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DMSA chelation the gentle detox for heavy metal exposure.

General Information

DMSA or Meso-2,3-dirnercaptosuccinic acid has been used as a heavy metal chelator since the 1950s, and was extensively researched in the People's Republic of China, Japan, and Russia before it spread to Europe and the USA. During February 1991, the US FDA (Federal Drug Administration) approved DMSA under the product name Chemet as a chelating agent for lead in children as young as two years of age. The FDA recommends the use of DMSA to intoxicated adults and it limits its use to children with blood levels >45 mcg per deciliter (450mcg per liter), by today's standards a rather excessive exposure.

Internet advertisements classify and sell DMSA as a "nutritional supplement," but legally, this chelating substance is considered a drug, and has been defined as such in section 201(g)(1) of the Federal Food, Drug, and Cosmetic Act (the Act); 21 U.S.C. [section] 321(g)(1). (1) DMSA is an official Antidote for the treatment of lead and other metal intoxication. The German Environmental Protection Agency (UBA) considers DMSA an effective and indispensible antidote, useful in the treatment of acute metal intoxication. (2)

Doctors have a long history of using this chelating agent to detoxify patients with heavy metal overexposure, and often combine oral DMSA with NaMgEDTA infusions. However, DMSA information as listed the Physician's Desk Reference recommends a 4 week "rest" period after the last dose of DMSA and before the initiation of any other chelator. (3) Combining chelators is not mentioned.

Chemically, DMSA is a dithiol, meaning it contains two sulfhydryl (SH) groups. Among the synthetic chelating agents, it is the least toxic. It effectively removes mercury, lead, aluminium, cadmium, arsenic, mercury, nickel and other metals.

The use of this oral chelator DMSA is considered safe for children, but it is not recommended for pregnant or lactating women and patients with kidney disorders. Side effects are rare, but heavily intoxicated patients may experience weakness during the day of chelation treatment, or "emptiness in the head" with difficulty concentrating. Some patients notice a temporary decrease in vision ability. Digestive spasms may occur after initial treatments, which may be due to a "toxic" GI tract problem that can be prevented if prior-to-treatment attention is paid to digestive health.

Preparing the digestive tract

Chelation has its origin in the Greek word chele that means claw of a lobster, thus depicting the concept of clinging or holding with a strong grip. If the chelating agent's 'claws' are saturated, the substance will pass through the system unable to bind more.

It thus makes sense to 'cleanse' the digestive tract prior to chelation, because a properly prepared intestinal tract will allow the oral chelator to pass relatively unbound through the mucous membranes into the blood stream from where it is transported to organ systems in need of detoxification.

Before the start of oral chelation, the patient should have daily bowel movements. If this is not the case, milk of magnesia or other products with laxative action may be considered. As soon as bowel movements are regular, the patient can be started with the following 2-week program prior to chelation:

* Probiotics 1 t.i.d. before meals for children. Double the dose for adults.

* A good nutritional program supports hepatic function and influences the intestinal pH. Chelators are supposed to function best in a slightly basic environment and pH is an important factor influencing complex formation and stability. Metal complexes are unstable at low pH.

Chelation Protocol:

Depending on exposure, patient age and constitution, DMSA is given in oral doses of 10 mg/kg body weight per day and no more than 30mg/kg/day. An oral chelation treatment schedule rarely needs to exceed 1 day per week, but some organizations list a treatment period of 3 days on and 11 days off cycle, which can be continued for several months until urinary excretion is decreased to near the reference range.

With a more frequent treatment schedule, close attention needs to be paid to patients' nutritional status, because chelating agents do not only bind toxic metals, they also bind nutritional elements. DMSA easily binds selenium.

* Highly sensitive patients can first be tested with a small 100 mg dose of DMSA, and the test is best performed under medical supervision. If a reaction occurs, it would be within 2-3 hours after intake.

* If no reaction to DMSA occurs, the 1st chelation can be started with 500mg (less for children under 6 years of age) or the recommended dose of 10 mg/kg body weight.

Do larger doses detox quicker?

It may be assumed that the administration of higher doses of a chelator such as DMSA (or others) increases metal binding and elimination. The following table contradicts this.

From our Micro Trace Minerals database, we selected data from various clinics which had used mobilization tests with either 500mg or 1000 mg of DMSA. We determined the mean concentration and found that there is hardly a difference in urinary metal excretion following a single dose of 500mg DMSA compared to 100 mg dose. Only the mean copper concentration increased significantly. The mean value for lead, mercury, zinc and iron remained nearly the same, indicating that an increase in dose does not increase (and certainly not double) urine metal concentration as one would expect.

DMSA treatment--Evaluation Program

Oral chelating agents are best given on an empty stomach. If medically possible, the patient should not eat for two hours following intake.

The patient should not eat fish four days prior to chelation, because fish, especially large ones from polluted waters, may contain considerable amounts of arsenic and mercury. If possible, the patient should avoid smoking prior to and during, chelation. Smoke contains nickel, cadmium, lead, beryllium and other metals.

Option A

* Tell the patient to wake up at 3 AM

* Patient should collect a baseline urine sample in a normal urine cup for metal testing.

* Patient then takes DMSA with one glass (200ml) of water on an empty stomach and goes back to sleep.

* Around 7 AM, patient can wake, collect some of the DMSA challenge urine in a normal urine cup and eat a meal. The patient can have coffee, tea and eat breakfast.

* Of the collected urine, 7ml need to be transferred to a metal-free urine tube, which is then placed in a protective container before it is shipped to the laboratory for testing.

* For the remainder of the day, the patient must drink plenty of water.

Option B

* Patient should collect a baseline urine sample in a normal urine cup for metal testing.

* Patient takes DMSA with one glass (100-200ml) water on an empty stomach.

* After 2 hrs the patient can eat 1-2 boiled eggs with bread or fruit and drink another glass (200ml) of water. Coffee or tea is not allowed.

* After 4 hrs, urine is collected in a normal collection cup for testing.

* Transfer 7ml of the collected urine into a metal-free urine tube. For shipping, the urine tube is placed in a protective container.

* Patient must drink plenty of water for the remainder of the day.

The baseline urine is collected prior to the first chelation treatment. The post chelation urine is repeated every 3-5 month to check treatment progress.

Why don't we need a 24h urine collection?

A twenty-four hour urine collection is often done to check renal function and to see how much creatinine clears through the kidneys. A 24h urine is used to measure protein, hormones, minerals, and other chemical compounds.

The aim of a mobilization or provocation test is to check the chelator's ability to bind metals. We are evaluating how chelation affected urinary metal excretion.

Metal binding is affected by the chelator's half-life. For DMSA, it is said to be about 2-3hrs (though statements differ) and this half-life is the time when metal binding peaks.

The following graph demonstrates that for this patient the mercury excretion after the oral intake of 500mg DMSA peaked after 2hrs and remained reasonable constant for a total of 6hrs. After 8hrs, the mercury concentration had fallen below the 2hr value. Lead levels peaked after 6hrs, and gradually dropped thereafter.

Because the binding of metals does vary, experience tells us that a 4hr urine collection is a good compromise. A 24hr urine collection would be less than optimal; urinary lead and mercury value would most likely drop below the peak, unless the metal intake is increased during this period through food, drink, smoking or work exposure. With a 24hr urine, we cannot safely say what we chelated. Did we chelate metals that had been deposited in organ systems or did we bind metals that we ingested through food, water, medicine or that we inhaled at the workplace, on busy streets?

Besides, no patient wants to walk around all day carrying a 24h urine container.

Why test urine creatinine?

Urine creatinine levels reflect fluid intake and excretion, and are utilized as mathematical factors for determining the urinary metal output. Metal levels based on urine creatinine take into account the fluid volume passing through the kidneys. Laboratories no longer need to ask the patient to provide information regarding the total urine volume.

During a chelation treatment program, clinics may order mobilization test results at 3 month intervals to evaluate the detoxification progress, and with results based on urine creatinine, fluctuations are less likely to occur. A comparison report allows both doctor and patient to assess results.

Research:

E. Blaurock-Busch, Albrecht Friedle, Michael Godfrey, Claus E.E. Schulte-Uebbing and Carin Smit. METAL EXPOSURE IN THE CHILDREN OF PUNJAB, INDIA: Clinical Medicine Insights: Therapeutics 2010:2 655-661. 12Jul2010

Conclusion. Our test results documented that hair and urine mineral analysis results support each other. This is of interest, because hair analysis evaluates past exposure while urine analysis detects immediate exposure. We evaluated barium, cadmium, manganese, lead and uranium in hair and urine. Our test results indicate that all of the children show evidence of past and immediate exposure to one or more metals. Hair mineral test results for the 114 children aged 12 and younger showed some type of toxic metal exposure for each one of the children; 88% exceeded the uranium reference range for hair. This indicates past and chronic exposure. After renal evaluation, 55 children aged 3-12 years who passed certain criteria were selected for urine baseline testing. Urine baseline concentrations are a direct reflection of immediate exposure. Of the 55 children, 47 showed elevated urine concentrations for one or more of the toxins listed above, demonstrating immediate exposure. DMSA is recommended as an oral antidote for lead and other metals. We selected 55 children aged 3-12 for a DMSA (dimercapto succinic acid) urine challenge test. Our results showed that 98% of this group showed lead concentrations above the baseline level, demonstrating lead binding and excretion. The DMSA challenge did not affect barium, cadmium, manganese and uranium, suggesting that for these elements, DMSA may not be the chelating agent of choice. In summary, hair and urine mineral testing demonstrated that chronic and immediate toxic exposure had affected our test group of Punjabi children. The DMSA challenge test was effective in detoxifying lead, but did not affect barium, cadmium, manganese or uranium.

James B Adams, Matthew Baral, Elizabeth Geis, Jessica Mitchell, Julie Ingram, Andrea Hensley, Irene Zappia, Sanford Newmark, Eva Gehn, Robert A Rubin, Ken Mitchell, Jeff Bradstreet and Jane El-Dahr

Safety and efficacy of oral DMSA therapy for children with autism spectrum disorders: Part B--Behavioral results. BMC Clinical Pharmacology 2009.

Abstract: This study investigated the effects of oral dimercapto succinic acid (DMSA) therapy on the behavioral symptoms of children with autism spectrum disorders (ASD) ages 3-8 years. Phase 1 involved 65 children with ASD who received one round of DMSA (3 days). Participants who had high urinary excretion of toxic metals were selected to continue on to phase 2. In phase 2, 49 participants were randomly assigned in a double-blind design to receive an additional 6 rounds of either DMSA or placebo. The groups receiving one round and seven rounds of DMSA had significant improvements on all the assessment measures. For the seven round group, the degree of improvement on the assessment measures could be partially explained by a regression analysis based on excretion of toxic metals and changes in glutathione (adjusted R2 of 0.28-0.75, p< 0.02 in all cases). One round of DMSA had nearly the same benefit as seven rounds. The assessment measures correlated reasonably with one another at the beginning of the study (r = 0.60-0.87) and even better at the end of the study (r = 0.63-0.94).

Conclusion: Overall, both one and seven rounds of DMSA therapy seems to be reasonably safe in children with ASD who have high urinary excretion of toxic metals, and possibly helpful in reducing some of the symptoms of autism in those children.

References:

1. www.fda.gov > ... > Enforcement Actions > Warning Letters

2. Offizielle Stellungsnahmen zum Antidota Einsatz. Bekanntmachung des Umweltbundesamtes (Auszug) Erschienen in: Bundesgesundheitsbl--Gesundheitsforsch Gesundheitsschutz 42 (19), (1999)

3. Chemet (Sanofi). In: PDR Physicians' desk reference. 53rd ed. 1999. Montvale, NJ: Medical Economics Company Inc; 1999. p. 2777-8. Read more: http://www.drugs.com/mmx/dmsa.html#ixzz0wgR6FpTQ

Additional References:

* Aposhian, H.V.; Aposhian, M.M. (1990). "Meso-2,3-dimercaptosuccinic acid: Chemical, pharmacological and toxicological properties of an orally effective metal chelating agent". Annual Review of Pharmacology and Toxicology 30 (1): 279-306

* Aasath, Jan; Dag Jacobsen, Ole Andersen, Elsa Wickstrom (March 1995). "Treatment of Mercury and Lead Poisonings with Dimercaptosuccinic Acid (DMSA) and Sodium Dimercaptopropanesulfonate (DMPS)". Analyst 120: 853ff.

* Gerecke M., Friedheim E. A. H., Brossi A. (1961). "Zur Kenntnis der 2,3-Dimercapto-bernsteinsauren". Helvetica Chimca Acta 44: 955 960.

* Guzzi, GianPaolo; Caterina A.M. La Porta (2008). "Molecular mechanisms triggered by mercury". Toxicology 244: 1-12

* Merck Index, 11th Edition, 8854. US patent 4550193, "Process for the preparation of 2,3-dimercaptosuccinic acid and its lower alkyl esters", assigned to Johnson & Johnson Baby Products

* Rooney, James (2007). "The role of thiols, dithiols, nutritional factors and interacting ligands in the toxicology of mercury". Toxicology 234: 145-156. For more information contact the author at info@tracemin.com or ebb@microtrace.de

by: E. Blaurock-Busch PhD

Mean value in mcg/g Creatinine

DMSA oral  N=number  Lead  Mercury  Copper  Iron  Zinc in
           of tests                               [micro]g/g Crea

500mg       169      12    3.7       57.8   15.8  700
1000mg      219      13.8  3.9       75.    15.6  700
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Title Annotation:meso-2,3-dirnercaptosuccinic acid
Author:Blaurock-Busch, E.
Publication:Original Internist
Date:Mar 1, 2016
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