Complementary and Alternative Medicine for Autism - A Systematic Review.

Monica Doherty, Kitty-Rose Foley, Janet Schloss
Author Information
  1. Monica Doherty: Faculty of Health, National Centre for Naturopathic Medicine, Southern Cross University, 1 Military Road, Lismore, NSW, 2480, Australia. m.doherty.12@student.scu.edu.au. ORCID
  2. Kitty-Rose Foley: Faculty of Health, Southern Cross University, Gold Coast, Qld, 4225, Australia.
  3. Janet Schloss: Faculty of Health, National Centre for Naturopathic Medicine, Southern Cross University, 1 Military Road, Lismore, NSW, 2480, Australia.

Abstract

Complementary and Alternative Medicine (CAM) is a therapeutic option currently used by autistic people with continued interest and uptake. There remains limited evidence regarding the efficacy of CAM use in autism. The aim of this systematic review is to comprehensively review published clinical trials to explore the efficacy of CAM in autism. A systematic literature review of available research published from June 2013 to March 2023 was conducted. Our literature search identified 1826 eligible citations, and duplications removed (n = 694) with 102 articles eligible for title/abstract screening. After full text review, 39 studies were included. The results of this systematic review identified that for autistic people, vitamin and mineral supplements may only be of benefit if there is a deficiency. The results also found that the main interventions used were dietary interventions and nutraceuticals, including targeted supplements, vitamins and minerals, omega 3 s and prebiotics, probiotics and digestive enzymes. The evidence does not support some of the most frequently utilised dietary interventions, such as a Gluten Free Casein Free (GFCF) diet, and the use of targeted nutraceutical supplements may be of benefit, but more conclusive research is still required to direct safe and effective treatment.

Keywords

References

  1. Abraham, D., Narasimhan, U., Christy, S., & Ganesan, R. (2020). Effect of l-carnosine as adjunctive therapy in the management of children with autism spectrum disorder: a randomized controlled study of children with autism spectrum disorder: a randomized controlled study, 2020. Amino Acids, 52, 1521–1528. https://doi.org/10.1007/s00726-020-02909-1 [DOI: 10.1007/s00726-020-02909-1]
  2. Abraham, D., Undela, K., Narasimhan, U., & Rajanandh, M. (2021). Effect of l-carnosine in children with autism spectrum disorders: a systematic review and meta-analysis of randomised controlled trials. Amino Acids, 53, 575–585. https://doi.org/10.1007/s00726-021-02960-6 [DOI: 10.1007/s00726-021-02960-6]
  3. Adams, J., Audhya, T., Geis, E., Gehn, E., Fimbres, V., Pollard, E., Mitchell, J., Ingram, J., Hellmers, R., Laake, D., Matthews, J., Li, K., Naviaux, J., Naviaux, R., Adams, R., Coleman, D., & Quig, D. (2018). Comprehensive nutritional and dietary intervention for autism spectrum disorder—a randomized, controlled 12-month trial. Nutrients, 10, 369. https://doi.org/10.3390/nu10030369 [DOI: 10.3390/nu10030369]
  4. Adams, J., Kirby, J., Audhya, T., Whitely, P., & Bain, J. (2022). Vitamin/Mineral/Micronutrient supplementation for autism spectrum disorders: a research survey. BMC Paediatrics, 22, 590. https://doi.org/10.1186/s12887-022-03628-0 [DOI: 10.1186/s12887-022-03628-0]
  5. Aishworiya, R., Valica, T., Hagerman, R., & Restreop, B. (2022). An update on the psychopharmacological treatment of autism spectrum disorders. Neurotherapeutics, 19, 248–262. https://doi.org/10.1177/070674371205700502 [DOI: 10.1177/070674371205700502]
  6. Akins, R., Angkustsuri, K., & Hansen, R. (2010). Complementary and Alternative Medicine in autism: an evidence-based approach to negotiating safe and effacious interventions with families. Neurotherapeutics, 7(3), 307–319. [DOI: 10.1016/j.nurt.2010.05.002]
  7. Alam, S., Westmark, C., & McCullagh, E. (2022). Diet in the treatment of autism spectrum disorders. Front Neurosciences, 16, 1031016. https://doi.org/10.3389/fnins.2022.1031016 [DOI: 10.3389/fnins.2022.1031016]
  8. Al-Ayadhi, L., & Elamin, N. E. (2013). Camel milk as a potential therapy as an antioxidant in autism spectrum disorder (ASD), 2013. Evidence-Based Complementary and Alternative Medicine. https://doi.org/10.1155/2013/602834 [DOI: 10.1155/2013/602834]
  9. Al-Ayadhi, L., Halepoto, D., AL-Dress, A., Mitwali, Y., Zainah, R. (2015). Behavioural benefits of Camel milk in subjects with autism spectrum disorder. Journal of the College of Physicians and Surgeons Pakistan, 25(11): 819–823
  10. Alwhabi, M., & Sambamoorthi, U. (2016). Sex differences in the use of complementary and alternative medicine among adults with multiple chronic conditions. Evidence Based Complementary and Alternative Medicine. https://doi.org/10.1155/2016/2067095 [DOI: 10.1155/2016/2067095]
  11. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.).
  12. Arnold, E., Luna, R., Williams, K., Chan, J., Parker, R., Wu, Q., Hollway, J., Jeffs, A., Lu, F., Coury, D., Hayes, C., & Savidge, T. (2019). Probiotics for gastrointestinal symptoms and quality of life in autism: a placebo-controlled pilot trial. Journal of Child and Adolescent Psychology. https://doi.org/10.1089/cap.2018.0156 [DOI: 10.1089/cap.2018.0156]
  13. Bargiela, S., Steward, R., & Mandy, W. (2016). The Experiences of late-diagnosed women with autism spectrum conditions: An investigation of the female autism phenotype. Journal of Autism and Developmental Disorders, 46, 3281–3294. https://doi.org/10.1007/s10803-016-2872-8 [DOI: 10.1007/s10803-016-2872-8]
  14. Bashir, S., & Al-Ayadhi, L. (2014). Effect of camel milk on thymus and activation-regulated chemokine in autistic children: double-blind study. Pediatric Research. https://doi.org/10.1038/pr.2013.248 [DOI: 10.1038/pr.2013.248]
  15. Baspinar, B., & Yardimci, H. (2020). Gluten-free casein-free diet for autism spectrum disorders: can it be effective in solving behavioural and gastrointestinal problems? The Eurasian Journal of Medicine, 52(3), 292–297. https://doi.org/10.5152/eurasianjmed.2020.19230 [DOI: 10.5152/eurasianjmed.2020.19230]
  16. Batch, J., Lamsal, S., Adkins, M., Sultan, S., & Ramirez, M. (2020). Advantages and disadvantages of the keto diet: a review article. Cureus. https://doi.org/10.7759/cureus.9639 [DOI: 10.7759/cureus.9639]
  17. Bellini, M., Tonatelli, S., Nagy, A., Pancetti, A., Costa, F., Ricchiuti, A., de Bortoli, N., Mosca, M., Marchi, S., & Rossi, A. (2020). A low FODMAP diet: Evidence, doubts, hopes. Nutrients, 12, 148. https://doi.org/10.3390/nu12010148 [DOI: 10.3390/nu12010148]
  18. Bent, S., & Hedren, R. (2015). Complementary and Alternative treatments for autism Part 1: evidence supported treatments. AMA Journal of Ethics, 17(4), 369–374. https://doi.org/10.1001/journalofethics.2015.17.4.sect1-1504 [DOI: 10.1001/journalofethics.2015.17.4.sect1-1504]
  19. Bent, S., Hendren, R., Zandi, T., Law, K., Choi, J., Widjaja, F., Kalb, L., Nestle, J., & Law, P. (2019). Internet-based, randomized controlled trial of Omega-3 Fatty Acids for hyperactivity in autism. Journal of the American Academy of Child & Adolescent Psychiatry, 53(6), 658–666. https://doi.org/10.1016/j.jaac.2014.01.018 [DOI: 10.1016/j.jaac.2014.01.018]
  20. Birch, R. C., Foley, K.-R., Pollack, A., Britt, H., Lennox, N., & Trollor, J. (2017). Problems managed and medications prescribed during encounters with people with autism spectrum disorder in Australian general practice. Autism, 22(8), 995–1004. https://doi.org/10.1177/070674371205700502 [DOI: 10.1177/070674371205700502]
  21. Brondino, N., Fusar-Poli, L., Rocchetti, M., Provenzani, U., Barale, F., & Politi, P. (2015). Complementary and Alternative therapies for autism spectrum disorder. Evidence Based Complementary and Alternative Medicine. http:/dx. https://doi.org/10.1155/2015/258589 [DOI: 10.1155/2015/258589]
  22. Castejon, A., Spaw, J., Rozenfeld, I., Sheinberg, N., Kabot, S., Shaw, A., Hardigan, P., Faillace, R., & Packer, E. (2021). Improving antioxidant capacity in children with autism: a randomized, double-blind controlled study with Cysteine-Rich Whey Protein. Frontiers in Psychiatry, 12, 669089. https://doi.org/10.3389/fpsyt.2021.669089 [DOI: 10.3389/fpsyt.2021.669089]
  23. Chahboun, S., Stenseng, F., & Page, A. G. (2022). The changing faces of autism: The fluctuating international diagnostic criteria and the resulting inclusion and exclusion—A Norwegian perspective. Frontiers in Psychiatry, 13, 787893. https://doi.org/10.3389/frsyt.2022-787893 [DOI: 10.3389/frsyt.2022-787893]
  24. Chiston, L., Mackintosh, V., & Myers, B. (2010). Use of complementary and alternative medicine (CAM) treatments by parents of children with autism spectrum disorders. Research in Autism Spectrum Disorders, 4, 249–259. https://doi.org/10.1016/j.rasd.2009.09.013 [DOI: 10.1016/j.rasd.2009.09.013]
  25. Colizzi, M., Bortoletto, R., Costa, R., & Zoccante, L. (2021). Palmitoylethanolamide (PEA) and it’s behavioural correlates in autism spectrum disorder: a systematic review of human and animal evidence. Nutrients, 13(4), 1346. https://doi.org/10.3390/nu13041346 [DOI: 10.3390/nu13041346]
  26. Complementary Medicines Association Australia. (2021). Pre-Budget Submission, 2021–2022. Complementary Medicines Association Australia.
  27. Davenport, M., Mazurek, M., Brown, A., & McCollom, C. (2018). A systematic review of cultural considerations and adaptation of social skills interventions for individuals with autism spectrum disorder. Research in Autism Spectrum Disorders, 52, 23–33. https://doi.org/10.1016/j.rasd.2018.05.003 [DOI: 10.1016/j.rasd.2018.05.003]
  28. de la Torre-Aguilar, M. J., Gomez-Fernandez, A., Flores-Rojas, K., Martin-Borreguero, P., Mesa, M. D., Perez-Navero, J. L., & Gil-Campos, M. (2022). Docosahexaenoic and Eicosapentaenoic intervention modifies plasma and erythrocyte Omega-3 fatty acid profiles but not the clinical course of children with autism spectrum disorder: A randomized control trial. Frontiers in Nutrition, 9, 790250. https://doi.org/10.3389/fnut.2022.790250 [DOI: 10.3389/fnut.2022.790250]
  29. Devnani, P., & Hedge, A. (2015). Autism and sleep disorders. Journal of Pediatric Neurosciences., 10(4), 304–307. https://doi.org/10.4103/1817-1745.174438 [DOI: 10.4103/1817-1745.174438]
  30. Dhanjal, D., Bhardwaj, S., Chopra, C., Singh, R., Patocka, J., Plucar, B., Neporimova, E., Valis, M., & Kuca, K. (2022). Millenium nutrient N, N-Dimethylglycine (DMG) and its effectiveness in autism spectrum disorders. Current Medicinal Chemistry, 29(15), 2632–2651. https://doi.org/10.2174/0929867328666211125091811 [DOI: 10.2174/0929867328666211125091811]
  31. Doaei, S., Bourbour, F., Teymoori, Z., Jafari, F., Kalantari, N., Torki, S., Ashoori, N., Gorgani, S., & Gholamalizadeh, M. (2021). The effect of omega-3 fatty acids supplementation on social and behavioural disorders of children with autism: A randomized clinical trial. Pediatric Endocrinology, Diabetes, and Metabolism, 27(1), 12–18. https://doi.org/10.5114/pedm.2020.101806 [DOI: 10.5114/pedm.2020.101806]
  32. 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, 1935–1941. https://doi.org/10.1007/s11011-017-0088-z [DOI: 10.1007/s11011-017-0088-z]
  33. Feng, J., Shan, L., Du, L., Wang, B., Li, H., Wang, W., Wang, T., Dong, H., Yue, Xu. Z., Staal, W., & Jia, F. (2017). Clinical improvement following vitamin D3 supplementation in autism spectrum disorder. Nutritional Neuroscience. https://doi.org/10.1080/1028415X.2015.1123847 [DOI: 10.1080/1028415X.2015.1123847]
  34. Feng, P., Zhao, S., Zhang, Y., & Li, E. (2023). A review of probiotics in the treatment of autism spectrum disorders: Perspectives from the gut–brain axis. Frontiers in Microbiology, 14, 1123462. https://doi.org/10.3389/fmicb.2023.1123462 [DOI: 10.3389/fmicb.2023.1123462]
  35. Frye, R., Slattery, J., Delhey, L., Furgerson, B., Strickland, T., Tippett, M., Sailey, A., Wynne, R., Rose, S., Melnyk, S., James, J., Sequeira, J. M., & Quadros, E. V. (2019). Folinic acid improves verbal communication in children with autism and language impairment: a randomized double-blind autism and language impairment: a randomized double-blind placebo-controlled trial. Molecular Psychiatry, 23, 247–256. https://doi.org/10.1038/mp.2016.168 [DOI: 10.1038/mp.2016.168]
  36. Gonzalez-Domenech, P., Atienza, F., Pablos, C., Fernández Soto, M., Martínez-Ortega, J. M., & Gutiérrez-Rojas, L. (2020). Influence of a combined Gluten-Free and Casein-Free diet on behaviour disorders in children and adolescents diagnosed with autism spectrum disorder: a 12-Month follow-up clinical trial, 2020. Journal of Autism and Developmental Disorders, 50, 935–948. https://doi.org/10.1007/s10803-019-04333-1 [DOI: 10.1007/s10803-019-04333-1]
  37. Gonzalez-Domenech, P., Atienza, F., Pablos, C., Nieto, S., Rodríguez, O., Gutiérrez-Rojas, L., & Martínez-Ortega, J. (2019). Influence of a Gluten-free, Casein-free Diet on behavioural disturbances in children and adolescents diagnosed with autism spectrum disorder: A 3-month follow-up pilot study. Journal of Mental Health Research in Intellectual Disabilities. https://doi.org/10.1080/19315864.2019.1654574 [DOI: 10.1080/19315864.2019.1654574]
  38. Grimaldi, R., Gibson, G., Vulevic, J., Giallourou, N., Castro-Mejía, J., Hansen, L., Gibson, E. L., Nielsen, D. S., & Costabile, A. (2018). A prebiotic intervention study in children with autism spectrum disorders (ASDs). Microbiome, 6, 133. https://doi.org/10.1186/s40168-018-0523-3 [DOI: 10.1186/s40168-018-0523-3]
  39. Happé, F. G., Mansour, H., Barrett, P., Brown, T., Abbott, P., & Charlton, R. A. (2016). Demographic and cognitive profile of individuals seeking a diagnosis of autism spectrum disorder in adulthood. Journal of autism and developmental disorders, 46, 3469–3480. https://doi.org/10.1007/s10803-016-2886-2 [DOI: 10.1007/s10803-016-2886-2]
  40. Hellings, J. (2023). Pharmacotherapy in autism spectrum disorders, including promising older drugs warranting trials. World Journal of Psychiatry, 13(6), 262–277. https://doi.org/10.1007/s10803-013-1985-6 [DOI: 10.1007/s10803-013-1985-6]
  41. Hendren, R. L., James, S. J., Widjaja, F., Lawton, B., Rosenblatt, A., & Bent, S. (2016). Randomized, placebo-controlled trial of methyl B12 for children with autism. Journal of child and adolescent psychopharmacology, 26(9), 774-783.6 https://doi.org/10.1089/cap.2015.0159
  42. Hofer, J., Hoffman, F., & Bachmann, C. (2017). Use of complementary and alternative medicine in children and adolescents with autism spectrum disorders: a systematic review. Autism, 21(4), 387–402. https://doi.org/10.1077/1362361316646559 [DOI: 10.1077/1362361316646559]
  43. Holtman, M., Bolte, S., & Poustka, F. (2007). Autism spectrum disorders: Sex differences in autistic behaviour domains and coexisting psychopathology. Developmental Medicine & Child Neurology, 49(361–366), 361. https://doi.org/10.1177/1362361319853442 [DOI: 10.1177/1362361319853442]
  44. Howlin, P., & Moss, P. (2012). Adults with autism spectrum disorders. The Canadian Journal of Psychiatry, 57(5), 275–283. https://doi.org/10.1177/070674371205700502 [DOI: 10.1177/070674371205700502]
  45. Hull, L., Petrides, K., Allison, C., Smith, P., Baron-Cohen, S., Lai, M. C., & Mandy, W. (2017). Putting on my best normal: Social camouflaging in adults with autism spectrum conditions. Journal of Autism and Developmental Disorders, 47(8), 2519–2534. https://doi.org/10.1007/s10803-017-3166-5 [DOI: 10.1007/s10803-017-3166-5]
  46. Hyman, S., Stewart, P., Foley, J., Cain, U., Peck, R., Morris, D., Wang, H., & Smith, T. (2016). The Gluten-Free/Casein-Free diet: A double-blind challenge trial in children with autism. Journal of Autism and Developmental Disorders, 46, 205–220. https://doi.org/10.1007/s10803-015-2564-9 [DOI: 10.1007/s10803-015-2564-9]
  47. Ianiro, G., Pecere, S., Giorgio, V., Gasbarrini, A., & Cammarota, G. (2016). Digestive enzyme supplementation in gastrointestinal diseases. Current drug metabolism, 17(2), 187–193 https://doi.org/10.2174/1389.2002.1702160114150137
  48. Javadfar, Z., Abdollahzad, H., Moludi, J., Rezaeian, S., Amirian, H., Foroughi, A., Nachvak, S., Goharmehr, N., & Mostafai, R. (2020). Effects of vitamin D supplementation on core symptoms, serum serotonin, and interleukin-6 in children with autism spectrum disorders: A randomized clinical trial, 2020. Nutrition, 7980, 110986. https://doi.org/10.1016/j.nut.2020.110986 [DOI: 10.1016/j.nut.2020.110986]
  49. Kerley, C., Power, C., Gallagher, L., & Coghlan, D. (2017). Lack of effect of vitamin D3 supplementation in autism: a 20-week, placebo-controlled RCT. Archives of disease in childhood, 102(11), 1030–1036. https://doi.org/10.1136/archdischild-2017-312783 [DOI: 10.1136/archdischild-2017-312783]
  50. Kerr-Gaffrey, J., Halls, D., Harrison, A., & Tchanturia, K. (2020). Exploring relationships between autism spectrum disorder symptoms and eating disorder symptoms in adults with Anorexia Nervosa: anetwork approach. Frontiers in Psychiatry, 11, 401. https://doi.org/10.3389/fpsyt.2020.00401 [DOI: 10.3389/fpsyt.2020.00401]
  51. Khachadourian, V., Mahjani, B., Sandin, S., et al. (2023). Comorbidities in autism spectrum disorder and their aetiologies. Translational Psychiatry, 13, 71. https://doi.org/10.1101/2022.03.10.22272202 [DOI: 10.1101/2022.03.10.22272202]
  52. Koithan, M. (2009). Introducing complementary and alternative therapies. The Journal for Nurse Practitioners, 5(1), 18–20. https://doi.org/10.1016/j.nurpra.2008.10.102 [DOI: 10.1016/j.nurpra.2008.10.102]
  53. Liu, Y. W., Liong, M., Chung, Y., Huang, H. Y., Peng, W. S., Cheng, Y. F., Lin, Y. S., Wu, Y. Y., & Tsai, Y. C. (2019). Effects of Lactobacillus plantarum PS128 on children with autism spectrum disorder in Taiwan: a randomized, double-blind. Placebo-Controlled Trial. Nutrients, 11, 820. https://doi.org/10.3390/nu11040820 [DOI: 10.3390/nu11040820]
  54. 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 [DOI: 10.1016/j.jaac.2017.03.013]
  55. Maenner, M. J. (2023). Prevalence and characteristics of autism spectrum disorder among children aged 8 years—Autism and Developmental Disabilities Monitoring Network, 11 sites, United States, 2020. MMWR. Surveillance Summaries, 72:1–14. https://doi.org/10.15585/mmwr.ss7202a1
  56. Magner, M., Thorová, K., Župová, V., Houška, M., Švandová, I., Novotná, P., Tríska, J., Vrchotová, N., Soural, I., Jílek, L. (2023). Sulforaphane treatment in children with autism: A prospective randomized double-blind study. Nutrients, 15:718. https://doi.org/10.3390/nu15030718
  57. Mankad, D., Dupuis, A., Smile, S., Roberts, W., Brian, J., Lui, T., Genore, L., Zaghloul, D., Iaboni, A., Marcon, P., & Anagnostou, E. (2015). A randomized, placebo controlled trial of omega-3 fatty acids in the treatment of young children with autism. Molecular Autism, 6, 18. https://doi.org/10.1186/s13229-015-0010-7 [DOI: 10.1186/s13229-015-0010-7]
  58. Manzini, A., Jones, E. J., Charman, T., Elsabbagh, M., Johnson, M. H., & Singh, I. (2021). Ethical dimensions of translational developmental neuroscience research in autism. Journal of Child Psychology and Psychiatry, 62(11), 1363–1373. https://doi.org/10.1111/jcpp.13494 [DOI: 10.1111/jcpp.13494]
  59. Mazahery, H., Conlon, C., Beck, K., Mugridge, O., Kruger, M., Stonehouse, W., Camargo, C., Jr., Meyer, B., Tsang, B., Jones, B., & von Hurst, P. (2019). A randomised-controlled trial of Vitamin D and Omega-3 Long Chain Polyunsaturated Fatty Acids in the treatment of core symptoms of autism spectrum disorder in children. Journal of Autism and Developmental Disorders, 49, 1778–1794. https://doi.org/10.1186/s13063-016-1428-8 [DOI: 10.1186/s13063-016-1428-8]
  60. Mehrazad-Saber, Z., Kheirouri, S., & Noorazar, S. G. (2018). Effects of L-Carnosine supplementation on sleep disorders and disease severity in autistic children: a randomized, controlled clinical trial. Basic & Clinical Pharmacology & Toxicology, 123, 72–77. https://doi.org/10.1111/bcpt.12979 [DOI: 10.1111/bcpt.12979]
  61. Millward, C., Ferriter, M., Calver, S. J., & Connell-Jones, G. G. (2008). Gluten-and casein-free diets for autistic spectrum disorder. Cochrane database of systematic reviews. https://doi.org/10.1002/14651858.CD003498 [DOI: 10.1002/14651858.CD003498]
  62. Mousavinejada, E., Ghaffaria, M., Riahic, F., Hajmohammadid, M., Tiznobeyke, Z., & Mousavinejad, M. (2018). Coenzyme Q10 supplementation reduces oxidative stress and decreases T antioxidant enzyme activity in children with autism spectrum disorders. Psychiatry Research, 265, 62–69. https://doi.org/10.1016/j.psychres.2018.03.061 [DOI: 10.1016/j.psychres.2018.03.061]
  63. Mu, C., Corley, M. J., Lee, R. W., Wong, M., Pang, A., Arakaki, G., & 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 [DOI: 10.1021/acs.jproteome.9b00581]
  64. Nasri, H., Baradaran, A., Shirzad, H., & Rafieian-Kopaei, M. (2014). New concepts in nutraceuticals as alternative for pharmaceuticals. International Journal of Preventive Medicine, 5(12), 1487–1499. [PMID: 25709784]
  65. Nogay, N., Walton, J., Roberts, K., Nahikian-Nelms, M., & Witwer, A. (2021). The effect of the low FODMAP diet on gastrointestinal symptoms, behavioural problems and nutrient intake in children with autism spectrum disorder: A randomized controlled pilot trial. Journal of Autism and Developmental Disorders, 51, 2800–2811. https://doi.org/10.1007/s10803-020-04717-8 [DOI: 10.1007/s10803-020-04717-8]
  66. Onal, S., Krol, M., & Kostecka, M. (2023). A review of the nutritional approach and role of dietary components in children with autism spectrum disorders in light of the latest scientific research. Nutrients, 15, 4852. https://doi.org/10.1186/1743-7075-8-34 [DOI: 10.1186/1743-7075-8-34]
  67. Ou, J., Smith, R., Tobe, R., et al. (2022). Efficacy of Sulforaphane in the treatment of children with autism spectrum disorder: a randomised double-blind placebo controlled multi-centre trial. Journal of Autism and Developmental Disorders. https://doi.org/10.1007/s10803-022-05784-9 [DOI: 10.1007/s10803-022-05784-9]
  68. Page, M. J., McKenzie, J. E., Bossuyt, P. M., Boutron, I., Hoffmann, T. C., Mulrow, C. D., et al. (2021). The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ, 372, n71. https://doi.org/10.1136/bmj.n71 [DOI: 10.1136/bmj.n71]
  69. Parellada, M., Llorentea, C., Calvoe, R., Guiterrez, S., Lazaro, L., Graell, M., Guisasola, M., Dorado, M., Boada, L., Romo, J., Dulin, E., Sanz, I., Arango, C., & Moreno, C. (2017). Randomized trial of omega-3 for autism spectrum disorders: Effect on cell membrane composition and behaviour. European Neuropsychopharmacology, 27, 1319–1330. https://doi.org/10.1016/j.euroneuro.2017.08.426 [DOI: 10.1016/j.euroneuro.2017.08.426]
  70. Piwowarczyk, A., Horvath, A., Pisula, E., Kawa, R., & Szajewska, H. (2020). Gluten-Free Diet in Children with Autism Spectrum Disorders: A randomized, controlled, single-blinded trial. Journal of Autism and Developmental Disorders, 50, 482–490. https://doi.org/10.1007/s10803-019-04266-9 [DOI: 10.1007/s10803-019-04266-9]
  71. Raghavan, K., Dedeepiya, V., Ikewaki, N., Sonoda, T., Iwasaki, M., Preethy, S., & Abraham, S. (2022). Improvement of behavioural pattern and alpha-synuclein levels in autism spectrum disorder after consumption of a beta-glucan food supplement in a randomised, parallel-group pilot clinical study. BMJ Neurology Open. https://doi.org/10.1136/bmjno-2021-000203 [DOI: 10.1136/bmjno-2021-000203]
  72. Renard, E., Leheup, B., Guerant-Rodriguez, R., Oussalah, A., Quadros, E., & Guerant, J. L. (2020). Folinic acid improves the score of Autism in the EFFET placebo- controlled randomized trial. Biochimie, 173, 57–61. https://doi.org/10.1016/j.biochi.2020.04.019 [DOI: 10.1016/j.biochi.2020.04.019]
  73. Rossignol, D., & Frye, R. (2021). The effectives of Cobalamin (B12) treatment for ASD: autism spectrum disorder: a systematic review and meta-analysis. Journal of Personalized Medicine, 11(8), 784. https://doi.org/10.3390/jpm11080784 [DOI: 10.3390/jpm11080784]
  74. Russel, G., Kapp, S., Elliot, D., Elphick, C., Gwerman-Jones, R., & Owens, C. (2019). Mapping the autistic advantage from accounts of adults diagnosed with autism: a qualitative study. Autism in adulthood. https://doi.org/10.1089/aut.2018.0035 [DOI: 10.1089/aut.2018.0035]
  75. Saad, K., Eltayeb, A., Mohamad, I., Al-Atram, A., Elserogy, Y., Bjørklund, G., El-Houfey, A., & Nicholson, B. (2015). A randomized, placebo-controlled trial of digestive enzymes in children with autism spectrum disorders. Clinical Psychopharmacology and Neuroscience, 13(2), 188–193. https://doi.org/10.9758/cpn.2015.13.2.188 [DOI: 10.9758/cpn.2015.13.2.188]
  76. Sanctuary, M., Kain, J., Chen, S. Y., Kalanetra, K., Lemay, D. G., Rose, D. R., Yang, H. T., Tancredi, D. J., German, J. B., Slupsky, C. M., Ashwood, P., Mills, D. A., Smilowitz, J. T., & Angkustsiri, K. (2019). Pilot study of probiotic/colostrum supplementation on gut function in children with autism and gastrointestinal symptoms. PLoS ONE, 14(1), e0210064. https://doi.org/10.1371/journal.pone.0210064 [DOI: 10.1371/journal.pone.0210064]
  77. Sauer, A., Stanton, J., Haus, S., Graubrucker, A. (2021). Autism Spectrum Disorders: Aetiology and Pathology. Autism Spectrum Disorders, edited by Graubrucker A. Exon Publications, Brisbane, Australia. https://doi.org/10.36255/exonpublications.autismspectrumdisorders.2021.etiology
  78. Schmitt, L. M., Smith, E. G., Pedapati, E. V., Horn, P. S., Will, M., Lamy, M., & Erickson, C. A. (2023). Results of a phase Ib study of SB-121, an investigational probiotic formulation, a randomized controlled trial in participants with autism spectrum disorder. Scientific Reports, 13(1), 5192. https://doi.org/10.1038/s41598-023-30909-0 [DOI: 10.1038/s41598-023-30909-0]
  79. Semple, S., Hewton, C., Paterson, F., Angley, M. (2011). Complementary Medicine products used in autism – evidence for the efficacy & safety. Autism Spectrum Disorder – from genes to environment. https://doi.org/10.5772/32438 .
  80. Shabo, Y., Barzel, R., Margoulis, M., & Yagil, R. (2005). Camel milk for food allergies in children. IMAJ, 7, 796–798. [PMID: 16382703]
  81. Shuai, B., & Hongiiao, J. (2020). Shi M (2020) Safety and efficacy of Complementary and Alternative Medicine in the treatment of autism spectrum disorder. Medicine (Baltimore)., 99(45), e23128. https://doi.org/10.1097/MD.0000000000023128 [DOI: 10.1097/MD.0000000000023128]
  82. Singh, K., Connors, L., Macklin, E., Smith, K., Fahey, J., Talalay, P., & Zimmerman, A. (2014). Sulforaphane treatment of autism spectrum disorder (ASD). Proceedings of the National Academy of Sciences, 111(43), 15550–15555. https://doi.org/10.1073/pnas.1416940111 [DOI: 10.1073/pnas.1416940111]
  83. Song, W., Zhang, M., Teng, Y., & Zhu, L. (2022). Prebiotics and probiotics for autism spectrum disorder: a systematic review & meta-analysis of controlled clinical trial. Journal of Medical Microbiology, 71, 001510. https://doi.org/10.1099/jmm.0.001510 [DOI: 10.1099/jmm.0.001510]
  84. Steel, A., McIntyre, E., Harnett, J., Foley, H., Adams, J., Sibbritt, D., Wardle, J., & Frawley, J. (2018). Complementary Medicine use in the Australian population: Results of a nationally representative cross-sectional survey. Nature, Scientific Reports, 8, 17325. https://doi.org/10.1038/s41598-018-35508-y [DOI: 10.1038/s41598-018-35508-y]
  85. Stoner, S. (2017). Management of serious cardiac adverse effects of antipsychotic meds. Mental Health Clinician., 7(6), 246–254. https://doi.org/10.9740/mhc.2017/11.246 [DOI: 10.9740/mhc.2017/11.246]
  86. Throop, C., & Stockmeier, C. (2011). SEC & SSER Patient Safety Measurement System for Healthcare. Healthcare Performance Improvement (HPI) White Paper Series
  87. Trudeau, M., Madden, R., Parnell, J., Gibbard, W. B., & Shearer, J. (2019). Dietary and supplement-based Complementary and Alternative Medicine use in paediatric autism spectrum disorder. Nutrients, 11, 1783. https://doi.org/10.3390/nu11081783 [DOI: 10.3390/nu11081783]
  88. Veselinovic, A., Petrovic, S., Zikic, V., Subotic, M., Jakovljevic, V., Jeremic, N., & Vucic, V. (2021). Neuroinflammation in autism and supplementation based on omega-3 polyunsaturated fatty acids: A narrative review. Medicina, 57, 893. https://doi.org/10.3390/medicina57090893 [DOI: 10.3390/medicina57090893]
  89. Voigt, R., Mellon, M., Katusic, S., Weaver, A., Matern, D., Mellon, B., Jensen, C., & Barbaresi, W. (2014). Dietary Docosahexaenoic Acid supplementation in children with autism. Journal of Pediatric Gastroenterology and Nutrition., 58(6), 715–722. https://doi.org/10.1097/MPG.0000000000000260 [DOI: 10.1097/MPG.0000000000000260]
  90. Wang, Y., Li, N., Yang, J.-J., Zhao, D.-M., Chen, B., Zhang, G.-Q., Chen, S., Cao, R.-F., Yu, H., Zhao, L.-Y., Zhao, L., Ge, Y.-S., Liu, Y., Zhang, L.-H., Hu, W., Zhang, L., & Gai, Z.-T. (2020). Probiotics and fructo-oligosaccharide intervention modulate the microbiota-gut brain axis to improve autism spectrum, reducing also the hyper-seretonergic state and dopamine metabolism disorder. Pharmacological Research, 157, 104784. https://doi.org/10.1016/j.phrs.2020.104784 [DOI: 10.1016/j.phrs.2020.104784]
  91. Wasilewskal, J., & Klukowski, M. (2015). Gastrointestinal symptoms and autism spectrum disorder: Links and risks – a possible new overlap syndrome. Paediatric Health, Medicine and Therapeutics, 6, 153–166. https://doi.org/10.2147/PHMT.S85717 [DOI: 10.2147/PHMT.S85717]
  92. Yu, Y., Huang, J., Chen, X., Fu, J., Wang, X., Pu, L., Gu, C., Chung, J., & Cai, C. (2022). Efficacy and safety of diet therapies in children with autism spectrum disorder: A systematic literature review and meta-analyses. Frontiers in Neurology. https://doi.org/10.3389/fneur.2022.844117 [DOI: 10.3389/fneur.2022.844117]
  93. Zimmerman, A., Singh, K., Connors, S., Liu, H., Panjwani, A., Lee, L. C., Diggins, E., Foley, A., Melnyk, S., Singh, I., James, J., Frye, R., & Fahey, J. (2021). Randomized controlled trial of sulforaphane and metabolite discovery in children with autism spectrum disorder. Molecular Autism, 12, 38. https://doi.org/10.1186/s13229-021-00447-5 [DOI: 10.1186/s13229-021-00447-5]
  94. Zuckerman, K., Lindly, O., Sinche, K., & Nicoladis, M. (2015). Parent health beliefs, social determinants of health and child health services utilisation among US school age children with autism. Journal of Developmental & Behavioral Paediatrics, 36(3), 146–157. https://doi.org/10.1097/DBP0000000000000136 [DOI: 10.1097/DBP0000000000000136]

Word Cloud

Created with Highcharts 10.0.0reviewinterventionsComplementaryCAMsystematicsupplementsAlternativeMedicineusedautisticpeopleevidenceefficacyuseautismpublishedliteratureresearchidentifiedeligibleresultsmaybenefitdietarytargetedFreeAutismtherapeuticoptioncurrentlycontinuedinterestuptakeremainslimitedregardingaimcomprehensivelyclinicaltrialsexploreavailableJune2013March2023conductedsearch1826citationsduplicationsremovedn = 694102articlestitle/abstractscreeningfulltext39studiesincludedvitaminmineraldeficiencyalsofoundmainnutraceuticalsincludingvitaminsmineralsomega3 sprebioticsprobioticsdigestiveenzymessupportfrequentlyutilisedGlutenCaseinGFCFdietnutraceuticalconclusivestillrequireddirectsafeeffectivetreatment-SystematicReviewAutisticalternativemedicineDietaryNutraceuticals

Similar Articles

Cited By