Influence of a Combined Gluten-Free and Casein-Free Diet on Behavior Disorders in Children and Adolescents Diagnosed with Autism Spectrum Disorder: A 12-Month Follow-Up Clinical Trial

  • Pablo José González-Domenech
  • Francisco Díaz Atienza
  • Carlos García Pablos
  • María Luisa Fernández Soto
  • José María Martínez-Ortega
  • Luis Gutiérrez-RojasEmail author
Original Paper


The use of alternative interventions, such as gluten-free and casein-free (GFCF) diets, is frequent due to limited therapies for Autism Spectrum Disorder (ASD). Our aims were to determine the influence of a GFCF diet on behavior disorders in children and adolescents diagnosed with ASD and the potential association with urinary beta-casomorphin concentrations. Thirty-seven patients were recruited for this crossover trial. Each patient consumed a normal diet (including gluten and casein) for 6 months and a GFCF diet for another 6 months. The order of the intervention (beginning with normal diet or with GFCF diet) was assigned randomly. Patients were evaluated at three time-points (at the beginning of the study, after normal diet and after GFCF diet). Questionnaires regarding behavior and autism and dietary adherence were completed and urinary beta-casomorphin concentrations were determined at each time-point. No significant behavioral changes and no association with urinary beta-casomorphin concentrations were found after GFCF diet. A 6-month GFCF diet do not induce significant changes in behavioral symptoms of autism and urinary beta-casomorphin concentrations. Further studies with a long follow-up period similar to ours and including placebo and blinding elements are needed to identify better those respondents to GFCF diets.


Autism spectrum disorder Diet Gluten Casein Beta-casomorphin 



We thank University of Granada, in particular, Professor Manuel Gurpegui Fernández de Legaria for his advices and suggestions regarding this manuscript. The authors acknowledge Nutraceutical Translations for translating this manuscript into English.

Author Contributions

PJG-D has participated in the design of the study, collected the data, participated in the statistical analysis, the interpretation of the data and the drafting of the article; he approved the final version of the manuscript. FDA, CGP, JMM-O, LG-R has participated in the statistical analysis, the interpretation of the data and the drafting of the article; she approved the final version of the manuscript. MLFS has participated in the design of the study, the statistical analysis, the interpretation of the data and the drafting of the article; he approved the final version of the manuscript.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Research Involving Human Participants

The investigation was carried out in accordance with the Helsinki Declaration of 1975, as revised in 2013. The research protocol was approved by the local Institutional Review Board.

Informed Consent

All patients gave written informed consent.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Pablo José González-Domenech
    • 1
    • 2
  • Francisco Díaz Atienza
    • 1
  • Carlos García Pablos
    • 1
  • María Luisa Fernández Soto
    • 3
  • José María Martínez-Ortega
    • 2
  • Luis Gutiérrez-Rojas
    • 2
    • 4
    • 5
    Email author
  1. 1.Child and Adolescent Mental Health UnitVirgen de las Nieves University HospitalGranadaSpain
  2. 2.Department of PsychiatryUniversity of GranadaGranadaSpain
  3. 3.Department of MedicineUniversity of GranadaGranadaSpain
  4. 4.Psychiatry ServiceHospital Clínico San CecilioGranadaSpain
  5. 5.CTS-549 Research Group, Institute of NeuroscienceGranadaSpain

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