Chelation therapy

Chelation therapy is the administration of chelating agents to remove heavy metals from the body. For the most common forms of heavy metal intoxication—those involving lead, arsenic or mercury—the standard of care in the USA dictates the use of Dimercaptosuccinic acid (DMSA). Other chelating agents, such as 2,3-dimercapto-1-propanesulfonic acid (DMPS) and alpha lipoic acid (ALA), are used in conventional and alternative medicine.

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Discovery and history in medicine

Chelating agents were introduced into medicine as a result of the use of poison gas in World War I. The first widely used chelating agent—the organic dithiol compound dimercaprol, also named British Anti-Lewisite or BAL—was used as an antidote to the arsenic-based poison gas, Lewisite. It binds the arsenic in Lewisite with two strong chemical bonds with the SH groups ("mercaptans"), forming a water soluble compound that entered the bloodstream, allowing it to be removed from the body by the kidneys and liver. BAL had severe side-effects.

After World War II, a large number of navy personnel suffered from lead poisoning as a result of their jobs repainting the hulls of ships. The medical use of EDTA as a lead chelating agent was introduced. Unlike BAL, it is a synthetic amino acid; it contains no mercaptans. While EDTA had some uncomfortable side effects, they were not as severe as BAL.

In the 1960s, BAL was modified into DMSA, a related dithiol with far fewer side effects. DMSA quickly replaced both BAL and EDTA, becoming the US standard of care for the treatment of lead, arsenic and mercury poisoning, which it remains today.

Research in the former Soviet Union led to the introduction of DMPS, another dithiol, as a mercury chelating agent. The Soviets also introduced ALA, which is transformed by the body into the dithiol dihydrolipoic acid, a mercury and arsenic chelating agent. DMPS has experimental status in the US FDA, while ALA is a common nutritional supplement.

Other chelating agents have been discovered. They all function by making several chemical bonds with metal ions, thus rendering them much less chemically reactive. The resulting complex is water soluble, allowing it to enter the bloodstream and be excreted harmlessly.

EDTA chelation is approved by the U.S. Food and Drug Administration (FDA) for treating lead poisoning and heavy metal toxicity.^[1]

Medical use

  Chelation therapy is used as a treatment for acute mercury, iron (including in cases of thalassemia), arsenic, lead, uranium, plutonium and other forms of toxic metal poisoning. The chelating agent may be administered intravenously, intramuscularly, or orally, depending on the agent and the type of poisoning.

One example of successful chelation therapy is the case of Harold McCluskey, a nuclear worker who became badly contaminated internally with americium in 1976. He was treated with diethylene triamine pentaacetic acid (DTPA) over many years, removing 41 MBq (1.1 mCi) of americium from his body. His death, 11 years later, was from unrelated causes.

Several chelating agents are available, having different affinities for different metals. Common chelating agents include:

• Alpha lipoic acid (ALA)
• Aminophenoxyethane-tetraacetic acid (BAPTA)
• Defarasirox
• Deferoxamine
• Diethylene triamine pentaacetic acid (DTPA)
• Dimercaprol (BAL)
• Dimercapto-propane sulfonate (DMPS)
• Dimercaptosuccinic acid (DMSA)
• Ethylenediamine tetraacetic acid (calcium disodium versante) (CaNa₂-EDTA)
• Ethylene glycol tetraacetic acid (EGTA)
• D-penicillamine

Use in alternative medicine

Alternative medicine uses chelation therapy in the treatment of heart disease,^[2] in cases of unrecognized but claimed heavy metal poisoning,^{[citation needed]} and in the treatment of autistic patients.^[3]

Heavy metal poisoning

Alternative practitioners claim to recognize extensive environmental exposures to heavy metals, such as through contact with treated lumber or pesticides. Many of their patients claim to have been exposed to mercury through their dental amalgam fillings. Others claim that they, or their children, have become exposed to mercury from thimerosal, an ethyl-mercury compound used as a preservative in some vaccines and contact lens solutions. It is the nonoccupational nature of these cases which distinguishes chelation therapy in alternative practice from that in conventional medicine.^{[citation needed]}

Cilantro (coriander) has been tested in mice,^[4] and is present in numerous alternative medications. Although cilantro was widely described as a chelator of lead, mercury or other heavy metals in internet literature,^[5][6] and is often used as such, there is a paucity of research about such claims.^[7]

Heart disease

Some alternative practitioners use chelation to treat hardening of the arteries. The original theory behind calcium chelation therapy was that EDTA forms a complex with the calcium in the walls of arteries. Drawbacks with this theory include EDTA's inability to penetrate the cell walls in the arteries and therefore inability to access the calcium, EDTA binding preferentially to other metals, and calcium posing minimal arterial danger in comparison to cholesterol and other deposits. A number of dangers have been associated with the therapy including hypocalcaemia, decreased blood coagulation ability (perhaps hypocalcaemia related), and the risk of leaching of necessary trace metals.

The safety and efficacy of EDTA chelation therapy as a treatment for coronary artery disease are being assessed by the National Center for Complementary and Alternative Medicine (NCCAM) in a five-year study which began in 2002.^[8][1]

Autism

Based on the speculation that heavy metal poisoning may trigger the symptoms of autism, particularly in small subsets of individuals who cannot excrete toxins effectively, some parents have turned to alternative medicine practitioners who provide chelation therapy. However, evidence to support this practice has been anecdotal and not rigorous. There is strong epidemiological evidence that refutes links between environmental triggers, in particular thimerosal containing vaccines, and the onset of autistic symptoms. No scientific data supports the claim that the mercury in the vaccine preservative thiomersal causes autism^[9] or its symptoms,^[10] and there is no scientific support for chelation therapy as a treatment for autism.^[11]

Controversy

The efficacy, safety, and much of the theory behind these alternative practices are disputed by the medical community. In 2001, researchers at the University of Calgary reported that cardiac patients receiving chelation therapy fared no better than those who received placebo treatment.^[12]

In 2003, the Supreme Court of Missouri, in State Board of Registration for the Healing Arts v. McDonagh, 123 S.W.3d 146, overturned a decision of the State Board of Registration sanctioning a doctor who used chelation therapy for the treatment of heart disease. The Court held that the therapy was not harming patients, and the standard for determining repeated negligence in using an alternative therapy such as chelation is not whether it is popular or commonly accepted by the medical community, but rather whether heart specialists would consider its use to be reasonable.

In 1998, the U.S. Federal Trade Commission (FTC) charged that the web site of the American College for Advancement in Medicine (ACAM) and a brochure they published had made false or unsubstantiated claims. In December 1998, the FTC announced that it had secured a consent agreement barring ACAM from making unsubstantiated advertising claims that chelation therapy is effective against atherosclerosis or any other disease of the circulatory system.^[13][14]

Prevalence

The American College for Advancement in Medicine (ACAM), a private corporation which promotes chelation therapy, claims that 800,000 patient visits for chelation therapy, with an average of 40 visits per patient, were made in the United States in 1997.^[15] A May 2004 survey by the National Center for Complementary and Alternative Medicine (NCCAM) estimated that 0.1%, plus or minus 0.02% of the adult US population had used chelation therapy at some point in their life.^{[citation needed]}

Side effects and safety concerns

There is a low occurrence of side effects when chelation is used at the dose and infusion rates approved by the U.S. FDA. A burning sensation at the site of delivery into the vein is common. Rarer side effects include fever, headache, nausea, stomach upset, vomiting, a drop in blood pressure and hypocalcemia. Kidney toxicity is a safety concern, but a rare occurrence. When EDTA is not administered correctly, more serious side effects can occur.^[1]

Chelation therapy can be hazardous. In August 2005, botched chelation therapy killed a 5-year-old autistic boy, a nonautistic child died in February 2005 and a nonautistic adult died in August 2003. These deaths were due to cardiac arrest caused by hypocalcemia during chelation therapy.^[16]

References