements and other chemicals. Distributed by: Association of Official Analytical Chemists. Arlington, VA.
 Clarkson TW, Hursh JB, Sager PR, Syversen JP. Mercury. In: Biological Monitoring of Toxic Metals (Clarkson TW, Friber L, Nordberg GF, Sager PR, eds). Plenum Press, New York 1988:199-246.
 Miettinen JK. Absorption and elimination of dietary mercury(2+)ion and methylmercury in man. In: Mercury, Mercurials, and Mercaptans (Miller MW and Clarkson TW, Eds), Proceedings 4th International Conference on Environmental Toxicology. Plenum Press, New York 1973.
 Grandjean P, Weihe P, Needham LL, Burse VW, Patterson DG, Sampson EJ, Jorgensen PJ, Vahter M. Relation of a seafood diet to mercury, selenium, arsenic and polychlorinated biphenyl and other organochlorine concentrations in human milk. Environ Res 1995;71:29-38.
 Skerfving S. Mercury in women exposed to methylmercury through fish consumption, and in their newborn babies and breast milk. Bull Environ Contam Toxicol 1988;41:475-482.
 Galster WA. Mercury in Alaskan Eskimo mothers and infants. Environ Health Perspect 1976;15:135-140
 Watanabe C, Satho H. Evaluation of our understanding of methylmercury as health threat. Environ Health Res 1996;104:367-378.
 Clarkson TW, Amin-Zaki L, Al-Tikriti SK. An outbreak of methylmercury poisoning due to consumption of contaminated grain. Fed Proc 1976;35:2395-2399.
 Vimy MJ, Lorsheider FL. Intra-oral air mercury released from dental amalgams. J Dent Res 1985;64(8):1069-1071.
 Vimy MF, Lorsheider FL. Serial measurements of intra-oral air mercury: estimation of daily dose from dental amalgams. J Dent Res 1985;64(8):1072-1075.
 Barregard L, Sallsten G, Jarvholm B. People with high mercury uptake from their own dental amalgam fillings. Occup. Environ Med 1995;52:124-128.
 Patterson JE, Weissberg B, Dennison PJ. Mercury in human breath from dental amalgam. Bull Environ Contam Toxicol 1985;34:459-68.
 Anthony H, Birtwistle S, Eaton K, Maberly J. eds. Environmental Medicine in Practice. Southhamptom: BSAENM Publications;1997:204-208.
 Engqvist A, Colmsjo A, Skare I. Speciation of mercury excreted in feces from individuals with amalgam fillings. Arch Environ Health 1998;53(3):205-213.
 De Souza Queiroz ML, Pena SC, Salles TSI, de Capitani EM, Olalla Saad ST. Abnormal antioxidant system in erythrocytes of mercury exposed workers. Human & Exp. Toxicol 1998;17:225-230.
 Abraham JE, Svare CW, Frank CW. The effect of dental amalgam restorations on blood mercury levels. J Dent Res 1984;63(1):71-73.
 Trepka MJ, Heinrich J, Krause C, Schulz C, Wjst M, Popescu M, Wichmann HE. Factors affecting internal mercury burdens among East German children. Arch Environ Health 1997;52(2):134-138.
 Oskarsson A, Schutz A, Skerfving S, Hallen IP, Ohlin B, Langerkvist BJ. Total and inorganic mercury in breast milk and blood in relation to fish consumption and amalgam fillings in lactating women. Arch Environ Health 1996;51(3):234-241.
 Hahn LJ, Kloiber R, Leininger RW, Vimy MJU, Lorscheider FL. Whole body imaging of the distribution of mercury released from dental fillings into monkey tissue. FASEB J 1990;4:3256-3260.
 Hahn LJ, Kloiber R, Vimy MJ, Takahashi Y, Lorscheider FL. Dental “silver” tooth fillings: a source of mercury exposure revealed by whole-body image scan and tissue analysis. FASEB J 1989;3:2641-2646.
 Zheng W, Perry DF, Nelson DL, Aposhian HV. Choroid plexus protects cerebrospinal fluid against toxic metals. FASEB J 1991;5:2188-2189.
 Stortebecker P. Mercury poisoning from dental amalgam, a hazard to human brain. Stockholm: Stortebecker Foundation for Research 1985:24.
 Cavalleri A, Gobba F. Reversible color vision loss in occupational exposure to metallic mercury. Environ Res 1998;77:173-177.
 Barth G. Ed. The Lewis and Clark Expedition, selections from the journals arranged by topic. New York: Bedford St. Martins; 1998:158-162.
 Kissel KP. Teens fall ill after taking, playing with mercury. The Seattle Times: January 15 (1998).
 Orloff KG, Ulirsch G, Wilder L, Block A, Fagliano J, Pasqualo. Human exposure to elemental mercury in a contaminated residential building. Arch Environ Health 1997;52(3):169-172.
 Fiedler N, Udasin I, Gochfeld M, Buckler G, Kelly-McNeil K, Kipen H. Neuropsychological and stress evaluation of residential mercury exposure. Environ Health Perspect 1999;107(5):343-347.
 Bonhomme C, Gladyszaczak-Kohler J, Cadou A, Ilef D, Kadi Z. Mercury poisoning by vacuum-cleaner aerosol. Lancet 1996;347:115.
 Harnly M, Seidel S, Rojas P, Fornes R, Flessel P, Smith D, Kreutzer R, Goldmar L. Environ Health Perspect 1997;105(4):424-429.
 Mercury poisoning cases traced to face cream. Epi Trends. Washington State Department of Health 1996;1(2):4.
 Durham HD, Minotti S, Caporicci E. Sensitivity of platelet microtubules to disassembly by methylmercury. J Toxicol Environ Health 1997;48;57-69.
 Falconer MM, Vaillant A, Reuhl KR, Laferriere N, Brown DL. The molecular basis of microtubule stability in neurons. Neurotoxicology 1994;15:109-122.
 Miura K, Koide N, Himeno S, Hakagawa I, Imura N. The involvement of microtubular disruption in methylmercury-induced apoptosis in neuronal and nonneuronal cell lines. Toxicol Appl Phamacol 1999;160:279-288.
 InSug O, Datar S, Koch CJ, Shapiro IM, Shenker BJ. Mercuric compounds inhibit human monocyte function by inducing apoptosis: evidence for formation of reactive oxygen species, development of mitochondrial membrane permeability transition and loss of reductive reserve. Toxicol 1997;124:211-224.
 Shenker BJ, Guo TL, Shapiro IM. Low-level methylmercury exposure causes human T-cells to undergo apoptosis: evidence of mitochondrial dysfunction. Environ Res 1998;77:149-159.
 Goldberg RL, Kaplan SR, Fuller GC. Effect of heavy metals on human rheumatoid synovial cell proliferation and collagen synthesis. Biochem Pharmacol1983;32(18):2763-2766.
 Ganther HE. Modification of methylmercury toxicity and metabolism by selenium and vitamin E: possible mechanisms. Environ Health Perspect 1978;25:71-76.
 Ganther HE. Selenium: relation to decreased toxicity of methylmercury in diets containing tuna. Science
 Zalups RK, Lash LH. Interactions between glutathione and mercury in the kidney, liver and blood. In: Chang, LW ed. Toxicology of Metals. Boca Raton: CRC Press; 1996:145-163.
 Miller OM, Lund BO, Woods JS. Reactivity of Hg(II) with superoxide: evidence for the catalytic dismutation of superoxide by Hg(II). J Biochem Toxicol 1991;6:293-298.
 Salonen JT, Seppanen K, Nyyssonen K, Korpela H, Kauhanen J, Kantola M, Tuomilehto J, Esterbauer H, Tatzber F, Salonen R. Intake of mercury from fish, lipid peroxidation, and the risk of myocardial infarction and coronary, cardiovascular, and any death in eastern Finnish men. Circulation 1995;91:645-655.
 Welsh SO, Soares JH Jr. The protective effect of vitamin E and selenium against methylmercury toxicity in the Japanese Quail. Nutr Rep Int 1976;13:43.
 Chang LW. Neurotoxic effects of mercury. A review. Environ Res 1977;14:329-373.
 Magour S, Maser H, Grein H. The effect of mercury and methylmercury on brain microsomal Na+, K+ ATPase after partial delipisation with lubrol. Pharmacol Toxicol 1987;60:184-186.
 Bapu C, Rao P, Sood PP. Restoration of methylmercury inhibited adenosine triphosphatases during vitamin and monothiol therapy. J Environ Path Toxicol Oncol 1998;17(1): 75-80.
 Aschner M, Eberle NB, Miller K, Kimelberg HK. Interactions of methylmercury with rat primary astrocyte cultures: inhibition of rubidium and glutamate uptake and induction of swelling. Brain Res 1990;530:245-250.
 Rajanna B, Hobson M, Harris L, Ware L, Chetty CS. Effects of cadmium and mercury on Na+, K+ ATPases and the uptake of 3H-dopamine in rat brain synaptosomes. Arch Int Physiol Biochem 1990;98(5):291-296.
 Oudar P, Caillard L, Fillon G. In vitro effects of organic and inorganic mercury on the serotonergic system. Pharmacol Toxicol 1989;65(4):245-248.
 Rajanna B, Hobson M. Influence of mercury on uptake of dopamine and norepinephrine by rat brain synaptosomes. Toxicol Lett 1985;27(1-3):7-14.
 Cooper GP, Manalis RS. Influence of heavy metals on synaptic transmission: a review. Neurotoxicology 1983;4(4):69-83.
 Coccini T, Randine G, Candura SM, Nappe RE, Prockop LD, Manzo L. Low-level exposure to methylmercury modifies muscarinic cholinergic receptor binding characteristics in rat brain and lymphocytes: physiologic implication and new opportunities in biological monitoring. Environ Health Perspect 2000;108(1):29-33.
 Atchison WD, Hare MF. Mechanisms of methylmercury-induce neurotoxicity. FASEB J.1994;8:622-629.
 Ninomiya T, Ohmori H, Hashimoto K, Tsuruta K, Ekino S. Expansion of methylmercury poisoning outside of Minamata: and epidemiological study on chronic methylmercury poisoning outside Minamata. Environ Res 1995;70:47-50.
 Fukuda Y, Ushinjima K, Kitano T, Sakamoto M, Futatsuka M. An analysis of subjective complaints in a population living in a methylmercury-polluted area. Environ Res 1999;81:100-107.
 Grandjean P, White RF, Nielsen A, Cleary D, de Oliveira Santos EC. Methylmercury neurotoxicity in Amazonian children downstream from gold mining. Environ Health Perspect 1999;107(7):587-591.
 Ngim CH, Foo SC, Boey KW, Jeyaratnam J. Chronic neurobehaviorual effects of elemental mercury in dentists. Br J Indust Med 1992;49:782-790.
 Thompson CM, Markesbery WR, Ehmann WD, Mao YX, Vance DE. Regional brain trace-element studies in Alzheimer’s disease. Neurotoxicology 1988;9(1):1-8
 Cornett CR, Markesbery WR, Ehmann WD. Imbalances of trace elements related to oxidative damage in Alzheimer’s disease brain. Neurotoxicology 1998;19(3):339-346.
 Pendergrass JC, Haley BE, Vimy MJ, Winfield SA, Lorscheider FL. Mercury vapor inhalation inhibits binding of GTP to tubulin in rat brain: similarity to a molecular lesion in Alzheimer disease brain. Neurotoxicity 1997;18(2):315-324.
 Pendergrass JC, Haley BE. Mercury-EDTA complex specifically blocks brain beta-tubulin-GTP interactions: similarity to observations in Alzheimer’s disease. In: Status Quo and Perspectives of Amalgam and other Dental Materials, Friberg LT, Scrauzer GN, eds. Stuttgart: Georg Thieme Verlag; 1995:98-105.
 Redhe O, Pleva J. Recovery form Amyotrophic Lateral Sclerosis and from allergy after removal of dental amalgam filling. Int J Risk Safety Med 1994;4:229-236.
 Siblerud Rl. The relationship between mercury from dental amalgam and mental health. Am J Psychotherapy 1989;43(4):575-587.
 Lieb J, Hershman D. Isaac Newton: mercury poisoning or manic depression. Lancet 1983;1479-1480.
 Bigazzi PE. Lessons from animal models: The scope of mercury-induced autoimmunity. Clin. Immunol Immunopathol 1992;65:81-84.
 Druet P, Druet E, Potdevin F, Sapin C. Immune type glomerulonephritis induced by HgCl2 in Brown-Norway rat. Ann Immunol (Inst Pasteur) 1978;129C:777-792.
 Enestrom S, Hultman P. Immune-mediated glomerular nephritis induced by mercuric chloride in mice. Experientia 1984;40:1234-1240.
 Enestrom S, Hultman P. Dose-response studies in murine mercury-induced autoimmunity and immune-complex disease. Toxicol Appl Pharmacol 1992;113:199-208.
 Diamond G, Zalups RK. Understanding renal toxicity of heavy metals. Toxicol Pathol 1998;26(1):92-103.
 Homma-Takeda S, Takenaka Y, Kumagai Y, Shimojo N. Selective induction of apoptosis of renal tubular cells caused by inorganic mercury in vivo. Environ Toxicol Pharmacol 1999;7:179-187.
 Boyd ND, Benediktsoon H, Vimy MJ, Hooper DE, Lorsheider FL. Mercury from dental “silver” tooth fillings impairs sheep kidney function. Am J Physiol 1991;261:R1010-1014.
 Herrstrom P, Schutz A, Raihle G, Holthuis N, Hogstedt B, Rastam L. Dental amalgan, low-dose exposure to mercury, and urinary proteins in young Swedish men. Arch Environ Health 1995:50(2) 103-110.
 Boogaard PJ, Houtsma AJ, Journee HL, Van Sittert NJ. Effects of exposure to elemental mercury on nervous system and the kidneys in workers producing natural gas. Arch Environ Health 1996;5(2):108-115.
 Szylman P, Benzakin A, Szjnader Y, Taitelman U. Potassium-wasting nephropathy in an outbreak of chronic organic mercurial intoxication. Am J Nephrol 1995;15:514-520.
 Crinnion WJ. Unpublished research. Healing Naturally, Kirkland, WA. 1999
 Langworth S, Elinder CG, Sundqvist KG. Minor effects of low exposure to inorganic mercury on the human immune system. Scan J Work Environ Health 1993;19:405-413.
 Blakley BR, Sisodia CS, Mukkur TK. The effect of methylmercury, tetraethyl lead, and sodium arsenite on the humoral immunity response in mice. Toxicol Appl Pharmacol 1980;52:245-254.
 Dieter MP, Luster MI, Boorman GA, Jameson CW, Dean JH, Cox JW. Immunological and biochemical responses in mice treated with mercuric chloride. Toxicol Appl Pharmacol 1983;68:218-228.
 Nordlind K. Inhibition of lymphoid-cell DNA synthesis by metal allergens at various concentrations. Effect on short-time cultured non-adherent cell compared to non-separated cells. Int Arch Allergy Appl Immunol 1983;70:191-192.
 Nakatsuru S, Oohashi J, Nozaki H, Nakada S, Imura N. Effect of mercurials on lymphocyte functions in vitro. Toxicology 1985;36:297-305.
 Wojdani A. Personal communication.
 Ortega HG, Lopez M, Takaki A, Huang QH, Arimura A, Salvaggio JE. Neuroimmunological effects of exposure to methylmercury forms in the Sprague-Dawley rats. Activation of the hypothalamic-pituitary-adrenal axis and lymphocyte responsiveness. Toxicol Indust Health 1997;13(1):57-66.
 Kolata G. New suspect in bacterial resistance: amalgam. The New York Times: April 24 (1993).
 Harada M, Nakanishi J, Kunuma S, Ohno K, Kimura T, Yamaguchi H, Tsuruta K, Kizaki T, Ookawara T, Ohno H. The present mercury contents of scalp hair and clinical symptoms in inhabitants of the Minamata area. Environ Res 1998;77:160-164.
 Abe T, Ohtsuka R, Hongo T, Suzuki T, Tohyama C, Nakano A, Akagi H, Akimichi T. High hair and urinary mercury levels of fish eaters in the nonpolluted environment of Papua New Guinea. Arch Environ Health 1995;50(5):367-373.
 Quig, D. Doctors Data Lab, Personal Communication.
 Halbach S, Kremers L, Willruth H, Mehl A, Welzl G, Wack FX, Hickel R, Greim H. Compartmental transfer of mercury released from amalgam. Hum Exp Toxicol 1997;16:667-672.
 Cianciola ME, Echeverria D, Martin MD, Aposian HV, Woods JS. Epidemiologic assessment of measures used to indicate low-level exposure to mercury vapor. J. Toxicol Environ Health 1997;52:19-33.
 Ely JT, Fudenberg HH, Muirhead RJ, LaMarche MG, Krone CA, Stern EA. Urine mercury in micromercurialism: a bimodal distribution and its diagnostic implications. Unpublished
 Ting KS, Liang YI, Shi J, Chen W, Gu T. Chelate stability of sodium dimercaptosuccinate on the intoxication from many metals. Chinese Med J 1965;64:1072-1075.
 Grazino JH, Lolacono NJ, Meyer P. Dose-response study of oral 2,3-dimercaptosuccinic acid in children with elevated blood lead concentrations. J. Pediatr 1988;113:751-757.
 Graziano JH. Role of 2,3-dimercaptosuccininc acid in the treatment of heavy metal poisoning. Med Toxicol 1986;1:155-162.
 Zalups RK, Cernichiari E. 2,3-dimercapto-1-propanesulfonic acid (DMPS) as a rescue agent for the nephropathy induced by mercuric chloride. The Toxicologist 1990;10(1):271(abstract only).
 Hibberd AR, Howard MA, Hunnisett AG. Mercury from dental amalgam fillings: studies on oral chelating agents for assessing and reducing mercury burdens in humans. J Nutr Environ Med 1998;8:219-231.
 Aposhian HV. DMSA and DMPS-water soluble antidotes for heavy metal poisoning.