1. A Review of Chelation Therapy in the Treatment of Autism
Kelly Ann LaPietra Caldwell College

2. Source Identification
Keywords: “chelation”, “chelation and autism”
Assigned Textbooks
Barnes and Noble bookstore “Special Needs Children section”
Pubmed Database
Academic Search Premier Database
Psychinfo Database
Google Scholar
Google Search Engine
Autism Resource Websites
References cited in articles and in books

3. OUTLINE TOPIC: Chelation Therapy I. Introduction A. Origin of the word
B. Description
II. History
III. Common Uses
A. Unapproved
B. Approved
IV. Chelation & autism
A. Theory
B. Basis
C. Contradictory evidence
V. Video
VI. Commonly Used Chelators
A. Drug names
B. Administration
VII. Chelation Therapy
A. Preparation
B. Sample Treatment Regimen

4. OUTLINE A. Methods B. Provoked urine excretion test
IIX. Testing
A. Methods
B. Provoked urine excretion test
1. Information gleaned
2. Limitations
IX. Effects of Chelation Therapy
A. Claimed benefit
B. Side effects
X. Treatment
XI. A. Guidelines
B. Qualifications
C. End of treatment indicators
D. Problems
XII. Participating Doctors
XIII. Research
XIV. Any Evidence?
XV. Points of View
X Pseudoscience

5. Chelation Therapy
Derived from the Greek word chele, which means “claw”
Named for the grabbing effect chelating agents have on metal molecules
Refers to the way certain synthetic chemical and body proteins can bind metal molecules
Walker, Morton. (1990). The Chelation Way. NY: Avery Publishing Group.

6. What is Chelation?
Detoxification process by which heavy metals are pulled from tissues and made water-soluble so they can be excreted through urine or stool.
Heavy metals have an affinity for the binding sites of chelators.
There are many different chelating agents and are selected for use based on the metal targeted for removal.
Jepson, B. (2007). Changing the course of autism: A scientific approach for parents and physicians. Boulder, CO: Sentient Publications.

7. HISTORY
First introduced into medicine to cure aresenic-based poison gas that was used in WWI
First chelating agent used was the organic dithiol compound dimercaprol AKA British Anti-Lewisite (BAL)
Large scale lead poisoning of Navy personnel in the wake of WWII, led to the use of EDTA
1960’s DMSA began use (a modified form of BAL with less side effects)
EDTA and BAL were used less after introduction of DMSA
DMSA- became the mainstay for lead, arsenic, and mercury poisoning in the US
Retrieved from
Lead poisoned for painting hulls of ships
DMSA still today

8. HISTORY
Former Soviet Union gave us DMPS, a mercury-chelating agent and ALA, a mercury and arsenic chelator
Today DMPS remains an experimental chelator; ALA is used as a nutritional supplement
EDTA approved by FDA for treating lead and heavy metal toxicity
American College for the Advancement of Medicine (ACAM) began claiming the restorative effects of EDTA in the treatment of atherosclerosis
1998, Federal Trade Commission (FTC) argued against this misrepresentation, citing a lack of evidence
1999, ACAM no longer advertised this claim
Retrieved from

9. A Note of Caution
“NOTE: Due to pharmacological property differences and mechanisms of action, each drug agent should be used as indicated by the FDA or off label usage noted. CIGNA HealthCare does not cover Chelation Therapy for the following indications because they are considered experimental, investigational or unproven!”
Retrieved from

10. What is chelation being used for?
• atherosclerotic vascular diseases
• coronary artery disease
• reperfusion injury during coronary angioplasty or cardiopulmonary
bypass surgery
• progressive renal insufficiency in Type II diabetic nephropathy
• Alzheimer’s disease
• Parkinson’s disease
• primary biliary cirrhosis
• ankylosing spondylitis
• autism
• glioblastoma
• scleroderma
• porphyria
• hypercholesterolemia
Retrieved from

11. Chelating Agents & the Condition they Treat
Coverage Policy
CIGNA HealthCare covers each respective Chelation Therapy agent as Medically necessary when it is used for its usage/FDA approved indication and associated condition as listed in the table below:
DRUGS: Edetate Calcium Disodium (Calcium EDTA) (Calcium Disodium Versenate®)
Succimer (DMSA) (Chemet®)
CONDITION: heavy metal overload or toxicity (e.g., lead, arsenic, mercury, iron,
copper, or gold) confirmed by appropriate laboratory results (e.g.,
blood, plasma, and/or urine) or clinical findings consistent with metal
toxicity
Retrieved from
There are several chelating agents that are dependent on the target metal, but again, for the purpose of this class, I will touch on the ones mentioned in the chelation/autism literature
Remember that these are only 2 of the chelators being commonly given for tx of autism

12. CHELATION AND AUTISM
THEORY: Children with autism carry a toxic heavy metal body burden (Bernard, S., Enayati, A., Redwood, L., Roger, H., & Binstock, T., 2001).
RATIONALE FOR TX: Chelating agents will remove the offending toxins from the body and the symptoms of autism will decrease.
If we are all exposed to heavy metals throughout our lives and proponents of chelation for autism claim these metals have a causal role in the onset of autism, why doesn’t everyone get autism?
High exposure in infancy or “pathophysiology” that impairs their ability to excrete heavy metal toxins from their body and makes them susceptible to metal toxicity

13. What evidence are they basing this theory on?
Low levels of mercury found in baby hair of children with autism compared to controls (Holmes, A. S., Blaxill, M. F., & Haley, B. E., 2003).
High levels of mercury in baby teeth of children with autism compared to controls (Adams, J. B., Romdalvik, J., Sadagopa, V. M., & Legator, M. S., 2007).
Higher mercury excretion after a 3-day treatment with DMSA in children with ASDs compared to controls (Bradstreet, J., Geier, D. A., Kartzinel, J. J., Adams, J. B., & Geier, M. R., 2003)
We will talk about the errors of higher excretion with challenge dose of chelator

14. CONTRADICTORY EVIDENCE
Williams, Hersh, and Sears (2008) found that there were no significant differences between mercury levels in hair of children with autism and their typically developing siblings.
In 2007, Soden, Lowry, Garrison, and Wasserman found that when a 24-hr DMSA provoked excretion test was administered to children with autism there was no measurable increase in excretion of toxic metals.

15. VIDEO Dateline MSNBC (2006): Interview with Dr. Jim Adams

16. 4 Most Commonly Used Chelators in the Treatment of Autism
DMSA (dimercaptosuccinic acid)*
EDTA (Calcium EDTA) *
DMPS (2, 3-dimercapto-1-propanesulfonic acid)
Jepson, B. (2007). Changing the course of autism: A scientific approach for parents and physicians. Boulder, CO: Sentient Publications.
TTFD (thiamine tetrahydrofurfuryl disulfide)
Lonsdale, D., Shamberger, R. J., & Aduhya, T (2002). Treatment of autism spectrum children with thiamine tetrahydrofurfuryl disulfide: A pilot study. Neuroendocrinological Letters, 23,
Note that only two of these were on Cigna’s list of approved chelating agents. That is right, there are doctors who are administering unapproved chelating agents to children by compounding…

17. How are they administered?
Orally
Transdermally
Intravenously
Rectally (suppositories)
Jepson, B. (2007). Changing the course of autism: A scientific approach for parents and physicians. Boulder, CO: Sentient Publications.

18. PREPARATION FOR CHELATION THERAPY FOR AUTISM
Reduce exposure to toxins
Ex. Consuming organic foods and drinking reverse osmosis water, remove mercury dental fillings, avoid pesticide use
Improve levels of essential vitamins and minerals
Improve glutathione levels
Treat gut dysbiosis
Retrieved from

19. RECOMMENDED TREATMENT REGIMEN
According to the Treatment Options for Mercury/Metal Toxicity in Autism and Related Developmental Disabilities: Consensus Paper (2005), chelation treatment should be administered as follows:
Oral/Rectal Suppository - 3 days of Tx, followed by 11 days off
Transdermal- Tx on alternating day schedule
TTFD: Oral, Transdermally, Rectal Suppository- no Tx recommendations
No treatment protocol for DMPS

20. How are metals being tested?
Hair
Stools
Urine
Blood
Baby teeth
Jepson, B. (2007). Changing the course of autism: A scientific approach for parents and physicians. Boulder, CO: Sentient Publications.
No standard way, except blood lead levels test for the presence of lead since lead exposures are usually from chronic exposure, but mercury, aluminum, arsenic more difficult
Mercury and other metals have a short half life in the blood (weeks)
Hair and urine are measures of excretion

21. PROVOKED URINE EXCRETION TEST
AKA Diagnostic Chelation Challenge
PROCEDURE:
Levels of toxic metals are measured in the urine before the
dose of chelator is administered and then urine is collected for
6-8 hours after and a sample of the accumulation of urine is
tested.
RISK: short-term, if any.
RATIONALE: Metals tend to hide in the body and these
hidden metals are not reflected by evidence- based testing methods
Zhiping, Y., Wu, Q., & Fan, D. (2009) Inappropriate diagnosis and chelation treatment of alleged heavy-metal toxicity Annals of Internal Medicine. 151, 8.
Possibly pro-chelation-autism treatment’s “ruler”

22. 1. Metal was present in the body
What an Increase in Toxic Metals in Urine tells us after Administration of a Challenge Dose of Chelator
1. Metal was present in the body
2. Chelator was able to assist in excretion of metals
Zhiping, Y., Wu, Q., & Fan, D. (2009) Inappropriate diagnosis and chelation treatment of alleged heavy-metal toxicity Annals of Internal Medicine. 151, 8.

23. LIMITATIONS OF PROVOKED TESTING
1. No provoked excretion reference range for comparison.
2. Collecting urine for less than 24-hrs. is not representative of excretion levels.
3. Provocation has been shown to artificially increase the 24-hour average urine mercury level.
Zhiping, Y., Wu, Q., & Fan, D. (2009) Inappropriate diagnosis and chelation treatment of alleged heavy-metal toxicity Annals of Internal Medicine. 151, 8.
End up comparing it against excretion of people not taking a chelator- so of course it would be higher (Consensus Paper) comparing provoked vs. unprovoked- not same thing
Call for a banning of provoked testing because it promotes inappropriate testing

24. CLAIMED BENEFITS OF CHELATION TREATMENT FOR AUTISM
Highly effective in:
removing toxic metals
improving glutathione
normalizing platelets (a marker of inflammation)
Adams, J. B., Baral, M., Geis, E., Mitchell, J., Ingram, J., Hensley, A., Zappia, I., Newmark, S., Gehn, E., Rubin, R. A., Mitchell, K., Bradstreet, J., and El-Dahr, J. (2009). Safety and efficacy of oral DMSA therapy for children with autism spectrum disorders: Part A-Medical results. BMC Clinical Pharmacology, 9, doi: /
Possibly beneficial in:
reducing the symptoms of autism
Rapid progression of language ability
Improved social interaction
Improved eye contact
Decreased Self-stimulatory behaviors
Improvement in both strength and coordinator Retrieved from
What do you think of that claim???

25. POTENTIAL SIDE EFFECTS OF CHELATION I
toxic epidermal necrolysis (TEN)
thrombocytopenia
erythema multiforme (Stevens-Johnson syndrome)
cardiac arythmias
hepatic enzyme elevation
hemolytic anemia
neutropenia
neuropathies
renal dysfunction
essential mineral depletion
potential for medical errors
death
Zhiping, Y., Wu, Q., & Fan, D. (2009) Inappropriate diagnosis and chelation treatment of alleged heavy-metal toxicity Annals of Internal Medicine. 151, 8.
Retrieved from
Metals that were settled now become unsettled and move to different areas of the body (Autism Book, Sears)
Stevens Johnson- self-limited inflammatory disorder of the skin and mucous membranes- get target shaped lesions, sore throat, mucous ulcers, fever- takes weeks to resolve and require care
TEN may be fatal if not recognized

26. POTENTIAL SIDE EFFECTS OF CHELATION II
abdominal cramps
various dermatological symptoms
diarrhea
vomiting
convulsions
severe constipation
bowel paralysis
acute toxicity
allergic reactions (Freeman, 2007)
brain damage (Strangle, D. E., Smith, D. R., Beaudin, S. A., Strawderman, M. S., Levitsky, D. A., & Strupp, B. J., )
regression in language and behavior
clinical symptoms of mercury poisoning
Retrieved from

27. GUIDELINES FOR CHELATION THERAPY
For lead poisoning, candidates are individuals with lead levels of >45mcg/100mL in their blood-only approved standard
Mineral and vitamin supplements should be given before, during, and after chelation therapy
Should be done under supervision of a physician
Kidney and liver function must be evaluated regularly
White blood cell count must be monitored
Adams, J. (2010). Chelation: Removal of toxic metals. In K. Siri & T. Lyons (Eds.), Cutting Edge Therapies for Autism (pp ). NY: Skyhorse Publishing.

28. QUALIFICATIONS FOR CHELATION THERAPY
No standard excretion level
Dr. Neubrander’s office: children’s urine excretion is categorized as in the normal, elevated, or highly elevated range, with those in the highly elevated range qualifying for chelation; based on a provoked urine test (6-8 hr. sample).
R. Neubrander, personal communication, June 1, 2010
When asked if there as any quantification of that measurement, I was told, “no”. Also told not every child with autism needs it- about 4/10 in their office- office manager

29. END OF TREATMENT INDICATORS
At least until urinary collections reveal only modest amounts of toxic metals
When improvement ceases
If the child shows no significant progress during therapy or if they experience regression
Retrieved from
Begin chelating with an agent that preferentially binds to a different metal than the one already chelated with
Adams, J. (2010). Chelation: Removal of toxic metals. In K. Siri & T. Lyons (Eds.), Cutting Edge Therapies for Autism (pp ). NY: Skyhorse Publishing.

30. PROBLEMS WITH CHELATION IN CHILDREN WITH AUTISM
Measures of unprovoked blood and urine reflect only acute, ongoing exposure, and are not a reflection of tissue levels or total body burden make it difficult to assess metal toxicity in the body.
There are no set standards for determining what qualifies as an abnormal or dangerous level in the general population on provocation challenges.
Single provocation challenge tests can be misleading in determining total body burden because of metal’s tendency to compartmentalize in the body.
There are no universal standards of qualifications for chelation therapy or for treatment protocol.
Jepson, B. (2007). Changing the course of autism: A scientific approach for parents and physicians. Boulder, CO: Sentient Publications.
Stop when improvement ceases
Shows no significant progress

31. Where can your child get chelated locally?
DAN! Physicians affiliated with Autism Research Institute Directory
New Generation Medical Doctors affiliated with Generation Rescue Directory

32. HOW DO YOU BECOME… a DAN! physician? 1. Be a medical doctor
2. Sign the ARI/DAN! philosophy statement
3. Pay $250
4. Attend a professional seminar 1x/2 years
Retrieved from
A New Generation Medical Doctor?
1. Be an M.D. or D.O.
2. Share the philosophy or Autism Research Institute
Retrieved from

33. RESEARCH
In a pilot study, Lonsdale et al. (2002) explored the effects TTFD have on children with autism. PARTICIPANTS: 10 children diagnosed with autism TREATMENT: 2x/day rectal suppository containing TTFD for 60 days MEASURE: Clinical effects-ATEC FINDINGS: Autistic spectrum symptoms improved in 8/10 children CONCLUSION: “TTFD might be valuable in the treatment of this devastating and increasingly common disease in children.”

34. LIMITATIONS Other therapies were allowed to continue
Group design masks individual results
No control group
Employed use of hair analysis as one of its measures

35. RESEARCH
In 2004, Dietrich et al. explored the effect DMSA would have on standardized tests of neurodevelopment at age 7 versus controls for children who presented with blood lead levels slightly below lead poisoning level. DESIGN: Randomized, double-blind placebo-controlled trial PARTICIPANTS: 780; completion TREATMENT: 6-13 month administration of DMSA + daily vitamin or placebo FINDINGS: Blood level levels were lowered by DMSA Tx, but no benefit in cognitive, behavioral, and neuromotor endpoints

36. RESEARCH
A controlled study by Strangle et al. (2007 ) looked at risks/benefits of succimer in the
tx of lead poisoning in rats.
Tx group rats exposed to neurotoxic levels of lead poisoning and then injected with succimer chelator
Control group rats with no lead poisoning were injected with succimer chelator
FINDINGS: 1. Learning ability returned to normal in the Tx group
Matches hypothesis that lead in the brain impairs brain function
2. Test scores went down in the control group- actually doing as poorly as the lead-poisoned rats
CONCLUSIONS: Chelation is an effective treatment for lead poisoning, but with no lead to pull from the control rats’ brains, the succimer started attacking the brain cells themselves.
REPERCUSSIONS: In 2008, the National Institutes of Health canceled a controlled trial of succimer treatment in children with ASD because of the risk of brain damage from succimer.
1. Not surprising, but what was surprising 2.

37. RESEARCH In 2009, Dr. James Adams et al. published a randomized,
double-blind investigation of the effect oral DMSA therapy
has on children with autism.
2-part study (Part A: Medical Results, Part B: Behavioral Results)
Phase 1: All 65 participants (3-8yrs old) received a round of DMSA to screen for excretion level.
Those with high urinary excretion of toxic metals (49/65) were randomly assigned to either a Tx or control group.
Phase 2: Tx group- 6 more rounds of DMSA therapy
Control group- 6 rounds of placebo
8 children did not qualify due to low excretion; another 7 dropped out report cited unrelated reasons, 1 dropped out due to adverse reactions before phase 1
4 dropped out due to adverse effects- 2 were tx, 2 were placebo in phase 1

38. Randomized in double-blind manner
RESEARCH
Children with ASD
Randomized in double-blind manner
Topical Glutathione days Placebo Cream
Phase 1
1 round of oral DMSA 3 doses/day 1 round of oral DMSA
x 3 days Metal excretors Metal excretors
Phase 2
6 rounds DMSA rounds of placebo
NOTE: 4 discontinued study due to adverse side effects.

39. RESEARCH How were they measuring effects? Parental Assessments
Pervasive Developmental Disorder Behavior Inventory (PDD-BI)
Autism Treatment Evaluation Checklist (ATEC)
Severity of Autism Scale (SAS)
Parent Global Impressions (PGI)
Trained Evaluator
Autism Diagnostic Observation Schedule (ADOS)

40. RESEARCH
FINDINGS: In a single round for all groups, glutathione and platelet counts were normalized-making study more a comparison of 1 vs. 7 rounds of DMSA. Those in the 7-round group continued to excrete metals (PART A). FINDINGS: The severity of autism significantly decreased during the study for both the Tx and control groups (PART B).
Authors seemed thrilled that they were getting tx effects for both groups- how they took it- just a single round of DMSA decreased everyone’s symptoms- great news! DMSA is effective, but based on parent report and parents were blinded

41. LIMITATIONS Urine collection for only 8 hours
Parents rated behavior change
“Lost” placebo comparison
Arbitrarily chosen level for qualification into Phase 2; above Doctor’s Data reference range- top 95% for typical children not undergoing chelation therapy
Nature of group design average may not reflect the effect for any one participant
Treatment and placebo group did not differ in treatment effects

42. SOME POINTS OF VIEW
does not endorse it, citing that it is not an evidence-based treatment for autism
cautions parents to research available treatments
endorses those treatments that are science-based and have proven effectiveness

43. American Academy of Pediatrics
“Preliminary data from the Centers for Disease Control does not suggest a relationship between thimerosal-containing vaccines and ASD.180 Hair analysis is not recommended for biomonitoring, because false elevations may occur if the specimen is not carefully collected. Provocative chelation tests for mercury have not been scientifically validated and are also not recommended. Several chelating agents, including succimer, dimercaprol, d-penicillamine, and N-acetylcysteine, have been shown to accelerate mercury elimination from the body.181 However, there is no evidence that chelation therapy will improve developmental function when given to treat mercury toxicosis. Moreover, chelating agents can have significant toxicity (eg, hepatotoxicity) and precipitate allergic reaction.182 Chelation therapy is therefore not recommended for the purpose of improving neurodevelopmental function in children with ASD.”
Committee on Children with Disabilities, Technical Report: The Pediatrician’s Role in the Diagnosis and Management of Autistic Spectrum Disorder in Children. Pediatrics, 107, e85.

44. Any Evidence?
Based on the theory that autism is a result of heavy metal poisoning, but there is no clear evidence to support this assertion
Diagnosis of autism is based on behavioral characteristics- Today still no commonly accepted, biological marker associated with autism
No medical test to diagnose autism
After chelation therapy still no biological marker we can use to see if there has been significant improvement in the child’s degree of autism
Use hair analysis which is not yet accepted by the mainstream community for this application
Freeman, S. K. (2007). The complete guide to autism treatments: A parent’s handbook Lynden, WA: SKF Books.

45. Any Evidence?
Is there scientific data published in peer-reviewed journals to suggest that chelation therapy is an effective treatment for autism?
No controlled studies with outcome data regarding the effectiveness of chelation in improving symptoms of autism
Claim that chelation can extract metals and repair possible damage to the brain has no supporting evidence in children with autism
There is much anecdotal support in the form of parental report.
Freeman, S. K. (2007). The complete guide to autism treatments: A parent’s handbook Lynden,WA: SKF Books.

46. Future Research?
Strangle et al. (2007) demonstrated that it would be unethical to test effects of chelation on children in clinical studies due to the potential health risks associated with the drugs.

47. CONTROVERSIAL CONTROVERSIAL CONTROVERSIAL
What part of using chelation in the treatment for autism
is NOT experimental?
From the experimental testing to the
unproven high body burden of chelable metals to the unapproved treatment to the lack of clinical trials.
THERE IS NOT ONE EVIDENCE-BASED LEG TO STAND ON!
DO NO HARM!
NOT ONLY DOES IT LACK SCIENTIFICALLY SOUND EVIDENCE, BUT IT IS A HARMFUL AND POTENTIALLY FATAL EXPERIMENT TO DO ON A CHILD!

48. PSEUDOSCIENCE?
Promoters benefit financially or otherwise from adoption of the therapy.
Authors of the studies and those with websites touting parent testimonials are the same professionals who are directly benefitting from the use of chelation therapy to treat autism.
Catchy, emotionally appealing slogans are used in marketing the therapy.
The two largest organizations that are promoting biomedical interventions, including metal detoxification/chelation therapy have as part of their slogans, “Autism is Reversible” (Generation Rescue) and “Autism is Treatable” (Autism Research Institute). The word, “recovery” is often used on both website.
Promoters resist objective evaluation and scrutiny of the therapy by others.
Maintain that their findings are accurate despite other studies showing contradictory evidence.
Testimonials, anecdotes, or personal accounts are offered in support of claims about the therapy's effectiveness, but little or no objective evidence is provided.
These websites are chockful of parent testimonials. Much credence is put on the Autism Research Institute’s “Parent Ratings of Behavior Effects of Biomedical Interventions” that report chelation therapy scores the highest (74%) for reports of children who “got better” and a low 3% of parent’s reporting that children “got worse.”
Retrieved from
Negative findings from scientific studies are ignored or dismissed.
Despite evidence that contradicts theory, continue to argue that the theory is supported by scientific evidence.

49. PSEUDOSCIENCE?
Critics and scientific investigators are often met with hostility, and are accused of persecuting the promoters, being "close-minded," or having some ulterior motive for "debunking" the therapy.
Argue there is a cover-up by the CDC and Big Pharm to prove their theory as unsubstantiated.
Rapid effects are promised.
Claim in the “studies” is that children improve with only a few rounds- in 1 study 1 round was sufficient! That is a total of 3 days! Wow, that WAS easy!
The "theory" behind the therapy contradicts objective knowledge (and sometimes, common sense).
Autism has not been shown to be a disease that can be tested medically. Yes, it may comorbidly exist with many other medical ailments, but it itself is not diagnosed medically. Treating the disorder by medical means contradicts all that we know about autism and its diagnosis.
The therapy is said to be easy to administer, requiring little training or expertise.
There are many parents at home chelating their child with autism.
High "success" rates are claimed.
Many children are being cured of autism by chelation therapy. Almost all in the study by Adams et al. (2009) showed improvement after just 1 round of DMSA according to the authors.
Use uncoventional ways to measure.
Blood test won’t show these metals- do a hair test or “provoke” the toxins out

50. PSEUDOSCIENCE? Professionals or other people recommend them.
Majority, if not all, of the people claiming that children with autism have a toxic metal body burden are the same people who are extolling the benefits of chelation. Who are these people? DOCTORS, one of the most historically trusted professions! If they are saying it, it has to be true!

51. Questions ?

52. THANK YOU

53. REFERENCES
Adams, J. B., Romdalvik, J., Sadagopa, V. M., and Legator, M. S. (2007). Mercury, lead, and zinc in baby teeth of children with autism versus controls. Journal of Toxicology and Environmental Health, 70, Adams, J. B., Baral, M., Geis, E., Mitchell, J., Ingram, J., Hensley, A., Zappia, I., Newmark, S., Gehn, E., Rubin, R. A., Mitchell, K., Bradstreet, J., and El- Dahr, J. (2009). Safety and efficacy of oral DMSA therapy for children with autism spectrum disorders: Part A-Medical results. BMC Clinical Pharmacology, 9, doi: / Adams, J. B., Baral, M., Geis, E., Mitchell, J., Ingram, J., Hensley, A., Zappia, I., Newmark, S., Gehn, E., Rubin, R. A., Mitchell, K., Bradstreet, J., and El- Dahr, J. (2009). Safety and efficacy of oral DMSA therapy for children with autism spectrum disorders: Part B-Behavioral results. BMC Clinical Pharmacology, 9, doi: /

54. REFERENCES
Adams, J. (2010). Chelation: Removal of toxic metals. In K. Siri & T. Lyons (Eds.), Cutting edge therapies for autism (pp 74-78). NY: Skyhorse Publishing. Bernard, S., Enayati, A, Redwood, L., Roger, H., & Binstock, T. (2001). Autism: A novel form of mercury poisoning. Medical Hypotheses, 56, Bradstreet, J., Geier, D. A., Kartzinel, J. J., Adams, J. B., and Geier, M. R. (2003). A case-control study of mercury burden in children with autistic spectrum disorders. Journal of American Physicians and Surgeons, 8, Committee on Children with Disabilities, Technical Report: The Pediatrician’s Role in the Diagnosis and Management of Autistic Spectrum Disorder in Children. Pediatrics, 107, e85. Coplan, J. (2010). Making sense of autistic spectrum disorders: Creating the brightest future for your child with the best treatment options. NY: Bantam Books.

55. REFERENCES
Dietrich, K. N., Ware, J. H., Salganik, M, Radcliffe, J., Rogan, W. J., Rhoads, G. G., Fay, M. E., Davoli, C. T., Denckla, M. B., Bornschein, R. L., Schwarz, D., Dockery, D. W., Adubato, S., & Jones, R. L. (2004). Effect of chelation therapy on the neuropsychological and behavioral development of lead- exposed children after school entry. Pediatrics, 114, Freeman, S. K. (2007). The complete guide to autism treatments: A parent’s handbook. Lynden, WA: SKF Books. Holmes, A. S., Blaxill, M. F., and Haley, B. E. (2003). Reduced levels of mercury in first baby haircuts of autistic children. Internal Journal of Toxicology, 22, Jepson, B. (2007). Changing the course of autism: A scientific approach for parents and physicians. Boulder, CO: Sentient Publications. Lonsdale, D., Shamberger, R. J., & Audhya, T. (2002). Neuroloendocrinology Letters, 23,

56. REFERENCES
R. Neubrander, personal communication, June 1, 2010
Soden, S., Lowry, J. A., Garrison, C. B., & Wasserman, G. S. (2007) Hour provoked urine excretion test for heavy metals in children with autism and typically developing controls, a pilot study. Clinical Toxicology. 45, doi: /
Strangle, D. E., Smith, D. R., Beaudin, S. A., Strawderman, M. S., Levitsky, D. A., & Strupp, B. J. (2007). Succimer chelation improves learning, attention, and arousal regulation in lead-exposed rats but produces lasting cognitive impairment in the absence of lead exposure. Environmental Health Perspectives, 115, 2,
Walker, Morton. (1990). The Chelation Way. NY: Avery Publishing Group.
Williams, P. G., Hersh, J. H., Allard, A., & Sears, L. L. (2008). A controlled study of mercury levels in hair samples of children with autism as compared to their typically developing siblings. Research in Autism Spectrum Disorders, 2, doi: /j. rasd

57. REFERENCES
Zhiping, Y., Wu, Q., & Fan, D. (2009). Inappropriate diagnosis and chelation treatment of alleged heavy-metal toxicity. Annals of Internal Medicine, 151,

58. RESEARCH
Autism: A Novel Form of Mercury Poisoning Bernard, et al. Hypothesized that the regressive form of autism represents another form of mercury poisoning based on similarity between traits of mercury poisoning and autism and physiological abnormalities + the known exposure to mercury in vaccines

59. RESEARCH In 2007, a pilot study was conducted by that in
24-Hour provoked urine excretion test for heavy metals in children with autism and typically developing controls, a pilot study (2007)
QUESTION POSED: Does a proportion of children with autism have an excess chelatable body burden of arsenic, cadmium, lead, or mercury?
FINDINGS: DMSA provoked excretion testing did not produce evidence of an excess chelatable body burden among the autistic participants in this study. The data presents no justification for chelation therapy for the participants.
CONCLUSIONS:NO DEFINITIVE EVIDENCE TO SUPPORT LIKELIHOOD THAT CHILDREN WITH A. ARE AT INCREASED RISK OF A CHELATABLE HEAVY METAL BODY BURDEN WITH THE POSSIBLE EXCEPTION OF CHILDREN WITH PICA OR MOUTHING BEHAVIORS SECONDARY TO AUTISM

60. RESEARCH
Reduced Levels of Mercury in First Baby Haircuts of Autistic Children
Holmes, et al.
FINDINGS: found children with autism had less mercury in their hair than age and gender-matched controls
IMPLICATIONS: children with autism may have impaired detoxification capacity and if reduced overall mercury elimination is related to hair elimination, then autistic infants will retain significantly higher levels of mercury in tissue, including the brain, than normal infants

61. RESEARCH
Williams, et al. -blind study Found no significant differences between mercury levels in hair of 15 children with autism and those of the hair of their typically developing siblings Question the theory that mercury toxicity causes autism and points to difficulty in quantifying chronic mercury exposure through currently available laboratory measures

62. Even if the claims that mercury causes ASD and that chelation helps are both true (and at present there is very contradictory support for and against these hypotheses), somewhere there has to be a tipping point between the risks of mercury exposure and the risk of brain damage from succimer, itself. If the child’s mercury is not high enough, the succimer will go after the child’s brain instead
Coplan

63. Disclaimer
I could talk for a whole semester on the theory behind these interventions and whether they have a leg to stand on and THEN whether the intervention proposed is effective at treating autism, but for the purpose of this class I will just inform you of the theory behind the rationale and then speak to the tx’s effectiveness in treating the symptoms of autism
Neither of these two txs are to be used in a vacuum- proponents of both call for multiple txs- making anecdotal report for these treatments in the autism community even less credible

64. A Review of Hyperbaric Oxygen Therapy in the Treatment of Autism
Kelly Ann LaPietra
Caldwell College

65. Source Identification
Keywords: “chelation”, “chelation and autism”, “hyperbaric oxygen therapy”, “hyperbaric oxygen therapy and autism”
Assigned Textbooks
Barnes and Noble bookstore “Special Needs Children section”
Pubmed Database
Academic Search Premier Database
Psychinfo Database
Google Scholar
Google Search Engine
Autism Resource Websites
References cited in articles and in books

66. OUTLINE

67. What is Hyperbaric Oxygen Therapy?
Hyperbaric oxygen therapy involves breathing up to 100% oxygen at greater than 1 atmosphere (ATA) in a pressurized chamber.
Hyperoxia- an increased level of oxygen in the tissues of the body (Coplan)
Explain that at sea level air breathed is 1 ATA; most clinical applications are between , but for autism we will talk about is at the low to mild pressure end

68. 3 factors that are varied to achieve tx protocols and clinical results for children with autism
1. how much pressure is applied ( )
2. how strong oxygen concentration is (24%-100%)
3. how long tx session lasts (1-1.5 hrs. per dive)
Neubrander

69. History of Hyperbaric Oxygen Therapy
1783 French physician Caillens- first to use oxygen as remedy
’s oxygen tolerance limits were established for divers- basis for oxygen recompression tables used today
Borema, “Father of Modern Hyperbaric Medicine”- late 50’s removed all red cells from pigs, with only plasma remaining, living under hyperbaric conditions
First Hyperbaric Oxygen Therapy textbook published by Davis and Hunt (1977)

70. Uses for Hyperbaric Oxygen Therapy
Wound healing (Coplan)
Carbon monoxide poisoning
Decompression sickness (Jepson)
Burns
Gas gangrene
Exceptional blood loss (Lerman)

71. HBOT AND AUTISM
THEORY: some children with autism have hypoxia, gut inflammation, compromised immune function
RATIONALE FOR TX: providing an elevated level of oxygen to the tissues in a pressurized chamber will decrease core symptoms of autism.
(2002) Heuser published SPECT scan results from a 4-yr. old with autism post-HBOT
Include what he found

72. What evidence are they basing this theory on?

73. Lerman reports such nerurological abnormalities have been verified and no controlled studies have been conducted on the behavioral outcomes of HBOT with this population

74. CLAIMED BENEFITS OF HBOT FOR AUTISM
Relieves hypoxia
Lowers the presence of anaerobic gut bacteria
Decreases inflammation
Improves immune function
Lowers oxidative stress
Increases glutathione levels
(Jepson)
Improves symptoms of autism (Rossignol 2006)

75. Dr. Neubrander’s PREDICTED OUTCOMES
Only mild or mild to moderate responses within first 40 hr set
Recommended to continue for several cycles- most powerful tx to induce language, increase awareness and cognition, and allow more normal socialization and emotional responses
Better with pre-tx adjunct therapies including, methyl-B12 shots and supplements

76. POTENTIAL SIDE EFFECTS OF HBOT
Increases oxidative stress which potentially can cause brain damage
Triggers cell death by a process known as apotosis
Leads to Alzheimer’s disease-related changes in the brain
Death
(Coplan)
Death (cite)
Increased oxidative stress
Barotruma
Sinus squeeze
Serous otitis
Claustrophobia
Reversible myopia
Seizures
Oxygen toxicity (Lerman)
Aspiration (Lerman)

77. Variations in Protocol
Pressure used ( ATA)
100% oxygen vs. oxygen concentrator
Length of session (between 60-90min.)
Number of sessions per day (1-2)
Time elapsed between sessions (2-12hrs.)
Number of treatment hours per treatment set (40-90hrs.)
Q. What is the right recipe?
A. No one knows right now.

78. GUIDELINES FOR HBOT Requires a medical doctor’s prescription
Remember it is a drug therapy- too little may not be effective, but too much is toxic

79. Where can you go for a dive?
Many clinics
No hospitals- not an approved indication for HBOT
Dr. Neubrander, Edison, NJ- home rental
Can purchase via (put price)

80. RESEARCH Rossignol (2007) first prospective study of HBOT with autism
The effects of hyperbaric oxygen therapy on oxidative stress, inflammation, and symptoms in children with autism: An open label pilot study
PURPOSE:
1. Measure the effects of HBOT on oxidative stress markers
2. Measure the impact of HBOT on an inflammatory marker
3. Examine the changes in clinical symptoms, as rated by parents or caregivers, after tx with HBOT
4. Evaluate the safety of HBOT, used at 1.3 and 24% oxygen and 1.5 ATA and 100% oxygen
Open study- no placebo control group

81. Rossignol (2007)
FINDINGS:
Not significantly associated with increased intracellular oxidative stress
Improved inflammation
HBOT was safely administered to all participants and all finished 40 dives without any major adverse events

82. RESEARCH Rossignol (2007) LIMITATIONS:
Clinical outcomes were based on parent-ratings
Parents were not blind
No placebo-control group
Small sample size
Parents may have been bias
Can’t rule out confounding variables
Small size may not be generalizable

83. RESEARCH Rossignol et al. 2006 67 medical hypotheses
PURPOSE: on 6 children with autism
Study Design: Retrospective pilot study
FINDINGS: showed modest behavioral improvements, especially in the younger patients, according to parent assessment using various behavior scales
40 1 hr. 1.3 ATA and 28-30% oxygen over 3 mos.

84. RESEARCH Rossignol et al. 2006 67 medical hypotheses LIMITATIONS:
based on parent report
not blind
no placebo group
allowed participants to continue with other treatments
and add new ones during the time of the study

85. RESEARCH
Granpeesheh, D. et al. Randomized trial of hyperbaric oxygen therapy for children with autism. PURPOSE: to test the hypothesis that HBOT would have a beneficial effect on ASD symptoms in the context of a double-blind placebo-controlled trial INDEPENDENT VARIABLE: 24% oxygen at 1.3 ATA DEPENDENT VARIABLE: direct observational measures of behaviors symptomatic of autism and standardized psychological assessments FINDINGS: there were no differences detected between HBOT and placebo groups across any of the outcomes

86. RESEARCH
Granpeesheh, D.
LIMITATIONS:

87. RESEARCH
Lerman et al.
Using behavior analysis to examine the outcomes of unproven therapies: An evaluation of hyperbaric oxygen therapy for children with autism
Purpose: to conduct a systematic evaluation of HBOT with children who were attending a day program for children with autism
Design: multiple-baseline across participants
Findings: HBOT did not improve task engagement or decrease problem behavior beyond that provided by ongoing behavior analytic services. Also not associated with changes in spontaneous communication for 2/3 participants.
Conclusion: The effects of HBOT were not worth the price.

88. RESEARCH Lerman et al. (continued) LIMITATIONS:
Small sample size, 1 participant dropped out after 27 due to a non-related ear infection
Only tested at 88% oxygen at 1.3 ATA, 40 dives at 60 minutes each
Along with HBOT, 60-minutes of access to preferred items was added to their day
A different combination of pressure and oxygen may yield different results as might number of dives and length of dives
60 min of preferred may have confounded- should have given 60 min of preferred before tx began

89. RESEARCH Rossignol et al. First randomized controlled trial of HBOT
62 children either received HBOT or placebo treatment
Authors used 3 scales- the Aberrant Behavior Checklist (ABC), the Autism Treatment Evaluation Checklist (ATEC), and the Clinical Global Impression (CGI) as outcome measures.
Found differences in favor of the HBOT group for one of six subscales on the ABC, 1/5 on the ATEC, and 3/18 on the CGI, but even those few beneficial results were inconsistent- while eye contact and receptive language were improved on the CGI post-tx, social awareness, social interaction, and speech/language were not
Authors completely disregard the research showing oxygen toxicity to the developing brain, asserting that it is generally regarded as safe on the basis of a single paper
TAKEN FROM COPLAN BUT WILL CITE ROSSIGNOL

90. FUTURE RESEARCH
More controlled research with randomized participants with autism
More controlled experimentation with magnitude and duration of independent variables
Replication, replication, replication

91. Even if you are convinced that the exposure to increased oxygen levels is effective in the treatment of ASD, and the risks of brain damage from oxygen are exaggerated, you may be surprised to learn that breathing oxygen from a mask can achieve the same increase in brain oxygen levels as going into a tank at a fraction of the cost- smells like quackery
Coplan

92. Questions ?

93. THANK YOU

94. REFERENCES
Jepson, B. (2007). Changing the course of autism: A scientific approach for parents and physicians. Boulder, CO: Sentient Publications. Coplan, J. (2010). Making sense of autistic spectrum disorders: Creating the brightest future for your child with the best treatment options. NY: Bantam Books. Freeman, S. K. (2007). The complete guide to autism treatments: A parent’s handbook. Lynden, WA: SKF Books.

95. REFERENCES
Siri, K., and Lyons, T. (2010). Cutting-edge therapies for autism: NY: Skyhorse Publishing. Rossignol, D. A., Rossignol, L. W., Smith, S., Schneider, C., Logerquist, S., Usman, A., Neubrander, J. Madren, E. M., Hintz, G., Grushkin, B., & Mumper, E. A. (2009). Hyperbaric treatment for children with autism: A multicenter, randomized, double- blind, controlled trial. BMC Pediatrics. 9:21 doi: /

96. REFERENCES

97. REFERENCES
Strangle, D. E., Smith, D. R., Beaudin, S. A., Strawderman, M. S., Levitsky, D. A., & Strupp, B. J. (2007). Succimer chelation improves learning, attention, and arousal regulation in lead- exposed rats but produces lasting cognitive impairment in the absence of lead exposure. Environmental Health Perspectives, 115, 2, Williams, P. G., Hersh, J. H., Allard, A., & Sears, L. L. (2008). A controlled study of mercury levels in hair samples of children with autism as compared to their typically developing siblings. Research in Autism Spectrum Disorders, 2, doi: /j. rasd

98. REFERENCES

99. Even if your child has proven metal toxicity, chelation is just one of the ones to address the problem (list ways- change diet, environment, add supplements, etc.)- many things you can do before you do that

100. Approved Indications
DRUG: Edetate Calcium Disodium (Calcium EDTA) (Calcium Disodium Versenate®)
USAGE/APPROVED FDA INDICATION:
Edetate calcium disodium is indicated for the reduction of
blood levels and depot stores of lead in lead poisoning (acute
and chronic) and lead encephalopathy, in both pediatric
populations and adults. Chelation therapy should not replace
effective measures to eliminate or reduce further exposure to
lead.
This is direct quote- figure out how to do it or paraphrase

101. Approved Indications
DRUG: Succimer (DMSA) (Chemet®) USAGE/APPROVED FDA INDICATION: Lead poisoning in pediatric patients with blood lead levels above 45 mcg/dL