Journal Article•
Dimercaptosuccinic Acid (DMSA), A Non-Toxic, Water-Soluble Treatment For Heavy Metal Toxicity
01 Jun 1998-Alternative medicine review : a journal of clinical therapeutic (Altern Med Rev)-Vol. 3, Iss: 3, pp 199-207
TL;DR: 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 and is established as the premier metal chelation compound, based on oral dosing, urinary excretion, and its safety characteristics compared to other chelating substances.
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)
Citations
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TL;DR: Current knowledge of Cd-induced oxidative stress and cardiovascular dysfunction and a possible protective effect conferred by the antioxidants curcumin and tetrahydrocurcumin are summarized.
Abstract: Cadmium (Cd) is a non-essential heavy metal with high toxicity potential. Humans are exposed to Cd present in diet, polluted air, and cigarette smoke. Cd exposure has been associated with increased risk of chronic diseases, including hypertension, atherosclerosis, diabetes, and nephropathy, all of which could be attributable to dysfunctional endothelial and smooth muscle cells. Cd toxicity is correlated with increased reactive oxygen formation and depletion of antioxidants, resulting in an oxidative stress. Chelation of Cd has proved useful in the removal of the Cd burden. However, several chelating agents cause side effects in clinical usage. Recent studies have shown that the antioxidant compounds curcumin and tetrahydrocurcumin can alleviate vascular dysfunction and high blood pressure caused by Cd toxicity. In chronic Cd exposure, these antioxidants protect vascular endothelium by increasing nitric oxide (NO•) bioavailability and improving vascular function. Antioxidant activity against Cd intoxication results directly and/or indirectly through free radical scavenging, metal chelation, enhanced expression of the antioxidant defense system, regulation of inflammatory enzymes, increase in NO• bioavailability, and reduction of gastrointestinal absorption and tissue Cd accumulation. This review summarizes current knowledge of Cd-induced oxidative stress and cardiovascular dysfunction and a possible protective effect conferred by the antioxidants curcumin and tetrahydrocurcumin.
61 citations
Cites background from "Dimercaptosuccinic Acid (DMSA), A N..."
...DMSA contains two sulfhydryl groups, which makes it a more effective chelator (Miller 1998)....
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TL;DR: It is concluded that consumption of commercially available fish can lead to elevated blood mercury concentrations and a recognized exposure source is a better predictor of significant mercury concentrations in biologic media than any particular symptom constellation.
Abstract: In the context of controversies surrounding fish consumption, amalgams, and commercial hair testing, we reviewed all cases from an occupational and environmental medicine clinic that had undergone mercury testing. Sixty-nine of 71 (97%) patients had no known mercury exposures other than diet or amalgams. Of these 69, 48 had blood mercury tested and 58 had urine testing. Regular-to-heavy fish consumption explained 10 of 11 cases with blood mercury concentrations > 15 micrograms/L (19 to 53 micrograms/L). Six of these 10 individuals reported regular swordfish consumption. For the 31 patients with adequate dietary history, there was a significant relationship between fish consumption and blood mercury concentration (P < 0.001). Higher blood mercury concentrations were, however, not associated with specific patterns of health complaints. Ninety-eight percent (57 of 58) of urine values were < 10 micrograms/L. Fourteen patients were evaluated because they were labeled as mercury toxic by other practitioners after unconventional commercial testing. Using standard tests of blood and urine, we could not document evidence of mercury toxicity in any of these 14 cases. We conclude that consumption of commercially available fish can lead to elevated blood mercury concentrations. A recognized exposure source is a better predictor of significant mercury concentrations in biologic media than any particular symptom constellation. Unconventional commercial panels that test hair or urine for multiple metals have questionable validity. Clinicians should use standard blood and urine tests to evaluate mercury exposure.
52 citations
TL;DR: The results suggest that Chinese parsley has suppressive activity on lead deposition, probably resulting from the chelation of lead by some substances contained in Chinese Parsley.
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TL;DR: Although Cd may prove to be a major risk factor for morbidity and mortality in humans, practical strategies for limiting its absorption and pathogenic impact are at hand.
47 citations
TL;DR: No clinical trial evidence was found to suggest that pharmaceutical chelation is an effective intervention for ASD, and the risks of using chelation for ASD currently outweigh proven benefits.
Abstract: Background
It has been suggested that the severity of autism spectrum disorder (ASD) symptoms is positively correlated with the level of circulating or stored toxic metals, and that excretion of these heavy metals, brought about by the use of pharmaceutical chelating agents, results in improved symptoms.
Objectives
To assess the potential benefits and adverse effects of pharmaceutical chelating agents (referred to as chelation therapy throughout this review) for autism spectrum disorder (ASD) symptoms.
Search methods
We searched the following databases on 6 November 2014: CENTRAL, Ovid MEDLINE, Ovid MEDLINE In-Process, Embase, PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and 15 other databases, including three trials registers. In addition we checked references lists and contacted experts.
Selection criteria
All randomised controlled trials of pharmaceutical chelating agents compared with placebo in individuals with ASD.
Data collection and analysis
Two review authors independently selected studies, assessed them for risk of bias and extracted relevant data. We did not conduct a meta-analysis, as only one study was included.
Main results
We excluded nine studies because they were non-randomised trials or were withdrawn before enrolment. We included one study, which was conducted in two phases. During the first phase of the study, 77 children with ASD were randomly assigned to receive seven days of glutathione lotion or placebo lotion, followed by three days of oral dimercaptosuccinic acid (DMSA). Forty-nine children who were found to be high excreters of heavy metals during phase one continued on to phase two to receive three days of oral DMSA or placebo followed by 11 days off, with the cycle repeated up to six times. The second phase thus assessed the effectiveness of multiple doses of oral DMSA compared with placebo in children who were high excreters of heavy metals and who received a three-day course of oral DMSA. Overall, no evidence suggests that multiple rounds of oral DMSA had an effect on ASD symptoms.
Authors' conclusions
This review included data from only one study, which had methodological limitations. As such, no clinical trial evidence was found to suggest that pharmaceutical chelation is an effective intervention for ASD. Given prior reports of serious adverse events, such as hypocalcaemia, renal impairment and reported death, the risks of using chelation for ASD currently outweigh proven benefits. Before further trials are conducted, evidence that supports a causal link between heavy metals and autism and methods that ensure the safety of participants are needed.
44 citations
References
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TL;DR: This article reviews the pharmacological properties and the uses of two important antidotes for heavy metal poisoning, DMSA and DMPS, water soluble chemical analogs of dimercaprol, which have less toxicity, greater water solubility, and lim ited lipid solubilities, and are effective when given orally.
Abstract: This article reviews the pharmacological properties and the uses of two important antidotes for heavy metal poisoning. Meso-dimercaptosuccinic acid (DMSA) and 2,3-dimercapto-l-propanesulfonic acid, Na salt (DMPS) are relatively new antidotes-new, that is, to the western world. Although DMSA was introduced originally by Friedheim et al (1) to increase uptake of antimony during schistosomiasis therapy, Liang et al (77) at Shanghai in 1957 were the first to report its effectiveness as an antidote for heavy metal poisoning. The synthesis and some of the metal binding properties of DMPS were reported in 1956 by Petrunkin from Kiev (3). Shortly thereaf ter, DMPS became an official drug in the Soviet Union, where it is known as Unithiol (4). Between 1956 and 1975, DMSA and DMPS were studied extensively, at both the basic science and clinical levels, in the People's Republic of China, the Soviet Union, and Japan. Some of these investigations have been cited and can be found in an earlier review (5). In the USA and western Europe, however, these two compounds received very little attention until recently. A paper by Friedheim & Corvi (6) in 1975, dealing with DMSA for the treatment of mercury poisoning, and the recent production and availability of DMPS from Heyl & Co., Berlin, stimulated investigators to "rediscover" and study these two metal-binding agents. DMSA and DMPS are water soluble chemical analogs of dimercaprol (British Anti-Lewisite, BAL). In contrast to BAL, they have less toxicity, greater water solubility, and lim ited lipid solubility, and are effective when given orally.
309 citations
"Dimercaptosuccinic Acid (DMSA), A N..." refers background in this paper
...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....
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...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)....
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TL;DR: It has been discovered that microtubules are destroyed by this form of mercury and this effect may explain the inhibition of cell division and cell migration, processes that occur only in the developmental stages, and other hypotheses will stimulate considerable experimental challenges in the future.
Abstract: The nervous system is the principal target for a number of metals. Inorganic compounds of aluminum, arsenic, lead, lithium, manganese, mercury, and thallium are well known for their neurological and behavioral effects in humans. The alkyl derivatives of certain metals--lead, mercury and tin--are specially neurotoxic. Concern over human exposure and in some cases, outbreaks of poisoning, have stimulated research into the toxic action of these metals. A number of interesting hypotheses have been proposed for the mechanism of lead toxicity on the nervous system. Lead is known to be a potent inhibitor of heme synthesis. A reduction in heme-containing enzymes could compromise energy metabolism. Lead may affect brain function by interference with neurotransmitters such as gamma-amino-isobutyric acid. There is mounting evidence that lead interferes with membrane transport and binding of calcium ions. Methylmercury produces focal damage to specific areas in the adult brain. One hypothesis proposes that certain cells are susceptible because they cannot repair the initial damage to the protein sythesis machinery. The developing nervous system is especially susceptible to damage by methylmercury. It has been discovered that microtubules are destroyed by this form of mercury and this effect may explain the inhibition of cell division and cell migration, processes that occur only in the developmental stages. These and other hypotheses will stimulate considerable experimental challenges in the future.
196 citations
"Dimercaptosuccinic Acid (DMSA), A N..." refers background in this paper
...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....
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...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....
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TL;DR: Analysis of the data from the questionnaires indicated that little or no exogenous exposure to mercury occurred among the two groups.
Abstract: Mercury levels in blood and in mouth air before and after chewing were measured in 47 persons with ana 14 persons without dental amalgam restorations. Questionnaires relating to exogenous sources of mercury exposure were administered to both groups. Differences in the mouth air mercury levels before and after chewing were statistically significant in the group with amalgams, but not in the group without amalgams. Analysis of the data from the questionnaires indicated that little or no exogenous exposure to mercury occurred among the two groups. Blood mercury concentrations were positively correlated with the number and surface area of amalgam restorations and were significantly lower in the group without dental amalgams.
194 citations
TL;DR: Animal and human experiments demonstrate that the uptake, tissue distribution, and excretion of amalgam Hg is significant, and that dental amalgam is the major contributing source to Hg body burden in humans.
Abstract: For more than 160 years dentistry has used silver amalgam, which contains approximately 50% Hg metal, as the preferred tooth filling material. During the past decade medical research has demonstrated that this Hg is continuously released as vapor into mouth air; then it is inhaled, absorbed into body tissues, oxidized to ionic Hg, and finally covalently bound to cell proteins. Animal and human experiments demonstrate that the uptake, tissue distribution, and excretion of amalgam Hg is significant, and that dental amalgam is the major contributing source to Hg body burden in humans. Current research on the pathophysiological effects of amalgam Hg has focused upon the immune system, renal system, oral and intestinal bacteria, reproductive system, and the central nervous system. Research evidence does not support the notion of amalgam safety.
178 citations
TL;DR: Results suggest that lead-induced oxidative stress in vivo can be mitigated by pharmacologic interventions, which encompass both chelating as well as thiol-mediated antioxidant functions.
172 citations