The Gluten-Free, Casein-Free Diet in Autism: An Overview With Clinical ImplicationsFrom the College of Nursing, University of Florida, Gainesville. Address correspondence to: Jennifer Harrison Elder, PhD, RN, FAAN, Box 100187 HPNP Building, Room 4221, University of Florida, College of Nursing, Gainesville, FL 32610; e-mail: elderjh{at}ufl.edu.
The prevalence of classic autism and autism spectrum disorder (ASD) appears to be on the rise, and to date, there remains no clear etiology or cure. Out of desperation, many families are turning to new therapies and interventions discovered through various media sources and anecdotal reports from other parents. Unfortunately, many of these newer, well-publicized interventions have little empirical support. One of the most popular yet currently scientifically unproven interventions for ASD is the gluten-free, casein-free (GFCF) diet. Clinicians working with families of individuals with ASD are often asked for advice and find themselves unable to offer the most up-to-date and scientifically credible information. This article provides an overview of ASD and the GFCF diet, a summary and critique of current research findings, recommendations for future research, and practical advice for families to use in deciding if a trial of the GFCF diet is in the best interest of their child and family.
Key Words: autism disorder • gluten • caseins Several years ago, I attended a conference that focused on complementary and alternative therapies in autism. While a few of the participants were professionals, most were parents, desperate to learn more about popular treatments that might offer hope in managing autism, which, to date, has no conclusive etiology or cure. A professionally dressed woman sitting next to me questioned my reason for attending, initially asking how old my autistic child was. I explained that while I did not have a child with autism, I had been working in the field for more than 25 years and had a particular interest in conducting research to provide credible scientific evidence for families to use when making treatment decisions. Respectfully, she turned to me and stated with firm conviction, "I am a college-educated woman with advanced degrees. I understand the importance of research. However, if I wait for `science' to provide the data, it will be too late. My child will be grown. I have to know something now. I have decisions to make now!" I thought to myself, "Well said," and assured my new friend that I, along with my research colleagues, have made this research area a priority, recognizing the importance of scientific evaluation of any proposed treatment. Before, and since that time, I have encountered numerous desperate parents seeking well-informed advice regarding interventions for their children with autism. Their needs and the needs of clinicians who work with these families have inspired our team's current research direction and this article, which focuses on one of the most popular interventions in autism, the gluten-free, casein-free (GFCF) diet. Clinicians are often asked to advise families and must be positioned to offer the most up-to-date and scientifically credible information. This article provides an overview of autism and the GFCF diet, a summary and critique of current research findings, recommendations for future research, and practical advice for families to use in deciding if a trial of the GFCF diet is in the best interest of their child and family.
Autism, as it is classically defined, occurs on a spectrum and is often referred to as autistic spectrum disorder (ASD) or simply autistic disorder. This is a lifelong complex neurobiological disorder that affects practically every aspect of the diagnosed person's life.1,2 The Centers for Disease Control and Prevention recently reported prevalence rates of 1 in 150 children diagnosed with autism (http://www.cdc.gov/mmwr/PDF/ss/ss5601.pdf). Although there is controversy regarding whether this is an actual rise in the number of cases or a result of increased publicity and better diagnostic measures, it remains clear that autism is a disorder that produces major challenges for families and society at large. To date, there is no clear etiology or known cure.3
Presenting Features
Current Treatment in Autism
One of the most popular, yet currently scientifically unproven, interventions for ASD is the GFCF diet.11,12 A number of theories have been used to explain the rationale for this diet that eliminates gluten (found in wheat, rye, and barley) and casein (the main protein in dairy products). It is hypothesized that some autistic symptoms (eg, stereotypical and ritualistic behaviors, perseveration, excessive activity, speech and language delays, and oddities) may be the result of opioid peptides formed from the incomplete breakdown of foods containing gluten and casein.13-15 Increased intestinal permeability, also referred to as the "leaky gut syndrome," allows these peptides to cross the intestinal membrane, enter the bloodstream, and cross the blood–brain barrier, affecting the endogenous opiate system and neurotransmission within the central nervous system. This may help explain why many children with autism have associated GI symptoms, including diarrhea, constipation, abdominal pain, and gastroesophageal reflux. Furthermore, because many of these children cannot adequately express their pain or GI discomfort verbally, they may react with extreme behaviors (eg, screaming, aggression, self-abuse).15-18
Background of the GFCF Diet Following this initial work in schizophrenia, Cade developed an interest in autism. While his views were considered controversial by some, Cade often compared schizophrenia and autism, noting similarities in behavioral presentations of the 2 disorders.19 Cade's next step was to expand his initial laboratory testing to applied settings. Again claiming similarities between the 2 disorders, Cade et al conducted a study including 120 individuals with schizophrenia and 149 who met the Diagnostic and Statistical Manual of Mental Disorders (3rd ed.), criteria for autism. All children with autism received a GFCF diet that was a synthesis of the Milk Free Kitchen by Kidder23 and the Gluten-Free Gourmet by Hagman.24 This open, unblinded trial included physiological measures as well as parental and teacher reports. Eighty-seven percent of the children with autism had high titer IgG antibodies to gliadin, and 30% had high titer transindolylacryloyl-glycine antibodies to gluten or casein. There were also parent and teacher reports of improvement in 81% of children within 3 months. While considered by some to be groundbreaking, this study lacked a control group and/or control conditions and relied heavily on subjective outcome measures from parents and teachers who knew when the children were on the GFCF diet.
GI Abnormalities in Autism Several studies have reported significant GI dysfunction in children with autism, which may result from gluten or casein sensitivity.17,32-36 Ashwood and colleagues37 found distinct mucosal pathologies in children with ASD and GI symptoms. They noted the apparent positive effect in the colonic mucosa between children on and off the GFCF diet and recommended further study. Wakefield et al38 demonstrated irregularities in the absorptive properties of the mucosa of the intestinal wall in children with autism. In a second study,35 more than 93% of their sample (n = 60) had GI symptoms, including abdominal pain, constipation, diarrhea, and bloating. Horvath and coworkers17 used endoscopy with biopsy to examine the upper GI tract of a convenience sample of 36 children diagnosed with autism who were experiencing abdominal pain, chronic diarrhea, bloating, nighttime awakening, or unexplained irritability. They found reflux esophagitis in all 36 children, and 24 had chronic duodenitis. Although results of these studies may be subject to selection bias, as the children with ASD all reported GI complaints at the time of sampling, the authors discuss individual symptoms in 2 later publications.39,40 These same investigators note that more than 85% of the autistic children suffered with at least 1 GI symptom, compared with only 12% of their control siblings. In contrast, Black et al32 reviewed medical records and concluded that, in general, there were no associations among GI inflammation, celiac disease, food intolerance, recurrent GI symptoms, and the development of autism. However, they acknowledged that GI symptoms may be present in a certain subgroup of individuals with autism. Once again, this highlights the variability in this population and the importance of further characterization.
Results of GFCF Dietary Clinical Trials in Autism Description of Knivsberg and colleagues' work. The 2002 Knivsberg et al study,25 described by Christison and Ivany10 as the most rigorous GFCF diet in autism study published prior to their review, involved a randomized, single-blind design with 20 subjects. Children in the control and experimental groups were matched according to severity of autistic symptoms, age, and cognitive level. Effects of the GFCF diet on children with ASD were assessed using urinary peptide levels, with high levels indicating that the origin of the peptides is of exogenous nature (ie, from food containing gluten, gliadin, and casein).41 The basic hypothesis is that the urinary peptide abnormalities reflect processes that have an opioid effect.12,28 Although changes were observed in both control and experimental groups in the Knivsberg et al study, the experimental group had significant improvement in autistic behavior, nonverbal cognitive level, and motor problems compared with those in the control group. Limitations to this work were the small sample size and lack of strict dietary control for children on the GFCF diet, a commonly encountered problem in conducting dietary research in children. Summary of Elder and colleagues' double-blind placebo controlled study. Published in the Journal of Autism and Related Disorders after Christison and Ivany's (2006) review article, our randomized double-blind clinical trial of the GFCF diet in children with autism11 addressed some of the prior concerns related to scientific rigor by using accepted diagnostic instruments under controlled conditions. The sample included 13 children with autism (range, 2-16 years). Under the direction of the University of Florida's General Clinical Research Center's (GCRC) Bionutrition staff, individual child food preferences were considered and participants were provided all meals and snacks (a 3- to 4-day supply twice a week) from the GCRC's Metabolic Kitchen throughout the trial. Data were collected in subjects' homes using the videotaping and observational procedure we have refined through our prior parent-training projects.46,47 We evaluated the effects of the GFCF diet on the following: (1) autistic symptoms as measured by the Childhood Autism Rating Scale, Ecological Communication Orientation Scale, and behavioral frequencies of child social and language behaviors; and (2) urinary peptide levels of gluten and casein. We videotaped the children during in-home play sessions with the primary caregiver for 15 minutes. This occurred before the diet's introduction, at the end of the first 6-week period, and at the completion of the 12-week protocol. While there were some anecdotal parent and teacher reports of positive dietary effects on language and behavior, group analysis data indicated no significant differences in the behavioral data or urinary peptide levels of gluten and casein. It is also interesting that parents of 9 children decided to keep their children on the GFCF diet even though there was no empirical support for continuing the diet. This project demonstrates that it was possible to develop and implement a double-blind condition using GFCF and placebo diets since 8 of the parents could not distinguish between the placebo and experimental diets.
Addressing Limitations Like other studies reviewed in this article, results from our work are preliminary and have implications for future research. First, consideration should be given to not only including larger numbers of participants but also thoroughly diagnosing and characterizing them using well-established diagnostic measures. Carefully diagnosing participants with instruments that have subdomains may assist in identifying subgroups and perhaps eventually help predict the most likely responders. Also, recognizing that ASD symptoms vary considerably, it may be useful to conduct an in-depth individual study using rigorous intrasubject, single-subject experimental measures with replication across subjects.48 Another consideration is that even though most parents in our study were conscientious regarding dietary restrictions, controlling access to food is difficult across settings (eg, home, school, homes of friends and relatives), and there were several reports of children sneaking food. That said, it would be ideal to extend data collection for a longer period of time, anticipating that there may be noncompliance incidents resulting in a need for washout periods during the course of the study. Another reason for extending the 12-week protocol is that there are clinical reports of some children who respond to the GFCF diet quickly, while others take several weeks before behavioral effects are detectable. As previously mentioned, another challenge of dietary research with children is the subjective nature of parental reports and the potential for parental placebo effects related to diet effectiveness.10,11 For example, 7 of the 13 families in our study reported improvements (increased child language, decreased hyperactivity, decreased tantrums) that were not empirically supported by objective measures. Interestingly, all of these families chose to continue the diet at the completion of the study, even after being told about the nonsignificant results.
Additional Considerations When Implementing the GFCF Diet
As noted in the beginning of this article, families of individuals with ASD often feel an urgency to make treatment decisions since they are ultimately responsible for the welfare of individuals with ASD. While research efforts related to use of the GFCF diet in autism have recently provided some preliminary evidence, there is much to learn and many questions left to answer. Until more is known, parents will continue facing challenges as they try to determine what is best for the person with ASD and the family as a whole. Professionals in a position to assist with decision making might consider the following questions to help families weigh pros and cons related to the GFCF diet:
Three additional considerations specific to the children themselves are as follows:
In summary, research momentum in autism has markedly increased over the past decade, and new discoveries are made daily. However, there is a great need for additional research to address current limitations and questions raised by families and researchers themselves. This article has provided an overview of one of the newest and perhaps most promising interventions. In conclusion, the individual needs of patients with ASD and their families are significant; the reader is encouraged to remain knowledgeable of the latest research in an effort to give the best and most thoughtful advice.
Financial disclosure: none declared.
Nutrition in Clinical Practice, Vol. 23, No. 6,
583-588 (2008) This article has been cited by other articles:
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Autism: An Overview
The GFCF Diet
