Chelation therapy

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Chelation therapy is a technique which involves the administration of chelating agents to remove heavy metals from the body.

Chelation therapy has a long history of use in clinical toxicology [1] and remains in use for some very specific medical treatments, although it is administered under very careful medical supervision due to various inherent risks.[2]

The use of chelation as alternative therapy can prove fatal,[3] and medical evidence does not support the effectiveness of chelation therapy for any purpose other than the treatment of heavy metal poisoning.[3] The U.S. Food and Drug Administration (FDA) considers over-the-counter (OTC) chelation products to be "unapproved".[4]

History[edit]

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. 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.

In the 1960s, BAL was modified into DMSA, a related dithiol with far fewer side effects.[5] 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.[5]

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.

Since the 1970s, iron chelation therapy has been used as an alternative to regular phlebotomy to treat excess iron stores in people with haemochromatosis.[6]

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.[citation needed]

Calcium-disodium EDTA chelation has been studied by the U.S. National Center for Complementary and Alternative Medicine for treating coronary disease.[7] 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.[8] In 1999, the ACAM agreed to stop presenting chelation therapy as effective in treating heart disease, avoiding legal proceedings.[9] In 2010 the 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."[4]

Approved medical use[edit]

Two molecules of deferasirox, an orally administered chelator, binding iron. Deferasirox is used in the treatment of transfusional iron overload in people with thalassemia.

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.[10]

Several chelating agents are available, having different affinities for different metals. For the most common forms of heavy metal intoxication – lead, arsenic, or mercury – a number of chelating agents are available. Dimercaptosuccinic acid (DMSA) has been recommended for the treatment of lead poisoning in children by Poison Centers around the world.[11] Other chelating agents, such as 2,3-dimercapto-1-propanesulfonic acid (DMPS) and alpha lipoic acid (ALA), are used in conventional and alternative medicine.

Common chelating agents follow:

Chelator Used in
Dimercaprol (British anti-Lewisite; BAL)
Dimercaptosuccinic acid (DMSA)
Dimercapto-propane sulfonate (DMPS)
  • severe acute arsenic poisoning[12]
  • severe acute mercury poisoning[12]
Penicillamine Mainly in:

Occasionally adjunctive therapy in:

Ethylenediamine tetraacetic acid (calcium disodium versante) (CaNa2-EDTA)
Deferoxamine and Deferasirox

Medically diagnosed heavy metal poisoning[edit]

Some common chelating agents are EDTA (ethylenediaminetetraacetic acid), DMPS (2,3-dimercaptopropanesulfonic acid), TTFD (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.[13]

Unapproved use in alternative medicine[edit]

Alternative medicine uses chelation therapy as a non-standard treatment for some ailments, including heart disease and autism.[14][15] In 2010 the 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."[4]

Attempts have been made to use it in treating kidney dysfunction, calcific band keratopathy (an eye disorder), and ovarian cancer. The U.S. National Center for Complementary and Alternative Medicine (NCCAM) conducted a trial on the chelation therapy's safety and efficacy for patients with coronary artery disease.[16] 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.[17] The proposed study has been criticized as unethical, unnecessary and dangerous, with multiple studies conducted in the past demonstrating that it provides no benefits.[2]

Cancer[edit]

The American Cancer Society says of chelation therapy: "Available scientific evidence does not support claims that it is effective for treating other conditions such as cancer. Chelation therapy can be toxic and has the potential to cause kidney damage, irregular heartbeat, and even death."[3]

Heart disease[edit]

The use of EDTA chelation therapy as a treatment for coronary artery disease has not been shown to be effective and is not approved by the U.S. Food and Drug Administration (FDA).[18] 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.[16] Patient enrollment was to be completed around July 2009[7] with final completion around July 2010,[16] 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.[19] The trial has been criticized for lacking prior Phase I and II studies, and particularly because previous controlled trials have not indicated benefits.[2] 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.[2] Atwood et al. have argued that methodological flaws and lack of prior probability make this trial "unethical, dangerous, pointless, and wasteful."[2]

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.[20][21][22]

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."[18] 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.[23] 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."[24]

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."[25]

Autism[edit]

Quackwatch says that autism is one of the conditions for which chelation therapy has been falsely promoted as effective, and practitioners falsify diagnoses of metal poisoning to "trick" parents into having their children undergo the process.[26] As of 2008, between 2–8% of children with autism had had the therapy.[27] Parents either have a doctor use a treatment for lead poisoning, or buy unregulated supplements, in particular DMSA and lipoic acid.[27] Aspies For Freedom, an autistic rights organization, considers this use of chelation therapy unethical and potentially dangerous.[28] There is strong epidemiological evidence that refutes links between environmental triggers, in particular thiomersal-containing vaccines, and the onset of autistic symptoms.[29][30][31][32] There is sparse scientific research about chelation therapy as a treatment for autism.[15][33][34][35][36][37][38]

Controversy[edit]

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.[39]

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.[8][40]

The use of chelation therapy by alternative medicine practitioners for behavioural and other disorders is considered pseudoscientific; there is no proof that it is effective,[41] and it can be fatal.[3]

Prevalence[edit]

The American College for Advancement in Medicine estimates that 800,000 patient visits for chelation therapy were made in the United States in 1997.[42]

Side effects and safety concerns[edit]

As approved pharmaceuticals, the various chelating agents may cause specific side effects if used improperly. When protocols are followed, there is a low occurrence of side effects.[citation needed] DMPS injections may cause skin reactions at the injection site. Other side effects reported include fever, headache, nausea. No death has been linked to DMPS.[43] The EDTAs when used according to protocol are equally safe. Most important is the correct use and a slow infusion time (1 g/h or less of NaEDTA or CaEDTA).[citation needed] Side effects are largely avoided if general medical caution is exercised.[citation needed] Most importantly, renal function has to be checked before any chelation substance is used.[44] 2007 research with lab rats indicates giving chelating agent DMSA to rats without high levels of lead may cause lasting cognitive damage.[45] The German Environmental Agency (Umweltbundesamt)listed DMSA along with DMPS as the two most useful and safe chelating agents available at this time.[46] In a 2011 publication S.J. Flora stated, "Chelation treatment is the preferred medical treatment for reducing toxic effects of metals."[47]

Chelation therapy can be hazardous when used inappropriately. In August 2005, chelation therapy conducted by an ACAM member killed a 5-year-old boy with autism;[2] a 3-year-old nonautistic girl 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. In two of the cases hypocalcemia appears to have been caused by the administration of Na2EDTA (Disodium EDTA) and in the third case the type of EDTA was unknown.[48][49] Only the 3-year-old girl had been medically assessed and found to have an elevated blood lead level and resulting low iron levels and anemia, a proper medical cause for chelation therapy to be conducted.[50] According to protocol,[clarification needed] EDTA should not be used in the treatment of children.[51] More than 30 deaths have been recorded in association with IV-administered disodium EDTA since the 1970s.[2]

See also[edit]

References[edit]

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  3. ^ a b c d "Chelation Therapy". American Cancer Society. 1 November 2008. Retrieved 14 September 2013. 
  4. ^ a b c Food and Drug Administration (FDA) (14 October 2010). "FDA issues warnings to marketers of unapproved ‘chelation’ products" (Press release). 
  5. ^ a b Kalia, Kiran; Flora, Swaran J.S. (2005). "Strategies for safe and effective therapeutic measures for chronic arsenic and lead poisoning". Journal of Occupational Health (Japan Society for Occupational Health) 47 (1): 1–21. doi:10.1539/joh.47.1. PMID 15703449. 
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  8. ^ a b "American College for Advancement in Medicine: Case Timeline" (FTC Case Timeline with links to documents). FTC Matter/File Number: 962 3147 (Docket Number:C-3882). Federal Trade Commission (FTC). 13 July 1999. Retrieved 1 July 2010. 
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  39. ^ Program to Assess Alternative Treatment Strategies to Achieve Cardiac Health (PATCH) Investigators; Knudtson, M.L.; Wyse, D.G.; Galbraith, P.D. et al. (2002). "Chelation therapy for ischemic heart disease: A randomized controlled trial". JAMA 287 (4): 481–6. doi:10.1001/jama.287.4.481. PMID 11798370. 
  40. ^ Federal Trade Commission (8 December 1998). "Medical Association Settles False Advertising Charges Over Promotion of 'Chelation Therapy'" (Press release). Retrieved 17 January 2014. 
  41. ^ "Boy with autism dies during 'chelation therapy'". Behavior News. Behavior Analysis Association of Michigan. 30 August 2005. 
  42. ^ "Physician Group Backs New NIH Chelation Therapy Study For Heart Disease" (Press release). American College for Advancement in Medicine. PRNewswire. 14 August 2002. Archived from the original on 2007-02-04. Retrieved 11 November 2007. [unreliable medical source?]
  43. ^ Ruprecht, Johann (January 2008), Dimaval and Dimaval 100 mg Hartkapseln (Product monograph) (7th ed.), Berlin: Heyl. [unreliable medical source?][full citation needed]
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  46. ^ Kommission Human-Biomonitoring des Umweltbundesamtes [Human Biomonitoring Committee of the Federal Environmental Agency (Federal Republic of Germany )] (1999). "Bekanntmachung des Umweltbundesamtes Einsatz von Chelatbildnern in der Umweltmedizin? Stellungnahme der Kommission 'Human-Biomonitoring' des Umweltbundesamtes" [Notice of the Federal Environmental Agency use of chelating agents in environmental medicine? Opinion of the Commission 'Human biomonitoring' of the German Federal Environment Agency]. Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz (in German) 42 (10): 823–4. doi:10.1007/s001030050288. 
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  50. ^ "Deaths associated with hypocalcemia from chelation therapy - Texas, Pennsylvania, and Oregon, 2003-2005". Morbidity and Mortality Weekly Report (Centers for Disease Control and Prevention) 55 (8): 204–7. 2006. 
  51. ^ Van der Schaar, Peter J. (2011). Textbook of Clinical Metal Toxicology (10th ed.). Leende, Netherlands: International Board of Clinical Metal Toxicology. [unreliable medical source?][full citation needed]

External links[edit]