NAC Autism research
A Randomized Controlled Pilot Trial of Oral N-Acetylcysteine in Children with Autism
Authors:
Hardan, A.Y., Fung, L.K., Libove, R.A., Obukhanych, T.V., Nair, S., Herzenberg, L.A., Frazier, T.W. and Tirouvanziam, R.
Research study
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Type
Study size
Abstract
LINK/DOI
Objective: The objective of this study was to assess the levels of ten toxic metals and essential elements in hair samples of children with autism, and to correlate the level of these elements with the severity of autism.
Method: The participants were 44 children, age 3 to 9 years, with Autistic Spectrum Disorder (ASD) according to Diagnostic and Statistical Manual of Mental Disorders 4th Edition, (DSM-IV). The severity of autistic symptomatology was measured by the Childhood Autism Rating Scale (CARS). Hair analysis was performed to evaluate the long term metal exposure and mineral level.
Results: By comparing hair concentration of autistic vs nonautistic children, elevated hair concentrations were noted for aluminum, arsenic, cadmium, mercury, antimony, nickel, lead, and vanadium. Hair levels of calcium, iron, iodine, magnesium, manganese, molybdenum, zinc, and selenium were considered deficient. There was a significant positive correlation between lead & verbal communication (p = 0.020) and general impression (p = 0.008). In addition, there was a significant negative correlation between zinc & fear and nervousness (p = 0.022).
Conclusion: Our data supports the historic evidence that heavy metals play a role in the development of ASD. In combination with an inadequate nutritional status the toxic effect of metals increase along with the severity of symptoms.
44
Observational cross-sectional study
2021
doi: 10.1016/j.biopsych.2012.01.014
Possible effects of N-acetylcysteine in autism spectrum disorders: major clinical aspects, eating behaviors, and sleeping habits
Authors:
Nalbant, K. and Erden, S.
Research study
Year
Type
Study size
Abstract
LINK/DOI
Background: N-acetylcysteine (NAC) is a promising agent for reducing irritability and hyperactivity and enhancing social responsiveness in children with autism spectrum disorders (ASD). This study aims to examine the effects of NAC on cardinal symptoms, eating, and sleeping habits in preschool children with autism.
Methods: The medical records of ASD patients were investigated retrospectively. 37 children with ASD who regularly received oral NAC in two divided doses per day (400-600 mg/day) for 8 weeks were included as the study group. The control group consisted of 21 children with ASD who were recommended NAC but never used it. The initial and second assessment scores after 8 weeks of regular use of the NAC group and control group on the Childhood Autism Rating Scale (CARS), Aberrant Behavior Checklist (ABC), Children Eating Behavior Questionnaire (CEBQ), and the Sleep Habits Questionnaire (CSHQ) were compared.
Results: Our findings suggested that oral NAC alleviated the intensity of cardinal autistic symptoms in areas of social withdrawal, interpersonal relationships, body use, listening response, and verbal communication. Corresponding problem behaviors such as irritability, stereotypic behavior, and hyperactivity were reduced. It was determined that there was no difference between the two groups in terms of eating behaviors and sleeping habits.
Conclusions: According to the results, NAC alleviated the severity of cardinal symptoms and reduced problem behaviors in autism. Additional trials with more systematic planning, controlling for confounding effects, and long-term follow-up should be provided in future studies.
37
Retrospective study
2023
doi: 10.24953/turkjped.2022.573
N-acetylcysteine as an adjunctive therapy to risperidone for treatment of irritability in autism: a randomized, double-blind, placebo-controlled clinical trial of efficacy and safety
Authors:
Nikoo, M., Radnia, H., Farokhnia, M., Mohammadi, M.R. and Akhondzadeh, S.
Research study
Year
Type
Study size
Abstract
LINK/DOI
Objectives: According to the proposed interference of N-acetylcysteine (NAC) with pathophysiologic processes of autistic disorders (ADs), we aimed to assess the effectiveness and safety of NAC as an adjunct to risperidone in the treatment of ADs in a randomized, double-blind, clinical trial.
Methods: The participants were referred outpatients between 4 and 12 years of age with the diagnosis of ADs and a score of more than 12 on Aberrant Behavior Checklist-Community (ABC-C) Irritability subscale score. The participants were randomized into 2 groups. One group received risperidone plus NAC, and the other group received risperidone plus placebo. The dose of risperidone was titrated between 1 and 2.0 mg/d, and the dose of NAC was 600 to 900 mg/d. The main outcome was mean decrease in the ABC-C irritability subscale score from baseline at 5 and 10 weeks. Changes in other subscales were considered as secondary outcome measures.
Results: Forty patients completed the 10-week trial. Baseline characteristics including age, sex and body weight, as well as baseline scores in 5 subscales did not demonstrate statistically significant difference between the 2 groups. Repeated-measures analysis showed significant effect for time treatment interaction in irritability (P = 0.01) and hyperactivity/ noncompliance (P = 0.02) subscales. By week 10, the NAC group showed significantly more reduction in irritability (P = 0.02) and hyperactivity/ noncompliance (P = 0.01) subscales scores.
Conclusions: N-acetylcysteine can be considered as an adjuvant therapy for ADs with beneficial therapeutic outcomes.
40
Randomise double blind placebo controlled trial
2015
doi: 10.1097/WNF.0000000000000063
Effectiveness of N-acetylcysteine in autism spectrum disorders: A meta-analysis of randomized controlled trials
Authors:
Lee, T.M., Lee, K.M., Lee, C.Y., Lee, H.C., Tam, K.W. and Loh, E.W.
Research study
Year
Type
Study size
Abstract
LINK/DOI
Objective: Currently, pharmaceutical treatment options for autism spectrum disorder are limited. Brain glutaminergic dysregulation is observed in autism spectrum disorder. N-acetylcysteine, which can be converted to glutathione and subsequently release glutamate into the extracellular space, and thus reduce glutamatergic neurotransmission at synapses, is considered a potential drug for autism spectrum disorder treatment. Here, we analyzed the treatment effects of N-acetylcysteine on autism spectrum disorder in randomized controlled trials.
Study design: Updated systematic review and meta-analysis.
Data sources: By systematically searching the PubMed, Embase and Cochrane Library, we obtained five randomized controlled trials.
Study selection: Meta-analyses were performed to examine the improvement in autistic behaviors as measured by the Aberrant Behavior Checklist, Social Responsiveness Scale and Repetitive Behavior Scale-Revised, using mean difference with a 95% confidence interval and a random-effects model.
Data synthesis: After 8-12 weeks of N-acetylcysteine supplementation, the pooled result of four trials revealed an improvement in Aberrant Behavior Checklist total score (mean difference = 1.31, 95% confidence interval = [0.42, 2.20]). When one trial was excluded, the sensitivity test result was stronger (mean difference = 1.88, 95% confidence interval = [0.92, 2.83]). The pooled results of three trials revealed significant improvements in hyperactivity (mean difference = 4.80, 95% confidence interval = [1.20, 8.40]) and irritability (mean difference = 4.07, 95% confidence interval = [1.13, 7.04]). Regarding Social Responsiveness Scale, the pooled result of two trials showed significant improvement in social awareness after 8-12 weeks of N-acetylcysteine supplementation (mean difference = 1.34, 95% confidence interval = [0.09, 2.59]). No differences were observed in the pooled results of two trials using Repetitive Behavior Scale, either in the total or the subscales.
Conclusion: We concluded that N-acetylcysteine is safe and tolerable, reduces hyperactivity and irritability and enhances social awareness in children with autism spectrum disorder. However, further evidence should be sought before a general recommendation.
5 trials
Meta-analysis
2021
doi: 10.1177/0004867420952540
