Gluten Dietary Intervention for Autistic Symptoms in Children With Autism Spectrum Disorders - Randomized Open Trial

Autism Spectrum Disorder (ASD) is a neurodevelopmental lifelong disorder, significantly impairing the quality of life of patients and their families. The symptoms are thought to result from interaction between genetics and environment. Treatment is multidisciplinary, based on behavioral therapy, education, and sometimes requires specialized care (i.e. genetics) and pharmacotherapy. The lack of consensus about the etiology of ASD directs researchers to define the condition as combination of symptoms, patient's history data, the impact of co-morbidities (including gastrointestinal disorders), and the effectiveness of various management therapies.

The use of complementary and alternative methods (CAM) of treatment is common and includes especially elimination diets, which are intended to minimize symptoms. The basis for the potentially beneficial impact of dietary intervention has been reported in connection to the correlation between congenital metabolic disorders (phenylketonuria) in patients with ASD and improvements in their overt symptoms in patients with schizophrenia Excessive activity of peptides derived from the metabolism of gluten and casein in individuals with ASD is thought to result in impaired neurotransmission in the brain. The increased permeability of the intestinal barrier, resulting from the inflammatory response (the theory of "leaky gut") in ASD patients, simultaneously promotes excessive absorption of those compounds. Another hypothesis assumes the effectiveness of elimination diets in children with ASD, suggesting allergic background of neuropsychiatric symptoms. Additionally it is emphasized that the lack of ability to communicate symptoms or atypical clinical manifestations (i.e. neuropsychiatric symptoms like hyperactivity, sleep disorders) in children with ASD can make the diagnosis of gastrointestinal symptoms, allergy and other symptoms particularly difficult. Moreover the pain or discomfort may increase the risk of behavioral symptoms.

Review of the literature concerning the effectiveness of gluten-free and casein-free diet (GFCFD) in individuals with ASD reveals a possible bias of the available studies and lack of a definite conclusion. Among 35 identified studies only two randomized controlled trials have been analyzed. The data/information on reported effectiveness of interventions in the behavioral symptoms [mean difference (MD-mean difference) -5.60, 95% CI -9.02 to -2.18, p = 0.001] in Knivsberg's study, is not reliable because of study limitations. Whiteley et al summarized in 2012 the positive effect of GFCFD on various symptoms in ASD patients. However the influence of GFCFD in ASD children can be defined mostly as suggestive because of the methodological limitations. The main biases include: small sample size, unclear process of randomization and allocation, use of different ASD assessment tools, short trial duration, lack of evaluation of patients' compliance to intervention, and other limitations.

The theory of excessive activity of exogenous opioids reports on specific allergies (gluten and casein) suggesting a connection with celiac disease (CD) in subjects with ASD and thus providing a rationale to determine the effect of gluten on gastrointestinal symptoms and consequently on potential behavioral changes in this group of patients.