EFFECTIVENESS OF THE KETOGENIC DIET IN TREATING SYMPTOMS OF AUTISM SPECTRUM DISORDER – A SYSTEMATIC REVIEW
Abstract
Introduction: Autism spectrum disorder is a multifactorial condition characterised by challenges in interpersonal engagement, communication deficits and distinct behavioural patterns that deviate from typical developmental norms. While this condition is estimated to affect about 1 in 100 children worldwide, its treatment options are still limited. The purpose of this systematic review is to determine the potential of ketogenic diet - high-fat, low-carbohydrate regimen valued primarily for anticonvulsant qualities - in alleviating autism spectrum disorder clinical signs.
Materials and methods: An extensive review of the literature was performed focusing on publications published since 2017.
Results: Evidence suggests that the ketogenic diet influences metabolic activity of cells, display anti-inflammatory benefits, alter gut microbiota composition, positively influence mitochondrial activity and modulate brain function and behavioural phenotypes via epigenetic pathways. Therefore, ketogenic diet has emerged as a potentially effective therapeutic option in ameliorating ASD symptoms. Additionally, combining ketogenic diet with other therapeutic diets and their beneficial effects seems reasonable and justifiable.
Conclusions: While these initial findings appear encouraging, extended research on larger and more diverse populations is required. Current evidence on the efficacy of ketogenic diet in treating symptoms of autism spectrum disorder is limited by variable study designs, small sample sizes, and frequently suboptimal adherence.
References
Alibrandi, A., Zirilli, A., Loschiavo, F., Gangemi, M. C., Sindoni, A., Tribulato, G., Lo Giudice, R., & Famà, F. (2023). Food Selectivity in Children with Autism Spectrum Disorder: A Statistical Analysis in Southern Italy. Children, 10(9), 1553. https://doi.org/10.3390/children10091553
Allan, N. P., Yamamoto, B. Y., Kunihiro, B. P., Nunokawa, C. K. L., Rubas, N. C., Wells, R. K., Umeda, L., Phankitnirundorn, K., Torres, A., Peres, R., Takahashi, E., & Maunakea, A. K. (2024). Ketogenic Diet Induced Shifts in the Gut Microbiome Associate with Changes to Inflammatory Cytokines and Brain-Related miRNAs in Children with Autism Spectrum Disorder. Nutrients, 16(10), 1401. https://doi.org/10.3390/nu16101401
Amin, S., Mohammad Mostafa Alkherkhisy, & Rania Elsayed Kasem. (2024). Assessment of brain-derived neurotrophic factor levels in serum of children with autism spectrum disorders. Middle East Current Psychiatry, 31(1). https://doi.org/10.1186/s43045-024-00403-y
Caradonna, E., Abate, F., Schiano, E., Paparella, F., Ferrara, F., Vanoli, E., Difruscolo, R., Goffredo, V. M., Amato, B., Setacci, C., Setacci, F., & Novellino, E. (2025). Trimethylamine-N-Oxide (TMAO) as a Rising-Star Metabolite: Implications for Human Health. Metabolites, 15(4), 220–220. https://doi.org/10.3390/metabo15040220
Castro, K., Baronio, D., Perry, I. S., Riesgo, R. dos S., & Gottfried, C. (2016). The effect of ketogenic diet in an animal model of autism induced by prenatal exposure to valproic acid. Nutritional Neuroscience, 20(6), 343–350. https://doi.org/10.1080/1028415x.2015.1133029
Chen, J., & Vitetta, L. (2020). The Role of Butyrate in Attenuating Pathobiont-Induced Hyperinflammation. Immune Network, 20(2). https://doi.org/10.4110/in.2020.20.e15
Chen, W.-J., Chen, Y.-T., Ko, J.-L., Chen, J.-Y., Zheng, J.-Y., Liao, J.-W., & Ou, C.-C. (2024). Butyrate modulates gut microbiota and anti-inflammatory response in attenuating cisplatin-induced kidney injury. Biomedicine & Pharmacotherapy, 181, 117689. https://doi.org/10.1016/j.biopha.2024.117689
Dhanasekara, C. S., Ancona, D., Cortes, L., Hu, A., Rimu, A. H., Robohm-Leavitt, C., Payne, D., Wakefield, S. M., Mastergeorge, A. M., & Kahathuduwa, C. N. (2023). Association Between Autism Spectrum Disorders and Cardiometabolic Diseases: A Systematic Review and Meta-analysis. JAMA Pediatrics, 177(3), 248–257. https://doi.org/10.1001/jamapediatrics.2022.5629
Drabińska, N. (2024). Current Perspective About the Effect of a Ketogenic Diet on Oxidative Stress – a Review. Polish Journal of Food and Nutrition Sciences, 92–105. https://doi.org/10.31883/pjfns/185366
El-Rashidy, O., El-Baz, F., El-Gendy, Y., Khalaf, R., Reda, D., & Saad, K. (2017). Ketogenic diet versus gluten free casein free diet in autistic children: a case-control study. Metabolic Brain Disease, 32(6), 1935–1941. https://doi.org/10.1007/s11011-017-0088-z
Esposito, C. M., Buoli, M., Ciappolino, V., Agostoni, C., & Brambilla, P. (2021). The Role of Cholesterol and Fatty Acids in the Etiology and Diagnosis of Autism Spectrum Disorders. International Journal of Molecular Sciences, 22(7), 3550. https://doi.org/10.3390/ijms22073550
Esposito, M., Mirizzi, P., Fadda, R., Pirollo, C., Ricciardi, O., Mazza, M., & Valenti, M. (2023). Food Selectivity in Children with Autism: Guidelines for Assessment and Clinical Interventions. International Journal of Environmental Research and Public Health, 20(6), 5092. https://doi.org/10.3390/ijerph20065092
Estes, M. L., & McAllister, A. K. (2015). Immune mediators in the brain and peripheral tissues in autism spectrum disorder. Nature Reviews. Neuroscience, 16(8), 469–486. https://doi.org/10.1038/nrn3978
Frye, R. E. (2020). Mitochondrial Dysfunction in Autism Spectrum Disorder: Unique Abnormalities and Targeted Treatments. Seminars in Pediatric Neurology, 35, 100829. https://doi.org/10.1016/j.spen.2020.100829
Guo, C., Sun, L., Chen, X., & Zhang, D. (2013). Oxidative stress, mitochondrial damage and neurodegenerative diseases. Neural Regeneration Research, 8(21), 2003–2014. https://doi.org/10.3969/j.issn.1673-5374.2013.21.009
Jobski, K., Höfer, J., Hoffmann, F., & Bachmann, C. (2016). Use of psychotropic drugs in patients with autism spectrum disorders: a systematic review. Acta Psychiatrica Scandinavica, 135(1), 8–28. https://doi.org/10.1111/acps.12644
Khaliulin I;Hamoudi W;Amal H. (2024). The multifaceted role of mitochondria in autism spectrum disorder. Molecular Psychiatry. https://doi.org/10.1038/s41380-024-02725-z
Korner, M., Kälin, S., Zweifel-Zehnder, A., Fankhauser, N., Nuoffer, J.-M., & Gautschi, M. (2019). Deficits of facial emotion recognition and visual information processing in adult patients with classical galactosemia. Orphanet Journal of Rare Diseases, 14(1). https://doi.org/10.1186/s13023-019-0999-3
Kurochkin, I., Khrameeva, E., Tkachev, A., Stepanova, V., Vanyushkina, A., Stekolshchikova, E., Li, Q., Zubkov, D., Shichkova, P., Halene, T., Willmitzer, L., Giavalisco, P., Akbarian, S., & Khaitovich, P. (2019). Metabolome signature of autism in the human prefrontal cortex. Communications Biology, 2(1). https://doi.org/10.1038/s42003-019-0485-4
Lee, R. W. Y., Corley, M. J., Pang, A., Arakaki, G., Abbott, L., Nishimoto, M., Miyamoto, R., Lee, E., Yamamoto, S., Maunakea, A. K., Lum-Jones, A., & Wong, M. (2018). A modified ketogenic gluten-free diet with MCT improves behavior in children with autism spectrum disorder. Physiology & Behavior, 188, 205–211. https://doi.org/10.1016/j.physbeh.2018.02.006
Lombardi, C., Berti, A., & Cottini, M. (2022). The emerging roles of eosinophils: Implications for the targeted treatment of eosinophilic-associated inflammatory conditions. Current Research in Immunology, 3, 42–53. https://doi.org/10.1016/j.crimmu.2022.03.002
Loomes, R., Hull, L., & Mandy, W. P. L. (2017). What Is the Male-to-Female Ratio in Autism Spectrum Disorder? a Systematic Review and Meta-Analysis. Journal of the American Academy of Child & Adolescent Psychiatry, 56(6), 466–474. https://doi.org/10.1016/j.jaac.2017.03.013
Masood, W., Uppaluri, K. R., Annamaraju, P., & Khan Suheb, M. Z. (2023). Ketogenic diet. National Library of Medicine; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK499830/
Matthews, J. S., & Adams, J. B. (2023). Ratings of the Effectiveness of 13 Therapeutic Diets for Autism Spectrum Disorder: Results of a National Survey. Journal of Personalized Medicine, 13(10), 1448–1448. https://doi.org/10.3390/jpm13101448
Monda, A., Ester, M., Messina, A., Maio, G. D., Monda, V., Moscatelli, F., Stefano, M. D., Marra, M. L., Padova, M. D., Dipace, A., Limone, P., Casillo, M., Monda, M., Messina, G., & Polito, R. (2024). Exploring the ketogenic diet’s potential in reducing neuroinflammation and modulating immune responses. Frontiers in Immunology, 15. https://doi.org/10.3389/fimmu.2024.1425816
Morton, J. T., Jin, D.-M., Mills, R. H., Shao, Y., Rahman, G., McDonald, D., Zhu, Q., Balaban, M., Jiang, Y., Cantrell, K., Gonzalez, A., Carmel, J., Linoy Mia Frankiensztajn, Martin-Brevet, S., Berding, K., Needham, B. D., María Fernanda Zurita, David, M. M., Averina, O. V., & Kovtun, A. S. (2023). Multi-level analysis of the gut–brain axis shows autism spectrum disorder-associated molecular and microbial profiles. Nature Neuroscience, 26(7), 1208–1217. https://doi.org/10.1038/s41593-023-01361-0
Mosner, M. G., Kinard, J. L., Shah, J. S., McWeeny, S., Greene, R. K., Lowery, S. C., Mazefsky, C. A., & Dichter, G. S. (2019). Rates of Co-occurring Psychiatric Disorders in Autism Spectrum Disorder Using the Mini International Neuropsychiatric Interview. Journal of Autism and Developmental Disorders, 49(9), 3819–3832. https://doi.org/10.1007/s10803-019-04090-1
Mu, C., Corley, M. J., Lee, R. W. Y., Wong, M., Pang, A., Arakaki, G., Miyamoto, R., Rho, J. M., Mickiewicz, B., Dowlatabadi, R., Vogel, H. J., Korchemagin, Y., & Shearer, J. (2019). Metabolic Framework for the Improvement of Autism Spectrum Disorders by a Modified Ketogenic Diet: A Pilot Study. Journal of Proteome Research, 19(1), 382–390. https://doi.org/10.1021/acs.jproteome.9b00581
Newell, C., Bomhof, M. R., Reimer, R. A., Hittel, D. S., Rho, J. M., & Shearer, J. (2016). Ketogenic diet modifies the gut microbiota in a murine model of autism spectrum disorder. Molecular Autism, 7(1). https://doi.org/10.1186/s13229-016-0099-3
Patil, O., & Kaple, M. (2023). Sensory processing differences in individuals with autism spectrum disorder: A narrative review of underlying mechanisms and sensory-based interventions. Cureus, 15(10). https://doi.org/10.7759/cureus.48020
Pizzo, F., Collotta, A. D., Di Nora, A., Costanza, G., Ruggieri, M., & Falsaperla, R. (2022). Ketogenic diet in pediatric seizures: a randomized controlled trial review and meta-analysis. Expert Review of Neurotherapeutics, 22(2), 169–177. https://doi.org/10.1080/14737175.2022.2030220
Ristori, M. V., Quagliariello, A., Reddel, S., Ianiro, G., Vicari, S., Gasbarrini, A., & Putignani, L. (2019). Autism, Gastrointestinal Symptoms and Modulation of Gut Microbiota by Nutritional Interventions. Nutrients, 11(11), 2812. https://doi.org/10.3390/nu11112812
Robinson-Agramonte, M. de los A., Noris García, E., Fraga Guerra, J., Vega Hurtado, Y., Antonucci, N., Semprún-Hernández, N., Schultz, S., & Siniscalco, D. (2022). Immune Dysregulation in Autism Spectrum Disorder: What Do We Know about It? International Journal of Molecular Sciences, 23(6), 3033. https://doi.org/10.3390/ijms23063033
Ruskin, D. N., Murphy, M. I., Slade, S. L., & Masino, S. A. (2017). Ketogenic diet improves behaviors in a maternal immune activation model of autism spectrum disorder. PLOS ONE, 12(2), e0171643. https://doi.org/10.1371/journal.pone.0171643
Ruskin, D. N., Svedova, J., Cote, J. L., Sandau, U., Rho, J. M., Kawamura, M., Boison, D., & Masino, S. A. (2013). Ketogenic Diet Improves Core Symptoms of Autism in BTBR Mice. PLoS ONE, 8(6), e65021. https://doi.org/10.1371/journal.pone.0065021
Schuck, R. K., Flores, R. E., & Fung, L. K. (2019). Brief Report: Sex/Gender Differences in Symptomology and Camouflaging in Adults with Autism Spectrum Disorder. Journal of Autism and Developmental Disorders, 49(6), 2597–2604. https://doi.org/10.1007/s10803-019-03998-y
Siddiqui, M. F., Elwell, C., & Johnson, M. H. (2016). Mitochondrial Dysfunction in Autism Spectrum Disorders. Autism-Open Access, 6(4). https://doi.org/10.4172/2165-7890.1000190
Siniscalco, D., Schultz, S., Brigida, A., & Antonucci, N. (2018). Inflammation and Neuro-Immune Dysregulations in Autism Spectrum Disorders. Pharmaceuticals, 11(2), 56. https://doi.org/10.3390/ph11020056
Welsink-Karssies, M. M., Oostrom, K. J., Hermans, M. E., Hollak, C. E. M., Janssen, M. C. H., Langendonk, J. G., Oussoren, E., Gozalbo, M. E. R., de Vries, M., Geurtsen, G. J., & Bosch, A. M. (2020). Classical galactosemia: neuropsychological and psychosocial functioning beyond intellectual abilities. Orphanet Journal of Rare Diseases, 15(1). https://doi.org/10.1186/s13023-019-1277-0
Williams, B. L., Hornig, M., Buie, T., Bauman, M. L., Cho Paik, M., Wick, I., Bennett, A., Jabado, O., Hirschberg, D. L., & Lipkin, W. I. (2011). Impaired Carbohydrate Digestion and Transport and Mucosal Dysbiosis in the Intestines of Children with Autism and Gastrointestinal Disturbances. PLoS ONE, 6(9), e24585. https://doi.org/10.1371/journal.pone.0024585
Won, H., Mah, W., & Kim, E. (2013). Autism spectrum disorder causes, mechanisms, and treatments: focus on neuronal synapses. Frontiers in Molecular Neuroscience, 6. https://doi.org/10.3389/fnmol.2013.00019
Wood-Downie, H., Wong, B., Kovshoff, H., Mandy, W., Hull, L., & Hadwin, J. A. (2020). Sex/Gender Differences in Camouflaging in Children and Adolescents with Autism. Journal of Autism and Developmental Disorders, 51(4). https://doi.org/10.1007/s10803-020-04615-z
Zarakoviti, E., Shafran, R., Skuse, D., McTague, A., Batura, N., Palmer, T., Dalrymple, E., Bennett, S. D., & Reilly, C. (2022). Factor associated with the occurrence of epilepsy in autism: a systematic review. Journal of Autism and Developmental Disorders, 53(10). https://doi.org/10.1007/s10803-022-05672-2
Zeidan, J., Fombonne, E., Scorah, J., Ibrahim, A., Durkin, M. S., Saxena, S., Yusuf, A., Shih, A., & Elsabbagh, M. (2022). Global Prevalence of autism: a Systematic Review Update. Autism Research, 15(5), 778–790. https://doi.org/10.1002/aur.2696
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