Gluten and casein-free diets as a therapeutic approach in autism spectrum disorders have no conclusive results


A study by researchers from the Department of Psychiatry at the University of Granada (UGR) has analyzed the effects of a gluten-free diet and a casein-free diet (that is, one with no milk protein) on the behavior of children diagnosed with autism spectrum disorders.

Given the limitations of attempts to treat such disorders, many families turn to alternative therapies.

Among these, gluten- and casein-free diets implemented as a therapeutic approach in autism-spectrum disorders have been the subject of significant interest and controversy in scholarly research.

Some authors have found such diets to have favorable effects on the symptoms of autism, while others–particularly the more recent studies–have found no conclusive results.

Research conducted at the UGR reaffirms that gluten- and casein-free diets are not helpful as a standardized treatment for all children diagnosed with an autism spectrum disorder.

It may be that those cases with associated gastrointestinal disorders may benefit from such an approach.

Beta-casomorphin is a peptide (amino acid-binding), so-called for its morphine-like opioid activity, which is formed in the intestine due to abnormal digestion of cow’s milk protein (casein).

People with autism-spectrum disorders may present an abnormal porosity in the intestinal barrier that enables beta-casomorphin to penetrate the barrier, enter the blood circulation and, from there, reach the central nervous system, producing a toxic effect.

Some scientists who have identified peptiduria (the abnormal presence of peptides in the urine) in children with autism spectrum disorders have detected a reduction of these peptides in subjects who have followed the gluten- and casein-free diet.

The primary aim of this research was twofold: to determine if gluten- and casein-free diets decrease behavioral disorders among children and adolescents diagnosed with autism spectrum disorders, and to examine whether there is a link between possible behavioral changes after implementing this diet and levels of beta-casomorphin found in urine.

Two studies and a sample of over 60 young people

The UGR research comprised two studies. First, a pilot clinical assay was carried out on 28 children and adolescents diagnosed with autism spectrum disorders, who followed a gluten-free diet for three months and then switched to a casein-free diet for a further three months.

Next, a second study was initiated, funded by the Spanish Association of Child and Adolescent Psychiatry (AEPNyA), in which 37 children and adolescents diagnosed with autism-spectrum disorders participated.

This sample followed the same procedure, except for a longer duration (one special diet for six months, then the other special diet, again for six months).

Variables relating to the efficacy, risk, and safety of following these diets were studied.

Research conducted at the UGR reaffirms that gluten- and casein-free diets are not helpful as a standardised treatment for all children diagnosed with an autism-spectrum disorder.

It may be that those cases with associated gastrointestinal disorders may benefit from such an approach.

In neither of the two studies (3 + 3 months vs. 6 + 6 months) were significant changes detected either in the behavioral scales or in the beta-casomorphin levels in urine after the subjects had followed the gluten-free and the casein-free diet.

The principal investigator on this project, Pablo José González Domenech, of the Department of Psychiatry of the UGR, notes that further research is necessary.

In addition to eliminating gluten and casein for a sufficient period of time (at least six months), future studies should include placebo and double-blind elements, as well as other biological markers to better define the subjects who may benefit from these diets.

To identify potential users, it would be interesting to include among the evaluation criteria measurements of intestinal permeability, examinations of intestinal bacterial populations, and gastrointestinal enzymatic and inflammatory activity, and to conduct brain imaging tests for the study of possible structural and functional changes.

Autism spectrum disorder (ASD) is a group of heterogeneous chronic neurodevelopmental disorders characterized by qualitative impairments in social interaction, communication, and repetitive stereotyped patterns of behavior [1].

The etiology of these conditions is thought to be multifactorial, involving genetic, prenatal, and postnatal factors [2]. The Centre for Disease Control (CDC) reports that 1 in 59 children are diagnosed with ASD, with boys 4 times more likely to be diagnosed than girls. As such, ASD is the fastest growing developmental disorder in the United States [3].

Treatment for ASD focuses on educational and behavioral interventions such as applied behavioral analysis [4].

Psychotropic drugs are commonly prescribed to treat core behavioral symptoms, decrease maladaptive behavior, and support learning and development [5].

In addition to conventional treatment options, some parents of children with ASD seek out complementary and alternative medicine (CAM) to treat symptoms.

The National Centre for Complementary and Integrative Health defines CAM as “a diverse group of medical and health care systems, practices, and products that are not generally considered part of conventional Western medicine” [6].

Complementary approaches fall broadly into 3 categories: Natural products such as dietary supplements and special diets, mind and body practices, and other complementary health approaches [7].

Evidence regarding the use of CAM in the general pediatric population is limited. Studies in the United States have shown that the prevalence of pediatric CAM use in populations with illness or disease can range up to 76% [8].

However, these studies are limited in several ways. First, while many employ sound methodologies, they often provide differing definitions of what constitutes a CAM therapy. For example, in their review of 136 studies on alternative medicines, Surette et al. [9] found 39 studies that included vitamins, 13 studies that excluded vitamins, and 41 studies that made no mention of their inclusion or exclusion criteria.

Further, many of the pediatric CAM studies are characterized by wide variation in study populations and size, prevalence measurements, and research methodologies, all of which hinder the formulation of evidence-based recommendations.

Though limited in number, some studies have examined CAM effects in ASD. Levy et al. [10] found that greater than 9% of children with ASD used potentially harmful CAM, such as chelation, antibiotics, or excessive amounts of vitamins.

These findings are consistent with anecdotal evidence of dangerous products used to “cure” ASD. For example, in 2014, the supplementation market saw an explosion of Miracle Mineral Solution, a solution of sodium chlorite and hydrochloric acid (i.e., bleach) as a treatment option for ASD.

The US Food and Drug Administration has issued several warnings about the product and the treatment has been linked to 1 death and several serious injuries; however, Miracle Mineral Solution is still widely available, with 1000 + followers on social media promoting its use [11].

From a public health perspective, supplement-based therapies and specialty diets, a subcategory of CAM, requires further evaluation. While many supplements such as melatonin, vitamins, gluten-casein-free diet, and omega 3 fatty acids may have few adverse effects, their safety and effectiveness in reducing ASD symptomology have not been reliably established [2,12,13].

Research estimates that up to 74% of children with ASD have been provided with CAM and that supplement-based therapies make up approximately 50% of CAM therapies used by this population [14].

Despite its popularity, disclosure of CAM use to physicians is often poor, with rates as low as 23% [15]. Concurrent use of CAM and prescription medications is widespread and poses a possible risk to patients who may be unaware of the potential for interactions [16].

Further, research has documented that knowledge of CAM use is important for health care professionals, as it provides insight into patient values and health beliefs. Importantly, considering patient values may assist in providing optimum care, especially in the context of supplements that pose a safety risk to patients [15].

Given the rates of concurrent use, in conjunction with lack of disclosure, there is a pressing need to assess pediatric CAM use and parental perceptions of these therapies.

As the prevalence of supplements and specialty diets are high and many are unsupported by research, a better understanding of the use of supplementation in pediatric ASD could help provide better integrative care by

(1) informing the public and health care professionals about the prevalence and types of supplement therapies and specialty diets used in children with ASD;

(2) assessing patient-physician communication and interactions surrounding supplement and specialty diet use; and

(3) highlighting priorities for evidence-based clinical trials for supplements in ASD. Therefore, this study seeks to describe the use of supplement-based CAM therapies in children with ASD.

University of Granada


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