the gluten-free link: adhd, autism, celiac disease and … · the gluten-free link: adhd, autism,...

The Gluten-Free Link: ADHD, Autism, Celiac Disease and Non-Celiac Gluten Sensitivity

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www.CeliacCentral.org Restoring Health … Reclaiming Lives. National Foundation for Celiac Awareness 2012. All rights reserved.


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NFCA Welcomes You! Marie-Nathalie Beaudoin, PhD

•  Training Director, Bay Area Family Therapy & Training Associates, Cupertino, CA

• Child and family therapist in private practice

•  Coauthor of 2011 article: • “ A medical issue affecting the diagnosis of mood,

attention and autistic disorders: a closer look at celiac disease and gluten sensitivity”

• Author of “The Skill-ionaire in every child: Boosting children’s socio-emotional skills using the latest in brain

research”

•  Both she and her son are diagnosed with celiac disease

Tonight’s Agenda


①  Review important definitions of key topics, including the link between diet and psychological problems.

②  Provide a summary of recent key research on the connections between the autism spectrum disorder, ADHD, celiac disease and non-celiac gluten sensitivity.

③  Share client stories relevant to the webinar’s topic, helping to bridge the gap between research and real-life applicability.

④  Teach the audience how to accurately understand the research that is presented in today’s news mediums.

⑤  You ask, we answer: Questions from the audience!

* Bonus! Dr. Beaudoin will share a simple checklist that webinar participants can reference when navigating academic research on their own.

“In the last few years, research has shown an increasing number of evidence for the existence of two categories of gluten-related problems:

celiac disease and gluten sensitivity.” Sapone et al, 2011

Setting the Stage: Definitions


Gluten-Related Disorders: All conditions related to gluten, including gluten ataxia, non-celiac gluten sensitivity and celiac disease.

Celiac Disease: •  A chronic small intestinal immune-mediated enteropathy precipitated by exposure to

dietary gluten in genetically predisposed individuals. •  A blood test indicating presence of specific antibodies EMA, tTG and/or DGP

strongly supports the diagnosis, but a small intestinal biopsy is necessary to confirm a diagnosis.

Volta, Oral presentation at ICDS 2011 Sapone et al, 2011 Sapone et al, 2012

Ludvigsson et al, 2012

“The literature suggests a lack of consensus on the use of terms related to celiac disease and gluten.” Ludviggson et al, 2012

  Non-Celiac Gluten Sensitivity (NCGS): • A non-specific innate immune response.

• Not accompanied by “the enteropathy, elevations in tissue-transglutaminase, endomysium or deamidated gliadin antibodies, and increased intestinal intestinal permeability that are characteristic of celiac disease.” (Ludvigsson et al, 2012)

• Causes possible but minimal intestinal damage that recedes with a gluten-free diet.

• Does not appear to be genetically based.

• Although early research indicates a possible prevalence of anti-gliadin antibodies (AGA), no laboratory or histological tests can currently diagnose NCGS, making the diagnosis a process of exclusion. Celiac disease and wheat allergy must be ruled out.

Setting the Stage: Definitions


Volta, Oral presentation at ICDS 2011 Sapone et al, 2011 Sapone et al, 2012


Celiac Disease

  Onset of symptoms can be weeks to years

  1% of the population, or 3 million Americans

  95% are undiagnosed

Non-Celiac Gluten Sensitivity

  Onset of symptoms is generally hours to days

  6% of the population, or 18 million Americans

  Diagnostic rate?


Side By Side

Sapone et al, 2011 Sapone et al, 2012

•  In NCGS, there is some overlap of symptoms with celiac disease such as abdominal pain, fatigue, headaches, tingling/numbness,

“foggy brain,” but often non-intestinal symptoms prevail.

•  Both treated by the gluten-free diet!


The Link: How can a food we eat change behavior?

Gut-Brain Connection •  Malnutrition

•  Leaky Gut

•  Inflammation

Did you know? Gluten is poorly digested in the human intestine, with or without celiac disease.

(Ludvigsson et al, 2012)

•  Damaged gut is unable to assimilate certain nutrients essential to proper functioning of a number of organs

•  Damaged villi cannot properly process and assimilate a number of nutrients, particularly:

•  Vitamin B, such as B6, B12, & Folate •  Iron •  Vitamin D, K •  Calcium

Hallert, C., Grant, C., Grehn, S., Granno, C., Hultén, S., Midhagen, G., Ström, M., Svensson, H. & Valdimarsson, T.(2002). Evidence of poor vitamin status in celiac patients on a gluten-free diet for 10 years. Alimentary Pharmacology & Therapeutics, 16, 1333-1339. Bhadada, S., Bhansali, A., Kochhar, R., Menon, A.S., Kant Sinha, S., Dutta, P., Kanwal Nain, C. (2008). Does every short stature child need screening for celiac disease? Journal of Gastroenterology and Hepatology, 23, 253-256. Mora, Barera, Beccio,Proverbio,Weber,Bianchi,Chiumello (1999). Bone density and bone metabolism are normal after long-term gluten free diet in young celiac patients.

The American Journal of Gastroenterology, 94(2), 398-403.

Understanding The Link: Malnutrition


•  The body becomes unable to produce enough tryptophan and other monoamine precursors needed for the production of key neurotransmitters in the brain such as serotonin, dopamine and norepinephrine.

•  This biochemical imbalance in the brain is associated with emotional problems.

Hernanz, A., & Polanco, I. (1991). Plasma precursor amino acids of central nervous system monoamines in children with coeliac disease. Gut, 32, 1478-1481.

Implications of Malnutrition and Deficiencies


  Characteristic of celiac disease: •  Increased intestinal permeability, or “leaky gut,” permits toxins, bacteria and undigested food proteins to seep through the GI barrier and into the bloodstream, and research suggests that it is an early biological change that comes before the onset of several autoimmune diseases.

  Poorly digested food overtax filtering organs such as the liver.

  Some toxins affect opioid receptors of the brain. For example, byproducts of milk entering the blood stream.


Sapone et al, 2011

Stevens, F.M. & Mc Loughlin, R.M. (2005). Is celiac disease a potentially treatable cause of liver failure? European Journal of Gastroenterology & Hepatology, 17, 1015-1017.

Whiteley, P., Haracopos, D., Knivsberg, A.M., Ludvig Reichelt, K., Parlar, S.,Jacobsen, J., Seim, A.,Pedersen, L., Schondel, M., Shattock, P. (2010). The ScanBrit randomized, controlled, single-blind study of a gluten- and casein-free dietary intervention for children with autism spectrum disorders. Nutritional Neuroscience, 13(2), 87-100.

Understanding the Link: “Leaky Gut”


•  Inflammation: The body’s natural response to assault •  Autoimmune Disease: Production of antibodies against own tissue •  Swelling, i.e. abdominal, joint pain, headaches, hypoperfusion in brain •  Production of stress hormones •  Byproducts of digestion end up in the blood stream and affect

different parts of the body such as joints

Toscano, Conti, Anastasi, Mariani, Tiberti, Poggi, et al. (2000). Importance of gluten in the induction of endocrine autoantibodies and organ dysfunction in adolescent celiac patients. The American Journal of Gastroenterology, 95(7), pp1742-1748.

Addolorato, G., Di Giuda, D., De Rossi, G., Valenza, V., Domenicali, M., Caputo, F. Gasbarrini, A, Capristo, E., Gasbarrini, G. (2004). Regional cerebral hypoperfusion in patients with celiac disease. � American Journal of Medicine, 116, 312-117.


Understanding the Link: Inflammation


Setting the Stage: Definitions Attention Deficit Hyperactivity Disorder (ADHD)

•  A persistent pattern of inattention and/or hyperactivity that is more severe than is typically observed in individuals at comparable level of development.

•  Symptoms and impairment must be present in at least 2 settings (clear evidence of impairment).

Setting the Stage: Definitions Autism Spectrum Disorder (including Asperger’s)

•  Persistent deficit in social interactions and communication across contexts.

•  Restricted, repetitive patterns of behaviors, interest or activity.

•  Symptoms limit and impair everyday functioning since early childhood. •  Differentiating factor: Children with Asperger’s exhibit a less severe impairment in communication and general functioning.



Research Findings: ADHD •  In the U.S., nearly 1 out of 10 children is prescribed medication to control their lack of attention and hyperactivity. That’s over 8 million children! (Zuvekas, Vitiello & Norquist, 2006)

•  Children and adolescents with untreated celiac disease or NCGS tend to exhibit more disruptive behavioral disorders and struggle with concentration. (Pynnonen et al., 2002, 2004, 2005)

•  In a Finnish study of 2,427 randomly selected “healthy adults,” undiagnosed silent celiac disease was significantly associated with underachievement as measured by education, employment and socio-economic status. (Verkasalo et al., 2005)

•  Subjects with undiagnosed celiac disease were 4 times less likely to have had a university or college degree or worked in managerial or professional positions.

Two breakthrough studies were published in recent years:

•  2006: 132 young participants diagnosed with celiac disease were followed beginning at initial diagnosis and implementation of gluten-free diet. ADHD symptoms were measured at baseline and 6 months after dietary intervention.

•  “The data indicate that ADHD-like symptomatology is markedly overrepresented among untreated CD patients and that a gluten-free diet may improve symptoms significantly within a short period of time.”

•  More attention to details, completion of tasks, concentration, ability to remain seated, less distractibility and hand fidgeting, less noise-making and blurting out. (Niederhofer & Pittschieler, 2006)

•  2011: 67 people diagnosed with ADHD were screened and 10 found to have celiac disease, i.e. 1 out of 7. These participants all showed a reduction in symptoms after at least 6 months on the gluten-free diet.

•  Celiac positive participants “showed a significant decrease in mean symptoms of ADHD including: no close attention to details, easily distracted, and often blurts out answer before the question is completed.” (Niederhofer, 2011)


Research Findings: ADHD


Client Story: ADHD

Example: •  Gluten-free diets can make a dramatic difference for some

children and adults suffering from ADHD •  The story of Leum


Research Findings: Autism

•  A 25-fold increase in prevalence over the past two decades:

•  1980: 1 in 2500 •  Today: 1 in 110 children; 1 in 70 boys

•  Connection between autism spectrum disorders and gluten-related disorders has been studied for a long time

Autism Speaks, 2012 CDC, 2010

Look familiar?



•  First article describing Asperger’s syndrome was written by Hans Asperger in 1961 and he was studying a group of 12 celiac children:

•  He described them as being afraid of people, moody, introverted, fearful, poor communicators and unable to enjoy human interactions.

•  Asperger reported that the children became friendly, approachable, flexible and independent thinkers after 2 years on a gluten-free diet.

Asperger, H. (1961). Psychopathology of children with celiac disease. Annal Paediatrica, 197, 346-351.

Hans Asperger



Since then many studies have examined this link.

Some studies show improvement… •  Cade et al., 1999; Genius & Bouchard, 2010; Knivsberg et al., 2002; Knivsberg, Reichelt, Nødland, & Høien, 1995; Knivsberg, Wiig, Lind, Nødland, & Reichelt, 1990; Lucarelli et al., 1995; Rimland, 2000; Whiteley, Rodgers, Savery, & Shattock, 1999; Whitely et al., 2010.

…Others do not. •  Batista, et al., 2012; Elder et al., 2006; Johnson et al., 2011; Seung, Rogalski, Shankar, & Elder, 2007.

Why such contradictory results?

①  Variations in children

②  Focus on diagnostic labels versus focus on treatment

③  Subjects’ adherence to the diet

④  Other issues of scientific methodology




1. Variations in Children •  As with ADHD and all other psychological issues, there are variations within the groups of people who suffer from these experiences and no single treatment will improve the unique experience of all.

•  Since improvement of some is evident, researchers are now attempting to identify different subgroups:

•  Past studies had noticed abnormal proteins in the urine of some autistic children and not others. (Vojdani et al., 2004)

•  More recent study confirmed that autistic children have a much higher percentage of abnormal intestinal permeability, which supports a leaky gut (celiac) connection. (Magistris, et al., 2010)

•  Another recent study showed a different intestinal bacteria in the gut of some ASD kids with GI-disturbances when compared to kids with just GI-disturbances. (Williams et al, 2012)


Autistic children do tend to have more tummy pain.

•  A strong correlation exists between the severity of autism and GI-disturbances. (Adams et a., 2011)

•  A study of 121 ASD children showed that those who have abdominal pain tend to have 6 times more communication problems than ASD children without abdominal pain. (Gorrindo et al. 2012)

•  “Odds of constipation were associated with younger age, increased social impairment, and lack of expressive language."

•  … A strong association had already been found between constipation and language impairment in 918 Autistic children. (Campbell et al, 2009)


If studies examining the effects of gluten-free/casein-free diets use subgroups of Autistic children with GI issues,

they have higher rates of success. Example: Knivsberg et al., 2002

•  Study Population:

•  20 autistic kids with urinary peptide abnormalities, with 10 as controls and 10 on the GFCF diet.

•  Significance of urinary peptide abnormalities that are derived from gluten, gliadin and casein.

•  Measures:

•  Five standardized tests of autistic features including behaviors; cognitive, social and emotional skills; and structured interviews conducted in the natural environment (home and school) of these children.

•  Results:

•  After one year, the GFCF diet group exhibited remarkable improvements in social skills as measured by physical contact, empathy, anxiety, peer relationships, non-verbal communication, eye contact, reaction when spoken to, cognitive factors, and sensory/motor.


2. Focus: Diagnostic or Treatment?

Studies obtain different results if the goal is to prove the number of autistic kids actually suffering from celiac disease or non-celiac gluten sensitivity, versus the benefits of the gluten-free diet itself.


When the focus is on the diagnostics…

A third variable is added - the accuracy of our measures.

If A is measured by B, and C is measured by D…your study then examines whether B and D have a relationship, and this becomes highly dependent on the accuracy of the tests and agreed upon diagnostic criteria.


Diagnostic Blood Tests Recommended Celiac Serology includes:

• IgA-tTG- Sensitivity and specificity (measures of accuracy) are excellent (~95%)

• IgA-EMA

• Iga/IgG-DGP

Keep in mind… •  Best to specify the antibody test since accuracy differs among each test

•  “Up to 5% of people with true celiac disease won’t have a measurable antibody response, so that alone cannot be an absolute differentiating point” (Leffler, email communication, 2012)

•  There is no test available for non-celiac gluten sensitivity

Role of Anti-Gliadin Antibodies •  “Elevated levels of AGAs have also been used for the investigation of possible increased gut permeability, but this use in clinical practice lacks a strong scientific background.” (Ludvigsson et al, 2012)

•  “AGAs are also relevant to gluten-induced disorders beyond the classical enteropathy. (The most well-known is gluten ataxia).” (Ludvigsson et al, 2012)

•  (Study on NCGS)….“Interestingly, AGA to IgA and IgG were positive in almost 50% of cases. Similarly, higher than expected titers of AGAs, signs and symptoms associated with non-celiac gluten sensitivity, have also been reported for schizophrenia and autism spectrum disorders.” (Sapone et al., 2011)


When the focus is on the diagnostics…

•  Well-designed study from Brazil found “no statistically demonstratable association between celiac disease or NCGS and autism spectrum disorder” (Batista et al., 2012)

•  tTG, anti-gliadin and endomysial antibodies were all tested

•  In an abstract presentation at 14th International Coeliac Disease Symposium in 2011, Sapone et al. reported:

•  Of 70 children with an autism spectrum disorder, 31.40% (22/70) tested positive for IgG-AGA.

•  Some studies report that an even bigger group of ASD responds to gluten-free diet treatment when it is combined with dairy free.


If the focus is on treatment directly…

•  A 2010 study followed 55 autistic children for 2 years. Ultimately, 35 participants completed the study:

•  Two group assignments: gluten-free/casein-free and control (no dietary intervention) •  Control group switched to dietary intervention at 12 months •  At 12 months, results showed a significant improvement on measures of communication, social interactions, inattention and hyperactivity.

•  Possible limitations? Importance?

•  Not tested for celiac disease •  At time, thought to be largest sample size using this type of intervention

•  This study was well-designed but not all follow a rigorous structure.

Whiteley et al., 2010


Why hasn’t my doctor told me about this? 3. Methodology Issues

Methodology is critical to verify that what we are measuring is really what we think we are measuring.

*Checklist! Main factors affecting the validity of findings:

①  Education and support of the subjects undergoing gluten-free or gluten-free, casein-free diet (Genius et Bouchard, 2010 versus Seung, et al., 2007)

②  Adherence to the diet (Whitely et al., 2010 versus Johnson et al., 2011)

③  Length of time the diet is tested (Whitely et al., 2010 versus Elder, et al. 2006)

④  Sample size, existence of control groups, measures used, and additional medical conditions and/or medications and/or interventions

•  Families with a child or adult struggling with ASD or ADHD are usually “stretched thin,” exhausted, and struggle with basic responsibilities of everyday life.

•  Asking them to undergo a major change in diet often seems completely overwhelming and inconceivable.

•  Example. Studies requesting such dramatic changes without providing adequate support run the risk of:

•  Participants resenting the diet and not following it, or

• Dropping out of the study, as seen in Whiteley et al, 2010


Main Factors Affecting the Validity of Findings: Education & Support

  Studies who report negative results but didn’t monitor their subjects’ adherence to the diet have very little validity.

• Can include using a skilled and knowledgeable dietitian and/or food records

 We know that in a number of people with a gluten-related disorder, a very small ingestion of gluten can have dramatic effects on their health and cause symptoms.


Main Factors Affecting the Validity of Findings: Dietary Adherence


Example:

•  A lady who was claiming to be completely gluten-free but still suffered from all her symptoms. After some time, it was discovered that she was eating the communion wafer at church every Sunday. Once she stopped, then her symptoms improved.

More specifically: • We know that adherence to the gluten-free diet “is the chief cause of persistent or recurrent symptoms” and that this occurs in up to 30% of patients with celiac disease. (Green and Cellier, 2007)

•  Gluten exposure is most common cause of non-responsive celiac disease. (Leffler et al, 2007)

Main Factors Affecting the Validity of Findings: Dietary Adherence

•  A successful diet change takes time. Even very motivated people make mistakes and struggle at first to determine what they can and cannot eat. This may take anywhere from a couple of weeks to a month depending on the amount of support and education they are receiving, and available time allotted to shop and explore completely new foods and recipes.

•  Once the new dietary lifestyle is in place, it may take a few weeks of completely gluten-free diet to witness improvement of health, psychological or behavioral issues.

•  Studies that measure the success rate of a diet change after only a few weeks are likely to miss the improvement of at least some of their subjects.


Main Factors Affecting the Validity of Findings: Length of Time Diet Is Tested


• Sample Size: A small sample does not allow to generalize the findings but can still provide evidence that a certain result is possible. Such studies exist in both the pro and the con studies.

•  Control Group: Measuring the progress of another group during the same period of time our subjects are undergoing the gluten-free diet allows us to take into account how people naturally change without interventions.

•  Measures Used: When only one or two measures of a characteristic are gathered, there is a risk that post-treatment changes will not be reflected n this narrow or specific manner leading researchers to assume there is no effects when in reality there may be.

•  Additional Medical Conditions and/or Medications and/or Interventions: Sometimes other health conditions can interfere with progress on gluten-free diets (i.e. thyroid issues, other food allergies/sensitivities). Must also take into account the medications and/or behavioral interventions children with autism or ADHD undergo.

Main Factors Affecting the Validity of Findings: Other Common Methodological Limitations


Research is contradictory and inconclusive.

It seems that there is some link to gluten among ADHD and Autism, BUT unsure if it is truly celiac disease or non-celiac gluten sensitivity.

Well-designed studies with bigger sample sizes are needed to help us better understand what links exist between ADHD, Autism and gluten-related disorders.

Conclusions

In the mean time…


Methodological limitations do not mean we eliminate the study.

It simply means we need to have some perspective as to the implications of the results.

So, What To Do?


Implications •  In 2003, Fasano et al. enrolled 13, 145 subjects from 32 states in the U.S. and found the prevalence of celiac disease to be:

• 1 in 68 for symptomatic adults • 1 in 25 for symptomatic children

•  In 2011, research from the University of Maryland Center for Celiac Research indicates that NCGS affects approximately 18 million people, or 6% percent of the population.

Dr. Beaudoin’s Perspective: “Given the increasing prevalence of gluten-related disorders, and as ethical and responsible clinicians, it is imperative that we consider celiac disease and NCGS before undergoing any other

treatment when people seek our assistance for psychological, behavioral, or relational problems.”

①  Asking questions about health issues that may appear insignificant, may in fact reflect gluten-related issues such as:

• Headaches, abdominal pains, “brain fog,” fatigue, behavioral/mood changes. • Visit DoIHaveCeliac.org for a more complete list.

②  Educating our clients about the potential contributors to the presenting complaint. • For example, with a family, I like to draw a circle in the middle of a page in which I write the word “problem”; I then draw 4-5 arrows towards the problem, distributed equally in the page, and labeled each with one of the following: nutrition, health, family relationships, school, context. I then provide a little introduction to how each of these factors could contribute to the problem and invite them to consider this bigger conceptualization.

③  Emphasizing the importance of consulting with a doctor and/or dietitian knowledgeable on the subject.

• It can avoid the unnecessary financial and emotional hardship of undergoing treatment which will never be fully effective if a gluten-related disorder is the underlying issue.

④  Providing access to books, DVD, and on-line resources.

⑤  Connecting with local support groups on the issue.


Applying Tonight’s Talk

• No one questions the fact that alcohol changes behaviors and alters the brain.

• No one would send a person struggling with alcoholism to be treated for depression or behavioral problems without addressing the issue of alcoholism.

• We need to get into the habit of verifying for a gluten-related disorder before initiating any other treatment of people with psychological issues such as ADHD and autism.

• At this moment in the history of our world, there is increasing medical evidence that we need to make this adjustment.


We Are What We Eat.

www.CeliacCentral.org Restoring Health … Reclaiming Lives. National Foundation for Celiac Awareness 2012 . All rights reserved.

You Ask, We Answer.

①  This research seems interesting, but my child with Asperger’s only eats bread, noodles and brownies. I can't imagine taking that away. It would trigger massive tantrums. Is there any way to facilitate this transition?

②  I'm totally on board with changing the diet of my child with ADHD, but he's rebelling against it, throwing away his lunch at school and eating everyone else’s food. My effort feels pointless, should I just give up until he's older?

③  Based on the information you've shared, I'm convinced that my 70-year-old father should be gluten-free, just as I am, but he says he's too old for such change and that it won't make a difference at his age. Is he right? Is it worth the effort so late in life?

④  I have a question about going gluten-free and being diagnosed with non-verbal learning disorder, as my 6 year-old son has been recently. No-one ever mentions this particular disorder! I'd love to know if there's any research or data that shows it can be helpful.

⑤  What information do you have in regards to Ritalin or any medication taken along with diet?

  Attention! Check out the #1hub for gluten-free kids & parents: CeliacCentral.org/kids

  New non-celiac gluten sensitivity information! Look for webinars and expert Q&A throughout 2012:

CeliacCentral.org/non-celiac-gluten-sensitivity


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Wednesday, April 18th at 8:30pm ET/5:30pm PT

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the gluten-free link: adhd, autism, celiac disease and … · the gluten-free link: adhd, autism,...

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