Chelation therapy
Encyclopedia
Chelation therapy is the administration of chelating agent
s to remove heavy metals
from the body. For the most common forms of heavy metal intoxication—those involving lead
, arsenic
or mercury
—the standard of care
in the United States dictates the use of dimercaptosuccinic acid
(DMSA). 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 other diseases or ailments.
. The first widely used chelating agent, the organic dithiol compound dimercaprol
(also named British anti-lewisite or BAL), was used as an antidote to the arsenic-based poison gas, lewisite
. The sulphur atoms in BAL's mercaptan groups strongly bond to the arsenic in lewisite, forming a water-soluble compound that entered the bloodstream, allowing it to be removed from the body by the kidneys and liver. BAL had severe side-effects.
After World War II, a large number of navy personnel suffered from lead poisoning
as a result of their jobs repainting the hulls of ships. The medical use of ethylenediaminetetraacetic acid (EDTA
) as a lead chelating agent was introduced. Unlike BAL, it is a synthetic amino acid
and contains no mercaptans. EDTA side effects were not considered as severe as BAL.
In the 1960s, BAL was modified into DMSA, a related dithiol with far fewer side effects. DMSA quickly replaced both BAL and EDTA, becoming the US standard of care
for the treatment of lead, arsenic, and mercury poisoning, which it remains today. More recently, esters of DMSA have been developed which are reportedly more effective; for example, the monoisoamyl ester (MiADMSA) is reportedly more effective than DMSA at clearing mercury and cadmium.
Research in the former Soviet Union led to the introduction of 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
.
Other chelating agents have been discovered. They all function by making several chemical bonds with metal ions, thus rendering them much less chemically reactive. The resulting complex is water-soluble, allowing it to enter the bloodstream and be excreted harmlessly.
Calcium-disodium EDTA chelation is approved by the U.S. Food and Drug Administration (FDA) for treating lead poisoning and heavy metal toxicity. In 1998, the U.S. Federal Trade Commission
(FTC) pursued the American College for Advancement in Medicine (ACAM), an organization that promotes "complementary, alternative and integrative medicine" over the claims made regarding the treatment of atherosclerosis
in advertisements for EDTA chelation therapy. The FTC concluded that there was a lack of scientific studies to support these claims and that the statements by the ACAM were false. In 1999, the ACAM agreed to stop misrepresenting chelation therapy as effective in treating heart disease, avoiding legal proceedings.
), 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.
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:
(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.
uses chelation therapy as a non-standard treatment for some ailments, including heart disease and autism. Attempts have been made to use it in treating kidney dysfunction, calcific band keratopathy (an eye disorder), and ovarian cancer
. Currently there is a US National Center for Complementary and Alternative Medicine (NCCAM) trial being conducted on the chelation therapy's safety and efficacy for patients with coronary artery disease. NCCAM Director Stephen E. Straus cited the "widespread use of chelation therapy in lieu of established therapies, the lack of adequate prior research to verify its safety and effectiveness, and the overall impact of coronary artery disease" as factors motivating the trial. The proposed study has been criticized as unethical, unnecessary and dangerous, with multiple studies conducted in the past demonstrating that it provides no benefits.
, to patients with atherosclerosis
. 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). Several possible mechanisms have been proposed, though none have been scientifically validated. The US National Center for Complementary and Alternative Medicine began conducting the Trial to Assess Chelation Therapy (TACT) in 2003. Patient enrollment was to be completed around July 2009 with final completion around July 2010, but enrollment in the trial was suspended on September 26, 2008 for an investigation by OHRP after complaints about ethical concerns such as inadequate informed consent
. The trial has been criticized for lacking prior Phase I and II studies, and particularly because previous controlled trials have not indicated benefits. The American College for Advancement in Medicine
, a controversial organization created to promote chelation therapy, has played a part in the adoption of the TACT clinical trial, which has led to further criticism of the trial. Atwood et al. have argued that methodological flaws and lack of prior probability
make this trial "unethical, dangerous, pointless, and wasteful."
The American Heart Association
states that there is "no scientific evidence to demonstrate any benefit from this form of therapy" and that the "United States Food and Drug Administration (FDA), the National Institutes of Health
(NIH) and the American College of Cardiology
all agree with the American Heart Association" that "there have been no adequate, controlled, published scientific studies using currently approved scientific methodology to support this therapy for cardiovascular disease." Like other scientific commentators, they note that any improvement among heart patients undergoing chelation therapy can be attributed to the placebo effect and lifestyle changes discovered in conventional medicine but recommended by chelationists; "quitting smoking, losing weight, eating more fruits and vegetables, avoiding foods high in saturated fats and exercising regularly". They note their concern that patients could put off proven treatments for heart disease like drugs or surgery. A 2005 systematic review
found that controlled scientific studies did not support chelation therapy for heart disease. It found that very small trials and uncontrolled descriptive studies have reported benefits while larger controlled studies have found results no better than placebo. The Mayo Clinic
states that 'chelation studies have found that chelation didn't work as a heart disease treatment.'
may trigger the symptoms of autism
, 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. Parents either have a doctor use a treatment for lead poisoning, or buy unregulated supplements. Aspies For Freedom
, an autistic rights organization, considers this use of chelation therapy unethical and potentially dangerous. There is strong epidemiological
evidence that refutes links between environmental triggers, in particular thiomersal
-containing vaccine
s, and the onset of autistic symptoms. There is no scientific support for chelation therapy as a treatment for autism.
reported that cardiac patients receiving chelation therapy fared no better than those who received placebo
treatment.
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.
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.
estimates that 800,000 patient visits for chelation therapy were made in the United States in 1997.
, cardiac arrhythmias, respiratory arrest, and hypocalcemia. Other concerns include kidney failure
, which can require permanent life-limiting and expensive dialysis
, or cause death.
2007 research with lab rats indicates giving chelating agent DMSA to rats without high levels of lead may cause lasting cognitive damage.
When EDTA is not administered by a health professional for the treatment of heavy metal poisoning more serious side effects can occur.
Chelation therapy can be hazardous, even conducted with the FDA-approved chelation agents. In August 2005, botched chelation therapy conducted by an ACAM member killed a 5-year-old boy with autism; 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. 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.
More than 30 deaths have been recorded in association with IV-administered disodium EDTA since the 1970s.
Chelation
Chelation is the formation or presence of two or more separate coordinate bonds between apolydentate ligand and a single central atom....
s to remove heavy metals
Heavy metals
A heavy metal is a member of a loosely-defined subset of elements that exhibit metallic properties. It mainly includes the transition metals, some metalloids, lanthanides, and actinides. Many different definitions have been proposed—some based on density, some on atomic number or atomic weight,...
from the body. For the most common forms of heavy metal intoxication—those involving lead
Lead
Lead is a main-group element in the carbon group with the symbol Pb and atomic number 82. Lead is a soft, malleable poor metal. It is also counted as one of the heavy metals. Metallic lead has a bluish-white color after being freshly cut, but it soon tarnishes to a dull grayish color when exposed...
, arsenic
Arsenic
Arsenic is a chemical element with the symbol As, atomic number 33 and relative atomic mass 74.92. Arsenic occurs in many minerals, usually in conjunction with sulfur and metals, and also as a pure elemental crystal. It was first documented by Albertus Magnus in 1250.Arsenic is a metalloid...
or mercury
Mercury (element)
Mercury is a chemical element with the symbol Hg and atomic number 80. It is also known as quicksilver or hydrargyrum...
—the standard of care
Standard of care
In tort law, the standard of care is the degree of prudence and caution required of an individual who is under a duty of care.The requirements of the standard are closely dependent on circumstances. Whether the standard of care has been breached is determined by the trier of fact, and is usually...
in the United States dictates the use of dimercaptosuccinic acid
Dimercaptosuccinic acid
Dimercaptosuccinic acid , is the organosulfur compound with the formula HO2CCHCHCO2H. This colorless solid contains two carboxylic acid and two thiol groups, the latter being responsible for its mildly unpleasant odour. It occurs in two diastereomers, meso and the chiral dl forms...
(DMSA). Other chelating agents
Chelation
Chelation is the formation or presence of two or more separate coordinate bonds between apolydentate ligand and a single central atom....
, such as 2,3-dimercapto-1-propanesulfonic acid
2,3-Dimercapto-1-propanesulfonic acid
2,3-Dimercapto-1-propanesulfonic acid and its sodium salt are chelating agents that form complexes with various heavy metals. They are related to dimercaprol, which is another chelating agent....
(DMPS) and alpha lipoic acid
Lipoic acid
Lipoic acid , also known as α-lipoic acid and Alpha Lipoic Acid is an organosulfur compound derived from octanoic acid. LA contains two vicinal sulfur atoms attached via a disulfide bond and is thus considered to be oxidized...
(ALA), are used in conventional
Medicine
Medicine is the science and art of healing. It encompasses a variety of health care practices evolved to maintain and restore health by the prevention and treatment of illness....
and alternative medicine
Alternative medicine
Alternative medicine is any healing practice, "that does not fall within the realm of conventional medicine." It is based on historical or cultural traditions, rather than on scientific evidence....
. No approved medical research has found any benefits to chelation therapy for other diseases or ailments.
History
Chelating agents were introduced into medicine as a result of the use of poison gas in World War IPoison gas in World War I
The use of chemical weapons in World War I ranged from disabling chemicals, such as tear gas and the severe mustard gas, to lethal agents like phosgene and chlorine. This chemical warfare was a major component of the first global war and first total war of the 20th century. The killing capacity of...
. The first widely used chelating agent, the organic dithiol compound dimercaprol
Dimercaprol
Dimercaprol or British anti-Lewisite , is a compound developed by British biochemists at Oxford University during World War II. It was developed secretly as an antidote for lewisite, the now-obsolete arsenic-based chemical warfare agent. Today, it is used medically in treatment of arsenic,...
(also named British anti-lewisite or BAL), was used as an antidote to the arsenic-based poison gas, lewisite
Lewisite
Lewisite is an organoarsenic compound, specifically an arsine. It was once manufactured in the U.S. and Japan as a chemical weapon, acting as a vesicant and lung irritant...
. 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
Lead poisoning
Lead poisoning is a medical condition caused by increased levels of the heavy metal lead in the body. Lead interferes with a variety of body processes and is toxic to many organs and tissues including the heart, bones, intestines, kidneys, and reproductive and nervous systems...
as a result of their jobs repainting the hulls of ships. The medical use of ethylenediaminetetraacetic acid (EDTA
EDTA
Ethylenediaminetetraacetic acid, widely abbreviated as EDTA , is a polyamino carboxylic acid and a colourless, water-soluble solid. Its conjugate base is named ethylenediaminetetraacetate. It is widely used to dissolve limescale. Its usefulness arises because of its role as a hexadentate ligand...
) as a lead chelating agent was introduced. Unlike BAL, it is a synthetic amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
and contains no mercaptans. EDTA side effects were not considered as severe as BAL.
In the 1960s, BAL was modified into DMSA, a related dithiol with far fewer side effects. DMSA quickly replaced both BAL and EDTA, becoming the US standard of care
Standard of care
In tort law, the standard of care is the degree of prudence and caution required of an individual who is under a duty of care.The requirements of the standard are closely dependent on circumstances. Whether the standard of care has been breached is determined by the trier of fact, and is usually...
for the treatment of lead, arsenic, and mercury poisoning, which it remains today. More recently, esters of DMSA have been developed which are reportedly more effective; for example, the monoisoamyl ester (MiADMSA) is reportedly more effective than DMSA at clearing mercury and cadmium.
Research in the former Soviet Union led to the introduction of DMPS
2,3-Dimercapto-1-propanesulfonic acid
2,3-Dimercapto-1-propanesulfonic acid and its sodium salt are chelating agents that form complexes with various heavy metals. They are related to dimercaprol, which is another chelating agent....
, 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
Bloodletting
Bloodletting is the withdrawal of often little quantities of blood from a patient to cure or prevent illness and disease. Bloodletting was based on an ancient system of medicine in which blood and other bodily fluid were considered to be "humors" the proper balance of which maintained health...
to treat excess iron stores in people with haemochromatosis
Haemochromatosis
Haemochromatosis type 1 is a hereditary disease characterized by excessive intestinal absorption of dietary iron resulting in a pathological increase in total body iron stores. Humans, like most animals, have no means to excrete excess iron...
.
Other chelating agents have been discovered. They all function by making several chemical bonds with metal ions, thus rendering them much less chemically reactive. The resulting complex is water-soluble, allowing it to enter the bloodstream and be excreted harmlessly.
Calcium-disodium EDTA chelation is approved by the U.S. Food and Drug Administration (FDA) for treating lead poisoning and heavy metal toxicity. In 1998, the U.S. Federal Trade Commission
Federal Trade Commission
The Federal Trade Commission is an independent agency of the United States government, established in 1914 by the Federal Trade Commission Act...
(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
Atherosclerosis
Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...
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 misrepresenting chelation therapy as effective in treating heart disease, avoiding legal proceedings.
Medical use
Chelation therapy is used as a treatment for acute mercury, iron (including in cases of thalassemiaThalassemia
Thalassemia is an inherited autosomal recessive blood disease that originated in the Mediterranean region. In thalassemia the genetic defect, which could be either mutation or deletion, results in reduced rate of synthesis or no synthesis of one of the globin chains that make up hemoglobin...
), arsenic, lead, uranium
Uranium
Uranium is a silvery-white metallic chemical element in the actinide series of the periodic table, with atomic number 92. It is assigned the chemical symbol U. A uranium atom has 92 protons and 92 electrons, of which 6 are valence electrons...
, plutonium
Plutonium
Plutonium is a transuranic radioactive chemical element with the chemical symbol Pu and atomic number 94. It is an actinide metal of silvery-gray appearance that tarnishes when exposed to air, forming a dull coating when oxidized. The element normally exhibits six allotropes and four oxidation...
and other forms of toxic metal
Toxic metal
Toxic metals are metals that form poisonous soluble compounds and have no biological role, i.e. are not essential minerals, or are in the wrong form. Often heavy metals are thought as synonymous, but lighter metals also have toxicity, such as beryllium, and not all heavy metals are particularly...
poisoning. The chelating agent may be administered intravenously
Intravenous therapy
Intravenous therapy or IV therapy is the infusion of liquid substances directly into a vein. The word intravenous simply means "within a vein". Therapies administered intravenously are often called specialty pharmaceuticals...
, intramuscularly
Intramuscular injection
Intramuscular injection is the injection of a substance directly into a muscle. In medicine, it is one of several alternative methods for the administration of medications . It is used for particular forms of medication that are administered in small amounts...
, or orally, depending on the agent and the type of poisoning.
One example of successful chelation therapy is the case of Harold McCluskey
Harold McCluskey
Harold R. McCluskey was a chemical operations technician at the Hanford Plutonium Finishing Plant located in Washington state who is known for having survived, on April 24, 1976, exposure to the highest dose of americium radiation ever recorded...
, a nuclear worker who became badly contaminated with americium
Americium
Americium is a synthetic element that has the symbol Am and atomic number 95. This transuranic element of the actinide series is located in the periodic table below the lanthanide element europium, and thus by analogy was named after another continent, America.Americium was first produced in 1944...
in 1976. He was treated with diethylene triamine pentaacetic acid (DTPA) over many years, removing 41 MBq
Becquerel
The becquerel is the SI-derived unit of radioactivity. One Bq is defined as the activity of a quantity of radioactive material in which one nucleus decays per second. The Bq unit is therefore equivalent to an inverse second, s−1...
(1.1 mCi
Curie
The curie is a unit of radioactivity, defined asThis is roughly the activity of 1 gram of the radium isotope 226Ra, a substance studied by the pioneers of radiology, Marie and Pierre Curie, for whom the unit was named. In addition to the curie, activity can be measured using an SI derived unit,...
) 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 Dimercaprol Dimercaprol or British anti-Lewisite , is a compound developed by British biochemists at Oxford University during World War II. It was developed secretly as an antidote for lewisite, the now-obsolete arsenic-based chemical warfare agent. Today, it is used medically in treatment of arsenic,... (BAL) |
|
| Dimercaptosuccinic acid Dimercaptosuccinic acid Dimercaptosuccinic acid , is the organosulfur compound with the formula HO2CCHCHCO2H. This colorless solid contains two carboxylic acid and two thiol groups, the latter being responsible for its mildly unpleasant odour. It occurs in two diastereomers, meso and the chiral dl forms... (DMSA) |
Lead poisoning Lead poisoning is a medical condition caused by increased levels of the heavy metal lead in the body. Lead interferes with a variety of body processes and is toxic to many organs and tissues including the heart, bones, intestines, kidneys, and reproductive and nervous systems... Arsenic poisoning Arsenic poisoning is a medical condition caused by increased levels of the element arsenic in the body. Arsenic interferes with cellular longevity by allosteric inhibition of an essential metabolic enzyme... Mercury poisoning Mercury poisoning is a disease caused by exposure to mercury or its compounds. Mercury is a heavy metal occurring in several forms, all of which can produce toxic effects in high enough doses... |
| Dimercapto-propane sulfonate (DMPS) |
|
| Penicillamine Penicillamine Penicillamine is a pharmaceutical of the chelator class. It is sold under the trade names of Cuprimine and Depen. The pharmaceutical form is D-penicillamine, as L-penicillamine is toxic... |
Mainly in:
Copper toxicity Copper toxicity refers to the consequences of an excess of copper in the body. Copper toxicity can occur from eating acid food that has been cooked in un-coated copper cookware, or from exposure to excess copper in drinking water or other environmental sources.... Occasionally adjunctive therapy in:
|
| Ethylenediamine tetraacetic acid (calcium disodium versante) EDTA Ethylenediaminetetraacetic acid, widely abbreviated as EDTA , is a polyamino carboxylic acid and a colourless, water-soluble solid. Its conjugate base is named ethylenediaminetetraacetate. It is widely used to dissolve limescale. Its usefulness arises because of its role as a hexadentate ligand... (CaNa2-EDTA) |
Lead poisoning Lead poisoning is a medical condition caused by increased levels of the heavy metal lead in the body. Lead interferes with a variety of body processes and is toxic to many organs and tissues including the heart, bones, intestines, kidneys, and reproductive and nervous systems... |
| Deferoxamine Deferoxamine Deferoxamine is a bacterial siderophore produced by the actinobacteria Streptomyces pilosus. It has medical applications as a chelating agent used to remove excess iron from the body... and Deferasirox Deferasirox Deferasirox is a rationally-designed oral iron chelator. Its main use is to reduce chronic iron overload in patients who are receiving long-term blood transfusions for conditions such as beta-thalassemia and other chronic anemias... |
Iron poisoning Iron poisoning is an iron overload caused by a large excess of iron intake and usually refers to an acute overload rather than a gradual one. The terms has been primarily associated with young children who consumed large quantities of iron supplement pills, which resemble sweets and are widely... |
Medically diagnosed heavy metal poisoning
Some common chelating agents are EDTAEDTA
Ethylenediaminetetraacetic acid, widely abbreviated as EDTA , is a polyamino carboxylic acid and a colourless, water-soluble solid. Its conjugate base is named ethylenediaminetetraacetate. It is widely used to dissolve limescale. Its usefulness arises because of its role as a hexadentate ligand...
(ethylenediaminetetraacetic acid), DMPS
2,3-Dimercapto-1-propanesulfonic acid
2,3-Dimercapto-1-propanesulfonic acid and its sodium salt are chelating agents that form complexes with various heavy metals. They are related to dimercaprol, which is another chelating agent....
(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.
Use in alternative medicine
Alternative medicineAlternative medicine
Alternative medicine is any healing practice, "that does not fall within the realm of conventional medicine." It is based on historical or cultural traditions, rather than on scientific evidence....
uses chelation therapy as a non-standard treatment for some ailments, including heart disease and autism. Attempts have been made to use it in treating kidney dysfunction, calcific band keratopathy (an eye disorder), and ovarian cancer
Ovarian cancer
Ovarian cancer is a cancerous growth arising from the ovary. Symptoms are frequently very subtle early on and may include: bloating, pelvic pain, difficulty eating and frequent urination, and are easily confused with other illnesses....
. Currently there is a US National Center for Complementary and Alternative Medicine (NCCAM) trial being conducted on the chelation therapy's safety and efficacy for patients with coronary artery disease. NCCAM Director Stephen E. Straus cited the "widespread use of chelation therapy in lieu of established therapies, the lack of adequate prior research to verify its safety and effectiveness, and the overall impact of coronary artery disease" as factors motivating the trial. The proposed study has been criticized as unethical, unnecessary and dangerous, with multiple studies conducted in the past demonstrating that it provides no benefits.
Heart disease
Some alternative medicine practitioners administer chelating agents, usually EDTAEDTA
Ethylenediaminetetraacetic acid, widely abbreviated as EDTA , is a polyamino carboxylic acid and a colourless, water-soluble solid. Its conjugate base is named ethylenediaminetetraacetate. It is widely used to dissolve limescale. Its usefulness arises because of its role as a hexadentate ligand...
, to patients with atherosclerosis
Atherosclerosis
Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...
. 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). Several possible mechanisms have been proposed, though none have been scientifically validated. The US National Center for Complementary and Alternative Medicine began conducting the Trial to Assess Chelation Therapy (TACT) in 2003. Patient enrollment was to be completed around July 2009 with final completion around July 2010, but enrollment in the trial was suspended on September 26, 2008 for an investigation by OHRP after complaints about ethical concerns such as inadequate informed consent
Informed consent
Informed consent is a phrase often used in law to indicate that the consent a person gives meets certain minimum standards. As a literal matter, in the absence of fraud, it is redundant. An informed consent can be said to have been given based upon a clear appreciation and understanding of the...
. The trial has been criticized for lacking prior Phase I and II studies, and particularly because previous controlled trials have not indicated benefits. The American College for Advancement in Medicine
American College for Advancement in Medicine
The American College for Advancement in Medicine is a membership-based association of alternative medicine physicians based in Irvine, California. ACAM is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians...
, a controversial organization created to promote chelation therapy, has played a part in the adoption of the TACT clinical trial, which has led to further criticism of the trial. Atwood et al. have argued that methodological flaws and lack of prior probability
Prior probability
In Bayesian statistical inference, a prior probability distribution, often called simply the prior, of an uncertain quantity p is the probability distribution that would express one's uncertainty about p before the "data"...
make this trial "unethical, dangerous, pointless, and wasteful."
The American Heart Association
American Heart Association
The American Heart Association is a non-profit organization in the United States that fosters appropriate cardiac care in an effort to reduce disability and deaths caused by cardiovascular disease and stroke. It is headquartered in Dallas, Texas...
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
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
(NIH) and the American College of Cardiology
American College of Cardiology
The American College of Cardiology is a nonprofit medical association established in 1949 to advocate for quality cardiovascular care through education, research promotion, development and application of standards and guidelines, and to influence health care policy...
all agree with the American Heart Association" that "there have been no adequate, controlled, published scientific studies using currently approved scientific methodology to support this therapy for cardiovascular disease." Like other scientific commentators, they note that any improvement among heart patients undergoing chelation therapy can be attributed to the placebo effect and lifestyle changes discovered in conventional medicine but recommended by chelationists; "quitting smoking, losing weight, eating more fruits and vegetables, avoiding foods high in saturated fats and exercising regularly". They note their concern that patients could put off proven treatments for heart disease like drugs or surgery. A 2005 systematic review
Systematic review
A systematic review is a literature review focused on a research question that tries to identify, appraise, select and synthesize all high quality research evidence relevant to that question. Systematic reviews of high-quality randomized controlled trials are crucial to evidence-based medicine...
found that controlled scientific studies did not support chelation therapy for heart disease. It found that very small trials and uncontrolled descriptive studies have reported benefits while larger controlled studies have found results no better than placebo. The Mayo Clinic
Mayo Clinic
Mayo Clinic is a not-for-profit medical practice and medical research group specializing in treating difficult patients . Patients are referred to Mayo Clinic from across the U.S. and the world, and it is known for innovative and effective treatments. Mayo Clinic is known for being at the top of...
states that 'chelation studies have found that chelation didn't work as a heart disease treatment.'
Autism
Based on the discredited hypothesis that mercury poisoningMercury poisoning
Mercury poisoning is a disease caused by exposure to mercury or its compounds. Mercury is a heavy metal occurring in several forms, all of which can produce toxic effects in high enough doses...
may trigger the symptoms of autism
Autism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
, 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. Parents either have a doctor use a treatment for lead poisoning, or buy unregulated supplements. Aspies For Freedom
Aspies For Freedom
Aspies For Freedom is a solidarity and campaigning group which aims at raising public awareness of the autism rights movement. The term "Aspies" refers to people who have been diagnosed with Asperger syndrome, but the group also welcomes anyone on the autism spectrum.-Aims:The aim of Aspies For...
, an autistic rights organization, considers this use of chelation therapy unethical and potentially dangerous. There is strong epidemiological
Epidemiology
Epidemiology is the study of health-event, health-characteristic, or health-determinant patterns in a population. It is the cornerstone method of public health research, and helps inform policy decisions and evidence-based medicine by identifying risk factors for disease and targets for preventive...
evidence that refutes links between environmental triggers, in particular thiomersal
Thiomersal
Thiomersal , and commonly known in the US as thimerosal, is an organomercury compound. This compound is a well established antiseptic and antifungal agent....
-containing vaccine
Vaccine
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins...
s, and the onset of autistic symptoms. There is no scientific support for chelation therapy as a treatment for autism.
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 CalgaryUniversity of Calgary
The University of Calgary is a public research university located in Calgary, Alberta, Canada. Founded in 1966 the U of C is composed of 14 faculties and more than 85 research institutes and centres.More than 25,000 undergraduate and 5,500 graduate students are currently...
reported that cardiac patients receiving chelation therapy fared no better than those who received placebo
Placebo
A placebo is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to deceive the recipient...
treatment.
In 1998, the U.S. Federal Trade Commission
Federal Trade Commission
The Federal Trade Commission is an independent agency of the United States government, established in 1914 by the Federal Trade Commission Act...
(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.
The use of chelation therapy by alternative medicine practitioners for behavioural and other disorders is considered pseudoscientific
Pseudoscience
Pseudoscience is a claim, belief, or practice which is presented as scientific, but which does not adhere to a valid scientific method, lacks supporting evidence or plausibility, cannot be reliably tested, or otherwise lacks scientific status...
as there is no proof that it is effective.
Prevalence
The American College for Advancement in MedicineAmerican College for Advancement in Medicine
The American College for Advancement in Medicine is a membership-based association of alternative medicine physicians based in Irvine, California. ACAM is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians...
estimates that 800,000 patient visits for chelation therapy were made in the United States in 1997.
Side effects and safety concerns
There is a low occurrence of side effects when chelation is used at the dose and infusion rates approved by the U.S. FDA as a treatment for heavy metal poisoning. A burning sensation at the site of delivery into the vein is common. Other side effects include fever, headache, nausea, stomach upset, vomiting, convulsions, bone marrow depression, hypotensionHypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
, cardiac arrhythmias, respiratory arrest, and hypocalcemia. Other concerns include kidney failure
Renal failure
Renal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...
, which can require permanent life-limiting and expensive dialysis
Dialysis
In medicine, dialysis is a process for removing waste and excess water from the blood, and is primarily used to provide an artificial replacement for lost kidney function in people with renal failure...
, or cause death.
2007 research with lab rats indicates giving chelating agent DMSA to rats without high levels of lead may cause lasting cognitive damage.
When EDTA is not administered by a health professional for the treatment of heavy metal poisoning more serious side effects can occur.
Chelation therapy can be hazardous, even conducted with the FDA-approved chelation agents. In August 2005, botched chelation therapy conducted by an ACAM member killed a 5-year-old boy with autism; 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
Cardiac arrest
Cardiac arrest, is the cessation of normal circulation of the blood due to failure of the heart to contract effectively...
caused by hypocalcemia during chelation therapy. 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
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
, a proper medical cause for chelation therapy to be conducted.
More than 30 deaths have been recorded in association with IV-administered disodium EDTA since the 1970s.