Chelation therapy is an FDA-approved procedure for metal toxicity that uses a chelating agent to remove heavy metals from the body. The term ‘chelation’ is derived from the Greek word ‘chele' meaning ‘claw’ . Chelating drugs (also called chelators or chelating agents) are compounds that have a high affinity for certain toxic metals and ‘grab’ onto them .
Overview of Chelation Therapy
Chelation therapy is an FDA-approved procedure for metal toxicity that uses a chelating agent to remove heavy metals from the body. The term ‘chelation’ is derived from the Greek word ‘chele' meaning ‘claw’ . Chelating drugs (also called chelators or chelating agents) are compounds that have a high affinity for certain toxic metals and ‘grab’ onto them . Chelating agents are injected intravenously, or ingested orally, and then bind to heavy metal ions in the body. The chelator and target metal ions remain bound in the bloodstream before being filtered by the kidneys or excreted by the liver and removed from the body .
A commonly used chelating agent is EDTA (ethylene diamine tetra-acetic acid), which can chelate most harmful heavy metals . However, numerous different types of chelators exist (both natural and synthetic). Chelating drugs can be used as the primary treatment or adjuvant therapy for a range of conditions that may be associated with metal toxicity . Chelators can be applied for diverse therapeutic purposes such as detoxification, antioxidant, anticancer, anti-inflammation, anti-infection, immune enhancement, and to modulate biological processes and pathways linked to various diseases .
Almost all heavy metals have toxic effects and are known carcinogens . Arsenic, cadmium, chromium, nickel, uranium, mercury and lead are classified as human carcinogens (known or probable) by the International Agency for Research on Cancer (IARC) . Research has shown that toxic metallic substances induce oxidative stress, DNA damage, and cell death processes, which results in an increased risk of cancer . Despite toxic effects, heavy metals are found in many industrial products such as batteries, paints and vehicle emissions . Our modern environment, food chain, and water supplies are often contaminated with heavy metals, which accumulate in humans and adversely affect health .
Certain metals such as copper, iron, and zinc are essential for biological processes in the human body. However, these metals also play an important role in cancer cell proliferation (rapid growth) and metastasis (spread of tumors) . A recent and promising direction in the development of cancer drugs is related to the inhibition of pathways that keep cancer cells alive and able to metastasize (spread) . Much attention has been directed towards copper and iron in particular with several copper and iron chelators being repurposed as anticancer agents  . Chelation therapy and chelating agents could have potential therapeutic application in both cancer prevention and treatment. However, more clinical research and drug development is still needed to better determine safety and efficacy for cancer patients  .
History of Chelation Therapy
The word chelation originates from the Greek word &_#x2018;_chele’, which means the claw of a crab . The term refers to how chelating agents bind, or ‘grab’, heavy metal ions in a pincer-like fashion. The origins of chelation can be traced back to 1935 when a German chemist, Ferdinand Münz, synthesized ethylene diamine tetra-acetic acid (EDTA) .
The first recorded use of chelation therapy dates back to World War II when a synthetic compound called dimercaprol, also called British Antilewisite (BAL), was developed as an antidote to lewisite, an arsenic-containing chemical warfare agent that causes serious blisters and lung irritation . After the war, BAL was used by a renowned neurologist Derek Denny-Brown to treat patients suffering from Wilson’s disease, which is caused by excessive accumulation of copper, primarily in the brain and liver . BAL was later modified into meso-2, 3-dimercaptosuccinic acid (DMSA), which has fewer side effects and became the primary treatment for lead, arsenic and mercury poisoning in the U.S .
The medical application of EDTA was only discovered after World War II when the U.S. Navy realized that it was an effective treatment for lead poisoning . Many naval shipyard workers suffered from lead poisoning due to the use of lead-based paint on ships . The first scientific study on the intravenous use of EDTA was published in The American Journal of Medical Sciences in 1956 by Clarke et al. as a treatment for atherosclerotic heart disease  . The study reported highly positive results with improvements in 19 of 20 angina patients  . The authors of the study noted that clinical benefits only occurred after about 20 infusions indicating a delayed onset of therapeutic effects .
In the 1960s and 1970s while dosages and rates of administration of EDTA chelation had not been standardized there were quite serious safety issues, including kidney damage and even deaths . Over the subsequent years, chelation practitioners developed safer protocols for EDTA usage, primarily by restricting dosage and infusion rates . In the 1980s and 1990s alternative medicine journals published numerous case studies reporting spectacular results in treating cardiovascular disease .
However, in 1998 the U.S. Federal Trade Commission (FTC) took action against the American College for Advancement in Medicine (ACAM) over claims that EDTA chelation therapy could treat atherosclerosis. They concluded that there was a lack of scientific evidence and that claims constituted false advertising . With early concerns around dangerous side-effects and later crackdowns on the promotion of the treatment, there has been limited scientific research on chelation therapy.
Further well-designed large-scale clinical trials are still needed to determine the potential therapeutic applications of chelation therapy in the prevention, treatment, and management of chronic diseases such as heart disease and cancer. There is some clinical research to support potential therapeutic benefits . Nevertheless, the treatment remains controversial in the medical community.
Research on Chelation Therapy and Cancer
Proponents of chelation therapy claim that it can prevent and help to treat cancer by removing heavy metals that may contribute to the development of cancer. However, there is currently no clinical scientific evidence to support the use of chelation therapy as a primary cancer treatment or prevention for cancer. Nevertheless, there is sound scientific evidence that heavy metals can cause cancer. Moreover, novel chelating agents are being developed as targeted anticancer drugs to suppress the bioavailability of certain metals in cancer cells to inhibit the development and spread of cancer .
Research shows that many metals and metal-containing compounds are potent mutagens and carcinogens . In fact, most heavy metals have toxic effects and are considered to be carcinogenic to varying degrees . Arsenic, cadmium, chromium, nickel, uranium, mercury, and lead are classified as human carcinogens (either known or probable) by the IARC . Numerous scientific studies have shown that heavy metals induce oxidative stress, DNA damage, and increase the risk of cancer . Advancements in molecular toxicology and carcinogenesis have shed light on the mechanisms behind metal-induced cancer. Conferences have been held on the link between heavy metals and cancer with hundreds of scientists presenting evidence .
There is little scientific research on the link between chelation therapy and cancer. A small study on cancer prevention observed a 90% reduction in cancer mortality attributed to chelation therapy . The study involved 59 patients with no evidence of cancer at the time of chelation treatment. They were then followed-up over a period of 18 years. Only 1 of 59 (1.7%) patients died of cancer over this period while 30 of 172 (17.6%) non-treated control subjects died of cancer. Death from atherosclerosis was also reduced. The control group and treated patients lived in the same small Swiss city. Both groups were considered to be exposed to the same amount of environmental pollutants and other carcinogens.
A promising and emerging direction in the development of anticancer drugs is related to the inhibition of molecular pathways that keep cancer cells alive and able to metastasize (spread) . Copper and iron are two essential metals that also play a significant role in the rapid proliferation of cancer cells, which has been demonstrated in numerous scientific studies  . As a result, various different chelators have been researched and developed to suppress the bioavailability of copper and iron in cancer cells with some making it to clinical trials as potential anticancer agents in humans .
The potential of iron chelators in cancer treatment first came to light in studies evaluating the effects of deferoxamine (DFO) and other iron chelators on leukemia cells in both cultures and patients   . This was then followed by studies on DFO for neuroblastoma and clinical trials in patients, which showed promising results . In subsequent years, numerous clinical trials have been carried out on iron chelating agents as potential therapeutic solutions for many diseases associated with iron metabolism and free radical pathology, including cancer . In recent years, significant advances have been made in understanding how chelators not only modulate iron metabolism, but also pathways related to tumor progression and metastasis . Chelating agents show promise as potential therapeutic agents in cancer treatment, but more research is currently still needed to validate clinical application for cancer patients.
Potential Applications of Chelation Therapy and Cancer
Chelating agents have potential therapeutic application as the primary, alternative, or adjuvant therapy in a wide range of human diseases, notably for conditions that are associated with essential or xenobiotic (toxic) metal overload and consequent free radical pathology  . Chelation can be applied for acute metal toxicity, as an antioxidant, and anti-infective purposes . Furthermore, chelators can modulate protein function and specific pathways that are linked to many different diseases, including cancer .
A major area affecting health and disease is free radical production. Increased production of free radicals and reactive oxygen species (ROS) have been linked to most diseases, including cancer and aging . Heavy metals are known to induce oxidative stress and produce free radicals in the body . Data shows that heavy metals damage DNA through oxidative stress and increase the risk of cancer .
It is claimed by alternative health practitioners that heavy metal detoxification through chelation therapy can help to prevent cancer and also support the healing process of cancer patients. Given that heavy metals act as free radicals in the body, damage the DNA of healthy cells and cause them to mutate into cancer cells, it is logically claimed and reported that removing heavy metals from the body can provide therapeutic benefits for those suffering from cancer or those wishing to prevent it.
Furthermore, heavy metal toxicity is believed to suppress the immune system, trigger inflammation, and negatively affect enzyme systems that are important for the proper functioning of the human body. In short, heavy metals can be highly detrimental to a patient’s overall health. Therefore, removing these toxic substances, especially if levels are elevated, could potentially help to support healing and prevent disease development or progression.
New research is emerging that chelators of specific metals (such as iron and copper) that play an important role in the proliferation (rapid growth), angiogenesis (formation of new blood vessels), and metastasis (spread) of cancer could be potent anticancer agents . Iron and copper are major catalysts of free radicals and reactive oxygen species . Furthermore, cancer cells are significantly more dependent on iron for growth and drastically more susceptible to iron depletion than non cancerous cells . The use of chelating agents to deplete levels of specific metals involved in cancer metabolism shows great promise as a new strategy to inhibit cancer growth and development in conjunction with other anticancer approaches .
Proponents of chelation therapy also claim it helps to improve blood flow and can be applied as a treatment for atherosclerosis (hardening of the arteries). It is believed that by removing calcium deposits, which are found in artery-clogging plaques, the treatment can help to restore blood flow in the arteries . There is scientific evidence to support heavy metal bioaccumulation as an important risk factor for atherosclerotic cardiovascular disease .
Moreover, chelation therapy, and certain chelating agents such as EDTA, are reported to have antioxidant effects and protect against the damaging effects of chronic inflammation . Chelation therefore also has potential therapeutic application in the treatment of inflammatory conditions such as osteoarthritis . Chelation is occasionally applied in the treatment of autism, Alzheimer’s and multiple sclerosis .
In summary, there are numerous potential therapeutic applications of chelation therapy. Scientific evidence indicates chelators may have clinical application for the following purposes :
- Removal of metals in diseases associated with essential metal overload
- All diseases related to free radical pathology
- Infectious diseases
- Neurodegenerative diseases
- Acute kidney disease
- Myocardial infarction
- Prevention of metal absorption in the gastrointestinal tract
- Xenobiotic metal detoxification
While chelation therapy is approved by the U.S. FDA to remove heavy metals from the body there is still a lack of clinical research on chelation as a primary or supportive treatment for any disease, including cancer. Due to the known carcinogenicity of heavy metals and potential adverse health effects, the removal of toxic or excess metals may provide benefits for patients with a range of conditions. Research is emerging on specific metal chelators, such as iron and copper, as anticancer agents . However, further clinical trials are still needed to better determine the direct therapeutic effects of chelation therapy in cancer care.
Risks and Side Effects of Chelation Therapy
While chelation therapy is considered to be relatively safe when used appropriately and supported with supplements to avoid mineral deficiencies, there are side effects that have been reported in the scientific literature .
Some of the possible adverse effects of chelation therapy include   :
- Pain or discomfort at the site of injection or infusion
- Nausea and vomiting
- Dizziness or lightheadedness
- Allergic reactions, such as rash, hives, or swelling
- Hypocalcemia (low levels of calcium in the blood)
- Hypoglycemia (low blood sugar)
- Hypotension (low blood pressure)
- Kidney damage
- Cardiac arrhythmias
Some studies have also reported serious adverse events associated with chelation therapy, such as cardiac events, including heart attacks and stroke . These events are rare but can be life-threatening.
It is important to note that while chelation therapy may be beneficial in certain cases, it is not a proven treatment for all conditions. The quality and quantity of scientific evidence on the safety and efficacy of chelation therapy for different conditions is limited and remains a subject of ongoing research and debate.
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References of Chelation Therapy
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