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'''Chelation therapy''' is the administration of [[chelation|chelating agent]]s to remove [[heavy metals]] from the body. Chelation therapy has a long history of use in clinical toxicology.<ref>http://www.poison.org/current/chelation%20therapy.htm</ref> For the most common forms of heavy metal intoxication—those involving [[lead]], [[arsenic]] or [[Mercury (element)|mercury]]—the [[standard of care]] a number of chelating agents are available. DMSA [[dimercaptosuccinic acid]] has been recommended for the treatment of lead poisoning in children by Poison Centers around the world.<ref>Chisholm JJ. Safety and Efficacy of Meso-2,3-Dimercaptosuccinic acid (DMSA)in Children with Elevated Blood Lead Concentrations. Clin.Tox.2000, Vol.38,No.4,365-375</ref> Other [[chelation|chelating agents]], such as [[2,3-dimercapto-1-propanesulfonic acid]] (DMPS) and [[lipoic acid|alpha lipoic acid]] (ALA), are used in [[medicine|conventional]] and [[alternative medicine]].
'''Chelation therapy''' is the administration of [[chelation|chelating agent]]s to remove [[heavy metals]] from the body. Chelation therapy has a long history of use in clinical toxicology.<ref>http://www.poison.org/current/chelation%20therapy.htm</ref> For the most common forms of heavy metal intoxication—those involving [[lead]], [[arsenic]] or [[Mercury (element)|mercury]]—the [[standard of care]] a number of chelating agents are available. DMSA [[dimercaptosuccinic acid]] has been recommended for the treatment of lead poisoning in children by Poison Centers around the world.<ref>{{cite journal |author=Chisolm JJ |title=Safety and efficacy of meso-2,3-dimercaptosuccinic acid (DMSA) in children with elevated blood lead concentrations |journal=J. Toxicol. Clin. Toxicol. |volume=38 |issue=4 |pages=365–75 |year=2000 |pmid=10930052 }}</ref> Other [[chelation|chelating agents]], such as [[2,3-dimercapto-1-propanesulfonic acid]] (DMPS) and [[lipoic acid|alpha lipoic acid]] (ALA), are used in [[medicine|conventional]] and [[alternative medicine]].


No approved medical research has found any benefits to chelation therapy for any use other than removal of heavy metals from the body,<ref name="AHA"/> 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."<ref name=FDA_2010_warning/>
No approved medical research has found any benefits to chelation therapy for any use other than removal of heavy metals from the body,<ref name="AHA"/> 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."<ref name=FDA_2010_warning/>
Line 107: Line 107:
==Side effects and safety concerns==
==Side effects and safety concerns==
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. 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.<ref>Heyl.Dimaval Monograph 2008</ref> The EDTAs when used according to protocol are equally safe. Most important is the correct use and a slow infusion time (1gr/hr or less of NaEDTA or CaEDTA). Side effects are largely avoided if general medical caution is exercised. Most importantly, renal function has to be checked before any chelation substance is used.<ref>Blaurock-Busch E. Toxic Metals and Antidotes.2012>[http://www.microtraceminerals.com/en/books-by-eblaurock-busch/e-book-chelation/</ref>
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. 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.<ref>Heyl.Dimaval Monograph 2008</ref> The EDTAs when used according to protocol are equally safe. Most important is the correct use and a slow infusion time (1gr/hr or less of NaEDTA or CaEDTA). Side effects are largely avoided if general medical caution is exercised. Most importantly, renal function has to be checked before any chelation substance is used.<ref>Blaurock-Busch E. Toxic Metals and Antidotes.2012>[http://www.microtraceminerals.com/en/books-by-eblaurock-busch/e-book-chelation/</ref>
2007 research with lab rats indicates giving chelating agent DMSA to rats ''without'' high levels of lead may cause lasting cognitive damage.<ref>[http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17384765 Succimer Chelation Improves Learning, Attention, and Arousal Regulation in Lead-Exposed Rats but Produces Lasting Cognitive Impairment in the Absence of Lead Exposure]</ref> The German Environmental Agency (Umweltbundesamt)listed DMSA along with DMPS as the two most useful and safe chelating agents available at this time.<ref>Bundesgesundheitsblatt42(19),1999,823-824</ref> Flora and Pachauri state'Chelation treatment is the preferred medica treatment for reducing toxic effects of metals.'<ref>Flora S.,Pachauri V.Chelation in Metal Intoxication.Int.J.Environ Res Publ Health 2010.7:2745-2788</ref>
2007 research with lab rats indicates giving chelating agent DMSA to rats ''without'' high levels of lead may cause lasting cognitive damage.<ref>{{cite journal |author=Stangle DE, Smith DR, Beaudin SA, Strawderman MS, Levitsky DA, Strupp BJ |title=Succimer chelation improves learning, attention, and arousal regulation in lead-exposed rats but produces lasting cognitive impairment in the absence of lead exposure |journal=Environ. Health Perspect. |volume=115 |issue=2 |pages=201–9 |year=2007 |month=February |pmid=17384765 |pmc=1831518 |doi=10.1289/ehp.9263 |url=http://ehponline.org/article/info:doi/10.1289/ehp.9263}}</ref> The German Environmental Agency (Umweltbundesamt)listed DMSA along with DMPS as the two most useful and safe chelating agents available at this time.<ref>{{cite journal |title=Bekanntmachung des Umweltbundesamtes Einsatz von Chelatbildnern in der Umweltmedizin? |journal=Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz |volume=42 |issue=10 |pages=823–4 |year=1999 |doi=10.1007/s001030050288 |url=http://link.springer.com/article/10.1007%2Fs001030050288}}</ref> Flora and Pachauri state 'Chelation treatment is the preferred medica treatment for reducing toxic effects of metals.'<ref>{{cite journal |author=Flora SJ, Pachauri V |title=Chelation in metal intoxication |journal=Int J Environ Res Public Health |volume=7 |issue=7 |pages=2745–88 |year=2010 |month=July |pmid=20717537 |pmc=2922724 |doi=10.3390/ijerph7072745 }}</ref>


Chelation therapy can be hazardous when used inappropriately. In August 2005, chelation therapy conducted by an [[American College for Advancement in Medicine | ACAM]] member killed a 5-year-old boy with autism;<ref name=Atwood2008/> 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.<ref name=hypocalcemia>Hazards of chelation therapy:
Chelation therapy can be hazardous when used inappropriately. In August 2005, chelation therapy conducted by an [[American College for Advancement in Medicine | ACAM]] member killed a 5-year-old boy with autism;<ref name=Atwood2008/> 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.<ref name=hypocalcemia>Hazards of chelation therapy:

Revision as of 13:11, 22 November 2012

Chelation therapy is the administration of chelating agents to remove heavy metals from the body. Chelation therapy has a long history of use in clinical toxicology.[1] For the most common forms of heavy metal intoxication—those involving lead, arsenic or mercury—the standard of care a number of chelating agents are available. DMSA dimercaptosuccinic acid has been recommended for the treatment of lead poisoning in children by Poison Centers around the world.[2] Other chelating agents, such as 2,3-dimercapto-1-propanesulfonic acid (DMPS) and alpha lipoic acid (ALA), are used in conventional and alternative medicine.

No approved medical research has found any benefits to chelation therapy for any use other than removal of heavy metals from the body,[3] and the 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."[4]

History

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. 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.[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.

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

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]

One example of successful chelation therapy is the case of Harold McCluskey, a nuclear worker who became badly contaminated 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 follow:

Chelator Used in
Dimercaprol (British anti-Lewisite; BAL)
Dimercaptosuccinic acid (DMSA)
Dimercapto-propane sulfonate (DMPS)
  • severe acute arsenic poisoning[11]
  • severe acute mercury poisoning[11]
Penicillamine Mainly in:

Occasionally adjunctive therapy in:

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

Medically diagnosed heavy metal poisoning

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.[12]

Unapproved use in alternative medicine

Alternative medicine uses chelation therapy as a non-standard treatment for some ailments, including heart disease and autism.[13][14] 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. 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.[15] 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.[16] The proposed study has been criticized as unethical, unnecessary and dangerous, with multiple studies conducted in the past demonstrating that it provides no benefits.[17]

Heart disease

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).[3] 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.[15] Patient enrollment was to be completed around July 2009[7] with final completion around July 2010,[18] 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.[17] 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.[17] Atwood et al. have argued that methodological flaws and lack of prior probability make this trial "unethical, dangerous, pointless, and wasteful."[17]

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."[3] 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.[20] 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.'[21]

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."[22]

The final results of TACT, published in November 2012, showed, as expected, no support for the use of chelation therapy in coronary heart disease, particularly the claims to reduce the need for coronary artery bypass grafting.[23][24]

Autism

Main article: Thiomersal controversy

Based on the discredited[25] hypothesis that mercury poisoning may trigger the symptoms of autism,[26] chelation therapy is widely used by alternative therapists to treat autism, with some surveys suggesting 2–8% of children with autism have had the therapy.[27] Parents either have a doctor use a treatment for lead poisoning, or buy unregulated supplements.[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.[25][29][30][31] There is no scientific support for chelation therapy as a treatment for autism.[14][32]

In August 2005, a young autistic boy died while receiving chelation therapy for autism.[33] The doctor responsible had his license to practise medicine suspended and was barred from chelating minors in future.[34]

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.[35]

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.[36][37]

The use of chelation therapy by alternative medicine practitioners for behavioural and other disorders is considered pseudoscientific as there is no proof that it is effective.[38]

Prevalence

The American College for Advancement in Medicine estimates that 800,000 patient visits for chelation therapy were made in the United States in 1997.[39]

Side effects and safety concerns

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. 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.[40] The EDTAs when used according to protocol are equally safe. Most important is the correct use and a slow infusion time (1gr/hr or less of NaEDTA or CaEDTA). Side effects are largely avoided if general medical caution is exercised. Most importantly, renal function has to be checked before any chelation substance is used.[41] 2007 research with lab rats indicates giving chelating agent DMSA to rats without high levels of lead may cause lasting cognitive damage.[42] The German Environmental Agency (Umweltbundesamt)listed DMSA along with DMPS as the two most useful and safe chelating agents available at this time.[43] Flora and Pachauri state 'Chelation treatment is the preferred medica treatment for reducing toxic effects of metals.'[44]

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;[17] 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.[45] 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.[46] According to protocol, EDTA should not be used in the treatment of children.[47] More than 30 deaths have been recorded in association with IV-administered disodium EDTA since the 1970s.[17]

References

  1. ^ http://www.poison.org/current/chelation%20therapy.htm
  2. ^ Chisolm JJ (2000). "Safety and efficacy of meso-2,3-dimercaptosuccinic acid (DMSA) in children with elevated blood lead concentrations". J. Toxicol. Clin. Toxicol. 38 (4): 365–75. PMID 10930052.
  3. ^ a b c "American Heart Association: Chelation Therapy". Retrieved 2008-04-03.
  4. ^ a b c FDA issues warnings to marketers of unapproved ‘chelation’ products. U.S. Food and Drug Administration (FDA), Press Release, Oct. 14, 2010
  5. ^ a b Kalia K, Flora SJ (2005). "Strategies for safe and effective therapeutic measures for chronic arsenic and lead poisoning". J Occup Health. 47 (1): 1–21. doi:10.1539/joh.47.1. PMID 15703449. {{cite journal}}: Unknown parameter |month= ignored (help)
  6. ^ "Hemochromatosis: Monitoring and Treatment". National Center on Birth Defects and Developmental Disabilities (NCBDDD). 2007-11-01. Archived from the original on 2008-02-24. Retrieved 2008-03-29.
  7. ^ a b "Questions and Answers: The NIH Trial of EDTA Chelation Therapy for Coronary Artery Disease". National Center for Complementary and Alternative Medicine (NCCAM). Archived from the original on 2007-10-15. Retrieved 2007-11-11.
  8. ^ "United States of America Federal Trade Commission In the Matter of American College for Advancement in Medicine, a corporation". Federal Trade Commission. 1999-07-01. Retrieved 2010-07-01.
  9. ^ "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". Federal Trade Commission. 1998-12-01. Retrieved 2010-07-01. notification letter
  10. ^ Natural Standard Professional Monograph. http://www.naturalstandard.com/monographs/monoframeset.asp?monograph=/monographs/alternativemodalities/chelation.asp%3Fprintversion%3Dtrue Accessed June 16, 2009.
  11. ^ a b c d e f g h i j k l m n o p Page 481-483 in: Masters, Susan B.; Trevor, Anthony J.; Katzung, Bertram G. (2008). Katzung & Trevor's pharmacology: examination & board review. s.l: McGraw Hill Medical. ISBN 0-07-148869-3.{{cite book}}: CS1 maint: multiple names: authors list (link)
  12. ^ Bridges, S. (2006). The promise of chelation. Mothering , 54-61.
  13. ^ Ernst E (2000). "Chelation therapy for coronary heart disease: An overview of all clinical investigations". Am. Heart J. 140 (1): 139–41. doi:10.1067/mhj.2000.107548. PMID 10874275.
  14. ^ a b Weber W, Newmark S (2007). "Complementary and alternative medical therapies for attention-deficit/hyperactivity disorder and autism". Pediatr Clin North Am. 54 (6): 983–1006. doi:10.1016/j.pcl.2007.09.006. PMID 18061787.
  15. ^ a b NCCAM.Trial to assess chelation therapy
  16. ^ NIH Launches Large Clinical Trial on EDTA Chelation Therapy for Coronary Artery Disease [NCCAM Health Information]
  17. ^ a b c d e f Atwood KC, Woeckner E, Baratz RS, Sampson WI (2008). "Why the NIH Trial to Assess Chelation Therapy (TACT) Should Be Abandoned". Medscape J Med. 10 (5): 115. PMC 2438277. PMID 18596934.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  18. ^ "Trial to Assess Chelation Therapy (TACT)". U.S. National Institutes of Health. Retrieved 2007-11-11.
  19. ^ "Government probes chelation-heart disease study". Washington Post (AP). Retrieved 2008-09-26. [dead link]
  20. ^ Seely DM, Wu P, Mills EJ (2005). "EDTA chelation therapy for cardiovascular disease: a systematic review". BMC Cardiovasc Disord. 5: 32. doi:10.1186/1471-2261-5-32. PMC 1282574. PMID 16262904.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  21. ^ Chelation therapy for heart disease: Results - MayoClinic.com
  22. ^ EDTA chelation for cardiovascular disease. Montana Board of Medical Examiners, Position paper, May 14, 2009
  23. ^ The Trial to Assess Chelation Therapy: Equivocal as Predicted, Kimball Attwood, Science Based Medicine, 4 Nov 2012
  24. ^ The result of the Trial to Assess Chelation Therapy (TACT): As underwhelming as expected, David Gorski, Science Based medicine, 5 Nov 2012
  25. ^ a b Immunization Safety Review Committee, Board on Health Promotion and Disease Prevention, Institute of Medicine (2004). Immunization Safety Review: Vaccines and Autism. Washington, DC: The National Academies Press. ISBN 0-309-09237-X.{{cite book}}: CS1 maint: multiple names: authors list (link) Cite error: The named reference "IOM2004" was defined multiple times with different content (see the help page).
  26. ^ Bernard S, Enayati A, Roger H, Binstock T, Redwood L (2002). "The role of mercury in the pathogenesis of autism" (PDF). Mol Psychiatry. 7 (Suppl 2): S42–3. doi:10.1038/sj.mp.4001177. PMID 12142947.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  27. ^ a b Stokstad E (2008). "Stalled trial for autism highlights dilemma of alternative treatments". Science. 321 (5887): 326. doi:10.1126/science.321.5887.326. PMID 18635766.
  28. ^ "Aspies For Freedom". Aspies For Freedom. Retrieved 2009-02-24.
  29. ^ Doja A, Roberts W (2006). "Immunizations and autism: a review of the literature". Can J Neurol Sci. 33 (4): 341–6. PMID 17168158.
  30. ^ Thompson WW, Price C, Goodson B; et al. (2007). "Early thimerosal exposure and neuropsychological outcomes at 7 to 10 years". N Engl J Med. 357 (13): 1281–92. doi:10.1056/NEJMoa071434. PMID 17898097. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  31. ^ Rutter M (2005). "Incidence of autism spectrum disorders: changes over time and their meaning". Acta Paediatr. 94 (1): 2–15. doi:10.1111/j.1651-2227.2005.tb01779.x. PMID 15858952.
  32. ^ Blakeslee, Sandra (2004-05-19). "Panel Finds No Evidence To Tie Autism To Vaccines". New York Times. Retrieved 2008-02-01. "An examination of scientific studies worldwide has found no convincing evidence that vaccines cause autism, according to a committee of experts appointed by the Institute of Medicine."
  33. ^ Boy dies during autism treatment
  34. ^ Casewatch
  35. ^ Knudtson ML, Wyse DG, Galbraith PD; 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. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  36. ^ "American College for Advancement in Medicine, File No. 962 3147, Docket No. C-3882". Federal Trade Commission. Retrieved 2007-11-11.
  37. ^ "Medical Association Settles False Advertising Charges Over Promotion of 'Chelation Therapy'". Quackwatch. December 8, 1998. Retrieved 2007-11-11.
  38. ^ Behavior Analysis Association, University of Michigan
  39. ^ "Physician Group Backs New NIH Chelation Therapy Study For Heart Disease" (Press release). American College for Advancement in Medicine. August 14, 2002. Retrieved 2007-11-11.
  40. ^ Heyl.Dimaval Monograph 2008
  41. ^ Blaurock-Busch E. Toxic Metals and Antidotes.2012>[http://www.microtraceminerals.com/en/books-by-eblaurock-busch/e-book-chelation/
  42. ^ Stangle DE, Smith DR, Beaudin SA, Strawderman MS, Levitsky DA, Strupp BJ (2007). "Succimer chelation improves learning, attention, and arousal regulation in lead-exposed rats but produces lasting cognitive impairment in the absence of lead exposure". Environ. Health Perspect. 115 (2): 201–9. doi:10.1289/ehp.9263. PMC 1831518. PMID 17384765. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  43. ^ "Bekanntmachung des Umweltbundesamtes Einsatz von Chelatbildnern in der Umweltmedizin?". Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz. 42 (10): 823–4. 1999. doi:10.1007/s001030050288.
  44. ^ Flora SJ, Pachauri V (2010). "Chelation in metal intoxication". Int J Environ Res Public Health. 7 (7): 2745–88. doi:10.3390/ijerph7072745. PMC 2922724. PMID 20717537. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: unflagged free DOI (link)
  45. ^ Hazards of chelation therapy:
  46. ^ Deaths Associated with Hypocalcemia from Chelation Therapy - Texas, Pennsylvania, and Oregon, 2003-2005
  47. ^ Van der Schaar P. Textbook of Clinical Metal Toxicology. IBCMT 2011

External links

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