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Effect of l-Carnosine as adjunctive therapy in the management of children with autism spectrum disorder: a randomized controlled study

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Abstract

l-Carnosine is an amino acid that acts as an anti-oxidant, anti-toxic and neuroprotective agent. There is a paucity of data about the effectiveness of l-Carnosine in the management of autism spectrum disorder (ASD) in children. This study aimed at investigating the effectiveness of l-Carnosine as adjunctive therapy in the management of ASD. This was a randomized controlled trial. Children aged 3–6 years with a diagnosis of mild to moderate ASD were assigned to standard care arm (occupational and speech therapy) and intervention care arm (l-Carnosine, 10–15 mg/kg in 2 divided doses) plus standard care treatment. The children were assessed at the baseline and the end of 2 months for the scores of Childhood Autism Rating Scale, Second Edition—Standard Version (CARS2-ST), Autism Treatment Evaluation Checklist (ATEC), BEARS sleep screening tool and 6-item Gastrointestinal Severity Index (6-GSI). Of the sixty-seven children enrolled, sixty-three children had completed the study. No statistically significant difference (p > 0.05) was observed for any of the outcome measures assessed. Supplementation of l-Carnosine did not improve the total score of CARS2-ST, ATEC, BEARS sleep screening tool and 6-GSI scores of children with ASD. Further investigations are needed with more objective assessments to critically validate the effectiveness of l-Carnosine on ASD children for more decisive results.

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Abbreviations

ASD:

Autism spectrum disorder

DSM-5:

Diagnostic and statistical manual of mental disorders, fifth edition

ADHD:

Attention deficit hyperactivity disorder

GABA:

Gamma-amino butyric acid

CAM:

Complementary and alternative medicine

NMDA:

N-Methyl-d-aspartate

mTOR:

Mammalian target of rapamycin

Akt:

Protein kinase B

p70S6K:

Ribosomal protein S6 kinase beta-1

TNF-α:

Tumor necrosis factor-α

CARS-2 ST:

Childhood autism rating scale, second edition-standard version

ATEC:

Autism treatment evaluation checklist

6-GSI:

6 Item gastrointestinal severity index

References

  • Adams JB, Audhya T, Geis E, Gehn E, Fimbres V, Pollard EL, Mitchell J, Ingram J, Hellmers R, Laake D, Matthews JS, Li K, Naviaux JC, Naviaux RK, Adams RL, Coleman DM, Quig DW (2018) Comprehensive nutritional and dietary intervention for autism spectrum disorder-a randomized, controlled 12-month trial. Nutrients 10(3):369

    PubMed Central  Google Scholar 

  • American Psychiatric Association, DSM-5 Task Force (2013) Diagnostic and statistical manual of mental disorders: DSM-5™ (5th edn). American Psychiatric Publishing, Inc

  • Bala KA, Doğan M, Mutluer T, Kaba S, Aslan O, Balahoroğlu R, Çokluk E, Üstyol L, Kocaman S (2016) Plasma amino acid profile in autism spectrum disorder (ASD). Eur Rev Med Pharmacol Sci 20(5):923–929

    CAS  PubMed  Google Scholar 

  • Barnett JE, Shale AJ (2012) The integration of Complementary and Alternative Medicine (CAM) into the practice of psychology: a vision for the future. Prof Psychol Res Pr 43(6):576–585

    Google Scholar 

  • Bastida-Pozuelo MF, Sánchez-Ortuño MM (2016) Preliminary analysis of the concurrent validity of the Spanish translation of the BEARS sleep screening tool for children. J Psychiatr Ment Health Nurs 23(8):513–520

    CAS  PubMed  Google Scholar 

  • Brondino N, Fusar-Poli L, Panisi C, Damiani S, Barale F, Politi P (2016) Pharmacological modulation of GABA function in autism spectrum disorders: a systematic review of human studies. J Autism Dev Disord 46(3):825–839

    PubMed  Google Scholar 

  • Brondino N, Fusar-Poli L, Rocchetti M, Provenzani U, Barale F, Politi P (2015) Complementary and alternative therapies for autism spectrum disorder. Evid Based Complement Alternat Med 2015:258589

    PubMed  PubMed Central  Google Scholar 

  • Burnside K, Wright K, Poulin-Dubois D (2017) Social motivation and implicit theory of mind in children with autism spectrum disorder. Autism Res 10(11):1834–1844

    PubMed  PubMed Central  Google Scholar 

  • Chaidez V, Hansen RL, Hertz-Picciotto I (2014) Gastrointestinal problems in children with autism, developmental delays or typical development. J Autism Dev Disord 44(5):1117–1127

    PubMed  PubMed Central  Google Scholar 

  • Chauhan A, Sahu JK, Jaiswal N, Kumar K, Agarwal A, Kaur J, Singh S, Singh M (2019) Prevalence of autism spectrum disorder in Indian children: a systematic review and meta-analysis. Neurol India 67(1):100–104

    PubMed  Google Scholar 

  • Chez MG, Buchanan CP, Aimonovitch MC, Becker M, Schaefer K, Black C, Komen J (2002) Double-blind, placebo-controlled study of l-carnosine supplementation in children with autistic spectrum disorders. J Child Neurol 17(11):833–837

    PubMed  Google Scholar 

  • Clark M, Vinen Z, Barbaro J, Dissanayake C (2018) School age outcomes of children diagnosed early and later with autism spectrum disorder. J Autism Dev Disord 48(1):92–102

    PubMed  Google Scholar 

  • Cooper K, Loades ME, Russell AJ (2018) Adapting psychological therapies for autism—therapist experience, skills and confidence. Res Autism Spectr Disord 45:43–50

    CAS  PubMed  PubMed Central  Google Scholar 

  • Elsabbagh M, Divan G, Koh YJ, Kim YS, Kauchali S, Marcín C, Montiel-Nava C, Patel V, Paula CS, Wang C, Yasamy MT, Fombonne E (2012) Global prevalence of autism and other pervasive developmental disorders. Autism Res 5(3):160–179

    PubMed  PubMed Central  Google Scholar 

  • Everson CA, Laatsch CD, Hogg N (2005) Antioxidant defense responses to sleep loss and sleep recovery. Am J Physiol Regul Integr Comp Physiol 288(2):R374–R383

    CAS  PubMed  Google Scholar 

  • Feng ZY, Zheng XJ, Wang J (2009) Effects of carnosine on the evoked potentials in hippocampal CA1 region. J Zhejiang Univ Sci B 10(7):505–511

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fleisher-Berkovich S, Abramovitch-Dahan C, Ben-Shabat S, Apte R, Beit-Yannai E (2009) Inhibitory effect of carnosine and N-acetyl carnosine on LPS-induced microglial oxidative stress and inflammation. Peptides 30(7):1306–1312

    CAS  PubMed  Google Scholar 

  • Gail Williams P, Sears LL, Allard A (2004) Sleep problems in children with autism. J Sleep Res 13(3):265–268

    CAS  PubMed  Google Scholar 

  • Geelhand P, Bernard P, Klein O, Tiel BV, Kissine M (2019) The role of gender in the perception of autism symptom severity and future behavioral development. Mol Autism 10:16

    PubMed  PubMed Central  Google Scholar 

  • Ghodsi R, Kheirouri S, Nosrati R (2019) Carnosine supplementation does not affect serum concentrations of advanced glycation and precursors of lipoxidation end products in autism: a randomized controlled clinical trial. Ann Clin Biochem 56(1):148–154

    CAS  PubMed  Google Scholar 

  • Ghosh A, Mahajan PB, Tripathy PR, Mishra BR, Mahapatra SC, Nanda P (2015) Exploring Health Situation of Indian Children with Autism Spectrum Disorder Using Autism Treatment Evaluation Checklist (ATEC) in an Urban Area of Odisha: a case study. J Clin Diagn Res 9(12):VC05–VC08

    PubMed  PubMed Central  Google Scholar 

  • Goel R, Hong JS, Findling RL, Ji NY (2018) An update on pharmacotherapy of autism spectrum disorder in children and adolescents. Int Rev Psychiatry 30(1):78–95

    PubMed  Google Scholar 

  • Gorrindo P, Williams KC, Lee EB, Walker LS, McGrew SG, Levitt P (2012) Gastrointestinal dysfunction in autism: parental report, clinical evaluation, and associated factors. Autism Res 5(2):101–108

    PubMed  PubMed Central  Google Scholar 

  • Gulati S, Kaushik JS, Saini L, Sondhi V, Madaan P, Arora NK, Pandey RM, Jauhari P, Manokaran RK, Sapra S, Sharma S, Paul VK, Sagar R (2019) Development and validation of DSM-5 based diagnostic tool for children with autism spectrum disorder. PLoS ONE 14(3):e0213242

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hajizadeh-Zaker R, Ghajar A, Mesgarpour B, Afarideh M, Mohammadi MR, Akhondzadeh S (2018) l-carnosine as an adjunctive therapy to risperidone in children with autistic disorder: a randomized, double-blind Placebo-Controlled Trial. J Child Adolesc Psychopharmacol 28(1):74–81

    CAS  PubMed  Google Scholar 

  • Ho MH, Lin LY (2020) Efficacy of parent-training programs for preschool children with autism spectrum disorder: a randomized controlled trial. Res Autism Spectr Disord 71:101495

    Google Scholar 

  • Höfer J, HoffmannF K-B, Küpper C, Poustka L, Roepke S, Roessner V, Stroth S, Wolff N, Bachmann CJ (2019) Complementary and alternative medicine use in adults with autism spectrum disorder in Germany: results from a multi-center survey. BMC Psychiatry 19(1):53

    PubMed  PubMed Central  Google Scholar 

  • Ibrahim SH, Voigt RG, Katusic SK, Weaver AL, Barbaresi WJ (2009) Incidence of gastrointestinal symptoms in children with autism: a population-based study. Pediatrics 124(2):680–686

    PubMed  PubMed Central  Google Scholar 

  • Lindly O, Thorburn S, Heisler K, Reyes N, Zuckerman K (2017) Parent disclosure of complementary health approaches used for children with autism spectrum disorder: barriers and facilitators. Complement Ther Med 35:47–52

    PubMed  PubMed Central  Google Scholar 

  • Lungato L, Marques MS, Pereira VG, Hix S, Gazarini ML, Tufik S, D’Almeida V (2013) Sleep deprivation alters gene expression and antioxidant enzyme activity in mice splenocytes. Scand J Immunol 77(3):195–199

    CAS  PubMed  Google Scholar 

  • Mahapatra S, Khokhlovich E, Martinez S, Kannel B, Edelson SM, Vyshedskiy A (2020) Longitudinal epidemiological study of autism subgroups using autism treatment evaluation checklist (ATEC) score. J Autism Dev Disord 50(5):1497–1508

    PubMed  Google Scholar 

  • Matsukura T, Tanaka H (2000) Applicability of zinc complex of l-carnosine for medical use. Biochemistry (Mosc) 65(7):817–823

    CAS  Google Scholar 

  • Mehrazad-Saber Z, Kheirouri S, Noorazar SG (2018) Effects of l-carnosine supplementation on sleep disorders and disease severity in autistic children: a randomized, controlled clinical trial. Basic Clin Pharmacol Toxicol 123(1):72–77

    CAS  PubMed  Google Scholar 

  • Ming X, Stein TP, Barnes V, Rhodes N, Guo L (2012) Metabolic perturbance in autism spectrum disorders: a metabolomics study. J Proteome Res 11(12):5856–5862

    CAS  PubMed  Google Scholar 

  • Ouyang L, Tian Y, Bao Y, Xu H, Cheng J, Wang B, Shen Y, Chen Z, Lyu J (2016) Carnosine decreased neuronal cell death through targeting glutamate system and astrocyte mitochondrial bioenergetics in cultured neuron/astrocyte exposed to OGD/recovery. Brain Res Bull 124:76–84

    CAS  PubMed  Google Scholar 

  • Owens JA, Dalzell V (2005) Use of the “BEARS” sleep screening tool in a pediatric residents’ continuity clinic: a pilot study. Sleep Med 6(1):63–69

    PubMed  Google Scholar 

  • Owen-Smith AA, Bent S, Lynch FL, Coleman KJ, Yau VM, Pearson KA, Massolo ML, Quinn V, Croen LA (2015) Prevalence and predictors of complementary and alternative medicine use in a large insured sample of children with autism spectrum disorders. ResAutism Spectr Disord 17:40–51

    Google Scholar 

  • Ozonoff S, Strayer DL, McMahon WM, Filloux F (1994) Executive function abilities in autism and Tourette syndrome: an information processing approach. J Child Psychol Psychiatry 35(6):1015–1032

    CAS  PubMed  Google Scholar 

  • Park HS, Han KH, Shin JA, Park JH, Song KY, Kim DH (2014) The neuroprotective effects of carnosine in early stage of focal ischemia rodent model. J Korean Neurosurg Soc 55(3):125–130

    PubMed  PubMed Central  Google Scholar 

  • Pfeiffer BA, Koenig K, Kinnealey M, Sheppard M, Henderson L (2011) Effectiveness of sensory integration interventions in children with autism spectrum disorders: a pilot study. Am J Occup Ther 65(1):76–85

    PubMed  PubMed Central  Google Scholar 

  • Prokopieva VD, Yarygina EG, Bokhan NA, Ivanova SA (2016) Use of carnosine for oxidative stress reduction in different pathologies. Oxid Med Cell Longev 2016:2939087

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rajanikant GK, Zemke D, Senut MC, Frenkel MB, Chen AF, Gupta R, Majid A (2007) Carnosine is neuroprotective against permanent focal cerebral ischemia in mice. Stroke 38(11):3023–3031

    CAS  PubMed  Google Scholar 

  • Rimland B, Edelson M (1999) Autism Treatment Evaluation Checklist. Autism Research Institute, 4812 Adams Avenue, San Diego, CA 92116. https://www.autismeval.com/ari-atec/report1.html

  • Samms-Vaughan M, Rahbar MH, Dickerson AS, Loveland KA, Hessabi M, Pearson DA, Bressler J, Shakespeare-Pellington S, Grove ML, Coore-Desai C, Reece J, Boerwinkle E (2017) The diagnosis of autism and autism spectrum disorder in low- and middle-income countries: experience from Jamaica. Autism 21(5):564–572

    PubMed  PubMed Central  Google Scholar 

  • Schneider CK, Melmed RD, Barstow LE, Enriquez FJ, Ranger-Moore J, Ostrem JA (2006) Oral human immunoglobulin for children with autism and gastrointestinal dysfunction: a prospective, open-label study. J Autism Dev Disord 36(8):1053–1064

    PubMed  Google Scholar 

  • Schön M, Mousa A, Berk M, Chia WL, Ukropec J, Majid A, Ukropcová B, de Courten B (2019) The potential of carnosine in brain-related disorders: a comprehensive review of current evidence. Nutrients 11(6):1196

    PubMed Central  Google Scholar 

  • Schopler E, Van Bourgondien ME, Wellman GJ, Love SR (2010) The Childhood Autism Rating Scale (2nd ed.) (CARS2). Los Angeles, CA: Western Psychological Services

  • Shen Y, Hu WW, Fan YY, Dai HB, Fu QL, Wei EQ, Luo JH, Chen Z (2007) Carnosine protects against NMDA-induced neurotoxicity in differentiated rat PC12 cells through carnosine-histidine-histamine pathway and H(1)/H(3) receptors. Biochem Pharmacol 73(5):709–717

    CAS  PubMed  Google Scholar 

  • Suzuki H, Mori M, Seto K, Miyazawa M, Kai A, Suematsu M, Yoneta T, Miura S, Ishii H (2001) Polaprezinc attenuates the Helicobacter pylori-induced gastric mucosal leucocyte activation in Mongolian gerbils–a study using intravital videomicroscopy. Aliment Pharmacol Ther 15(5):715–725

    CAS  PubMed  Google Scholar 

  • Thulasi V, Steer RA, Monteiro IM, Ming X (2019) Overall severities of gastrointestinal symptoms in pediatric outpatients with and without autism spectrum disorder. Autism 23(2):524–530

    PubMed  Google Scholar 

  • Trombley PQ, Horning MS, Blakemore LJ (1998) Carnosine modulates zinc and copper effects on amino acid receptors and synaptic transmission. NeuroReport 9(15):3503–3507

    CAS  PubMed  Google Scholar 

  • Wang LW, Tancredi DJ, Thomas DW (2011) The prevalence of gastrointestinal problems in children across the United States with autism spectrum disorders from families with multiple affected members. J Dev Behav Pediatr 32(5):351–360

    PubMed  Google Scholar 

  • Weiner RH, Greene RL (2014) Intention-based therapy for autism spectrum disorder: promising results of a wait-list control study in children. Explore (NY) 10(1):13–23

  • Wu XH, Ding MP, Zhu-Ge ZB, Zhu YY, Jin CL, Chen Z (2006) Carnosine, a precursor of histidine, ameliorates pentylenetetrazole-induced kindled seizures in rat. Neurosci Lett 400(1–2):146–149

    CAS  PubMed  Google Scholar 

  • Zhang Z, Miao L, Wu X, Liu G, Peng Y, Xin X, Jiao B, Kong X (2014) carnosine inhibits the proliferation of human gastric carcinoma cells by retarding Akt/mTOR/p70S6K signaling. J Cancer 5(5):382–389

    PubMed  PubMed Central  Google Scholar 

  • Zuckerman KE, Lindly OJ, Sinche BK, Nicolaidis C (2015) Parent health beliefs, social determinants of health, and child health services utilization among U.S. school-age children with autism. J Dev Behav Pediatr 36(3):146–157

    PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Authors are thankful to Brio Bliss Life Science Pvt. Ltd., Chennai, India for providing L-Carnosine syrup to study children. We thank James B Adams, Autism/Asperger’s Research Program, Arizona State University, USA, Xue Ming, New Jersey Medical School, Rutgers University, USA and Denise Fulton, Autism Research Institute, USA for providing valuable guidance and questionnaires for this study. We express our gratitude to the children, parents and all the administrators and staff of KCDU and VidyaSudha, Sri Ramachandra learning centre for children with special needs, SRIHER for their support throughout this study. We acknowledge the assistance provided by Sri Ramachandra Founder-Chancellor Shri N.P.V. Ramasamy Udayar Research Fellowship.

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Authors and Affiliations

  1. Department of Pharmacy Practice, Sri Ramachandra Faculty of Pharmacy, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai, Tamil Nadu, 600 116, India

    Debi Ann Abraham & Rajanandh Muhasaparur Ganesan

  2. Department of Paediatric Medicine, Sri Ramachandra Medical College and Research Institute, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India

    Udayakumar Narasimhan

  3. Karthikeyan Child Development Unit, Sri Ramachandra Medical Centre, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India

    Senta Christy

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  1. Debi Ann Abraham
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  2. Udayakumar Narasimhan
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  3. Senta Christy
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  4. Rajanandh Muhasaparur Ganesan
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Contributions

DAA, MGR, NU, SC conceived and drafted the study protocol. DAA, NU, SC assisted with subject recruitment and data collection. DAA, MGR was involved in manuscript preparation. MGR provided data analysis and interpretation. DAA, MGR, NU and SC critically revised and gave final approval of the manuscript. All authors agree with their contributions to this work.

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Correspondence to Rajanandh Muhasaparur Ganesan.

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The authors have indicated that they have no conflicts of interest regarding the content of this article.

Ethics approval

The study was approved by the Human Institutional Ethical Committee (IEC) of SRIHER before the commencement of the study (Ethical clearance number: IEC/19/JUN/151/39) and the study was registered in the Clinical Trial Registry-India (CTRI/2019/07/020102). Written informed consent was obtained from the parents and the study was conducted according to the 2018 amendment of the International Conference on Harmonization Good Clinical Practice (ICH-GCP) guidelines.

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Ann Abraham, D., Narasimhan, U., Christy, S. et al. Effect of l-Carnosine as adjunctive therapy in the management of children with autism spectrum disorder: a randomized controlled study. Amino Acids 52, 1521–1528 (2020). https://doi.org/10.1007/s00726-020-02909-1

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