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Chelation therapy is a medical procedure that involves the administration of chelating agents to remove heavy metals from the body. Chelation therapy has a long history of use in clinical
toxicology Toxicology is a scientific discipline, overlapping with biology, chemistry, pharmacology, and medicine, that involves the study of the adverse effects of chemical substances on living organisms and the practice of diagnosing and treating e ...
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. 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 must be administered with care as it has a number of possible side effects, including death. 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. Over-the-counter chelation products are not approved for sale in the United States.


Medical uses

Chelation therapy is the preferred medical treatment for
metal poisoning Metal toxicity or metal poisoning is the toxic effect of certain metals in certain forms and doses on life. Some metals are toxic when they form poisonous soluble compounds. Certain metals have no biological role, i.e. are not essential minerals, ...
, including acute mercury,
iron Iron () is a chemical element with symbol Fe (from la, ferrum) and atomic number 26. It is a metal that belongs to the first transition series and group 8 of the periodic table. It is, by mass, the most common element on Earth, right in ...
(including in cases of
sickle-cell disease Sickle cell disease (SCD) is a group of blood disorders typically inherited from a person's parents. The most common type is known as sickle cell anaemia. It results in an abnormality in the oxygen-carrying protein haemoglobin found in red ...
and thalassemia),
arsenic Arsenic is a chemical element with the symbol As and atomic number 33. Arsenic occurs in many minerals, usually in combination with sulfur and metals, but also as a pure elemental crystal. Arsenic is a metalloid. It has various allotropes, b ...
,
lead Lead is a chemical element with the symbol Pb (from the Latin ) and atomic number 82. It is a heavy metal that is denser than most common materials. Lead is soft and malleable, and also has a relatively low melting point. When freshly cut, ...
,
uranium Uranium is a chemical element with the symbol U and atomic number 92. It is a silvery-grey metal in the actinide series of the periodic table. A uranium atom has 92 protons and 92 electrons, of which 6 are valence electrons. Uranium is weak ...
,
plutonium Plutonium is a radioactive chemical element with the symbol Pu and atomic number 94. It is an actinide metal of silvery-gray appearance that tarnishes when exposed to air, and forms a dull coating when oxidized. The element normally exh ...
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.


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 –
lead Lead is a chemical element with the symbol Pb (from the Latin ) and atomic number 82. It is a heavy metal that is denser than most common materials. Lead is soft and malleable, and also has a relatively low melting point. When freshly cut, ...
,
arsenic Arsenic is a chemical element with the symbol As and atomic number 33. Arsenic occurs in many minerals, usually in combination with sulfur and metals, but also as a pure elemental crystal. Arsenic is a metalloid. It has various allotropes, b ...
, or mercury – a number of chelating agents are available.
Dimercaptosuccinic acid Succimer, sold under the brand name Chemet among others, is a medication used to treat lead, mercury, and arsenic poisoning. When radiolabeled with technetium-99m, it is used in a number of types of diagnostic testing. A full course is 19 day ...
(DMSA) has been recommended for the treatment of lead poisoning in children by poison control centers around the world. Other
chelating agents Chelation is a type of bonding of ions and molecules to metal ions. It involves the formation or presence of two or more separate coordinate bonds between a polydentate (multiple bonded) ligand and a single central metal atom. These ligands a ...
, such as 2,3-dimercaptopropanesulfonic acid (DMPS) and
alpha lipoic acid Lipoic acid (LA), also known as α-lipoic acid, alpha-lipoic acid (ALA) and thioctic acid, is an organosulfur compound derived from caprylic acid (octanoic acid). ALA is made in animals normally, and is essential for aerobic metabolism. It is ...
(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. The German Environmental Agency (Umweltbundesamt) listed DMSA and DMPS as the two most useful and safe chelating agents available.


Side effects

When used properly in response to a diagnosis of harm from
metal toxicity Metal toxicity or metal poisoning is the toxic effect of certain metals in certain forms and doses on life. Some metals are toxic when they form poisonous soluble compounds. Certain metals have no biological role, i.e. are not essential minerals, o ...
, side effects of chelation therapy include dehydration,
low blood calcium Hypocalcemia is a medical condition characterized by low calcium levels in the blood serum. The normal range of blood calcium is typically between 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L) while levels less than 2.1 mmol ...
, harm to kidneys, increased enzymes as would be detected in
liver function tests Liver function tests (LFTs or LFs), also referred to as a hepatic panel, are groups of blood tests that provide information about the state of a patient's liver. These tests include prothrombin time (PT/INR), activated partial thromboplastin ti ...
, allergic reactions, and lowered levels of dietary elements., which cites * * * When administered inappropriately, there are the additional risks of
hypocalcaemia Hypocalcemia is a medical condition characterized by low calcium levels in the blood serum. The normal range of blood calcium is typically between 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L) while levels less than 2.1 mmol ...
(low calcium levels), neurodevelopmental disorders, and death.


History

Chelation therapy can be traced back to the early 1930s, when
Ferdinand Münz Ferdinand Münz (1888-1969) was an Austrian chemist who first synthesized EDTA (ethylenediaminetetraacetic acid) at the IG Farben in 1935, patented both in Germany (anonymously) and in the USA (with his name), with the aim of producing a citric a ...
, a German chemist working for
I.G. Farben Interessengemeinschaft Farbenindustrie AG (), commonly known as IG Farben (German for 'IG Dyestuffs'), was a German chemical and pharmaceutical conglomerate. Formed in 1925 from a merger of six chemical companies—BASF, Bayer, Hoechst, Agfa, ...
, first synthesized ethylenediaminetetraacetic acid (EDTA). Munz was looking for a replacement for
citric acid Citric acid is an organic compound with the chemical formula HOC(CO2H)(CH2CO2H)2. It is a colorless weak organic acid. It occurs naturally in citrus fruits. In biochemistry, it is an intermediate in the citric acid cycle, which occurs in ...
as a water softener. Chelation therapy itself began during
World War II World War II or the Second World War, often abbreviated as WWII or WW2, was a world war that lasted from 1939 to 1945. It involved the World War II by country, vast majority of the world's countries—including all of the great power ...
when chemists at the
University of Oxford , mottoeng = The Lord is my light , established = , endowment = £6.1 billion (including colleges) (2019) , budget = £2.145 billion (2019–20) , chancellor ...
searched for an antidote for lewisite, an
arsenic Arsenic is a chemical element with the symbol As and atomic number 33. Arsenic occurs in many minerals, usually in combination with sulfur and metals, but also as a pure elemental crystal. Arsenic is a metalloid. It has various allotropes, b ...
-based chemical weapon. The chemists learned that EDTA was particularly effective in treating lead poisoning. Following World War II, chelation therapy was used to treat workers who had painted United States naval vessels with lead-based paints. 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. 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. He hypothesized that "EDTA could dissolve disease-causing plaques in the coronary systems of human beings." In a series of 283 patients treated by Clarke et al. From 1956 to 1960, 87% showed improvement in their symptomatology. 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). In 1973, a group of practicing physicians created the Academy of Medical Preventics (now the American College for Advancement in Medicine). The academy trains and certifies physicians in the safe administration of chelation therapy. Members of the academy continued to use EDTA therapy for the treatment of vascular disease and developed safer administration protocols. In the 1960s, BAL was modified into
DMSA Succimer, sold under the brand name Chemet among others, is a medication used to treat lead, mercury, and arsenic poisoning. When radiolabeled with technetium-99m, it is used in a number of types of diagnostic testing. A full course is 19 day ...
, a related dithiol with far fewer side effects. 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. 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 Phlebotomy is the process of making a puncture in a vein, usually in the arm, with a cannula for the purpose of drawing blood. The procedure itself is known as a venipuncture, which is also used for intravenous therapy. A person who performs ...
to treat excess iron stores in people with haemochromatosis. Other chelating agents have been discovered. They all function by making several chemical bonds with metal ions, thus rendering them much less chemically reactive. The resulting complex is water-soluble, allowing it to enter the bloodstream and be excreted harmlessly. Calcium-disodium EDTA chelation has been studied by the U.S. National Center for Complementary and Alternative Medicine for treating coronary disease. In 1998, the U.S. Federal Trade Commission (FTC) pursued the American College for Advancement in Medicine (ACAM), an organization that promotes "complementary, alternative and integrative medicine" over the claims made regarding the treatment of atherosclerosis in advertisements for EDTA chelation therapy. The FTC concluded that there was a lack of scientific studies to support these claims and that the statements by the ACAM were false. In 1999, the ACAM agreed to stop presenting chelation therapy as effective in treating heart disease, avoiding legal proceedings. In 2010 the 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."


Society and culture

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. In August 2005, doctor error led to the death of a five-year-old boy with autism who was undergoing chelation therapy. Others, including a three-year-old nonautistic girl and a nonautistic adult, have died while undergoing chelation therapy. 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. Only the 3-year-old girl had found to have an elevated
blood lead level Blood lead level (BLL), is a measure of the amount of lead in the blood. Lead is a toxic heavy metal and can cause neurological damage, especially among children, at any detectable level. High lead levels cause decreased vitamin D and haemog ...
and resulting low iron levels and anemia, which is the conventional medical cause for administration of chelation therapy. According to protocol, EDTA should not be used in the treatment of children. More than 30 deaths have been recorded in association with IV-administered disodium EDTA since the 1970s.


Use in alternative medicine

In alternative medicine, some practitioners claim chelation therapy can treat a variety of ailments, including heart disease and autism. The use of chelation therapy by alternative medicine practitioners for behavioral and other disorders is considered pseudoscientific; there is no proof that it is effective. Chelation therapy prior to heavy metal testing can artificially raise urinary heavy metal concentrations ("provoked" urine testing) and lead to inappropriate and unnecessary treatment. The
American College of Medical Toxicology The American College of Medical Toxicology is a professional association of medical toxicologists that was founded in 1993. Its aim is to support quality medical care for persons exposed to potentially harmful chemicals (whether medications, drug ...
and the
American Academy of Clinical Toxicology The American Academy of Clinical Toxicology (AACT) is a non-profit multidisciplinary health association that promotes research, education, prevention, and treatment of diseases caused by chemicals. Its membership consists of clinical and resear ...
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.


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."


Cardiovascular disease

According to the findings of a 1997 systematic review, EDTA chelation therapy is not effective as a treatment for coronary artery disease and this use is not approved in the United States by the US Food and Drug Administration (FDA). The American Heart Association stated in 1997 that there is "no scientific evidence to demonstrate any benefit from this form of therapy." The United States Food and Drug Administration (FDA), the
National Institutes of Health The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the lat ...
(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." They speculate that any improvement among heart patients undergoing chelation therapy can be attributed to the placebo effect and generally recommended lifestyle changes such as "quitting smoking, losing weight, eating more fruits and vegetables, avoiding foods high in saturated fats and exercising regularly." They also are concerned that patients could put off proven treatments for heart disease like drugs or surgery. A systematic review published in 2005 found that controlled scientific studies did not support chelation therapy for heart disease. It found that very small trials and uncontrolled descriptive studies have reported benefits while larger controlled studies have found results no better than placebo. 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." 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. NCCAM Director Stephen E. Straus cited the "widespread use of chelation therapy in lieu of established therapies, the lack of adequate prior research to verify its safety and effectiveness, and the overall impact of coronary artery disease" as factors motivating the trial. The study has been criticized by some who said it was unethical, unnecessary and dangerous, and that multiple studies conducted prior to it demonstrated that the treatment provides no benefit. The US National Center for Complementary and Alternative Medicine began the Trial to Assess Chelation Therapy (TACT) in 2003. Patient enrollment was to be completed around July 2009 with final completion around July 2010, but enrollment in the trial was voluntarily suspended by organizers in September 2008 after the
Office for Human Research Protections The Office for Human Research Protections (OHRP) is a small office within the United States Department of Health and Human Services (DHHS), specifically the Office of the Assistant Secretary for Health in the Office of the Secretary of DHHS, that d ...
began investigating complaints such as inadequate informed consent. Additionally, the trial was criticized for lacking prior Phase I and II studies, and critics summarized previous controlled trials as having "found no evidence that chelation is superior to placebo for treatment of CAD or PVD." The same critics argued that methodological flaws and lack of prior probability made the trial "unethical, dangerous, pointless, and wasteful." The American College of Cardiology supported the trial and research to explore whether chelation therapy was effective in treating heart disease. Evidence of insurance fraud and other felony convictions among (chelation proponent) investigators further undermined the credibility of the trial. The final results of TACT were published in November 2012. The authors concluded that disodium EDTA chelation "modestly" reduced the risk of adverse cardiovascular outcomes among stable patients with a history of
myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which ma ...
. The study also showed a "marked" reduction in cardiovascular events in diabetic patients treated with EDTA chelation. 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." Critics of the study characterized the study as showing no support for the use of chelation therapy in coronary heart disease, particularly the claims to reduce the need for
coronary artery bypass grafting Coronary artery bypass surgery, also known as coronary artery bypass graft (CABG, pronounced "cabbage") is a surgical procedure to treat coronary artery disease (CAD), the buildup of plaques in the arteries of the heart. It can relieve chest pa ...
(CABG, pronounced "cabbage").


Autism

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 risky process. , up to 7% of children with autism worldwide had been subjected to chelation therapy. 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. Parents either have a doctor use a treatment for lead poisoning, or buy unregulated supplements, in particular
DMSA Succimer, sold under the brand name Chemet among others, is a medication used to treat lead, mercury, and arsenic poisoning. When radiolabeled with technetium-99m, it is used in a number of types of diagnostic testing. A full course is 19 day ...
and lipoic acid. Aspies For Freedom, an autism rights organization, considers this use of chelation therapy unethical and potentially dangerous. There is little to no credible scientific research that supports the use of chelation therapy for the effective treatment of autism.


See also

* List of ineffective cancer treatments *
Detoxification Detoxification or detoxication (detox for short) is the physiological or medicinal removal of toxic substances from a living organism, including the human body, which is mainly carried out by the liver. Additionally, it can refer to the period of ...


References


External links


Chelation Therapy: Unproven Claims and Unsound Theories
- Quackwatch {{Toxicology Detoxification Alternative therapies for developmental and learning disabilities Alternative detoxification Alternative medical treatments Autism pseudoscience