Impact of Sublingual Glutathione on Oxidative Biomarkers and Behavior in Children with Autism: A Pilot Investigation with Pharmacist Involvement
Main Article Content
Keywords
Autism Spectrum Disorder (ASD), Sublingual glutathione, Antioxidant markers, Behavioral outcomes, Good health, Glutathione supplementation, Autism
Abstract
Background: Autism Spectrum Disorder (ASD) is defined by impairments in social communication, repetitive behaviors, and cognitive variability. Oxidative stress is associated with the pathogenesis of ASD, characterized by imbalances between oxidants and antioxidants, particularly reduced glutathione (GSH). Although glutathione supplementation shows potential, its clinical efficacy remains inconsistent due to limited bioavailability when administered orally. Objectives: This study aimed to assess the impact of sublingual glutathione supplementation on oxidative stress indicators and behavioral outcomes in children diagnosed with ASD. Methods: A total of 25 children with ASD, aged 7 to 18 years, and 25 matched healthy controls participated in an openlabel, pre-post intervention trial. The ASD group administered sublingual reduced glutathione for a duration of six weeks. A clinical pharmacist, member of research team, supervised supplement dispensing, provided caregiver counseling, and monitored adherence throughout the study. Serum oxidative stress markers, comprising reduced glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG ratio, total antioxidant capacity (TAC), total oxidant status (TOS), malondialdehyde (MDA), and protein carbonyl levels, were assessed at baseline, three weeks, and six weeks. evaluations utilized the Assessment of Basic Language and Learning Skills-Revised (ABLLS-R). Results: Baseline oxidative stress markers showed elevated stress levels and diminished antioxidant capacity in patients with ASD compared to controls (p < 0.05). Following the intervention, notable improvements in antioxidant status, as measured by GSH, the GSH/GSSG ratio, and TAC, were observed. Behavioral improvements were significant in specific domains, including cooperation, imitation, social interaction, visual performance, vocal imitation, play, and receptive language. Conclusions: Sublingual glutathione supplementation significantly elevated antioxidant levels and specifically improved behavioral functioning in children with ASD. Pharmacist involvement contributed to proper administration and adherence, supporting the effective delivery of the intervention. These data indicate the possible usefulness of antioxidant therapy in the management of oxidative stress-related symptoms in ASD. Additional randomized controlled trials are advised.
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8. Besag FMC, Vasey MJ. Seizures and Epilepsy in Autism Spectrum Disorder. Psychiatr Clin North Am. 2021;44(1):51-68. doi:10.1016/j.psc.2020.11.005.
9. Moreno RJ, Ashwood P. An Update on Microbial Interventions in Autism Spectrum Disorder with Gastrointestinal Symptoms. Int J Mol Sci. 2024;25(23). doi:10.3390/ijms252313078.
10. Taylor MA, Schreck KA, Mulick JA. Sleep disruption as a correlate to cognitive and adaptive behavior problems in autism spectrum disorders. Res Dev Disabil. 2012;33(5):1408-1417. doi:10.1016/j.ridd.2012.03.013.
11. Dell’Osso L, Amatori G, Bonelli C, et al. Autism spectrum disorder, social anxiety and obsessive–compulsive disorders: beyond the comorbidity. BMC Psychiatry. 2025;25(1). doi:10.1186/s12888-024-06340-8.
12. Liu J, Chezan LC, Zhao Y, Hood SK, Drasgow E, Wang H. Utilizing network analysis to identify core items of quality of life for children with autism spectrum disorder. Autism Res. 2025;18(2):370-386. doi:10.1002/aur.3292.
13. Ayasrah M, Al Khateeb A, Beirat M, Bani Ahmad T, Al-Maqableh H. Behavioral Consequences Among Children with Autism Spectrum Disorders at the Special Care Centers. Clinical Schizophrenia & Related Psychoses. 2022;16(2):2-5. doi:10.3371/CSRP.MMWY.100123.
14. Ayasrah M, Alkhateeb A, Beirat M, Alkhawaldeh M. Parental Adjustments to the Behaviour of Children with ASD. Clinical Schizophrenia & Related Psychoses. 2022;16(2). doi:10.3371/CSRP.MMWY.100124.
15. Kadi R, Gayed F, Kauzman P, et al. Autism spectrum disorder: Practice guidelines for pharmacists. Can Pharm J (Ott). 2024;157(2):58-65. doi:10.1177/17151635241228495.
16. Tomiyama S, Yoshida K, Tani H, Uchida H. Pharmacological Treatment of Autism Spectrum Disorder: A Systematic Review of Treatment Guidelines. Pharmacopsychiatry. 2025;58(3):100-116. doi:10.1055/a-2514-4452.
17. Wongpakaran R, Suansanae T, Tan-khum T, Kraivichian C, Ongarjsakulman R, Suthisisang C. Impact of providing psychiatry specialty pharmacist intervention on reducing drug-related problems among children with autism spectrum disorder related to disruptive behavioural symptoms: A prospective randomized open-label study. J Clin Pharm Ther. 2017;42(3):329-336. doi:10.1111/jcpt.12518.
18. Breik N, Kuo IF, Bugden S, Moffat M, Alessi-Severini S. Treating children with ASD: The perspective of caregivers. J Pharm Pharm Sci. 2018;21(1S):74s-87s. doi:10.18433/jpps29829.
19. Alshahrani SM, Ishaqui AA, Kadasah SF. Assessment of Community Pharmacists’ Perception toward Autism Spectrum: A Cross-sectional Study from Saudi Arabia. J Disabil Res. 2025;4(2). doi:10.57197/JDR-2025-0006.
20. Alhyasat RAE, Khleifat K, Khlaifat AM, et al. Oxidative Stress and its connection to Jordanians’ Red Blood Cell Storage. Res J Pharm Technol. 2024;17(9):4304-4310. doi:10.52711/0974-360X.2024.00665.
21. Abu-Gharbieh E, Shehab NG, Almasri IM, Bustanji Y. Antihyperuricemic and xanthine oxidase inhibitory activities of Tribulus arabicus and its isolated compound, ursolic acid: In vitro and in vivo investigation and docking simulations. PLoS ONE. 2019;13(8). doi:10.1371/journal.pone.0202572.
22. Bajes H, Oran S, Bustanji Y. Phytochemical Analysis, In vitro Assessment of Antioxidant Properties and Cytotoxic Potential of Thymus capitatus Essential Oil. Res J Pharm Technol. 2023;16(3):1100-1108. doi:10.52711/0974-360X.2023.00183.
23. El-Huneidi W, Anjum S, Saleh MA, Bustanji Y, Abu-Gharbieh E, Taneera J. Carnosic Acid Protects INS-1 β-Cells against Streptozotocin-Induced Damage by Inhibiting Apoptosis and Improving Insulin Secretion and Glucose Uptake. Molecules. 2022;27(7). doi:10.3390/molecules27072102.
24. Liu X, Lin J, Zhang H, et al. Oxidative Stress in Autism Spectrum Disorder—Current Progress of Mechanisms and Biomarkers. Front Psychiatry. 2022;13. doi:10.3389/fpsyt.2022.813304.
25. Belokoskova SG, Tsikunov SG. Role of oxidative stress in the pathogenesis of autism spectrum disorders. Rev Clin Pharmacol Drug Ther. 2023;21(3):215-230. doi:10.17816/RCF567781.
26. Mousavinejad E, Ghaffari MA, Riahi F, Hajmohammadi M, Tiznobeyk Z, Mousavinejad M. Coenzyme Q10 supplementation reduces oxidative stress and decreases antioxidant enzyme activity in children with autism spectrum disorders. Psychiatry Res. 2018;265:62-69. doi:10.1016/j.psychres.2018.03.061.
27. Ghanizadeh A, Akhondzadeh S, Hormozi M, Makarem A, Abotorabi-Zarchi M, Firoozabadi A. Glutathione-related factors and oxidative stress in autism, A review. Curr Med Chem. 2012;19(23):4000-4005. doi:10.2174/092986712802002572.
28. Kuźniar-Pałka A. The Role of Oxidative Stress in Autism Spectrum Disorder Pathophysiology, Diagnosis and Treatment. Biomedicines. 2025;13(2). doi:10.3390/biomedicines13020388.
29. Schiavi S, La Rosa P, Petrillo S, et al. N-Acetylcysteine Mitigates Social Dysfunction in a Rat Model of Autism Normalizing Glutathione Imbalance and the Altered Expression of Genes Related to Synaptic Function in Specific Brain Areas. Front Psychiatry. 2022;13. doi:10.3389/fpsyt.2022.851679.
30. Rababah T, Flieh SM, Al-u’datt M, et al. Omega-3 and omega-6 polyunsaturated fatty acid intake and aberrant behaviors in Jordanian children with autism spectrum disorders (ASD): A pilot study. Res Autism Spectr Disord. 2024;114. doi:10.1016/j.rasd.2024.102386.
31. Zhang L, Ji J, Wang Y, Wang L, Zheng R, Jiang Y. Plasma vitamin levels and pathway analysis in boys with autism spectrum disorders. Sci Rep. 2024;14(1). doi:10.1038/s41598-024-82260-7.
32. Kaczmarek KA, Dobrzyńska M, Drzymała-Czyż S. Iron, magnesium, zinc and selenium - The most common elemental deficiencies in children with autism spectrum disorder. Res Autism Spectr Disord. 2024;110. doi:10.1016/j.rasd.2023.102288.
33. Shudifat RM, Al-samydai A, Al-Halaseh LK, et al. Digital strategies intervention and impact in promoting health education and making health decisions among individuals. Pharmacia. 2024;71:1-9. doi:10.3897/PHARMACIA.71.E136398.
34. Colak H, Sariyer ET, Nogay NH. The effect of nutritional interventions reducing oxidative stress on behavioural and gastrointestinal problems in autism spectrum disorder. Int J Dev Neurosci. 2023;83(2):135-164. doi:10.1002/jdn.10254.
35. Al-Omari LM, Hunaiti AA, Beirat MA, Bustanji YK. Study of MTHFR C677T Polymorphism and Associated Oxidative Stress Biomarkers among Autism Spectrum Disorder Patients in Jordan. Jordan J Biol Sci. 2020;13(2):247-252.
36. Ghanizadeh A, Moghimi-Sarani E. A randomized double blind placebo controlled clinical trial of N-Acetylcysteine added to risperidone for treating autistic disorders. BMC Psychiatry. 2013;13. doi:10.1186/1471-244X-13-196.
37. Kern JK, Geier DA, Adams JB, Garver CR, Audhya T, Geier MR. A clinical trial of glutathione supplementation in autism spectrum disorders. Med Sci Monit. 2011;17(12):CR677-CR682. doi:10.12659/MSM.882125.
38. Hagen TM, Wierzbicka GT, Sillau AH, Bowman BB, Jones DP. Bioavailability of dietary glutathione: Effect on plasma concentration. Am J Physiol Gastrointest Liver Physiol. 1990;259(4):G524-G529. doi:10.1152/ajpgi.1990.259.4.g524.
39. Bjørklund G, Doşa MD, Maes M, et al. The impact of glutathione metabolism in autism spectrum disorder. Pharmacol Res. 2021;166. doi:10.1016/j.phrs.2021.105437.
40. Radwan K, Wu G, Banks-Word K, Rosenberger R. An Open-Label Case Series of Glutathione Use for Symptomatic Management in Children with Autism Spectrum Disorder. Med Sci. 2023;11(4). doi:10.3390/medsci11040073.
41. Farag A, Abass W, Qassem H. Evaluation of the antioxidant and anti-inflammatory effect of sublingual glutathione on COPD patients. J Med Life. 2023;16(12):1796-1801. doi:10.25122/jml-2023-0161.
42. Aboubakr EM, Mohammed HA, Hassan AS, Mohamed HB, El Dosoky MI, Ahmad AM. Glutathione-loaded non-ionic surfactant niosomes: A new approach to improve oral bioavailability and hepatoprotective efficacy of glutathione. Nanotechnol Rev. 2021;11(1):117-137. doi:10.1515/ntrev-2022-0010.
43. Chan HK, Hassali MA, Lim CJ, Saleem F, Ghani NA. Improving pediatric liquid medication labeling of the hospital information system in Malaysia: Qualitative analysis of pharmacists’ perceptions. Pharm Pract. 2016;14(2). doi:10.18549/PharmPract.2016.02.699.
44. Agnol RD, dos Santos MT, Michalowski MB, Einsfeld L. Pharmacists’ interventions on 2 years of drug monitoring in an oncology pediatric inpatient ward. J Oncol Pharm Pract. 2022;28(8):1754-1762. doi:10.1177/10781552211041037.
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Mar 12, 2026
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Impact of Sublingual Glutathione on Oxidative Biomarkers and Behavior in Children with Autism: A Pilot Investigation with Pharmacist Involvement. Pharm Pract (Granada) [Internet]. 2026 Mar. 12 [cited 2026 Mar. 26];24(1):1-11. Available from: https://pharmacypractice.org/index.php/pp/article/view/3366
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How to Cite
1.
Impact of Sublingual Glutathione on Oxidative Biomarkers and Behavior in Children with Autism: A Pilot Investigation with Pharmacist Involvement. Pharm Pract (Granada) [Internet]. 2026 Mar. 12 [cited 2026 Mar. 26];24(1):1-11. Available from: https://pharmacypractice.org/index.php/pp/article/view/3366