World Journal of Pediatrics

, Volume 14, Issue 3, pp 215–223 | Cite as

Are therapeutic diets an emerging additional choice in autism spectrum disorder management?

  • M. GogouEmail author
  • G. Kolios
Review Article



A nutritional background has been recognized in the pathophysiology of autism and a series of nutritional interventions have been considered as complementary therapeutic options. As available treatments and interventions are not effective in all individuals, new therapies could broaden management options for these patients. Our aim is to provide current literature data about the effect of therapeutic diets on autism spectrum disorder.

Data source

A systematic review was conducted by two reviewers independently. Prospective clinical and preclinical studies were considered.


Therapeutic diets that have been used in children with autism include ketogenic and gluten/casein-free diet. We were able to identify 8 studies conducted in animal models of autism demonstrating a beneficial effect on neurophysiological and clinical parameters. Only 1 clinical study was found showing improvement in childhood autism rating scale after implementation of ketogenic diet. With regard to gluten/casein-free diet, 4 clinical studies were totally found with 2 of them showing a favorable outcome in children with autism. Furthermore, a combination of gluten-free and modified ketogenic diet in a study had a positive effect on social affect scores. No serious adverse events have been reported.


Despite encouraging laboratory data, there is controversy about the real clinical effect of therapeutic diets in patients with autism. More research is needed to provide sounder scientific evidence.


Autism Children Gluten/casein-free diet Ketogenic diet Therapeutic diet 


Author contributions

MG collected and analyzed data and wrote the manuscript. GK designed the study, collected and analyzed data and supervised the drafting of the manuscript.


No financial or non-financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article.

Compliance with ethical standards

Ethical approval

Not needed.

Conflicts of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Modabbernia A, Velthorst E, Reichenberg A. Environmental risk factors for autism: an evidence-based review of systematic reviews and meta-analyses. Mol Autism. 2017;8:13.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Moody L, Chen H, Pan YX. Early-life nutritional programming of cognition-the fundamental role of epigenetic mechanisms in mediating the relation between early-life environment and learning and memory process. Adv Nutr. 2017;8:337–50.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    van De Sande MM, van Buul VJ, Brouns FJ. Autism and nutrition: the role of the gut-brain axis. Nutr Res Rev. 2014;27:199–214.CrossRefGoogle Scholar
  4. 4.
    Dovrolis N, Kolios G, Spyrou GM, Maroulakou I. Computational profiling of the gut-brain axis: microflora dysbiosis insights to neurological disorders. Brief Bioinform. 2017. Scholar
  5. 5.
    Israelyan N, Margolis KG. Serotonin as a link between the gut-brain-microbiome axis in autism spectrum disorders. Pharmacol Res. 2018;132:1–6.CrossRefPubMedGoogle Scholar
  6. 6.
    Yang Y, Tian J, Yang B. Targeting gut microbiome: a novel and potential therapy for autism. Life Sci. 2018;194:111–9.CrossRefPubMedGoogle Scholar
  7. 7.
    Ranjan S, Nasser JA. Nutritional status of individuals with autism spectrum disorders: do we know enough? Adv Nutr. 2015;6:397–407.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Wasilewska J, Klukowski M. Gastrointestinal symptoms and autism spectrum disorder: links and risks - a possible new overlap syndrome. Pediatric Health Med Ther. 2015;6:153–66.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Li YJ, Li YM, Xiang DX. Supplement intervention associated with nutritional deficiencies in autism spectrum disorders: a systematic review. Eur J Nutr. 2017. Scholar
  10. 10.
    Lange KW, Hauser J, Reissmann A. Gluten-free and casein-free diets in the therapy of autism. Curr Opin Clin Nutr Metab Care. 2015;18:572–5.CrossRefPubMedGoogle Scholar
  11. 11.
    Ly V, Bottelier M, Hoekstra PJ, Arias Vasquez A, Buitelaar JK, Rommelse NN. Elimination diets’ efficacy and mechanisms in attention deficit hyperactivity disorder and autism spectrum disorder. Eur Child Adolesc Psychiatry. 2017;26(9):1067–79.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Ułamek-Kozioł M, Pluta R, Bogucka-Kocka A, Czuczwar SJ. To treat or not to treat drug-refractory epilepsy by the ketogenic diet? That is the question. Ann Agric Environ Med. 2016;23:533–6.CrossRefPubMedGoogle Scholar
  13. 13.
    Branco AF, Ferreira A, Simões RF, Magalhães-Novais S, Zehowski C, Cope E, et al. Ketogenic diets: from cancer to mitochondrial diseases and beyond. Eur J Clin Invest. 2016;46:285–98.CrossRefPubMedGoogle Scholar
  14. 14.
    Hartman AL, Gasior M, Vining EP, Rogawski MA. The neuropharmacology of the ketogenic diet. Pediatr Neurol. 2007;36:281–92.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Erecinska M, Nelson D, Daikhin Y, Yudkoff M. Regulation of GABA level in rat brain synaptosomes: fluxes through enzymes of the GABA shunt and effects of glutamate, calcium, and ketone bodies. J Neurochem. 1996;67:2325–34.CrossRefPubMedGoogle Scholar
  16. 16.
    Daikhin Y, Yudkoff M. Ketone bodies and brain glutamate and GABA metabolism. Dev Neurosci. 1998;20:358–64.CrossRefPubMedGoogle Scholar
  17. 17.
    Verrotti A, Iapadre G, Pisano S, Coppola G. Ketogenic diet and childhood neurological disorders other than epilepsy: an overview. Expert Rev Neurother. 2017;17:461–73.CrossRefPubMedGoogle Scholar
  18. 18.
    Haznedar MM, Buchsbaum MS, Wei TC, Hof PR, Cartwright C, Bienstock CA, et al. Limbic circuitry in patients with autism spectrum disorders studied with positron emission tomography and magnetic resonance imaging. Am J Psychiatry. 2000;157:1994–2001.CrossRefPubMedGoogle Scholar
  19. 19.
    Purcell AE, Jeon OH, Zimmerman AW, Blue ME, Pevsner J. Postmortem brain abnormalities of the glutamate neurotransmitter system in autism. Neurology. 2001;57:1618–28.CrossRefPubMedGoogle Scholar
  20. 20.
    Tirouvanziam R, Obukhanych TV, Laval J, Aronov PA, Libove R, Banerjee AG, et al. Distinct plasma profile of polar neutral amino acids, leucine, and glutamate in children with autism spectrum disorders. J Autism Dev Disord. 2012;42:827–36.CrossRefPubMedGoogle Scholar
  21. 21.
    Moreno-Fuenmayor H, Borjas L, Arrieta A, Valera V, Socorro-Candanoza L. Plasma excitatory amino acids in autism. Invest Clin. 1996;37:113–28.PubMedGoogle Scholar
  22. 22.
    Aldred S, Moore KM, Fitzgerald M, Waring RH. Plasma amino acid levels in children with autism and their families. J Autism Dev Disord. 2003;33:93–7.CrossRefPubMedGoogle Scholar
  23. 23.
    Cheng N, Rho JM, Masino SA. Metabolic dysfunction underlying autism spectrum disorder and potential treatment approaches. Front Mol Neurosci. 2017;10:34.PubMedPubMedCentralGoogle Scholar
  24. 24.
    Napoli E, Dueñas N, Giulivi C. Potential therapeutic use of the ketogenic diet in autism spectrum disorders. Front Pediatr. 2014;2:69.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Kasprowska-Liśkiewicz D, Liśkiewicz AD, Nowacka-Chmielewska MM, Nowicka J, Małecki A, Barski JJ. The ketogenic diet affects the social behavior of young male rats. Physiol Behav. 2017;179:168–77.CrossRefPubMedGoogle Scholar
  26. 26.
    Ruskin DN, Fortin JA, Bisnauth SN, Masino SA. Ketogenic diets improve behaviors associated with autism spectrum disorder in a sex-specific manner in the EL mouse. Physiol Behav. 2017;168:138–45.CrossRefPubMedGoogle Scholar
  27. 27.
    Mychasiuk R, Rho JM. Genetic modifications associated with ketogenic diet treatment in the BTBRT + Tf/J mouse model of autism spectrum disorder. Autism Res. 2017;10:456–71.CrossRefPubMedGoogle Scholar
  28. 28.
    Verpeut JL, DiCicco-Bloom E, Bello NT. Ketogenic diet exposure during the juvenile period increases social behaviors and forebrain neural activation in adult Engrailed 2 null mice. Physiol Behav. 2016;161:90–8.CrossRefPubMedGoogle Scholar
  29. 29.
    Smith J, Rho JM, Teskey GC. Ketogenic diet restores aberrant cortical motor maps and excitation-to-inhibition imbalance in the BTBR mouse model of autism spectrum disorder. Behav Brain Res. 2016;304:67–70.CrossRefPubMedGoogle Scholar
  30. 30.
    Castro K, Baronio D, Perry IS, Riesgo RD, Gottfried C. The effect of ketogenic diet in an animal model of autism induced by prenatal exposure to valproic acid. Nutr Neurosci. 2016;8:1–8.Google Scholar
  31. 31.
    Ahn Y, Narous M, Tobias R, Rho JM, Mychasiuk R. The ketogenic diet modifies social and metabolic alterations identified in the prenatal valproic acid model of autism spectrum disorder. Dev Neurosci. 2014;36:371–80.CrossRefPubMedGoogle Scholar
  32. 32.
    Ruskin DN, Svedova J, Cote JL, Sandau U, Rho JM, Kawamura M Jr. Ketogenic diet improves core symptoms of autism in BTBR mice. PLoS One. 2013;8:e65021.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Wegiel J, Kuchna I, Nowicki K, Imaki H, Wegiel J, Marchi E, et al. The neuropathology of autism: defects of neurogenesis and neuronal migration, and dysplastic changes. Acta Neuropathol. 2010;119:755–70.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Evangeliou A, Vlachonikolis I, Mihailidou H, Spilioti M, Skarpalezou A, Makaronas N, et al. Application of a ketogenic diet in children with autistic behavior: pilot study. J Child Neurol. 2003;18:113–8.CrossRefPubMedGoogle Scholar
  35. 35.
    Herbert MR, Buckley JA. Autism and dietary therapy: case report and review of the literature. J Child Neurol. 2013;28:975–82.CrossRefPubMedGoogle Scholar
  36. 36.
    Lin A, Turner Z, Doerrer SC, Stanfield A, Kossoff EH. Complications during ketogenic diet initiation: prevalence, treatment, and influence on seizure outcomes. Pediatr Neurol. 2017;68:35–9.CrossRefPubMedGoogle Scholar
  37. 37.
    Duchowny MS. Food for thought: the ketogenic diet and adverse effects in children. Epilepsy Curr. 2005;5:152–4.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    See JA, Kaukinen K, Makharia GK, Gibson PR, Murray JA. Practical insights into gluten-free diets. Nat Rev Gastroenterol Hepatol. 2015;12:580–91.CrossRefPubMedGoogle Scholar
  39. 39.
    Elder JH. The gluten-free, casein-free diet in autism: an overview with clinical implications. Nutr Clin Pract. 2008;23:538–83.CrossRefGoogle Scholar
  40. 40.
    Pellissier LP, Gandía J, Laboute T, Becker JAJ, Le Merrer J. μ opioid receptor, social behaviour and autism spectrum disorder: reward matters. Br J Pharmacol. 2017. Scholar
  41. 41.
    Genuis SJ, Lobo RA. gluten sensitivity presenting as a neuropsychiatric disorder. Gastroenterol Res Pract. 2014;2014:293206.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Hyman SL, Stewart PA, Foley J, Cain U, Peck R, Morris DD, et al. The gluten-free/casein-free diet: a double-blind challenge trial in children with autism. J Autism Dev Disord. 2016;46:205–20.CrossRefPubMedGoogle Scholar
  43. 43.
    Whiteley P, Haracopos D, Knivsberg AM, Reichelt KL, Parlar S, Jacobsen J, et al. The ScanBrit randomised, controlled, single-blind study of a gluten- and casein-free dietary intervention for children with autism spectrum disorders. Nutr Neurosci. 2010;13:87–100.CrossRefPubMedGoogle Scholar
  44. 44.
    Elder JH, Shankar M, Shuster J, Theriaque D, Burns S, Sherrill L. The gluten-free, casein-free diet in autism: results of a preliminary double blind clinical trial. J Autism Dev Disord. 2006;36:413–20.CrossRefPubMedGoogle Scholar
  45. 45.
    Knivsberg AM, Reichelt KL, Høien T, Nødland M. A randomised, controlled study of dietary intervention in autistic syndromes. Nutr Neurosci. 2002;5:251–61.CrossRefPubMedGoogle Scholar
  46. 46.
    Lee RWY, Corley MJ, Pang A, Arakaki G, Abbott L, Nishimoto M, et al. A modified ketogenic gluten-free diet with MCT improves behavior in children with autism spectrum disorder. Physiol Behav. 2018;188:205–11.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Harris C, Card B. A pilot study to evaluate nutritional influences on gastrointestinal symptoms and behavior patterns in children with Autism Spectrum Disorder. Complement Ther Med. 2012;20:437–40.CrossRefPubMedGoogle Scholar
  48. 48.
    Lange KW, Hauser J, Reissmann A. Gluten-free and casein-free diets in the therapy of autism. Curr Opin Clin Nutr Metab Care. 2015;18:572–5.CrossRefPubMedGoogle Scholar
  49. 49.
    Pennesi CM, Klein LC. Effectiveness of the gluten-free, casein-free diet for children diagnosed with autism spectrum disorder: based on parental report. Nutr Neurosci. 2012;15:85–91.CrossRefPubMedGoogle Scholar
  50. 50.
    Marí-Bauset S, Zazpe I, Mari-Sanchis A, Llopis-González A, Morales-Suárez-Varela M. Evidence of the gluten-free and casein-free diet in autism spectrum disorders: a systematic review. J Child Neurol. 2014;29:1718–27.CrossRefPubMedGoogle Scholar
  51. 51.
    Buie T. The relationship of autism and gluten. Clin Ther. 2013;35:578–83.CrossRefPubMedGoogle Scholar
  52. 52.
    Leaf JB, Leaf JA, Milne C, Taubman M, Oppenheim-Leaf M, Torres N, et al. An evaluation of a behaviorally based social skills group for individuals diagnosed with autism spectrum disorder. J Autism Dev Disord. 2017;47:243–59.CrossRefPubMedGoogle Scholar
  53. 53.
    Mohammadzaheri F, Koegel LK, Rezaei M, Bakhshi E. A randomized clinical trial comparison between pivotal response treatment (PRT) and Adult-Driven Applied Behavior Analysis (ABA) intervention on disruptive behaviors in public school children with autism. J Autism Dev Disord. 2015;45:2899–907.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Mohammadzaheri F, Koegel LK, Rezaee M, Rafiee SM. A randomized clinical trial comparison between pivotal response treatment (PRT) and structured applied behavior analysis (ABA) intervention for children with autism. J Autism Dev Disord. 2014;44:2769–77.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Children's Hospital, Zhejiang University School of Medicine 2018

Authors and Affiliations

  1. 1.2nd Department of Pediatrics, School of Medicine, University General Hospital AHEPAAristotle University of ThessalonikiThessaloníkiGreece
  2. 2.Laboratory of Pharmacology, School of MedicineDemocritus University of ThraceAlexandroupolisGreece

Personalised recommendations