The Effect of a Combined Gluten- and Casein-Free Diet on Children and Adolescents with Autism Spectrum Disorders: A Systematic Review and Meta-Analysis.

Amélie Keller,Marlene Briciet Lauritsen,Christoffer Bruun Korfitsen,Simon Tarp,Birgitte Holm Petersen,Jeanett Friis Rohde,Marie Louise Rimestad,Mina Nicole Händel

doi:10.3390/nu13020470

Abstract

There has been a growing interest in the gastrointestinal system and its significance for autism spectrum disorder (ASD), including the significance of adopting a gluten-free and casein-free (GFCF) diet. The objective was to investigate beneficial and safety of a GFCF diet among children with a diagnosis of ASD. We performed a systematic literature search in Medline, Embase, Cinahl, and the Cochrane Library up to January 2020 for existing systematic reviews and individual randomized controlled trials (RCTs). Studies were included if they investigated a GFCF diet compared to a regular diet in children aged 3 to 17 years diagnosed with ASD, with or without comorbidities. The quality of the identified existing reviews was assessed using A Measurement Tool to Assess Systematic Reviews (AMSTAR). The risk of bias in RCTs was assessed using the Cochrane Risk of Bias Tool, and overall quality of evidence was evaluated using Grades of Recommendation, Assessment, Development, and Evaluation (GRADE). We identified six relevant RCTs, which included 143 participants. The results from a random effect model showed no effect of a GFCF diet on clinician-reported autism core symptoms (standardized mean difference (SMD) −0.31 (95% Cl. −0.89, 0.27)), parent-reported functional level (mean difference (MD) 0.61 (95% Cl −5.92, 7.14)) or behavioral difficulties (MD 0.80 (95% Cl −6.56, 10.16)). On the contrary, a GFCF diet might trigger gastrointestinal adverse effects (relative risk (RR) 2.33 (95% Cl 0.69, 7.90)). The quality of evidence ranged from low to very low due to serious risk of bias, serious risk of inconsistency, and serious risk of imprecision. Clinical implications of the present findings may be careful consideration of introducing a GFCF diet to children with ASD. However, the limitations of the current literature hinder the possibility of drawing any solid conclusion, and more high-quality RCTs are needed. The protocol is registered at the Danish Health Authority website.

Highlights

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by qualitatively impaired behavior within the core areas of social interaction and communication as well as behavior characterized by a pattern of limited, stereotypical, and repetitive actions and interests [1,2]
Rleemfeernetnacreysmofathereiathl.rReeefienrcelnucdeesdosfytshteemtharteiec irnecvliuedwesdcsoynsttreimbuatteicdreviews contributed with five Randomized Controllled Trial (RCT) [20,2w1,3it6h–3fi8v]e(RFiCgTusre[220),.21,36–38] (Figure 2)
Based on the collective evidence from the six identified RCTs [20,21,36,37,38,39], there are no indications that following a gluten-free and casein-free (GFCF) diet has a positive effect on core symptoms of autism, behavioral difficulties, or adaptive functional level, and there is a high degree of uncertainty due to very low quality of evidence

Summary

Introduction

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by qualitatively impaired behavior within the core areas of social interaction and communication as well as behavior characterized by a pattern of limited, stereotypical, and repetitive actions and interests [1,2]. ASD is believed to be a lifelong disability, but the clinical presentation and level of functioning may change over time [1,3]. By-products from the microbiota have been suggested to influence the synthesis of neuropeptides like serotonin, and peptides from gluten and casein have been hypothesized to increase the activity of the opioid system [10].

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