Advertisement

Gluten-Free Diet in Children with Autism Spectrum Disorders: A Randomized, Controlled, Single-Blinded Trial

  • Anna Piwowarczyk
  • Andrea Horvath
  • Ewa Pisula
  • Rafał Kawa
  • Hania SzajewskaEmail author
Original Paper

Abstract

To determine whether a gluten-free diet (GFD) compared with a gluten-containing diet (GD) influences functioning of children with autism spectrum disorders (ASD), we performed a randomized, controlled, single-blinded trial. Sixty-six children (36–69 months) with ASD, within the normal IQ (> 70) range, who had been on a GFD for at least 8 weeks before enrollment were eligible for inclusion. After an 8-week run-in period on a GFD, the GFD group continued this diet and the GD group consumed at least one normal meal containing gluten per day for 6 months. There were no differences between groups in autistic symptoms, maladaptive behaviors, or intellectual abilities after the intervention. A GFD compared with a GD did not affect functioning of children with ASD.

Trial registration ClinicalTrials.gov, number NCT02280746.

Keywords

Randomized controlled trial Autism spectrum disorder Children Gluten 

Notes

Acknowledgments

We thank Monika Hodyra, Agata Misiak, Majka Niedzielska, for their help in conducting the assessments; Joanna Rachtan-Janicka for her help with the dietetic consultations, and all the families who participated in this study.

Author Contributions

AH and HS initially conceptualized this study. AH, AP, HS, and EP contributed to the study protocol. AP, AH, and RK conducted the study. AP and RK analyzed the data under the supervision of AH and EP. AP, AH, and HS wrote the first draft of the manuscript. All authors contributed to (and agreed upon) the final version. AH and HS are the guarantors for the data.

Funding

This work was supported by the Nutricia Foundation research Grant [RG8/2013]. The Foundation had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

Compliance with Ethical Standards

Conflict of interest

HS is a member of the Scientific Board of the Nutricia Foundation. HS and AH had academic-associated speaking engagements with Nutricia. AP had participated in the training sponsored by Nutricia. Other co-authors declare no conflicts of interest.

References

  1. Aldred, C., Green, J., & Adams, C. (2004). A new social communication intervention for children with autism: A pilot randomized controlled treatment study suggesting effectiveness. Journal of Child Psychology and Psychiatry, 45, 1420–1430.  https://doi.org/10.1111/j.1469-7610.2004.00848.x.CrossRefPubMedGoogle Scholar
  2. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Washington, DC: American Psychiatric Association.CrossRefGoogle Scholar
  3. Buie, T., Campbell, D. B., Fuchs, G. J., Furuta, G. T., Levy, J., Vandewater, J., et al. (2010). Evaluation, diagnosis and treatment of gastrointestinal disorders in individuals with ASDs: A consensus report. Pediatrics, 125(1), 1–18.  https://doi.org/10.1542/peds.2009-1878C.CrossRefGoogle Scholar
  4. Charman, T., Taylor, E., Drew, A., Cockerill, H., Brown, J. A., & Baird, G. (2005). Outcome at 7 years of children diagnosed with autism at age 2: Predictive validity of assessments conducted at 2 and 3 years of age and pattern of symptom change over time. Journal of Child Psychology and Psychiatry, 46, 500–513.  https://doi.org/10.1007/s10803-016-2745-1.CrossRefPubMedGoogle Scholar
  5. Christison, G. W., & Ivany, K. (2006). Elimination diets in autism spectrum disorders: Any wheat amidst the chaff? Journal of Developmental and Behavioral Pediatrics, 27(2), 162–171.CrossRefGoogle Scholar
  6. Drossman, D. A. (2006). The functional gastrointestinal disorders and the Rome III process. Gastroenterology, 30(5), 1377–1390.  https://doi.org/10.1053/j.gastro.2006.03.008.CrossRefGoogle Scholar
  7. Dupont, W. D., & Plummer, W. D. (1990). Power and sample size calculations: A review and computer program. Controlled Clinical Trials, 11, 116–128.CrossRefGoogle Scholar
  8. Elliott, C. (2018). The nutritional quality of gluten-free products for children. Pediatrics, 142(2), e20180525.  https://doi.org/10.1542/peds.2018-0525.CrossRefPubMedGoogle Scholar
  9. Fulceri, F., Morelli, M., Santocchi, E., Cena, H., Del Bianco, T., Narzisi, A., et al. (2016). Gastrointestinal symptoms and behavioral problems in preschoolers with Autism Spectrum Disorder. Digestive and Liver Disease, 48(3), 248–254.  https://doi.org/10.1016/j.dld.2015.11.026.CrossRefPubMedGoogle Scholar
  10. Ghalichi, F., Ghaemmaghami, J., Malek, A., & Ostadrahimi, A. (2016). Effect of gluten free diet on gastrointestinal and behavioral indices for children with autism spectrum disorders: A randomized clinical trial. World Journal of Pediatrics, 12(4), 436–442.  https://doi.org/10.1007/s12519-016-0040-z.CrossRefPubMedGoogle Scholar
  11. Gidrewicz, D. et al. (2019). Canadian Celiac Association Professional Advisory Council. The gluten challenge. https://www.celiac.ca/wp-content/uploads/2019/07/CCA-Gluten-Challenge-for-MDs-Final-2019.pdf. Accessed 26 Sept 2019.
  12. Goldstein, S., & Naglieri, J. A. (2009). Autism spectrum rating scales (ASRS). Tonawanda, NY: Multi-Health Systems.Google Scholar
  13. Horvath, K., Papadimitriou, J. C., Rabsztyn, A., Drachenberg, C., & Tildon, J. T. (1999). Gastrointestinal abnormalities in children with autism. The Journal of Pediatrics, 135, 559–563.CrossRefGoogle Scholar
  14. Husby, S., Koletzko, S., Korponay-Szabo, I. R., Mearin, M. L., Phillips, A., Shamir, R., et al. (2012). Guidelines for the diagnosis of coeliac disease. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. Journal of Pediatric Gastroenterology and Nutrition, 54, 136–160.CrossRefGoogle Scholar
  15. Israngkun, P. P., Newman, H. A., Patel, S. T., Duruibe, V. A., & Abou-Issa, H. (1986). Potential biochemical markers for infantile autism. Neurochemical Pathology, 5(1), 51–70.CrossRefGoogle Scholar
  16. Jyonoushi, H. (2010). Autism spectrum disorders and allergy: Observation from a pediatric allergy/immunology clinic. Expert Review of Clinical Immunology, 6(3), 397–411.  https://doi.org/10.1586/eci.10.18.CrossRefGoogle Scholar
  17. Kang, V., Wagner, G. C., & Ming, X. (2014). Gastrointestinal dysfunction in children with autism spectrum disorders. Autism Research, 7(4), 501–506.  https://doi.org/10.1002/aur.1386.CrossRefPubMedGoogle Scholar
  18. Klin, A. (2009). Subtyping the autism spectrum disorders: Theoretical, research, and clinical considerations. In S. Goldstein, J. A. Naglieri, & S. Ozonoff (Eds.), Assessment of autism spectrum disorders (pp. 91–116). New York: Guilford Press.Google Scholar
  19. Knivsberg, A. M., Reichelt, K. L., & Nødland, M. (1995). Autistic syndromes and diet: A follow-up study. Scandinavian Journal of Educational Research, 39, 223–236.  https://doi.org/10.1080/0031383950390304.CrossRefGoogle Scholar
  20. Leffler, D., Schuppan, D., Pallav, K., Najarian, R., Goldsmith, J. D., Hansen, J., et al. (2013). Kinetics of the histological, serological and symptomatic responses to gluten challenge in adults with celiac disease. Gut, 62(7), 996–1004.  https://doi.org/10.1136/gutjnl-2012-302196.CrossRefPubMedGoogle Scholar
  21. Leiter, R. G. (1980). International performance scale instruction manual. Chicago: Stoelting.Google Scholar
  22. Lord, C., Rutter, M., DiLavore, P., Risi, S., Gotham, K., & Bishop, S. (2012). Autism diagnostic observation schedule, second edition (ADOS-2) Manual (Part I): Modules 1–4. Torrance, CA: Western Psychological Services.Google Scholar
  23. Lord, C., Wagner, A., Rogers, S., Szatmari, P., Aman, M., Charman, T., et al. (2005). Challenges in evaluating psychosocial interventions for Autistic Spectrum Disorders. Journal of Autism and Developmental Disorders, 35, 695–708.  https://doi.org/10.1007/s10803-005-0017-6.CrossRefPubMedGoogle Scholar
  24. Matson, J. L., & Shoemaker, M. (2009). Intellectual disability and its relationship to autism spectrum disorders. Research in Developmental Disabilities, 30(6), 1107–1114.  https://doi.org/10.1016/j.ridd.2009.06.003.CrossRefPubMedGoogle Scholar
  25. McElhanon, B. O., McCracken, C., Karpen, S., & Sharp, W. G. (2014). Gastrointestinal symptoms in autism spectrum disorder: A meta-analysis. Pediatrics, 133(5), 872–883.  https://doi.org/10.1542/peds.2013-3995.CrossRefPubMedGoogle Scholar
  26. Myszkowska-Ryciak, J., Harton, A., & Gajewska, D. (2015). Analysis of nutritional value and costs of gluten-free diet compared to standard food ration. Medycyna Ogólna i Nauki o Zdrowiu, 21(3), 312–316.CrossRefGoogle Scholar
  27. National Institute for Health and Clinical Excellence (NICE). (2009). Coeliac disease: Recognition and assessment of coeliac disease. https://www.nice.org.uk/guidance/ng20. Accessed 21 June 2019.
  28. Piwowarczyk, A., Horvath, A., Łukasik, J., Pisula, E., & Szajewska, H. (2018). Gluten- and casein-free diet and autism spectrum disorders in children: A systematic review. European Journal of Nutrition, 57(2), 433–440.  https://doi.org/10.1007/s00394-017-1483-2.CrossRefPubMedGoogle Scholar
  29. Rubenstein, E., Schieve, L., Bradley, C., DiGuiseppi, C., Moody, E., Thomas, K., et al. (2018). The prevalence of gluten free diet use among preschool children with autism spectrum disorder. Autism Research, 11(1), 185–193.  https://doi.org/10.1002/aur.1896.CrossRefPubMedGoogle Scholar
  30. Rutter, M., Bailey, A., & Lord, C. (2003). The social communication questionnaire manual. Los Angeles, CA: Western Psychological Services.Google Scholar
  31. Shattock, P., & Whiteley, P. (2002). Biochemical aspects in autism spectrum disorders: Updating the opioid-excess theory and presenting new opportunities for biomedical intervention. Expert Opinion on Therapeutic Targets, 6(2), 17583.  https://doi.org/10.1517/14728222.6.2.175.CrossRefGoogle Scholar
  32. Sparrow, S. S., Cicchetti, D., & Balla, D. A. (2005). Vineland adaptive behavior scales-2nd edition manual. Minneapolis: NCS Pearson Inc.Google Scholar
  33. Whiteley, P., Haracopos, D., Knivsberg, A. M., Reichelt, K. L., Parlar, S., Jacobsen, J., et al. (2010). The ScanBrit randomised, controlled, singleblind study of a gluten- and casein-free dietary intervention for children with autism spectrum disorders. Nutritional Neuroscience, 13(2), 87–100.  https://doi.org/10.1179/147683010X12611460763922.CrossRefPubMedGoogle Scholar
  34. Whiteley, P., Rodgers, J., Savery, D., & Shattock, P. (1999). A gluten-free diet as an intervention for autism and associated spectrum disorders: Preliminary findings. Autism, 3, 45–65.  https://doi.org/10.1177/1362361399003001005.CrossRefGoogle Scholar
  35. WHO Multicentre Growth. (2006). Reference Study Group. Child Growth Standards: Length/height-for-age, Weight-for-age, Weight-for-length, Weight-for-height and Body mass index-for-age: Methods and Development. Geneva.Google Scholar
  36. Winburn, E., Charlton, J., McConachie, H., McColl, E., Parr, J., O'Hare, A., et al. (2014). Parents' and child health professionals' attitudes towardsdietary interventions for children with autism spectrum disorders. Journal of Autism and Developmental Disorders, 44(4), 747–757.CrossRefGoogle Scholar
  37. World Health Organization. (1995). Physical status: The use and interpretation of anthropometry. Report of a WHO Expert Committee. Technical Report Series, 854, 1–452.Google Scholar

Copyright information

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

Authors and Affiliations

  • Anna Piwowarczyk
    • 1
  • Andrea Horvath
    • 2
  • Ewa Pisula
    • 3
  • Rafał Kawa
    • 3
  • Hania Szajewska
    • 2
    Email author
  1. 1.Department of Paediatrics with Clinical Assessment UnitThe Medical University of WarsawWarsawPoland
  2. 2.Department of PaediatricsThe Medical University of WarsawWarsawPoland
  3. 3.Department of Health and Rehabilitation Psychology, Faculty of PsychologyUniversity of WarsawWarsawPoland

Personalised recommendations