Vitamin D3 Supplementation and Aquatic Exercise Combination as A Safe- Efficient Therapeutic Strategy to ameliorate Interleukin-6 and 10, and social interaction in Children with Autism

Subject Areas : Journal of Physical Activity and Hormones

Fahimeh AdibSaber ¹ , Soleyman Ansari Kolachahi ² , Alireza Elmieh ³ , Akbar Allahyari Karnagh ⁴ , Babak Barkadehi ⁵

1 - Assistant Professor, Department of Physical Education and Sports Science, Rasht Branch, Islamic Azad University, Rasht, Iran
2 - Ph.D. in Exercise Physiology, Department of Physical Education and Sports Science, Rasht Branch, Islamic Azad University, Rasht, Iran
3 - Associate Professor, Department of Physical Education and Sports Science, Rasht Branch, Islamic Azad University, Rasht, Iran
4 - MA in Psychology, Department of Psychology, Rasht Branch, Islamic Azad University, Rasht, Iran
5 - Department of Physical Education and Sports Science, Rasht Branch, Islamic Azad University, Rasht, Iran

Received: 2023-05-07 Accepted : 2023-09-23 Published : 2023-09-01

Keywords: Swimming, interleukin-6, Children with autism, interleukin-10, vitamin D supplementation,

Abstract :

AbstractIntroduction: Increasing evidence demonstrated that there are altered levels of both pro- and anti-inflammatory cytokines in children with autism spectrum disorder (ASD) and pointed out that immune dysfunction may also relate to social deficits. This study investigated the effect of aquatic exercise combined with vitamin D supplementation on social interaction and two related cytokines (Interleukin-6 and Interleukin-10) in children with ASD.Material & Methods: Forty boys with ASD (mean age: 10.90; age range: 6–14 years) were randomly assigned to the three interventions (groups 1, 2, and 3) and one control group (each 10 participants). Participants in the group 1 and 3 received a 10-week aquatic exercise program. Subjects in groups 2 and 3 took orally 50,000 IU of vitamin D3/ week. We evaluated the serum levels of IL-6 and IL-10 and the participants' social interaction at baseline and post-intervention. Results:Compared to the control group, all three interventions improved social skills scores (p< 0.001). surprisingly, the combination strategy could significantly reduce IL-6 and increase IL-10 serum levels in children with ASD (p< 0.001).Conclusion: It is recommended that aqua-based exercise programs combined with vitamin D supplementation maximize the improvement of social and communication dysfunction in children with ASD.

References:

References

1. Mohammadi MR, Ahmadi N, Khaleghi A, et al. Prevalence of autism and its comorbidities and the relationship with maternal psychopathology: a national population-based study. Arch Iran Med 2019;22.


2. Balestrieri E, Cipriani C, Matteucci C et al. Children with autism spectrum disorder and their mothers share abnormal expression of selected endogenous retroviruses families and cytokines. Front Immunol 2019;10:2244. doi: 10.3389/fimmu.2019.02244


3. Ashwood P, Krakowiak P, Hertz-Picciotto I, et al. Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome. Brain Behav Immun 2011; 25:40-45. doi: 10.1016/j.bbi.2010.08.003.


4. Goines PE, & Ashwood P. Cytokine dysregulation in autism spectrum disorders (ASD): possible role of the environment. Neurotoxicol Teratol 2013; 36:67-81. https://doi.org/10.1016/j.ntt.2012.07.006


5. Yang CJ, Tan HP, Yang FY, et al. The roles of cortisol and pro-inflammatory cytokines in assisting the diagnosis of autism spectrum disorder. Res Autism Spectr Disord 2015; 9:174-181. https://doi.org/10.1016/j.rasd.2014.10.012


6. Alzghoul L, Abdelhamid S, Yanis A, Qwaider Y, Aldahabi M, & Albdour S. The association between levels of inflammatory markers in autistic children compared to their unaffected siblings and unrelated healthy controls. Turk J Med Sci 2019; 49:1047-1053. doi:10.3906/sag-1812-167


7. Dinarello CA. Proinflammatory cytokines. Chest 2000; 118:503-508. https://doi.org/10.1378/chest.118.2.503


8. Zerbo O, Yoshida C, Grether JK, et al. Neonatal cytokines and chemokines and risk of Autism Spectrum Disorder: the Early Markers for Autism (EMA) study: a case-control study. J Neuroinflammation 2014; 11:1-9. https://doi.org/10.1186/1742-2094-11-113


9. Xu N, Li X, & Zhong Y. Inflammatory cytokines: potential biomarkers of immunologic dysfunction in autism spectrum disorders. Mediators Inflamm 2015;531518 https://doi.org/10.1155/2015/531518


10. Starkie R, Ostrowski SR, Jauffred S, Febbraio M & Pedersen BK. Exercise and IL‐6 infusion inhibit endotoxin‐induced TNF‐α production in humans. The FASEB Journal 2003; 17:1-10. https://doi.org/10.1096/fj.02-0670fje


11. Moore KW, de Waal Malefyt R, Coffman RL, & O'Garra A. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 2001;19:683.


12. Saghazadeh A, Ataeinia B, Keynejad K, Abdolalizadeh A, Hirbod-Mobarakeh A, Rezaei N. Anti-inflammatory cytokines in autism spectrum disorders: A systematic review and meta-analysis. Cytokine. 2019;123:154740. https://doi.org/10.1016/j.cyto.2019.154740


13. Ansari Kolachahi S, Hojjati Zidashti Z, Elmieh A, Bidabadi E, Filli J. The relationship between the cytokines and hs-CRP levels in children with autism and their comparison with healthy ones. Medical Science Journal of Islamic Azad Univesity-Tehran Medical Branch. 2019;29(3):240-8. Doi: ‎ 10.29252/iau.29.3.240


14. Abdallah MW, Larsen N, Grove J, Nørgaard-Pedersen B, Thorsen P, Mortensen EL, Hougaard DM. Amniotic fluid inflammatory cytokines: potential markers of immunologic dysfunction in autism spectrum disorders. The World Journal of Biological Psychiatry. 2013;14(7):528-38. https://doi.org/10.3109/15622975.2011.639803

 

15. Abruzzo P, Matté A, Bolotta A, Federti E, Ghezzo A, Guarnieri T, et al. Plasma peroxiredoxin changes and inflammatory cytokines support the involvement of neuro-inflammation and oxidative stress in Autism Spectrum Disorder. Journal of translational medicine. 2019;17(1):1-12. https://doi.org/10.1186/s12967-019-2076-z


16. Movahedi A, Bahrami F, Marandi SM, & Abedi A. Improvement in social dysfunction of children with autism spectrum disorder following long term Kata techniques training. Res Autism Spectr Disord 2013; 7:1054-1061. https://doi.org/10.1016/j.rasd.2013.04.012


17. Ross HE, Guo Y, Coleman K, Ousley O, & Miller AH. Association of IL-12p70 and IL-6: IL-10 ratio with autism-related behaviors in 22q11. 2 deletion syndrome: a preliminary report. Brain Behav Immun 2013;31:76-81. https://doi.org/10.1016/j.bbi.2012.12.021


18. Jyonouchi H, Sun S, & Le H. Proinflammatory and regulatory cytokine production associated with innate and adaptive immune responses in children with autism spectrum disorders and developmental regression. J Neuroimmunol 2001;120:170-179. https://doi.org/10.1016/S0165-5728(01)00421-0


19. LeClerc S & Easley D. Pharmacological therapies for autism spectrum disorder: a review. Pharmacy and Therapeutics 2015;40:389.


20. Jonsson U, Olsson NC, Coco C et al. Long-term social skills group training for children and adolescents with autism spectrum disorder: a randomized controlled trial. Eur Child Adolesc Psychiatry 2019;28:189-201. https://doi.org/10.1007/s00787-018-1161-9


21. DeVilbiss EA, Magnusson C, Gardner RM et al. Antenatal nutritional supplementation and autism spectrum disorders in the Stockholm youth cohort: population based cohort study. Bmj 2017;359. doi: https://doi.org/10.1136/bmj.j4273


22. Johnson NL, Bekhet AK, Karenke T, & Garnier-Villarreal M. Swim program pilot for children with autism: impact on behaviors and health. West J Nurs Res 2021;43:356-363. https://doi.org/10.1177/0193945920948867


23. Pan CY. Effects of water exercise swimming program on aquatic skills and social behaviors in children with autism spectrum disorders. Autism 2010;14:9-28. https://doi.org/10.1177/1362361309339496


24. Petruzzelli MG, Marzulli L, Margari F et al. Vitamin D deficiency in autism spectrum disorder: A cross-sectional study. Dis Markers 2020. https://doi.org/10.1155/2020/9292560


25. Lee BK, Eyles DW, Magnusson C et al. Developmental vitamin D and autism spectrum disorders: findings from the Stockholm Youth Cohort. Mol Psychiatry 2021; 26:1578-1588. https://doi.org/10.1038/s41380-019-0578-y


26. Javadfar Z, Abdollahzad H, Moludi J et al. Effects of vitamin D supplementation on core symptoms, serum serotonin, and interleukin-6 in children with autism spectrum disorders: A randomized clinical trial. Nutrition 2020;79:110986. https://doi.org/10.1016/j.nut.2020.110986


27. Feng J, Shan L, Du L, et al. Clinical improvement following vitamin D3 supplementation in autism spectrum disorder. Nutr Neurosci 2017;20:284-290. https://doi.org/10.1080/1028415X.2015.1123847


28. Zheng S, Wang B, Han W e al. Vitamin D supplementation and inflammatory and metabolic biomarkers in patients with knee osteoarthritis: post hoc analysis of a randomised controlled trial. Br J Nutr 2018;120:41-48. https://doi.org/10.1017/S0007114518001174


29. Karonova T, Stepanova A, Bystrova A, & Jude EB. High-dose vitamin D supplementation improves microcirculation and reduces inflammation in diabetic neuropathy patients. Nutrients 2020;12:2518. https://doi.org/10.3390/nu12092518


30. Ansari S, Hosseinkhanzadeh AA, AdibSaber F, Shojaei M, & Daneshfar A. The effects of aquatic versus kata techniques training on static and dynamic balance in children with autism spectrum disorder. J Autism Dev Disord 2020;51:3180-3186. https://doi.org/10.1007/s10803-020-04785-w


31. Caputo G, Ippolito G, Mazzotta M, Sentenza L, Muzio MR, Salzano S, & Conson M. Effectiveness of a multisystem aquatic therapy for children with autism spectrum disorders. J Autism Dev Disord 2018;48:1945-1956. https://doi.org/10.1007/s10803-017-3456-y


32. Kolachahi SA, AdibSaber F, Zidashti ZH, Elmieh A, Bidabadi E, & Hosseinkhanzadeh AA. Water-based training in combined with vitamin D supplementation improves lipid profile in children with ASD. Res Autism Spectr Disord 2020;76:101603. https://doi.org/10.1016/j.rasd.2020.101603


33. Azimigarosi S, Arjmandnia A, Mohseni Ezhei A & Asgari M. Effectiveness of hydrotherapy on communication skills of children with autism spectrum disorder: a single case study. Quarterly Journal of Child Mental Health 2020;6:35-50. http://childmentalhealth.ir/article-1-821-en.html


34. Battaglia G, Agrò G, Cataldo P, Palma A, & Alesi M. Influence of a specific aquatic program on social and gross motor skills in adolescents with autism spectrum disorders: Three case reports. J Funct Morphol Kinesiol 2019;4:27. https://doi.org/10.3390/jfmk4020027


35. Mortimer R, Privopoulos M, & Kumar S. The effectiveness of hydrotherapy in the treatment of social and behavioral aspects of children with autism spectrum disorders: a systematic review. J Multidiscip Healthc2014;7:93. doi: 10.2147/JMDH.S55345


36. Oriel KN, Kanupka JW, DeLong KS & Noel K. The impact of aquatic exercise on sleep behaviors in children with autism spectrum disorder: A pilot study. Focus Autism Other Dev Disabl 2016;31:254-261. https://doi.org/10.1177/1088357614559212


37. Bezheh N, Soltani M, & Khaleghzade H. Effects of aerobic training in water on IL-6 and IL-10 in patients with Multiple Sclerosis. Evidence Based Care 2014;4:63-72. http://eprints.mums.ac.ir/id/eprint/532


38. Qin L, Yao ZQ, Chang Q et al. Swimming attenuates inflammation, oxidative stress, and apoptosis in a rat model of dextran sulfate sodium-induced chronic colitis. Oncotarget 2017;8:7391. doi: 10.18632/oncotarget.14080


39. Gilliam JE. Gilliam Autism Rating Scale: GARS 2. Pro-ed. 2006.


40. AdibSaber F, Shojaei M, Daneshfar A, & Hossein Khanzadeh A. Aquatic Exercise on Stereotypic Behaviors and Sleep Habits in Children with Autism Spectrum Disorder. Middle Eastern Journal of Disability Studies 2019;9:110-110. http://jdisabilstud.org/article-1-1174-en.html


41. Cannell JJ. Vitamin D and autism, what’s new?. Rev Endocr Metab Disord 2017;18:183-193. https://doi.org/10.1007/s11154-017-9409-0


42. Calle MC, & Fernandez ML. Effects of resistance training on the inflammatory response. Nutr Res Pract 2010;4:259-269.


43. Doostdar M, Fathei M, & Hejazi K. The Effect of Eight Weeks of Aerobic Training on Leptin, Interlukin-6, and Tumor Necrosis Factor-alpha Levels in Inactive Elderly Women. Pathobiology Research 2017;19:13-25. http://mjms.modares.ac.ir/article-30-10248-en.html


44. Azizbeigi K, Azarbayjani MA, Atashak S, & Stannard, SR. Effect of moderate and high resistance training intensity on indices of inflammatory and oxidative stress. Res Sports Med 2015;23:73-87. https://doi.org/10.1080/15438627.2014.975807


45. Forti LN, Van Roie E, Njemini R, Coudyzer W, Beyer I, Delecluse C, & Bautmans I. Effects of resistance training at different loads on inflammatory markers in young adults. Eur J Appl Physiol 207;117:511-519. https://doi.org/10.1007/s00421-017-3548-6


46. Gleeson M. Immune function in sport and exercise. Eur J Appl Physiol 2007;103:693-699. https://doi.org/10.1152/japplphysiol.00008.2007