DMSA and Detoxing Heavy Metals
By Ward Dean, M.D.
In several previous issues of Vitamin Research News, both intravenous and oral chelation therapy with EDTA were discussed. EDTA (ethylenediaminetetraacetic acid) is a synthetic amino acid food preservative that has been used for nearly 50 years to clinically treat heavy metal toxicity and chronic degenerative diseases—especially, cardiovascular disease and cancer.
Nevertheless, most orthodox physicians often deride claims of any benefit from chelation therapy, belittling the concerns of health-conscious people worried about potential adverse effects from toxic metals, such as lead, mercury, and aluminum.
It is now clear that low levels of heavy metals—even at levels that were once considered “safe”—are, in fact, highly dangerous. Evidence of the toxic effects of these metals as they accumulate in the body over time is very strong.
Chelation therapy provides benefits by reducing the body burden of these toxins, resulting in improved physiological functioning and better health. The two most widely used oral chelating agents are EDTA and DMSA.
DMSA (meso-2,-3-dimercaptosuccinic acid) is a sulfhydryl-containing, water-soluble, non-toxic, orally administered metal chelator1 that has been in use as an antidote to heavy metal toxicity since the 1950s.
Research confirms this substance’s efficacy and safety, and supports its use as the premier oral metal chelator for mercury—and its efficacy for other heavy metals. DMSA’s water-solubility, oral dosing, large therapeutic window and low toxicity make it the chelator of choice for many applications.
About 20 percent of orally administered DMSA is absorbed from the gastrointestinal tract. This is two to four times the percentage of EDTA that is absorbed. It is believed that one of the sulfhydryls in DMSA binds to a cysteine molecule on albumin, leaving the other S-H to chelate metals.2,3
Lead Increases Vascular Disease, Cancer and Overall Mortality
Lead poisoning has long been recognized as a health hazard. Lead has been historically used in a number of industrial processes, including the manufacture of batteries, paints, and as an additive in gasoline. Acute lead poisoning (short-term, high exposure) causes symptoms of abdominal pain or “lead colic,” cognitive deficits, peripheral neuropathy, arthralgias, decreased libido and anemia. It can be diagnosed by a characteristic “lead line” at the junction of the teeth and gums, and by high blood lead levels (over 80 micrograms per deciliter).4
However, the effects of chronic exposure to low levels of lead are more difficult to determine. Long-term exposure to low levels of lead may result in the gradual accumulation of lead and the development of a number of disorders and diseases, including learning and behavior problems, cardiovascular and kidney diseases, decreased fertility, hypertension and cancer.5
To determine the effects of chronic exposure to low levels of lead, Drs. Mark Lustberg, of the University of Maryland School of Medicine, and Ellen Silbergeld, of Johns Hopkins University, compared data gathered from the 2000 U.S. census and the massive Third National Health and Nutrition Examination Survey (NHANES-III).6
Based on these data, Lustberg and Silbergeld estimated that 29 million people (15 percent of the adult population over the age of 20) had blood lead levels of at least 20 mcg/dL from 1976 to 1980, and that currently at least 1.7 million people in the United States have blood lead levels of at least 20 mcg/dL.
The authors examined the death rates of participants in the NHANES Survey who had lead blood levels less than 30 mcg per dL (30 mcg per dL is the level normally considered “toxic”) in order to determine the comparative incidence of disease with low levels of lead. They found that blood lead levels ranging from as little as 20 to 29 mcg per dL were associated with a 39 percent increase in mortality from all causes.
Additionally, these “low” levels of lead were associated with a 46 percent increase in mortality from cardiovascular diseases, and a whopping 68 percent increase in mortality due to cancer.
Even lower blood lead levels, measuring from 10 to 19 mcg/dL were associated with a significant 17 percent increase in mortality from all causes and 46 percent increase in mortality from cancer, when compared with blood lead levels less than 10 mcg/dL (Fig. 1.).
Thus, it appears that there is no safe level of lead. Lead at any level contributes to increased disease-related mortality—especially from heart disease and cancer.
Lead is still found in millions of pre-1940s homes. Lead toxicity impairs calcium uptake and utilization, and also interferes with calcium-facilitated cellular metabolism.
Lead is especially toxic to the central nervous system, as evidenced by its harmful effects on mental development and intelligence in children, who are especially susceptible to lead’s deadly effects. In addition, behavioral disorders such as attention deficit disorder have been attributed to lead exposure.7 In children, 20 to 25 mg/100 ml can cause irreversible brain damage.8 In adults, acute lead exposure leads to renal proximal tubular damage, while chronic exposure can cause renal failure, hypertension, hyperuricemia, and gout.9
Mercury and Cardiovascular Disease
Until recently, the notion of treating heart disease with chelation therapy—one of the mechanisms of which is to remove heavy metals—was scorned by the medical establishment. But it appears that, once again, the field of “alternative medicine” has been ahead of its time.
In an article in the November 28, 2002, issue of the New England Journal of Medicine, “Mercury, fish oils, and the risks of myocardial infarction,” the authors stated: “Mercury may promote atherosclerosis and hence increase the risk of myocardial infarction in several ways. Mercury promotes the production of free radicals…and may bind selenium [so that it] cannot serve as a cofactor for glutathione peroxidase. Mercury may…inactivate the antioxidant properties of glutathione, catalase, and superoxide dismutase.
Mercury may induce lipid peroxidation, and mercury levels were a strong predictor of oxidized LDL levels…Mercury compounds can also promote platelet aggregability and blood coagulability, inhibit endothelial-cell formation and migration, and affect apoptosis and the inflammatory response. Increased rates of cardiovascular disease were found in mercury-exposed workers, and mercury levels in hair predicted the progression of carotid atherosclerosis in a longitudinal study.” 10
The article found that mercury levels were directly associated with the risk of myocardial infarction (heart attacks), and that this partially offset the protective effects of DHA derived from eating fish. The New England Journal editorialized: “The notion that methylmercury contributes to cardiovascular disease is certainly a testable hypothesis and one that warrants further testing.” 11
Fish consumption is directly associated with methylmercury levels in blood and hair.12,13 Mercury in dental amalgams is probably the major source of inorganic mercury exposure in humans.14 The most commonly used dental amalgam material contains approximately 50 percent liquid metallic mercury.
Thus, amalgam preparation and placement results in mercury vapor exposure for the patient, dentist and technician. Mercury vapor continues to be released as the patient chews,15 brushes, or drinks hot beverages,16 after which it is inhaled into the lungs and enters the bloodstream. Studies have shown a direct correlation between the number of amalgam fillings and mercury concentration in blood and urine.17 Amalgam removal reduces blood-mercury levels.
DMSA treatment results in the greatest urinary excretion of mercury, compared to other heavy metal chelators,18 as well as being the most effective at removing mercury from the blood, liver, brain, spleen, lungs, large intestine, skeletal muscle and bone. Mercury excretion is greatest in the first eight to 24 hours after ingestion. In animal studies, DMSA has been shown to be the most efficient chelator for brain mercury, removing two-thirds of the brain mercury deposits.
Safety of DMSA
DMSA is very safe, and usually causes few side effects. Some patients may experience slight gastrointestinal distress or itching, when higher doses are used.
As with any chelating agent, DMSA can cause deficiencies of copper, manganese, molybdenum and zinc, if they are not replaced by supplementation. DMSA doesn’t directly bind magnesium, cysteine, or glutathione, but heavy metal detoxification can result in depletion of these nutrients as well.
Dosage recommendations for DMSA vary widely. The dosage regimen recommended in conventional medical publications such as the Physicians’ Desk Reference (PDR) is 10 mg per kg every eight hours for five days; then reduce the dose to twice daily for two more weeks, off for two weeks, and repeat as necessary. I think this is pretty aggressive, and often results in gastrointestinal side effects.
Heavy metal detoxification is a long-term process, as the heavy metals in the body compartments are in a constant state of equilibrium.
Consequently, for adults and older children, I recommend a more conservative regimen of 100 mg three times every other day, to be administered for a minimum of five weeks—although continuous therapy for months is usually required. DMSA is best absorbed when taken on an empty stomach (one hour before or two hours after meals).
Children with Autism: Smaller Dosage Now Available
In one popular chelation protocol for children with autism, the dosage of DMSA is calculated based on the child’s weight, at 1/8 to 1/2 mg per pound. It is administered in divided doses, every four hours. This dose is given every day for three days, followed by a rest period of four days. Many children have remained on this regimen for as long as two to three years, with continued improvement over the course of therapy.
VRP now offers DMSA in reduced dosage of 25 mg capsules to make it more convenient for those following such a protocol.
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2. Aposhian H, Maiorino R, Rivera M, et al. Human studies with the chelating agents, DMPS and DMSA. J Toxicol Clin Toxicol 1992, 30:505-528.
3. Maiorino R, Bruce D, Aposhian H. Determination and metabolism of dithiol chelating agents. VI. Isolation and identification of the mixed disulfides of meso-2,3-dimercdatosuccinic acid with L-cysteine in human urine.Toxicol Appl Pharmacol 1989, 97:338-349.
4. Marsden PA. Increased lead burden—Cause or consequence of chronic renal insufficiency? New England J Med 2003, 4:345-346.
5. Lustberg Mark, Silbergeld Ellen. Blood lead levels and mortality. Arch Intern Med 2002, 162:2443-2449.
6. Pinkle JL, Brody DJ, Gunter EW, et al. The decline in blood lead levels in the United States: the National Health and Nutrition Examination Surveys (NHANES). JAMA 1994, 272:284-291.
7. Winneke G, Kramer U. Neurobehavioral aspects of lead neurotoxicity in children. Cent Eur J Public Health 1997, 5:65-69.
8. Landrigan P, Baker E. Exposure of children to heavy metals from smelters: Epidemiology and toxic consequences. Environ Res 1981:25:204-224.
9. Perazella M. Lead and the kidney: Nephropathy, hypertension and gout. Conn Med 1996, 60:521-526.
10. Guallar E, Sanz-Gallardo I, Van’t Veer P, et al. Mercury, fish oils, and the risk of myocardial infarction. New England J Med 2002, 347:22, 1747-1754.
11. Bolger PM, Schwetz BA. Mercury and Health, New England J Med 2002, 347:22, 1735-1736.
12. Turner M, Marsh D, Smith J. Methylmercury in populations eating large quantities of marine fish. Arch Environ Health 1980, 35:367-377.
13. 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.
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15. 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.
16. Derand, T. Mercury vapor from dental amalgams, an in vitro study. Swed Dent J 1989, 13:169-175.
17. Snapp K, Boyer D, Peterson L, Svare C. The contribution of dental amalgam to mercury in blood. J Dent Res 1989, 68:780-785.
18. Bluhm R, Bobbitt R, Welch I, 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.