{{short description|Medical procedure to remove heavy metals from the body}} {{Infobox medical intervention | name = Chelation therapy | image = Deferasirox–iron(III) complex.png | caption = Two molecules of deferasirox, an orally administered chelator, binding iron. Deferasirox is used in the treatment of transfusional iron overload in people with thalassemia. | alt = | pronounce = | synonyms = | ICD10 = | ICD9 = | ICD9unlinked = | MeshID = | LOINC = | other_codes = | MedlinePlus = | eMedicine = }} '''Chelation therapy''' is a medical procedure that involves the administration of chelating agents to remove heavy metals from the body.<ref name=crisponi>{{cite book |first1= Jan|last1= Aaseth|first2=Guido|last2=Crisponi|first3=Ole|last3=Anderson|title= Chelation Therapy in the Treatment of Metal Intoxication |year=2016|publisher=Academic Press|page=388| isbn =978-0-12-803072-1}}</ref> Chelation therapy has a long history of use in clinical toxicology<ref>{{cite web|url=https://www.poison.org/current/chelationtherapy.htm|title=Chelation: Therapy or "Therapy"? |date= 6 May 2013 |orig-date= 2010 |publisher= National Capital Poison Center |work= poison.org |access-date=9 October 2013}}</ref> and remains in use for some very specific medical treatments, although it is administered under very careful medical supervision due to various inherent risks, including the mobilization of mercury and other metals through the brain and other parts of the body by the use of weak chelating agents that unbind with metals before elimination, exacerbating existing damage.<ref name=Atwood2008>{{cite journal |last1= Atwood |first1= K.C. IV |author-link1= Kimball Atwood |last2= Woeckner |first2= E. |last3= Baratz |first3= R.S. |author3-link= Robert Baratz |last4= Sampson |first4= W.I. |author4-link= Wallace Sampson |title=Why the NIH Trial to Assess Chelation Therapy (TACT) should be abandoned |journal= Medscape Journal of Medicine |volume=10 |issue=5 |page=115 |year=2008 |pmid=18596934 |pmc=2438277 }}</ref> To avoid mobilization, some practitioners of chelation use strong chelators, such as selenium, taken at low doses over a long period of time.

Chelation therapy also has a history of fraudulent use in alternative medicine, to treat claimed effects of heavy-metal exposure on problems as disparate as heart disease, cancer, and autism.

Chelation therapy must be administered with care as it has a number of possible side effects, including death.<ref name="acs">{{cite web|title=Chelation Therapy|url=http://www.cancer.org/treatment/treatmentsandsideeffects/complementaryandalternativemedicine/pharmacologicalandbiologicaltreatment/chelation-therapy|date=1 November 2008|publisher=American Cancer Society|archive-url=https://web.archive.org/web/20100705115407/http://www.cancer.org/treatment/treatmentsandsideeffects/complementaryandalternativemedicine/pharmacologicalandbiologicaltreatment/chelation-therapy|archive-date=5 July 2010|access-date=14 September 2013}}</ref><ref>{{Cite web|url=https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5508a3.htm|title=Deaths Associated with Hypocalcemia from Chelation Therapy - Texas, Pennsylvania, and Oregon, 2003-2005|website=www.cdc.gov|access-date=2016-10-13}}</ref> In response to increasing use of chelation therapy as alternative medicine and in circumstances in which the therapy should not be used in conventional medicine, various health organizations have confirmed that medical evidence does not support the effectiveness of chelation therapy for any purpose other than the treatment of heavy metal poisoning.<ref name=acs/> Over-the-counter chelation products are not approved for sale in the United States.<ref name="FDA_2010_warning">{{cite press release|url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm229320.htm|title=FDA issues warnings to marketers of unapproved 'chelation' products|author=Food and Drug Administration (FDA)|date=14 October 2010|archive-url=https://wayback.archive-it.org/7993/20170111123610/http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm229358.htm|archive-date=January 11, 2017}}</ref>

== Medical uses == Chelation therapy is the preferred medical treatment for metal poisoning,<ref name=crisponi/><ref>{{Cite journal|last1=Flora|first1=Swaran J. S.|last2=Pachauri|first2=Vidhu|date=2010-06-28|title=Chelation in Metal Intoxication|journal=International Journal of Environmental Research and Public Health|language=en|volume=7|issue=12|pages=2745–2788|doi=10.3390/ijerph7072745|pmc=2922724|pmid=20717537|doi-access=free}}</ref> including acute mercury, iron (including in cases of sickle-cell disease and thalassemia),<ref>{{Cite journal |last1=Fortin |first1=Patricia M. |last2=Fisher |first2=Sheila A. |last3=Madgwick |first3=Karen V. |last4=Trivella |first4=Marialena |last5=Hopewell |first5=Sally |last6=Doree |first6=Carolyn |last7=Estcourt |first7=Lise J. |date=May 8, 2018 |title=Interventions for improving adherence to iron chelation therapy in people with sickle cell disease or thalassaemia |journal=The Cochrane Database of Systematic Reviews |volume=2018 |issue=5 |article-number=CD012349 |doi=10.1002/14651858.CD012349.pub2 |issn=1469-493X |pmc=5985157 |pmid=29737522}}</ref><ref>{{cite book |first1=Robert C. |last1=Hider |first2=Xiaole |last2=Kong |editor=Astrid Sigel, Helmut Sigel and Roland K. O. Sigel |title=Interrelations between Essential Metal Ions and Human Diseases |series=Metal Ions in Life Sciences |volume=13 |year=2013 |publisher=Springer |pages=229–294 |chapter=Chapter 8. Iron: Effect of Overload and Deficiency |doi=10.1007/978-94-007-7500-8_8 |pmid=24470094 |isbn=978-94-007-7499-5 }}</ref> 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.<ref>{{Citation|last1=Flora|first1=Govinder|title=26 - Medical Countermeasures—Chelation Therapy|date=2015-01-01|url=http://www.sciencedirect.com/science/article/pii/B9780124186880000265|work=Handbook of Arsenic Toxicology|pages=589–626|editor-last=Flora|editor-first=S. J. S.|place=Oxford|publisher=Academic Press|language=en|isbn=978-0-12-418688-0|access-date=2020-12-07|last2=Mittal|first2=Megha|last3=Flora|first3=Swaran J. S.}}</ref>

===Chelating agents===

There are a variety of common chelating agents with differing affinities for different metals, physical characteristics, and biological mechanism of action. For the most common forms of heavy metal intoxication&nbsp;&ndash; lead, arsenic, or mercury&nbsp;&ndash; a number of chelating agents are available. Dimercaptosuccinic acid (DMSA) has been recommended by poison control centers around the world for the treatment of lead poisoning in children.<ref>{{cite journal |last= Chisolm | first= J.J. Jr. |title=Safety and efficacy of meso-2,3-dimercaptosuccinic acid (DMSA) in children with elevated blood lead concentrations |journal=Journal of Toxicology: Clinical Toxicology |volume=38 |issue=4 |pages=365–75 |year=2000 |pmid=10930052 |doi=10.1081/CLT-100100945 |s2cid= 21793727 }}</ref> Other chelating agents, such as 2,3-dimercaptopropanesulfonic acid (DMPS) and alpha lipoic acid (ALA), are used in conventional and alternative medicine. Some common chelating agents are ethylenediaminetetraacetic acid (EDTA), 2,3-dimercaptopropanesulfonic acid (DMPS), and thiamine tetrahydrofurfuryl disulfide (TTFD). 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.<ref>{{cite news |last= Bridges |first= Sarah |date= January 2006 |title= The promise of chelation |magazine= Mothering |issue= 134 |pages= 54–61}}</ref>{{Unreliable medical source|date=January 2014}}

The German Environmental Agency (Umweltbundesamt) listed DMSA and DMPS as the two most useful and safe chelating agents available.<ref>{{cite journal |title=Bekanntmachung des Umweltbundesamtes Einsatz von Chelatbildnern in der Umweltmedizin? Stellungnahme der Kommission 'Human-Biomonitoring' des Umweltbundesamtes |trans-title= 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 |journal=Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz |volume=42 |issue=10 |pages=823–4 |year=1999 |doi=10.1007/s001030050288 |author= Kommission Human-Biomonitoring des Umweltbundesamtes [Human Biomonitoring Committee of the Federal Environmental Agency (Federal Republic of Germany )]|s2cid= 30922256 |language= de}}</ref>

{|class="wikitable" |- ! Chelator !! Used in |- | Ethylenediaminetetraacetic acid (EDTA) | * early chelation-therapy research<ref name=royalsociety/> |- | Dimercaprol ("British anti-Lewisite", or BAL) | * acute arsenic poisoning<ref name=KatzungTrevor2008>{{cite book |last1=Masters |first1= Susan B. |last2= Trevor |first2= Anthony J. |last3= Katzung |first3= Bertram G. |title=Katzung & Trevor's Pharmacology: Examination & Board Review |publisher= McGraw Hill Medical |edition= 8th |year=2008 |isbn=978-0-07-148869-3 |pages= 481–3}}</ref> * acute mercury poisoning<ref name=KatzungTrevor2008/> * lead poisoning (in addition to EDTA)<ref name=KatzungTrevor2008/> * Lewisite poisoning (for which it was developed as an antidote) |- | Dimercaptosuccinic acid (DMSA, "Succimer") | *lead poisoning<ref name=KatzungTrevor2008/> * arsenic poisoning<ref name=KatzungTrevor2008/> * mercury poisoning<ref name=KatzungTrevor2008/> |- | Dimercapto-propane sulfonate (DMPS, "Dimaval") | * severe acute arsenic poisoning<ref name=KatzungTrevor2008/> * severe acute mercury poisoning<ref name=KatzungTrevor2008/> |- | Penicillamine | ''Mainly in:'' * copper toxicity<ref name=KatzungTrevor2008/> ''Occasionally adjunctive therapy in:'' *gold toxicity<ref name=KatzungTrevor2008/> *arsenic poisoning<ref name=KatzungTrevor2008/> *lead poisoning<ref name=KatzungTrevor2008/> *rheumatoid arthritis<ref name=KatzungTrevor2008/> |- | Ethylenediamine tetraacetic acid (calcium disodium versenate) (CaNa<sub>2</sub>-EDTA) | *lead poisoning<ref name=KatzungTrevor2008/> |- | Deferoxamine, Deferasirox and Deferiprone | *acute iron poisoning<ref name=KatzungTrevor2008/> *iron overload<ref>{{cite book|last1=Crisponi |first1=Guido |last2=Nurchi |first2=Valeria M. |last3=Lachowicz |first3=Joanna|editor1-last=Sigel|editor1-first=Astrid|editor2-last=Freisinger|editor2-first=Eva |editor3-last=Sigel|editor3-first=Roland K. O. |editor4-last=Carver|editor4-first=Peggy L.|title=Essential Metals in Medicine:Therapeutic Use and Toxicity of Metal Ions in the Clinic |series=Metal Ions in Life Sciences |volume=19 |date=2019 |publisher=de Gruyter GmbH|location=Berlin|isbn=978-3-11-052691-2|doi=10.1515/9783110527872-009|pmid=30855104|pages=49–86|chapter=Chapter 3. Iron Chelation for Iron Overload in Thalassemia|s2cid=73727755 }}</ref>

|}

===Side effects===

Chelation therapy carries a range of potential side effects. When administered appropriately under medical supervision, side effects may include dehydration, hypocalcemia (low calcium levels), renal impairment, elevated liver enzymes, electrolyte imbalance, and allergic reactions.<ref>{{Citation |last1=Flora |first1=Govinder |title=Medical Countermeasures—Chelation Therapy |date=2015 |work=Handbook of Arsenic Toxicology |pages=589–626 |publisher=Elsevier |isbn=978-0-12-418688-0 |last2=Mittal |first2=Megha |last3=Flora |first3=Swaran J.S. |doi=10.1016/b978-0-12-418688-0.00026-5 }}</ref> The loss of essential dietary elements such as zinc, magnesium, and iron is common, especially with prolonged therapy, potentially leading to fatigue, weakened immunity, or neurological disturbances.<ref>{{Cite book |last=Barceloux |first=Donald G. |title=Medical Toxicology of Natural Substances |date=2008-01-02 |publisher=Wiley |doi=10.1002/9780470330319 |isbn=978-0-471-72761-3}}</ref>

In contrast, inappropriate or non-medical use for example, in unapproved treatments for autism or cardiovascular disease, has been associated with serious complications, including severe hypocalcemia, neurodevelopmental disorders, and even death.<ref>{{Cite journal |last1=Brown |first1=Mary Jean |last2=Willis |first2=Teresa |last3=Omalu |first3=Bennet |last4=Leiker |first4=Richard |date=2006-08-01 |title=Deaths Resulting From Hypocalcemia After Administration of Edetate Disodium: 2003-2005 |journal=Pediatrics |volume=118 |issue=2 |pages=e534–e536 |doi=10.1542/peds.2006-0858 |pmid=16882789 |issn=0031-4005}}</ref> Notably, disodium EDTA had been linked to fatal outcomes when used incorrectly, such as through rapid IV administration.<ref>{{Cite journal |date=2005 |title=CDC Issues Recommendations for Lead Poisoning Prevention in Newly Arrived Refugee Children |website=PsycEXTRA Dataset |doi=10.1037/e411502005-001 }}</ref> For these reasons, regulating authorities like FDA, CDC strongly discourage off label or unsupervised use of chelation agents.

==Use in alternative medicine== In alternative medicine, some practitioners claim chelation therapy can treat a variety of ailments, including heart disease and autism.<ref>{{cite journal |last=Ernst |first= E. |author-link= Edzard Ernst |title=Chelation therapy for coronary heart disease: An overview of all clinical investigations |journal=American Heart Journal |volume=140 |issue=1 |pages=139–41 |year=2000 |pmid=10874275 |doi=10.1067/mhj.2000.107548}}</ref><ref name=Weber/> There has been scientific evidence that chelation therapy for heart disease is modestly successful. However, there is no proof that chelation therapy is effective for behavioral disorders such as autism.<ref>{{cite web |url= http://www.baam.emich.edu/baamnewsarchive/BAAMbnachelationdeath.htm |title= Boy with autism dies during 'chelation therapy' |work= Behavior News |publisher= Behavior Analysis Association of Michigan |date= 30 August 2005 |access-date= 4 August 2010 |archive-url= https://web.archive.org/web/20161129083241/http://www.baam.emich.edu/baamnewsarchive/BAAMbnachelationdeath.htm |archive-date= 29 November 2016 }}</ref> Chelation therapy prior to heavy metal testing can artificially raise urinary heavy metal concentrations ("provoked" urine testing) and lead to inappropriate and unnecessary treatment.<ref name="toxicfive">{{Citation |author1 = American College of Medical Toxicology |author1-link = American College of Medical Toxicology |author2 = American Academy of Clinical Toxicology |author2-link = American Academy of Clinical Toxicology |date = February 2013 |title = Five Things Physicians and Patients Should Question |publisher = American College of Medical Toxicology and American Academy of Clinical Toxicology |work = Choosing Wisely: an initiative of the ABIM Foundation |url = http://www.choosingwisely.org/doctor-patient-lists/american-college-of-medical-toxicology-and-the-american-academy-of-clinical-toxicology/ |access-date = 5 December 2013}}</ref> The American College of Medical Toxicology and the American Academy of Clinical Toxicology warn the public that chelating drugs used in chelation therapy may have serious side effects, including liver and kidney damage, blood pressure changes, allergies and in some cases even death of the patient.<ref name="toxicfive"/>

===Cancer=== 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."<ref name=acs/>

===Cardiovascular disease=== Chelation therapy for heart disease began in the 1950s after anecdotal reports that people treated with chelation for heavy metal poisoning had experienced an unexpected relief from symptoms of angina.<ref name = "Rakel5">David Rakel, ''Integrative Medicine'' 5th edition, Elsevier, 2023.</ref> In the 1980s-2000s, its practitioners estimated that between 100,000 and 200,000 Americans per year were undergoing chelation therapy for heart disease, at a cost of about $5,000 per course of treatment.<ref name = "washingtonpost1985">{{cite news |first=Sally |last=Squires |url=https://wapo.st/4kToCY7 |title=Study Would Test Chelation's Claims |date=17 December 1985 |newspaper=The Washington Post}}</ref><ref name = "NYTTACT"/>

The American College of Cardiology and the Mayo Clinic do not currently endorse chelation therapy for heart disease.<ref name = "AAC2024">{{cite press release |publisher=American College of Cardiology |url=https://www.acc.org/About-ACC/Press-Releases/2024/04/07/14/01/chelation-therapy-does-not-improve-outcomes-after-heart-attack |title=Chelation Therapy Does Not Improve Outcomes after Heart Attack: Infusions reduce lead levels but show no effect on clinical endpoints |date=April 7, 2024}}</ref><ref>{{cite press release |publisher=Mayo Clinic |url=https://www.mayoclinic.org/diseases-conditions/heart-disease/expert-answers/chelation-therapy/faq-20157449 |title=Chelation therapy for heart disease: Does it work? |date=18 March 2025}}</ref> However, a large-scale clinical study published in 2012 did find a modest benefit from chelation therapy in improving outcomes for patients with a prior heart attack.<ref name = "NYTTACT">Andrew Pollack, [https://www.nytimes.com/2012/11/05/health/chelation-therapy-shows-slight-benefit-in-heart-disease-clinical-trial.html "Much-Debated Treatment for Heart Disease Shows Slight Benefit in Clinical Trial"], ''The New York Times'', Nov. 4, 2012.</ref>

In the 1990s and early 2000s, the weight of scientific evidence was against any benefit of chelation therapy for heart disease.<ref name="Ernst1997">{{cite journal |journal= Circulation |title= Chelation therapy for peripheral arterial occlusive disease: A systematic review |last= Ernst |first= E. |author-link= Edzard Ernst |volume= 96 |issue= 3 |pages= 1031–3 |pmid= 9264515 |doi= 10.1161/01.CIR.96.3.1031 |year= 1997|doi-access= free }}</ref><ref>{{cite journal |last1=Seely |first1= D.M. |last2= Wu |first2= P. |last3= Mills |first3= E.J. |title=EDTA chelation therapy for cardiovascular disease: A systematic review |journal=BMC Cardiovascular Disorders |volume=5|article-number=32 |year=2005 |pmid=16262904 |pmc=1282574 |doi=10.1186/1471-2261-5-32 |doi-access= free }}</ref>

In 1998, the U.S. Federal Trade Commission (FTC) charged a chelation-advocacy group, the "American College for Advancement in Medicine" (ACAM), with making false or unsubstantiated claims when they promoted chelation therapy for heart disease on their website and on a brochure they published. In December 1998, the FTC announced that it had secured a consent agreement barring ACAM from making claims that chelation therapy is effective against atherosclerosis or any other disease of the circulatory system.<ref name="FTC ACAM timeline" /><ref>{{cite press release |url= http://www.ftc.gov/news-events/press-releases/1998/12/medical-association-settles-false-advertising-charges-over |date=8 December 1998 |title= Medical Association Settles False Advertising Charges Over Promotion of 'Chelation Therapy' |author= Federal Trade Commission |access-date= 17 January 2014|author-link=Federal Trade Commission }}</ref>

However, in 2003-2012, the National Institutes of Health (NIH) sponsored a $30 million controlled trial of chelation therapy, conducted by their National Center for Complementary and Alternative Medicine (NCCAM). This was known as the Trial to Assess Chelation Therapy or TACT. In contrast to prior controlled studies that had produced negative findings, the TACT trial found that chelation therapy modestly improves outcomes for patients with a prior heart attack or history of heart attacks, and markedly improves outcomes if the patients were also diabetic.<ref name = "NYTTACT"/><ref name = "TACT">Lamas, G.A., et al. [https://jamanetwork.com/journals/jama/fullarticle/1672238 "Effect of disodium EDTA chelation regimen on cardiovascular events in patients with previous myocardial infarction: the TACT randomized trial"]. ''JAMA'' 309.12 (2013): 1241-1250.</ref><ref>{{cite journal|title=The Effect of an EDTA-based Chelation Regimen on Patients With Diabetes Mellitus and Prior Myocardial Infarction in the Trial to Assess Chelation Therapy (TACT)|journal=Circulation: Cardiovascular Quality and Outcomes|volume=7|issue=1|pages=15–24|publisher=CircoutComes|doi=10.1161/CIRCOUTCOMES.113.000663|pmid=24254885|pmc=4111470|year=2014|last1=Escolar|first1=E.|last2=Lamas|first2=G. A.|last3=Mark|first3=D. B.|last4=Boineau|first4=R.|last5=Goertz|first5=C.|last6=Rosenberg|first6=Y.|last7=Nahin|first7=R. L.|last8=Ouyang|first8=P.|last9=Rozema|first9=T.|last10=Magaziner|first10=A.|last11=Nahas|first11=R.|last12=Lewis|first12=E. F.|last13=Lindblad|first13=L.|last14=Lee|first14=K. L.}}</ref><ref>{{cite journal|url=http://www.clinicaltrials.gov/ct2/show/NCT00044213|title=Trial to Assess Chelation Therapy (TACT)|date=August 2013|journal=ClinicalTrials.gov|publisher=U.S. National Library of Medicine, National Institutes of Health, U.S. Dept. of Health and Human Services|issue=ClinicalTrials.gov identifier NCT00044213|last=Lamas|first=Gervasio}}</ref>

In the leadup to the TACT trial, 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.<ref>{{cite press release|url=http://nccam.nih.gov/news/2002/chelation/pressrelease.htm|title=NIH Launches Large Clinical Trial on EDTA Chelation Therapy for Coronary Artery Disease|work=NIH News|publisher=(NIH)|author1=National Institutes of Health (NIH)|author2-link=National Center for Complementary and Alternative Medicine|author2=National Center for Complementary and Alternative Medicine|author3=((National Heart, Lung, and Blood Institute))|date=7 August 2002|access-date=28 December 2008|archive-url=https://web.archive.org/web/20141228031307/http://nccam.nih.gov/news/2002/chelation/pressrelease.htm|archive-date=28 December 2014}}</ref> Patient enrollment was to be completed around July 2009<ref name="NCCAMQA">{{cite web |date=March 2007 |title=Questions and Answers: The NIH Trial of EDTA Chelation Therapy for Coronary Artery Disease |url=http://nccam.nih.gov/news/2002/chelation/q-and-a.htm |archive-url=https://web.archive.org/web/20071015044954/http://nccam.nih.gov/news/2002/chelation/q-and-a.htm <!-- Bot retrieved archive --> |archive-date=2007-10-15 |access-date=11 November 2007 |publisher=National Center for Complementary and Alternative Medicine (NCCAM), National Institutes of Health, U.S. Dept. of Health and Human Services |issue=NCCAM Pub. No. D166}}</ref> with final completion around July 2010,<ref name=TACT/> but enrollment in the trial was voluntarily suspended by organizers in September 2008 after the U.S. government's Office for Human Research Protections began investigating complaints such as inadequate informed consent.<ref name="ap2008">{{cite web |agency=Associated Press |url=https://www.cbc.ca/news/science/u-s-government-probes-chelation-heart-disease-study-1.707682 |title=U.S. government probes chelation-heart disease study |date=26 September 2008 |publisher=CBC}}</ref> At the time of suspension, the trial was criticized for other methodological flaws, including being conducted by "fringe" clinicians, and lacking prior Phase I and II studies.<ref name = "NYTTACT"/> The same critics claimed that previous controlled trials "found no evidence that chelation is superior to placebo for treatment of CAD [Coronary Artery Disease] or PVD [Peripheral Vascular Disease]," making the trial "unethical, dangerous, pointless, and wasteful."<ref name=Atwood2008/> Evidence of insurance fraud and other felony convictions among (chelation proponent) investigators further undermined the credibility of the trial.<ref name="NIH-Fraudsters">{{cite web|url=http://www.sciencebasedmedicine.org/nih-awards-30-million-research-dollars-to-convicted-felons-cliffs-notes-version/|title=NIH Awards $30 Million Research Dollars To Convicted Felons: Cliff's Notes Version|author=Jones, Valerie|date=2009-07-09|publisher=Science-Based Medicine|access-date=December 5, 2014}}</ref> However, the American College of Cardiology supported the trial.<ref name=ap2008/>

The final results of the TACT trial were published in November 2012. The study enrolled 1708 patients who were in stable condition, at least 50 years old, and had had a prior heart attack. The patients were divided into two groups, receiving chelation therapy by infusions of disodium EDTA, or receiving normal recommended therapy including statins and aspirin. The study found an 18% reduction in heart events (death, another heart attack, stroke, stenting or bypass, and hospitalization for heart pains) in the patients receiving chelation therapy. And in patients with diabetes mellitus, there was a 41% reduction in clinical events, including a 43% reduction in deaths over 5 years. However, the results barely achieved statistical significance.<ref name = "TACT"/>

An editorial published in the ''Journal of the American Medical Association'' said that "the study findings may provide novel hypotheses that merit further evaluation to help understand the pathophysiology of secondary prevention of vascular disease."<ref>{{cite journal|author1=Bauchner H|author2=Fontanarosa PB|author3=Golub RM|title=Evaluation of the Trial to Assess Chelation Therapy (TACT): The Scientific Process, Peer Review, and Editorial Scrutiny|journal=JAMA|year=2013|volume=309|issue=12|pages=1291–1292|doi=10.1001/jama.2013.2761|pmid=23532245|doi-access=free}}</ref> Critics of the study characterized it as showing no support for the use of chelation therapy in coronary heart disease, particularly the claims that chelation reduces the need for coronary bypass surgeries.<ref name="Attwood2012">{{cite web |url= http://www.sciencebasedmedicine.org/index.php/the-trial-to-assess-chelation-therapy-equivocal-as-predicted/ |title= The Trial to Assess Chelation Therapy: Equivocal as Predicted |first= Kimball |last= Atwood |author-link= Kimball Atwood |work= Science-Based Medicine |date= 4 November 2012}}</ref><ref name="Gorski2012">{{cite web |url= http://www.sciencebasedmedicine.org/index.php/the-result-of-the-trial-to-assess-chelation-therapy-tact-as-underwhelming-as-expected/ |title= The result of the Trial to Assess Chelation Therapy (TACT): As underwhelming as expected |first= David |last= Gorski |author-link= David Gorski |work= Science-Based Medicine |date= 5 November 2012}}</ref><ref>{{cite web | url = http://newsroom.heart.org/pr/aha/chelation-therapy-doesn-t-alter-240495.aspx | title = Chelation therapy doesn't alter quality of life in heart attack patients | date = 4 November 2012 | publisher = American Heart Association | access-date = 30 November 2012 | archive-url = https://web.archive.org/web/20121109153039/http://newsroom.heart.org/pr/aha/chelation-therapy-doesn-t-alter-240495.aspx | archive-date = 9 November 2012 | df = dmy-all }}</ref> After the TACT study, further controlled studies in 2015-2022 concluded with cautious endorsements of chelation therapy for heart disease, particularly in patients with diabetes mellitus and prior heart attacks.<ref name = "Ravalli2022">{{cite journal | last1=Ravalli | first1=Filippo | last2=Vela Parada | first2=Xavier | last3=Ujueta | first3=Francisco | last4=Pinotti | first4=Rachel | last5=Anstrom | first5=Kevin J. | last6=Lamas | first6=Gervasio A. | last7=Navas-Acien | first7=Ana | title=Chelation Therapy in Patients with Cardiovascular Disease: A Systematic Review | journal=Journal of the American Heart Association | date=2022 | volume=11 | issue=6 | article-number=e024648 | doi=10.1161/JAHA.121.024648 | pmid=35229619 | pmc=9075296 }}</ref><ref>{{cite journal | last1=Lamas | first1=Gervasio A. | title=Chelation Therapy | journal=Circulation | date=2015 | volume=131 | issue=21 | pages=e505-6 | doi=10.1161/CIRCULATIONAHA.114.010774 | pmid=26015468 | pmc=4448121 }}</ref> However, an attempt to replicate the results of the TACT trial in diabetics with prior heart attacks failed to find any benefit.<ref name = "TACT2">Lamas, G.A., et al. [https://jamanetwork.com/journals/jama/fullarticle/2822472 "Edetate disodium–based chelation for patients with a previous myocardial infarction and diabetes: TACT2 randomized clinical trial"]. ''JAMA'' 332.10 (2024): 794-803.</ref>

=== Autism === {{Main|Thiomersal controversy}}

According to Quackwatch, 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 risky process.<ref name="qw">{{cite web|url=https://www.quackwatch.org/01QuackeryRelatedTopics/chelationindex.html|title=Why Chelation Therapy Should Be Avoided|date=15 May 2004|publisher=Quackwatch|access-date=7 October 2013}}</ref> {{as of|2008}}, up to 7% of children with autism worldwide<ref name="Davis-review" /> had been subjected to chelation therapy.<ref name=stokstad>{{cite journal |journal=Science |year=2008 |volume=321 |issue=5887 |page=326 |title= Stalled trial for autism highlights dilemma of alternative treatments |last= Stokstad |first= E. |doi=10.1126/science.321.5887.326 |pmid=18635766|s2cid=206581219 |doi-access=free }}</ref> The death of two children in 2005 was caused by the administration of chelation treatments, according to the American Center for Disease Control. One of them had autism.<ref>{{Cite news|url=http://www.nbcnews.com/id/11640868/ns/health-childrens_health/t/fda-links-child-deaths-chelation-therapy/|title=FDA links child deaths to chelation therapy|date=February 3, 2006|work=NBC News |publisher=Associated Press|access-date=August 30, 2018|archive-url=https://web.archive.org/web/20180830103211/http://www.nbcnews.com/id/11640868/ns/health-childrens_health/t/fda-links-child-deaths-chelation-therapy/|archive-date=August 30, 2018}}</ref> Parents either have a doctor use a treatment for lead poisoning, or buy unregulated supplements, in particular DMSA and lipoic acid.<ref name=stokstad/> Aspies For Freedom, an autism rights organization, considers this use of chelation therapy unethical and potentially dangerous.<ref name='AspFF'>{{cite web|url=http://www.aspiesforfreedom.com/ |title=Aspies For Freedom |access-date=24 February 2009 |publisher=Aspies For Freedom |archive-url= https://web.archive.org/web/20100117120908/http://aspiesforfreedom.com/ |archive-date= 2010-01-17}}</ref> There is little to no credible scientific research that supports the use of chelation therapy for the effective treatment of autism.<ref name=Weber>{{cite journal |journal= Pediatric Clinics of North America |year=2007 |volume=54 |issue=6 |pages=983–1006 |title= Complementary and alternative medical therapies for attention-deficit/hyperactivity disorder and autism |last1= Weber |first1= W. |last2= Newmark |first2= S. |doi=10.1016/j.pcl.2007.09.006 |pmid=18061787}}</ref><ref name="Davis-review">{{cite journal | display-authors=4 | first1=Tonya N. | first10=Austin | last1=Davis | last10=Mulloy | title=Chelation treatment for autism spectrum disorders: A systematic review | last2=O'Reilly | first2=Mark | last3=Kang | first3=Soyeon | last4=Lang | first4=Russell | last5=Rispoli | first5=Mandy | last6=Sigafoos | first6=Jeff | last7=Lancioni | first7=Giulio | last8=Copeland | first8=Daelynn | last9=Attai | first9=Shanna | journal=Research in Autism Spectrum Disorders | year=2013 | volume=7 | issue=1 | pages=49–55 | doi=10.1016/j.rasd.2012.06.005 | quote=However, given the significant methodological limitations of these studies, the research reviewed here does not support the use of chelation as a treatment for ASD}}</ref><ref name="NYT_autism">{{cite news | url=https://query.nytimes.com/gst/fullpage.html?res=9C02E2D6123FF93AA25756C0A9629C8B63 | title=Panel finds no evidence to tie autism to vaccines | date=19 May 2004 | access-date=2008-02-01 | last=Blakeslee | first=Sandra | newspaper=New York Times}}</ref><ref>{{cite journal|pmc=3566884|year=2012|last1=Blaucok-Busch|first1=E.|last2=Amin|first2=O.R.|last3=Dessoki|first3=H.H.|last4=Rabah|first4=T.|title=Efficacy of DMSA therapy in a sample of Arab children with autistic spectrum disorder|volume=7|issue=3|pages=214–21|journal=Mædica|pmid=23400264}}</ref><ref>{{cite journal|pmc=2770991|last1=Adams|first1=J.B.|last2=Baral|first2=M.|last3=Geis|first3=E.|last4=Mitchell|first4=J.|last5=Ingram|first5=J.|last6=Hensley|first6=A.|last7=Zappia|first7=I.|last8=Newmark|first8=S.|last9=Gehn|first9=E.|last10=Rubin|first10=R.A.|last11=Mitchell|first11=K.|last12=Bradstreet|first12=J.|last13=El-Dahr|first13=J.|display-authors= 4 |title=Safety and efficacy of oral DMSA therapy for children with autism spectrum disorders: Part B - Behavioral results|volume=9|article-number=17|doi=10.1186/1472-6904-9-17|journal=BMC Clinical Pharmacology|year=2009|pmid=19852790 |doi-access=free }}</ref><ref>{{cite journal|pmc=2809421|year=2009|last1=Adams|first1=J.B.|last2=Baral|first2=M.|last3=Geis|first3=E.|last4=Mitchell|first4=J.|last5=Ingram|first5=J.|last6=Hensley|first6=A.|last7=Zappia|first7=I.|last8=Newmark|first8=S.|last9=Gehn|first9=E.|last10=Rubin|first10=R.A.|last11=Mitchell|first11=K.|last12=Bradstreet|first12=J.|last13=El-Dahr|first13=J.M.|author-link13=Jane El-Dahr |display-authors= 4 |title=The severity of autism is associated with toxic metal body burden and red blood cell glutathione levels|volume=2009|article-number=532640|doi=10.1155/2009/532640|journal=Journal of Toxicology|pmid=20107587|doi-access=free}}</ref><ref>{{cite journal|pmc=2774660|last1=Adams|first1=J.B.|last2=Baral|first2=M.|last3=Geis|first3=E.|last4=Mitchell|first4=J.|last5=Ingram|first5=J.|last6=Hensley|first6=A.|last7=Zappia|first7=I.|last8=Newmark|first8=S.|last9=Gehn|first9=E.|last10=Rubin|first10=R.A.|last11=Mitchell|first11=K.|last12=Bradstreet|first12=J.|last13=El-Dahr|first13=J. |display-authors= 4 |title=Safety and efficacy of oral DMSA therapy for children with autism spectrum disorders: Part A - Medical results|volume=9|article-number=16|doi=10.1186/1472-6904-9-16|journal=BMC Clinical Pharmacology|year=2009|pmid=19852789 |doi-access=free }}</ref>

=== Deaths from chelation therapy === In August 2005, a five-year-old boy with autism died while undergoing chelation therapy.<ref name=Atwood2008/> Others have also died while undergoing chelation therapy, including a three-year-old non-autistic girl and a non-autistic adult.<ref name=Atwood2008/> 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.<ref>{{cite journal |journal= Pediatrics |year= 2006 |volume= 118 |issue= 2 |pages= e534–6 |title= Deaths resulting from hypocalcemia after administration of edetate disodium: 2003–2005 |last1= Brown |first1= M.J. |last2= Willis |first2= T. |last3= Omalu |first3= B. |last4= Leiker |first4= R. |doi= 10.1542/peds.2006-0858 |pmid= 16882789 |s2cid= 28656831 |url= http://pediatrics.aappublications.org/cgi/content/full/118/2/e534 |access-date= 2007-11-13 |archive-date= 2009-07-27 |archive-url= https://web.archive.org/web/20090727080307/http://pediatrics.aappublications.org/cgi/content/full/118/2/e534 |url-access= subscription }}</ref><ref>{{cite journal |last1= Baxter |first1= A.J. |last2= Krenzelok |first2= E.P. |title= Pediatric fatality secondary to EDTA chelation |journal= Clinical Toxicology |volume= 46|issue= 10|pages= 1083–4|year=2008 |pmid=18949650 |doi=10.1080/15563650701261488|s2cid= 24576683 }}</ref> Only the three-year-old girl had been found to have an elevated blood lead level and resulting low iron levels and anemia, which is the conventional medical cause for administration of chelation therapy.<ref>{{cite journal |url= https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5508a3.htm |title= Deaths associated with hypocalcemia from chelation therapy - Texas, Pennsylvania, and Oregon, 2003-2005 |journal= Morbidity and Mortality Weekly Report |year= 2006 |volume= 55 |issue= 8 |pages= 204–7 |publisher= Centers for Disease Control and Prevention|pmid= 16511441 |author1= Centers for Disease Control Prevention (CDC) }}</ref>

According to protocol,<ref>{{Cite journal|last=Drugs|first=Committee on|date=1995-07-01|title=Treatment Guidelines for Lead Exposure in Children|url=https://pediatrics.aappublications.org/content/96/1/155|journal=Pediatrics|language=en|volume=96|issue=1|pages=155–159|doi=10.1542/peds.96.1.155 |issn=0031-4005|pmid=7596706|s2cid=2477907 |url-access=subscription}}</ref> EDTA should not be used in the treatment of children.<ref>{{cite book |last= Van der Schaar |first= Peter J. |title= Textbook of Clinical Metal Toxicology |publisher= International Board of Clinical Metal Toxicology |location= Leende, Netherlands |year= 2011 |edition= 10th }}{{Unreliable medical source|date=January 2014}}{{Full citation needed|date=January 2014}}</ref> More than 30 deaths have been recorded in association with IV-administered disodium EDTA since the 1970s.<ref name=Atwood2008/>

== History ==

Chelation therapy can be traced back to the early 1930s, when Ferdinand Münz, a German chemist working for I.G. Farben, first synthesized ethylenediaminetetraacetic acid (EDTA).<ref name=royalsociety>{{cite web|url=https://www.rsc.org/chemistryworld/podcast/CIIEcompounds/transcripts/EDTA.asp|title=Chemistry in its element: compounds|publisher=Royal Society of Chemistry|access-date=30 June 2014}}</ref> Munz was looking for a replacement for citric acid as a water softener.<ref name=royalsociety/> Chelation therapy itself began during World War II when chemists at the University of Oxford searched for an antidote for lewisite, an arsenic-based chemical weapon.<ref name=royalsociety/> The chemists learned that EDTA was particularly effective in treating lead poisoning.<ref name=royalsociety/>

Following World War II, chelation therapy was used to treat workers who had painted United States naval vessels with lead-based paints.<ref name=royalsociety/> In the 1950s, Norman Clarke Sr. was treating workers at a battery factory for lead poisoning when he noticed that some of his patients had improved angina pectoris following chelation therapy.<ref>{{cite journal | last1=Grebe | first1=Heidi Braun | last2=Gregory | first2=Philip J. | title=Inhibition of Warfarin Anticoagulation Associated with Chelation Therapy | journal=Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy | publisher=Wiley | volume=22 | issue=8 | year=2002 | issn=0277-0008 | doi=10.1592/phco.22.12.1067.33602 | pages=1067–1069| pmid=12173793 }}</ref> Clarke subsequently administered chelation therapy to patients with angina pectoris and other occlusive vascular disease and published his findings in ''The American Journal of the Medical Sciences'' in December 1956.<ref name=olszewer88>{{cite journal|title=EDTA Chelation Therapy in Chronic Degenerative Disease|first1=Efrain|last1=Olszewer|first2=James P.|last2=Carter|journal=Medical Hypotheses|volume=27|pages=41–49|year=1988|issue=1|doi=10.1016/0306-9877(88)90082-5|pmid=3144646}}</ref> He hypothesized that "EDTA could dissolve disease-causing plaques in the coronary systems of human beings."<ref>{{cite journal|title=Chelation therapy for cardiovascular disease. Review and commentary.|journal=Tex Heart Inst J|year=1997|volume=24|issue=2|pages=81–89|first=M R|last=Lewin|pmid=9205980|pmc=325409}}</ref> In a series of 283 patients treated by Clarke et al. From 1956 to 1960, 87% showed improvement in their symptomatology.<ref name=olszewer88/> Other early medical investigators made similar observations of EDTA's role in the treatment of cardiovascular disease (Bechtel, 1956; Bessman, 1957; Perry, 1961; Szekely, 1963; Wenig, 1958: and Wilder, 1962). However, later systemic reviews found that chelation was no better than placebo in treating heart disease.

In the 1960s, a chelating agent known as "British Anti-Lewisite" (BAL) was modified into DMSA, a related dithiol with far fewer side effects.<ref name=Kalia2005>{{cite journal |last1=Kalia |first1=Kiran |last2= Flora |first2= Swaran J.S. |title=Strategies for safe and effective therapeutic measures for chronic arsenic and lead poisoning |journal=Journal of Occupational Health |publisher= Japan Society for Occupational Health |volume=47 |issue=1 |pages=1–21 |year= 2005 |pmid=15703449 |doi= 10.1539/joh.47.1|url=https://www.jstage.jst.go.jp/article/joh/47/1/47_1_1/_pdf|doi-access=free |url-access=subscription }}</ref> DMSA quickly replaced both BAL and EDTA as the primary treatment for lead, arsenic and mercury poisoning in the United States. 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.<ref name=Kalia2005/> 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 United States, 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.<ref name='CDC_Hemo'>{{citation|chapter-url=https://www.cdc.gov/ncbddd/hemochromatosis/training/treatment/monitoring_treatment.htm |title=Hemochromatosis for healthcare professionals |chapter= Treatment & Management: Monitoring Treatment |access-date=29 March 2008 |date= 1 November 2007 |publisher= Division of Nutrition and Physical Activity, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, U.S. Dept. of Health and Human Services |archive-url = https://web.archive.org/web/20080224192906/http://www.cdc.gov/ncbddd/hemochromatosis/training/treatment/monitoring_treatment.htm <!-- Bot retrieved archive --> |archive-date = 2008-02-24}}</ref> 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.

In 1973, a group of practicing physicians created the Academy of Medical Preventics, later renamed the American College for Advancement in Medicine (ACAM).<ref name="olszewer88" /> The academy trains and certifies physicians in the safe administration of chelation therapy.<ref>{{cite web |first=Ronald L. |last=Hoffman |date=February 2014 |title=The facts and fictions of chelation therapy |url=http://issuu.com/clinicaladvisor/docs/february_2014_issue/25 |access-date=30 June 2014 |publisher=The Clinical Advisor}}</ref> Members of the academy continued to use EDTA therapy for the treatment of vascular disease and developed safer administration protocols.<ref name="olszewer88" /> However, in 1998 the U.S. Federal Trade Commission (FTC) pursued the 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.<ref name= "FTC ACAM timeline">{{cite web | url = http://www.ftc.gov/os/1999/07/9623147c3881acamcmp.htm | title = American College for Advancement in Medicine: Case Timeline |volume= FTC Matter/File Number: 962 3147 |issue= Docket Number:C–3882 | publisher = Federal Trade Commission (FTC) | date = 13 July 1999 | access-date = 1 July 2010 |type= FTC Case Timeline with links to documents }}</ref> In 1999, the ACAM agreed to stop presenting chelation therapy as effective in treating heart disease, avoiding legal proceedings.<ref>{{cite web | url = http://www.ftc.gov/sites/default/files/documents/cases/1998/12/9623147agr.htm | title = United States of America Federal Trade Commission In the Matter of American College for Advancement in Medicine, a corporation. File no. 962 3147. '''Agreement Containing Consent Order''' | publisher = Federal Trade Commission | date = 12 January 1998 | access-date = 1 July 2010}} {{cite web |url= http://www.ftc.gov/sites/default/files/documents/cases/1998/12/9623147att.htm |title= Attachment A |type= Notification letter}}</ref> 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."<ref name=FDA_2010_warning/>

== See also == * List of ineffective cancer treatments * Detoxification * Chelation of heavy metals in autism

== References == {{reflist|30em}}

== External links == * [https://www.quackwatch.org/01QuackeryRelatedTopics/chelation.html Chelation Therapy: Unproven Claims and Unsound Theories] - Quackwatch

{{Chelating agents}} {{Toxicology}} {{Autism spectrum}} {{Unproven and disproven cancer treatments}}

Category:Detoxification Category:Alternative therapies for developmental and learning disabilities Category:Alternative cancer treatments Category:Alternative detoxification Category:Alternative medical treatments Category:Autism pseudoscience Category:Toxic effects of metals Category:Metal metabolism