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Efficacy and Safety of Gluten-Free and Casein-Free Diets Proposed in Children Presenting with Pervasive Developmental Disorders (Autism and Related Syndromes)

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Efficacy and Safety of Gluten-Free and Casein-Free Diets Proposed in Children Presenting with Pervasive Developmental Disorders (Autism and Related Syndromes) FRENCH FOOD SAFETY AGENCY Efficacy and safety of gluten-free and casein-free diets proposed in children presenting with pervasive developmental disorders (autism and related syndromes) April 2009 1 Chairmanship of the working group Professor Jean-Louis Bresson Scientific coordination Ms. Raphaëlle Ancellin and Ms. Sabine Houdart, under the direction of Professor Irène Margaritis 2 TABLE OF CONTENTS Table of contents ................................................................................................................... 3 Table of illustrations .............................................................................................................. 5 Composition of the working group ......................................................................................... 6 List of abbreviations .............................................................................................................. 7 1 Introduction .................................................................................................................... 8 1.1 Context of request ................................................................................................... 8 1.2 Autism: definition, origin, practical implications ........................................................ 8 1.2.1 Definition of autism and related disorders ......................................................... 8 1.2.2 Origins of autism .............................................................................................. 8 1.1.2.1 Neurobiological studies ............................................................................. 8 1.1.2.2 Genetic studies ......................................................................................... 9 1.2.3 Practical implications .......................................................................................10 1.3 Tools for diagnosis and evaluation of the course of autistic children .......................10 1.3.1 Diagnostic instruments ....................................................................................10 1.2.1.1 Autism Diagnostic Interview - R (ADI - R) (Lord et al, 1994) ....................10 1.2.1.2 ADOS (autism diagnostic observational schedule, Lord et al., 2000) .............10 1.2.1.3 Children Autistic Rating Scale (CARS) (Schopler et al., 1980) ................11 1.3.2 Scales measuring behavioural traits ................................................................11 1.2.2.1 BSE - Behavioural Summarized Evaluation scale ..................................11 1.2.2.2 ABC scale (Aberrant Behavior Checklist, Aman et al., 1985)...................11 1.3.3 Conclusions ....................................................................................................11 1.4 Conventional and alternative management of autism and view point of the families of patients .........................................................................................................................12 1.4.1 Management of autism ....................................................................................12 1.4.2 Alternative management .................................................................................12 1.4.3 Viewpoint of representatives of patients and their families ..............................12 1.3.3.1 On diet .....................................................................................................13 1.3.3.2 On the perception of disorders in autism .................................................13 2 Evaluation of the efficacy of food avoidance regimens in autism ...................................14 2.1 Origin of avoidance regimens in autism ..................................................................14 2.2 Scientific publications dedicated to the effects of a gluten-free and casein-free diet in autism ...........................................................................................................................14 2.2.1 Bibliographical search .....................................................................................14 2.2.2 Identification of communications .....................................................................15 2.2.3 Pre-selection of communications .....................................................................15 2.2.4 Evaluation of communications .........................................................................15 2.2.5 Selection of communications ...........................................................................15 2.2.6 Description of trials on food avoidance diets (see synthetic table in Annexe 1) 16 2.2.6.1 Reichelt et al., 1990 (a) ............................................................................16 2.2.6.2 Knivsberg et al., 1990, 1995 (b and c) ......................................................16 2.2.6.3 Sponheim, 1991 (d) ..................................................................................17 2.2.6.4 Lucarelli et al., 1995 (e) ............................................................................17 2.2.6.5 Whiteley et al., 1999 (f) ............................................................................18 2.2.6.6 Cade et al., 2000 (g) ................................................................................18 2.2.6.7 Knivsberg et al., 2002 (h) .........................................................................19 2.2.6.7 Elder et al., 2006 (i) ..................................................................................19 2.2.7 Overall observations .......................................................................................20 2.2.8 Synthesis and conclusion ................................................................................21 3 Evaluation of safety of food avoidance diets in autism ...................................................22 3.1 Spontaneous food intake and nutritional status of autistic children .........................22 3.1.1 Spontaneous food intake of autistic children ...................................................22 3.1.2 Nutritional status of autistic children ................................................................22 3 3.2 Eating patterns and nutritional status of autistic children receiving a gluten-free and casein-free diet .................................................................................................................23 3.2.1 Eating patterns with an avoidance diet ............................................................24 3.2.2 Nutritional status with an avoidance diet .........................................................24 3.2.3 Gluten-free and casein-free diet: theoretical estimation of nutritional intake ....24 3.2.4 Other possible effects of an avoidance diet .....................................................25 3.2.5 Long term nutritional effects of a gluten-free diet in non autistic children: experience with coeliac disease ....................................................................................25 3.2.6 Nutritional effects of a milk protein-free diet in non autistic children: experience with milk protein intolerance ..........................................................................................26 3.2.7 Conclusion ......................................................................................................26 4 Indirect evidence proposed in support of a gluten-free and casein-free diet ..................27 4.1 Opioid peptides: origins and biological effects ........................................................27 4.1.1 Sources of opioid peptides in food ..................................................................27 4.1.1.1 Milk casein ...............................................................................................28 4.1.1.2 Cereal gluten ............................................................................................28 4.1.1.3 Other plant and animal proteins ...............................................................28 4.1.1.4 Characterisation of pharmacological properties of these peptides ............28 4.1.1.5 Conclusion ...............................................................................................29 4.1.2 Intestinal production and absorption, urinary excretion of opioid peptides in humans 31 4.1.2.1 Production of dietary opioid peptides in the intestinal lumen in animals and in humans 31 4.1.2.2 Passage of opioid peptides across the intestinal mucosa .........................31 4.1.2.3 Bioavailability and biological effects in vivo of dietary bioactive peptides ..31 4.1.2.4 Urinary excretion of opioid peptides ........................................................32 4.1.3 Effects of opiate antagonists in autism ............................................................34 4.1.3.1 Open-label series ....................................................................................34 4.1.3.2 Controlled clinical trials .............................................................................34 4.1.3.3 Conclusion ...............................................................................................36 4.2 Autism, gastrointestinal disorders and change in intestinal permeability .................36 4.2.1 Autism and specific gastrointestinal disorders .................................................36 4.2.1.1 Autism and coeliac disease ......................................................................36 4.2.1.2 Autism and inflammatory digestive tract diseases ....................................37 4.2.2 Autism and food
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