{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:28:37Z","timestamp":1790958517120,"version":"4.1.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,28]],"date-time":"2021-06-28T00:00:00Z","timestamp":1624838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Psychiatry"],"abstract":"<jats:p>Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition, whose etiology remains poorly understood in most cases. Several genetic, epigenetic and environmental factors have been implicated in ASD pathogenesis and numerous studies have provided evidences for increased levels of oxidative stress and reduced antioxidant capacity in patients with ASD. Recent clinical trials explored supplementation with antioxidant agents as a potential therapeutic strategy for ASD, investigating the impact of this treatment on behavioral symptoms and on most common comorbidities of the disease, including sleep disturbances. Among all medical conditions associated to ASD, sleep problems are highly prevalent and are supposed to be positively related to the severity of the disease. Moreover, studies on animal models support the hypothesis of a relationship between oxidative stress and sleep deprivation. The aim of this review is to summarize the current state of the literature on the effect of antioxidant treatment on sleep disturbances in patients with ASD. Twenty-one articles were included in final synthesis. Of them, 15 studies involved Melatonin, 1 Tryptophan and 5 focused on supplementation with other antioxidant agents (namely Coenzyme Q10, L-Carnosine, Luteolin and Quercetin). Despite the high prevalence of comorbid sleep troubles in ASD, there is a paucity of data on the efficacy of antioxidant agents in those patients. Further research is needed to better define the role of antioxidants agents as adjunctive therapy in the management sleep disorders in children and adolescents affected with ASD.<\/jats:p>","DOI":"10.3389\/fpsyt.2021.689277","type":"journal-article","created":{"date-parts":[[2021,6,28]],"date-time":"2021-06-28T04:55:56Z","timestamp":1624856156000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["Effects of Supplementation With Antioxidant Agents on Sleep in Autism Spectrum Disorder: A Review"],"prefix":"10.3389","volume":"12","author":[{"given":"Elena","family":"Zambrelli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Althea","family":"Lividini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Spadavecchia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Turner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Paola","family":"Canevini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,28]]},"reference":[{"key":"B1","article-title":"Diagnostic and Statistical Manual of Mental Disorders","year":"2013"},{"key":"B2","doi-asserted-by":"publisher","first-page":"771","DOI":"10.12740\/PP\/89948","article-title":"Autism spectrum disorder (ASD) \u2013 biomarkers of oxidative stress and methylation and transsulfuration cycle","volume":"53","author":"Walig\u00f3ra","year":"2019","journal-title":"Psychiatr Pol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1111\/pcn.12860","article-title":"Autism spectrum disorder: trends in research exploring etiopathogenesis","volume":"73","author":"Gyawali","year":"2019","journal-title":"Psychiatry Clin Neurosci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"761264","DOI":"10.1155\/2014\/761264","article-title":"Oxidative stress, prooxidants, and antioxidants: the interplay","volume":"2014","author":"Rahal","year":"2014","journal-title":"Biomed Res Int."},{"key":"B5","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.freeradbiomed.2020.07.017","article-title":"The role of glutathione redox imbalance in autism spectrum disorder: a review","volume":"160","author":"Bj\u00f8rklund","year":"2020","journal-title":"Free Radic Biol Med."},{"key":"B6","first-page":"923","article-title":"Plasma amino acid profile in autism spectrum disorder (ASD)","volume":"20","author":"Bala","year":"2016","journal-title":"Eur Rev Med Pharmacol Sci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"150","DOI":"10.3389\/fphys.2014.00150","article-title":"Evidence linking oxidative stress, mitochondrial dysfunction, and inflammation in the brain of individuals with autism","volume":"5","author":"Rossignol","year":"2014","journal-title":"Front Physiol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.pathophys.2006.05.007","article-title":"Oxidative stress in autism","volume":"13","author":"Chauhan","year":"2006","journal-title":"Pathophysiology."},{"key":"B9","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1152\/ajpregu.00565.2004","article-title":"Antioxidant defense responses to sleep loss and sleep recovery","volume":"288","author":"Everson","year":"2005","journal-title":"Am J Physiol Regul Integr Comp Physiol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"234952","DOI":"10.1155\/2015\/234952","article-title":"Sleep deprivation and oxidative stress in animal models: a systematic review","volume":"2015","author":"Villafuerte","year":"2015","journal-title":"Oxid Med Cell Longev."},{"key":"B11","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1016\/j.nurt.2010.06.001","article-title":"Medical comorbidities in autism: challenges to diagnosis and treatment","volume":"7","author":"Bauman","year":"2010","journal-title":"Neurother J Am Soc Exp Neurother."},{"key":"B12","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.spen.2015.03.006","article-title":"Sleep in autism spectrum disorder and attention deficit hyperactivity disorder","volume":"22","author":"Singh","year":"2015","journal-title":"Semin Pediatr Neurol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1906","DOI":"10.1007\/s10803-016-2723-7","article-title":"Sleep and behavioral problems in children with autism spectrum disorder","volume":"46","author":"Mazurek","year":"2016","journal-title":"J Autism Dev Disord."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.3906\/sag-1507-68","article-title":"Plasma levels of serotonin, gastrointestinal symptoms, and sleep problems in children with autism","volume":"46","author":"Kheirouri","year":"2016","journal-title":"Turkish J Med Sci."},{"key":"B15","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.psychres.2017.10.040","article-title":"Are gastrointestinal and sleep problems associated with behavioral symptoms of autism spectrum disorder?","volume":"259","author":"Yang","year":"2018","journal-title":"Psychiatry Res."},{"key":"B16","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1038\/s41386-019-0409-5","article-title":"Sleep as a translationally-relevant endpoint in studies of autism spectrum disorder (ASD)","volume":"45","author":"Missig","year":"2020","journal-title":"Neuropsychopharmacology."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/brainsci10070441","article-title":"Sleeping without prescription: management of sleep disorders in children with autism with non-pharmacological interventions and over-the-counter treatments","volume":"10","author":"Esposito","year":"2020","journal-title":"Brain Sci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.neuchi.2015.03.002","article-title":"Melatonin: physiological effects in humans","volume":"61","author":"Claustrat","year":"2015","journal-title":"Neurochirurgie."},{"key":"B19","doi-asserted-by":"publisher","first-page":"326","DOI":"10.2174\/15748847113086660072","article-title":"Melatonin in autism spectrum disorders","volume":"9","author":"Rossignol","year":"2014","journal-title":"Curr Clin Pharmacol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"4000","DOI":"10.2174\/092986712802002572","article-title":"Glutathione-related factors and oxidative stress in autism, a review","volume":"19","author":"Ghanizadeh","year":"2012","journal-title":"Curr Med Chem."},{"key":"B21","doi-asserted-by":"publisher","first-page":"15550","DOI":"10.1073\/pnas.1416940111","article-title":"Sulforaphane treatment of autism spectrum disorder (ASD)","volume":"111","author":"Singh","year":"2014","journal-title":"Proc Natl Acad Sci USA."},{"key":"B22","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1097\/WNF.0000000000000063","article-title":"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","volume":"38","author":"Nikoo","year":"2015","journal-title":"Clin Neuropharmacol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.1007\/s00726-020-02909-1","article-title":"Effect of L-Carnosine as adjunctive therapy in the management of children with autism spectrum disorder: a randomized controlled study","volume":"52","author":"Ann Abraham","year":"2020","journal-title":"Amino Acids."},{"key":"B24","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1111\/bcpt.12979","article-title":"Effects of l-Carnosine supplementation on sleep disorders and disease severity in autistic children: a randomized, controlled clinical trial","volume":"123","author":"Mehrazad-Saber","year":"2018","journal-title":"Basic Clin Pharmacol Toxicol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.psychres.2018.03.061","article-title":"Coenzyme Q(10) supplementation reduces oxidative stress and decreases antioxidant enzyme activity in children with autism spectrum disorders","volume":"265","author":"Mousavinejad","year":"2018","journal-title":"Psychiatry Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"798957","DOI":"10.1155\/2014\/798957","article-title":"Ubiquinol improves symptoms in children with autism","volume":"2014","author":"Gvozdj\u00e1kov\u00e1","year":"2014","journal-title":"Oxid Med Cell Longev."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2013.04.006","article-title":"An open-label pilot study of a formulation containing the anti-inflammatory flavonoid luteolin and its effects on behavior in children with autism spectrum disorders","author":"Taliou","year":"2013","journal-title":"Clin Ther."},{"key":"B28","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1186\/s12888-020-02847-y","article-title":"Long-term melatonin treatment for the sleep problems and aberrant behaviors of children with neurodevelopmental disorders","volume":"20","author":"Yuge","year":"2020","journal-title":"BMC Psychiatry."},{"key":"B29","doi-asserted-by":"publisher","first-page":"3218","DOI":"10.1007\/s10803-019-04046-5","article-title":"Pediatric prolonged-release melatonin for sleep in children with autism spectrum disorder: impact on child behavior and caregiver's quality of life","volume":"49","author":"Schroder","year":"2019","journal-title":"J Autism Dev Disord."},{"key":"B30","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1089\/cap.2018.0020","article-title":"Long-term efficacy and safety of pediatric prolonged-release melatonin for insomnia in children with autism spectrum disorder","volume":"28","author":"Maras","year":"2018","journal-title":"J Child Adolesc Psychopharmacol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"948","DOI":"10.1016\/j.jaac.2017.09.414","article-title":"Efficacy and safety of pediatric prolonged-release melatonin for insomnia in children with autism spectrum disorder","volume":"56","author":"Gringras","year":"2017","journal-title":"J Am Acad Child Adolesc Psychiatry."},{"key":"B32","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1586\/14737175.2015.1041511","article-title":"Melatonin for sleep disturbance in children with neurodevelopmental disorders: prospective observational naturalistic study","volume":"15","author":"Ayyash","year":"2015","journal-title":"Expert Rev Neurother."},{"key":"B33","doi-asserted-by":"publisher","first-page":"2525","DOI":"10.1007\/s10803-014-2123-9","article-title":"Melatonin in children with autism spectrum disorders: endogenous and pharmacokinetic profiles in relation to sleep","volume":"44","author":"Goldman","year":"2014","journal-title":"J Autism Dev Disord."},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1007\/s10803-011-1418-3","article-title":"Melatonin for sleep in children with autism: a controlled trial examining dose, tolerability, and outcomes","author":"Malow","year":"2012","journal-title":"J Autism Dev Disord."},{"key":"B35","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1111\/j.1365-2869.2012.01021.x","article-title":"Controlled-release melatonin, singly and combined with cognitive behavioural therapy, for persistent insomnia in children with autism spectrum disorders: a randomized placebo-controlled trial","volume":"21","author":"Cortesi","year":"2012","journal-title":"J Sleep Res."},{"key":"B36","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1007\/s10803-010-1036-5","article-title":"Melatonin versus placebo in children with autism spectrum conditions and severe sleep problems not amenable to behaviour management strategies: a randomised controlled crossover trial","volume":"41","author":"Wright","year":"2011","journal-title":"J Autism Dev Disord."},{"key":"B37","doi-asserted-by":"publisher","first-page":"145","DOI":"10.5664\/jcsm.27443","article-title":"The efficacy of melatonin for sleep problems in children with autism, fragile X syndrome, or autism and fragile X syndrome","volume":"5","author":"Wirojanan","year":"2009","journal-title":"J Clin sleep Med JCSM."},{"key":"B38","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1177\/0883073807309783","article-title":"Melatonin for insomnia in children with autism spectrum disorders","volume":"23","author":"Andersen","year":"2008","journal-title":"J Child Neurol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1111\/j.1600-079X.2007.00528.x","article-title":"A randomized, placebo-controlled trial of controlled release melatonin treatment of delayed sleep phase syndrome and impaired sleep maintenance in children with neurodevelopmental disabilities","volume":"44","author":"Wasdell","year":"2008","journal-title":"J Pineal Res."},{"key":"B40","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1111\/j.1365-2214.2006.00616.x","article-title":"Randomized controlled trial of melatonin for children with autistic spectrum disorders and sleep problems","volume":"32","author":"Garstang","year":"2006","journal-title":"Child Care Health Dev."},{"key":"B41","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1007\/s10803-006-0116-z","article-title":"An open-label study of controlled-release melatonin in treatment of sleep disorders in children with autism","volume":"36","author":"Giannotti","year":"2006","journal-title":"J Autism Dev Disord."},{"key":"B42","doi-asserted-by":"publisher","first-page":"608","DOI":"10.37212\/jcnos.334393","article-title":"Tryptophan-enriched antioxidant cereals improve sleep in children with autistic spectrum and attention deficit hyperactivity disorders","volume":"9","author":"Gal\u00e1n","year":"2017","journal-title":"J Cell Neurosci Oxidative Stress."},{"key":"B43","doi-asserted-by":"publisher","first-page":"e1000097","DOI":"10.1371\/journal.pmed.1000097","article-title":"Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement","volume":"6","author":"Moher","year":"2009","journal-title":"PLoS Med."},{"key":"B44","doi-asserted-by":"publisher","first-page":"185","DOI":"10.14797\/mdcj-15-3-185","article-title":"Coenzyme Q(10)","volume":"15","author":"Raizner","year":"2019","journal-title":"Method Debakey Cardiovasc J."},{"key":"B45","doi-asserted-by":"publisher","first-page":"43","DOI":"10.4137\/CMPed.S38337","article-title":"Identification and treatment of pathophysiological comorbidities of autism spectrum disorder to achieve optimal outcomes","volume":"10","author":"Frye","year":"2016","journal-title":"Clin Med Insights Pediatr."}],"container-title":["Frontiers in Psychiatry"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2021.689277\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,28]],"date-time":"2021-06-28T04:56:08Z","timestamp":1624856168000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2021.689277\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,28]]},"references-count":45,"alternative-id":["10.3389\/fpsyt.2021.689277"],"URL":"https:\/\/doi.org\/10.3389\/fpsyt.2021.689277","relation":{},"ISSN":["1664-0640"],"issn-type":[{"value":"1664-0640","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,28]]},"article-number":"689277"}}