DMSA: Dimercaptosuccinic Acid
Premier Treatment For Heavy Metal Toxicity

by Ralph C. Cinque, D.C.                   Order DMSA

Meso-2,3-dimercaptosuccinic acid (DMSA) is a sulfur-containing organic compound that is FDA approved for the treatment of lead and mercury toxicity both in children and adults. Although it is sold as a prescription drug, it is also available as a dietary supplement. DMSA has been administered as a heavy metal chelator since the 1950s, and no other substance has been found to be more practical, more safe, and more effective for this purpose.

Mercury contamination is most often associated with fish consumption, mercury amalgam dental fillings, mercury preservatives in vaccines, and other modern industrial exposures. Historically, lead contamination has been connected chiefly to lead-based paints and leaded gasolines, both of which have been discontinued. However, children can still be exposed to old lead-based paint, and lead contamination is still an issue in areas where lead is being mined or smelted.

Other heavy metals include cadmium and arsenic, which are derived chiefly from cigarette smoke but also from occupational and environmental exposures.

It has long been recognized that sulfur-containing compounds have the ability to chelate heavy metals. Within the normal operation of the human body, there are natural sulfur-containing compounds which perform this service, and these include N-acetyl cysteine (NAC), R-lipoic acid, S-adenysyl methionine (SAMe), and glutathione (GSH).

Meso-2,3-dimercaptosuccinic acid (DMSA), does not occur naturally in the human body, nor is it a constituent of food. However, it has been studied for over 40 years as an effective oral chelator of heavy metals. Initial studies took place in the People's Republic of China, Japan, and Russia and then spread to Europe and the USA.

Chemically, DMSA is a dithiol, which means that it contains two sulfhydryl (also know as S-H) groups, plus an analogue of dimercaprol, also known as BAL, which is a lipid-soluble substance also used alone for metal chelation. However, unlike DMSA, BAL cannot be taken orally, rather it has to be injected deep into muscles in an oil solution. Moreover, BAL is much more toxic than DMSA. DMSA has a large therapeutic window, meaning that there is a wide margin between the amount needed to produce desired results and the amount that is potentially toxic. It can be said that DMSA is the least toxic of the dithiol compounds.

LEAD
Lead exposure is still a public health concern in the United States because there are still approximately 21 million homes which have old lead-based paint on their walls. Flaking, weathering, and chalking paint contaminate dust and soil which also contributes to chronic lead exposure. Lead competes in the body with calcium, causing numerous malfunctions in calcium-facilitated cellular mechanisms.

The central nervous system appears to be most affected by lead. Children in particular are susceptible to its devastating effects on mental development and intelligence. Cerebro-behavioral deficits, such as Attention Deficit Disorder, have also been found in lead-exposed children. Blood lead concentrations of 20-25 µg/100 ml can cause irreversible CNS damage in children.

Acute adult lead exposure often affects the kidneys, leading to renal proximal tubular damage. Chronic lead exposure causes kidney dysfunction characterized by hypertension, high uric acid levels, gout, and chronic kidney failure.

After lead is absorbed, the human body tries to use its natural thiol compounds, such as glutathione, to eliminate it. Unfortunately, hepatic (liver) glutathione can be depleted very quickly in this manner, resulting in less glutathione being available for the conjugation of other toxic substances. Without effective intervention, lead stored in the bones has a half-life of 25 years. That's how inefficient the natural body mechanisms are at excreting lead.

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 then concentrates in seafood and fish. Dietary fish intake has been found to have a direct correlation with methyl mercury levels in blood and hair.

Mercury-based dental fillings are the major source of inorganic mercury exposure in humans. The cheapest and most common dental filling material, known as "amalgams," contain approximately 50 percent liquid metallic mercury, 35 percent silver, 9 percent tin, 6 percent copper, and a trace of zinc. As they are prepared and placed in the patient's mouth, the dentist, any assistant, and 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, brushes, and drinks hot beverages. 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 fold increase in mercury in expired air after chewing. Mercury release was found to be greater in old corroded amalgams compared to new, polished ones. Mercury vapor from amalgams enters the bloodstream after being inhaled into the lungs.

In humans, 90 percent of mercury elimination is via the feces in association with glutathione, with only 10 percent normally being excreted in the urine. A decrease in hepatic glutathione resulting from mercury excretion can compromise other hepatic functions dependent upon glutathione.

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.

How DMSA works
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. 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 (where DMSA is attached to one or two cysteine molecules), and 10 percent was free unchanged DMSA. No mixed disulfides were found in the blood. It is thought these disulfides are formed as albumin releases DMSA in the kidneys.

There is no question that DMSA is more readily absorbed when it is taken on an empty stomach. However, some people experience gastric upset when they take DMSA apart from food, and that is more likely to occur in children. Therefore, caution and flexibility are required in regard to this.

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. 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.

Co-administration of N-acetylcysteine (NAC) and Vitamin C have been found to enhance the effectiveness of DMSA at eliminating lead from the body.

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
In the USA, DMSA was first reported by Friedheim to promote mercury excretion. He reported on experiments with mice in 1975, noting DMSA's low toxicity and favorable efficacy compared to other compounds, such as BAL and D-penicillamine. Since that time, numerous animal and human studies have shown DMSA administration increases urinary mercury excretion and reduces blood and tissue mercury concentration.

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.

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.

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.

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.

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.

Mercury Diagnostic and Treatment Protocol
Hair analysis is an inexpensive and valuable tool for evaluating prior mercury exposure. However, there has been some controversy about the accuracy of laboratory results in hair analysis.

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. 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. 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. More studies need to be done to define optimal dosing strategies for this substance. Be aware that sulfhydryl compounds in DMSA will make urine very smelly. Patients should be warned about that so that they won't be surprised.

Some advocate the use of hydrolyzed whey protein as an adjunct to DMSA because it contains a lot of cysteine and cysteine residues which can be of benefit while using DMSA. Cysteine is the rate-limiting step in glutathione production, which is necessary for fecal heavy metal excretion and hepato-protection. Whey also contains branched-chain amino acids which 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.

A multi-mineral supplement is a must when taking DMSA, and it should also be taken between cycles and for some time after treatment is ended. This is so because, besides heavy metals, DMSA also chelates and eliminates good minerals, such as zinc and magnesium.

DMSA for the brain
The organic mercury species with greatest toxicity are methylmercury compounds, which have a high affinity for the brain and nervous system. No other substance has been found to absorb better and cross the blood brain barrier and remove mercury from the brain more effectively than DMSA. DMPS is much less effective. DMPS is also 3 times more toxic than DMSA, based on its LD-50 (the dose at which 50 percent of laboratory animals die). Animal studies show DMSA to be almost 3 times more effective than DMPS in removing brain mercury. DMSA has the added advantage that it is taken by mouth in capsule form, whereas DMPS must be given by injection.

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The information in this article is not intended to provide personal medical advice, which should be obtained from a medical professional, and has not been approved by the U.S. FDA.

Copyright by Dr. Ralph Cinque, and intended solely for individual, non-commercial use. All other uses are prohibited without written permission from Dr. Cinque.