Science of Autism

Disclaimer: The information presented on this site is not intended as medical advice. www.autismiscurable.com is solely informational and educational. The information on this web site should not be used for diagnosing any medical or health condition. www.autismiscurable.com is not liable for any direct or indirect claim, loss or damage resulting from use of this web site and/or any web site(s) linked to/from it. If the information on this site intrigues you, please contact a Defeat Autism Now! (DAN!) clinician. (Please see Links section to access a list of DAN! clinicians.)

The Science of Autism

All quotations in this section are used with the lead author’s permission.

For an overwhelmed parent looking for answers, the amount of scientific and medical information about autism is staggering. In fact, if you Google “autism”, you’ll get 18,700,000 websites to weed through! Thanks to the efforts of many talented and dedicated scientists, critical discoveries have been made that help understand the decline into and recovery from autism. This information is being used to recover autistics of all ages.  My goal is to simplify this information and highlight the essential elements. Following is what I have learned about the science of autism along with my observations from autism recoveries.  

In summary:

Autism is a complex biological disorder involving simultaneous and interrelated dysfunction of the detoxification, immune, digestive and neurological systems.

In the body of an autistic individual, portions of the detoxification system, as well as specific metabolic processes become dysfunctional, leading to a diminished ability to completely break down certain foods. When analyzed by sophisticated scientific instruments, a portion of these partially digested substances are shown to resemble morphine (yes, morphine). These neurotoxins (opioid substances) leak out of the digestive tract, into the blood stream and attack the brain/nervous system, producing the symptoms and complications associated with autism. Diminished levels of critical substances such as glutathione (resulting in oxidative stress) keep this process in place.

Recovery of autism requires:

-                Stop the production of neurotoxins (opioid substances)

-                Reduce or eliminate oxidative stress

-                Heal the nervous system

 

DAN! physicians are qualified to treat autism using methods that accomplish these objectives.

The Detoxification and Immune Systems

In October of 2001, a team of clinicians and researchers led by William Walsh, Ph.D. then at the Pheiffer Treatment Center, affiliated with the Health Research Institute now of Warrenville, IL, made available a scientific study entitled “Metallothionein and Autism”.  Metallothionein is a protein that is critical to the process of detoxification of harmful substances, particularly heavy metals and toxic chemicals. (1)

The paper describes a study of 503 patients on the autism spectrum vs. aged-matched non-autistic patients. The conclusion of this study was that “most autistic patients exhibit evidence of metallothionein (MT) dysfunction and this dysfunction may be a universal characteristic of autism-spectrum disorders”.

Translation: the detox systems of autistics are impaired.

Walsh also concluded that “MT dysfunction and autism may result from the intersection of two factors: (a) a genetic defect involving marginal or defective MT functioning, followed by (b) an environmental insult during early development which disables MT.”

According to Walsh’s paper, once MT becomes compromised, a host of other dysfunctions occur, including:

-         Detoxification of mercury and other toxic metals

-         Development and functioning of the immune system

-         Development and paring of brain neurons

-         Regulation of zinc and copper levels in blood

-         Prevention of yeast overgrowth in the intestines

-         Production of enzymes that break down casein and gluten

-         Response to intestinal inflammation

-         Production of stomach acid

-         Taste and texture discrimination of tongue epithelia

-         Hippocampus function and behavior control

-         Development of emotional memory

(Bold emphasis provided by AIC)

Walsh’s paper continues: “Examples of biochemical factors which can disable MT proteins include (a) severe zinc depletion, (b) abnormalities in the glutathione redox system, (c) cysteine deficiency, and (d) malfunction of metal regulating elements (MRE’s).”

(Note: Pheiffer Treatment Center is responsible for a couple hundred of the >1,000 recoveries from autism documented by the Autism Research Institute. See links section for access to PTC’s website.)

Glutathione is frequently mentioned in biomedical discussions of autism due to its critical role in the detoxification pathway. Glutathione is produced by a metabolic process known as the methionine cycle.  Important work has been performed describing the most vulnerable parts of the methionine cycle.  This cycle starts with methionine and is supposed to end with glutathione. However, because this metabolic process has been disrupted in autistics, little or no glutathione is produced. Indeed, oxidative stress, or low levels of glutathione have been described as a hallmark traits of autism.


 

Source: Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism   S Jill James et al. (2)

 

 

 

 

 

 

Because glutathione is so critical in the detoxification pathway, diminished levels begin to interfere with a variety of other metabolic processes as initially described  by Dr. Walsh and borne out via subsequent research.  These include the dysfunction of  the methylation and sulfation processes. Following is an excerpt from “Autism is Curable. How a Generation Was Poisoned And How To Correct It” (3) by Dr. Stuart H Freedenfeld describing these processes. 

 “Methylation is an extremely important process that is essential to our health.  It activates brain-signaling molecules and inactivates DNA and RNA (it is how liver cells learn to be different from muscle cells and how we inactivate viruses).  Impairment of the methylation mechanism impairs another process called sulfation.  Sulfation is necessary to produce many substances including the protective coating of the digestive tract and the connective tissues of the body.  It is also the source of the most important detoxifying substance in our body, glutathione.  This substance is so important that if its level falls below a certain amount in any cell, that cell will self-destruct.  Glutathione is also the essential mechanism to remove toxic metals from inside the cells.

“Another substance, metalothionine, serves a role as guardian preventing toxic metals from gaining entrance to our body and brain by binding to these metals at the surface of the GI tract and at the blood-brain barrier.  This barrier protects the brain from dangerous substances that may be circulating in our blood stream.

 “When we study the genetics of autistic children and their parents we see weakness in the methylation, sulfation, glutathione production and low metalothionine levels.”

 With all of the metabolic dysfunction going on in the bodies of autistic individuals:, “it is not unfair to say they (autistics) are biochemical train wrecks” concludes Dr. Freedenfeld.

 A friend of mine, a talented Immunology researcher, has explained to me that a significant portion of the immune system’s job is defending the gut – namely the intestinal tract. This is because damage to the digestive tract could cause an infection that can quickly kill. He explained that when the immune system is compromised in certain ways, it leaves the digestive tract open to vulnerabilities that include gut permeability and fungal overgrowth. Many parents of autistic children describe horrific gut problems, such as severe bloating and diarrhea, in their autistic children, particularly around the time the child’s autistic symptoms become apparent. (More about the importance of these conditions in the next section.)  

The Digestive System

 Believe it or not, the digestive system is where most of the “action” occurs related to autism, because it is here that the materials are produced that eventually attack the nervous system, producing autism symptoms.

 In typical digestive systems, food is broken down by digestive enzymes, eventually into individual amino acids. Since enzymes are compromised in autistic individuals, some foods are improperly digested, resulting in substances that are typically not found in nature. Specifically, analysis the urine of autistic individuals reveals improperly digested proteins with an end terminal resembling a morphine-like substance.  These substances have been referred to as casomorphines, gliadomophins, neurotoxins, urinary peptides and other names.

 Here is a Wikipedia citation regarding the phenomenon: “The possibility of a relationship between autism and the consumption of gluten and casein was first articulated by Kalle Reichelt in 1991. Based on studies showing correlation between autism and increased urinary peptide levels, Reichelt hypothesized that some of these peptides may have an opiate effect. This led to the development of the Opioid Excess Theory, expounded by Paul Shattock and others, which speculates that peptides with opioid activity cross into the bloodstream from the lumen of the intestine, and then into the brain. These peptides were speculated to arise from incomplete digestion of certain foods, in particular gluten from wheat and certain other cereals and from casein from milk and dairy produce. Further work confirmed opioid peptides such as casomorphines (from casein) and gluten exorphines and gliadorphin (from gluten) as possible suspects, due to their chemical similarity to opiates. Reichelt hypothesized that long term exposure to these opiate peptides may have effects on brain maturation and contribute to social awkwardness and isolation. On this basis, Reichelt and others have proposed a gluten-free casein-free (GFCF) diet for sufferers of autism to minimize the buildup of opiate peptides. (4)

 Because the digestive tract is now in a more permeable state, these undigested proteins resembling morphine leak out of the gut, into the bloodstream, and finally, move into and attack the brain.  

 Ok, you might say, how could this be true? How can you prove this? Well, one way would be if these opioid substances can be found in the urine of autistic individuals and NOT in the urine of unaffected siblings. Secondly, would be to withhold milk (casein) and wheat (gluten) from the diets of affected individuals to see if there is improvement.

 As discussed in “Our Story”, I was fortunate to be involved in an informal study group that examined the urine of autistics for the presence of these opioid substances with a sophisticated research tool known as mass spectrometer. I was instructed to collect Amanda’s urine, immediately freeze it and bring it in to have it analyzed via mass spec. I was also instructed to bring in the urine of my non-affected son.

 The way this works is that urine is literally “exploded” or broken apart into individual components by the mass spec. The output of this, seen on a display screen, is a series of peaks that correspond to each individual element, along with an associated identifying molecular weight. Scientists can then look up the identifier in a database to determine the substance in question.

 Mass spec analysis on my daughter’s urine revealed MANY peaks. Bob, the wonderful mass spec scientist, pointed out which peaks were caseomorphins. He also pointed out the peak he thought corresponded to gliadomorphins. I didn’t ask about the dozen or so other peaks that also appeared on the screen.  Next Bob loaded my son’s urine into the mass spec – not one peak appeared. The evidence was striking. All I could think was “Holy crap – this is real.”

 Eventually the study group grew to about ten families with children diagnosed with autism and the same results were demonstrated over and over – parents observed peaks galore in the urine samples of their autistic children, and none in their non-affected children.

 As a parent stares in disbelief at the screen of the mass spec output, their next question is the same: “What can be done about this?” The answer: put the child on a casein-free and gluten-free diet to see if it affects their peaks and their autistic symptoms.

 I discuss our experiences with the casein-free, gluten-free (CFGF) diet more in the section “Our Story”, so I will cut to the chase in this section. In our study group, we had one full recovery of a child that began a casein-free diet at the age of two. It took about 18 months for the child to fully recover. A one in ten recovery rate with the CFGF diet in a small, informal study.

 And our child? Only slight improvement in her autism symptoms despite being on a CFGF diet for over six months. The other children in our study group had nearly the same results. The casomorphin and gliadomorphin peaks had disappeared from Amanda’s mass spec analysis over time as a result of the CFGF, but other peaks remained.  I speculated that my older child had been exposed to a variety of food for nearly a decade of her life with compromised detox, immune and digestive systems could possibly be making morphine-like substances to a variety of things she ate.

 I believe a casein-free, gluten-free diet is extremely important and life changing for some autistic children (this is how, I understand, Jenny McCarthy’s child was recovered), has significant improvement for others, but doesn’t seem to work at all for others. There’s a good reason the CFGF diet works: because casein and gluten are key culprits resulting in opioid substances that produce the symptoms of autism. However, the CFGF diet doesn’t work if children are making opioid substances to a wider variety foods. I have observed that in general, the younger the child, the more effective the diet appears. However, I have read about children being fully recovered having started the diet as late as age 9. In any case, it’s an extremely important tool in our treatment toolkit, and it’s worth a serious try.

 Here are the results of a more recent study published in involving Dr. Reichelt, who postulated the opioid excess theory: “The aim of this single-blind, controlled study was to evaluate the effect of a gluten-free and casein-free diet for children with autism and urinary peptide abnormalities. Observations and tests were carried out with the 20 participating children before they were randomly assigned to either the diet or the control group. The experimental period was 1 year, after which observations and tests were repeated. Significant reduction of autistic behavior was registered for participants in the diet group, but not for those in the control group.”

Effect of a Dietary intervention on Autistic Behavior. Knivsberg, AM, Reichelt, KL, et al. (5)

 A couple last notes on identification of opioid substances: the informal study that my family participated in was conducted about ten years ago. Since that time, thousands of samples of urine from autistics have been analyzed via mass spec, mostly at the request of DAN! physicians. The results: opiod substances are present in the urine of about 90% of autistics. In fact, it is such a common finding that clinicians tend to no longer order the test.

 And what about the 10% that don’t produce opiod substances? I don’t think it’s a coincidence that about 10% of autistics fully recover doing ONLY ABA (Applied Behavioral Analysis, or “Lovaas” for us old-timers). In other words, it appears that in this “lucky” 10%, the production of neurotoxins stops on its own without any biological intervention. Then the only task left is to “heal the nervous system”. I  personally know of one such case.

 The Neurological System

Imagine for a moment the impact of having a dose of morphine delivered into your bloodstream and brain after every meal, day in and day out. Now observe the way an autistic child or adult behaves. Is it possible that they have been living under the burden of a highly potent and destructive opioid neurotoxin on a daily basis for a large portion of their lives?

Following are quotes from “Unraveling the Mystery of Autism and Pervasive Developmental Disorder: A Mother’s Story of Research & Recovery” by Karyn Seroussi, which beautifully describes the recovery of her son from autism via diet. “…these opiates, if they are permitted to enter the brain, can have a widespread effect on the nervous system similar to that of hallucinogenic drugs; and this results, in a developing child’s brain, in autistic behaviors. The proof of this lies in the presence of such drugs in the urine of the autistic children. . .These effects will include disrupting neurotransmission in all the main systems (dopamine, serotonin, GABA, etc.). Consequently, perceptions by all of the senses (hearing, sight, taste, proprioception, pain, etc.) will be affected to a varying degree. At the same time, so will the ability to filter out what is important from what is not.”   From “Unravelling the Mysteries of Autism and Pervasive Developmental Disorder” by Karyn Seroussi (6)

 Other evidence that morphine-like substances are reaching the brain is the frequent observation that autistics tend to crave and eat the same food, diary and wheat based, all the time. Mac and cheese. Pizza. They appear to be addicted to their own food. They fly into fits when they don’t get it. Once they eat it they appear to lapse into a “food coma” until the addiction once again overwhelms them and they demand more.

Other observed neurological manifestations could be the result of opioids reaching the brain include seizures and changes to brain structure observed on imaging studies. But the real proof is in the ability to reverse the processes causing these symptoms resulting in improvement and recovery.

Recovery from autism:

(1)            Stop production of opioid neurotoxins

(2)            Reduce or eliminate oxidative stress

(3)            Heal the nervous system

Knowing the metabolic processes at play that result in the symptoms of autism, one can begin to envision that reversal of these processes could lead to recovery or at least diminishment of symptoms. This is exactly what happened with recovered autistics.

Stop the production of Opioid Neurotoxins and Reduce or Eliminate Oxidative Stress (Yes, these can sometimes be addressed with the same treatment methods):

Special diets -  have already been discussed.

Methlyated B-12 shots

Another key method to halt the production of opioid neurotoxins and reduce oxidative stress isthe use of methyl-B12 shots. Administration of methlyated B12 via shots seems to get the methionine process (described earlier) going again in short spurts, resulting in the availability of greater levels of glutathione for critical metabolic processes. Once glutathione is produced, many of the “downstream” problems (enzyme function, digestive system permeability, etc.) seem to right themselves, and production of neurotoxins is inhibited or stopped. But the process takes place only while methyl -B12 is present. So a continuous supply of M-B12 is required. One shot (which can be administered in a painless way to the buttocks) is required approximately every three days.

Use of M-B12 shots made a significant difference in the life and recovery of our daughter and in the recovery of a number of children that we have sent to DAN! (Defeat Autism Now) doctors for treatment. M-B12 represents a real alternative for older kids when the CFGF diet is less effective. DAN! clinicians I have spoken to report that a high percentage (but not all) autistic kids that receive M- B12 shots are “responders”,  and some are eventually recovered. The protocol for administration must be followed precisely (see www.drneubrander.com for video and written instructions).

Heal the nervous system

There are many “mainstream” methods of treatment that have already likely been suggested or used to help your children. They include: ABA (Applied Behavior Analysis Therapy), hearing desensitization, Occupational Therapy, Speech Therapy.  I assume you are already familiar with these so I won’t discuss them in detail.

HBOT

Another tool that is gaining prominence in the “Heal the Nervous System” category is the use of Hyperbaric Oxygen Therapy (HBOT). HBOT involves the administration of oxygen while a patient’s body is in a pressurized situation. It sounds scary and actually looks even scarier if you saw a chamber in use, but in fact it is simple and straightforward.  Under the care and guidance of DAN! clinicians, families can rent or buy “soft” chambers and set them up at home. HBOT allows for greater levels of oxygen to be available to the nervous system/brain by creating a gradient that gently “pushes” oxygen into these starved cells. Increased levels of oxygen in brain cells allows for cell repair. Small studies and anecdotal use of HBOT with autistic children appears to support that this is an important emerging tool in the healing of autistics. In addition, use of HBOT appears to decrease the frequency and severity of seizures that occur in a significantly high percentage of autistic cases.  (Also see “Tales of Healing” for a story about the use of HBOT in a child with autism and seizures.)

Below is a summary of a paper assessing use of HBOT on autistic patients. Note: CRP is a blood marker of inflammation. The presumption is that the brain becomes inflamed as a result of the repeated exposure to neurotoxin/opioid substances and oxidative stress. HBOT seeks to reduce this inflammation by movement of greater amounts of oxygen into the brain vs. non-pressurized conditions.

HBOT and Autism Study (published March, 2009)

Abstract

Background: Several uncontrolled studies of hyperbaric treatment in children with autism have reported clinical improvements; however, this treatment has not been evaluated to date with a controlled study. We performed a multicenter, randomized, double-blind, controlled trial to assess the efficacy of hyperbaric treatment in children with autism.

Methods: 62 children with autism recruited from 6 centers, ages 2–7 years (mean 4.92 ± 1.21), were randomly assigned to 40 hourly treatments of either hyperbaric treatment at 1.3 atmosphere (atm) and 24% oxygen (”treatment group”, n = 33) or slightly pressurized room air at 1.03 atm and 21% oxygen (”control group”, n = 29). Outcome measures included Clinical Global Impression (CGI) scale, Aberrant Behavior Checklist (ABC), and Autism Treatment Evaluation Checklist (ATEC).

Results: After 40 sessions, mean physician CGI scores significantly improved in the treatment group compared to controls in overall functioning (p = 0.0008), receptive language (p < 0.0001), social interaction (p = 0.0473), and eye contact (p = 0.0102); 9/30 children (30%) in the treatment group were rated as “very much improved” or “much improved” compared to 2/26 (8%) of controls (p = 0.0471); 24/30 (80%) in the treatment group improved compared to 10/26 (38%) of controls

(p = 0.0024). Mean parental CGI scores significantly improved in the treatment group compared to controls in overall functioning (p = 0.0336), receptive language (p = 0.0168), and eye contact (p = 0.0322). On the ABC, significant improvements were observed in the treatment group in total score, irritability, stereotypy, hyperactivity, and speech (p < 0.03 for each), but not in the control group. In the treatment group compared to the control group, mean changes on the ABC total

score and subscales were similar except a greater number of children improved in irritability (p = 0.0311). On the ATEC, sensory/cognitive awareness significantly improved (p = 0.0367) in the treatment group compared to the control group. Post-hoc analysis indicated that children over age 5 and children with lower initial autism severity had the most robust improvements. Hyperbaric treatment was safe and well-tolerated.

Conclusion: Children with autism who received hyperbaric treatment at 1.3 atm and 24% oxygen for 40 hourly sessions had significant improvements in overall functioning, receptive language, social interaction, eye contact, and sensory/cognitive awareness compared to children who received slightly pressurized room air.

Source: Hyperbaric treatment for children with autism: a multicenter,

randomized, double-blind, controlled trial  D. Rossignol et al, March, 2009 (7)

Other tools

Chelation is the active detoxification of heavy metals and other toxic substances built up in the tissues of autistics. These result from the impaired detoxification processes previously discussed. Chelation is facilitated by a substance that helps lift the toxin from the tissues so that it may be eliminated by the body.

Chelation is one of the most controversial subjects in the treatment of autistics. Chelation can be “intense” when DMSO (Dimethyl sulfoxide) is used to facilitate the detox, or “gentle” as in the case of transdermal glutiotione. I have heard reports of kids going “off the wall” trying to cope with the effects of intense chelation. No wonder, if you consider that the process is unearthing gobs of toxic metals previously stored in tissues. Our daughter received the “gentle” detox method of transdermal gultiothione and experienced no apparent detox reaction. However, this method may not be effective enough to detox some individuals. This is a decision that must be made between a physician experienced in detox and autism treatment procedures, and parents.

What to do next

If you are interested in further investigation of the biomedical mechanisms of autism, we encourage you to speak to a DAN! clinician who has experience using the methods described above to help heal autistic children. The DAN! treatment protocol was developed and honed from many case studies of “what works” and is responsible for the vast majority of the documented cases of recovery from autism on file with the Autism Research Institute in San Diego, CA.

Good luck! Please keep in touch and let us know how your child is doing!

 

Sources:

(1)   Metallothionein and Autism, W. J. Walsh et.al., Pfeiffer Treatment Center, Naperville, IL, October, 2001

(2)                 Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism   S Jill James et al. 2004 American Society for Clinical Nutrition

(3)    “Autism is Curable. How a Generation Was Poisoned And How To Correct It” by Dr. Stuart H Freedenfeld

(4) http://en.wikipedia.org/wiki/Gluten-free,_casein-free_diet

(5)Effect of a Dietary intervention on Autistic Behavior. Knivsberg, AM, Reichelt, KL, et al. H Høien, T, Nødland, Magne. Focus on Autism and Other Developmental Disabilities, Vol. 18, No. 4, 248-257 (2003)

(6) Unraveling the Mystery of Autism and Pervasive Developmental Disorder: A Mother’s Story of Research & Recovery” by Karyn Seroussi, Broadway(Publisher) January 8, 2002 – Paperback edition

(7) D. Rossignol et al, March, 2009. BMC Pediatrics. This article is available from: http://www.biomedcentral.com/1471-2431/9/21 © 2009 Rossignol et al. http://www.biomedcentral.com/content/pdf/1471-2431-9-21.pdf


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