No approved medical research has found any benefits to chelation therapy for any use other than removal of heavy metals from the body,* as well as essential first row transition metals and the Food and Drug Administration (United States)|U.S. Food and Drug Administration (FDA) considers over-the-counter (OTC) chelation products to be "unapproved drugs and devices and that it is a violation of federal law to make unproven claims about these products. There are no FDA-approved OTC chelation products."*
HistoryChelating 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. The sulphur atoms in BAL's mercaptan groups strongly bond to the arsenic in lewisite, 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 ethylenediaminetetraacetic acid (EDTA) as a lead chelating agent was introduced. Unlike BAL, it is a synthetic amino acid and contains no mercaptans. EDTA side effects were not considered 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. More recently, esters of DMSA have been developed which are reportedly more effective; for example, the monoisoamyl ester (MiADMSA) is reportedly more effective than DMSA at clearing mercury and cadmium.*
Research in the former Soviet Union led to the introduction of 2,3-dimercapto-1-propanesulfonic acid|DMPS, another dithiol, as a mercury-chelating agent. The Soviets also introduced Alpha lipoic acid|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.
Since the 1970s, iron chelation therapy has been used as an alternative to regular Bloodletting|phlebotomy to treat excess iron stores in people with haemochromatosis.*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.
Calcium-disodium EDTA chelation is approved by the U.S. Food and Drug Administration (FDA) for treating lead poisoning and heavy metal toxicity.* In 1998, the U.S. Federal Trade Commission (FTC) pursued the American College for Advancement in Medicine (ACAM), an organization that promotes "complementary, alternative and integrative medicine" over the claims made regarding the treatment of atherosclerosis in advertisements for EDTA chelation therapy. The FTC concluded that there was a lack of scientific studies to support these claims and that the statements by the ACAM were false.* In 1999, the ACAM agreed to stop presenting chelation therapy as effective in treating heart disease, avoiding legal proceedings.* In 2010 the Food and Drug Administration (United States)|U.S. Food and Drug Administration (FDA) warned companies who sold over-the-counter (OTC) chelation products and stated that such "products are unapproved drugs and devices and that it is a violation of federal law to make unproven claims about these products. There are no FDA-approved OTC chelation products."*
Approved medical useChelation 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 Intravenous therapy|intravenously, Intramuscular injection|intramuscularly, or orally, depending on the agent and the type of poisoning.*Several chelating agents are available, having different affinities for different metals. Common chelating agents follow:
Medically diagnosed heavy metal poisoningSome common chelating agents are EDTA (ethylenediaminetetraacetic acid), 2,3-Dimercapto-1-propanesulfonic acid|DMPS (2,3-dimercaptopropanesulfonic acid), TTFD (Fursultiamine|thiamine tetrahydrofurfuryl disulfide), and DMSA (2,3-dimercaptosuccinic acid). Calcium-disodium EDTA and DMSA are only approved for the removal of lead by the Food and Drug Administration while DMPS and TTFD are not approved by the FDA. These drugs bind to heavy metals in the body and prevent them from binding to other agents. They are then excreted from the body. The chelating process also removes vital nutrients such as vitamins C and E, therefore these must be supplemented.*
Unapproved use in alternative medicineAlternative medicine uses chelation therapy as a non-standard treatment for some ailments, including heart disease and autism.* In 2010 the Food and Drug Administration (United States)|U.S. Food and Drug Administration (FDA) warned companies who sold over-the-counter (OTC) chelation products and stated that such "products are unapproved drugs and devices and that it is a violation of federal law to make unproven claims about these products. There are no FDA-approved OTC chelation products."*Attempts have been made to use it in treating kidney dysfunction, calcific band keratopathy (an eye disorder), and ovarian cancer. Currently there is a US National Center for Complementary and Alternative Medicine (NCCAM) trial being conducted on the chelation therapy's safety and efficacy for patients with coronary artery disease.* NCCAM Director Stephen E. Straus cited the "widespread use of chelation therapy in lieu of established therapies, the lack of adequate prior research to verify its safety and effectiveness, and the overall impact of coronary artery disease" as factors motivating the trial.* The proposed study has been criticized as unethical, unnecessary and dangerous, with multiple studies conducted in the past demonstrating that it provides no benefits.*
Heart diseaseThe use of EDTA chelation therapy as a treatment for atherosclerosis|coronary artery disease has not been shown to be effective and is not approved by the Food and Drug Administration (United States)|U.S. Food and Drug Administration (FDA).* Several possible mechanisms have been proposed, though none have been scientifically validated. The US National Center for Complementary and Alternative Medicine began conducting the Trial to Assess Chelation Therapy (TACT) in 2003.* Patient enrollment was to be completed around July 2009* with final completion around July 2010,* but enrollment in the trial was suspended on September 26, 2008 for an investigation by OHRP after complaints about ethical concerns such as inadequate informed consent.* The trial has been criticized for lacking prior Phase I and II studies, and particularly because previous controlled trials have not indicated benefits.* The American College for Advancement in Medicine, a controversial organization created to promote chelation therapy, has played a part in the adoption of the TACT clinical trial, which has led to further criticism of the trial.* Atwood et al. have argued that methodological flaws and lack of prior probability make this trial "unethical, dangerous, pointless, and wasteful."*
The final results of TACT, published in November 2012, showed no support for the use of chelation therapy in coronary heart disease, particularly the claims to reduce the need for coronary artery bypass grafting.*The American Heart Association states that there is "no scientific evidence to demonstrate any benefit from this form of therapy" and that the "United States Food and Drug Administration (FDA), the National Institutes of Health (NIH) and the American College of Cardiology all agree with the American Heart Association" that "there have been no adequate, controlled, published scientific studies using currently approved scientific methodology to support this therapy for cardiovascular disease."* Like other scientific commentators, they note that any improvement among heart patients undergoing chelation therapy can be attributed to the placebo effect and lifestyle changes discovered in conventional medicine but recommended by chelationists; "quitting smoking, losing weight, eating more fruits and vegetables, avoiding foods high in saturated fats and exercising regularly". They note their concern that patients could put off proven treatments for heart disease like drugs or surgery. A 2005 systematic review found that controlled scientific studies did not support chelation therapy for heart disease.* It found that very small trials and uncontrolled descriptive studies have reported benefits while larger controlled studies have found results no better than placebo. The Mayo Clinic states that "chelation studies have found that chelation didn't work as a heart disease treatment."*In 2009, the Montana Board of Medical Examiners issued a position paper concluding that "chelation therapy has no proven efficacy in the treatment of cardiovascular disease, and in some patients could be injurious."*