Effectiveness of N-acetylcysteine in autism spectrum disorders: A meta-analysis of randomized controlled trials

Abstract

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.

N-acetylcysteine is effective as add-on therapy to risperidone-based combination for children with autistic disorders

“…Therefore, we conducted a meta-analysis in a different way by putting NAC-risperidone combination as one group and grouping NAC supplementation to other treatments as another. Our results, which were quite different from those of that meta-analysis (Lee et al, 2021), failed to show effectiveness of NAC supplementation for improving irritability in patients with ASD (Figure 1[a]). Instead, NAC was only effective when used as add-on therapy to risperidone when compared with risperidone treatment alone in respect of improving irritability among patients with ASD (Figure 1[b]).…”

“…We read with great interest a recent meta-analysis by Lee et al (2021) that investigated the effectiveness of N-acetylcysteine in patients with autism spectrum disorders (ASD). The authors of that study showed that N-acetylcysteine (NAC) supplementation was effective for treating irritability and hyperactive in this patient population with an overall improvement in the aberrant behavior checklist (ABC) total score, thereby concluding that NAC is safe, tolerable and effective in improving ASD’s comorbid symptoms (Lee et al, 2021). However, there is a potential concern regarding how the results of individual studies were pooled to produce total effect sizes.…”

N-Acetylcysteine (NAC): Impacts on Human Health

“…Therefore, a systematic review with meta-analysis assessed that NAC supplementation allowed a significant reduction in hyperactivity and irritability, as well as increased social awareness in children with autism spectrum disorder. However, the authors recommended that more studies need to be carried out to have an effective NAC recommendation [ 196 ].…”

Ratings of the Effectiveness of Nutraceuticals for Autism Spectrum Disorders: Results of a National Survey

“…The results of this study found significant benefits for many nutraceuticals with minimal adverse effects and are consistent with the findings of a number of clinical trials studying nutraceuticals in ASD. For example, double-blind, placebo-controlled studies, and/or meta-analyses have reported improvements in children with ASD using L-carnitine [ 32 , 33 ], Coenzyme Q10 (ubiquinone) [ 34 ], digestive enzymes [ 35 , 36 ], high dose folinic acid (1–2 mg/kg/day) [ 24 , 25 , 26 ], MB12 injections [ 37 ], melatonin [ 9 , 38 , 39 , 40 , 41 , 42 ], a multivitamin/mineral supplement designed specifically for ASD [ 26 , 27 ], NAC [ 29 , 43 , 44 , 45 ], omega 3 fatty acids [ 46 , 47 ], vitamin C [ 48 ], vitamin D3 [ 49 , 50 ], and possibly B6/Mg [ 51 , 52 ]. Open-label studies in ASD have also reported benefits for B vitamins [ 53 , 54 ], biotin [ 55 ], folic acid [ 56 ], an herbal formula [ 57 ], glutathione [ 58 ], iron [ 59 ], vitamin A [ 60 ] and zinc [ 61 , 62 ].…”

“…Some of the medical comorbidities and biochemical abnormalities reported in individuals with ASD might improve with nutraceuticals. For example, randomized clinical trials for ASD have demonstrated the efficacy of melatonin supplementation [ 9 ], folinic acid [ 24 , 25 , 26 ], vitamin/mineral supplements [ 27 , 28 ], comprehensive nutritional interventions [ 19 ], N-acetyl cysteine (NAC) [ 29 ], and sulforaphane [ 30 ].…”