In my years of helping children with autism, I have heard many times (erroneously) that there is no science behind diet for autism, or the gluten-free casein-free diet (GFCF diet) for autism. 

This is simply not true. There is a great deal of research illustrating why gluten and dairy can cause and contribute to symptoms and the condition of an autism spectrum disorder, and how a GFCF diet can help. 

On one of my live Q&A calls recently, a wonderful medical doctor earnestly asked about what research existed on a gluten-free, casein-free diet for autism. While I’ve been writing and speaking on it for years, this request sparked my desire to put together the LATEST science to help fellow practitioners looking for science-based support for using the GFCF diet in your practice. 

In this article, I will share seven underlying biochemical mechanisms for which gluten and casein cause problems in autism, and studies showing how a GFCF diet helps, including one I was part of.

Recommending and helping your clients implement a gluten-free and casein-free diet for their child with autism (or themselves) can be beneficial in many ways, even life changing.  I’ve seen children:

  • Improve language skills and communication
  • Reduce hyperactivity and increase focus and attention
  • Improve eye contact
  • Reduce anxiety and increase calm
  • Improve socialization
  • Reduce irritability and aggression
  • Decrease digestive symptoms
  • Improve sleep

You may have your own “success stories” from families in your practice and may know firsthand how beneficial the diet can be (I’d love to hear them in the comments below).

While this research is on autism, you’ll notice that the underlying factors apply to many other conditions including ADHD, anxiety, neurological conditions, digestive disorders, autoimmune conditions, and more. 

Gluten and Casein 

Gluten is a protein found in wheat, barley, rye, and triticale, and products made from them. The actual problematic component of gluten is called gliadin. But most often you’ll hear it referred to as simply gluten.

 “Glu-ten” acts as a “glue” and helps flour-based foods maintain their shape. You can find gluten in many types of foods, such as pasta, soups, cereals, baked goods, even in  dressings, sauces, and processed meats. 

Casein is a protein in milk. While there are different types of casein in different animal milks (a conversation for another day), a casein-free diet avoids all milk and dairy products from all animals. 

Some practitioners personalize their client’s diet plan with special milk products like camel milk or ghee once they see how their client does 100% casein-free. However, to really know how a casein-free diet works for a client, I always recommend to the practitioners in my BioIndividual Nutrition® Pediatric Program to remove all animal milk of any kind.  

We will discuss the challenges related to gluten and casein and how they impact autism symptoms in depth later in this article.

Soy

Soy is also important to remove on a GFCF diet. 

Soy has many of the same characteristics and effects as gluten and casein. Soy is one of the most common food sensitivities and is inflammatory. Soy can also form opioid compounds like gluten and casein. 

So, when I’m working with clients or educating practitioners, I recommend removing soy as well. 

To me, a GFCF diet is really a GFCFSF diet. 

Personalized Autism Diet Plan

A personalized, BioIndividual Nutrition approach is one that is focused on the unique needs of the individual, and while a gluten-free casein-free diet is not the only “autism diet” out there, it is one of the most widely used and effective diets.  

As a nutrition practitioner or health professional, you are likely aware that the body and brain are intricately connected. Autism is a whole body disorder. So for your clients, following a therapeutic diet plan based on their unique needs can reduce, or in some cases even alleviate, both their autism symptoms, as well as the physical symptoms and comorbid conditions like diarrhea, constipation, sleeping challenges, and skin rashes. While these are not part of an autism diagnosis, these physical symptoms are common in autism because of the underlying biochemistry that affects both body and brain.. As you improve the body, you improve the brain.

The result is healing that brings improved health, learning, mood, and behavior. 

I use many diets in my nutrition practice for children with autism; however, the most common is gluten-free casein-free because I find it extremely helpful and fairly easy to implement. Given the prevalence of negative reactions associated with both gluten and dairy (in the autism and general population as well), it’s often the first therapeutic diet I suggest to people when getting started.

If your client needs more help you may want to consider a grain-free diet such as the Specific Carbohydrate Diet, GAPS diet, or Paleo. And I always recommend understanding how a low salicylate diet or low amine diet can improve behavior and mood. And other diets that I teach to practitioners in my BioIndividual Nutrition Pediatric Program include the low oxalate diet, low FODMAPs diet, low glutamate diet, ketogenic diet, and more. 

A Safe and Effective Intervention

 A question I get from both clients and practitioners is “Is a gluten-free and casein-free diet safe to implement?” 

I have found that improving the nutritional density of foods, removing harmful additives and things devoid of nutritional value, and tailoring a diet to the unique needs of the individual has virtually no downside. 

Additionally, eating foods that cause inflammation, like gluten and dairy, cause nutrients to not be able to be absorbed and cause deficiencies. So when someone says, “children ‘need’ dairy for the nutritional value,” I would argue that they do not, and that it can actually harm nutrient status. 

On the other hand, it is important that we help clients eat a nutritious diet and meet their nutritional needs through foods and added supplementation when required.

I want to share a video from my friend and colleague Dr. James Adams, PhD on nutritional intervention and our published study.

Meal Planning On An Autism Diet?

A healthy gluten-free and casein-free diet includes foods such as: red meat, chicken, eggs, vegetables, fruits, nuts, seeds, potatoes, rice, and beans. There is a wide variety when it comes to naturally gluten-free and casein-free foods available. But, your clients may need coaching, meal ideas, and food lists to understand just how varied a diet they can have until they get the hang of it. 

Another important piece of education your clients will need is to understand food labels and hidden sources of gluten and casein. Identifying hidden sources of these inflammatory and problematic foods goes a long way in getting your clients the results they are seeking. 

Providing your client handouts to guide them with dietary implementation is important. My BioIndividual Nutrition Pediatric Program includes many handouts and guides that can be given to your clients related to this and other nutritional education. Whether you make your own or have access to already done-for-you handouts like mine, equipping your clients with tools is important to their success… and yours.

The Science and Research on How Gluten and Casein Negatively Affect Autism

As we move into the science behind the gluten-free and casein-free diet for autism, please pay particular attention to the issue of inflammation. This applies to both the gut and the brain. Localized inflammation in the gut can impact digestion and nutrient absorption, and gastrointestinal inflammation can become systemic causing inflammation in the brain. Neurological inflammation has been linked to many chronic conditions and diseases such as autism, ADHD, depression, anxiety, and more. 

Reducing inflammation is critical for our clients to heal. Therapeutic diet intervention targeted to their personalized nutrition needs is a key to reducing inflammation, and the GFCF diet is a great place to start.  

Opiates from Gluten and Casein Impact the Brain in Autism

Certain long-chain peptides have a very similar structure to natural opioid-binding peptides. Gluten and casein are two of these proteins. Gliadorphin (also known as gluteomorphin) is the name of the opiate peptide formed during the incomplete or partial digestion of gluten, and casomorphin is the opiate peptide derived from dairy. 

There can be a few reasons as to why these peptides enter the bloodstream. Firstly, the body requires adequate enzymes to break down these proteins effectively. Specifically the DPP-IV enzyme is required. It has been shown that children with autism have lower DPP-IV activity. [1]

Leaky gut, a condition you may be very familiar with already, is another way these peptides can get into the bloodstream. Leaky gut, a condition where the intestinal lining becomes permeable, is common in autism. [2] When these peptides get into the bloodstream, they can bind to opiate receptors in the brain, causing issues like high pain tolerance or a feeling of being disconnected or “foggy”. Many clients report that their child self-selects foods with gluten and/or dairy, often at the exclusion of other foods because of this opiate connection. Removing gluten and/or dairy can then result in withdrawal symptoms in the beginning. However, after removal of these foods from the body, some families report an improvement in restrictive eating!  

Additional research on how opioids in foods impact individuals with autism: 

  • This study postulated that the opioids from gluten and casein excreted in the urine are possible etiological factors, and the diet a treatment option, in autism. And researchers stated, “A gut-to-brain axis is both possible and probable” [3]
  • Studies have linked A1 beta-casein (BCM-7) from certain forms of dairy with autism and schizophrenia [4]
  • Gluteomorphins and casomorphins are found in the urine of people with autism [5]
  • Studies show gluteomorphin/gliadorphin and casomorphin can impact neurotransmitters in the central nervous system  resulting in the social impairment seen in autism [6]

Another consideration related to opioids is the inflammation they cause in both the gut and brain. Their direct impact on the brain can cause issues such as irritability, pain, anxiety, foggy thinking, as well as addiction to foods with gluten and dairy.

The Role of Zonulin in Leaky Gut and Autism Spectrum Disorders

Gluten is known to trigger a protein called zonulin so that is an additional advantage of a gluten-free diet. What is so problematic with zonulin is that it modulates the permeability of the GI tract in humans. It has been shown to “unzip” the tight junctions causing leaky gut. Scientific research has shown zonulin’s link to gut permeability in autism [7, 8] and other chronic inflammatory disorders including cancer, neuroinflammation, autoimmune disorders, and metabolic issues. [9]

Gut permeability can cause higher reactions to other food components for children with autism. As a result, your clients may see an increase in trouble concentrating, inflammation, diarrhea, constipation, and of course food allergies/intolerances. The brain cannot function optimally if the gut is unhealthy because of the gut-brain connection. 

Individuals with ASD have a higher prevalence of gastrointestinal distress (read my article on NourishingHope.com). Additionally, the severity of GI symptoms has been linked to autism symptom severity in a study by Dr. James Adams. [10]

The study referenced above on zonulin from 2021 showed that children with severe autism had significantly higher serum zonulin than controls. This could be the missing link from Dr. Adams’ study in regards to the correlation between autism severity and GI severity! It may be related to increased  permeability of the gut. 

Children who follow a gluten-free diet have lower incidence of leaky gut than those children who do consume it.

Gluten and Casein Food Sensitivities and Inflammation in Autism 

Inflammation can be created in the body and GI tract in response to IgG antibodies to foods. This issue is even more critical in the autism community. Researchers found high IgG antibodies levels to gliadin (i.e. gluten) in 87% of people with autism, as well as 86% of those with schizophrenia. They also found high IgG antibodies to casein in 90% of individuals with ASD and 93% in schizophrenia. [11]

Another study found elevated cytokines (inflammatory markers) to gluten in people with autism who had GI symptoms. [12]

This cycle of inflammation, issues in the gut, and symptoms such as constipation, diarrhea, gas, and pain can create systemic inflammation that also impacts the brain. In addition, the individual suffers because of incomplete breakdown of foods and poor nutrient absorption as well. 

Histamine Released by Gluten and Casein and Mast Cell Activation in Autism

High histamine levels and mast cell activation are common in autism. And research even suggests that this activation leads to inflammation both in the brain and in the gut causing or exacerbating the symptoms of autism, and when exposed perinatally may even be a possible cause of the development of autism. [13]  

Histamine release can be caused by general food allergies, as well as gluten and casein. [14] Gastrointestinal disorders can also be triggered by high histamine [15] along with resulting in high acid in the stomach and/or GERD. And in a converse manner, histamine can exacerbate food allergies.

Digestive disorders, high histamine, and mast cell activation in autism can lead to increased symptoms and severity of autism.

Higher risk of Celiac in Autism 

Celiac disease is defined as an autoimmune response to gluten. This results in the body attacking the lining of the digestive tract, and causes severe digestive symptoms, along with other health conditions. While the majority of the time we see non-celiac gluten intolerance in autism, there is an increased risk of celiac disease as well. 

In fact, there is research that shows people with autism are more likely to carry the HLA gene with the HLA-DRB1 *11-DQB1*07 structure, which raises the risks of celiac disease. [16]

The Connection Between Gluten, Casein, and Glutamate in Autism

Studies show that individuals with autism have a higher risk of elevated glutamate. [17

Some children and adults with autism are more sensitive to glutamate, an excitatory neurotransmitter. And they have less ability to convert glutamate to the calming neurotransmitter GABA. As a result, their brains are more responsive to the effects of glutamate and you can see increased hyperactivity, irritability, restlessness, anxiety, migraines, seizures, and many more symptoms in these individuals. 

A diet rich in gluten and casein can increase glutamate levels because gluten is 25% glutamate by weight, and casein is 20%. For those sensitive individuals or those with high levels of glutamate such as those with autism, foods with gluten and dairy can worsen neurological symptoms, including stress, anxiety, irritability, and hyperactivity. Glutamate has also been shown to cause inflammation in the brain and gastrointestinal system. [18]

Reducing gluten and dairy in the diet can help reduce the symptoms of autism in some individuals, in part because of this glutamate connection.

Cerebral Folate Deficiency and Dairy

Cerebral folate deficiency involves folate not being able to be adequately transported into the brain because of autoantibodies to the folate receptor. This means the brain does not have adequate folate. Some children with autism have this condition. Cerebral folate deficiency can cause slow head growth, low muscle tone, irritability and sleep problems, loss of bodily movement, speech complications, and seizures. 

There is scientific data showing that 75.3% of children with autism had autoantibodies to folate receptors. [19

So for children with autism who have cerebral folate deficiency, studies show that soluble folate-binding proteins in milk cross react with folate receptors, this increases autoantibodies to folate receptors making the problem even worse by decreasing folate to the brain even further. But, the good news is that studies show removing dairy from the diet can reduce folate receptor autoimmunity in cerebral folate deficiency syndrome. [20] 

Removing dairy from the diet reduces folate receptor autoantibodies and autoimmunity.

Scientific Research: Gluten-Free Casein-Free (GFCF) Diet Improves Autism Symptoms

Now that I have given you the underlying factors that can cause gluten and dairy to be problematic for individuals with autism, I want to also share the growing scientific data on the efficacy and benefits of removing gluten and casein from the diet.

Study Shows 91% of Children with Autism Had Improved Behavior, Speech, and/or GI Symptoms with GFCFSF

We’ve learned through the research that autism may be accompanied by inflammatory immune responses. This mechanism may also be what predisposes them to sensitivity to the proteins in wheat, dairy, and soy. Inflammation of the digestive system is the result of this increased sensitivity to these dietary proteins and this often exacerbates negative behaviors.

One very interesting study showed clinical improvement in 91% of the children as observed by therapists, teachers, and parents following the implementation of a gluten-free, casein-free and soy-free (GFCFSF) diet. Improvements were seen in speech, focus, sleep, GI symptoms, and less hyperactivity. [21]

6.7 points in Non-Verbal IQ and 4.5x Developmental Age Improvement  from GFCFSF Diet and Nutrition Intervention in Autism

I am particularly proud of this next study because I was part of it! It showed a 6.7 pts increase in non-verbal IQ and a 4.5 fold developmental age improvement. 

The study included individuals aged 3-58 years old who implemented a healthy gluten-free, casein-free, and soy-free diet, a multivitamin/mineral formula, an essential fatty acid supplement, carnitine supplementation, digestive enzymes, and epsom salt baths. Read my complete write up here.

Major improvements outside of development and IQ included: a reduction in autism symptoms, decrease gastrointestinal symptoms, improved language, increased focus, reduced anxiety, and more. [22]

Increased Social and Communication Skills Along with Reduced Autism Behaviors with GFCF Diet

A review of the existing scientific literature found consistently positive results with a gluten-free and casein-free diet for autism. The literature included both individual case studies and papers where groups of children were studied. 

What researchers found was an overall decrease in autism behaviors as well as increased social skills and communicative skills. 

It is important to note that they found the autism traits reappeared after the diet was broken. [23]

Better Development for Individuals with Autism on a GFCF Diet

This study evaluated the effects of a gluten-free and casein-free diet for children with autism in regards to urinary opioid peptides associated with gluten, gliadin, and casein. 

The study concluded that children following a gluten-free and casein-free diet had better development than the control group. [24]

Significant Improvement in Autism and ADHD Symptoms in Children with ASD on the GFCF Diet

In this two-stage, 24-month, randomized, controlled trial,  72 Danish children (ranging from 4 years old to 10 years 11 months) were assigned to diet (A) or non-diet (B) groups. To assess core autism behaviors they used the Autism Diagnostic Observation Schedule and the Gilliam Autism Rating Scale. Vineland Adaptive Behaviour Scales was used to determine developmental level, and the Attention-Deficit Hyperactivity Disorder – IV scale was used to determine inattention and hyperactivity. 

There were significant improvement scores in the diet group on all of the scales by 12 months. Group B was also assigned to the diet midway through the trial because of the improvement seen in group A! The results indicated that dietary intervention using a gluten-free and casein-free diet may positively affect developmental outcomes for children with ASD. [25]

GFCF and Keto Diets Improve Autism Symptoms

One interesting study looked at the differences between the GFCF diet and the ketogenic diet for autism. Both diets resulted in significant improvement in autism symptoms. There were some differences between the diet results, one diet had better results in behavior, while the other diet group showed better scores for cognitive awareness and sociability. For a more detailed review of this study, you can check out my article on NourishingHope.com. The end result was that both diets appear to improve symptoms of autism, depending on the individual needs of the person. This study highlights yet another example of how the gluten-free casein-free diet can be beneficial to those with autism. [26]

Closing Thoughts

The science is clear, following a gluten-free and casein-free diet can help improve autism. 

Creating a personalized autism diet plan for your clients can help them implement a GFCF diet smoothly and successfully. 

The great news is that our BioIndividual Nutrition Institute community continues to set the standard for dietary intervention for autism. 

Do you share my interest in clinical nutrition and therapeutic diets to improve conditions like ADHD and autism?  Have you considered specializing in this niche and serving this clientele in need? 

A special group is forming right now; I’m cultivating an exclusive group of 25 nutrition professionals to be on the cutting edge of helping children. 

My BioIndividual Nutrition Training: Pediatric Program, is the most advanced training program in personalized nutrition for children. I launched it seven years ago to fill a gap in the application of special diets targeted to an individual’s specific needs. 

Now we’ve got hundreds of professionals from 46 countries; nutritionists, dietitians, integrative medical practitioners, health coaches, and more! 

These are people just like you – who have a passion for helping kids with ADHD, autism, and other pediatric special needs.

For those ready to connect with colleagues who are as equally passionate as you …. some of the smartest in the nutrition community, and want to have the confidence to work with any client who walks through your door…

Join our Exclusive Pediatric Nutrition Professionals Group – Open right now!

  • 25 nutrition practicing professionals talking their career to the next level
  • Virtual meet-and-greet with like-minded colleagues
  • Roundtable symposium on autism, ADHD and other pediatric topics
  • Discounted enrollment (& payment plan)
  • Combo-Diet Meal Planning Package (saves you hours customizing meal plans and food list for complex, combination diet needs) 

The need for this expertise is at an all time high…so, if now feels like the right time for you, click here to email me and I’ll get you the details you need to join.

References for this article

  1. Bashir, S. and Laila, A.A., 2014. Alterations in plasma dipeptidyl peptidase IV in autism: A pilot study. Neurology, Psychiatry and Brain Research, 20(2), pp.41-44.
  2. Fowlie, G., Cohen, N. and Ming, X., 2018. The perturbance of microbiome and gut-brain axis in autism spectrum disorders. International journal of molecular sciences, 19(8), p.2251.
  3. Reichelt, K.L., Knivsberg, A.M., Lind, G. and Nødland, M., 1991. Probable etiology and possible treatment of childhood autism. Brain Dysfunction.
  4. Kamiński, S., Cieślińska, A. and Kostyra, E., 2007. Polymorphism of bovine beta-casein and its potential effect on human health. Journal of applied genetics, 48(3), pp.189-198.
  5. Tveiten, D., Finvold, A., Andersson, M. and Reichelt, K.L., 2014. Peptides and exorphins in the autism spectrum. Open Journal of Psychiatry, 2014
  6. Horvath, K. and Perman, J.A., 2002. Autism and gastrointestinal symptoms. Current gastroenterology reports, 4(3), pp.251-258.
  7. Esnafoglu, E., Cırrık, S., Ayyıldız, S.N., Erdil, A., Ertürk, E.Y., Daglı, A. and Noyan, T., 2017. Increased serum zonulin levels as an intestinal permeability marker in autistic subjects. The Journal of pediatrics, 188, pp.240-244
  8. Karagözlü, S., Dalgıç, B. and İşeri, E., 2021. The Relationship of Severity of Autism with Gastrointestinal Symptoms and Serum Zonulin Levels in Autistic Children. Journal of Autism and Developmental Disorders, pp.1-7.
  9. Fasano, A., 2020. All disease begins in the (leaky) gut: Role of zonulin-mediated gut permeability in the pathogenesis of some chronic inflammatory diseases. F1000Research, 9.
  10. Adams, J.B., Johansen, L.J., Powell, L.D., Quig, D. and Rubin, R.A., 2011. Gastrointestinal flora and gastrointestinal status in children with autism–comparisons to typical children and correlation with autism severity. BMC gastroenterology, 11(1), pp.1-13.
  11. Cade, R., Privette, M., Fregly, M., Rowland, N., Sun, Z., Zele, V., Wagemaker, H. and Edelstein, C., 2000. Autism and schizophrenia: intestinal disorders. Nutritional Neuroscience, 3(1), pp.57-72.
  12. Jyonouchi, H., Geng, L., Ruby, A., Reddy, C. and Zimmerman-Bier, B., 2005. Evaluation of an association between gastrointestinal symptoms and cytokine production against common dietary proteins in children with autism spectrum disorders. The Journal of pediatrics, 146(5), pp.605-610.
  13. Theoharides, T.C., Angelidou, A., Alysandratos, K.D., Zhang, B., Asadi, S., Francis, K., Toniato, E. and Kalogeromitros, D., 2012. Mast cell activation and autism. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 1822(1), pp.34-41.
  14. Miller, M.J.S., Zhang, X.J., Gu, X., Tenore, E. and Clark, D.A., 1991. Exaggerated intestinal histamine release by casein and casein hydrolysate but not whey hydrolysate. Scandinavian journal of gastroenterology, 26(4), pp.379-384.
  15. Schnedl, W.J. and Enko, D., 2020. Considering histamine in functional gastrointestinal disorders. Critical Reviews in Food Science and Nutrition, pp.1-8.
  16. Rahmoune, H. and Boutrid, N., 2018. Autism & Gluten: The Proof By Regression!. Pediatric neurology briefs, 32, p.9.
  17. Shinohe, A., Hashimoto, K., Nakamura, K., Tsujii, M., Iwata, Y., Tsuchiya, K.J., Sekine, Y., Suda, S., Suzuki, K., Sugihara, G.I. and Matsuzaki, H., 2006. Increased serum levels of glutamate in adult patients with autism. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 30(8), pp.1472-1477.
  18. Xu, L., Sun, J., Lu, R., Ji, Q. and Xu, J.G., 2005. Effect of glutamate on inflammatory responses of intestine and brain after focal cerebral ischemia. World journal of gastroenterology: WJG, 11(5), p.733.
  19. Frye, R.E., Sequeira, J.M., Quadros, E.V., James, S.J. and Rossignol, D.A., 2013. Cerebral folate receptor autoantibodies in autism spectrum disorder. Molecular psychiatry, 18(3), pp.369-381.
  20. Ramaekers, V.T., Sequeira, J.M., Blau, N. and Quadros, E.V., 2008. A milk‐free diet downregulates folate receptor autoimmunity in cerebral folate deficiency syndrome. Developmental Medicine & Child Neurology, 50(5), pp.346-352.
  21. Jyonouchi, H., Sun, S. and Itokazu, N., 2002. Innate immunity associated with inflammatory responses and cytokine production against common dietary proteins in patients with autism spectrum disorder. Neuropsychobiology, 46(2), pp.76-84.
  22. Adams, J.B., Audhya, T., Geis, E., Gehn, E., Fimbres, V., Pollard, E.L., Mitchell, J., Ingram, J., Hellmers, R., Laake, D. and Matthews, J.S., 2018. Comprehensive nutritional and dietary intervention for autism spectrum disorder—a randomized, controlled 12-month trial. Nutrients, 10(3), p.369.
  23. Knivsberg, A.M., Reichelt, K.L. and Nødland, M., 2001. Reports on dietary intervention in autistic disorders. Nutritional Neuroscience, 4(1), pp.25-37.
  24. Knivsberg, A.M., Reichelt, K.L., Høien, T. and Nødland, M., 2002. A randomised, controlled study of dietary intervention in autistic syndromes. Nutritional neuroscience, 5(4), pp.251-261.
  25. Whiteley, P., Haracopos, D., Knivsberg, A.M., Reichelt, K.L., Parlar, S., Jacobsen, J., Seim, A., Pedersen, L., Schondel, M. and Shattock, P., 2010. The ScanBrit randomised, controlled, single-blind study of a gluten-and casein-free dietary intervention for children with autism spectrum disorders. Nutritional neuroscience, 13(2), pp.87-100.
  26. El-Rashidy, O., El-Baz, F., El-Gendy, Y., Khalaf, R., Reda, D. and Saad, K., 2017. Ketogenic diet versus gluten free casein free diet in autistic children: a case-control study. Metabolic brain disease, 32(6), pp.1935-1941.

Nutritional and dietary intervention is effective at improving non-verbal IQ, autism symptoms, developmental age in children and adults with ASD.

I’m very excited to share the results of a new scientific study on autism: this is my first published paper!

You read that right! I am one of the co-authors of this study, which was led by James Adams, PhD, entitled “Comprehensive Nutritional and Dietary Intervention for Autism Spectrum Disorder—A Randomized, Controlled 12-Month Trial.”[1]

Dr. Adams is the director of the Autism/Asperger’s Research Program at Arizona State University, where he has been studying this condition for the past 15 years. He’s also the father of a daughter with autism.

Five years ago, Dr. Adams approached me and my colleague Dana Laake to help with a study on autism; specifically researching how nutrition and diet can improve the symptoms of autism. He asked that we contribute to the research by educating and guiding participants how to implement a healthy GFCF diet, which was a core intervention of the study.

The Highlights

As a nutritionist specializing in Autism Spectrum Disorder, I’ve been investigating the unique physiology, etiologies, and “bioindividual” biochemistry in people with ASD since 2002; specifically, how food and nutrition choices affect the body and behavior (symptoms) in autism, and how to devise individualized therapeutic diet strategies that help alleviate these symptoms. I’ve witnessed significant improvements in the health and happiness of children with ASD using special diets and nutritional supplementation; from modest digestive improvement to complete recovery. Regardless of the degree to which the person with autism recovers, we see improvement, across the board, with a healthy, gluten free, casein free, soy free diet.

This study supports what many practitioners and parents have been seeing in practice all along. Finally, we have conclusive evidence that nutritional and dietary intervention is effective at improving non-verbal IQ, autism symptoms, and developmental age in children and adults with ASD! There were improvements in anxiety, mood, aggression, hyperactivity, focus, and more!

Thus, I’m thrilled to share the results of this 1-year comprehensive study with all of you. The outcomes were life changing for many of the children that participated, and their families and communities, too.

And there were some stunning recoveries. One study participant recovered so quickly through treatment that she no longer has to use her wheelchair! Simply from dietary and nutritional approaches, another boy no longer has to be catheterized! Other stunning results from this study include: eliminating pica (eating non-food items which can be life threatening) in two children, improving symptoms of autism, helping them connect more with loved ones, and having a better quality of life… all of which were found from this research.

Furthermore, the hope that it brings to the rest of us: that this simplifed approach is safe, accessible. and doable for any autism family!

This study should greatly influence the medical and educational community regarding treating those with autism: for awareness and progress is so necessary, as most doctors are poorly informed. Even the Academy of Nutrition and Dietetics (formally the ADA) erroneously indicates that there “not enough science to support dietary intervention for autism.”

In this article, I’ll discuss the details in this recently published study, and clarify how we used specific supplements with an allergen-free diet, to address the most common etiologies and co-morbidities within the ASD subpopulation.

Who was included in the research?

A total of 117 individuals, aged 3 to 58, enrolled in the study. None of them had taken nutritional supplements (vitamins, minerals, essential fatty acids, carnitine) or consumed “special” diets in the previous two months.

67 of the participants had been previously diagnosed with ASD (autism, Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS), or Asperger’s). Arizona State University staff verified the participant’s ASD diagnosis using the Autism Diagnostic Observation Schedule (ADOS) and/or the 2nd edition of the Childhood Autism Rating Scale (CARS-2).

The remaining 50 participants were neurotypical, meaning that none of them had been diagnosed with a mental disorder including ASD, ADHD, depression, or anxiety. Moreover, none of these participants had a first-degree relative with ASD.

How was the study conducted?

The study was designed as follows:

Assessment of ASD symptoms

After enrollment, autism severity and overall functioning level were assessed among participants with ASD. ADOS, CARS-2, Reynolds Intellectual Assessment Scales (RIAS), or Severity of Autism Scale (SAS-Pro) were utilized during the evaluation.

Moreover, parents or high-functioning adult participants filled in a medical history form at the beginning of the study. They also completed various questionnaires at the beginning and end of the intervention to assess autism and related symptoms.

Random Assignment

The participants with ASD were then randomly assigned to either the ASD treatment group or to the ASD Non-treatment group as outlined below:

  • The treatment group consisted of 37 participants (30 males and 7 females). This group was composed of 28 children (ages 3 to 12), 6 teenagers (ages 13 to 20), and 6 adults (over 20 years old).
  • The non-treatment group included 30 participants (25 males and 5 females). This group consisted of 20 children, 7 adolescents, and 3 adults.

The neurotypical group consisted of 41 males and 9 females (34 children, 11 teenagers, and 5 adults).

Health and Biomarker Assessments

The study physician physically examined all the participants to ensure that they were sufficiently healthy to participate in the research.

First-morning urine and blood samples were collected once at the start of the study in the neurotypical group and at the beginning and end of the study in the treatment and non-treatment groups and.

These samples were sent for analysis to commercial laboratories approved by the Clinical Laboratory Improvement Amendments (CLIA) program.

The blood biomarkers measured included:

  • Ammonia
  • Lactic acid
  • Creatine Kinase
  • C-Reactive protein
  • Thyroid panel (TSH, T3, T4)
  • Complete Blood Count (CBC)
  • Red blood cells (RBC) minerals and fatty acids
  • Homocysteine-related metabolites (homocysteine, cysteine, methionine)

Treatment protocol

Only participants in the ASD treatment group received the combined treatment protocol.

Participants in the non-treatment group were promised that they would obtain all the supplements and diet advice once the study was completed. The only condition was that they made no significant change to their nutritional therapy, medical treatment, or education treatment for 12 months. This step helped reduce drop-outs.

The treatment group started treatment with a multivitamin/mineral supplementation. The dose was adjusted based on the child’s weight and split into 3 doses (breakfast, lunch, and dinner).

On day 30 of the study, the participants received an essential fatty acid supplement containing 609mg omega-3’s (425mg EPA, 110mg DHA, 74mg other omega 3’s), 198mg omega-6 (including 128mg GLA), and 15mg omega-9. The participants started with 1 capsule daily and then increased to a maximum of 4 capsules daily depending on their weight.

On day 60, participants were asked to take one warm Epsom salt bath for 20 minutes, twice a week. Two cups of Epsom salts and half a cup of baking soda were added to the bath.

On day 90, participants started taking 50mg of acetyl-L-carnitine/kg bodyweight-day. This dosage was gradually increased to a maximum of 2 grams/day over 4 weeks and split into two doses (breakfast and dinner).

On day 180, the participants were advised to take a plant-based digestive enzyme supplement. The dose was as follows:

  • 1 capsule for a snack or small adult meal
  • 2 capsules for a typical adult meal
  • 3 capsules for a large adult meal

On day 210, the participants started a healthy, gluten-free, casein-free, soy-free (HGCSF) diet outlined below.

All the supplements and dietary changes were continued until the end of the study.

Why this protocol?

  • Vitamins/minerals: As mentioned earlier, individuals with ASD have profound nutritional deficiencies which can have deleterious effects on overall health and ASD symptoms. Supplementation can help increase several biomarkers and vitamin status.
  • Essential fatty acids (EFAs): These fatty acids help maintain cell membrane health. It is, therefore, no surprise that an EFA deficiency could adversely affect brain health and lead to depression and psychological disorders.But did you know that our intestines need EFAs to function correctly? In fact, an EFA deficiency could explain why supplementation can help improve GI symptoms that are common in ASD.
  • Epsom salt baths: Epsom salts are magnesium sulfate salts and have been found to be highly effective in increasing plasma sulfate levels. Healthy sulfate levels are required for optimal detoxification, synthesis of healthy brain tissue, intestinal and brain barrier function, neurotransmitter and gastrointestinal functions.
  • Acetyl-L-carnitine: Carnitine is involved in energy metabolism and mitochondrial protection. This compound helps remove potentially harmful substances from the mitochondria and cell so that they can be excreted from the body. In previous research, Dr. Adams found that individuals with ASD who supplemented with carnitine scored better on scales that assessed severity of autism symptoms and global functioning [4].
  • Digestive enzymes: Gastrointestinal symptoms can predict autism severity. Digestive enzymes enhance digestive function and alleviate gastric upset, thus relieving pain and associated autistic behaviors, as well as improving nutrient absorption and nutrition levels.
  • HGCSF diet: If not properly digested, gluten, casein, and soy can favor the production of opiates, which can fit opiate receptors in the brain. This can cause brain fog, trouble concentrating, constipation, and inflammation. Moreover, gluten, casein, and soy can increase intestinal permeability – this can severely affect the gut-brain axis.

Besides removing potential food triggers, the HGCSF diet also aims to heal cells throughout the body (including the gut) by reducing inflammatory proteins, support detoxification pathways, and strengthen the immune system.

My role in this study

Dana Laake and I were the two nutritionists on the team of 15 other medical professionals and academic researchers. I really enjoyed working with Dana – she’s very collaborative, passionate and knowledgeable. I’ve known this lovely person for years, and I’m very impressed with her super smart nutrition brain. Dana is also the author of two successful books.

So, for this study, Dana and I designed a 1-hour power point presentation with audio for the families of the participants in the treatment group. The presentation aimed to help these families better grasp:

  • What the HGCSF diet is all about
  • The science, or what we called the [numerous] “whys” behind the diet
  • How to implement the HGCSF diet easily
  • How to assess the effectiveness of this diet

Dietary changes recommended in this study

In a nutshell, the intervention group was advised to:

  • Consume a nutrient dense diet with adequate organic produce, quality protein, and sufficient calories from healthy fats like coconut oil, olive oil, ghee (certified casein-free if no dairy IgE allergy), and grass-fed tallow.
  • Remove food toxins that place extra burden on detoxification pathways (like MSG, artificial flavors, colors, and preservatives) by avoiding processed foods.
  • Remove foods that promote gut inflammation (such as gluten, casein, soy, sugar, and industrial seed oils).

Now, that you know everything there is to know about this study, let’s discuss the study’s findings.

Findings of this study

Improvements in cognitive, GI function, and medical biomarkers

Compared to the control group, the treatment group experienced significant changes in:

  • Cognitive function as indicated by considerable improvements in non-verbal IQ tests with gains of 6.7 IQ points.
  • The treatment group ‘gained an average of 18 months of development’ with substantial progress in communication, social, and daily living skills. This was 5 times the development over the control group. They also performed significantly better on all of the ASD/behavioral assessments.
  • Gastrointestinal symptoms: Constipation and diarrhea improved as well as stool smell.
  • Carnitine levels increased in the treatment group.
  • Fatty acids levels: DHA and EPA levels increased in the treatment group. Levels of arachidonic acid decreased and could result in a reduced production of pro-inflammatory molecules.
  • Red blood cell minerals: Selenium and chromium levels increased in the treatment group.
  • Homocysteine pathway: The combined treatment helped reduce homocysteine levels to normal.
  • Vitamins: Levels of vitamin B2, B5, folic acid, CoQ10H2, one vitamin B6 biomarker, and cyanocobalamin (a form of vitamin B12) improved in the treatment group.

Improvements in mood, behavior, and focus 

There were significant improvements in the diet and nutrition treatment group based on Parent Global Impressions. These included statistically significant improvement in:

  • Mood/happiness
  • Anxiety
  • Sociability
  • Attention focus
  • Hyperactivity
  • Tantrums
  • Aggression

There were three exceptional cases

Three participants in the treatment group also showed remarkable improvements:

  • A 7-year-old boy with pica was healed entirely within one week of starting the HGCSF diet. Pica is the eating of non-food items like rocks, twigs, or batteries, and it can be very dangerous.
  • A 27-year-old male with severe ASD and a history of severe urinary retention requiring daily catheterization was able to urinate on his own after only 4 days eliminating dairy products. By the end of the study, the young man no longer needed catheterization and had zero episodes of kidney stones, urinary tract or bladder infections.
  • One 9-year-old girl with severe ASD had poor strength, endurance, and energy levels at the beginning of the study. Four months after the treatment, she no longer needed her wheelchair. We found out that her pre-treatment diet was deficient in carnitine due to total avoidance of beef and pork products, so supplementation showed to be critical for her strength and stamina.

Some adverse effects were observed

The following treatments caused a few reactions:

  • Vitamins/Minerals: Two brothers experienced a moderate worsening of behavior and stopped all supplements after 4 months. They did, however, benefit from the HGCSF diet which cured severe pica for one child.
  • Carnitine: This supplement made one child “feel sick” and was discontinued by the parent.
  • Digestive enzymes: The enzymes caused intestinal symptoms in one child who discontinued use after one month. Extended use of this supplement triggered facial rash in another participant who eventually decided to stop taking it despite noticing improvements in behavior and constipation.
  • HGCSF diet: Removing one child’s favorite foods led to frustration and caused behavioral problems as well as an inability to solve problems.

There is No Magic Window

Some people believe in a “window” for treatment, that the older an individual gets the less likely treatment will help. This study proves that wrong! And thank goodness!

It’s always bothered me that people would think that, because I have found it not to be true – and that people of all ages can improve. After all, our message behind “Nourishing Hope” doesn’t exclude anyone, no matter their age or diagnosis. I certainly believe no one should dash the hope of older children and adults unnecessarily and erroneously.

The study found under Age Effects, “An evaluation of changes on all the outcome measures suggests that there was no significant correlation of benefits with age, so children and adults of all ages are likely to benefit from this combination treatment.”

Implementing nutritional and dietary intervention at any age is worthwhile. It’s never too late to be nourishing hope.

Additional insights

  • L-carnitine may be better absorbed than acetyl-l-carnitine.
  • Some vitamins that did not increase significantly during the study, such as vitamin D, may be needed in larger doses and/or more bioavailable forms to have a therapeutic value.

What does this research confirm?

1.    Autism is a whole-body disorder and the brain is downstream

Autism has long been considered as a cluster of psychiatric/psychological behaviors caused by defective genes that induced structural changes in the brain before birth. However, current research clearly shows that autistic individuals have suboptimal biochemical pathways that affect neurological function.

For example, a majority of children with autism have issues with:

  • Methylation which is responsible for controlling DNA synthesis, building neurotransmitters (brain chemicals), and enzyme production. This pathway also ensures that neurons fire in sync. It also helps the body create ATP (or cellular energy).
  • Transsulfuration, which is the primary part of the body’s innate detoxification system, depends on a healthy methylation pathway.
  • Sulfation which helps the body eliminate toxins by binding them to sulfates. This renders the toxins more water-soluble and, hence, safer to excrete. Sulfation relies on methylation and transsulfuration.

So, as you can imagine, if any of these pathways are ‘broken,’ a cascade of symptoms will occur. For example, individuals with autism often suffer from:

  • Digestive issues
  • An inflamed gut
  • Decreased detoxification
  • Increased intestinal permeability
  • An imbalanced gut flora (with too many pathogens and few beneficial bacteria)

All of these symptoms can significantly impact the brain since they impair nutrient absorption, cause oxidative stress, and increase inflammation. The good news is that various studies show that supporting these pathways can considerably improve ASD symptoms.

2.    Individuals with ASD are severely deficient in various nutrients

As I have mentioned in a previous article, multiple studies indicate that children with ASD often have deficiencies in:

  • Vitamins
  • Essential fatty acids
  • Sulfate
  • Digestive enzymes
  • Antioxidants like glutathione

These studies also indicate that supplements can correct these deficiencies and alleviate ASD symptoms.

3.    Food sensitivities are common in autism

Studies have shown that children with ASD often have abnormal immune responses to:

  • Gluten (in wheat, rye, oats, barley)
  • Casein (from dairy products)
  • Soy (not always)

In one study, 81% of children who eliminated gluten and casein for 1 year improved considerably [2]. These improvements continued over the next 12 months!

What kind of study was this?

This research used a single-blinded approach where the clinical evaluators, but not the participants, were blinded. What this means is that only the participants knew whether they were receiving the combined intervention or no treatment at all.

Since clinical evaluators are blinded, this approach eliminates the possibility of bias or manipulation of results during assessments and laboratory measurements. A single-blind study is also more realistic and practical and better mimics real-world implementation. It also reduces the possibility that participants will drop out of the study.

I proudly assert that this study followed the strictest scientific rigor for research of its kind, and that it’s findings are credible. Some diet naysayers may dismiss the current study, arguing that it’s not the “gold standard” of a randomized, double blind, placebo controlled study, or that it studies too many variable at once.

Firstly, when dealing with whole foods, it is very difficult, or nearly impossible, to conduct a double-blind study (one in which both the evaluators and the participants are blinded). The participants are eating real food and need to know what they are eating; anybody would agree, it’s hard to get around that. Secondly, with multiple interventions being used, it more closely depicts how most families conduct a dietary intervention and nutrition program. Families are not going to try one intervention, wait a year and then try the second, and the third, etc. And there is synergy among diet and nutrient treatments: vitamins and minerals are co-factors for each other enhancing their individual effects, and diet and nutrients also have improved results when used together.

What sets this study apart?

Why did we conduct this study when previous studies already indicate that dietary changes and specific nutritional supplements can improve ASD symptoms?

Well, these earlier studies looked at either the effects of diet or nutrition therapy individually and over a short period of time. None of them investigated whether combining these two treatments over the long-term could be more efficient.

So what sets this study apart?

Comprehensive approach

Since autism is a whole-body disorder, combining a comprehensive nutritional intervention with specific dietary modifications could be more effective in improving many ASD symptoms.

Duration of the study

Individuals with ASD often use supplements over an extended period. And the effects of nutritional interventions are often slower than those of pharmaceutical interventions.

Therefore, we conducted this research over 12 months to assess the long-term effects of this combined approach on ASD symptoms among adults and children. The long duration of the study also allowed for a more extensive evaluation of possible adverse effects.

Quality of supplements used

Dr. Adams has improved the vitamin/mineral supplements used in this study based on findings from his previous research [3]. The new and improved version of the supplement contains:

  • A higher dose of vitamin D, niacin, pantothenic acid, biotin, selenium, mixed tocopherols.
  • Added vitamin K, potassium, carnitine, vanadium, and boron.
  • A lower dose of manganese, molybdenum, lithium.

Note: Dr. Adams makes no money from the sale of the supplements used in the study.

Quality of study design

This study utilized a very robust study design, as described below, to ensure that the findings are reliable and not due to chance or bias.

Takeaway Message and Conclusion

  • Combining nutritional supplements and dietary changes is safe and efficient at improving ASD symptoms.
  • Even adults with autism can improve with nutritional and dietary intervention.

In my opinion, future studies may yield ever greater results with a more refined bioindividual approach. For example, certain approaches like carnitine did not offer noticeable improvements for a majority of the participants, but for those that it did, like the girl in the wheelchair, it was life changing. While this study wasn’t looking at this specifically, customizing a nutritional approach to the biochemical and individual needs of the person, can likely yield even more beneficial results.

The study’s conclusion says it all, “The positive results of this study suggest that a comprehensive nutritional and dietary intervention is effective at improving non-verbal IQ, autism symptoms, developmental age, and other symptoms in most individuals with ASD, with the vitamin/mineral supplement, essential fatty acids, and healthy HGCSF diet reported by parents to be the most beneficial.”

It was an honor to be part of this study. The finding supports the clinical results I have been seeing in my clinical nutrition practice for the past 16 years. And this study helps support clinicians and parents all over the world that want to use a diet and nutrition approach to help children and adults with ASD

Now, I’d love to hear from you: have you tried any of the supplements or dietary changes described in this study? If so, it would be wonderful if you could share your experience in the comment section below. I’m sure your feedback could help others take the lead.

By Julie Matthews

References

1. Adams, J.B.; Audhya, T.; Geis, E.; Gehn, E.; Fimbres, V.; Pollard, E.L.; Mitchell, J.; Ingram, J.; Hellmers, R.; Laake, D.; Matthews, J.S.; Li, K.; Naviaux, J.C.; Naviaux, R.K.; Adams, R.L.; Coleman, D.M.; Quig, D.W. Comprehensive Nutritional and Dietary Intervention for Autism Spectrum Disorder—A Randomized, Controlled 12-Month Trial. Nutrients 2018, 10, 369.

2. Cade R, Privette M et al. “Autism and Schizophrenia: Intestinal Disorders” Neurosci 3 (2000) 57-72. Published by Overseas Publishers Association, (OPA) N.V.

3. Adams JB, Audhya T, Mcdonough-Means S, Rubin RA, Quig D, Geis E, Gehn E, Loresto M, Mitchell J, Atwood S, Barnhouse S, Lee W Effect of a Vitamin/Mineral Supplement on Children with Autism, BMC Pediatrics 2011, 11:111

4. Geier DA, Kern JK, Davis G, King PG, Adams JB, Young JL, Geier MR. A prospective double-blind, randomized clinical trial of levocarnitine to treat autism spectrum disorders. Med Sci Monit 2011 Jun;17(6):PI15-23.

What do berries, apples, and grapes have in common?

Salicylates.

A vast majority of children with autism and ADHD in my nutrition practice have salicylate reactions. The most common symptoms are red cheeks. red ears, hyperactivity, and irritability..

SALICYLATES are a #1 food related cause of BEHAVIOR issues.

There is a reasonable explanation for the prevalence I see in my practice. It’s not just because I am aware of reactions and so I recognize more than the average nutritionist, although that is true too.

It is because there are underlying factors and biochemistry that can cause an inability to process these food compounds and has such, reactions are common.

The good news is that there are things you can do.

What are Salicylates?

Salicylates are naturally-occurring food chemicals in fruits, vegetables, and other plant foods like herbs, spices, nuts, etc.).  In the 1950’s and 60’s, Dr. Ben Feingold observed that artificial additives and high salicylate foods caused hyperactivity and other symptoms in some children.  Biochemically, salicylates are a type of “phenolic acid” or “phenol.” Phenols need to be broken down in the body, i.e. “detoxified,” which occurs through a process called sulfation.

Salicylates to Avoid

Fruits (most fruit is high)

  • Grapes
  • Strawberries
  • Blueberries
  • Raspberries
  • Most melons including watermelon
  • Peaches
  • Nectarines
  • Plums
  • Apples

Vegetables

  • Red bell peppers
  • Cucumbers and pickles
  • Tomato sauce and ketchup (technically a fruit)
  • Spinach
  • Zucchini (with the peel on)

Herbs and spices

  • Cinnamon
  • Cloves
  • Rosemary
  • Thyme
  • Turmeric
  • Ginger

Additional high salicylate foods

  • Almonds
  • Honey

These fruits are delicious and plentiful, children eat quite a bit more during summer than any other time.  The resulting increase in salicylate consumption can cause a child’s body to become overloaded, and cause physical, emotional, and behavioral symptoms.  

Symptoms of Salicylates

Symptoms vary by individual, but some of the most common salicylate sensitivity symptoms are:

  • Red cheeks and ears (not from the heat)
  • Hyperactivity
  • Irritability
  • Defiant behavior
  • Aggression toward self or others
  • Overly emotional/crying
  • Bedwetting and day-wetting accidents
  • Sleeping challenges

Artificial Additives

Junk food with artificial additives are more plentiful during summer.  Artificial additives such as artificial colors, flavors and preservatives are strong phenols–and require the same biochemical processes.

If you don’t consume these, good for you. You shouldn’t.

In the average American family, however, blue-colored sports drinks on hot days, cotton candy from the beach boardwalk or fair, shaved ice or blended slushies from the amusement park are all to common occurrences (sadly).   Alone they are known to cause hyperactivity, combined with these other stressors and they can be particularly problematic.

Underlying Contributors and Biochemistry

Inadequate sulfation is the underlying biochemical issue in salicylate intolerance. This can be due to depletion of sulfate from sources such as food or a pathogen. It can be due to inadequate supply. Or the kidneys can dump sulfate, wasting it.

Without proper sulfate we cannot have proper sulfation. Sulfation handles many processes such as sealing up the gut so it’s not leaky. And detoxifying chemicals and processing salicylates and phenolic compounds.

Poor sulfation, and salicylate reactions, are common in autism and ADHD.

Salicylates can mask your GFCF Success

A very common scenario is that a family will go gluten-free and dairy-free, typically a great choice. And then start eating more healthy foods. But instead of feeling better the child has just as many, if not more, reactions and behavior issues than before.

Sadly, parents often think this means the diet is not working or wrong for them. However, that’s an incorrect assumption most of the time.

What’s usually going on is that the salicylate reactions mask the GFCF diet success. When they reduce salicylates the symptoms go away and they see the benefit they had been hoping for from dietary intervention.

Experience from a Mom…

“I was at a conference listening to nutritionist Julie Matthews. She was showing a slide of various behaviors, pretty accurately describing my son. At that time, my son had started showing some aggressive behaviors, mostly directed towards me (biting, causing bruises), and I was getting phone calls from school about him lashing out. The follow up slide was which foods to eliminate in order to stop the behaviors. It was all of my son’s favorites. I immediately texted my husband and told him, when I got home, we were doing a diet overhaul. We took out all of the problem foods, and his behaviors stopped! The change was so dramatic that his doctor, who had wanted to start medication, decided it was unnecessary. Do not discount diet!”

-Jennifer S.

What can you do?

Avoid Junk Food

Firstly, if your child eats artificial additives, cut them all out. It’s the first step of my Nourishing Hope for Healing Kids nutrition program. And it can be a simple, yet tremendously helpful step.

Look for Reactions

If you want to determine a food intolerance to salicylates, you might start by simply observing your child within the hour after they eat, and before bedtime—making correlations with high salicylate consumption.  The best way to determine salicylate intolerance is to avoid high salicylate foods for a period of time and observe any improvements, and then add them back and see if you notice a reaction.

What to Eat

There are two diets that I like that address this: The Feingold Diet and The Failsafe Diet.  The Feingold Diet is a smaller list of salicylates to avoid—it includes many of the big offenders (but misses some) and is easier to do.  The Failsafe diet is much more comprehensive, but more complex and restricts more foods. And at Nourishing Hope, we have our own list that I created from 17 years of working with this diet with my clients.

Below are some of my favorite low salicylate replacements to eat.

Fruit:

  • Pears

Vegetables:

  • Brussels Sprouts
  • Butternut Squash
  • Celery
  • Green Beans
  • Lettuce (head)
  • Rutabagas

Nuts:

  • Cashews

Herbs, Spices. and Seasoning:

  • Chives
  • Green onions
  • Vanilla
  • Salt

Most meats, grains, and beans/legumes are low salicylate.

Do a Dietary Trial

Try taking these foods out of your child’s diet for a few weeks and see what happens. Do you notice improvement? Which symptoms have gone away? Record what your child is eating and what you are noticing. You can do a dietary provocation, adding foods back to see if the reaction returns.

Add Back Allowed Foods

And remember you don’t want to overly restrict a diet, so add back any foods that are not causing a reaction. There are testing phases to the diet to help you determine: 1) if salicylates are causing a problem, 2) what your child’s threshold is.

And get support so your child has a healthy diet while on this diet. Make sure you find a practitioner that can address the underlying factors so you can go back to eating a more variety diet in time.

Epsom salt baths

You can also try Epsom salt (magnesium sulfate) baths or magnesium sulfate cream—the sulfate absorbs and helps supply sulfate for sulfation/detoxification.  This can help a child process the salicylates better, and reduce reactions from salicylates.

Support

To learn more on whether a low salicylate diet is right for your child and for tools on how to implement it easily and effectively, check out my Nourishing Hope for Healing Kids nutrition program for parents.

With the popularity of the ketogenic (keto) diet these days and the amazing results people are reporting, my clients have been asking whether the ketogenic diet is right for their child with autism.

I have been looking for good science that can guide us as to whether the ketogenic diet improves the symptoms of autism. And how it compares to other diets, and which diet is best.

And I have found the science!

In this 6-month study, Egyptian researchers compared the effects of two different dietary interventions versus a normal (control) diet on core symptoms of autism. Although more research is needed, findings from this study are promising.

How the study was conducted

The study population consisted of 45 children – 33 boys and 12 girls – aged between 3 and 8. Two senior psychologists specializing in the diagnosis and management of children with ASD confirmed the participants’ diagnosis of autism using the DSM-5 criteria.

The researchers assessed the following:

  • Anthropometric measurements such as weight, height, and head circumference
  • ASD symptom severity using the “Childhood Autism Rating Scale” (CARS) once at the beginning of the study, before implementing any dietary changes and again after 6 months. The higher the score the more severe the autism symptoms.
  • Treatment efficacy using the “Autism Treatment Evaluation Test” (ATEC) questionnaire before starting the diet and 6 months later. As with the CARS test, the higher the ATEC score the more severe the autism.
  • Fasting lipid profile, liver function tests, complete blood count, and fasting blood sugar levels
  • Urinary ketones and random blood sugar levels were checked weekly

The children were randomly assigned to three groups:

  • Group 1 received the ketogenic diet as the Modified Atkins Diet (MAD). The MAD was used in this study to make the ketogenic diet less restricting for the children and account for their growth requirements.

The original ketogenic diet consists of 80% dietary fat (mostly from long-chain triglycerides), 15% protein, and 5% carbohydrates.

The MAD used in this study consisted of 60% fat, 30% proteins, and 10% carbohydrates. Carbohydrates were restricted to 8 to 10g per day based on the patients’ age and weight.

A team of expert dietitians explained the principles of MAD to the 15 children’s parents. The parents were also taught how to:

(i) Prepare meals at home by following meal plans designed by the dietitians
(ii) Count dietary carbohydrates
(iii) Measure urine ketones at home using the ketostix
(iv) Detect signs and symptoms of ketosis and hypoglycemia

  • Group 2 received a gluten-free, casein-free diet. The 15 children in this group were asked to avoid the proteins casein (found in all milk and derived products) and gluten (found in wheat, barley, rye, and some types of oats).

The dietitians taught the parents how to:

(i) Create and maintain the GFCF diet by following meal plans
(ii) Read food labels

(iii) Complete 24-hour food recalls

  • Group 3, the control group, received balanced nutrition. The remaining 15 children weren’t on any type of diet therapy and allowed to eat at their own preferences. Their parents were explained how to provide balanced diets to their children during one session with the dietitians.

What the researchers found

Keto Group

Five of the fifteen children (33%) in the Keto/MAD group dropped out of the study due to poor compliance to the diet (vs. 0 % dropped out in the GFCF group).

The remaining 10 children in the Keto group showed significant improvements in their:

  • Childhood Autism Rating Scale (CARS) scores  
  • Total ATEC scores, as well as ATEC scores for speech, sociability and cognitive awareness.

Behavioral problems in this group decreased but no statistically significant changes were observed.

GFCF Group

All children in the GFCF group compiled with the diet. In the GFCF group, children showed significant improvements in:

  • Childhood Autism Rating Scale (CARS) scores
  • Total ATEC scores, and ATEC scores for speech and behavior improved.  

Participants showed improvements sensory/cognitive awareness but they were not statistically significant.

The Keto group showed more improvements in terms of CARS and ATEC scores, compared to the GFCF diet group.

No significant changes were seen in the control group.

Charting the Results

After I plugged the data into a spreadsheet, the results became more clear to me. The following charts compare the results of Keto, GFCF and the control group. Notice how both the GFCF and Keto group have significant improvements compared to the control group (that did not do a special diet). There were some differences, but overall the results show that a special diet is very helpful to improving autism symptoms.

What the findings mean

So what do we do with this data. This is MY interpretation of the findings. (This is not the study author’s opinion.)

  1. Autism severity decreased among children in groups 1 and 2 indicating that the Keto and GFCF diet were effective in improving autism symptoms.
  2. The ketogenic diet yielded better results than the GFCF diet. The ketogenic diet can be a great diet for autism… for the right person. The keto diet can address some underlying mitochondrial issues and neuroinflammation that can be wonderful!! By improving the underlying biochemistry, the symptoms of autism can be significantly reduced (as we saw in the study).
  3. However, 1/3 of the children dropped out of the Keto group. The fact that the keto diet is more restrictive is one of its challenges. If a child goes on keto, but the family stops because it’s too difficult to maintain (no judgement), then the child doesn’t receive any of the results that were seen in the study. (Unless they transition to a different diet.) No one dropped out of the GFCF group and great benefits were seen by that group too. In this case, the “best” diet is the one the family can do, that yields positive results. For some it’s keto, for some it’s GFCF.
  4. Since results were better on the ketogenic diet, this might lead people to think the ketogenic diet is the best place to start or the best diet for everyone. It might be, especially if you have reasons to think that approach would address underlying biochemical problems and be a better diet. As I mentioned, the keto diet can address metabolic issues and neuroinflammation and be very helpful.  However, the ketogenic diet has some challenges and deficiencies that can result. I have seen children with autism do really well on the ketogenic diet, and other children do poorly on the ketogenic diet. Although, for the right people, most are negatives are outweighed by the benefit of keto or can be overcome with diet hacks. More study will help us determine the reasons the ketogenic diet was helpful and if the benefits continue for long term. The choice is a bioindividual one.
  5. Why did keto help people? The study did not isolate why the ketogenic diet worked better. The keto diet removes: gluten, grains, starches, and other compounds in foods that can be irritating to the system. So, if keto is showing improvement, we don’t know what caused the improvement. It might be the 1) removal of gluten, 2) the removal of grains and starches, 3) “lower” carbs (but not ketosis), 4) a decrease in total sugar (or some other compound like FODMAPs, oxalates or salicylates) that was reduced that was the key to the diet’s success. Graduating the food removal from simple to more restrictive is a good way to see WHAT about the diet was helping. This leads me to #6…
  6. In my clinical experience, if someone is transitioning from the Standard American Diet, it might be easier and better to start with a GFCF diet. It’s an easier diet and lifestyle choice (if it’s effective), and can eliminate some of the most common reactions: gluten and casein. Going step by step can help determine which diet is ideal.  It’s helpful to start with gluten and casein, then eliminate all grains and starches to see if the issue are foods that irritate the gut (i.e. grains and starches), then proceed to the ketogenic diet. While it is true that some people can jump right into the ketogenic diet, gradually decreasing the amount of carbohydrates consumed with a grain-free diet first can help the body adapt to a lower carbohydrate diet before starting the ketogenic diet. And since we don’t know exactly what it is that’s contributing to the improvements on a ketogenic diet, taking it step by step, helps someone figure out how far they need to restrict their diet, and help them understand the reason they are benefiting from the diet change.
  7. Diet support. This study shows us that having access to foods that meet the specifications of the dietary regimen can improve compliance. In this study, participants in groups 1 and 2 had access to a specialized kitchen that provided group 1 children with low carbohydrate biscuits, cakes, and bread and group 2 children with alternatives to gluten and casein. Having support with ready-made meals, or even building into your schedule to prepare the meals, can help increase your success. For instance, Seek out help when doing a special diet if you need the extra support. Even though some people dropped out of the study, from my experience they had very good compliance. And I believe part of the success was this diet support.
  8. Individuals with autism have impaired gut function and various nutrient deficiencies which can slow down gut healing and how quickly you see results. As such, someone with ASD may require several months of dietary intervention before seeing significant symptom improvement. Remember, this study was 6 months. You often need to give dietary intervention some time to see what improvements unfold.

Conclusion

This research is further proof that a special diet helps people with autism. And it shows: both a GFCF diet and a keto diet were effective.

I hope this study helped you see how ketogenic can be a wonderful option for certain children with autism. And further proof that a GFCF diet is very helpful.

It’s an exciting time (as always) in the field of nutrition.

Reference:

El-Rashidy, O., El-Baz, F., El-Gendy, Y., Khalaf, R., Reda, D., & Saad, K. (2017). Ketogenic diet versus gluten free casein free diet in autistic children: a case-control study. Metabolic brain disease32(6), 1935-1941.

The gut-brain axis is a well established connection suggesting that the intestinal microbiota (the good bacteria in our gut) signal to the brain in a myriad of ways. This delicate balance of gut microbes can influence emotional development, modulation of stress and pain, mental health, and neurotransmitter systems in the brain. 

The gut-brain axis is a well established connection suggesting that the intestinal microbiota (the good bacteria in our gut) signal to the brain in a myriad of ways. This delicate balance of gut microbes can influence emotional development, modulation of stress and pain, mental health, and neurotransmitter systems in the brain. 

Research encourages that improvements in our gut microbiome can improve overall mood, anxiety-like symptoms, pain, and more in people with autism. 

There is substantial evidence that using prebiotics and probiotics, such as strains of Lactobacillus, can have a positive effect on the gut-brain axis, but is there something more at play? 

In this article I share the results of a cutting edge study that examines the gut brain axis in autism. I give you my analysis, what’s lacking, and key takeaways for those wanting to be informed.

The researchers propose amino acids as a potential treatment. 

Today, I take a closer look at the ins and outs of this new study, a review paper entitled, The Gut-Immune-Brain Axis in Autism Spectrum Disorders; A Focus on Amino Acids. I explore its findings and discuss practical implications for therapeutic intervention.

How the Gut-Brain Axis Influences Autism

I’ve written previously on how dealing with your child’s digestive issues can address both gastrointestinal and neurological symptoms of autism. It’s no secret that children with autism spectrum disorder are significantly more likely to have food allergies than those without it.

However, a startling statistic is that children with autism are seven times more likely to experience frequent diarrhea and colitis than those without a developmental disability. 

The link between digestive problems and autism is undeniable, and it’s related to inflammatory bowel issues, acid reflux within the gastrointestinal tract, and possibly more. This is partially due to the inflammation that food allergies and digestive issues can bring on, which can be painful and influence behavior negatively.

This brain-gut link also puts these children at risk of nutritional deficiencies, which can aggravate cognition problems and adversely affect immune responses.

Early life environmental factors can also play a part in the development of autism spectrum disorder. The study cites prenatal and postnatal diet, gut microbiota, and immune system triggers as contributors to the disorder’s prevalence.

Furthermore, it addresses the inflammatory responses that are so common in autism spectrum disorder. It proposes they may be linked to the aforementioned common food allergies, causing increased production of pro-inflammatory cytokines and allergy-associated Th2 cytokines.

This study also suggests that microglia and astroglia (certain brain cells) are deregulated in the brains of people with ASD, altering their immune-like responses. An impaired ability to remove toxins that’s commonly found in individuals with autism can play an important role in a compromised immune system.

A look at the weakened ability to detoxify and a less responsive central nervous system makes it clear: the gut brain axis has a profound effect on autism. While you’re reading, be sure to look into my guide on where environmental toxins are commonly hiding and what to do about them.

These behavioral, digestive, inflammatory, and immunological issues all play a part in the nervous system’s role throughout the body. Patients with ASD have a nervous system battered with these issues, playing a complex role in the disorder. While we know that psychobiotics (gut-supporting supplements that positively influence the gut-brain axis) can be of some help with microbial composition and brain interactions, what about amino acids?

The mTOR Pathway and Amino Acids

Preclinical and mouse model studies have indicated that when mice are allergic to their food intake, their reaction produces many similar symptoms to those seen in individuals with autism and alters processing in the prefrontal cortex.

As mast cells and T cells are unusually activated in the brains of those with ASD, the study suggests that their hyperactivation is linked to symptoms associated with autism. If so, food allergies may be a driving force of the symptoms and behaviors associated with ASD, along with increased intestinal permeability.

So, how can amino acids help these digestive woes? Well, it starts with the mTOR pathway. The activation of the mammalian target of rapamycin (mTOR) is reported frequently in cases of autism. 

This activation is also noted in many other health problems, such as insulin resistance and tumor formation, and is increasingly studied for its overarching effects on health, neural communication, brain function, and immune cells. Mutations in mTOR pathway-related genes are widely associated with ASD.

While the first instinct to treat these mutations may be pharmacological, the severe immune system detriments can make mTOR inhibitors an extreme prescription to write. This drug can hamper cell growth, and in other cases, increase unwanted cell signaling. 

This study proposes that a safer, nutritionally-based approach using amino acids is possible. For me, this type of research is vital — I believe improving nutrition is hope in action. 

Amino acids show a promising effect on the mTOR pathway. They do an excellent job at modulating the function of the proteins that translate both global and specifically selected mRNA for mTOR.

While the research isn’t exactly conclusive, it seems that the amino acid’s transporters enter through the plasma membrane, interact with and activate a multi-protein complex, and activate mTOR at appropriate levels. 

A promising trial showed that a developed amino acid diet was able to normalize or reduce mTOR signaling in ASD mice, reducing repetitive behaviors and improving social interactions. 

Just as exciting, the potential issues in this dietary change do not have the severe side effects that rapamycin dosages have shown. However, the study notes that proof of principle clinical studies are still needed to see the effects of a diet that specifically adds helpful amino acids.

Can amino acids be used to improve symptoms of autism?

It seems likely. Multiple studies have pointed to reducing inflammation as an effective means of improving the symptoms of autism. This evidence further shows just how impactful the gut microbiome is in autism. Used properly, combinations of amino acids can be helpful in combating not only this inflammation, but harmful mutations as well. 

A promising preclinical trial mentioned above developed a combination of relatively higher amounts of histidine (His), lysine (Lys), and threonine (Thr) and relatively lower amounts of leucine (Leu), isoleucine (Ile), and valine (Val) for further studies in ASD, and saw a reduction in mTOR hyperactivity.

Another in vitro study found that dosages of Leu, Ile and Val individually reduced the mRNA and protein levels of the pro-inflammatory cytokine IL-6. It can be inferred from the results of amino acid tests that increasing the availability of amino acids has a positive, anti-inflammatory result on immune cells.

Conversely, some evidence points to a lowered amount of amino acids as a detriment to antibody production. Immunologically speaking, it seems that certain amino acids reduce inflammatory response and assist in antibody production.

In rats with colitis, a condition seen seven times more frequently in those with ASD than neurotypical individuals, amino acid mixtures were seen to positively affect intestinal function and balance gut microbiota composition.

So, what does this mean for nutrition and patients with ASD? Well, with guidance from a doctor or nutritionist, here’s what we may be able to implement:

  • Leu, Ile, and Val raise mast cells and epithelial cells in mTOR pathways, while His, Thr, and Lys all lower it while also negatively affecting brain function when used in tandem. These latter three amino acids have a “synergistically negative effect.” Both of these groupings affect the brain in converse ways, which is why it’s important to work on this type of therapy with a licensed doctor or nutritionist/dietician.
  • Leu, Ile, and Val also lower pathogenic bacteria levels in the microflora. However, these same three also lower the neuroprotective factor microglia.
  • There are many more amino acid combinations, but as we can see, supplementing amino acids must be done mindfully and with proper healthcare supervision. Some can have unintended effects that augment undesirable symptoms in individuals with autism. However, keeping in mind possible negative or synergistic effects, we can begin to formulate the best ratios of potentially helpful amino acid mixtures.

Areas of Further Research and Conclusions

While I find this study to be rather comprehensive in its approach, there is still much more to be done. Firstly, almost all of the current research on amino acid interaction with the gut brain axis and its effect on autism is still in germ-free mice. This is certainly a limitation.

Progression to clinical trials at some point will tell us much more about the possibilities for the future.

I’d also like to hear more from this research about the practical implications for nutritionists and parents seeking to make dietary adjustments. While there are some takeaways, I felt there were limitations in how to apply our current understanding of the link between amino acids, mTOR, inflammation, and brain development.

It is also worth further exploring how to balance each amino acid in combination — some can have extremely neuroinflammatory effects when out of balance. This is the opposite of our goal in helping those with ASD.

Even with its limitations, this study provides us an important look into mTOR in autism and how amino acids may be helpful in improving the gut-brain axis.

In Summary

  • The gut brain axis is a significant issue in patients with ASD. Outside of behavioral issues, this is not only a sign but also an aggravation of ongoing symptoms associated with individuals with autism.
  • Rectifying an imbalance in gut bacteria can positively affect not only behavior, but also inflammation and digestive symptoms.
  • The studied amino acids show promise of modulating negative mTOR pathway signaling, which may reduce a great number of issues that present with ASD.
  • If administered properly, neuroactive amino acids show great promise of treating the gut brain axis imbalance in autism, with far fewer side effects than rapamycin medication.
  • These findings call for a closer look into amino acids and their properties in relationship to ASD. There are many possible uses for nutritional interventions and alleviation of symptoms within this study.

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Recent advances in the understanding and treatment of autism
Dietary and therapeutic strategies for inflammation in autism spectrum disorders
Specific biomarkers could facilitate ASD diagnosis

Fighting back with fat: the modified ketogenic diet and MCT oil for autism
PANDAS and PANS: The inflammatory aspect of autism
Picky eating: The relationship between sensitivity to touch and mouthfeel


Recent advances in the understanding and treatment of autism

Autism spectrum disorders are one of the biggest challenges of modern medicine and several theories have been proposed to explain how these conditions develop and how they can be treated.

In this new review, researchers from Tehran University highlight the following modern theories of ASD development:

  • Impaired connection between the neurons – this could affect language function
  • Misplacement of neurons during the antenatal period – this may disable further brain development
  • Genetic mutation of the methyl CpG binding protein 2 gene – this could lead to impaired maturation of the synapses
  • An excitation-inhibition imbalance which is essential for representation of sensory information and cognitive processes
  • Alterations in the immune system, or increased intestinal permeability, causing oxidative stress and inflammation in the brain
  • Maternal infection that can cause early immune dysregulation and contribute to ASD development

The researchers also highlighted the following evidence-based natural therapies and lifestyle recommendations:

  • A gluten free casein free diet
  • A modified ketogenic diet
  • Vitamin B6, methylcobalamin, and folate
  • Omega-3 fatty acids
  • Exercise and animal assisted therapy
  • Digestive enzymes

Dietary and therapeutic strategies for inflammation in autism spectrum disorders.

Brain development and function can be influenced by the environment, gut health, and diet in utero and after the child is born.

For instance, lab studies indicate that offspring of mothers who were obese during pregnancy were more likely to develop social communication impairment and repetitive behavior. Scientists explain that the low-grade inflammation caused by obesity could impair the brain’s neuronal circuit which controls behavior in the offspring.

Moreover, anything that adversely influences the development of the gut microbiome (such as the mode of delivery, stress, antibiotics, and diet) will also affect the gut-brain axis. Since gut microbes produce neurochemicals that play a role in social cognition, emotion, and behavior, improving the gut’s health during pregnancy could decrease risks of ASD in the offspring.

As such, this paper highlights promising adjuvant therapies for ASD include:

  • A gluten-free and casein free diet – this free step-by-step guide can help you get started
  • The specific carbohydrate diet
  • A diet low in oxalates
  • Adequate intake of micronutrients such as carnitine, zinc, selenium, vitamins A, D, E, and B-complex and omega-3s and omega-6s from real foods and/or high-quality supplements
  • Prebiotics and probiotics from the Lactobacillus and Bifidobacterium genus
  • Fecal transplants which involve transferring fecal microbiota from healthy donors to an unhealthy individual

Specific biomarkers could facilitate ASD diagnosis

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Current methods to diagnose and evaluate ASD rely mainly on observing the patient’s behavior using tools that involve great variability.

Numerous studies indicate that abnormalities in the folate-related metabolism pathway could increase likelihood of both genetic and environmental predisposition to ASD.

In a new study, Chinese researchers investigated the following biomarkers in a group of 89 autistic patients and 89 healthy controls aged 3 to 12 years old:

  • Folic acid
  • Vitamin B12
  • Tetrahydrofolate (THF)
  • 5-methylenetetrahydrofolate (5-MTHF)
  • Methionine
  • S-adenoslymethionine (SAM)
  • S-adenosylhomocysteine (SAH)
  • SAM/SAH
  • Homocysteine
  • Methionine synthase
  • Folate receptor alpha
  • Transcobalamin II
  • Cystathionine-β-synthase (CBS)

Each participant was given a standardized dietary guidelines and exercised moderately about a week before fasting blood samples were collected.

The researchers reported that, compared to healthy controls, children with ASD were more likely to have:

  • Reduced methionine and SAM/SAH levels – these are associated with methylation potential and influence key developmental periods.
  • Low levels of folic acid, vitamin B12, 5-MTHF, and SAM.
  • Higher homocysteine and lower transcobalamin II levels – this could indicate vitamin B12 deficiency in the ASD population.

Results from this study suggest that, using Fisher Discriminant Analysis, the following six metabolites could help identify – with great accuracy –  84.3% of patients with ASD:

  • 5-MTHF
  • SAM/SAH
  • Methionine
  • Vitamin B12
  • Transcobalamin II
  • Methionine synthase

Fighting back with fat: the modified ketogenic diet and MCT oil for autism

Low in carbohydrate, moderate in protein, and high in fat, the ketogenic diet has shown promises in the treatment of ASD.

In this study, 15 children aged 2 to 17 were prescribed a modified ketogenic diet with supplemental medium-chain triglycerides (MCT) oil for 3 months.

Individuals with ASD suffer from mitochondrial dysfunction –mitochondria act like the cell’s “engine” and helps produce energy. The scientists wanted to see if adding MCT to the modified ketogenic diet could improve ketone and fatty acid production which would optimize mitochondrial efficiency.

The children’s caregivers received 2 hours of training on the modified ketogenic, gluten free diet and MCT protocol. This diet consisted of:

  • 20 – 25g of carbohydrates per day
  • Protein, twice the RDA requirements, based on the child’s weight and height
  • Various types of fats including 20% of pure MCT oil or coconut oil

At the end of the study, 50% of the children showed moderate to considerable improvement in ADOS-2 scores for the social affect component. No significant difference was observed in restricted and repetitive behavior scores.

Furthermore, 50% showed improvement on CARS-2 scores in the areas of imitation, body use, and fear or nervousness.

Findings from this study suggest that this modified diet could improve inflammation levels, gut health, and cellular health in ASD patients.


PANDAS and PANS: The inflammatory aspect of autism

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) and Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) are both autoimmune conditions induced by infections.

Both PANS and PANDAS disrupt normal neurologic function since they affect basal ganglia nuclei, a cluster of nerve cells at the base of the brain. As such, PANS and PANDAS can trigger acute and dramatic onset of neuropsychiatric symptoms in children.

The difference between PANS and PANDAS is that, unlike PANDAS which is associated only with streptococcal infections, specifically group A streptococcal infection, PANS can be caused by various types of infections.

Unfortunately, due to the abrupt onset of symptoms, children with PANS and PANDAs are often misdiagnosed as having a psychiatric illness and treated only with psychotropic drugs.

This does not address the root of the problem since, in some individuals, exposure to certain bacteria, viruses, or germs can disturb the immune system which can start producing autoantibodies.

These antibodies attack both the invaders and the brain, causing inflammation in the brain and leading to a sudden onset of neurological symptoms. Therefore, a safer alternative would be to try an anti-inflammatory protocol combined with an anti-infective treatment.


Picky eating: The relationship between sensitivity to touch and mouthfeel

When talking about foods, what do taste, smell, appearance, and texture have in common?

Well, “love-hate relationships” with foods are often based on these characteristics. For instance, kids are more likely to dislike bits and pieces of foods in a homogenous texture. The same goes for tough, gummy or slimy foods vs. foods that are crispy or crunchy.

And in an interesting new study, scientists have found that tactile sensitivity – a person’s emotional response to textures and the touch of objects – could promote picky eating even into adulthood.

The study involved 89 undergraduate students aged 18 to 25 enrolled at Maastricht University. The students were requested to fill in a self-report questionnaire that measured:

  1. 1. Picky eating – On a scale of 1 to 5, participants were asked to rate how much they liked 30 food items prepared differently.
  2. 2. Subjective tactile sensitivity – The students were blindfolded and asked to feel nine different objects with various textures. They then rated how much they liked the feel of these objects on a 1 to 5 scale.
  3. 3. Evaluation of mouthfeel – Using the same 1 to 5 scale, the students rated how much they liked the texture of nine foods. They were blindfolded and wore a nose clip to reduce influence of sight of the food and its flavor.

It turns out that “participants who disliked textures more when feeling them by hand, also disliked the mouthfeel of different foods more and in turn liked fewer foods.”
Take home-message: Match the food’s texture to your child’s preferences. For instance, if your child doesn’t like pureed meats, try minced meat or slow-cooked meat. These are easier to digest than beef strips and don’t look like a paste.  Additionally, if your child doesn’t like the texture of mushy vegetables make them crispy and crunchy.

Hi. I’m Julie Matthews, a Certified Nutrition Consultant, Author, and Published Researcher. I teach practitioners (and parents) that children and adults with neurological, digestive, and immune conditions, most notably autism, can improve and heal with BioIndividual Nutrition®. My diet and nutrition guidance and methodology is backed by scientific research and applied clinical experience. I train clinicians (and support families) from around the world with my nutrition learning tools and professional training courses. My BioIndividual Nutrition Training teaches you to practice BioIndividual Nutrition for a wide range of conditions, and my Pediatric Intensive is for practitioners specializing in autism and neurodevelopmental disorders.

Join the BioIndividual Nutrition email list to get the latest articles, clinical tips, and nutrition science for practitioners, and FREE access to The 10 Pivotal Questions Nutrition Professionals Must Ask to Improve their Clinical Results.

 
 
 

If you are a nutrition practicing health professional you’ve likely heard of methyl B12. If you’re a patient or this is new to you as a practitioner, you will enjoy learning about this important subject.

An exciting study indicates that supplementation with methyl B12 (the coenzyme or active form of vitamin B12 which is also known as methylcobalamin) could lead to an overall amelioration of autism symptoms by improving DNA methylation [1]. You see, not all genes are active at all times: it is the role of DNA methylation, an epigenetic mechanism, to turn a cell’s genes on and off at the appropriate time – this process appears to be impaired in many individuals with autism [2].

methyl-B12-autismWhat exactly is methylation?

It seems that methylation has become the latest buzzword in the health world and for good reason: methylation is an essential biochemical process that occurs over a billion times per second in every single cell of our body. To keep things simple (and avoid putting you to sleep), methylation occurs when a methyl group (a carbon atom linked to three hydrogen atoms) is passed to another molecule.

So why should you care about methylation?

Listing all the roles of methylation is beyond the scope of this article but, in a nutshell, methylation is a necessary process used by cells to control gene expression – this type of methylation, known as DNA methylation, is vital for healthy growth and development. DNA methylation also enables suppression of retroviral genes as well as other potentially hazardous sequences of DNA that may impair a person’s health.

Methylation is also involved in:

  • The production of vital substances such as glutathione which controls oxidative stress or melatonin, a hormone involved in sleep regulation.
  • The body’s optimal use of nutrients.
  • The body’s production of energy (ATP).
  • Immune function.
  • Natural detoxification pathways.
  • The brain’s activities and the production of neurotransmitters – defects in the methylation cycle have been linked to various cognitive behavioral issues and may contribute to the development of autism [3]. Moreover, children with autism also experience higher oxidative stress levels and have lower levels of biotin, vitamins B5 and E and total carotenoids [4]. These vitamins are involved in energy production in the body and also possess antioxidant properties. Put simply, children with autism have a decreased capacity for methylation which makes them more vulnerable to depression, infections, brain fogs, irritability and fatigue. Now that you have the basics, let’s go back to the methyl B12 study.

The study protocol

A total of 50 children with autism spectrum disorder completed this 8-week study – they were either given subcutaneous injections of methyl B12 (75μg/kg) or saline placebo (the control group) every three days. Neither the researchers nor the participants knew who was receiving the methyl B12 and who was getting the placebo until after the study. To determine the efficacy of the treatment, the researchers utilized the Clinical Global Impressions Improvement (CGI-I) scale after the 8-week study period. In this study, this scale was used to assess overall improvement of autism symptoms by evaluating the severity of the symptoms from 1 (very much improved) to 7 (very much worse). The researchers also used the Aberrant Behavior Checklist and the Social Responsiveness Scale during their assessment. Laboratory assessments were also conducted to evaluate methionine methylation and antioxidant glutathione metabolism.

Study findings

Compared to the children who received the saline injections, those who were treated with methyl B12 showed considerable improvements in overall symptoms as shown by the CGI-I scale results. However, no significant difference was found between the two groups regarding the two other measures which assessed the severity of specific autism symptoms.

Why did the researchers use methyl B12 (and not another member of the B12 family)?

Previous research indicates that individuals with autism have low levels of vitamin B12 in their brain which could explain why neurological and neuropsychiatric symptoms are common in this population [5]. To understand why methyl B12 was used in this study, it can help to understand that out of the vitamin B12 family, only methyl B12 is able to directly activate the methionine/homocysteine pathway which is involved in fueling the brain, metabolism and muscle growth. If this pathway is not activated (that is homocysteine is not re-methylated and converted back to methionine, homocysteine will build up in the blood where it can cause numerous health issues).

In a nutshell, here’s how the remethylation of homocysteine to methionine occurs: initially, methionine synthase catalyzes this remethylation reaction by using a methyl (CH3) group from 5-methyltetrahydrofolate (5-MTHF). This methyl group is then transferred to the reduced form of cobalamin to generate methylcobalamin (methyl B12) and tetrahydrofolate. Next, the methyl group is transferred from methyl B12 to homocysteine – this generates methionine. As you can see, for methylation to be effective, the body needs both folate and methyl B12.

What this means for a client/patient:

  • Keep in mind that there are many forms of vitamin B12 on the market. As a nutrition or health care professional, you want to ensure that you recommend a quality methylcobalamin supplement and not cyanocobalamin which is a cheap, dangerous synthetic form of the vitamin.
  • Note that folic acid is also the synthetic version of folate – in other words, they are totally different. Everybody should steer clear of folic acid, not only those individuals with autism or methylation issues.

I always recommend individuals work with a good integrative physician or nutrition professional.  They can test B12 status, most often with an organic acid urine test looking at MMA levels (methylmalonic acid), rather than blood levels which can be deceiving. If you are a nutrition professional you will want to  recommend the proper dose and form. Most often that will be methylcobalamin as the study highlights, but there are also adenosyl- and hydroxy- forms, as well as sublingual, injections, and other methods of administration. Other articles in the future (and our BioIndividual Nutrition Training), address these other forms; however, since the focus of this study was on methyl B12, we’ll save the others for another day.

References:

1. Hendren, R. L., James, S. J., Widjaja, F., Lawton, B., Rosenblatt, A., & Bent, S. (2016). Randomized, placebo-controlled trial of methyl B12 for children with autism. Journal of child and adolescent psychopharmacology. [Access the original article here.]

2. Menezo, Y. J., Elder, K., & Dale, B. (2015). Link between Increased Prevalence of Autism Spectrum Disorder Syndromes and Oxidative Stress, DNA Methylation, and Imprinting: The Impact of the Environment. JAMA pediatrics169(11), 1066-1067.

3. James, S. J., Cutler, P., Melnyk, S., Jernigan, S., Janak, L., Gaylor, D. W., & Neubrander, J. A. (2004). Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. The American journal of clinical nutrition80(6), 1611-1617.

4. Adams, J. B., Audhya, T., McDonough-Means, S., Rubin, R. A., Quig, D., Geis, E., … & Barnhouse, S. (2011). Nutritional and metabolic status of children with autism vs. neurotypical children, and the association with autism severity. Nutrition & metabolism8(1), 1.

5. Zhang, Y., Hodgson, N. W., Trivedi, M. S., Abdolmaleky, H. M., Fournier, M., Cuenod, M., … & Deth, R. C. (2015). Decreased Brain Levels of Vitamin B12 in Aging, Autism and Schizophrenia. PloS one11(1), e0146797-e0146797.

In my earlier article about oxalates, I explained how oxalates influence the biochemical progression and symptomatic expression of varied chronic diseases. Through an overarching “lens” of 18 years’ research and clinical experience with autism, I identified multiple areas for scientific inquiry and therapeutic direction for a variety of chronic health conditions and underlying symptomatology.

This article specifically investigates oxalates and autism; where the range of metabolic implications is vast – from impairment of mitochondrial function (and energy production) to disruption of mineral balance and the creation of severe oxidative stress in the body. The downstream effects of these biochemical aberrations touch dozens of systemic avenues.

I’ll explain some of the processes that can be severely affected in autism, that are likewise noted in those with high oxalate, and explore the potential role of oxalates in the body as a pathogenesis (biological mechanism or cause) of autism. These symptomatic expressions, and the findings from several key studies highlighted in this article, prompt eager investigation of the role of oxalates in autism.

Before we begin, to understand the basics: what oxalate is, where it comes from, and common symptoms read my previous article on oxalate.

Oxalates in Autism Study

In 2012, the European Journal of Paediatric Neurology published a study that investigated the role of oxalates in autism. Researchers measured a 2.5-fold greater level of oxalates in the urine, and a three-fold greater level of oxalate in the plasma, in children with autism.1

Their finding was specifically, hyperoxaluria; a condition of high oxalate. Interestingly though, high oxalate levels in urine did not necessarily correlate with high levels in the plasma. One child might have high urinary levels, but not high plasma; another might have high plasma levels, but not high urine.

A clinical challenge we face today is that only urinary levels are being used as an indicator of oxalate levels.

Plasma oxalate testing is only available in a research setting. The 2012 study tells us that not every child with oxalate impairment will present with high oxalate in their urine (they might have high oxalate in their plasma). This makes determining high oxalate, via testing (urine only), very challenging.

It’s significant to note that the study on autism and oxalate excluded the following groups from their selection criteria: those on a special diet, those with a history of seizures or antibiotic use, those with gastrointestinal disease (in addition to those with kidney stones). This is important to note, because all of these can be conditions of or cause hyperoxaluria.

Also noteworthy is a chart representing all of the controls (you can look at the study online here) on the top of page 5. You’ll notice all the controls have little blue boxes. There’s almost an invisible line at 0.05, and all of the controls fit within that 0.05 level. But the autism subjects were all over the map. Apparently, healthy controls are able to regulate the oxalate much better than other people (in this study, people with autism).

A history of antibiotic use can make oxalate issues worse, as can gastrointestinal diseases. Clinicians report that children with autism have higher rates of antibiotic use and seem less able to fight infection, and research demonstrates that gastrointestinal conditions are higher in autism than for neurotypical children.[4],[5],[6] Also, many autistic children suffer seizures, and oxalates can cause seizures.[7],[8],[9]

The study’s selection criteria (omissions) may affect an underrepresentation of the range of oxalate (plasma and urinary) that would occur in a full range of autistic patients. Even with the exclusions, significant oxalate issues were identified. This warrants further study, without excluded variables, to investigate how results may differ. If these groups had been included, rates and levels of oxalate would most likely be even higher.

Interestingly, the researchers had expert oxalate scientists review their findings, specifically the 2.5 – 3-fold increase in oxalate levels. The scientists were concerned for the children’s health. The levels were so high that they felt the children should (and may) have serious health implications based on oxalates in this elevated range; they’ve witnessed the detrimental effects of oxalate levels that high.

In summary, the study concluded that: “hyperoxalemia or hyperoxaluria may be involved in the pathology of autism spectrum disorders in children.” 1 It then continues to explain that based on the high oxalate finding, certain treatment options, such as a low oxalate diet, probiotic therapy, possibly with Oxalobacter formigenes, and a variety of supplementation may be helpful in these children.1

Oxalates are significant in autism because clinically we see a great deal of oxidative stress, considerable inflammation, mitochondrial damage or dysfunction, as well as faulty sulfation and seizures—areas where oxalates can wreck havoc. The discovery and clear indication that high oxalate may be involved in the pathology of autism is both significant and hopeful. This research and the biochemical connections we are highlighting provide further hope and direction for helping children with autism.

How Oxalates Cause Problems in Autism

OxalateCrystalsI’ll next explain some of the systemic processes that can be severely affected in those with autism, that are likewise noted in those with oxalate problems – then I’ll explore the link between the two, and the possibility of high oxalates as a pathogenesis of autism.

Firstly, let’s discuss how the health (or dis-ease) in the gut and certain nutrient deficiencies affect whether someone is more susceptible to a condition of high oxalate. And then let’s explore how oxalates can cause or exacerbate the conditions often found in autism:

  • Oxidative stress
  • Inflammation
  • Mitochondrial damage[10]
  • Seizures7,8,9
  • Faulty sulfation

Gastrointestinal Tract

As noted in my earlier article, the health of the gastrointestinal tract influences whether someone develops a problem with oxalates. Leaky gut, insufficient beneficial bacteria (including but not limited to a species called Oxalobacter Formigenes), poor fat digestion, and insufficient mineral intake affect whether (and how much) oxalate gets absorbed into the bloodstream from the gut. Many of these conditions, particularly leaky gut and a poor microbial balance, are common in those with autism.

Gut issues are so prevalent in autism,[11] and this condition in the gut compounds the potential problems with oxalate, and makes issues with oxalate more likely.

Compromised digestive capacity and an impaired ability to metabolize oxalate compounds may be linked to complications in autism. According to autism advocate and activist Dr. Leigh Ann Chapman, “Ordinarily, not much oxalate is absorbed from the diet, but the level of absorption has to do with the condition of the gut. There is a lot of medical literature showing that when the gut is inflamed, when there is poor fat digestion (steatorrhea), when there is a leaky gut, or when there is prolonged diarrhea or constipation, excess oxalate from foods that are eaten can be absorbed from the GI tract and become a risk to other cells in the body. Since these gastrointestinal conditions are found frequently in autism, it seems reasonable to see if lowering the dietary supply of oxalates could be beneficial.” [12]

Nutrient Deficiencies and Endogenous Production

Each person’s ability to process oxalate varies, based on the health of their gut as mentioned above, as well as nutrient deficiencies, systemic conditions, and genetic differences. Some deficiencies, including vitamin B6 and B1 deficiency can cause the body to produce oxalate (endogenously) in problematic amounts. This means that in children deficient in these important B vitamins, their body can create oxalate, rather than requiring it to come in from the diet. B6 deficiency is very common in autism, and for decades studies have shown the benefits of B6 supplementation in autism. Other deficiencies such as vitamin A deficiency can cause the body to absorb excess oxalate through the gut.

Further, because one’s body chemistry can convert a substance into oxalate; such as supplements like ascorbic acid or the amino acid glycine (a key component in bone broth) – complications can arise. Fructose, xylitol, and other sugar alcohols can also convert to oxalate. Certain supplements, as well as a diet too high in meat, can be a problem for some people.

In addition to oxalate levels increasing with nutrient deficiency, oxalates themselves can cause nutrient deficiency.  When oxalate is present from the diet, oxalate in the gut binds to minerals and inhibits absorption. This means diets high in oxalate can cause mineral deficiency including calcium and magnesium deficiency.

Oxidative Stress and Inflammation

Oxalates can lead to oxidative stress, and subsequently cause inflammation and injury.[13], [14] Because high oxalates can elevate superoxide (i.e. free radicals), they deplete glutathione and antioxidant status.[15]

Oxidative stress, inflammation, and low glutathione status are common occurrences in autism[16], [17], as well as many other chronic diseases. By understanding this relationship and recognizing a potential source of chronic inflammation and stress, practitioners can better address what may be causing the problems. And in this case, oxalate is an important factor to consider.

Mitochondrial Damage

Oxalates can also damage mitochondria. In the 2008 Veena study, researchers concluded that mitochondrial damage is an essential event in hyperoxaluria, so when you have high oxalates, you will have damage to the mitochondria. The same study indicated that oxalate impairs mitochondrial function. They found high oxalate created 30% depression of Complex I, a 54% depression of Complex II, a 35% depression of Complex III, and a 63% depression of Complex IV.12

Further, mitochondrial dysfunction has been found in autism.14, [18] Oxalates decrease mitochondrial function and increase oxidative stress, which is really important to consider for the many different conditions that can seriously affect the mitochondria, including autism.

Seizures

Twenty-two to thirty percent of children with autism suffer seizures.[19], [20] It is also postulated that one cause for these seizures may be neuro-inflammation.[21] We know that oxalates can cause seizures and also create inflammation. Therefore it is quite possible that oxalates may be a cause of seizures in autism.

Carambola Starfruit

Interestingly, the fruit carambola (also known as starfruit) is popular throughout Southeast Asia and the South Pacific and contains a high amount of oxalate. One study noted that “Carambola contains a large quantity of oxalate, which can induce depression of cerebral function and seizures.” 9

Studies have shown that high oxalate levels can cause seizures in individuals. Specifically, people with high oxalate whether from poisoning from accidental ingestion or antifreeze, or in other cases due to liver or kidney transplants, what the researchers found in essence was that oxalate can cause seizures.

As noted in the Oxalates and Autism study, the researchers did not “count” people that were on a special diet or those with a history of seizures. And, as explained earlier, seizures can stem from a condition of high oxalate. Again, it would be useful to repeat this study and include people with seizures, to see if prevalence of oxalate issues in autism is even higher than initially measured – and if oxalates may play a role in the etiology of seizures or exacerbate seizures.

Sulfur and Poor Sulfation

It’s equally important to understand sufate and sulfation when investigating autism and oxalates.

The body requires sulfate for vital sulfation processes, including processing phenolic foods. If certain foods or substances are consumed (or even inhaled) when sulfate is low, it can cause phenol reactions such as red cheeks and ears, hyperactivity, irritability, aggression, sleep issues, and more. There is much literature about poor sulfation and autism; I see these noted reactions often in my nutrition practice. Therefore, some children and adults with autism that have low sulfate often also have an issue with phenols and with oxalates. Not always, but these biochemical relationships suggest that some children may find relief by avoiding both for a period of time.

In regard to oxalate, when sulfate is low, oxalate can get into the cell on the sulfate transporter and interfere with cellular function.

There is a two-way relationship with oxalate and sulfate. Not only can oxalates lead to poor sulfation (as mentioned above) oxalate can also interfere with the body’s ability to allow sulfate into the cell inhibiting sulfation. And as mentioned above, low sulfate levels can allow oxalate into the cell on the (unoccupied) sulfate transporter. When this happens, it can affect the mitochondria and subsequently virtually every system of the body.

In autism, there seems to be a vicious ATP/sulfate challenge that we see. We often find high sulfate in the urine, and this gives some practitioners the false notion that sulfate is sufficient, if not high. However, while it’s high in the urine, we often find low sulfate and poor sulfation in autism. Why is this?

My hypothesis: oxalates could be at play. If ATP is low, the kidneys need ATP to recycle sulfate and, with low ATP, it could cause sulfate to be low. If sulfate is low, it allows oxalate to get into the cell, and it can decrease ATP production. When ATP is low, it can lead to low sulfate, both because it can decrease SAMe going through that pathway, as well as low ATP in the kidneys, causing the dumping of sulfate (causing it to be high in the urine when the body desperately needs it).
Either way, regardless of the cause of low sulfate, children with autism are known to have low sulfate and poor sulfation.[22],[23],[24] Therefore addressing high oxalates and low sulfate when they are an issue can be very helpful to children with autism.

Conclusion

Oxalates are a promising and emerging field that far exceeds kidney stone issues. Investigating their effects on the mitochondria, inflammation, and all systems of the body, reveals that oxalates play a role in many chronic diseases. The study “A potential pathogenic role of oxalate in autism” revealed hyperoxaluria in autism, further helping define the role of oxalate in autism.

With autism, oxalates can cause oxidative stress, inflammation, and seizures; something that is corroborated by the actual prevalence of these conditions in those with autism. Moreover, the conditions under which oxalates can become most problematic: disrupted microbiome, leaky gut, poor sulfation, B6 deficiency, and diets high in oxalate, are also common in autism.

I’ve been researching the influence of oxalates and utilizing a low oxalate diet for more that a dozen years. My future articles on this subject with explain: high oxalate foods, low oxalate diets, and important supplement support. Most importantly, I’ll provide best practices for implementing a low oxalate diet; how to decrease oxalates in food, know when it’s enough, and other ways to support the body during this process. Sometimes one key clinical insight can “course correct” someone’s existing diet and lead to new breakthroughs; often, it’s oxalates.

It’s critical that, as practitioners and professionals, we look at the role of oxalates in autism, so we can encourage further research and best support our patients, clients, and families in need.


microscope and abstract molecules isolated

Scientific References:

[1] Konstantynowicz, J., Porowski, T., Zoch-Zwierz, W., Wasilewska, J., Kadziela-Olech, H., Kulak, W., Owens S.C., Piotrowska-Jastrzebska J., and Kaczmarski, M. (2012). A potential pathogenic role of oxalate in autism. European Journal of Paediatric Neurology, 16(5), 485-491.

[2] Terribile, Maurizio, Maria Capuano, Giovanni Cangiano, Vincenzo Carnovale, Pietro Ferrara, Michele Petrarulo, and Martino Marangella. “Factors increasing the risk for stone formation in adult patients with cystic fibrosis.” Nephrology Dialysis Transplantation 21, no. 7 (2006): 1870-1875.

[3] Danese, Silvio, Stefano Semeraro, Alfredo Papa, Italia Roberto, Franco Scaldaferri, Giuseppe Fedeli, Giovanni Gasbarrini, and Antonio Gasbarrini. “Extraintestinal manifestations in inflammatory bowel disease.” World Journal of Gastroenterology 11, no. 46 (2005): 7227.

[4] Molloy CA, Manning-Courtney P: Prevalence of chronic gastrointestinal symptoms in children with autism and autistic spectrum disorders. Autism 2003, 7(2):165-171.

[5] Nikolov Roumen N, Bearss Karen E, Jelle Lettinga, Craig Erickson,
Maria Rodowski, Aman Michael G, McCracken James T, McDougle Christopher J, Elaine Tierney, Benedetto Vitiello, Eugene Larnold, Bhavik Shah, Posey David J, Louise Ritz, Lawrence Scahill: Gastrointestinal Symptoms in a Sample of Children with Pervasive Developmental Disorders. J Autism Dev Disord 2009, 39:405-413.

[6] Adams, J. B., Johansen, L. J., Powell, L. D., Quig, D., & Rubin, R. A. (2011). Gastrointestinal flora and gastrointestinal status in children with autism–comparisons to typical children and correlation with autism severity. BMC gastroenterology, 11(1), 22.

[7] Díaz, Cándido, et al. “Long Daily Hemodialysis Sessions Correct Systemic Complications of Oxalosis Prior to Combined Liver–Kidney Transplantation: Case Report.” Therapeutic Apheresis and Dialysis 8.1 (2004): 52-55.

[9] Chen, Chien-Liang, et al. “Neurotoxic effects of carambola in rats: the role of oxalate.” Journal of the Formosan Medical Association 101.5 (2002): 337-341.

[10] Veena, C. K., Josephine, A., Preetha, S. P., Rajesh, N. G., & Varalakshmi, P. (2008). Mitochondrial dysfunction in an animal model of hyperoxaluria: a prophylactic approach with fucoidan. European journal of pharmacology, 579(1), 330-336.

[11] McElhanon, Barbara O., Courtney McCracken, Saul Karpen, and William G. Sharp. “Gastrointestinal Symptoms in Autism Spectrum Disorder: A Meta-analysis.” Pediatrics 133, no. 5 (2014): 872-883.

[12] Chapman, L. A. (2007). A Low Oxalate Diet for Autism. Retrieved December 1, 2015, from www.http://chapmannd.com

[13] Biswas, Subrata K., et al. “Which comes first: renal inflammation or oxidative stress in spontaneously hypertensive rats?.” Free radical research 41.2 (2007): 216-224.

[14] Khan, Saeed R. “Hyperoxaluria-induced oxidative stress and antioxidants for renal protection.” Urological research 33.5 (2005): 349-357.

[16] Rose, S., S. Melnyk, O. Pavliv, S. Bai, T. G. Nick, R. E. Frye, and S. J. James. “Evidence of oxidative damage and inflammation associated with low glutathione redox status in the autism brain.” Translational psychiatry 2, no. 7 (2012): e134.

[17] Rossignol, D. A., and R. E. Frye. “A review of research trends in physiological abnormalities in autism spectrum disorders: immune dysregulation, inflammation, oxidative stress, mitochondrial dysfunction and environmental toxicant exposures.” Molecular psychiatry 17.4 (2011): 389-401.

[18] Rossignol, D. A., and R. E. Frye. “Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis.” Molecular psychiatry 17, no. 3 (2011): 290-314.

[19] Volkmar FR, Nelson DS: Seizure disorders in autism. J Am Acad Child Adolesc Psychiatry 1990, 29:127-129.

[20] Tuchman R, Rapin I: Epilepsy in autism. Lancet Neurol 2002, 1:352-358.

[21] Theoharides, Theoharis C., and Bodi Zhang. “Neuro-inflammation, blood-brain barrier, seizures and autism.” J Neuroinflammation 8.1 (2011): 168.

[22] Waring, R. H., and L. V. Klovrza. “Sulphur metabolism in autism.” Journal of Nutritional and Environmental Medicine 10, no. 1 (2000): 25-32.

[23] Alberti, Antonino, Patrizia Pirrone, Maurizio Elia, Rosemary H. Waring, and Corrado Romano. “Sulphation deficit in “low-functioning” autistic children: a pilot study.” Biological psychiatry 46, no. 3 (1999): 420-424

[24] Waring, R. H., Ngong, J. M., Klovrza, L., Green, S., & Sharp, H. (1997). “Biochemical parameters in autistic children.” Developmental Brain Dysfunction, 10, 40-43.

Pesticides-feature-image2A study out of the University of North Carolina Medical School found pesticides linked to autism. Researchers discovered that pesticides caused changes in the brain consistent with autism and neurodegenerative diseases. These chemicals were found to inhibit mitochondrial complex I and III, stimulate free radical production and disrupt microtubules in neurons – underlying conditions we find in autism.

Read more about this study and the positive benefits researchers found from sulforaphane at Nourishing Hope.

nutrients_elementsRecently, there has been quite a lot of controversy in the media (and even in the nutrition field) on whether diet and nutritional supplements can help autism. I’ve been focused on the science and application of nutrition and special diets for autism for 14 years. The scientific rationale for giving strategic attention to the food and nutrition children with autism receive is strong.

This recent “controversy” was in response to a new study that came out last week, that I feel is quite flawed. I’ll be addressing these “findings” in the coming days and look forward to sharing my broader thoughts with you.

However, before I do, I wanted to share a very important study published by Dr. James Adams, a prolific autism researcher, who has published dozens of studies on autism, and has conducted many specifically on nutritional status and supplementation in children with autism, with more to come.

Today I want to share the results from, “Effect of a vitamin/mineral supplement on children and adults with autism.”

This study is actually a follow up to another study he did.  So before I get to the study on the effects of supplementation in autism, I wanted to summarize the findings in the first study, Nutritional and metabolic status of children with autism vs. neurotypical children, and the association with autism severity, described in detail here.

Researchers found deficiencies and metabolic abnormalities in children with autism, including: low levels of biotin, plasma glutathione, SAM, plasma uridine, plasma ATP, NADH, NADPH, plasma sulfate, and plasma tryptophan. The children with autism had high oxidative stress markers and plasma glutamate. Biotin was the only vitamin with a significant difference in the children – it was 20% lower in the children with autism. Interestingly, their mean levels of vitamins, minerals, and most amino acids commonly measured in clinical care were within published reference ranges.”   However, while most nutrients were within “reference range,” the study found – along with the deficiencies and metabolic abnormalities above – many additional differences and deficiencies that are noteworthy:

  • B5, vitamin E and total carotenoids levels showed “possibly significant” lower levels in children with autism.
  • Folate and Niacin – possibly significant in autism (Functional needs assessed using FIGLU and n-methyl-nicotinamide)
  • Low lithium in autism
  • Twenty-five percent of the autism group was below the reference range for iodine and calcium.
  • Tryptophan, a precursor to serotonin was significantly lower in the autism group. (Low tryptophan plays a role in depression and poor sleep)
  • Glutamate, an excitatory neurotransmitter, was significantly higher (Glutamate is a factor in hyperactivity)
  • Other differences were possibly significant such as slightly decreased tyrosine and phenylalanine and slightly higher serine.

So while most of the vitamins and mineral levels fell within “published reference ranges,” the study found many metabolic differences and a number of markers indicating deficiency and concluded that “The autism group had many statistically significant differences in their nutritional and metabolic status, including biomarkers indicative of vitamin insufficiency, increased oxidative stress, reduced capacity for energy transport, sulfation and detoxification. Several of the biomarker groups were significantly associated with variations in the severity of autism.”

The next study published by Dr. Adams, and the one I want to highlight today, looked at the “Effect of a vitamin/mineral supplement on children and adults with autism” in this same group of individuals. This study was a randomized, double-blind, placebo-controlled treatment study on the use of a vitamin/mineral formula for three months. The study used a previous version of this multivitamin/mineral formula  – ANRC Essentials is now available as a slightly reformulated supplement to account for some of the findings in these studies.

The study results were impressing. In this study they found improvements in nutrient status, biomarkers, and autism symptoms. The study showed:

Vitamins

  • 3 months of supplementation increased the level of most vitamins, including vitamins B1, B3, B5, B6, folate, B12, C, E, and biotin.
  • The supplement also improved two functional biomarkers in urine, FIGLU and methylmalonic acid, indicating the supplement improve functional vitamin status of folate and vitamin B12.

So while vitamins were theoretically “in range” in the previous study, levels increased and improved to a more optimal level (not excess) with supplementation.

In the case of the functional biomarkers for folate and B12, this brings up an important biochemical point. For some individuals, laboratory values “appear” in normal range in the blood. However, this can be misleading as these nutrients may not be able to be utilized properly, so an actual deficiency is present. For example, with folic acid, it’s difficult for many people (such as those with methylation issues) to convert folic acid to the usable active folate form, so while levels of “folic acid” appear sufficient and “in range,” the active usable form of folate is actually insufficient and the individual is really deficient. With B12, many experts feel the standard reference range (for “normal” blood levels) is too low and some people need more, or a different form. Therefore, testing blood levels only may miss many people that are deficient. Therefore MMA which is an indicator of functional B12 status, is preferred by many clinicians and researchers to assess B12 status.

This study’s results may be illustrating these points – while levels of folic acid and vitamin B12 were in range, supplementation improved these biomarkers and likely vitamin status.

Minerals

  • The supplement increased the levels of many essential minerals including: calcium, iodine, lithium, manganese, molybdenum, and selenium.
  • The increase in lithium levels was large (this form of lithium was very well absorbed), so researchers felt less lithium may be better in future studies.

Biomarkers – Sulfation, Methylation, Glutathione and Oxidative Stress

The wonderful thing about this study is that it assessed biomarkers of important biochemical processes such as sulfation, methylation, and low glutathione (transsulfuration), all of which which researchers have found to be low in autism. They also measured oxidative stress, a process found to be high in autism. By studying these metabolic biomarkers and well as nutrient status, they were able to not only see what supplementation did for nutrient lab values, but what supplementation did for system and biochemical functioning. In this study they found:

  • After treatment, there was a significant increase in total sulfate, and a large and marginally significant increase in free sulfate. Adequate sulfate levels are important for sulfation, for which there are hundreds of functions in the body including proper gut barrier function and detoxification.
  • The level of SAM increased significantly, and there was a marginally significant decrease (improvement) in uridine, a marker of impaired methylation, indicating that supplementation may have improved methylation.  Methylation is important for adequate neurotransmitter levels and gene expression.
  • Reduced glutathione improved significantly and nearly normalized. Glutathione is a major antioxidant (important to neutralize oxidative stress), and has many functions including detoxification.

This means that in addition to having better levels of nutrients in the body, these nutrients helped to boost and improve functioning of many systems including biochemical processes that handle immune function, proper inflammatory response, detoxification, gastrointestinal health, and hundreds of other functions.

Symptom Improvement

Furthermore, this study also measured parents impressions from the supplementation and found improvements in every area assessed, and some were quite significant. Notice the improvements in language, hyperactive, tantruming and more.

Adams_study_image

Dr. Adams, et al. concluded in this study, “The vitamin/mineral supplement was found to be generally well-absorbed and metabolically active, resulting in improvements in biotin, glutathione, methylation, oxidative stress, ATP, NADPH, NADPH, and sulfate. The data from this study strongly suggests that oral vitamin/mineral supplementation is beneficial in improving the nutritional and metabolic status of children with autism, and in reducing their symptoms.”

This study greatly supports the use of vitamin and mineral supplementation in autism.

Study Citation:

Adams, James B., Tapan Audhya, Sharon McDonough-Means, Robert A. Rubin, David Quig, Elizabeth Geis, Eva Gehn et al. “Effect of a vitamin/mineral supplement on children and adults with autism.” BMC pediatrics 11, no. 1 (2011): 111.