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Chelation and Autism Ranking: Mildly Hazardous Insufficient/Mixed evidence

Chelating agent Chelation (also known as detoxification or detox) is a medical procedure used to remove heavy metals like mercury or lead from the body.

Chelation involves using one or more 'chelators' (chemicals such as DMSA, DMPS and EDTA) to remove the metals from the body.

The chelators may be given orally, by intravenous infusion, or in the form of nasal sprays, suppositories or creams. Once in the body, they are designed to ‘bind’ to the metals, allowing them to be flushed out of the body through your urine.

Some people think that the core features of autism and other problems faced by autistic people (such as poor strength and coordination) are caused by, or made worse, by the presence of heavy metals.

They also think that chelation can be used to prevent or reduce those core features and those other problems.

Please Note

The National Institute of Health and Care Excellence (NICE) made the following recommendations:

'Do not use chelation for the management of core symptoms of autism in adults.' (NICE, 2012)

'Do not use [chelation] to manage autism in any context in children and young people' (NICE, 2013)

Our Opinion

There is no high quality research evidence to show that heavy metals (such as lead or mercury) cause autism or any of problems faced by autistic people.

There is no high quality research evidence to suggest that chelators (such as DMSA, DMPS or EDTA) prevent or reduce the core features of autism in autistic people.

There is no high quality research evidence to suggest that chelators (such as DMSA, DMPS or EDTA) prevent or reduce any of the problems faced by autistic people.

There is mixed research evidence on the benefits of N-Acetyl-L-cysteine which is sometimes used as a chelator. However there is no evidence to suggest that any benefits which may or may not have arisen from the use of N-Acetyl-L-cysteine were due to the effects of removing heavy metals.

There is some high quality research evidence which suggests that some chelators are potentially extremely hazardous.

For these reasons, we strongly recommend that chelation is not used as an intervention for autistic people.

Disclaimer

Please read our Disclaimer on Autism Interventions


Audience

The proponents of chelation claim that it is suitable for most children with autism because ‘most children with autism suffer from mercury/metal toxicity.’ (DAN!, 1999).

However this claim is not accepted by the majority of academic researchers.

Aims and Claims

Aims

According to Davis et al (2013)

“Chelation treatment aims to eliminate specific metals from the body. However, empirical evidence has yet to support the hypothesis that the core ASD symptoms are caused by the presence of such metals in the body. Because empirical evidence does not support the hypothesis that the core ASD symptoms are associated with specific levels of metals in the body, the use of chelation to remove metals from the body in order to ameliorate ASD symptoms could be seen as unfounded and illogical.”

and

“Moreover, even if metal poisoning contributed to the ASD symptoms, it would still be unclear whether chelation treatment would have the ability to reverse existing neurological problems caused by such exposure, or whether it would only be able to prevent further damage (i.e., worsening of symptoms). In other words, even if the metal poisoning theories held true, it does not necessarily lead to an expectation that chelation would ameliorate current communication and social skills deficits and behavioral impairments, rather than prevent additional or more extensive impairments.”

Claims

There have been various claims for chelation as a treatment for autistic people. For example, Defeat Autism Now! (2005) claimed that

“Many DAN! physicians have reported good improvements with DMSA, although the improvements are sometimes accompanied by gut problems. Reported benefits include rapid progression of language ability, improved social interaction, improved eye contact, and decreased self-stimulatory behaviors (stimming). Children with motor problems have experienced significant improvement in both strength and coordination.”

Key Features

Chelation involves using one or more chemicals or other substances to correct chemical imbalances in the bodies of individuals with autism.

Chelating agents

There is a wide range of different chelating agents, each of which has different properties (such as effectiveness and side effects).

They include

  • Alpha lipoic acid, aka dihydrolipoic acid, lipoic acid, lipolate or thiotic acid.
  • Cysteine, aka acetylcysteine, cystein, cystin, L-cysteine, N-acetylcysteine or NAC.
  • DMSA, aka chemet, dimercaptosuccinic acid or succimer
  • DMPS, aka 2,3-Dimercapto-1-propanesulfonic acid or sodium dimercaptopropanesulfonate
  • EDTA, aka H4EDTA, diaminoethanetetraacetic acid, edetic acid, edetate, ethylenedinitrilotetraacetic acid, tetrine acid, trilon BS, vinkeil 100, versene acid or warkeelate acid
  • NDF, aka nanocolloidal detox factors
  • TTFD, aka thiamine tetrahydrofurfuryl disulfide - a form of thiamine (vitamin B-1)
  • Zeolite, aka cellular zeolite

However not all chelating practitioners agree as to which of these chelating agents is appropriate to use. For example, Defeat Autism Now! states that cysteine should not be used because it may worsen mercury intoxication by spreading it to other tissues. It may also promote or worsen intestinal candidiasis.

Process

Different practitioners of chelation follow different processes. The following processes are those recommended by Defeat Autism Now! in its Mercury Detoxification Consensus Group position paper of 2005.

First stage: Provocation Test

The purpose of the provocation test is to find out if a toxic metal is present in the body, and if the given chelating agent can remove it.
This is done by using a small dose of a given chemical, such as DMSA, followed by a collection of urine or stool depending on the mode of excretion.

Second stage Pre-Detoxification Treatment

  • All sources of the metal are removed from the immediate environment of the child e.g. mercury or lead based paint, flame retardant materials, water which contains uranium.
  • Existing nutritional problems are corrected e.g. the practitioner checks that the child has sufficient vitamins, minerals and amino acids, especially zinc.
  • Glutathione, an anti-oxidant peptide, levels are normalised (usually by giving the child glutathione supplements).
  • Any existing gastro-intestinal problems, such as constipation, diarrohea, bacterial and yeast infections, are corrected. If this is not done, the adverse side effects of the therapy may be made worse e.g. explosive growth of abnormal or pathogenic bacteria or fungi.
  • Liver, kidney and Complete Blood Count are monitored before and during detoxification. Some chelating agents can adversely affect liver/kidney function, platelet count, and lymphocytes.

Third stage  Treatment

The third and last stage of treatment is to give full doses of the chelating agent, along with supplements of minerals and vitamins.

Depending on the chelating agent, it may be given orally, by intravenous infusion, or in the form of nasal sprays, suppositories or creams.

The dosage is determined by the individual's reaction to the initial testing and to subsequent doses of the chelating agent.

Cost and Time

Cost

The costs of undertaking chelation will depend to a large extent on whether you undertake the chelation yourself and/or whether you consult any kind of CAM therapist.

If you undertake the chelation yourself you will need to buy the chelators. The cost of 100 chelating tablets varies between £10 and £100 in the UK depending on the supplier and the specific chelating agent.

If you consult a CAM therapist, the costs may include the chelators, consultation fees, plus any travel and accommodation expenses.

Time

Different people suggest different amounts of time required to undertake chelation for autistic individuals. For example

Davis et al (2013) reported that “The duration of chelation treatment ranged from approximately 1.5–7 months.  Frequencies of administration ranged from 1 to 12 times weekly.”

James et al (2015) reported that “One of the more commonly used chelating substances, oral dimercaptosuccinic acid (DMSA; also called succimer), is given on a cyclical basis at doses of 10 mg/kg/d every eight hours for three days, followed by 11 days with no DMSA. These two-weekly cycles are repeated up to six times, totalling approximately three months of treatment.”

Risks and Safety

Hazards

According to Davis et al (2013)

“The chemical substances utilized in chelation treatment have a myriad of potential and potentially serious, side effects, including fever, vomiting, diarrhea, loss of appetite, hypertension, hemorrhoid symptoms, metallic taste, hypotension, cardiac arrhythmias, hypocalcemia, the latter of which can in turn cause fatal cardiac arrest.  In 2005, for example, a 5-year-old boy with ASD died from cardiac arrest caused by hypocalcemia while receiving intravenous chelation. The potential safety risks associated with chelation recently resulted in a suspension of a clinical study of chelation treatment for autism. Additional safety issues arose from a rodent study that found lasting cognitive impairment.”

According to the American College of Medical Toxicology (2009) even some forms of testing for metal toxicity are potentially harmful.

“It is ... the position of the American College of Medical Toxicology that post-challenge urinary metal testing has not been scientifically validated, has no demonstrated benefit, and may be harmful when applied in the assessment and treatment of patients in whom there is concern for metal poisoning.”

Specific chelators

  • Alpha lipoic acid: According to the University of Maryland Medical Center (2014), side effects are generally rare and may include insomnia, fatigue, diarrhea, and skin rash.
  • DMSA:  According to Flora and Pachauri (2010), “Adverse reaction of DMSA includes gastrointestinal discomfort, skin reaction, mild neutropenia and elevated liver enzymes.” According to Defeat Autism Now! (2005) “Serious side effects of DMSA are extremely rare and include allergic reaction, toxic epidermal necrolysis (TEN) and erythema multiforme (Stevens-Johnson syndrome). Potentially dangerous neutropenia and thrombocytopenia may also occur.”
  • DMPS: According to Flora and Pachauri (2010), “Adverse reactions during treatment with DMPS include gastrointestinal discomfort, skin reactions, mild neutropenia, and elevated liver enzymes.” However, Van Der Linde et al (2008) reported that DMPS had caused Stevens-Johnson syndrome in one child and they concluded that “… chelation therapy with DMPS is not harmless medication; it can have serious side effect and should therefore only be used in patients with proven intoxication.”
  • EDTA: According to Flora and Pachauri (2010), “The risks associated with CaNa2EDTA therapy are substantial, including renal failures, arrhythmias, tetany, hypocalcaemia, hypotension, bone marrow depression, prolonged bleeding time, convulsions, respiratory arrest, etc.”
  • N-Acetyl-L-cysteine: According to the University of Maryland Medical Center (2014), toxic forms of cysteine that should be avoided include D-cysteine, D-cystine, 5-methyl cysteine.  Very high doses (more than 7 grams) of cysteine may be toxic to human cells and may even lead to death. Taking NAC by mouth may cause nausea, vomiting, and diarrhea.
  • TTFD: According to the WebMD website, accessed on 5 August 2016, “Thiamine is likely safe when taken by mouth in appropriate amounts, although rare allergic reactions and skin irritation have occurred”.
  • Zeolite: According to the Memorial Sloan Kettering Cancer Center (2016), some forms of airborne zeolite [a form of zeolite unlikely to be used as a chelator] can cause fibrosis, pneumoconiosis and mesothelioma,

Contraindications

There are a number of contraindications (something which makes a particular treatment or procedure potentially inadvisable) for different groups of people. For example

  • Alpha lipoic acid: According to the University of Maryland Medical Center (2014), alpha-lipoic acid has not been studied in children, so it is not recommended for pediatric use. In addition, alpha lipoic acid should only be used under careful medical supervision in people with certain medical conditions (such as diabetes) or who are taking certain medications (such as those used in chemotherapy).
  • DMSA:  We have been unable to identify any contraindications for DMSA.
  • DMPS: According to the Trace Minerals International Laboratory website, accessed on 3 August 2016, DMPS should only be used under careful medical supervision in people with reduced kidney function, in people with hypersensitivity to DMPS and in people with some allergies or with asthma.
  • EDTA: According to the WebMD website, accessed on 3 August 2016, EDTA should not be used in people who are taking certain medications (such as insulin and wafarin) and should only be used under careful medical supervision in people using diuretic medications [increase urine].  EDTA should only be used under careful medical supervision in people with specific medical conditions such as asthma, epilepsy and heart problems.
  • N-Acetyl-L-cysteine: According to the University of Maryland Medical Center (2014), NAC should only be used under careful medical supervision in people with some heart conditions, in people with cystinuria and in people with asthma.
  • TTFD: According to the WebMD website, accessed on 5 August 2016, there are no known contraindications for TTFD.
  • Zeolite: According to the Memorial Sloan Kettering Cancer Center (2016), you should not take zeolite if you are taking any medications especially if you are a transplant patient and/or taking drugs to suppress the immune system, if you are taking drugs as part of chemotherapy, you are using antibiotics or drugs that contain iron.

Explanation of terms

Arrhythmias (disturbed heart rhythm); cystinuria ( kidney condition); erythema multiforme aka Stevens-Johnson syndrome (potentially fatal skin condition), fibrosis (increase in fibrous tissue); hypocalcemia (low calcium serum levels in the blood; hypertension (low blood pressure); mesothelioma (cancer of the lining of the organs in the body); neutropenia (low levels of a type of blood cell);  pneumoconiosis (respiratory disease); tetany (intermittent muscular spasms); thrombocytopenia  (low amount of blood platelets); toxic epidermal necrolysis (potentially fatal skin condition).

Suppliers and Availability

Suppliers

Most of the substances used in chelation are widely available within Europe, the US and other countries. For example, some chelating agents, such as alpha lipoic acid, are available without a prescription in chemists and health food stores. However the National Capital Poison Center (2010) reported

“Several unapproved ‘chelators’ are marketed for home use. The U.S. Food and Drug Administration (FDA) recently warned several companies that they are breaking the law by marketing such ‘therapies’. FDA noted that all approved chelating drugs require a prescription.”

Credentials

Some providers of chelation will have professional credentials and qualifications, while others will not.

The UK and the US governments do not strictly regulate herbs and supplements. Because of this there is no guarantee of strength, purity or safety of some chelating agents and their effects may vary.

History

Chelation, using synthetic chelating agents, has been practiced for over a century. Chelation was initially used by the military for treating acute exposure to heavy metals and other toxic substances. It has since been developed for use in other medical conditions, including cardiovascular disease, Alzheimer’s disease and cancer.

At the end of the 20th century various researchers suggested that chelating agents could be used to remove heavy metals, especially mercury, from autistic people.

Current Research

We have identified six scientific studies of chelation for autistic people published in peer-reviewed journals, four of which examined the chelating agent DMSA. We have been unable to identify any studies which examined the use of alpha lipoic acid, EDTA or zeolite as chelators.

These trials included more than 180 individuals aged from three to 14 years old and included people with a diagnosis of Asperger syndrome and pervasive developmental disorder - not otherwise specified. 109 of these individuals came from the single study by Adams et al (2009).

The paper by Adams et al (2009) included 2 studies of DMSA, the first included 109 children in an open trial, the second included 65 of those children in a randomised controlled trial.  It stated that DMSA appears to be generally safe, and possibly effective in reducing the symptoms of autism in some children. However it also reported that the DMSA appeared to decrease essential minerals, such as potassium, which is worrying.

  • The study by Blaucok-Busch et al (2012) examined DMSA in 44 autistic children, aged between 3 and 9. It reported improvements in a range of behaviours such as verbal and nonverbal communication; taste, smell and touch; and relating to other people.
  • The study by Eppright et al (1996) examined DMSA and a range of other interventions in a single 4 year-old boy diagnosed with autism and attention deficit hyperactivity disorder. It stated that these interventions led to a reduction in repetitive behaviours.
  • The study by Geier and Geier (2006) examined DMSA in 11 autistic children. It reported “significant improvements in sociability, cognitive awareness, behavior, and clinical symptoms / behaviors of hyperandrogenemia [excessive levels of androgen hormones] were also observed.”
  • The study by Lonsdale et al (2002) examined the effect of TTFD on 10 autistic children. It stated that TTFD appears to have a “beneficial clinical effect.”
  • The study by Patel and Curtis (2007) examined N-Acetyl-L-cysteine as one component of a multi-component biomedical intervention in 10 primary school children. It reported that “All 10 children showed significant improvement in many areas of social interaction, concentration, writing, language, and behavior”.

Please note: we have not included any other studies of N-Acetyl-L-cysteine in our evaluation of chelation because, in none of those studies, was it used as a chelating agent.

Status Research

There are limitations to all of the studies of chelation and autistic individuals identified to date. For example

  • Some of the studies had small numbers of participants. One of the studies (Eppright et al, 1996) had a single participant. Three of the other studies (Geier and Geier, 2006; Lonsdale et al, 2002; Patel and Curtis, 2007) had either 10 or 11 participants.
  • Some of the studies (such as Blaucok-Busch et al, 2012; Geier and Geier, 2006; Lonsdale et al, 2002; Patel and Curtis, 2007) were open label (the participants and researchers knew who got the treatment) and/or had no comparison control group.
  • Some of the studies (such as Eppright et al, 1996; Geier and Geier, 2006; Patel and Curtis, 2007) combined several forms of treatment, making it difficult to evaluate the effectiveness or otherwise of the chelating agent.
  • Some of the studies (Eppright et al, 1996; Patel & Curtis, 2007) used anecdotal reports or researcher created questionnaires to measure change instead of using standard outcome measures.
  • One of the studies (Lonsdale et al, 2002) did not provide enough detail for us to be able to make a considered assessment of the efficacy of the treatment (stating only that TTFD appears to have a “beneficial clinical effect.”
  • Some of the studies (such as Geier & Geier, 2006; Patel & Curtis, 2007) actually reported mixed or negative results which is not necessarily clear from the abstracts or the way that the authors of these studies have represented those results.
  • The study by Adams et al (2009) appears to be more robust than other studies (because it was a large randomised controlled trial) but it is still limited by several significant methodological weaknesses.
  • There was a high attrition rate, with between a quarter and a third of participants dropping out.
  •  It is not clear if parents were truly unaware of which children received DMSA and which children received the placebo during the second phase of the study.
  • There is a high likelihood of carry-over effects (both the experimental group and the control group received an initial round of oral DMSA in phase one)
  • There is missing data from some of the behaviour checklists, although the ADOS scores were unchanged, which makes it difficult to evaluate the real behavioural effect of the intervention.

According to the Cochrane Review - James et al. (2015) - the study by Adams et al (2009) is actually deeply flawed.

“Only one trial was included in this review, and we judged it to have high or uncertain risk of bias and methodological problems that limited the interpretation of outcomes presented. Of particular concern are the trialists’ questionable data analytical approach and interpretation of findings. It is interesting that trialists found differential directions of heavy metal excretion and change in ASD indices, yet they attempted to convince the reader not to read too much into these differences. Given the deleterious effects of chelation, misinterpretation and misuse of the study of Adams et al to justify the use of chelation for ASD is unethical and potentially places children unnecessarily in harm’s way. Moreover, if these findings are in fact valid, they actually undermine the heavy metal toxicity theory and the rationale for chelation treatment, suggesting that it should not be used in the first place."

For a comprehensive list of potential flaws in research studies, please see ‘Why some autism research studies are flawed’.

Future Research

Summary of Existing Research

There is no high quality research evidence to show that heavy metals (such as lead or mercury) cause autism or any of the associated problems faced by autistic people.

There is no high quality research evidence to suggest that chelating agents (such as DMSA, DMPS or EDTA) prevent or reduce the core features of autism in autistic people.

There is no high quality research evidence to suggest that chelating agents (such as DMSA, DMPS or EDTA) prevent or reduce any of the problems faced by autistic people.

There is mixed research evidence on the benefits of N-Acetyl-L-cysteine which is sometimes used as a chelating agent. However there is no evidence to suggest that any benefits which may or may not have arisen from the use of N-Acetyl-L-cysteine were due to the effects of removing heavy metals from the body.

There is some high quality research evidence which suggests that some chelating agents (whether used in treatment or in provocation tests) are potentially extremely hazardous.

Recommendations for Future Research

We agree with the authors of the Cochrane Review of chelation for autism spectrum disorder (ASD) - James et al (2015) - which made the following recommendations

“At the present time, the theory that heavy metals may cause autism or might worsen symptoms has not been established. This underlying theory needs to be tested and confirmed before future trials that assess chelation for ASD symptoms are implemented. However, the numerous side effects of chelation therapy, including hypocalcaemia, renal impairment, musculoskeletal and gastrointestinal symptoms and even death (Morgan, 2002; Brown, 2006; Kosnett, 2010), have led to the withdrawal of at least one planned study. It is therefore unlikely that institutional review boards will approve future trials for chelation for ASD unless safety in children can be assured through the current approach to research.

“If evidence emerges that supports a causal link between heavy metals and autism, further trials with methods suitable to ensure safety and to demonstrate that chelation removes heavy metals, improves social communication and reduces restricted repetitive behaviours seen in autism will be needed.”

Studies and Trials

This section provides details of scientific studies into the effectiveness of this intervention for people with autism which have been published in English-language, peer-reviewed journals.

If you know of any other publications we should list on this page please email info@informationautism.org

Please note that we are unable to supply publications unless we are listed as the publisher. However, if you are a UK resident you may be able to obtain them from your local public library, your college library or direct from the publisher.

Related Studies and Trials


Other Reading

This section provides details of other publications on chelation.

You can find more publications on this topic in our publications database.

If you know of any other publications we should list on this page please email info@informationautism.org

Please note that we are unable to supply publications unless we are listed as the publisher. However, if you are a UK resident you may be able to obtain them from your local public library, your college library or direct from the publisher.

Related Other Reading


Additional Information

According to Goldman and Woolf  (2012)

“Sometimes chelation therapy is recommended based on the results of non-standard laboratory tests for multiple elements performed on samples of hair, blood, urine or other specimens. Such testing may show levels of chemicals above the laboratory’s reference range, but these are not necessarily levels that cause health problems. Sometimes a laboratory test known as “provocation testing” is used which involves giving a chelation medicine to "provoke" and measure the excretion of toxicants. This type of testing is not recommended. It does not reliably show high or toxic levels in the body nor prove the benefit of taking chelation therapy. It is also misleading to compare test results after taking “provoking” chelation medicine to test results from the reference population who have not taken the medicine. In standard medical practice, chelation therapy is given after carefully considering the results of standard laboratory tests, clinical factors, and scientific evidence.”

Related Additional Information


Updated
16 Jun 2022
Last Review
01 Dec 2016
Next Review
01 Apr 2023