Chelation therapy

Chelators or chelating agents are either organic or inorganic compounds that can bind with metals and form ring-like structures called chelates. An ideal chelating agent should have the following properties:

• Low toxicity
• Highly soluble in water
• Ability to cross cell membranes
• Not affected by the pH of body fluids
• Have the same distribution as the metal (so it can reach all places the metal is)
• High affinity towards the metal (so it can quickly bind with the metal and eliminate any competition)
• Ability to form chelates that are less toxic than the metal itself 

Here are some of the commonly used chelators:

1. BAL (British Anti Lewisite) or 2,3-Dimercaprol: This is one of the oldest chelating agents that is used for the treatment of lead poisoning, gold and mercury poisoning, and arsenic poisoning. BAL solution is oily but clear and has a pungent smell. Due to its oily nature, BAL is given through a deep intramuscular injection. The compound has some of the following side effects:

• Fever
• Headache
• Conjunctivitis
• Nausea
• Tingling sensations
• Tremors
• A constricted feeling in the body, especially the chest, abdomen, arms and legs, and jaw
• Liver damage
• High blood pressure
• Infection at the injection site
• Skin irritation
• Toxicity on swallowing

BAL has the following drawbacks:

• A pungent rotting egg-like odour
• Cannot be given orally and the intramuscular injection is painful and can trigger allergies in some
• Has a low therapeutic index (can be toxic even at slightly elevated doses)   
• Can cause arsenic accumulation in the brain and testes

2. DMSA/Succimer or meso 2,3-dimercaptosuccinic acid: DMSA is an analogue of BAL that is mainly used to treat lead poisoning. It may also be used to treat mercury or arsenic poisoning. Unlike BAL, DMSA can be given orally as it can get absorbed in the digestive tract. Additionally, it has a greater therapeutic window than BAL and is not very toxic. 

A major drawback of DMSA is that it cannot cross cell membranes. Some side effects of this compound include:

• It may increase the levels of serum aminotransferase, indicating slight liver toxicity. Though, no major effects on liver have been reported in clinical settings so far.
• It may alter copper metabolism in the body
• Respiratory discomfort
• Eye irritation
• May affect fertility and negatively affect the fetus 

3. Calcium disodium edetate (CaNa2EDTA): CaNa2EDTA is a derivative of a chelating agent called EDTA (ethylenediaminetetraacetic acid) and the most commonly used chelator for the treatment of heavy metal poisoning, especially lead poisoning. It is also said to be beneficial for removing plaque from blood vessels and reducing blood vessel inflammation (read more: what is atherosclerosis?). CaNa2EDTA looks like a white crystalline powder. It is soluble in water and organic solvents and is not absorbed properly in the gut. So, this chelator is administered through the intravenous (IV) route. Some drawbacks of CaNa2EDTA include:

• It cannot cross cell membranes and hence is unable to chelate heavy metals inside body cells.
• CaNa2EDTA injection can be painful.
• It tends to promote the redistribution of lead from other tissues to the brain.

CaNa2EDTA use is associated with the following risks and side effects:

• Skin irritation
• Headache
• Nasal congestion
• Fever
• Frequent urination
• Muscle pain
• Stomach problems
• Fatigue
• Arrhythmia
• Tetany, or overstimulated neuromuscular activity leading to muscle cramps and contraction
• Hypocalcemia
• Low blood pressure
• Kidney damage or renal failure (this is usually dose dependant and at small doses, the damage may be reversed)
• Seizures
• Respiratory arrest

Long-term treatment with CaNa2EDTA can also deplete the body’s reserves of manganese, copper and zinc.

4. d-Penicillamine or DPA: DPA is a degradation product of penicillin. It is easily absorbed in the gut and is hence given both orally or through an intravenous line. The drug does not have many adverse reactions though symptoms like thrombocytopenia, aplastic anaemia and leukocytopenia may occur. Thrombocytopenia refers to low platelet count. Aplastic anaemia is a type of anaemia in which the body doesn't make enough red blood cells. Leukocytopenia is lower than normal white blood cells.

Long-term use of DPA can lead to nausea, vomiting and anorexia. Some other toxic effects of DPA include:

• Gastrointestinal problems
• Proteinuria or presence of protein in urine
• Loss of taste 

Those who are allergic to penicillin may develop an allergic reaction to DPA administration.

In severe cases, DPA may lead to lupus erythematosus, membranous glomerulopathy (a disease that affects the filtering capacity of kidneys) and hypersensitivity pneumonitis (inflammation of lungs).

5. Deferoxamine: Deferoxamine has a higher affinity for iron than any other heavy metal and is hence used for the management of iron related diseases like thalassaemia major. It is also used to reduce aluminium accumulation that occurrs in dialysis patients and in some anaemia patients who need blood transfusions. However, deferoxamine does not bind to iron in haemoglobin or transferrin (the protein that transports iron in the body). Once it binds with iron, deferoxamine is mostly expelled through kidneys and faeces (through bile). Some side effects of deferoxamine include:

• Auditory (ear) and ophthalmic (eye) toxicity
• Allergy
• Skin irritation
• Infections
• Adverse effects on kidneys, lungs and brain

Deferoxamine is avoided in less severe cases of iron toxicity due to its various side effects on body.

Here are some approved and not approved uses of chelation therapy:

• Removal of heavy metals from the body: Chelation therapy is most commonly used for the treatment of heavy metal poisoning—that is, toxicity occurring due to accumulation of heavy metals like lead, arsenic, mercury, iron, copper and manganese in the soft tissues.
  Some heavy metals including zinc, iron, copper and manganese are important for body functions but they are only needed in small amounts. In excess, these heavy metals lead to various symptoms that vary as per the metal. For example, manganese poisoning can damage the nervous system and also lead to pneumonia, while overexposure to lead can lead to high blood pressure, high protein levels in the blood, ataxia (a movement disorder), and damage to reproductive organs.
  Heavy metal poisoning can occur due to occupational exposure such as exposure to arsenic while manufacturing paint or glass and exposure to mercury in thermometer manufacturing plants, ingestion of insecticides, herbicides or fungicides or foods or water contaminated with high levels of certain heavy metals.
  Dialysis patients often end up having excess aluminium in their body and those with thalassemia have high iron levels. Wilson’s disease is a hereditary disorder that leads to copper accumulation in certain areas in the body, mainly the liver, eyes and brain.  

Unapproved uses of chelation therapy

The following are some unapproved uses of chelation therapy: 

• Heart disease treatment: Chelation therapy is believed to be effective in breaking down plaques in blood vessels, and to prevent a coronary artery bypass graft surgery. Mostly, CaNa2EDTA is said to help by chelating the calcium present in plaques or by promoting the release of certain hormones that promote the removal of calcium and reduce cholesterol levels in the body. EDTA is also theorised to be an antioxidant and anti-inflammatory agent and hence effective in reducing blood vessel inflammation.
  A number of studies indicate that CaNa2EDTA may be effective against coronary artery disease. However, a large scale study called TACT (Trial to Assess Chelation Therapy) including more than 1,000 people found that chelation therapy only shows moderate effects in cardiovascular conditions and that too only in diabetic people. Another huge study called TACT2 is now being conducted to study the effect of chelation therapy on the cardiovascular health of diabetics. (Read more: Diabetes symptoms)
• Autism: According to the National Capital Poison Center, a US-based NGO, the use of chelation therapy for autism comes from a belief that mercury exposure leads to autism. The belief is that a mercury compound called thimerosal present in vaccines leads to autism. Exposure to mercury in the womb may occur if the expecting mother takes certain medications, eats food that may contain mercury like some types of fish (oral ingestion), or inhales mercury somehow. In fact, a lot of symptoms of autism and mercury poisoning overlap. For example, delay in intellectual development.
  However, there isn’t strong evidence to prove any link between mercury exposure and autism. A case-control study including 256 children with autism spectrum disorder suggested that prenatal or early life exposure to thimerosal does not lead to autism. Another study done in Italy indicated that there is no difference in mercury levels in autistic patients. Some studies have found high levels of lead in autism patients instead of mercury. Additionally, one theory suggests that autism occurs due to high levels of intracellular mercury instead of mercury in the blood. But this hypothesis is not yet proven either.
• Alzheimer’s: Alzheimer’s is a neurological disease with no known cause and no treatment. Amyloid plaques, which are accumulated beta-amyloid peptides, found in the brain of Alzheimer’s patients is suggested to be a possible cause of the disease. However, some suggest that only amyloid peptide accumulation cannot be the cause of Alzheimer’s. Instead, abnormal levels of heavy metals like zinc, iron and copper in the brain create an abnormal form of beta-amyloid protein that tends to get aggregated. Also, the heavy metals increase oxidative stress which then drives the disease. HIgh aluminium concentration in the brain has also been associated with Alzheimer’s. Hence, a lot of chelating agents are proposed to be beneficial in the management of Alzheimer’s. However, there isn’t much evidence to show the benefits of chelation therapy in Alzheimer’s treatment. On the contrary, several studies indicate that there is no link between aluminium exposure and Alzheimer’s. Experts suggest that most of the currently used chelators are too big to pass the blood-brain barrier. The blood-brain barrier is a term used to refer to the endothelial membranes of blood vessels in the brain that regulate the movement of molecules between the blood and the brain.
• Parkinson’s disease: Parkinson’s is a neurodegenerative disorder that causes loss of balance and coordination, impaired memory, tremors and shakiness. The disease occurs due to nerve damage (or death) and reduction in the amounts of dopamine (a neurotransmitter) in the brain. Though the exact cause of neuron death is not known, iron accumulation in the brain is suggested to be a possible cause. Research is currently going on to study the benefits (if any) of chelation therapy for Parkinson’s disease. So far, the evidence is inconclusive.

Before recommending chelation therapy, your doctor will ask you to undergo some tests like a urine test or blood test to check the levels of heavy metals in your body. Some examples include:

• Lead urine test
• Mercury urine test
• Lead blood test
• Cadmium blood test
• Chromium blood test
• Copper blood test
• Mercury blood test
• Arsenic blood test
• Aluminium blood test

Based on the heavy metal you have an excess of, the doctor will choose a chelating agent and administer it either orally or intravenously (depending on the chelator). You may feel a little discomfort when the needle is inserted. You would be asked to stay in the clinic/hospital for a while so the doctor can ascertain you are not showing any side effects of the therapy. 

Depending on how much heavy metal you have in your body. You may need multiple sittings spread over a period of time—it may take anywhere from a few weeks to a few months. The chelating agents and the heavy metals they bind with will keep on being expelled from your body, usually through urine but could also be through faeces. 

While the therapy is going on, you will be asked to avoid further exposure to the heavy metal or consuming foods that are high in that metal.

As mentioned before, every chelating agent has its own set of side effects which include: 

• Fever
• Headache
• Nausea and vomiting
• Fatigue
• Muscle pain
• Low blood pressure or high blood pressure
• Hypocalcemia
• Arrhythmia
• Skin irritation or rashes
• Damage to kidneys or liver

Chelators that are given through the intravenous route also carry the risk of infection when not given correctly. Some chelators can also lead to allergic reactions and deficiency of other minerals.

Pregnant women and those with kidney failure should not take chelation therapy. If you smoke or drink or have a chronic disease, talk to your doctor about it before starting chelation therapy.