Efficacy of Sulforaphane in Treatment of Children with Autism Spectrum Disorder: A Randomized Double-Blind Placebo-Controlled Multi-center Trial

Ou, Jianjun; Smith, Robert C.; Tobe, Russell H.; Lin, Jingjing; Arriaza, Jen; Fahey, Jed W.; Liu, Ruiting; Zeng, Ying; Liu, Yanan; Huang, Lian; Shen, Yidong; Li, Yamin; Cheng, Daomeng; Cornblatt, Brian S.; Davis, John M.; Zhao, Jingping; Wu, Renrong; Jiang, Hua

doi:10.1007/s10803-022-05784-9

Cited by 7 publications

(10 citation statements)

References 30 publications

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“…Sulforaphane has been shown to ameliorate autistic behavior in human subjects. ASD subjects treated with sulforaphane showed improvement in autism-related behaviors such as social interaction and verbal communication [ 63 , 64 , 65 ]. However, a recent study showed no significant clinical improvement in the behavioral outcomes in ASD subjects after treatment with sulforaphane [ 66 ].…”

Section: Discussionmentioning

confidence: 99%

Thioredoxin 1 and Thioredoxin Reductase 1 Redox System Is Dysregulated in Neutrophils of Subjects with Autism: In Vitro Effects of Environmental Toxicant, Methylmercury

Alshehri,

Ahmad,

Albekairi

et al. 2023

Toxics

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Autism spectrum disorder (ASD) is a complex developmental disorder in children that results in abnormal communicative and verbal behaviors. Exposure to heavy metals plays a significant role in the pathogenesis or progression of ASD. Mercury compounds pose significant risk for the development of ASD as children are more exposed to environmental toxicants. Increased concentration of mercury compounds has been detected in different body fluids/tissues in ASD children, which suggests an association between mercury exposure and ASD. Thioredoxin1 (Trx1) and thioredoxin reductase1 (TrxR1) redox system plays a crucial role in detoxification of oxidants generated in different immune cells. However, the effect of methylmercury and the Nrf2 activator sulforaphane on the Trx1/TrxR1 antioxidant system in neutrophils of ASD subjects has not been studied previously. Therefore, this study examined the effect of methylmercury on Trx1/TrxR1 expression, TrxR activity, nitrotyrosine, and ROS in neutrophils of ASD and TDC subjects. Our study shows that Trx1/TrxR1 protein expression is dysregulated in ASD subjects as compared to the TDC group. Further, methylmercury treatment significantly inhibits the activity of TrxR in both ASD and TDC groups. Inhibition of TrxR by mercury is associated with upregulation of the Trx1 protein in TDC neutrophils but not in ASD neutrophils. Furthermore, ASD neutrophils have exaggerated ROS production after exposure to methylmercury, which is much greater in magnitude than TDC neutrophils. Sulforaphane reversed methylmercury-induced effects on neutrophils through Nrf2-mediated induction of the Trx1/TrxR1 system. These observations suggest that exposure to the environmental toxicant methylmercury may elevate systemic oxidative inflammation due to a dysregulated Trx1/TrxR1 redox system in the neutrophils of ASD subjects, which may play a role in the progression of ASD.

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Section: Discussionmentioning

confidence: 99%

Thioredoxin 1 and Thioredoxin Reductase 1 Redox System Is Dysregulated in Neutrophils of Subjects with Autism: In Vitro Effects of Environmental Toxicant, Methylmercury

Alshehri,

Ahmad,

Albekairi

et al. 2023

Toxics

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“…The data and stool samples of ASD patients were obtained from previous clinical trials ( 6 ), and healthy controls were recruited by age-matched. Eleven healthy controls and six individuals with ASD were recruited by the Department of Psychiatry, Second Xiangya Hospital, which is affiliated with Central South University in Changsha, Hunan Province of China.…”

Section: Methodsmentioning

confidence: 99%

“…The score of the ASD group was assessed at baseline and on the last day of week 12. Refer to our previous clinical studies for specific SFN usage, safety measures, and OARS-4 measures ( 6 ).…”

Section: Methodsmentioning

confidence: 99%

Therapeutic efficacy of sulforaphane in autism spectrum disorders and its association with gut microbiota: animal model and human longitudinal studies

Yang,

He,

Dai

et al. 2024

Front. Nutr.

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IntroductionSulforaphane (SFN) has been found to alleviate complications linked with several diseases by regulating gut microbiota (GM), while the effect of GM on SFN for autism spectrum disorders (ASD) has not been studied. Therefore, this study aimed to investigate the relationship between the effects of SFN on childhood ASD and GM through animal model and human studies.MethodsWe evaluated the therapeutic effects of SFN on maternal immune activation (MIA) induced ASD-like rat model and pediatric autism patients using three-chamber social test and OSU Autism Rating Scale-DSM-IV (OARS-4), respectively, with parallel GM analysis using 16SrRNA sequencing.ResultsSFN significantly improved the sniffing times of ASD-like rats in the three-chamber test. For human participants, the average verbal or non-verbal communication (OSU-CO) scores of SFN group had changed significantly at the 12-wk endpoint. SFN was safe and no serious side effects after taking. GM changes were similar for both ASD-like rats and ASD patients, such as consistent changes in order Bacillales, family Staphylococcaceae and genus Staphylococcus. Although the gut microbiota composition was significantly altered in SFN-treated ASD-like rats, the alteration of GM was not evident in ASD patients after 12 weeks of SFN treatment. However, in the network analysis, we found 25 taxa correlated with rats' social behavior, 8 of which were associated with SFN treatment in ASD-like rats, For ASD patients, we found 35 GM abundance alterations correlated with improvements in ASD symptoms after SFN treatment. Moreover, family Pasteurellaceae and genus Haemophilus were found to be associated with SFN administration in the network analyses in both ASD-like rats and ASD patients.DiscussionThese findings suggest that SFN could provide a novel avenue for preventing and treating ASD, and its therapeutic effects might be related to gut microbiota.

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“…As a natural antioxidant, sulforaphane has been shown in randomized clinical trials to have a significant remission effect on ASD (Ou et al, 2022), and thus, it is a favorable plant-derived functional active substance. Another clinical trial has also shown that sulforaphane can be used in conjunction with the medication risperidone in the treatment of ASD, and that it is effective at reducing irritability and hyperactivity in children with ASD (Momtazmanesh et al, 2020).…”

Section: Other Natural Products From Food Sourcesmentioning

confidence: 99%

“…A blueberry extract (rich in anthocyanins) intervention in a mouse model of valproic acid‐induced ASD resulted in regulation of the composition of the gut microbiota and the levels of serotonin and a significant improvement in ASD phenotypes (Serra et al., 2022). As a natural antioxidant, sulforaphane has been shown in randomized clinical trials to have a significant remission effect on ASD (Ou et al., 2022), and thus, it is a favorable plant‐derived functional active substance. Another clinical trial has also shown that sulforaphane can be used in conjunction with the medication risperidone in the treatment of ASD, and that it is effective at reducing irritability and hyperactivity in children with ASD (Momtazmanesh et al., 2020).…”

Section: Food‐derived Nutrients That Have Effects On Asdmentioning

confidence: 99%

Dietary nutrients that potentially mitigate autism spectrum disorder and dietary recommendations for children and pregnant women

Li,

Kong,

Tian

et al. 2024

Food Frontiers

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The increasing incidence of autism spectrum disorder (ASD) worldwide poses serious social and family problems. Various risk factors for ASD are gradually being recognized, and there are also various options for the treatment of ASD. It is worth noting that dietary interventions have been shown to have a positive effect in terms of mitigating and preventing some psychiatric disorders, such as epilepsy, Parkinson's disease, and ASD, and they are gradually receiving attention as a safe adjuvant treatment. In this review, based on the current understanding of the pathogenic factors and intervention strategies for ASD, different dietary patterns that can be selected for children with ASD are discussed in depth. Moreover, a review was conducted on the use of dietary factors, such as natural products from food sources, prebiotics, and probiotics, as effective supplements to existing dietary patterns. As increasing evidence shows that maternal risk factors, such as obesity, diabetes, and hypertension, are associated with an increased risk of ASD in offspring, dietary suggestions are also made for pregnant woman with ASD‐related risk factors to counteract the impact of these risk factors. With compensation from food‐derived natural products, prebiotics, and probiotics, suitable dietary patterns can further enhance the effectiveness of dietary interventions for ASD. In addition, dietary recommendations for pregnant woman may reduce the potential impact of obesity, diabetes, and hypertension and may help to prevent the occurrence of ASD to the maximum extent possible.

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Efficacy of Sulforaphane in Treatment of Children with Autism Spectrum Disorder: A Randomized Double-Blind Placebo-Controlled Multi-center Trial

Cited by 7 publications

References 30 publications

Thioredoxin 1 and Thioredoxin Reductase 1 Redox System Is Dysregulated in Neutrophils of Subjects with Autism: In Vitro Effects of Environmental Toxicant, Methylmercury

Thioredoxin 1 and Thioredoxin Reductase 1 Redox System Is Dysregulated in Neutrophils of Subjects with Autism: In Vitro Effects of Environmental Toxicant, Methylmercury

Therapeutic efficacy of sulforaphane in autism spectrum disorders and its association with gut microbiota: animal model and human longitudinal studies

Dietary nutrients that potentially mitigate autism spectrum disorder and dietary recommendations for children and pregnant women

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