Roels et al. (1985) examined 131 male and 54 female workers occupationally exposed to mercury vapor for an average duration of 4.8 years. Urinary mercury (52 and 37 ug/g creatinine for males and females respectively) and blood mercury levels (14 and 9 ug/L for males and females respectively) were recorded but atmospheric mercury concentration was not provided. Symptoms indicative of CNS disorders were reported but not related to mercury exposure. Minor renal tubular effects were detected in mercury-exposed males and females and attributed to current exposure intensity rather (urinary Hg >50 ug/g creatinine) than exposure duration. Male subjects with urinary mercury levels 50 ug/g creatinine exhibited preclinical signs of hand tremor. It was noted that females did not exhibit this effect and that their urinary mercury never reached the level of 50 ug/g creatinine.
A companion study (Roels et al. 1987) related air mercury (Hg-air)levels to blood mercury (Hg-blood) and urinary mercury (Hg-U) values in 10 workers in a chloralkali battery plant. Duration of exposure was not specified. A high correlation was reported for Hg-air and Hg-U for preshift exposure (r=0.70 p<0.001) and post-shift (r=0.81 p<0.001) measurements. Based on these data and the results of their earlier (1985) study the investigators suggested that some mercury-induced effects may occur when Hg-U levels exceed 50 ug/g creatinine and that this value corresponds to a mercury TWA of about 40 ug/cu.m.
This is an excerpt from the website posted above.
in limbo
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scary--so what did they do? Chelate with DMSA? Live with CNS disorders? (or die) lol
Dimercaptosuccinic Acid (DMSA) A Non-Toxic Water-Soluble Treatment For Heavy Metal Toxicity by Alan L. Miller N.D.
Abstract
Heavy metals are unfortunately present in the air water and food supply. Cases of severe acute lead mercury arsenic and cadmium poisoning are rare; however when they do occur an effective non-toxic treatment is essential. In addition chronic low-level exposure to lead in the soil and in residues of lead-based paint; to mercury in the atmosphere in dental amalgams and in seafood; and to cadmium and arsenic in the environment and in cigarette smoke is much more common than acute exposure. Meso-2 3-dimercaptosuccinic acid (DMSA) is a sulfhydryl-containing water-soluble non-toxic orally-administered metal chelator which has been in use as an antidote to heavy metal toxicity since the 1950s. More recent clinical use and research substantiates this compound's efficacy and safety and establishes it as the premier metal chelation compound based on oral dosing urinary excretion and its safety characteristics compared to other chelating substances. (Altern Med Rev 1998;3(3):199-207
Introduction
Contamination of water air and food by numerous chemicals and non-essential elements such as heavy metals is an unfortunate byproduct of a complex industrialized high-tech society. The resultant accumulation of heavy metals in the human body poses a significant health risk leading to a wide array of symptomatology including anemia learning deficits reduced intelligence behavioral and cognitive changes tremor gingivitis hypertension irritability cancer depression memory loss fatigue headache hyperuricemia gout chronic renal failure male infertility osteodystrophies and possibly multiple sclerosis and Alzheimer's disease.
Although human lead toxicity has decreased in the United States since discontinuation of the use of lead as a gasoline additive it continues to be a significant problem especially in urban areas where lead-based paint exposure is still an issue and in areas where lead is mined and/or smelted. Chronic mercury toxicity from occupational environmental dental amalgam and contaminated food exposure is a significant threat to public health. Other heavy metals including cadmium and arsenic can also be found in the human body due to cigarette smoke and occupational and environmental exposure. Diagnostic testing for the presence of heavy metals and subsequently decreasing the body's burden of these substances should be an integral part of the overall treatment regimen for individuals with the above-mentioned symptomatology or a known exposure to these substances.
It has long been acknowledged that sulfhydryl-containing compounds have the ability to chelate metals. The sulfur-containing amino acids methionine and cysteine cysteine's acetylated analogue N-acetylcysteine the methionine metabolite S-adenosylmethionine alpha-lipoic acid and the tri-peptide glutathione (GSH) all contribute to the chelation and excretion of metals from the human body.
Meso-2 3-dimercaptosuccinic acid (DMSA) is a water-soluble sulfhydryl-containing compound which is an effective oral chelator of heavy metals. Initial studies over forty years ago identified DMSA as an effective antidote to heavy metal poisoning. DMSA was subsequently studied for twenty years in the People's Republic of China Japan and Russia before scientists in Europe and the United States "discovered" the substance and its potential usefulness in the mid-1970s.1
DMSA is a dithiol (containing two sulfhydryl or S-H groups) and an analogue of dimercaprol (BAL British Anti-Lewisite) a lipid-soluble compound also used for metal chelation (see Figure 1). DMSA's water solubility and oral dosing create a distinct advantage over BAL which has a small therapeutic index and must be administered in an oil solution via painful deep intramuscular injection.2 DMSA on the other hand has a large therapeutic window and is the least toxic of the dithiol compounds.3
Lead
Lead exposure is still a public health problem in the United States being found in approximately 21 million pre-1940 homes. Dust and soil lead derived from flaking weathering and chalking paint also contribute to chronic exposure.
Lead competes in the body with calcium causing numerous malfunctions in calcium-facilitated cellular metabolism and calcium uptake and usage including inhibition of neurotransmitter release and blockade of calcium channels and calcium-sodium ATP pumps.
The central nervous system (CNS) appears to be affected the greatest by lead. Children in particular are susceptible to its devastating effects on mental development and intelligence. Neurobehavioral deficits resembling attention deficit disorder have also been found in lead-exposed children.4 Blood lead concentrations of 20-25 µg/100 ml can cause irreversible CNS damage in children.5
Poor quality nutrition including deficiencies in iron and calcium are known to exacerbate the manifestations of lead exposure including its CNS effects. Acute adult lead exposure leads to renal proximal tubular damage; chronic exposure causes renal dysfunction characterized by hypertension hyperuricemia gout and chronic renal failure.6
Inorganic lead is absorbed distributed and excreted. Once in the blood lead is distributed primarily among three compartments blood soft tissue (kidney bone marrow liver and brain) and mineralizing tissue (bones and teeth). Mineralizing tissue contains about 95 percent of the total body burden of lead in adults.
After lead is absorbed in the human body it reacts with thiol (sulfhydryl) groups on peptides and proteins inhibiting enzymes involved in heme synthesis and interfering with normal neurotransmitter functions.7 This natural reaction with thiols is also the body's method of eliminating lead especially from the liver. Hepatic glutathione attaches to lead and enhances its excretion in the feces. Unfortunately hepatic glutathione can be depleted in this manner resulting in less glutathione being available for conjugation of other toxic substances. In addition to these hepatic effects individuals with higher concentrations of blood lead have been noted to have lower levels of erythrocyte reduced glutathione.8 Decreased erythrocyte glutathione is due to the fact that 99 percent of lead in the blood is attached to red blood cells; the remaining one percent is in the plasma. Lead stored in bone has a half-life of 25 years although lead in bone can be mobilized into the blood and subsequently to other tissues
Mercury
Humans are exposed to mercury primarily in two forms: mercury vapor and methyl mercury compounds. Unfortunately mercury is a ubiquitous substance in our environment. Mercury vapor in the atmosphere makes its way into fresh and salt water by falling in precipitation. Methyl mercury compounds are created by bacterial conversion of inorganic mercury in water and soil which subsequently concentrates in seafood and fish. Dietary fish intake has been found to have a direct correlation with methyl mercury levels in blood and hair.9 10
"Silver" amalgam dental fillings are the major source of inorganic mercury exposure in humans.11 This term however is a misnomer as this compound is not predominately silver; the proper term should be "mercury amalgam." The most common dental filling material amalgams contain approximately 50 percent liquid metallic mercury 35 percent silver 9 percent tin 6 percent copper and a trace of zinc.12 As they are prepared and placed in the patient's mouth the dentist and the person preparing the amalgam 13 14 as well as the patient are exposed to mercury vapor (HgO). The patient is further exposed to mercury vapor as the amalgam releases HgO when the individual chews 15-17 brushes 18 or drinks hot beverages.16-18 Studies of mercury content in expired air of those with and without amalgams have found significantly higher baseline mercury levels in subjects with amalgams and up to a 15.6-fold increase in mercury in expired air after chewing.15 16 Mercury release was found to be greater in corroded amalgams compared to new polished fillings.18 Mercury vapor from amalgams enters the bloodstream after being inhaled into the lungs.
Comparisons of blood levels of mercury and the number of amalgams show a direct correlation between number of amalgam fillings and concentration of blood17 19 and urine mercury.13 14 20 In addition a statistically significant correlation was found between the number of dental amalgam fillings and mercury content of the kidney cortex (p <0.0001) and the occipital lobe cortex of the brain (p <0.0016) in cadavers.21
After removal of all amalgams there is a transient increase in mercury concentration in the blood plasma and feces followed by a decrease in blood levels below the pre-removal baseline.11 19 22 23
Mercury vapor is lipid soluble freely passing through cell membranes and across the blood-brain barrier. Methyl mercury also easily crosses the blood-brain barrier and the placenta.7 Inorganic and methyl mercury have a high affinity for sulfhydryls reacting intracellularly with the sulfhydryl group on glutathione and cysteine and histidine residues in proteins and allowing transport out of the cell. In rats it was found that mercury secretion into the bile was dependent on glutathione secretion into the bile suggesting the biliary secretion of mercury is in large part dependent on the biliary transport of GSH.24-26 In humans 90 percent of mercury elimination is via the feces with only 10 percent normally being excreted in the urine.12 A decrease in hepatic glutathione content secondary to excretion of mercury can decrease hepatic cell viability by mechanisms stated earlier
Arsenic and Cadmium
Environmental arsenic and cadmium exposure comes from pollutants discharged from industries utilizing these metals including herbicide and battery manufacturers. These metals are also found in cigarette smoke.
Cadmium as well as lead and mercury can interact metabolically with nutritionally essential metals. Cadmium interacts with calcium in the skeletal system to produce osteodystrophies and competes with zinc for binding sites on metallothionein which is important in the storage and transport of zinc during development.
Biliary excretion seems to be an essential factor for the fecal elimination of cadmium and arsenic although these metals may be also excreted in the urine.27 28
Pharmacokinetics of DMSA
In healthy individuals approximately 20 percent of an oral dose of DMSA is absorbed from the gastrointestinal tract. Ninety-five percent of the DMSA that makes it to the bloodstream is bound to albumin. Most likely one of the sulfhydryls in DMSA binds to a cysteine residue on albumin leaving the other S-H available to chelate metals. In healthy fasting men 90 percent of the DMSA recovered in the urine was found to be mixed disulfides of DMSA (DMSA attached to one or two cysteine molecules) and 10 percent was free unchanged DMSA. No mixed disulfides were found in the blood.29-31 It is thought these are formed as albumin releases DMSA in the kidney.32
In three children with lead poisoning free DMSA was found in the blood of all subjects while it was found in only one out of five healthy adult subjects. It is not known whether this is an age-related phenomenon or exactly what the significance of this finding might be. It is unknown if these pharmacokinetic parameters are different in other metal toxicities or concomitant disease processes. For instance if the patient has increased gut permeability does this increase DMSA absorption?
Studies addressing the possibility that DMSA may chelate metal stored in the gut because a significant percentage of an oral dose is not absorbed have yet to be done. A study of whole body retention in mice of radioactively-tagged orally-administered mercuric chloride revealed DMSA and its analogue DMPS (2 3-dimercapto-propanesulfonate) (see Figure 1) given orally at the same time as the mercury significantly decreased the absorption and whole body retention of the metal.33 This is an important finding which suggests administration of DMSA a short time after an acute ingestion of mercury will chelate the metal and decrease the amount absorbed. It does not however answer the question of whether DMSA will bind gut reservoirs of mercury or whether it will assist the liver in elimination of mercury due to chronic exposure
DMSA Treatment in Lead Toxicity
DMSA has been used since the 1950s as an antidote for lead poisoning in Russia Japan and the Peoples Republic of China. DMSA has been shown in recent studies to be a safe and effective chelator of lead reducing blood levels significantly.1 34 35 At a dose of 10 mg/kg for five days in adult males DMSA lowered blood lead levels 35.5 percent; a more aggressive approach utilizing a 30 mg/kg dose lowered blood lead 72.5 percent. Clinical symptoms and biochemical indices of lead toxicity also improved.35
An animal study indicated DMSA is an effective chelator of lead in soft tissue but it may not chelate lead from bone.36 Another found DMSA or calcium disodium ethylenediamine tetraacetic acid (CaNa2EDTA) produced significant reductions in kidney bone and brain lead levels but DMSA produced greater reductions of bone lead.37
In a preliminary animal study combination therapy with DMSA and CaNa2EDTA was more effective than either individual chelator at increasing urinary and fecal elimination of lead and reducing hepatic renal and femur lead concentrations in rats.38
It has been suggested that chelating agents including BAL and CaNa2EDTA may mobilize and redistribute lead to soft tissue including the brain. Lead-exposed rats given CaNa2EDTA showed an initial decrease in bone and kidney lead and an increase in hepatic and brain lead concentrations indicating redistribution to these organs.39 Rats administered DMSA in combination with CaNa2EDTA showed increased urinary lead output and decreased tissue burden versus use of these therapeutic substances individually. No redistribution of lead to the brain was observed with the combined therapy. A decrease in blood zinc level was noted with the combination as has been observed with CaNa2EDTA monotherapy.40
In a study of lead's pro-oxidant activity and the effect of thiol substances as antioxidants five weeks of lead exposure in mice depleted hepatic and brain glutathione (GS) levels and increased malondialdehyde (MDA) a marker of lipid peroxidation. DMSA administration for seven days resulted in a reduction in blood liver and brain lead levels. N-acetylcysteine supplementation decreased MDA levels indicating amelioration of oxidative stress by NAC but it did not decrease lead levels.41
In an animal study co-administration of ascorbic acid (vitamin C) with DMSA enhanced the urinary excretion of lead in rats compared to DMSA alone.42
A suggested protocol for lead toxicity is to identify and remove the environmental exposure and use DMSA 10 mg/kg three times a day for the first five days followed by 14 days at 10 mg/kg twice a day
DMSA Treatment in Mercury Toxicity
DMSA has been in recent use as a treatment for mercury poisoning since Friedheim reported on DMSA treatment of experimental toxicity in mice in 1975 noting its low toxicity and favorable efficacy compared to BAL and D-penicillamine.43 Since that time numerous animal and human studies have shown DMSA administration increases urinary mercury excretion and reduces blood and tissue mercury concentration.3 33 44-47
In a comparison study of chelating agents eleven construction workers with acute mercury poisoning were treated with either DMSA or N-acetyl-D L-penicillamine (NAP) another sulfhydryl-containing metal chelator. DMSA treatment resulted in greater urinary excretion of mercury than NAP.48
In a study of single-dose DMSA-induced urinary excretion in occupationally-poisoned workers a significant increase in urinary mercury excretion was noted especially in the first 24 hours. Mercury excretion was greatest in the first eight hours after oral DMSA administration.49
After methylmercuric chloride administration in rats DMSA DMPS and NAP were studied for their ability to remove mercury from blood and tissue. DMSA was the most effective at removing mercury from the blood liver brain spleen lungs large intestine skeletal muscle and bone. DMPS was more effective at removing mercury from the kidneys.50
Chelation of Mercury from the Brain
In rats following intravenous administration of methyl mercury DMSA was found to be the "most efficient chelator for brain mercury."51
In another animal study DMSA was given four days after methyl mercury injection in mice and continued for eight days. DMSA removed two-thirds of the brain mercury deposits NAP removed approximately one-half while DMPS did not remove significant amounts of mercury from the brain.44
DMSA has also been used effectively in arsenic and cadmium poisoning.2 3 53
Mercury Diagnostic and Treatment Protocol
Hair analysis is an inexpensive and valuable tool for evaluating prior mercury exposure.10 53 An effective way to evaluate mercury toxicity quantitatively is to determine the amount of mercury excreted in the urine after a challenge dose of DMSA. A baseline 24-hour urine is collected before the challenge then again on day three of a three-day dosing of 200 mg three times a day.
The therapeutic dosage of DMSA for mercury toxicity is not well defined in the literature. Doses as high as 30 mg/kg per day have been used with no serious side effects noted.34 One DMSA treatment protocol suggests 10 mg/kg day taken in divided doses for three days. The patient then discontinues taking DMSA for 14 days then takes it again for 3 days. Five to 10 treatment cycles may be necessary.54 Another protocol suggests 500 mg per day on an empty stomach every other day for a minimum of five weeks. For very sensitive patients 250 mg per day every other day may be necessary with an increase to 500 mg after two to three weeks for a total of five weeks of therapy.55 More studies need to be done to define optimal dosing strategies for this substance. Be aware that sulfhydryl compounds in DMSA will make urine smell very sulfurous. Adequate communication with the patient regarding this issue is important so they are not taken by surprise.
Adjunctive nutrient therapy includes hydrolyzed whey protein as it contains cysteine and cysteine residues which can be of benefit while using DMSA. Cysteine is the rate-limiting step in glutathione production necessary for fecal heavy metal excretion and hepatoprotection. Whey also contains branched-chain amino acids which will occupy transport sites at the blood-brain barrier effectively keeping bound metals from being re-deposited in the brain. Supplemental dosing of N-acetylcysteine 500 mg three times per day can also be helpful.54 A multi-mineral supplement can be taken between cycles
References
1. Aposhian HV. DMSA and DMPS Water-soluble antidotes for heavy metal poisoning. Ann Rev Pharmacol Toxicol 1983;23:193-215
2. Muckter H Liebl B Reichl FX et al. Are we ready to replace dimercaprol (BAL) as an arsenic antidote? Hum Exp Toxicol 1997;16:460-465.
3. Graziano JH. Role of 2 3-dimercaptosuccinic acid in the treatment of heavy metal poisoning. Med Tox 1986;1:155-162.
4. Winneke G Kramer U. Neurobehavioral aspects of lead neurotoxicity in children. Cent Eur J Public Health 1997;5:65-69.
5. Landrigan PJ Baker EL. Exposure of children to heavy metals from smelters: epidemiology and toxic consequences. Environ Res 1981;25:204-224.
6. Perazella MA. Lead and the kidney: nephropathy hypertension and gout. Conn Med 1996;60:521-526.
7. Clarkson TW. Metal toxicity in the central nervous system. Environ Health Perspect 1987;75:59-64.
8. Ignacak J Brandys J Danek M Moniczewski A. [Selected biochemical indicators of the effect of environmental lead on humans]. Folia Med Cracov 1991;32:111-118. [Article in Polish].
9. Turner MD Marsh DO Smith JC et al. Methylmercury in populations eating large quantities of marine fish. Arch Environ Health 1980;35:367-377.
10. Wilhelm M Muller F Idel H. Biological monitoring of mercury vapour exposure by scalp hair analysis in comparison to blood and urine. Toxicol Lett 1996;88:221-226.
11. Sandborgh-Englund G Elinder CG Langworth S et al. Mercury in biological fluids after amalgam removal. J Dent Res 1998;77:615-624.
12. Lorscheider FL Murray JV Summers AO. Mercury exposure from "silver" tooth fillings: emerging evidence questions a traditional dental paradigm. FASEB J 1995;9:504-508.
13. Jokstad A. Mercury excretion and occupational exposure of dental personnel. Community Dent Oral Epidemiol 1990;18:143-148.
14. Nilsson B Nilsson B. Mercury in dental practice. II. Urinary mercury excretion in dental personnel. Swed Dent J 1986;10:221-232.
15. Vimy MJ Lorscheider FL. Intra-oral air mercury released from dental amalgam. J Dent Res 1985;64:1069-1071.
16. Svare C Peterson L Reinhardt J et al. The effect of dental amalgams on mercury levels in expired air. J Dent Res 1981;60:1668-1671.
17. Abraham JE Svare CW Frank CW. The effect of dental amalgam restorations on blood mercury levels. J Dent Res 1984;63:71-73.
18. Derand T. Mercury vapor from dental amalgams an in vitro study. Swed Dent J 1989;13:169-175.
19. Snapp KR Boyer DB Peterson LC Svare CW. The contribution of dental amalgam to mercury in blood. J Dent Res 1989;68:780-785.
20. Jokstad A Thomassen Y Bye E et al. Dental amalgam and mercury. Pharmacol Toxicol 1992;70:308-313.
21. Maas C Bruck W Haffner HT Schweinsberg F. [Study on the significance of mercury accumulation in the brain from dental amalgam fillings through direct mouth-nose-brain transport]. Zentralbl Hyg Umweltmed 1996;198:275-291. [Article in German]
22. Ekstrand J Bjorkman L Edlund C Sandborgh-Englund G. Toxicological aspects on the release and systemic uptake of mercury from dental amalgam. Eur J Oral Sci 1998;106:678-686
23. Bjorkman L Sandborgh-Englund G Ekstrand J. Mercury in saliva and feces after removal of amalgam fillings. Toxicol Appl Pharmacol 1997;144:156-162.
24. Ballatori N Clarkson TW. Biliary secretion of glutathione-metal complexes. Fundam Appl Toxicol 1985;5:816-831.
25. Ballatori N Clarkson TW. Dependence of biliary secretion of inorganic mercury on the biliary transport of glutathione. Biochem Pharmacol 1984;33:1093-1098
26. Gregus Z Varga F. Role of glutathione and hepatic glutathione S-transferase in the biliary excretion of methyl mercury cadmium and zinc: a study with enzyme inducers and glutathione depletors. Acta Pharmacol Toxicol 1985;56:398-403.
27. Gregus Z Klaassen CD. Disposition of metals in rats: a comparative study of fecal urinary and biliary excretion and tissue distribution of eighteen metals. Toxicol Appl Pharmacol 1986;85:24-38.
28. Ishihara N Matsushiro T. Biliary and urinary excretion of metals in humans. Arch Environ Health 1986;41:324-330
29. Aposhian HV Maiorino RM Rivera M et al. Human studies with the chelating agents DMPS and DMSA. J Toxicol Clin Toxicol 1992;30:505-528.
30. Maiorino RM Bruce DC Aposhian HV. Determination and metabolism of dithiol chelating agents. VI. Isolation and identification of the mixed disulfides of meso-2 3-dimercaptosuccinic acid with L-cysteine in human urine. Toxicol Appl Pharmacol 1989;97:338-349.
31. Maiorino RM Akins JM Blaha K et al. Determination and metabolism of dithiol chelating agents: X. In humans meso-2 3-dimercaptosuccinic acid is bound to plasma proteins via mixed disulfide formation. J Pharmacol Exp Ther 1990;254:570-577.
32. Aposhian HV Maiorino RM Dart RC Perry DF. Urinary excretion of meso-2 3-dimercaptosuccinic acid in human subjects. Clin Pharmacol Ther 1989;45:520-526
33. Nielson JB Andersen O. Effect of four thiol-containing chelators on the disposition of orally administered mercuric chloride. Hum Exp Toxicol 1991;10:423-430.<
34. Fournier L Thomas G Garnier R et al. 2 3-Dimercaptosuccinic acid treatment of heavy metal poisoning in humans. Med Toxicol Adverse Drug Exp 1988;3:499-504.
35. Graziano JH Siris ES Lolacono N et al. 2 3-dimercaptosuccinic acid as an antidote for lead intoxication. Clin Pharmacol Ther 1985;37:432-438
36. Cory-Slechta DA. Mobilization of lead over the course of DMSA chelation therapy and long-term efficacy. J Pharmacol Exp Ther 1988;246:84-91.
37. Jones MM Basinger MA Gale GR et al. Effect of chelate treatments on kidney bone and brain lead levels of lead-intoxicated mice. Toxicology 1994;89:91-100.
38. Tandon SK Floras SJS. Therapeutic efficacy of dimercaptosuccinic acid and thiamine/ascorbic acid on lead intoxication in rats. Bull Environ Contam Toxicol 1989;43:705-712.
39. Cory-Slechta DA Weiss B Cox C. Mobilization and redistribution of lead over the course of calcium disodium ethylenediamine tetraacetate chelation therapy. J Pharmacol Exp Ther 1987;243:804-813.
40. Flora SJ Bhattacharya R Vijayaraghavan R. Combined therapeutic potential of meso-2 3-dimercaptosuccinic acid and calcium disodium edetate on the mobilization of lead in experimental lead intoxication in rats. Fundam Appl Toxicol 1995;25:233-240.
41. Ercal N Treeratphan P Hammond TC et al. In vivo indices of oxidative stress in lead-exposed C57BL/6 mice are reduced by treatment with meso-2 3-dimercaptosuccinic acid or N-acetylcysteine. Free Radic Biol Med 1996;21:157-161.
42. Tandon SK Singh S Jain VK. Efficacy of combined chelation in lead intoxication. Chem Res Toxicol 1994;7:585-589.
43. Friedheim E Corvi C. Meso-dimercaptosuccinic acid a chelating agent for the treatment of mercury poisoning. J Pharm Pharmacol 1975;27:624-626
44. Aaseth J Friedheim EA. Treatment of methyl mercury poisoning in mice with 2 3-dimercaptosuccinic acid and other complexing thiols. Acta Pharmacol Toxicol 1978;42:248-252
45. Aaseth J Alexander J Raknerud N. Treatment of mercuric chloride poisoning with dimercaptosuccinic acid and diuretics: preliminary studies. J Toxicol Clin Toxicol 1982;19:173-186.
46. Grandjean P Guldager B Larsen IB et al. Placebo response in environmental disease. Chelation therapy of patients with symptoms attributed to amalgam fillings. J Occup Environ Med 1997;39:707-714.
47. Ramsey DT Casteel SW Faggella AM et al. Use of orally administered succimer (meso-2 3-dimercaptosuccinic acid) for treatment of lead poisoning in dogs. J Am Vet Med Assoc 1996;208:371-375
48. Bluhm RE Bobbitt RG Welch LG et al. Elemental mercury vapour toxicity treatment and prognosis after acute intensive exposure in chloralkali workers. Part I: History neurophysical findings and chelator effects. Hum Exp Toxicol 1992;11:201-210.
49. Roels HA Boeckx M Ceulemans E Lauwerys RR. Urinary excretion of mercury after occupational exposure to mercury vapour and influence of the chelating agent meso-2 3-dimercaptosuccinic acid (DMSA). Br J Ind Med 1991;48:247-253.
50. Planas-Bohne F. The influence of chelating agents on the distribution and biotransformation of methylmercuric chloride in rats. J Pharmacol Exp Ther 1981;217:500-504.
51. Butterworth RF Gonce M Barbeau A. Accumulation and removal of Hg203 in different regions of the rat brain. Can J Neurol Sci 1978;5:397-400
52. Lenz K Hruby K Druml W et al. 2 3-Dimercaptosuccinic acid in human arsenic poisoning. Arch Toxicol 1981;47:241-243
53. Schweinsberg F. Risk estimation of mercury intake from different sources. Toxicol Lett 1994;72:345-351.
54. Quig David PhD. Doctor's Data Chicago IL. Personal communication. May 1998
55. Frackelton JP Christensen RL. Mercury poisoning and its potential impact on hormone regulation and aging: preliminary clinical observations using a new therapeutic approach. J Adv Med 1998;11:9-25.
in limbo
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hmmm? It is very interesting. But what is your take on....
Wednesday 14-Feb-2001 23:15:28
the dosage.
It discusses the different protocols. One of them is 10mg/kg divided into three doses over three days/off 14 days for 5 to 10 cycles
Then there is another one that says 500 mg on an empty stomach every other day for 5 weeks.
And then Dr. Holmes goes by weight on a 3 days on/11 days off. The mg. is around 600mg. a day for small child.
Please tell me your take on the differences in protocols. I'm particularly concerned about the mg. Giving too much or too little where it won't work. Thanks!!! (And thanks for posting this!)
Shirley
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I just don't know Shirley...
Saturday 17-Feb-2001 17:45:25
And from reading all the varying protocols I get the feeling that there is no one "set in stone" way to approach this thing. Because the whole chelation thing for autism is relatively new I think that our kids will be considered the groundbreakers. And because there is no specific studies to back this theory up there is really no evidence of a true and appropriate dosage. But I feel certain that the ones who contribute to the whole idea/protocol are some of the best available. And I am thankful everyday that at least someone is doing something. I know my baby is sick from something proven through testing to be heavy metals. He does not have a psychological illness that we will just go home and do nothing about until we need medication and possibly institutionalization. He has much more potential than that and I will see to it that he reaches his full potential. I just wonder how many children face that fate with no encouragement of a better way?
WOW I got totally off subject didn't I? Sorry.
But to answer your question as to my opinion...I think that 500 mg every other day is just asking for more trouble. My guess would be that Dr. Miller pulled that protocol from one of the references he listed that dated late 70's or early 80's. That's just a wild guess.
The 10mg/kg seems to be a relativley low dose compared to what we are doing. Now the 5-10 cycle thing really has me wondering. Because we were told this treatment could take 2 years possibly longer. But maybe they are just now finding out that mercury can and does bind very tightly in the body making more cycles necessary. Another one of my hypothetical guesses. I have many. Stick around they get really interesting and sometimes humorous.
in limbo
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Your hypothetical guesses sound interesting to me.
Sunday 18-Feb-2001 15:32:52
Now the "cycles" are they just done in "cycles" so the body has time to recover in between? Or is there more to it than that?
And I agree. 500 mg. every other day seems one extreme and 10 mg. seems the other. Oh well Dr.Amy is a happy medium.
Thanks!!Shirley
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Re: Your hypothetical guesses sound interesting to me.
Tuesday 20-Feb-2001 10:19:08
I had to do a little more reading on that one Shirley. I hadn't really thought much on it before. Like you I assumed the breaks were so the supplements could build back up before the next round but after doing some reading I have come upon something that I wasn't even aware of. Here's how I understand it...
The majority of the mercury is bound to the core of a cell. But a certain amount remains on the exterior of the cell. This outer mercury is what the DMSA will remove. When that outer bit of mercury is removed then the core tends to "let go" of more mercury to the exterior of the cell. This takes time hence the need for a break. Did that make sense? I'll try to round up some info that explains it a little better and email to you.
in limbo
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Actually that makes ALOT of sense. Thank you. (and where have you been?)
Wednesday 21-Feb-2001 01:11:48
I've been dying to chat. I figured you were on another "round" and may be very very busy though.
Shirley
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Who is this autismas person and what is her goal?
Tuesday 13-Feb-2001 13:05:51 Beth
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gf
Tuesday 13-Feb-2001 14:29:07
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And she has a daughter with Aspergers and a son with autism....
Tuesday 13-Feb-2001 16:38:17
She believes that school district always have the child's best at heart and you should trust your school districts even if you see them abusing them. (for she uses straight jackets and locks her son in his room--she doesn't blame them)
She doesn't believe that the vaccines have anything to do with autism because she has a huge hereditary history in her family. She often confuses MR issues with autism because her son has both and she can't seem to separate the two of them in her mind. (MR is clearly hereditary)
She loves to argue it doesn't matter what about but vaccines is clearly her fav. She hates to be ignored. She antagonizes people then when they respond she verbally abuses them. When she isn't getting enough attention she posts things and says "I hope you don't get mad but..." or "Don't take this wrong..." And she knows when she addresses people she will. She purposely opposes certain people regularly.
Shirley
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She is the Genetic Only lady... She doesn't beleive in therapys. Nothing you do for your kids is ever going to work... because it all comes down to genetics. She is waiting on some "miracle cure" for her son. She wants some kind of shot that will cure him... actually she is pretty pitiful!
Tuesday 13-Feb-2001 15:38:18 Ha Ha!
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How many cyles of DMSA does it take before mercury starts coming out?
Tuesday 13-Feb-2001 13:02:54
We have just finished round 3 of DMSA following the DAN subcommittee protocol. We have had our son'e urine checked after each round. The onlymetals he is excreting is aluminum nickel and tin (especially tin). Does anyone know if DMSA is excreting this other metals? Also how long before the mercury shows up? In other words how long do we keep up the chelation before giving up?
Stick with it a while. You are doing your child some good right now. It takes a while. And sometimes you won't see much untill you ad ALA to the protocol. Best wishes.
Tuesday 13-Feb-2001 15:40:31 Stacie
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This is from the autism mercury list--I asked a similar question to In Limbo and she was kind enough to send this to me....Dr. Amy Holmes story with her son. (it talks about how long it is taking)
Tuesday 13-Feb-2001 16:42:19
>>Amy
Would you mind sharing your sons history and chelation response for our case studies. I'm really excited to hear of his response to DMSA. It sounds only a little short of miraculous.
This is a repost for amterry. These results are very similiar to you son's. Lyn ----- Original Message ----- From: Amy Holmes <aholmesmd@p... </group/Autism-Mercury/post?protectID=243015253078038198090154004248021063248048166189043>> To: <Autism-Mercury@m... </group/Autism-Mercury/post?protectID=100075114009099192217005163148062077039158044034053123009193242002198057157061151110147>>
Sent: Tuesday May 02 2000 8:58 AM
Subject: Re: Re: [Autism-Mercury] Doctors
Lyn
I would be happy to share Mike's history with you for your case studies. But first let me thank you for all the work you have done in this very important area. I am becoming increasingly convinced that mercury poisoning underlies all of autism. I finally figured out that Mike's case was most likely due to mercury about a year ago but I had no idea of the scope of the mercury problem until I went back into practice (this time as a DAN! doctor). Almost every child I tested had the same lab abnormalities as my son including the high levels of various heavy metals. Very uncanny! Anyway thank you for starting this list and for everything else you have done in the pursuit of the truth about what happened to our children. Feel free to edit this because I'm not sure exactly what info you want.
Mike - DOB 10/18/94
Unremarkable pregnancy. Born by planned C-section (advanced maternal age and very large baby). Weight 9 pounds 2 oz. Very healthy. Apgars 8/9. Uneventful first year. Got all immunizations on time. Sat at 4 months crawled at 7 months walked at 10 months. Spoke first word at 9 months. By 12 months had 10 to 15 words. Good eye contact good imitative skills very social.
Stopped talking 5 days after MMR plus Hep B at 12 months gradually lost all imitative skills all interaction and eye contact. By 18 months was in his own world. Would not even respond to his name. We asked everyone why he was acting this way including several pediatricians - no answers. Finally diagnosed as autistic at 26 months.
We began an intensive ABA program (Lovaas) at 28 months. We took him to see Dr. Stephanie Cave at 29 months. She ran a number of tests including hair analysis for heavy metals. He was very high in lead aluminum and antimony. Mercury was only slightly elevated. She gave him DMSA 100 three times a day for 5 days followed by 100 mg twice a day for 2 weeks (the old treatment).
By 1 month after this first chelation course he had improved noticeably - behavior was better no longer as "zoned out" as before was no longer pale looked healthier. Repeated the hair analysis several months later. This showed a significant drop in lead but still high antimony and aluminum and to our surprise a high level of mercury. No one knew what this meant at the time - this subsequent high level of mercury meant that mercury had been mobilized back into the bloodstream thus could finally show up in the hair. Looking back if we had realized the significance of this finding then Mike would be completely recoved now.
After this we pursued other areas like getting rid of yeast and pathogenic bacteria gluten and casein-free diet getting rid of multiple food allergies and did not return to the heavy metal issue until he was 4 years old. By this time I had taken over his case. I repeated a hair analysis for heavy metals when he was 4. Mercury had dropped (of course - it had gone back into its favorite storage areas) but aluminum and antimony were still very very high and the lead was back up to elevated range.
I started him on a kinder gentler course using DMSA 200 mg TID for 3 days off for 11 days while repleting minerals. I repeated this 2 week cycle for a total of 4 cycles then got a toxic urine screen on the last cycle. To my surprise tons of mercury were coming out. That is when I started investigating mercury-autism connection in Mike's case. After a few weeks I was convinced that mercury was responsible for a lot of his problems so we continued with the same 2 week cycles of DMSA for several more months repeated the urine toxic metal screen with almost the same findings. From April of 1999 to the present I have been doing these 2 week cycles 4 to 6 at a time then allowing him a month off now and then to fully recover from the chelation. We got a urine toxic metal screen last month (4/00) which showed mercury at 2.7 ("normal" range > 0 - 3). This is the first time he has ever been in the "normal" range for mercury (provocative urine).
One year ago Mike was essentially non-verbal and preferred to engage in meaningless self-stimulatory behaviors. Today (5/00) he speaks in sentences addresses people by name to get their attention and no longer "stims" non-stop. His receptive language is excellent expressive is still 2 years behind his peers (but is catching up fast). His pronunciation which had been so bad as to make any words completely unintelligible is now improving to the point that we can understand almost everything he says.
I intend to continue chelation until no more mercury comes out on provocative urine toxic metal screen.
Hope this helps
Shirley
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Shirley thank you for posting this... It is trully wonderful
Tuesday 13-Feb-2001 22:05:17 Stacie
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Re: This is from the autism mercury list--I asked a similar question to In Limbo and she was kind enough to send this to me....Dr. Amy Holmes story with her son. (it talks about how long it is taking)
Wednesday 21-Feb-2001 00:31:41
Does anyone know of any success stories involving older children? My son will be 10 inMarch and after reading about Ms. Holmes son...my son was almost identical right down to the crawling and walking ages...MMR..loss of speech etc. I still refuse to give up hope for my son! I feel deep in my heart that there is a cure for him and I told him that tonight when he sat here crying into my shoulder. He is AWARE he is very AWARE!........
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Dr. Amy Holmes website??
Wednesday 21-Feb-2001 00:46:21
Can anyone give me Amy Holmes's website???
My son is almost identical to hers and I would like to learn more...Thanks and God bless!
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Beth I have a question for you please.
Tuesday 13-Feb-2001 22:52:22
You said your son is excreting aluminum and I was wondering if you are using magnesium malate? Do you think that may be causing the aluminum to come out? I am concerned because my son can't tolerate magnesium malate I think it's the malic acid (apples) part that he's having trouble with. But they say this is the best way to get the aluminum out. I worry because his aluminum level registered a 25 with <8 being the reference range. I plan to try the magnesium malate again later after a few more rounds. Some say that after some of the other metals come out that our kids can tolerate some things that they couldn't previously. I sure hope so. Also if it's not to much to ask could you elaborate as to how much aluminum is coming out after these 3 rounds? And what did the original levels of aluminum show before chelating? We will begin round 3 in about a week. So it sounds like we are traveling this path almost hand in hand.
Thanks for sharing.
in limbo
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Just read on the egroups autims/mercury board that Andy it takes from 3 to 6 months before mercury really begins to come out.
Wednesday 14-Feb-2001 12:03:19 Stacie
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Re: Just read on the egroups autims/mercury board that Andy it takes from 3 to 6 months before mercury really begins to come out.
Thursday 22-Feb-2001 08:25:21
Hi everyone. I have a 10 year old autistic son. I have just started hearing about Mercury this past week. I am very interested in having my son tested for Mercury. How have you been going about getting your children tested? What tests should be done? Are you using your normal family doctor or is this similar to Secretin and only certain doctors are willing to work with you? If so can anyone recommend a specific doctor to work with?
Lance
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Help!!
Saturday 10-Feb-2001 22:46:28
I am trying to preload my son before chelating. Yesterday wasn't too tough. Today was.
He won't eat hardly anything today because either ....
1) he thinks their is supplements in them or
2) he is getting sick
also he has been gagging and making himself throw up. I don't know if it because he really is or not. I really don't think he is though. He used to throw up during therapy and got out of doing it with new therapists. Last week he threw up at school and I'm sure they made a big deal out of it. I think he thinks I will stop. (I was trying to teach him to swallow pills when he did it)
Does anyone have any advice???? I don't want to start the DMSA and have him do this. I want this part to be over.
Shirley
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Re: Help!!
Sunday 11-Feb-2001 02:11:41
This happened to us too in the beginning. Here's what I did.
Start with a fourth or half dose of whatever you intend to add. Over the course of 3-4 days increase to full dose if all goes well. Add only one supplement at a time. That will give his body time to adjust to the supplement and it will give you time to observe any reactions. Go slow. Wait a day or two between supplements. That is the key. If you think he is having a problem with a particular supplement wait a few days and add it again in very small amounts. It took us about 6-8 weeks to get everything in but we still didn't get a couple of things because Cody just couldn't tolerate them even at minute doses. One was CoQ10 and the other was magnesium malate. We couldn't do the pill swallowing thing because he is too little. Another suggestion...Many supplements come in a liquid or sublingual form and that may help conquer the pill swallowing gagging throwing up issue. If you can sneak things into drinks without all that gunky powdery gritty junk at the bottom of the glass he may not notice as much. The way to find things in a liquid form is to do a search (I use google.com) for example zinc + liquid + order. I find the best prices for supplements doing that too. And I always have to stay with certain brands; reading each ingredient because he is so very allergic. Some of the better sites have each and every ingredient listed. Very few supplements contain the one ingredient without binders and fillers or preservatives and colors/flavors. I feel that Kirkman's lab goes out of their way to help avoid these because they realize how sensitive most of our kids can be.
I think preloading was the hardest part for us also. I had to stop everything at one point and start all over again because I tried to go too fast in the beginning. But going slow and waiting a day or two between additions seemed to be most crucial in our situation. I know you are anxious to start but don't make the mistake I did...wasting about 2 1/2 weeks then he had extreme irritability with loss of appetite (CoQ10) then he had really bad diarrhea (magnesium malate). I had to stop and start all over because I just couldn't figure out what was doing it. Sigh...One more lesson learned. I hope this helps.
in limbo
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Thank you In Limbo--you've rescued me again.
Sunday 11-Feb-2001 19:36:52
I think that is exactly what I need to do...slow down. Too much at one time. Today his appetite is starting to pick up. So I'll try again soon. Thanks!
Shirley
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Chelation: anyone on the board who has been through it and what are the results??
Saturday 10-Feb-2001 03:52:15
Went to another board (that was pretty hard to follow) and there was only one success story on there from chelation - the rest were on the first stages of chelation.
Is CLO then DMSA the first steps?
Sandy
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Hi Sandy...
Saturday 10-Feb-2001 05:56:26
We are pretty much in the beginning stages of chelation too. The clo question is interesting but I haven't heard of that being the first stage of the treatment. And I have asked Amy Holmes site if the fact that Daniel had Mercruy in his hair analysis - when it had been 4 years after exposure could the clo be cleaning up the gut in that respect. I never heard back. Dr. Megsons's office refused to comment.
I don't know if CLO has anything to do with chelation
Saturday 10-Feb-2001 09:11:14
CLO is used to help with visual stims better eye contact etc. based on the fact that a lot of these kids have vitamin A deficiency.Mary Megson says that the reason for a lot of their autistic behaviors is because they can't see well because of this deficiency. They use their peripheral vision alot.CLO helps with this.,karen,
It doesn't. But it isn't a bad idea to supplement...,Saturday 10-Feb-2001 12:06:48,,CLO is high in vitamin A and is a good supplement to try but be sure you get a high quality CLO from a company you trust (like Kirkman's). Cod liver oil can contain mercury and it must be filtered out.
It really doesn't have anything to do with chelation.
Susan
smdevlin5@earthlink.net
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I agree
Saturday 10-Feb-2001 18:38:55
This board is alot easier to follow. And I would like to hear about the gains children are having. It helps keep me motivated. Right now I am starting to preload him with vitamins. It is very discouraging sometimes.
The Cod Liver Oil makes my son's eye contact MUCH better. It also makes his big brown eyes shiny and he has more expression in them.
Shirley
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we are about to start chelating. Our DAN dr said to give my son 185mg DMSA every 8 hous for 3 days. He is 4 and weighs 40lbs. Does that sound like too much?
Friday 9-Feb-2001 19:32:37 karen
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Re: we are about to start chelating. Our DAN dr said to give my son 185mg DMSA every 8 hous for 3 days. He is 4 and weighs 40lbs. Does that sound like too much?
Friday 9-Feb-2001 19:47:51
My son's DAN doctor prescribed 300mg DMSA every 8 hours for 3 days. My son weighs 68 pounds. He used a formula of 10mg of DMSA for every kilogram my son weighs (there are 2.2 pounds in a kilogram).,Julie,
Web site for the list of physicians certified in chelation,Friday 9-Feb-2001 15:02:59,,The web site is www.acam.org
