Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder with repetitive behaviour which affects interaction and communication. Sulforaphane (SFN), an isothiocyanate abundant in the seeds and sprouts of cruciferous vegetables, has been shown to be effective in alleviating autistic behaviour. We performed a prospective double-blind placebo-controlled study to examine the possible effect of SFN in a paediatric cohort aged three to seven years based on measurements of the Autism Diagnostic Observation Schedule-2 (ADOS-2), the Social Responsiveness Scale-2 (SRS-2), and the Aberrant Behaviour Checklist (ABC). The study consisted of three visits over the duration of 36 weeks (baseline, 18 weeks, and 36 weeks). Twenty-eight of the 40 randomized children completed the study. The mean total raw scores on ABC and SRS-2 improved in both groups, but none of the changes reached statistical significance (ABC: 0 weeks p = 0.2742, 18 weeks p = 0.4352, and 36 weeks 0.576; SRS-2: 0 weeks p = 0.5235, 18 weeks p = 0.9176, and 36 weeks 0.7435). Changes in the assessment of the ADOS-2 subscale scores also did not differ between the two study cohorts (ADOS-2: 0 weeks p = 0.8782, 18 weeks p = 0.4788, and 36 weeks 0.9414). We found no significant clinical improvement in the behavioural outcome measures evaluated in children with ASD aged 3-7 years that were treated with sulforaphane.

Department of Paediatrics and Inherited Metabolic Disorders 1st Faculty of Medicine Charles University General University Hospital 128 08 Prague 2 Czech Republic

Faculty of Horticulture Mendel University in Brno 691 44 Lednice Czech Republic

Food Research Institute Prague 102 00 Prague 10 Czech Republic

Global Change Research Institute CAS 603 00 Brno Czech Republic

National Institute for Autism 180 00 Prague 8 Czech Republic

Pure Food Norway 1400 Ski Norway

See more in PubMed

American Psychiatric Association . Diagnostic and Statistical Manual of Mental Disorders. 5th ed. American Psychiatric Publishing; Washington, DC, USA: 2013. Cautionary statement for forensic use of DSM-5. DOI

Lord C., Brugha T.S., Charman T., Cusack J., Dumas G., Frazier T., Jones E.J.H., Jones R.M., Pickles A., State M.W., et al. Autism spectrum disorder. Nat. Rev. Dis. Prim. 2020;6:5. doi: 10.1038/s41572-019-0138-4. PubMed DOI PMC

Shen L., Zhao Y., Zhang H., Feng C., Gao Y., Zhao D., Yao F. Advances in biomarker studies in autism spectrum disorders. Adv. Exp. Med. Biol. 2013;1118:207–233. PubMed

Shen L., Liu X., Zhang H., Lin J., Feng C., Iqbal J. Biomarkers in autism spectrum disorders: Current progress. Clin. Chim. Acta. 2020;502:41–54. doi: 10.1016/j.cca.2019.12.009. PubMed DOI

Farmer C., Thurm A., Grant P. Pharmacotherapy for the core symptoms in autistic disorder: Current status of the research. Drugs. 2013;73:303–314. doi: 10.1007/s40265-013-0021-7. PubMed DOI PMC

Rossignol D.A., Frye R.E. A review of research trends in physiological abnormalities in autism spectrum disorders: Immune dysregulation, inflammation, oxidative stress, mitochondrial dysfunction and environmental toxicant exposures. Mol. Psychiatry. 2012;17:389–401. doi: 10.1038/mp.2011.165. PubMed DOI PMC

Rose S., Melnyk S., Pavliv O., Bai S., Nick T.G., Frye R.E., James S.J. Evidence of oxidative damage and inflammation associated with low glutathione redox status in the autism brain. Translantional Psychiatry. 2012;2:e134. doi: 10.1038/tp.2012.61. PubMed DOI PMC

Liu X., Lin J., Zhang H., Khan N.U., Zhang J., Tang X., Cao X., Shen L. Oxidative Stress in Autism Spectrum Disorder-Current Progress of Mechanisms and Biomarkers. Front. Psychiatry. 2022;13:813304. doi: 10.3389/fpsyt.2022.813304. PubMed DOI PMC

Masi A., Quintana D.S., Glozier N., Lloyd A.R., Hickie I.B., Guastella A.J. Cytokine aberrations in autism spectrum disorder: A systematic review and meta-analysis. Mol. Psychiatry. 2015;20:440–446. doi: 10.1038/mp.2014.59. PubMed DOI

Liu H., Talalay P., Fahey J.W. Biomarker-Guided Strategy for Treatment of Autism Spectrum Disorder (ASD) CNS Neurol. Disord.-Drug Targets. 2016;15:602–613. doi: 10.2174/1871527315666160413120414. PubMed DOI

Rossignol D.A., Frye R.E. Evidence linking oxidative stress, mitochondrial dysfunction, and inflammation in the brain of individuals with autism. Front. Physiol. 2014;5:150. doi: 10.3389/fphys.2014.00150. PubMed DOI PMC

Klomparens E.A., Ding Y. The neuroprotective mechanisms and effects of sulforaphane. Brain Circ. 2019;5:74–83. PubMed PMC

Yang J., Fu X., Liao X., Li Y. Nrf2 Activators as Dietary Phytochemicals Against Oxidative Stress, Inflammation, and Mitochondrial Dysfunction in Autism Spectrum Disorders: A Systematic Review. Front. Psychiatry. 2020;11:561998. doi: 10.3389/fpsyt.2020.561998. PubMed DOI PMC

Singh K., Connors S.L., Macklin E.A., Smith K.D., Fahey J.W., Talalay P., Zimmerman A.W. Sulforaphane treatment of autism spectrum disorder (ASD) Proc. Natl. Acad. Sci. USA. 2014;111:15550–15555. doi: 10.1073/pnas.1416940111. PubMed DOI PMC

Evans S., Fuller D.J. Initial outcomes from an autism treatment demonstration. Clin. Med. Investig. 2016;1:16–19. doi: 10.15761/CMI.1000103. DOI

Bent S., Lawton B., Warren T., Widjaja F., Dang K., Fahey J.W., Hendren R.L. Identification of urinary metabolites that correlate with clinical improvements in children with autism treated with sulforaphane from broccoli. Mol. Autism. 2018;9:35. doi: 10.1186/s13229-018-0218-4. PubMed DOI PMC

Zimmerman A.W., Singh K., Connors S.L., Liu H., Panjwani A.A., Lee L., Fahey J.W. Randomized controlled trial of sulforaphane and metabolite discovery in children with Autism Spectrum Disorder. Mol. Autism. 2021;12:38. doi: 10.1186/s13229-021-00447-5. Erratum in Mol. Autism 2021, 12, 44. PubMed DOI PMC

Politte L. Sulforaphane for the Treatment of Young Men with Autism Spectrum Disorder. NCT02909959 2020. [(accessed on 1 January 2023)]; Available online: https://www.clinicaltrials.gov/ct2/show/NCT02909959?cond=NCT02909959.

Smith R., Ou J., Jin H., Wu R., Fahey J., Arriaza J., Davis J.M. ACNP 59th Annual Meeting: Poster Session I: Neuropsychopharmacology. Volume 45. Springer; Berlin, Germany: 2020. Sulforaphane as a Treatment for Autism: A Randomized Double-Blind Study; pp. 68–169. PubMed

Gotham K., Pickles A., Lord C.J. Standardizing ADOS scores for a measure of severity in autism spectrum disorders. Autism Dev. Disord. 2009;39:693–705. doi: 10.1007/s10803-008-0674-3. PubMed DOI PMC

Frazier T.W., Ratliff K.R., Gruber C., Zhang Y., Law P.A., Constantino J.N. Confirmatory factor analytic structure and measurement invariance of quantitative autistic traits measured by the social responsiveness scale-2. Autism. 2014;18:31–44. doi: 10.1177/1362361313500382. PubMed DOI

Egner P.A., Chen J.G., Wang J.B., Wu Y., Sun Y., Lu J.H., Kensler T.W. Bioavailability of Sulforaphane from two broccoli sprout beverages: Results of a short-term, cross-over clinical trial in Qidong, China. Cancer Prev. Res. (Phila) 2021;4:384–395. doi: 10.1158/1940-6207.CAPR-10-0296. PubMed DOI PMC

Goin-Kochel R.P., Mazefsky C.A., Riley B.P. Level of functioning in autism spectrum disorders: Phenotypic congruence among affected siblings. J. Autism Dev. Disord. 2008;38:1019–1027. doi: 10.1007/s10803-007-0476-z. PubMed DOI PMC

Stewart-Williams S., Podd J. The placebo effect: Dissolving the expectancy versus conditioning debate. Psychol. Bull. 2004;120:324–340. doi: 10.1037/0033-2909.130.2.324. PubMed DOI

Yasir M., Angelakis E., Bibi F. Comparison of the gut microbiota of people in France and Saudi Arabia. Nutr. Diabetes. 2015;5:e153. doi: 10.1038/nutd.2015.3. PubMed DOI PMC

Gupta V.K., Paul S., Dutta C. Geography, Ethnicity or Subsistence-Specific Variations in Human Microbiome Composition and Diversity. Front. Microbiol. 2017;8:1162. doi: 10.3389/fmicb.2017.01162. PubMed DOI PMC

Porras A.M., Shi Q., Zhou H., Callahan R., Montenegro-Bethancourt G., Solomons N., Brito I.L. Geographic differences in gut microbiota composition impact susceptibility to enteric infection. Cell Rep. 2021;36:109457. doi: 10.1016/j.celrep.2021.109457. PubMed DOI PMC

Siafis S., Çıray O., Wu H., Schneider-Thoma J., Bighelli I., Krause M., Leucht S. Pharmacological and dietary-supplement treatments for autism spectrum disorder: A systematic review and network meta-analysis. Mol. Autism. 2022;13:10. doi: 10.1186/s13229-022-00488-4. PubMed DOI PMC

Barbaresi W.J., Katusic S.K., Voigt R.G. Autism: A review of the state of the science for pediatric primary health care clinicians. Arch. Pediatr. Adolesc. Med. 2006;160:1167–1175. doi: 10.1001/archpedi.160.11.1167. PubMed DOI

Coplan J., Souders M.C., Mulberg A.E., Belchic J.K., Wray J., Jawad A.F., Levy S.E. Children with autistic spectrum disorders. II. Parents are unable to distinguish secretin from placebo under double-blind conditions. Arch. Dis. Child. 2003;88:737–739. doi: 10.1136/adc.88.8.737. PubMed DOI PMC

Silva Pereira A., Helena R., Almeida L. A Comparison of Parent and Professional Perceptions of Children with Autism Spectrum Disorder in Portugal. Br. J. Spéc. Educ. 2017;44:257–272.

McGuinness G., Kim Y. Sulforaphane treatment for autism spectrum disorder: A systematic review. EXCLI J. 2020;19:892–903. PubMed PMC

Momtazmanesh S., Amirimoghaddam-Yazdi Z., Moghaddam H.S., Mohammadi M.R., Akhondzadeh S. Sulforaphane as an adjunctive treatment for irritability in children with autism spectrum disorder: A randomized, double-blind, placebo-controlled clinical trial. Psychiatry Clin. Neurosci. 2020;74:398–405. doi: 10.1111/pcn.13016. PubMed DOI

Aishworiya R., Valica T., Hagerman R., Restrepo B. An Update on Psychopharmacological Treatment of Autism Spectrum Disorder. Neurotherapeutics. 2022;19:248–262. PubMed PMC

Reply to Curtis, L. Comment on "Magner et al. Sulforaphane Treatment in Children with Autism: A Prospective Randomized Double-Blind Study. Nutrients 2023, 15, 718"