Sulforaphane treatment of autism spectrum disorder (ASD)
Open accessAbstract
Autism spectrum disorder (ASD), characterized by both impaired communication and social interaction, and by stereotypic behavior, affects about 1 in 68, predominantly males. The medico-economic burdens of ASD are enormous, and no recognized treatment targets the core features of ASD. In a placebo-controlled, double-blind, randomized trial, young men (aged 13-27) with moderate to severe ASD received the phytochemical sulforaphane (n = 29)--derived from broccoli sprout extracts--or indistinguishable placebo (n = 15). The effects on behavior of daily oral doses of sulforaphane (50-150 µmol) for 18 wk, followed by 4 wk without treatment, were quantified by three widely accepted behavioral measures completed by parents/caregivers and physicians: the Aberrant Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and Clinical Global Impression Improvement Scale (CGI-I). Initial scores for ABC and SRS were closely matched for participants assigned to placebo and sulforaphane. After 18 wk, participants receiving placebo experienced minimal change (<3.3%), whereas those receiving sulforaphane showed substantial declines (improvement of behavior): 34% for ABC (P < 0.001, comparing treatments) and 17% for SRS scores (P = 0.017). On CGI-I, a significantly greater number of participants receiving sulforaphane had improvement in social interaction, abnormal behavior, and verbal communication (P = 0.015-0.007). Upon discontinuation of sulforaphane, total scores on all scales rose toward pretreatment levels. Dietary sulforaphane, of recognized low toxicity, was selected for its capacity to reverse abnormalities that have been associated with ASD, including oxidative stress and lower antioxidant capacity, depressed glutathione synthesis, reduced mitochondrial function and oxidative phosphorylation, increased lipid peroxidation, and neuroinflammmation.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In a controlled trial of young men ages 13 to 27 with moderate to severe ASD treated with sulforaphane (n = 29) compared to placebo (n = 15) for 18 weeks, significant improvements were seen on the ABC, CGI-I, and SRS.
“There have been a few studies in patients with ASD [68, 69] including a controlled trial of young men ages 13 to 27 with moderate to severe ASD treated with sulforaphane (n = 29) compared to placebo (n = 15) for 18 weeks. Significant improvements were seen on the Aberrant Behavior Checklist (ABC), the Clinical Global Improvement Scale (CGI-I), and the Social Responsiveness Scale 2 (SRS) [69].”
From An Update on Psychopharmacological Treatment of Autism Spectrum Disorder (2022) · cites this paper as [69]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Baio, J., Wiggins, L., Christensen, D. L., Maenner, M. J., Daniels, J., Warren, Z., Kurzius-Spencer, M., Zahorodny, W., Robinson, C., Rosenberg, et al. (2018) · MMWR. Surveillance Summaries · doi:10.15585/mmwr.ss6706a1 · Cited by 6,078 · see citing works
Maenner, M. J., Shaw, K. A., Baio, J., EdS1, Washington, A., Patrick, M., DiRienzo, M., Christensen, D. L., Wiggins, L. D., Pettygrove, S., et al. (2020) · MMWR. Surveillance Summaries · doi:10.15585/mmwr.ss6904a1 · Cited by 3,780 · see citing works
Neuroglial activation and neuroinflammation in the brain of patients with autism
Vargas, D. L., Nascimbene, C., Krishnan, C., Zimmerman, A. W., & Pardo, C. A. (2005) · Annals of Neurology · doi:10.1002/ana.20315 · Cited by 2,149 · cited 1× · see citing works
“phosphorylation, increased lipid peroxidation, and neuroinflammation (11-17).”
Self-citationZhang, Y., Talalay, P., Cho, C. G., & Posner, G. H. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.6.2399 · Cited by 1,682 · see citing works
Self-citationConstantino, J. N., Davis, S. A., Todd, R. D., Schindler, M. K., Gross, M. M., Brophy, S. L., Metzger, L. M., Shoushtari, C. S., Splinter, R., & Reich, W. (2003) · Journal of Autism and Developmental Disorders · doi:10.1023/a:1025014929212 · Cited by 1,611 · see citing works
Naarden Braun, K. V., Lopez, M., White, T., et al. (2023) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/y3kk-5x30 · Cited by 1,381 · see citing works
The cytoprotective role of the Keap1–Nrf2 pathway
Baird, L., & Dinkova‐Kostova, A. T. (2011) · Archives of Toxicology · doi:10.1007/s00204-011-0674-5 · Cited by 1,029 · see citing works
James, S. J., Cutler, P., Melnyk, S., Jernigan, S., Janak, L., Gaylor, D. W., & Neubrander, J. A. (2004) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/80.6.1611 · Cited by 955 · see citing works
Zhang, Y., Kensler, T. W., Cho, C., Posner, G. H., & Talalay, P. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.8.3147 · Cited by 746 · see citing works
Self-citationMolecular basis for chemoprevention by sulforaphane: a comprehensive review
Juge, N., Mithen, R. F., & Τράκα, Μ. (2007) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-007-6484-5 · Cited by 696 · see citing works
Child Health, Developmental Plasticity, and Epigenetic Programming
Hochberg, Z., Feil, R., Constância, M., Fraga, M. F., Junien, C., Carel, J., Boileau, P., Bouc, Y. L., Deal, C., Lillycrop, K. A., et al. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0039 · Cited by 631 · see citing works
Mitochondrial dysfunction in autism
Giulivi, C., Zhang, Y.-F., Omanska-Klusek, A., Ross-Inta, C., Wong, S., Hertz-Picciotto, I., Tassone, F., & Pessah, I. N. (2010) · JAMA · doi:10.1001/jama.2010.1706 · Cited by 466 · see citing works
Maternal lifestyle and environmental risk factors for autism spectrum disorders
Lyall, K., Schmidt, R. J., & Hertz-Picciotto, I. (2014) · International Journal of Epidemiology · doi:10.1093/ije/dyt282 · Cited by 427 · see citing works
Chemoprotection against cancer by induction of Phase 2 enzymes
Talalay, P. (2000) · BioFactors · doi:10.1002/biof.5520120102 · Cited by 421 · see citing works
Self-citationKeap1–Nrf2 Signaling: A Target for Cancer Prevention by Sulforaphane
Kensler, T. W., Egner, P. A., Agyeman, A. S., Visvanathan, K., Groopman, J. D., Chen, J., Chen, T.-Y., Fahey, J. W., & Talalay, P. (2012) · Topics in current chemistry · doi:10.1007/128_2012_339 · Cited by 363 · see citing works
Self-citationHeat shock proteins: Cellular and molecular mechanisms in the central nervous system
Stetler, R. A., Gan, Y., Zhang, W., Liou, A. K. F., Gao, Y., Cao, G., & Chen, J. (2010) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2010.05.002 · Cited by 306 · see citing works
Danielsson, S., Gillberg, I. C., Billstedt, E., Gillberg, C., & Olssøn, I. (2005) · Epilepsia · doi:10.1111/j.1528-1167.2005.57504.x · Cited by 296 · see citing works
The incidence of seizures among children with autistic symptoms
Deykin, E. Y., & MacMahon, B. (1979) · American Journal of Psychiatry · doi:10.1176/ajp.136.10.1310 · Cited by 239 · see citing works
James, S. J., Rose, S., Melnyk, S., Jernigan, S., Blossom, S. J., Pavliv, O., & Gaylor, D. W. (2009) · The FASEB Journal · doi:10.1096/fj.08-128926 · Cited by 223 · see citing works
Egner, P. A., Chen, J., Wang, J. B., Wu, Y., Sun, Y., Lu, J. H., Zhu, J., Zhang, Y. H., Chen, Y. S., Friesen, M. D., et al. (2011) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-10-0296 · Cited by 213 · see citing works
Self-citationEgner, P. A., Chen, J., Zarth, A. T., Ng, D. K., Wang, J.-B., Kensler, K. H., Jacobson, L. P., Muñoz, Á., Johnson, J. L., Groopman, J. D., et al. (2014) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-14-0103 · Cited by 195 · see citing works
Self-citationMarshburn, E. C., & Aman, M. G. (1992) · Journal of Autism and Developmental Disorders · doi:10.1007/bf01048240 · Cited by 171 · see citing works
Neuroinflammation in autism spectrum disorders
El-Ansary, A. K., & AL-Ayadhi, L. Y. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-265 · Cited by 167 · see citing works
Behaviors Associated With Fever in Children With Autism Spectrum Disorders
Curran, L. K., Newschaffer, C. J., Lee, L.-C., Crawford, S. O., Johnston, M. V., & Zimmerman, A. W. (2007) · Pediatrics · doi:10.1542/peds.2007-0360 · Cited by 158 · see citing works
Self-citationGan, N., Wu, Y.-C., Brunet, M., Garrido, C., Chung, F., Dai, C., & Mi, L. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.152686 · Cited by 142 · see citing works
Psychosocial Profile of Bullies, Victims, and Bully-Victims: A Cross-Sectional Study
Leiner, M. A., Dwivedi, A. K., Villanos, M. T., Singh, N., Blunk, D. I., & Peinado, J. (2014) · Frontiers in Pediatrics · doi:10.3389/fped.2014.00001 · Cited by 141 · see citing works
Developmental course of autistic social impairment in males
Constantino, J. N., Abbacchi, A. M., LaVesser, P., Reed, H., Givens, L., Chiang, L., Gray, T., Gross, M. M., Zhang, Y., & Todd, R. D. (2009) · Development and Psychopathology · doi:10.1017/s095457940900008x · Cited by 121 · see citing works
Epigenetics, Autism Spectrum, and Neurodevelopmental Disorders
Rangasamy, S., D’Mello, S. R., & Narayanan, V. (2013) · Neurotherapeutics · doi:10.1007/s13311-013-0227-0 · Cited by 118 · see citing works
Deficits in bioenergetics and impaired immune response in granulocytes from children with autism
Napoli, E., Wong, S., Hertz-Picciotto, I., & Giulivi, C. (2014) · Pediatrics · doi:10.1542/peds.2013-1545 · Cited by 117 · see citing works
Autism, fever, epigenetics and the locus coeruleus
Mehler, M. F., & Purpura, D. P. (2008) · Brain Research Reviews · doi:10.1016/j.brainresrev.2008.11.001 · Cited by 115 · see citing works
Wiggins, J. L., Peltier, S., Ashinoff, S., Weng, S.-J., Carrasco, M., Welsh, R. C., Lord, C., & Monk, C. S. (2010) · Brain Research · doi:10.1016/j.brainres.2010.10.102 · Cited by 106 · see citing works
Treatments for Biomedical Abnormalities Associated with Autism Spectrum Disorder
Frye, R. E., & Rossignol, D. A. (2014) · Frontiers in Pediatrics · doi:10.3389/fped.2014.00066 · Cited by 90 · see citing works
Notes from the Field: “Green” Chemoprevention as Frugal Medicine
Fahey, J. W., Talalay, P., & Kensler, T. W. (2012) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-11-0572 · Cited by 71 · see citing works
Self-citationActivation of the stress proteome as a mechanism for small molecule therapeutics
Brose, R. D., Shin, G., McGuinness, M. C., Schneidereith, T., Purvis, S. H., Dong, G.-X., Keefer, J. R., Spencer, F. A., & Smith, K. D. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds247 · Cited by 46 · see citing works
Self-citationDinkova‐Kostova, A. T. (2012) · Scientifica · doi:10.6064/2012/606104 · Cited by 35 · see citing works
Olsson, N. C., & Bölte, S. (2013) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-013-2029-y · Cited by 31 · see citing works
Frackowiak, J., Mazur‐Kolecka, B., Schanen, N. C., Brown, W. T., & Węgiel, J. (2013) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-1-61 · Cited by 29 · see citing works
Stanghellini, G., Ballerini, M., & Lysaker, P. H. (2014) · Giornale italiano di psicopatologia/Journal of psychopathology/Italian journal of psychopathology · Cited by 25 · see citing works
Health Span Extension through Green Chemoprevention
Fahey, J. W., & Kensler, T. W. (2013) · The AMA Journal of Ethic · doi:10.1001/virtualmentor.2013.15.4.stas1-1304 · Cited by 22 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 3
- [1]American Psychiatric Association . Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) American Psychiatric Association; Arlington, VA: 2000. [Google Scholar]
- [33]Miles JH. 2010. Workshop Report: Fever and Autism. Available at http://sfari.org/news-and-opinion/workshop-reports/2010/workshop-report-fever-and-autism. Accessed August 20, 2014.
- [39]Liang KY, Zeger S. Longitudinal data analysis of continuous and discrete responses for pre–post designs. Sankhyā: The Indian Journal of Statistics. 2000;62(1):134–148. [Google Scholar]
Cited by
Sorted by citations
Targeting oxidative stress in disease: Promise and limitations of antioxidant therapy
Forman, H. J., & Zhang, H. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00233-1 · Cited by 2,900 · see citing works
Lord, C., Elsabbagh, M., Baird, G., & Veenstra-Vanderweele, J. (2018) · The Lancet · doi:10.1016/s0140-6736(18)31129-2 · Cited by 2,819 · see citing works
The KEAP1-NRF2 system: a thiol-based sensor-effector apparatus for maintaining redox homeostasis
Yamamoto, M., Kensler, T. W., & Motohashi, H. (2018) · Physiological Reviews · doi:10.1152/physrev.00023.2017 · Cited by 1,968 · see citing works
Long-term benefit of microbiota transfer therapy on autism symptoms and gut microbiota
Kang, D.-W., Adams, J. B., Coleman, D. M., Pollard, E. L., Maldonado, J., McDonough-Means, S., Caporaso, J. G., & Krajmalnik-Brown, R. (2019) · Scientific Reports · doi:10.1038/s41598-019-42183-0 · Cited by 749 · see citing works
The multifaceted role of Nrf2 in mitochondrial function
Holmström, K. M., Kostov, R. V., & Dinkova-Kostova, A. T. (2016) · Current Opinion in Toxicology · doi:10.1016/j.cotox.2016.10.002 · Cited by 368 · see citing works
Thirty years of NRF2: advances and therapeutic challenges.
Zhang, D. D. (2025) · Nature Reviews Drug Discovery · doi:10.1038/s41573-025-01145-0 · Cited by 282 · see citing works
An Update on Psychopharmacological Treatment of Autism Spectrum Disorder
Aishworiya, R., Valica, T., Hagerman, R., & Restrepo, B. (2022) · Neurotherapeutics · doi:10.1007/s13311-022-01183-1 · Cited by 233 · see citing works
The KEAP1–NRF2 System as a Molecular Target of Cancer Treatment
Taguchi, K., & Yamamoto, M. (2020) · Cancers · doi:10.3390/cancers13010046 · Cited by 195 · see citing works
Yao, W., Zhang, J.-C., Ishima, T., Dong, C., Yang, C., Ren, Q., Ma, M., Han, M., Wu, J., Suganuma, H., et al. (2016) · Scientific Reports · doi:10.1038/srep30659 · Cited by 154 · see citing works
Pearson, B. L., Simon, J. M., McCoy, E. S., Salazar, G., Fragola, G., & Zylka, M. J. (2016) · Nature Communications · doi:10.1038/ncomms11173 · Cited by 127 · see citing works
Sulforaphane produces antidepressant- and anxiolytic-like effects in adult mice
Wu, S., Gao, Q., Zhao, P., Gao, Y., Xi, Y., Wang, X., Liang, Y., Shi, H., & Ma, Y. (2016) · Behavioural Brain Research · doi:10.1016/j.bbr.2015.12.030 · Cited by 97 · see citing works
Essential Role of Keap1-Nrf2 Signaling in Mood Disorders: Overview and Future Perspective
Hashimoto, K. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.01182 · Cited by 98 · see citing works
Frye, R. E., & Rossignol, D. A. (2016) · Clinical Medicine Insights Pediatrics · doi:10.4137/cmped.s38337 · Cited by 96 · see citing works
Pharmacology and Clinical Drug Candidates in Redox Medicine
Dao, V. T.-V., Casas, A. I., Maghzal, G. J., Seredenina, T., Kaludercic, N., Robledinos-Anton, N., Di Lisa, F., Stocker, R., Ghezzi, P., Jaquet, V., et al. (2015) · Antioxidants & Redox Signaling · doi:10.1089/ars.2015.6430 · Cited by 88 · see citing works
Dietary Interventions for Autism Spectrum Disorder: A Meta-analysis
Fraguas, D., Díaz-Caneja, C. M., Pina-Camacho, L., Moreno, C., Durán-Cutilla, M., Ayora, M., González-Vioque, E., de Matteis, M., Hendren, R. L., Arango, C., et al. (2019) · PEDIATRICS · doi:10.1542/peds.2018-3218 · Cited by 80 · see citing works
Immunological Dysfunction in Autism Spectrum Disorder: A Potential Target for Therapy
Marchezan, J., Winkler dos Santos, E. G. A., Deckmann, I., & Riesgo, R. D. S. (2018) · Neuroimmunomodulation · doi:10.1159/000492225 · Cited by 70 · see citing works
Keap1-Nrf2 signaling pathway confers resilience versus susceptibility to inescapable electric stress
Zhang, J.-C., Yao, W., Dong, C., Han, M., Shirayama, Y., & Hashimoto, K. (2018) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-017-0848-0 · Cited by 66 · see citing works
Nadeem, A., Ahmad, S. F., Attia, S. M., AL-Ayadhi, L. Y., Bakheet, S. A., & Al-Harbi, N. O. (2019) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2018.12.002 · Cited by 63 · see citing works
Bennett (2023) · doi:10.1097/yco.0000000000000775 · Cited by 51 · see citing works
Endocrine insights into the pathophysiology of autism spectrum disorder
Wilson, H. A., Creighton, C., Scharfman, H., Choleris, E., & MacLusky, N. J. (2021) · The Neuroscientist · doi:10.1177/1073858420952046 · Cited by 23 · see citing works
Slattery, J., MacFabe, D., Kahler, S., & Frye, R. (2016) · Current Pharmaceutical Design · doi:10.2174/1381612822666160905123953 · Cited by 20 · see citing works
- Authors
- Singh, K., Connors, S. L., Macklin, E. A., Smith, K. D., Fahey, J. W., Talalay, P., & Zimmerman, A. W.
- Affiliations
- Harvard University (US)
- McKusick–Nathans Institute for Genetic Medicine and
- Johns Hopkins University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-10-13
- Volume
- 111
- Issue
- 43
- Pages
- 15550-15555
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4217462
- OpenAlex
- W2025450822
- Cited by
- 449
- References
- 40
- Citations by year
- 2026: 18 · 2025: 30 · 2024: 31 · 2023: 34 · 2022: 51 · 2021: 54 · 2020: 46 · 2019: 40 · 2018: 36 · 2017: 33 · 2016: 43 · 2015: 30 · 2014: 2
- FWCI
- 20.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Health Sciences › Medicine › Psychiatry and Mental health › Child Nutrition and Feeding Issues
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- sulforaphane, autism spectrum disorder, broccoli sprout extract, dietary phytochemicals, aberrant behavior, social responsiveness, oxidative stress, glutathione synthesis, mitochondrial dysfunction, neuroinflammation, lipid peroxidation, antioxidant capacity, treatment discontinuation, young men
- MeSH terms
- Adolescent, Adult, Child Development Disorders, Pervasive, Humans, Male, Placebos, Social Behavior, Sulfoxides, Treatment Outcome, Isothiocyanates, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
