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

Abstract

Background

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.

Result

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.

Conclusion

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.

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References

  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.

    Article  PubMed  PubMed Central  CAS  Google 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.

    Article  PubMed  PubMed Central  Google 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.

    Article  CAS  Google 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. https://doi.org/10.1093/bib/bbx154.

    PubMed  Article  Google 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.

    Article  PubMed  CAS  Google 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.

    Article  PubMed  CAS  Google 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.

    Article  PubMed  PubMed Central  Google 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.

    Article  PubMed  PubMed Central  Google 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. https://doi.org/10.1007/s00394-017-1528-6.

    Article  PubMed  Google 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.

    Article  PubMed  CAS  Google 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.

    Article  PubMed  PubMed Central  Google 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.

    Article  PubMed  CAS  Google 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.

    Article  PubMed  Google Scholar 

  14. 14.

    Hartman AL, Gasior M, Vining EP, Rogawski MA. The neuropharmacology of the ketogenic diet. Pediatr Neurol. 2007;36:281–92.

    Article  PubMed  PubMed Central  Google 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.

    Article  PubMed  CAS  Google Scholar 

  16. 16.

    Daikhin Y, Yudkoff M. Ketone bodies and brain glutamate and GABA metabolism. Dev Neurosci. 1998;20:358–64.

    Article  PubMed  CAS  Google 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.

    Article  PubMed  CAS  Google 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.

    Article  PubMed  CAS  Google 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.

    Article  PubMed  CAS  Google 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.

    Article  PubMed  Google 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.

    PubMed  CAS  Google 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.

    Article  PubMed  Google 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.

    PubMed  PubMed Central  Google 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.

    Article  PubMed  PubMed Central  Google 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.

    Article  PubMed  CAS  Google 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.

    Article  PubMed  CAS  Google 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.

    Article  PubMed  Google 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.

    Article  PubMed  CAS  Google 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.

    Article  PubMed  CAS  Google 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.

    Article  PubMed  CAS  Google 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.

    Article  PubMed  PubMed Central  CAS  Google 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.

    Article  PubMed  PubMed Central  Google 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.

    Article  PubMed  Google 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.

    Article  PubMed  Google 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.

    Article  PubMed  Google Scholar 

  37. 37.

    Duchowny MS. Food for thought: the ketogenic diet and adverse effects in children. Epilepsy Curr. 2005;5:152–4.

    Article  PubMed  PubMed Central  Google 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.

    Article  PubMed  CAS  Google 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.

    Article  Google 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. https://doi.org/10.1111/bph.13808.

    PubMed  Article  Google Scholar 

  41. 41.

    Genuis SJ, Lobo RA. gluten sensitivity presenting as a neuropsychiatric disorder. Gastroenterol Res Pract. 2014;2014:293206.

    Article  PubMed  PubMed Central  Google 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.

    Article  PubMed  Google 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.

    Article  PubMed  CAS  Google 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.

    Article  PubMed  Google 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.

    Article  PubMed  CAS  Google 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.

    Article  PubMed  PubMed Central  CAS  Google 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.

    Article  PubMed  Google 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.

    Article  PubMed  CAS  Google 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.

    Article  PubMed  CAS  Google 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.

    Article  PubMed  Google Scholar 

  51. 51.

    Buie T. The relationship of autism and gluten. Clin Ther. 2013;35:578–83.

    Article  PubMed  CAS  Google 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.

    Article  PubMed  Google 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.

    Article  PubMed  PubMed Central  Google 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.

    Article  PubMed  PubMed Central  Google Scholar 

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Funding

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.

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

Corresponding author

Correspondence to M. Gogou.

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The authors declare that they have no conflict of interest.

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Gogou, M., Kolios, G. Are therapeutic diets an emerging additional choice in autism spectrum disorder management?. World J Pediatr 14, 215–223 (2018). https://doi.org/10.1007/s12519-018-0164-4

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Keywords

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