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Evidence of the Gluten-Free and Casein-Free Diet in Autism Spectrum Disorders: A Systematic Review
Open accessAbstract
In autism spectrum disorders, many parents resort to alternative treatments and these are generally perceived as risk free. Among these, the most commonly used is the gluten-free, casein-free diet. The objective of this work was to conduct a systematic review of studies published from 1970 to date related to the gluten-free, casein-free diet in autism spectrum disorder patients. Few studies can be regarded as providing sound scientific evidence since they were blinded randomized controlled trials, and even these were based on small sample sizes, reducing their validity. We observed that the evidence on this topic is currently limited and weak. We recommend that it should be only used after the diagnosis of an intolerance or allergy to foods containing the allergens excluded in gluten-free, casein-free diets. Future research should be based on this type of design, but with larger sample sizes.
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“while other studies highlighted that the adoption of this elimination diet could decrease fiber intake [103], thus probably aggravating the GI problems.”
From Autism, Gastrointestinal Symptoms and Modulation of Gut Microbiota by Nutritional Interventions (2019) · cites this paper as [103]
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Ristori, M. V., Quagliariello, A., Reddel, S., Ianiro, G., Vicari, S., Gasbarrini, A., & Putignani, L. (2019) · Nutrients · doi:10.3390/nu11112812 · Cited by 214
Metabolic syndrome in patients with coeliac disease on a gluten‐free diet
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“In particular, it has been proposed as an affective dietary approach to noncoeliac gluten sensitivity,(50) irritable bowel syndrome,(51) inflammatory bowel diseases(52) and several other conditions.(53) The findings from our study have relevance for 100”
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McClafferty, H. H., Vohra, S., Bailey, M. L., Brown, M. L., Esparham, A. E., Gerstbacher, D., Golianu, B. J., Niemi, A., Sibinga, E. M. S., Weydert, J. A., et al. (2017) · PEDIATRICS · doi:10.1542/peds.2017-1961 · Cited by 155
Ghalichi, F., Ghaemmaghami, J., Malek, A., & Ostadrahimi, A. (2016) · World Journal of Pediatrics · doi:10.1007/s12519-016-0040-z · Cited by 150
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“A gluten-free and casein-free (GFCF) diet is considered as one of the effective food-based alternative treatments for ASD since the peptides derived from gluten and casein can trigger inflammation [99,100].”
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“In particular, a gluten-free and/or casein-free diet might be recommended to combat leaky gut and intestinal inflammation, and although some studies suggest behavioral improvements following the diet, the scientific evidence regarding the effectiveness of this alternative treatment is still very limited [87,88].”
μ opioid receptor, social behaviour and autism spectrum disorder: reward matters
Pellissier, L. P., Gandía, J., Laboute, T., Becker, J. A. J., & Merrer, J. L. (2017) · British Journal of Pharmacology · doi:10.1111/bph.13808 · Cited by 115
“In further questioning of the excessive opioid theory, reviews and meta-analyses have examined clinical evidence for the efficacy of dietary intervention in autism and found a lack of consistent effects (Dosman et al., 2013; Mari-Bauset et al., 2014; Lange et al., 2015).”
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Diet: the keystone of autism spectrum disorder?
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Lange, K. W., Hauser, J., & Reißmann, A. (2015) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000000228 · Cited by 100
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Dietary Interventions for Autism Spectrum Disorder: A Meta-analysis
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Marí-Bauset, S., Llopis-González, A., Zazpe, I., Marí-Sanchis, A., & Suárez-Varela, M. M. (2016) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-015-2582-7 · Cited by 75
“Research to date has not confirmed the effectiveness of the GFCF diet but the evidence available remains limited and weak (Marı́-Bauset et al. 2014).”
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“In a systematic review, elimination diets were recommended only when there was intolerance or sensitivity to food containing gluten or casein [47].”
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“A GFCF diet should be implemented only with the help of a registered dietitian, and only for individuals who have sensitivities or allergies to the foods that are being eliminated.(19)”
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“People with ASD, on the other hand, have higher intestinal permeability to such compounds, resulting in inflammation [48–52].”
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“Another study reports results from even shorter time periods; indeed, meta-reviews (Dosman et al., 2013; Marí-Bauset et al., 2014; Millward et al., 2008; Mulloy et al., 2010; Sathe et al., 2017; Whiteley et al., 2010b) point to this as one of the main limitations for this type of studies.”
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“Nevertheless, a placebo design and monitoring concomitant treatments are absent, determining a lack of scientific robustness and the chance of being a recommendation in the field [48].”
BackgroundA Scoping Literature Review of the Relation between Nutrition and ASD Symptoms in Children
van der Wurff, I. S. M., Oenema, A., de Ruijter, D., Vingerhoets, C., van Amelsvoort, T., Rutten, B. P. F., Mulkens, S., Köhler, S., Schols, A. M. W. J., & de Groot, R. H. M. (2022) · Nutrients · doi:10.3390/nu14071389 · Cited by 11
Ha, V. S., & Whittaker, A. M. (2022) · Disability and Rehabilitation · doi:10.1080/09638288.2022.2040613 · Cited by 10
Dietary and Micronutrient Treatments for Children with Neurodevelopment Disorders
Taylor, M. R., Chuang, C.-C., Carrasco, K., Nagatomo, S., & Rucklidge, J. J. (2018) · Current Developmental Disorders Reports · doi:10.1007/s40474-018-0150-5 · Cited by 11
“Existing treatments for these conditions include medication and behavioral treatments [3]; however, many families choose to explore dietary treatments for neurobehavioral disorders [4].”
BackgroundShi, A., Liu, D., Wu, H., Zhu, R., Deng, Y., Yao, L., Xiao, Y., Lorimer, G. H., Ghiladi, R. A., Xu, X., et al. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.116191 · Cited by 9
Parents’ assessments of their child’s autism-related interventions
Shepherd, D., Landon, J., Goedeke, S., Ty, K., & Csákó, R. I. (2018) · Research in Autism · doi:10.1016/j.rasd.2018.02.005 · Cited by 9
Abirami, G. P. P., Radhakrishnan, R. K., Johnson, E., Roshan, S. A., Yesudhas, A., Parveen, S., Biswas, A., Ravichandran, V. R., Anusuyadevi, M., & Kandasamy, M. (2020) · Advances in neurobiology · doi:10.1007/978-3-030-30402-7_8 · Cited by 8
Gastrointestinal Issues in Infants and Children with Autism and Developmental Delays
Jiang, X., Matson, J. L., Cervantes, P. E., Matheis, M., & Burns, C. O. (2017) · Journal of Developmental and Physical Disabilities · doi:10.1007/s10882-017-9532-6 · Cited by 9
Glutensiz diyet; gerçekten her zaman yararlı mı?
Kutlu, T. (2019) · Türk Pediatri Arşivi · doi:10.14744/turkpediatriars.2019.82609 · Cited by 8
“When 24 articles published on this subject since 1970 were examined, however, a low level of scientific evidence could be observed in only 4 articles (21).”
BackgroundActon, R. K., Imberman, S. A., & Lovenheim, M. (2021) · Journal of Health Economics · doi:10.1016/j.jhealeco.2021.102489 · Cited by 6
The opioid excess theory in autism spectrum disorders - is it worth investigating further?
Tarnowska, K., Gruczyńska–Sękowska, E., Kowalska, D., Majewska, E., Kozłowska, M., & Winkler, R. (2021) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2021.1996329 · Cited by 9
Cravero, C., Guinchat, V., Claret, A., Sahnoun, C., Bonniau, B., Bodeau, N., Danion-Grilliat, A., Cohen, D., & Chamak, B. (2017) · Neuropsychiatrie de l Enfance et de l Adolescence · doi:10.1016/j.neurenf.2016.10.002 · Cited by 6
Diet, Microbiome, and Neuropsychiatric Disorders
Javitt, G. A., & Javitt, D. C. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-811440-7.00013-2 · Cited by 6
History of Non-Evidence-Based Practices for Individuals Diagnosed with ASD
Kryszak, E. M., & Mulick, J. A. (2022) · Autism and child psychopathology series · doi:10.1007/978-3-030-96478-8_3 · Cited by 5
Barnhart, G. (2017) · Journal of Neurology and Neurological Disorders · doi:10.15744/2454-4981.3.106 · Cited by 5
Dehghani, E., Karimi, K., Arekhi, S., Ardeshir, M., Rezapour, R., Shayestehfar, M., & Memari, A. H. (2025) · BMC Nutrition · doi:10.1186/s40795-025-01043-z · Cited by 5
The Relationship of Autism Spectrum Disorders and Celiac Disease and Gluten-free Diet
Szaflarska‐Popławska, A. (2016) · International Journal of Celiac Disease · doi:10.12691/ijcd-3-4-1 · Cited by 4
“Moreover, the affinity of exogenous opioids to opioid receptors is low, and in food products there are also peptides of antagonistic action to these receptors [2].”
BackgroundMethodInfluentialAutism Spectrum Disorders and Gluten/Casein Free Diet Treatment: A Systematic Review (1990-2016)
Çöpür, M., & Çöpür, S. (2017) · International Journal Of Nutrition · doi:10.14302/issn.2379-7835.ijn-17-1710 · Cited by 4
“…Hurwitz et al, 2013 39 1 Systematic review Journal of Early Intervention Herbert and Buckley, 2013 40 6 1 The Journal of Child Neurology Mar ı ´-Bauset et al, 2014 41 1 Systematic review Journal of Child Neurology Elder et al, 2015 42 1 Systematic review Nutrition and Dietary Supplements…”
Harrington, J. W., & Bora, S. (2017) · Elsevier eBooks · doi:10.1016/b978-0-323-35868-2.00008-6 · Cited by 4
Bicer, A. H., & Alsaffar, A. A. (2016) · Integrative Food Nutrition and Metabolism · doi:10.15761/ifnm.1000135 · Cited by 4
“Although adopted by many families, systematic reviews of GFCF diets could not support the use of such diets in the treatment of ASD [50,51].”
BackgroundAngelopoulou, M., Siaperas, P., Livadas, S., Karantana, E., Papadimitriou, D. T., & Angelopoulos, N. (2025) · Neuroscience · doi:10.1016/j.neuroscience.2025.09.009 · Cited by 4
Autismo: aspectos nutrológicos das dietas e possível etiologia
Anderle, T., & de Mello, E. D. (2018) · International Journal of Nutrology · doi:10.1055/s-0038-1670668 · Cited by 4
Comorbidity and the Need for Interdisciplinary Treatments
Matson, J., & Burns, C. (2019) · Handbook of Interdisciplinary Treatments for Autism Spectrum Disorder · doi:10.1007/978-3-030-13027-5_3 · Cited by 3
Long, M., & Register‐Brown, K. (2021) · Pediatrics in Review · doi:10.1542/pir.2020-000547 · Cited by 4
Pei, J., Wei, S., Pei, Y., Wu, H., & Wang, D. (2019) · Current Medicinal Chemistry · doi:10.2174/0929867326666190409120716 · Cited by 3
Substantiated and Unsubstantiated Interventions for Individuals with ASD
Kodak, T. M., & Carroll, R. A. (2017) · Autism and child psychopathology series · doi:10.1007/978-3-319-61738-1_2 · Cited by 3
The cost of being gluten-free: a hedonic pricing analysis of food products for celiac patients
Soler, L., & Borzykowski, N. (2025) · Health Economics Review · doi:10.1186/s13561-025-00677-w · Cited by 2
Differential Hallmarks of Celiac Versus Non-Celiac Gluten Sensitivity
Mohan, M., & Sestak, K. (2017) · InTech eBooks · doi:10.5772/67545 · Cited by 2
Gluten-free diet among school-age children in Olmsted County, Minnesota
Almallouhi, E., & Absah, I. (2017) · Avicenna Journal of Medicine · doi:10.4103/ajm.ajm_42_17 · Cited by 2
“Despite the lack of strong medical evidence to support GFD in children with autism spectrum disorders, many families elect to eliminate gluten because of autism or behavioral concerns.[16,17]”
BackgroundAutism in Children Connected with Gastrointestinal Symptoms
Walecki, P. K., Kawala‐Sterniuk, A., & Siwek, J. (2018) · IntechOpen eBooks · doi:10.5772/intechopen.79863 · Cited by 2
“Many studies on the GFCF diet focus on the safety of the intervention [31].”
BackgroundInfluentialSiddiqi, S., & Urooj, A. (2021) · Research in Autism · doi:10.1016/j.rasd.2021.101885 · Cited by 2
Gluten: do only celiac patients benefit from its removal from the diet?
Franckilin, L. R. D. S., dos Santos, A. C. P. M., Freitas, F. E. D. A., Vieira, I. G., Jorge, C. E. D. F., Neri, D. G., de Abreu, M. V. C., Fonseca, J. K., Loffi, R. G., & Foureaux, G. (2022) · Food Reviews International · doi:10.1080/87559129.2021.2024566 · Cited by 3
Sanchez, K. A. S., Ledesma, V. B., Sepúlveda, G., et al. (2018) · RESPYN Revista de Salud Pública y Nutrición · doi:10.29105/respyn17.4-3 · Cited by 2
A Qualitative Assessment Of Eating Behaviors In Adults With Autism
Barbier, S. (2015) · ISU Red - Research and eData (Illinois State University) · doi:10.30707/etd2015.barbier.s · Cited by 2
Metadata
- Authors
- Marí-Bauset, S., Zazpe, I., Mari-Sanchis, A., Llopis-González, A., & Morales-Suárez-Varela, M.
- Affiliations
- Universitat de València (ES)
- Department of Nutrition and Food Sciences and Physiology, University of Navarra, Navarra, Spain
- Clinical Nutrition and Dietetics Unit, Navarra Hospital Complex, Navarra, Spain
- Unit of Public Health and Environmental Care, Department of Preventive Medicine, University of Valencia, Valencia, Spain
- Venue
- Journal of Child Neurology
- Publisher
- SAGE Publications
- Published
- 2014-04-30
- Volume
- 29
- Issue
- 12
- Pages
- 1718-1727
- ISSN
- 0883-0738 (ISSN-L)
- 1708-8283
- OpenAlex
- W2011447176
- Semantic Scholar
- 1d7091aa87f7bd44dce0d3436ece1b2ebd569bc0
- Cited by
- 136
- References
- 67
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 8 · 2023: 4 · 2022: 10 · 2021: 17 · 2020: 11 · 2019: 12 · 2018: 15 · 2017: 18 · 2016: 9 · 2015: 12 · 2014: 8
- FWCI
- 11.96
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Locations
- Journal of Child Neurology (publishedVersion)
- PubMed (publishedVersion)
- Deposito Adademico Digital Universidad De Navarra (University of Navarra) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Child Nutrition and Feeding Issues
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Social Sciences › Psychology › Developmental and Educational Psychology › Behavioral and Psychological Studies
- Keywords
- gluten-free diet, casein-free diet, autism spectrum disorder, dietary intervention, food intolerance, food allergy, alternative treatment, quality of evidence
- MeSH terms
- Caseins, Child Development Disorders, Pervasive, Diet Therapy, Humans, Diet, Gluten-Free
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