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Discovery in medicineChelating 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.
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 conventional medicine
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 agentsThe choice of chelating agent depends on which metal is involved. Common chelating agents include:
Uses in alternative medicineThere 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. Such practitioners commonly employ DMSA, DMPS, ALA or EDTA. The second is in the area of heart disease. Such practitioners make use of EDTA. Heavy metal poisoningUse of chelating agents for heavy metal poisoning began with the introduction of BAL during the First World War. 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 both alternative and conventional medicine 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". These 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 has also been introduced[2] and is present in numerous alternative medications like "PCA-Rx", "Metal-Free" (both of which also contain ALA) and "NDF". Since no one seems to know what chelating substances may or may not be in cilantro, and since chelators can be dangerous due to their movement of neurotoxic heavy-metals, they should be approached with caution. In general Cilatro consists of an extract of Coriander fructus, being a plant cultivated in The Netherlands, France, Germany, Italy, Russia. The ingredient used by pharmacists and doctors is an etheric oil (0,5% w/w). Main part of this 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 ist 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 present in the oil is trans-tridecen-2-al-1 an aldehyde, being responsible for the tpical 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 action are known from the etheric oils of Fructus chamomillae and Fructus foeniculi. Due to the combintion 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 present in Mexican salsa and can kill bacteria such as Salmonella typhi. Similar pharmacological action 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 microgramm / gramm 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, hoewever, 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 being phased out for some time, and is now nearly, if not completely, eliminated from all vaccines recommended to children under 6 years old.[3] Still other patients are treated for mercury, lead or arsenic poisoning of unspecified etiology. Heart diseaseSome alternative practitioners use chelation to treat hardening of the arteries. The concept was first introduced by a podiatrist named Palmer from California[citations needed]. 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. [4][5] 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, say, cholesterol. 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",[6] such as coronary artery disease and macular degeneration. 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. A private corporation calling itself the American College for Advancement in Medicine (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.[7] That is about 0.007% of the total US population. They claim that by 2001 that the number of people who have undergone chelation therapy equaled the number of people having had bypass surgery. 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. In 1998, the U.S. Federal Trade Commission charged that ACAM's Web site 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.[8] The efficacy, safety, and much of the theory behind these practices are disputed by legitimate scientists. In 2001, researchers at the University of Calgary reported that cardiac patients receiving chelation therapy fared no better than those who received placebo treatment.[9] 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. Side effects and safety concernsSide effects can include headaches, skin irritation, nausea or stomach upset, diarrhea, extreme fatigue, cramps, joint pain, feeling like fainting, and in rare cases (0.02%) fever.[10] Safety concerns include kidney toxicity.[11] 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.[12] 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.[13] References
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