'Chelation therapy' is a process involving the use of
chelating agents 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 US dictates the use of
DMSA. This, in addition to other
chelating agents such as
DMPS and
alpha lipoic acid (ALA), are used in conventional and alternative
medicine.
Discovery in medicine
Chelating (pronounced key-lating) agents were introduced into medicine as a result of the
use of poison gas in World War I. The first widely used chelating agent,
dimercaprol, also named British Anti-
Lewisite, or BAL, was used as an antidote to the arsenic based poison gas, Lewisite. BAL bound the arsenic in Lewisite, forming a water soluble compound that entered the blood-stream, allowing it to be removed from the body by the kidneys and liver. BAL is an organic di-thiol compound which binds arsenic with two strong chemical bonds formed between the arsenic and the
thiols, SH groups, which are also known as "
mercaptans". The latter name comes from their ability to react and form strong bonds with, or "capture,"
mercury - in addition to lead and arsenic. BAL had severe side-effects.
After World War II, medicine was confronted with a large number of navy personnel suffering from lead poisoning through their jobs repainting the hulls of navy ships. It is at this time that
EDTA was introduced into medicine as a lead chelating agent. EDTA is a synthetic amino-acid of different structure from chemicals like BAL. In particular, it contains no mercaptans. While EDTA had some uncomfortable side effects, they were nowhere near as severe as BAL.
Subsequent to this, in the 1960s, BAL was modified into
DMSA, a related di-thiol 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.
Research in the former Soviet Union led to the introduction of
DMPS, another di-thiol, as a mercury chelating agent. They also introduced
ALA, which is transformed by the body into a di-thiol, dihydrolipoic acid, which is a mercury and arsenic chelating agent. DMPS has been given only experimental FDA status in the US. ALA is a common nutritional supplement.
Other chelating agents have been discovered. They all have the properties that they bind with metallic ions so that the ion is held by several chemical bonds and thus render it much less chemically reactive, produce a complex that is water soluble, and thus allow the ion to enter the blood-stream and be excreted harmlessly.
Uses in medicine
Heavy metal poisoning is a medical condition usually identified among those occupationally exposed, and which can have significant effects on nearly every organ system
[1].
Mercury, for example, has been strongly implicated as "a potential etiological factor in neurodegeneration".
[1] Chelation therapy is used as a treatment for acute mercury,
iron,
arsenic,
lead,
uranium,
plutonium and other forms of
heavy metal poisoning, where the amounts are so high that there is enough risk to the health of the patient to justify the therapy. The buildup of iron in
thalassemia has led to use in treatment of that disease as well.
One example of successful chelation therapy is the case of
Harold McCluskey, a nuclear worker who became very badly contaminated internally with
americium in 1976. He was treated with diethylene triamine pentaacetic acid (DTPA) over many years to remove americium from his body. While it was not possible to remove all of the americium, it was possible to mitigate the effects of the accident. Harold McCluskey had 41
MBq (1.1
mCi) of
241Am removed from his body, a significant proportion. Harold McCluskey died of unrelated causes 11 years after being contaminated.
The chelating agent may be administered intravenously, intramuscularly, or orally, depending on the agent and the type of poisoning.
Examples of chelating agents
The choice of chelating agent depends on which metal is involved. Common chelating agents include:
★
Dimercaptosuccinic acid (DMSA)
★
Dimercapto-propane sulfonate (DMPS)
★
Alpha lipoic acid (ALA)
★
Calcium disodium versante (CaNa
2-EDTA)
★
D-penicillamine
★
Deferoxamine
★
Defarasirox
★
Dimercaprol (BAL)
★ The
calcium salt of diethylene triamine pentaacetic acid (DTPA) can be used to reduce the amount of
plutonium retained in the human body by a factor of about ten, if it is given within about twenty minutes of plutonium entering an open wound. For long term treatment, the
zinc salt should be used, as this removes fewer vital trace metals from the body. Zinc is a well known inducer of
metallothionein, a protein of molecular weight of approximately 6000, comprising 30% of its aminoacids by cystein, being capable to chelating lead, copper, zinc, nickel and many other heavy metals.
[2] Metallothionein-metal-complexes are excreted via the gastrointestinal tract or kidneys. Metallothioneins are expressed in many biological systems, including humans, due to the influence of heavy metals and electromagnetic input.
[3] A well known, unwanted, reaction of metallothionein is the 'detoxification' of platinum, core metal of cis-platinum, a chemotherapeutic agent, given to patients with carcinoma of the ovary. After the third cycle or so, cis-platinum does not work any more, due to the 'detoxification' of platinum through metallothionein. A good and wanted application is the 'detoxification' of copper through induction of metallothionein with oral zinc.
Use by alternative practitioners
There are two general areas of
alternative medicine in which
chelation is used. One is in the area of what the practitioners claim to be common but conventionally unrecognized heavy metal poisoning. The second is in the area of heart disease.
[http://drcranton.com/newhope.htm][4]
Heavy metal poisoning
In the past, certain doctors claimed to see substantial lead and arsenic poisoning in their patients due to the heavy use of pesticides. The most common early pesticides were the arsenic-based "Paris Green", later supplanted by lead-arsenate; both of which were extensively used on fruit.
BAL, having serious side effects, was given up by alternative practitioners when alternatives appeared. Today DMSA, developed in the US, is the conventional chelating agent of choice. Alternative practitioners make use of this agent; they also make use of DMPS and ALA, both developed in and first studied extensively in the ex-Soviet Union. In addition, EDTA, considered by the conventional medical system as an obsolete lead chelating agent with undesirable side effects (though nowhere near as severe as BAL), continues to be used by some alternative practitioners.
Furthermore, folklore has given rise to the use of various high sulfur foods as "chelating agents". Those include onions, garlic, green foods and sea-weeds. Sulfur supplements like MSM or NAC have also been used. These are not actually chelating agents, as chelators involve multiple bonds to the metal atom and these foods and supplements involve compounds that are only mono-thiols.
Cilantro (coriander) has also been introduced
[5] and is present in numerous alternative medications like "PCA-Rx", "Metal-Free" (both of which also contain ALA) and "NDF". Cilantro is a leafy food plant cultivated in the Netherlands, France, Germany, Italy, and Russia. Although cilantro was widely described as a chelator of lead, mercury or other heavy metals in internet literature, and is often used as such, the claims are seemingly based on a paucity of research and no traditional use. The original case report by Omura did not involve prior or subsequent testing of tissue or blood levels of mercury, and involved relatively unorthodox "O-ring"
muscle testing before and after a meal of Vietnamese soup with cilantro:
The researcher stated that he noticed an increased amount of mercury
in organs follow ing the injection of radioactive Thallium for cardiac SPECT imaging. Following a meal of Vietnamese soup containing cilantro, he claimed “successful elimination” of the mercury deposits. Further research supposedly confirmed his initial observations and demonstrated cilantro’s efficacy in promoting the excretion of lead and aluminum as well. The researcher then claimed that cilantro aided the excretion of heavy metals putatively associated with persistent chlamydia and herpes infections [6], and facilitated the excretion of mercury following the removal
of dental amalgam fillings [7].
Surprisingly these case reports have become the foundation for subsequent cilantro and heavy metal literature, despite their evidentiary paucity, and without subsequent replica of their results in peer-reviewed literature. First the concentration and location of mercury and other heavy metals were assessed using a Bi-Digital O-Ring Test, a highly unorthodox and unreliable method of diagnosis via muscle testing. Second,
the reports lack controls. In both reports cilantro was administered in conjunction with electroacupuncture
and antibiotic or antiviral medications. In the absence of legitimate diagnostic tests or the use of controls enabling sound conclusions, these reports do not warrant the biochemical claims about cilantro that have been
extrapolated from them.[8]
In addition,
Dr. Garry Gordon one of the developers of intravenous
chelation in the 1950s has tested patients for heavy metals before and after substantial cilantro intake but has found no increase of increased mercury or lead excretion in urine or fecal tests.
[9] He has however found increased excretion when Calcium disodium EDTA is combined with pectin and garlic.
[10]
The ingredient used by pharmacists and doctors is an etheric oil (0,5% w/w). The main part of that oil is (+)-Linalool (60% w/v). The chemical name of Linalool is 3,7-dimethyl-1-6-octadien-3-ol. It is also called Coriandroleum, reflecting its origin from Coriander fructus. The boiling point of Linalool is 198-200 degrees Celsius. Other ingredients of the oil are Limonen, Geraniol, Citronellol, and Borneol, all having a similar chemical structure as Linalool, i.e. they are terpenes. Another molecule in the oil is trans-tridecen-2-al-1 an aldehyde, responsible for the typical smell of Fructus coriander (like bugs). Geraniol is the isomeric form of Linalool and found in the oil of rose and palmarosa.
The pharmacological action of terpenes such as Linalool is mainly spasmolytic and carminative. Similar actions are known from the etheric oils of Fructus chamomillae and Fructus foeniculi. Due to the combination of spasmolytic and carminative action of the terpenes, heavy metals are excreated via increasing the renal flux and the G.I. tract. Neither Fructus coriander nor terpenes are capable of chelating heavy metals such as mercury or lead due to the lack of sulfur, nitrogen, or an organic acid structure within the chemical molecule. Fructus coriander is in Mexican salsa and can kill bacteria such as Salmonella typhi.
Similar pharmacological actions are transmitted by the oil of Carvi fructus, i.e. Carvi aethericum. Spasmolytic and carminative acting remedies should be used carefully for detoxification of heavy metals because of the lack of chelating power. If the concentration of heavy metals in the urine increases to over 17 micrograms / gram of creatinine, then the epithelium of the promimal tubulus of the kidney might be destroyed by the heavy metal, since it is not "detoxified" by a chelating agent. Lesions of the epithelium are, however, reversible.
What continues to distinguish alternative practitioners' use of these chelating agents for heavy metal poisoning is that conventional medicine rarely diagnoses heavy metal poisoning outside of occupational medicine.
Alternative practitioners claim to recognize extensive environmental exposures, such as through contact with
treated lumber. Many of their patients claim to have been exposed to mercury through their
dental amalgam fillings. Others claim that they, or their children, have become mercury poisoned from
thimerosal, an
ethyl-mercury compound used as a preservative in vaccines, which has been phased out for some time, and is now nearly, if not completely, eliminated from all vaccines recommended for children under 6 years old.
[11] Still other patients are treated for mercury, lead or arsenic poisoning of unspecified etiology.
Heart disease
Some alternative practitioners use chelation to treat
hardening of the arteries. The safety and efficacy of EDTA chelation therapy as a treatment for coronary artery disease are being assessed by NCCAM in a five-year study which began in 2002.
[12][13]
The original theory behind calcium chelation therapy was that EDTA forms a
complex with the
calcium in the walls of
arteries. Drawbacks with this theory include EDTA's inability to penetrate the cell walls in the arteries and therefore inability to access to the calcium, EDTA binding preferentially to other metals, and calcium posing minimal arterial danger in comparison to cholesterol and other deposits.
A number of dangers have been associated with the therapy including
hypocalcaemia and decreased blood
coagulation ability (possibly due to loss of calcium). Also associated with this practice is the risk of
leaching of necessary
trace metals.
Some alternative practitioners believe intravenous chelation therapy "reverses and slows the progression of atherosclerosis and other age-related and degenerative diseases",
[ such as coronary artery disease and macular degeneration. ]
Controversy
In 1998, the U.S. Federal Trade Commission charged that the American College for Advancement in Medicine (ACAM) website and a brochure 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.[14]
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.[15]
In 2003, the Supreme Court of Missouri, in ''State Board of Registration for the Healing Arts v. McDonagh'', 123 S.W.3d 146, overturned a decision of the State Board of Registration sanctioning a doctor who used chelation therapy for the treatment of heart disease. The Court held that the therapy was not harming patients, and the standard for determining repeated negligence in using an alternative therapy such as chelation is not whether it is popular or commonly accepted by the medical community, but rather whether heart specialists would consider its use to be reasonable.
Autism Treatment
Some chelation advocates claim that autism, a neurodevelopmental disorder that appears in early childhood, might be caused or aggravated by heavy metal poisoning and might be ameliorated by chelation therapy, but there is no scientific evidence to support this hypothesis.
Roy E. Kerry has been charged with involuntary manslaughter following the 2005 death of a five year old autistic boy.[16]
Prevalence of chelation therapy
ACAM claims that 800,000 patient visits for chelation therapy, with an average of forty visits per patient, were made in the United States in 1997.[17] That is about 0.007% of the total US population. A May 2004 survey by the National Center for Complementary and Alternative Medicine (NCCAM) estimated that 0.1%, plus or minus 0.02% of the adult US population had used chelation therapy at some point in their life.
Side effects and safety concerns
Side effects can include headaches, skin irritation, nausea or stomach
upset, diarrhea, extreme fatigue, cramps, joint pain, feeling
faint, and in rare cases (0.02%) fever.[18] Safety concerns include kidney toxicity.[19]
In August 2005, an autistic boy went into cardiac arrest fifty minutes after an infusion of acidic Endrate and died with hypocalcemia. The initial coroner's report ruled the death accidental.[20] Dr. Mary Jean Brown, chief of the Lead Poisoning Prevention Branch of the Centers for Disease Control and Prevention, said that the child died because he was given the wrong chelation agent.[21]
References
1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11277574&query_hl=8
2. Vasak, M., 2005, “Advances in metallothionein structure and functions”, J. Trace Elem. Med. Biol., 19 (1): page 13-17
3. Liu, J., Kershaw, W.C., Klaasen, C.D., 1991, The protective effect of metallothionein in the toxicity of various metals in rat primary hepatocyte culture“, ''Toxicol. Appl. Pharmacol'', 197: page 27-34
4. http://www.garynull.com/Documents/Chelation_Therapy.htm
5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=11535365&query_hl=11&itool=pubmed_docsum
6. Omura Y, Beckman SL. Role of mercury (Hg) in resistant infections & effective treatment of Chlamydia trachomatis and Herpes family viral infections (and potential treatment for cancer) by removing localized Hg deposits with Chinese parsley and
delivering effective antibiotics using various drug uptake enhancement methods. Acupunct Electrother Res. 1995;20(3-4):
195-229
7. Omura Y, Shimotsuura Y, Fukuoka A, Fukuoka H, Nomoto T.
Significant mercury deposits in internal organs following the removal of dental amalgams, & development of precancer on the gingiva and the sides of the tongue and their represented organs as a result of inadvertent exposure to strong curing light (used to solidify synthetic dental filling material) & effective treatment: a clinical case report, along with or gan representation areas for each tooth. Acupunct Electrother Res. 1996;
21(2): 133-160
8. http://medherb.com/eletter/Cilantro-Millet.pdf John Millet, NAIMH, C.Hom "Cilantro, Chlorella and Heavy Metals" Medical Herbalism Vol. 14 No. 4
9. http://www.gordonresearch.com/answers/chelating_for_mercury_in_amalgams.html
10. http://www.gordonresearch.com/articles_oral_chelation/new_breakthroughs_chelation_therapy.html
11. http://www.fda.gov/cber/vaccine/thimerosal.htm#t1
12. http://www.clinicaltrials.gov/ct/show/NCT00044213?order=1
13. http://nccam.nih.gov/news/2002/chelation/q-and-a.htm
14. http://www.ftc.gov/opa/1998/12/acam.htm
15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11798370&dopt=Abstract
16. Doctor Charged in Autistic Boy's Death [2]
17. http://www.acam.org/press_releases/20020814.htm
18. http://www.holisticonline.com/Chelation/chel_side_effects.htm
19. http://www.holisticonline.com/Chelation/chel_safety.htm
20. http://www.post-gazette.com/pg/06006/633541.stm
21. http://www.post-gazette.com/pg/06018/639721.stm
External links
★ garynull.com "Chelation Therapy: The Controversial Medical Marvel" by Gary Null, Ph.D. and Luanne Pennesi, RN, BSN (extensively researched study with 50 citations) Accessed May 26, 2007
★ Your-Doctor.com - 'Quack Therapies: Chelation Therapy' (discusses use of chelation therapy in conventional medicine and the hazards of chelation therapy by alternative practitioners)
★ Quackwatch "Chelation Therapy: Unproven Claims and Unsound Theories" by Sam Green
★ GenerationRescue.org - Parent-led advocacy group promoting use of chelation therapy as a cure for autism
★ Gordon Research Garry Gordon, father of chelation therapy's web site for doctors.
Pervasive developmental disorders
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