Autism is complex neuro-developmental disorder which has a symptomatic diagnosis in patients characterized by disorders in language/communication, behavior, and social interactions. The exact causes for autism are largely unknown, but is has been speculated that immune and inflammatory responses, particularly those of Th2 type, may be involved. Thiazolidinediones (TZDs) are agonists of the peroxisome proliferator activated receptor gamma (PPARγ), a nuclear hormone receptor which modulates insulin sensitivity, and have been shown to induce apoptosis in activated T-lymphocytes and exert anti-inflammatory effects in glial cells. The TZD pioglitazone (Actos) is an FDA-approved PPARγ agonist used to treat type 2 diabetes, with a good safety profile, currently being tested in clinical trials of other neurological diseases including AD and MS. We therefore tested the safety and therapeutic potential of oral pioglitazone in a small cohort of children with diagnosed autism.

Case description

The rationale and risks of taking pioglitazone were explained to the parents, consent was obtained, and treatment was initiated at either 30 or 60 mg per day p.o. A total of 25 children (average age 7.9 ± 0.7 year old) were enrolled. Safety was assessed by measurements of metabolic profiles and blood pressure; effects on behavioral symptoms were assessed by the Aberrant Behavior Checklist (ABC), which measures hyperactivity, inappropriate speech, irritability, lethargy, and stereotypy, done at baseline and after 3–4 months of treatment.

Discussion and evaluation

In a small cohort of autistic children, daily treatment with 30 or 60 mg p.o. pioglitazone for 3–4 months induced apparent clinical improvement without adverse events. There were no adverse effects noted and behavioral measurements revealed a significant decrease in 4 out of 5 subcategories (irritability, lethargy, stereotypy, and hyperactivity). Improved behaviors were inversely correlated with patient age, indicating stronger effects on the younger patients.

Conclusion

Pioglitazone should be considered for further testing of therapeutic potential in autistic patients.

The Centre for Disease Control in the United States released the latest autism prevalence statistics this year. 2018 saw an increase in the prevalence statistics of autism from 1 in 68 just two years ago to 1 in 59. This is a 15% increase, which is astronomical.

One might be inclined to think this number must be an over-estimation. Quite the contrary – at sites where researchers had full access to school records, higher numbers were recorded. This suggests that the new numbers reflect a persistent underestimation of autism’s true prevalence.

Other interesting findings were that:

  • The gender gap in autism has decreased. In 2012, boys were 4.5 times more likely to be diagnosed than girls. By 2014, this had decreased to a ratio of 4:1. This appears to reflect improvement in identification of autism in girls, many of whom do not fit the stereotypical picture of autism seen in boys.
  • White children are still more likely to be diagnosed with autism than children from other racial groups, but this gap has also decreased and reflects improved awareness and screening in ‘minority communities’ in the US.
  • Disappointingly, there has been no overall decrease in the age of diagnosis, with most children still being diagnosed after age 4, even though autism can reliably be diagnosed by age 2. This is important because research and experience shows that early intervention leads to the best outcomes.
  • The change in diagnostic criteria (from the DSM IV TR to the DSM 5, which did away with diagnoses such as Asperger’s Syndrome and moved to a catch-all diagnosis of Autism Spectrum Disorder) caused only a slight decrease in prevalence estimates.
  • The US still lacks any reliable estimate of autism’s prevalence among adults. South Africa

Awareness in South Africa is increasing, which is good in terms of the safety of our children and in terms of families accessing treatment earlier, but we cannot stop there. What is really needed is financial support for Applied Behaviour Analysis, declared by the US surgeon general to be a medical necessity for children on the autism spectrum, and greater acceptance of children with autism in general education schools, with trained facilitators where necessary.

The importance of folate
Folic acid (vitamin B9, also known as folate) is a water-soluble B vitamin that is essential for numerous physiological systems of the body. Folate derives its name from the Latin word folium, which means leaf, to signify that the main natural source of this vitamin is from leafy vegetables. However, in the modern western diet, the main source of folate is from folate-fortified foods. Folic acid is the inactive, oxidized form of the folate compounds. The main active form of folate in the body is 5-methyltetrahydrofolate (5-MTHF). Folic acid is converted to dihydrofolate and then to tetrahydrofolate (THF) by the enzyme dihydrofolate reductase. This reaction, which requires niacin (vitamin B3), can be inhibited by certain medications. 5-MTHF is also converted to THF by the enzyme methylenetetrahydrofolate reductase (MTHFR). 5-MTHF is then converted back to THF through a cobalamin (vitamin B12) dependent enzyme called methionine synthase, a process that recycles methionine from homocysteine. Folate is important for the de novo synthesis of purine and pyrimidine nucleic acids that are the molecules from which DNA and RNA are produced. DNA stores the genetic code and needs to be duplicated when a cell divides and replicates. Thus, folate is extremely important during cell replication, especially prior to birth during the development of the embryo and fetus. It is also essential during early life when cells are growing quickly.
The folate cycle interacts with the methionine cycle as well as the tetrahydrobiopterin production and salvage pathways. Deficiencies in folates can lead to abnormalities in these pathways. The methionine cycle is essential for the methylation of DNA, a process that is important in controlling gene expression. Tetrahydrobiopterin is essential for the production of nitric oxide, a substance critical for the regulation of blood flow and for the production of the monoamine neurotransmitters, including dopamine, serotonin, and norepinephrine. Production of these neurotransmitters and nitric oxide converts tetrahydrobiopterin to dihydropterin. The conversion of tetrahydrobiopterin back to dihydropterin again requires conversion of 5-MTHF to THF. In addition, tetrahydrobiopterin is produced de novo using the precursor purine guanosine triphosphate, a substance that requires THF to be produced. Several disorders have been linked to folate deficiency. For example, since blood cells need to be constantly replenished, a lack of folate commonly leads to anemia, an insufficiency of red blood cells. Folate deficiency during pregnancy leads to fetal neural tube defects such as spina bifida.
In 2002, my older son, Isaiah, was diagnosed with autism. At the time I had been practicing as a family physician for about five years. Prior to his diagnosis, Isaiah loved to get down on the floor and spin objects, and I thought it was cool, so I helped him. He also used to shake his hands back and forth in the air for hours. When I tried to shake my hands like him, I tired out in a couple of minutes. I couldn’t figure out how he could do it for hours! He had a significant speech delay and walked very late. However, despite all of these problems, I did not have a CLUE that he had autism. I remember when my wife and I went to his psychological evaluation to determine what was wrong with him. He was evaluated by a pediatric neurologist and several psychologists, and we spent the morning with him during the testing. We were then told to go to lunch while the team met to determine a diagnosis. I remember as we sat in McDonalds eating French fries and cheeseburgers that my wife and I discussed that maybe the team would say he had “autistic tendencies.” It was quite a shock to us when Isaiah was actually diagnosed with autism! For the first year after his diagnosis, my wife started looking into biomedical treatments, which I considered “quackery.”

The term MTHFR (methylenetetrahydrofolate) may sounds like a “bad word,” but it isn’t.  It is just an acronym for a very important enzyme our bodies need.  The MTHFR plays an important role in the methylation cycle.  Cutting edge research has clearly linked impaired methylation problems with autoimmune conditions like autism and so much more. The good news about if your child has the MTHFR gene mutation, it can be treated with medications like Leucovorin or Deplin.  These prescription medications have the potential to help the body produce the neurotransmitters that are necessary and important for developing speech.  For my son, who is now an aerospace engineer, Leucovorin was life-changing.

I’m not a doctor and sometimes this medical research is way above my head, but I’m going to try to explain the MTHFR gene mutation. in simple Dr. Mom terms.  If you have the MTHFR defect, your body has trouble processing folic acid. When this enzyme isn’t functioning properly, as can happen in an estimated 30-60% of the population, it can cause many medical problems and life-altering issues.  Researchers have discovered that this gene, among many others are associated with autoimmune disorders like autism, recurrent miscarriage, birth defects, strokes, neurodegenerative disorders, blood clots, heart attacks and so many other medical issues.

If a child has the MTHFR gene mutation, their immune system doesn’t function properly and they have trouble eliminating the toxins we are all exposed to.  Toxic substances (like the heavy metals used to preserve vaccines) can create problems in a compromised immune systems. A simple blood test ordered by your pediatrician will help you know if your child has the MTHFR gene mutation.

One of my mom’s sent me this adorable picture of her son to share and gave me permission to tell you about how Leucovorin helped her son. I never share names, but love to share the success stories!!!

After I helped her find a doctor near her location. The doctor did a simple blood test to see if her son had the MTHFR gene mutation.  Then this informed physician prescribed Leucovorin to counteract the effects of his MTHFR gene mutation.

Mom reported, “[Our Boy] …started Leucovorin in Dec at a very low dose. Two weeks ago we doubled it, and his language exploded.”

Now for the fun part of this success story…

Mom said, “We are so happy with his progress. Yesterday…. he told a kid…. “Chill out”…. and today… he told me “Whatever.” He has a bit of a ‘tude…. and an impressive sense of humor. His eye contact is awesome. He is interacting so much more.”

This “Warrior Parent” is the shining example of what I hope my book “I KNOW YOU’RE IN THERE”can do our kids on the spectrum. This mom took the information I shared in the book, put her own spin on it, and ran with it. (The book can be previewed on Amazon or on my website www.autism-and-treatment.com)

All of us want our kids to have more speech.  And we are constantly searching for that “instant cure.” We think that if only our kids could only talk more, our problems will be solved.  But that isn’t exactly true.

Although more speech does reduces frustration and does improve behavior, it doesn’t solve the real medical issues.  Even if we could wave a magic wand and fix the problems with our children’s immune function, it is important to realize it takes a “healthy and typical” kid three years to become proficient in speech.  So don’t use speech as an indicator that the biomedical treatments are working.

My wish every year when I blew out my birthday candles was that Ryan would talk more and have just one real friend. I longed for a time when could actually tell me what he was thinking. After helping his immune system function better, my son was able to learn what he couldn’t before.  Treating his MTHFR gene mutation with Leucovorin was part of making that happen. Ryan has always been under a doctor’s care. Regular blood tests are given to insure none of the meds he takes cause any damage.

Autism is complicated and it took many things combined to reduce “the total load” on my son’s broken immune system.  Recovery is a long process.  Ryan is now an aerospace engineer.  But when he was in middle school, even I didn’t think he ever completely recover. My dream back then was that maybe someday he could hold a job at McDonald’s and live independently.  Who knew he could accomplish all he has?

When I first asked Ryan’s doctor about adding Leucovorin to the mix he said a large portion of the population have the MTHFR gene mutation, and I don’t think this will really change anything. Then he added, “If it’s not broke… don’t fix it.” That’s when I asked him if we could try it anyway.

It was Ryan’s improvement that taught our physician about the benefits of the medications that improve methylation.  At that time my son was already  working as an engineer and I wasn’t sure he could really improve much. I knew Ryan was doing great, but after starting this med, his sense of humor exploded. A developed sense of humor is higher level thinking. Now Ryan keeps us laughing all the time.

Last month, when Ryan asked his doc if he could stop the Leucovorin, his doctor answered…absolutely not!!! And it is also important to note one of the children this medication helped didn’t test positive for the MTHFR. I’m not a doctor, only Ryan’s mom, so I don’t fully understand why that is true. Now Ryan’s doctor prescribes it for all of his patients who test positive for the MTHFR gene mutation! Sometimes even moms and dads teach our amazing docs a thing or two along the way.

NOTE FROM MARCIA HINDS – Megan and Ryan’s mom:

Ryan became an aerospace engineer, because he received proper medical treatment combined with behavioral, and educational interventions.  To preview my book, “I Know You’re In There – winning our war against autism”go to Amazon or my website www.autism-and-treatment.com

http://autism-and-treatment.com/2018/02/03/heck-mthfr-gene-mutation-autism/

What first led to your interest in PANS/PANDAS?

​When I opened my laboratory at the University of Oklahoma Health Sciences Center in Oklahoma City, I began by working on rheumatic fever because I thought it was actually a good example of autoimmunity caused by infection. I thought it would lead to a better understanding of how the immune system was affected by an infection attacking our bodies and causing disease. My PhD training was in the field of streptococcal immunology and infection.  I was working on a streptococcal vaccine in the 1970s with Dr Edwin Beachey and Dr Gene Stollerman who led a well-known streptococcal research group in Memphis, TN. After joining the faculty at the University of Oklahoma School of Medicine in the Department of Microbiology and Immunology, I initially decided to study autoimmunity and infection and the group A streptococcal sequelae. This led to the investigation of both heart and brain sequelae of streptococcal infections, which primarily affect children. Rheumatic fever peaks during the ages 5-15 years old which are the peak years of streptococcal infection in children.  When I opened my laboratory in 1980, medical researchers in immunology were looking for reasons for why autoimmune disease occurred and how it could be controlled. I wrote grants on rheumatic heart disease and discovered that cardiac myosin was the link between streptococci and heart disease and the NHLBI funded my laboratory with a career development award to study rheumatic heart disease caused by group A streptococci following a sore throat or pharyngitis. Rheumatic fever and heart disease is rare in children but occasionally children will get rheumatic fever which could lead to rheumatic heart disease. We began seeing patients who had Sydenham Chorea. Sydenham Chorea could be present with rheumatic heart disease. We collected blood from a hospitalized patient with Sydenham Chorea and began to produce monoclonal antibodies to study the disease pathogenesis. I was called by Dr Susan Swedo at the NIMH to study the streptococcal brain sequelae associated with infections. Dr. Swedo knew that I studied streptococcal sequelae and that she had identified a disease that she was interested in studying that was related to Sydenham Chorea.  Dr Swedo was investigating the effect of plasmapheresis on the outcome of Sydenham chorea. The monoclonal antibodies we produced from Sydenham chorea patients in Oklahoma were from B cells making the antibodies that attack the brain in Sydenham chorea. Because B cells produce the antibody in the Sydenham chorea, it actually directed us to the mechanism by which the antibodies work. Dr Swedo also found that plasmapheresis led to improvement of Sydenham chorea. Dr. Swedo wanted us to study her patients with pediatric autoimmune neuropsychiatric disorder associated with streptococci or PANDAS in addition to children with Sydenham Chorea. That is the story of how our research in PANDAS and PANS began. We published our first paper in Nature Medicine in 2003 on Sydenham Chorea and it was very well accepted because the mechanism had not been known previously which was that the antibodies signal neuronal cells to produce too much dopamine which affects movement and behaviors.

Is Sydenham Chorea a form of autoimmune encephalitis?

Yes.  Now we realize Sydenham chorea is a dopamine receptor and basal ganglia autoimmune encephalitis.  We actually put the human antibody gene derived from Sydenham chorea B cells into mice and the antibody expressed in mouse B cells targeted dopaminergic neurons in the basal ganglia in the brain of the mice.

Is dopamine always too high in kids who have PANS and PANDAS?

I don’t know that because we have not studied the dopamine neurotransmitter elevation in the brain in humans.  We do have an animal model where the antibodies were introduced directly into the brains through a catheter and the dopamine levels were elevated after injection of the antibodies into the brain.

So if Sydenham Chorea is a form of autoimmune encephalitis, then some autoimmune encephalitis can be treated just with antibiotics?

Antibiotics like penicillin kill bacteria in infections but they can have other effects—such as on the microbiome in the colon or the brain beyond the elimination of the infection. We have one animal model where we used antibiotics and the animals improved. Animals were immunized (not infected) with streptococcal antigens and the antibiotics had an effect either on the microbiome or they were anti-inflammatory or affected dopamine output. In that animal model the aberrant behaviors subsided and the dopamine levels went down when the antibiotics were given.  I do not know the mechanisms for this response to antibiotics in the absence of infection.  Sydenham Chorea is the brain manifestation of Rheumatic Fever.  If you were diagnosed with Sydenham Chorea, you would be treated with penicillin or azithromycin or other antibiotics until you were 21.  That is what the guidelines are for treatment of rheumatic fever, and rheumatic fever can be just a single symptom of Sydenham Chorea. It doesn’t have to be the valvular heart disease (heart murmur) or arthritis.

Do we know if Sydenham Chorea is a B cell or T cell mediated disease?

We would say it is B cell mediated disease because it’s the antibodies that get into the brain but it doesn’t mean that T cells don’t help those B cells produce the antibody or that T cells do not get into the brain and affect behaviors. Antibody is produced with T cell help usually. We see lots of IgG in serum with the same specificity of human monoclonal antibodies we produced from the patient.

Is PANDAS autoimmune encephalitis?

Both Sydenham chorea and PANDAS are considered dopamine receptor and /or basal ganglia autoimmune encephalitis which occurs after streptococcal infection. This conclusion is based on data collected on patients, animal models and specifically a transgenic mouse model where the antibodies in SC target the basal ganglia of the brain. The autoantibodies in SC and PANDAS are targeted against the D1 and D2 dopamine receptors. The autoantibodies in SC and PANDAS cause the neuronal cells to release too much dopamine which lead to the symptoms of PANDAS. Studies are in progress examining the mechanism of the autoantibody impact on the D1 dopamine receptor.  Thus, PANDAS would be a type of encephalitis, which means inflammation of the brain. It might not seem as severe as Sydenham Chorea because the chorea is an involuntary movement disorder which can be quite dramatic. In PANDAS, neuropsychiatric symptoms can be overwhelming for children and their families.  OCD and tics, characteristic of PANDAS, may be seen in Sydenham Chorea prior to the movement disorder onset.

Is the same true for PANS and PANDAS?

PANDAS is specifically caused by strep but in PANS, strep could be just one of many triggers. There are people who are resistant to treatment and may not have autoantibodies. Years of relapsing and remitting disease may or may not be associated with autoantibodies after a long time since the infections, and the neuronal circuits may be set in the brain and those may respond better to neuropsychiatric drugs. Dr Tanya Murphy has explained that the drugs should be initiated at very low doses and titrated up based on a child’s response. Regular doses of psychotropic drugs at the beginning of treatment may make the symptoms worse according to Dr Murphy. She has also had several successful antibiotic trials.

How many Cunningham panels have you completed?

Over 7000 at my laboratory and Moleculera Labs combined.  Moleculera Labs has been open about five years and has received more samples over time as the disease and the autoantibody panel have become more recognized.

Is the Cunningham Panel helpful for adults or is it only meant to be used with children?

We only have evidence of its use in children but that doesn’t mean it couldn’t be useful for adults. In fact we have many physicians that utilize the panel in adults.  We are in the process of establishing adult controls so all we can do is report what we find compared to pediatric controls. We have studies in progress of adult chorea and PANDAS (children) from a sampling at Mayo Clinic in Rochester, MN and also two studies of Lyme disease samples but those results are yet to be published.

Can you comment on the study funded by Autism Speaks in which you looked for the presence of anti-neuronal antibodies in children with autism?

Yes. First we are so grateful for the funding from Autism Speaks. The research into autism would not have been possible without the Autism Speaks Trailblazer awards twice, and we are in the process of finishing the paper to report what we found in the study. It clearly shows that ASD can be comorbid with PANDAS symptoms. If PANDAS is discovered in an ASD patient, it might potentially be treated the same way you normally treat PANDAS, with IVIG and/or antibiotics.  Clearly there are children with autism and overlapping PANDAS symptoms and the anti-neuronal autoantibodies are evident in certain patients with the PANDAS symptoms.

Can you comment on the Swedish study?

They found that the sensitivity of the Cunningham panel was approximately the same as our sensitivity if used as a panel all together.  The Swedish study identified 100% of their PANDAS/PANS children or adults with symptoms. At my laboratory, we found that the sensitivity was 91%. These sensitivity numbers are very close. However, they focused on the tests singly rather than as the panel, and they also found low specificity due to the control population that they compared with the PANDAS patients they enrolled in their study. Controls in their study were not assayed for streptococcal infections or other infections. My laboratory and Dr. Harvey Singer had already published 4 sets of controls demonstrating that some control sets could be elevated if not screened for pharyngitis or tonsillitis or other infections. Children or adults with pharyngitis or tonsillitis will demonstrate the anti-neuronal autoantibodies and you can cannot use these subjects as a healthy control for comparison. If you don’t screen for that in your control group then your results might display low sensitivity. Also, if adults are in the control group, then the control group may also be high and give a lower specificity. The interesting thing is the autoantibodies in pharyngitis go away quickly in a couple of weeks, but the ones in PANDAS and Sydenham Chorea do not go away and remain elevated. Dr Hilla Ben Pazi at Shaare Zedek Medical Center in Jerusalem and I are ready to publish this analysis in a new article. Our specificity for the test panel is approximately 70%.

A major issue with the Swedish study is that invalid blood collection tubes were unknowingly used for sampling, as was acknowledged in the Corrigendum to their article. We find that collection tubes with clot activators and other additives sporadically interfere within the assay and the results. This would lead to unreliable data and could explain the difference between all our previous work and their results.

Even if the specificity is low, you’re not ever going to treat someone who doesn’t have symptoms. The antibodies are not present in other diseases such as multiple sclerosis and the specificity of the autoantibodies for the ganglioside antigen is a different specificity than seen in the Guillain Barre Syndrome. It is important that you can identify nearly all children with the disease using the autoantibody test panel. So far we do not see false negatives with the autoantibody panel. If you are positive and have symptoms then it is conclusive that you have a diagnosis of PANDAS or Sydenham Chorea, or if you want to call it something else, you could say that it confirms the diagnosis of dopamine receptor or basal ganglia autoimmune encephalitis. In addition, autoantibodies present in OCD and tics are not surprising since inflammation has been reported in Tourette’s syndrome. The antibodies will remain high over time during the symptoms over months and then the titers decrease when the symptoms improve based on our studies of samples collected at Yale University and the NIMH.

Are you planning on adding any other anti-neuronal autoantibodies to the Cunningham panel?

Not at this time. Although we are researching additional markers and will be screening the samples we have to see if we can identify additional biomarkers that may assist in the future.  Possibly other ways of testing that might be genetic or related to genetics to determine other risk factors.

What percentage of children with positive Cunningham panels have had an abrupt onset vs. subacute onset and in tracking them over time, do both groups respond to similarly to immunomodulatory treatments?

Those PANDAS children who are positive for the autoantibodies against the dopamine receptor(s) and have a positive CaMKII or other antibody in the panel are likely to have a good response to immunomodulatory treatment. The autoantibodies against the dopamine receptors indicate an autoimmune dopamine receptor encephalitis while autoantibodies against lysoganglioside or tubulin suggest a basal ganglia encephalitis if they are not positive when tested against the dopamine receptors.

Do you have a sense for how many children with PANS might also have mitochondrial disorders?

No, it is probably more in ASD.

It seems IVIG is often failing or provides relief for a time but not lasting relief. Do you know why this is or what the next steps should be?

I do not really know the answer to that question. However, we find that the autoantibody panel may likely be an excellent predictor of a positive response to the IVIG. This is because autoantibodies provide a rational basis for immunotherapy and may suggest that immunotherapies would work. IVIG also protects children with borderline immunodeficiency against infections and is also thought to be anti-inflammatory.


~Thank you to Dr. Cunningham for taking the time to be interviewed by FCND President Anna Conkey.

Autism Spectrum Disorder (ASD) is associated with a high rate of seizures and epilepsy. Some estimates suggest that up to 45% of individuals with ASD are affected by seizures by the time they reach adulthood, and it is estimated that up to 60% have subclinical electrical dis-charge—many without any obvious clinical seizures. In this article, we review some of the more important basic facts about seizures and epilepsy as well as treatments in order to enhance the understanding of caretakers of individuals with ASD.
Seizures: What are they and Why are they Important?
The brain works by transmitting electrical impulses from nerve cell to nerve cell. When the brain is working correctly the local rhythm of one part of the brain is rather random since many different nerve cells are working with other nerve cells on different thoughts and sensations. There is also an electrical rhythm, known as the background rhythm, which orchestrates all of the overall higher brain’s activity like a conductor. When a seizure occurs, there is an abrupt change in the brain’s electrical rhythm, such that the neurons in the brain become abnormally synchronized. When this happens, the nerve cells become enslaved to this abnormal rhythm preventing them from functioning normally. This disturbance in the electrical rhythm of the brain primarily
affects the evolutionarily newer part of the brain known as the cerebral cortex (higher brain). This abnormal brain activity typically shows up as abnormal rhythmic movements of the arms, legs and / or face, which reflect this synchronous rhythm stimulating nerve cells responsible for controlling the limbs.
Sometimes these movements are associated with a loss of consciousness since the nerve cells in the brain cannot function normally.

A study by researchers into the presence of potentially dangerous chemicals in eight brands of cling wrap, which is used to package food has revealed that one brand had a high concentration, which may result in adverse health effects and cancer risks.

The study was conducted by the University of Pretoria’s (UP) Environmental Chemical Pollution and Health Research Unit, and was led by UP Dean of Health Sciences, Prof Tiaan de Jager and Director of the Unit, Dr Natalie Aneck-Hahn. It had collaborators from Stellenbosch University and the Council for Scientific and Industrial Research. It selected eight of the most common cling film brands in South Africa, that are used domestically and commercially for food packaging. They investigated the presence, concentration and potential health risks of the EDCs, para-Nonylphenol (p-NP); Bisphenol A (BPA); Di (2-ethylhexyl) adipate (DEHA) and selected phthalates.

The study found that one of the cling film brands had a very high concentration of DEHA, which may result in adverse health effects and carcinogenic risks. Cancer risks resulting from exposure to DEHA equated to about five in 1000 people, which is 50 times higher than the acceptable cancer risk, said Prof de Jager.

Only two of the eight brands were below the detection limit for all target chemicals and also had the CANSA-smart choice seal on them.

High levels of DEHA and di-2-propyl heptyl phthalate (DEHP) were found in the commercial brands tested, posing significant health risks (such as reproductive and developmental effects and liver toxicity), while exposure to the EDC DEHP results in carcinogenic risks that are regarded slightly higher than the acceptable level (1 in 100 000). These risks represent a worst-case scenario and are based on using cling film daily over a 30-year period, said Prof de Jager.

He explained that exposure to EDCs during highly sensitive life stages such as foetal development and early childhood can result in the development of non-communicable diseases, problems with metabolism, as well as immune system dysfunction, problems with neurodevelopment, and reproductive function. ‘It is also possible that there can be an effect in children at an epigenetic level (heritable changes that affect gene expression and activity, but do not involve changes in the DNA sequence) in their adult years, as well as the potential carcinogenic effects to long term exposure,’ said Prof de Jager.

EDCs, which are mostly man-made, have significant effects on the environment, as well as on human and animal health.  They are found in pesticides; metals and electronics; pharmaceuticals and personal care products; as well as in additives in food and food packaging materials.

Cling film contains plasticizers, which are additives that increase the plasticity and flexibility of a material and decreases its viscosity and brittleness. Some plasticizers are EDCs and may be released from the material with time, use and under certain conditions.

Prof de Jager explained that EDCs can leach from the cling film used to package food. This leaching process, whereby chemicals are transferred from the plastic to the food is known as migration. ‘Migration depends on the chemical properties of the packaging and the type of food. Migration of EDCs into foods that are particularly high in fat, such as cheeses, fatty fish and meat are said to be more likely. Migration is also dependent on temperature, exposure to ultraviolet light and the duration that the product is stored.’

Previous studies on the migration of plasticizers (and therefore EDCs) into foods wrapped in PVC film showed substances do occur when packaged foods are defrosted or cooked in the microwave.  Food wrapped in cling film is a source of human exposure to EDCs. Since these studies, plasticizers which contain Phthalate esters DEHP and Dibutyl phthalate (DBP) have been prohibited or regulated in some countries because of their EDC effects.

While levels of BPA and p-NP were detected in cling film samples of this study, Prof de Jager stressed that the levels of these EDCs were lower when compared with a previous South African study in 1997. ‘This means that manufacturers of cling film are using safer alternatives compared to the materials previously used,’ he said.

According to Prof de Jager, as the awareness of EDCs slowly rises among the general public, ‘we should all try take it upon ourselves to become more informed of the materials that contain EDCs and the potential health risks that they can have on us and the environment.’

‘A start would be to make small changes to our daily choices. Perhaps, for example, if we all try to reduce the amount of food packaging – both in what we buy and in our own homes, we will not only be trying to reduce our exposure to EDCs, but we will also be making a bonus effort of reducing the amount of plastic on the planet.’

He cautioned that when purchasing cling film, people should always check for the CANSA-smart choice seal.

– Author Louise de Bruin

This document is intended to provide a simple summary for families and physicians of the major dietary, nutritional, and medical treatments available to help children and adults with autism spectrum disorders. The discussion is limited to those treatments which have scientific research support, with an emphasis on nutritional interventions. This report excludes psychiatric medications for brevity. The dietary, nutritional, and medical treatments discussed here will not help every individual with autism, but they have helped thousands of children and adults improve, usually slowly and steadily over months and years, but sometimes dramatically.

This summary is primarily based on review of the scientific literature, and includes over 150 references to peer-reviewed scientific research studies. It is also based on discussions with many physicians, nutritionists, researchers, and parents. This summary generally follows the philosophy of the Autism Research Institute (ARI), which involves trying to identify and treat the underlying causes of the symptoms of autism, based on medical testing, scientific research, and clinical experience, with an emphasis on nutritional interventions. Many of these treatments have been developed from observations by parents and physicians.

This study involved a randomized, controlled, single-blind 12-month treatment study of a comprehensive nutritional and dietary intervention. Participants were 67 children and adults with autism spectrum disorder (ASD) ages 3–58 years from Arizona and 50 non-sibling neurotypical controls of similar age and gender. Treatment began with a special vitamin/mineral supplement, and additional treatments were added sequentially, including essential fatty acids, Epsom salt baths, carnitine, digestive enzymes, and a healthy gluten-free, casein-free, soy-free (HGCSF) diet. There was a significant improvement in nonverbal intellectual ability in the treatment group compared to the non-treatment group (+6.7 +- 11 IQ points vs. +-0.6 11 IQ points, p = 0.009) based on a blinded clinical assessment. Based on semi-blinded assessment, the treatment group, compared to the non-treatment group, had significantly greater improvement in autism symptoms and developmental age. The treatment group had significantly greater increases in EPA, DHA, carnitine, and vitamins A, B2, B5, B6, B12, folic acid, and Coenzyme Q10. The positive results of this study suggest that a comprehensive nutritional and dietary intervention is effective at improving nutritional status, non-verbal IQ, autism symptoms, and other symptoms in most individuals with ASD. Parents reported that the vitamin/mineral supplements, essential fatty acids, and HGCSF diet were the most beneficial.