Effect of Adjuvant Vitamin C on Brain-Derived Neurotrophic Factor Levels and Improvement of Negative Symptoms in Schizophrenic Patients


  • Andi Jayalangkara Tanra Department of Psychiatry, Medical Faculty, Hasanuddin University, South Sulawesi 90245, Indonesia
  • Herwina Sabaruddin Department of Psychiatry, Medical Faculty, Hasanuddin University, South Sulawesi 90245, Indonesia
  • Kristian Liaury Department of Psychiatry, Medical Faculty, Hasanuddin University, South Sulawesi 90245, Indonesia
  • Andi Alfian Zainuddin Department of Psychiatry, Medical Faculty, Hasanuddin University, South Sulawesi 90245, Indonesia




Vitamin C, BDNF, Negative Symptoms, Schizophrenia


AIM: This study aims to determine the effect of adjuvant Vitamin C on brain-derived neurotropic factors (BDNF) levels and improvement of negative symptoms in schizophrenic patients.

METHODS: This study was conducted at Hasanuddin University Hospital and its affiliate with 60 schizophrenic patients (30 controls, 27 treatments, and three dropout patients). The ELISA sample examination method was used to examine blood levels of BDNF, and Vitamin C levels before and after administration of Vitamin C. In addition, the negative symptoms were measured using the PANSS score.

RESULTS: There was a significant increase in BDNF levels in treatments group compared the control at 4th–8th weeks with p = 0.005 (4th week) and ≤0.0001 (<0.05) (8th week). The improvement in PANSS scores for negative symptoms in the treatment groups compared to the controls at the 2nd, 4th, and 8th weeks resulted in p = 0.042 (2nd week) and <0.0001 (4th–8th weeks). Furthermore, there was an increase in serum Vitamin C levels in the treatment groups with an initial average value = 4.762 and after 8 weeks = 148.155. Strong correlation between increased BDNF levels and improvement in negative symptoms on the PANSS score was found with p = 0.001 (4th week) and ≤0.0001 (8th week).

CONCLUSION: The administration of Vitamin C significantly increases BDNF levels and improves the PANSS score for negative symptoms in the treatments compared to the control groups.


Download data is not yet available.


Metrics Loading ...

Plum Analytics Artifact Widget Block


Kaplan HI, Sadock BJ. Schizophrenia. In: Synopsis of Psychiatry: Behavioral Sciences Clinical Psychiatry. Lippincott Williams and Wilkins Co.; 2015.

Amir N, Kusumawardhani A, Husain A, Adikusumo A, Damping C. Buku ajar Psikiatri. Jakarta: Fakultas Kedokteran Universitas Indonesia; 2010.

Millan MJ, Fone K, Steckler T, Horan WP. Negative symptoms of schizophrenia: Clinical characteristics, pathophysiological substrates, experimental models and prospects for improved treatment. Eur Neuropsychopharmacol. 2014;24(5):645-92. https://doi.org/10.1016/j.euroneuro.2014.03.008 PMid:24820238 DOI: https://doi.org/10.1016/j.euroneuro.2014.03.008

Correll CU, Schooler NR. Negative symptoms in schizophrenia: A review and clinical guide for recognition, assessment, and treatment. Neuropsychiatr Dis Treat. 2020;16:519-34. https://doi.org/10.2417/NDT.S225643 PMid:32110026 DOI: https://doi.org/10.2147/NDT.S225643

Noto C, Ota VK, Gadelha A, Noto MN, Barbosa DS, Bonifácio KL, et al. Oxidative stress in drug naïve first episode psychosis and antioxidant effects of risperidone. J Psychiatr Res. 2015;68:210-6. https://doi.org/10.1016/j.jpsychires.2015.07.003 PMid:26228421 DOI: https://doi.org/10.1016/j.jpsychires.2015.07.003

Numakawa T, Suzuki S, Kumamaru E, Adachi N, Richards M, Kunugi H. BDNF function and intracellular signaling in neurons. Histol Histopathol. 2010;25(2):237-58. https://doi.org/10.14670/ hh-25.237 PMid:20017110

Nazari H, Heydarpoor S, Mohamadi Mofrad A, Nazari Y, Nazari A. Effect of Vitamin C on serum concentration of brain-derived neurotrophic factor among healthy inactive young men. Neurosci J Shefaye Khatam. 2016;4(2):27-32. DOI: https://doi.org/10.18869/acadpub.shefa.4.2.27

Figueroa-Méndez R, Rivas-Arancibia S. Vitamin C in health and disease: Its role in the metabolism of cells and redox state in the brain. Front Physiol. 2015;6:397-408. https://doi.org/10.3389/fphys.2015.00397 PMid:26779027 DOI: https://doi.org/10.3389/fphys.2015.00397

Hoenders HR, Bartels-Velthuis AA, Vollbehr NK, Bruggeman R, Knegtering H, de Jong JT. Natural medicines for psychotic disorders: A systematic review. J Nerv Ment Dis. 2018;206(2):81-101. https://doi.org/10.1097/NMD.0000000000000782 PMid:29373456 DOI: https://doi.org/10.1097/NMD.0000000000000782

Dakhale GN, Khanzode SD, Khanzode SS, Saoji A. Supplementation of Vitamin C with atypical antipsychotics reduces oxidative stress and improves the outcome of schizophrenia. Psychopharmacology. 2005;182(4):494-8. https://doi.org/10.1007/s00213-005-0117-1 PMid:16133138 DOI: https://doi.org/10.1007/s00213-005-0117-1

Oberlies, T. Vitamins in schizophrenia: A literature review. Indo Iran J. 2012;37(4):333-49. https://doi.org/10.1163/000000094790084162 DOI: https://doi.org/10.1163/000000094790084162

Khodaie M, Alibeigi N, Mirzaei VG. The effect of Ascorbic Acid as supplementary treatment with risperidone in controlling the symptoms of schizophrenia: A double-blind, placebo-controlled clinical trial. J Basic Clin Pathophysiol. 2019;7(1):7-14. https://doi.org/10.22070/jbcp.2019.3616.1104

Yusuf M. Perbedaan Total Skor PANSS pada Laki-laki Skizofrenia yang Mendapat Risperidon dengan Penambahan Vitamin C dan yang Hanya Mendapat Risperidon di Rumah Sakit Jiwa Prof. M. Ildrem Medan; 2019.

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Washington, DC: American Psychiatric Association; 2013. DOI: https://doi.org/10.1176/appi.books.9780890425596

Vahia IV, Palmer BW, Depp C, Fellows I, Golshan S, Kraemer HC, Jeste DV. Is late‐onset schizophrenia a subtype of schizophrenia? Acta Psychiatr Scand. 2010;122(5):414-26. https://doi.org/10.1111/j.1600-0447.2010.01552 PMid:20199491 DOI: https://doi.org/10.1111/j.1600-0447.2010.01552.x

Magalhães PV, Dean O, Andreazza AC, Berk M, Kapczinski F. Antioxidant treatments for schizophrenia. Cochrane Database Syst Rev. 2016;2016(2):1-93. https://doi.org/10.1002/14651858. CD008919.pub2 PMid:26848926 DOI: https://doi.org/10.1002/14651858

Moretti M, Fraga DB, Rodrigues AL. Ascorbic acid to manage psychiatric disorders. CNS Drugs. 2017;31(7):571-83. https://doi.org/10.1007/s40263-017-0446-8 PMid:28600627 DOI: https://doi.org/10.1007/s40263-017-0446-8

Zheng F, Zhou X, Moon C, Wang H. Regulation of brain-derived neurotrophic factor expression in neurons. Int J Physiol Pathophysiol Pharmacol. 2012;4(4):188-200. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544221 PMid:23320132

Qian L, Zhao J, Shi Y, Zhao X, Feng G, Xu F, et al. Brain-derived neurotrophic factor and risk of schizophrenia: An association study and meta-analysis. Biochem Biophys Res Commun. 2007;353(3):738-43. https://doi.org/10.1016/j.bbrc.2006.12.121 PMid:17196936 DOI: https://doi.org/10.1016/j.bbrc.2006.12.121

Grillo RW, Ottoni GL, Leke R, Souza DO, Portela LV, Lara DR. Reduced serum BDNF levels in schizophrenic patients on clozapine or typical antipsychotics. J Psychiatr Res. 2007;41(1-2):31-5. https://doi.org/10.1016/j.jpsychires.2006.01.005 PMid:16546213 DOI: https://doi.org/10.1016/j.jpsychires.2006.01.005

Toyooka K, Asama K, Watanabe Y, Muratake T, Takahashi M, Someya T, et al. Decreased levels of brain-derived neurotrophic factor in serum of chronic schizophrenic patients. Psychiatry Res. 2002;110(3):249-57. https://doi.org/10.1016/S0165-1781(02)00127-0 PMid:12127475 DOI: https://doi.org/10.1016/S0165-1781(02)00127-0

Xiu MH, Hui L, Dang YF, De Hou T, Zhang CX, Zheng YL, et al. Decreased serum BDNF levels in chronic institutionalized schizophrenia on long-term treatment with typical and atypical antipsychotics. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33(8):1508-12. https://doi.org/10.1016/j.pnpbp.2009.08.011 PMid:19720106 DOI: https://doi.org/10.1016/j.pnpbp.2009.08.011

Ikeda Y, Yahata N, Ito I, Nagano M, Toyota T, Yoshikawa T, et al. Low serum levels of brain-derived neurotrophic factor and epidermal growth factor in patients with chronic schizophrenia. Schizophr Res. 2008;101(1-3):58-66. https://doi.org/10.1016/j.schres.2008.01.017 PMid:18289832 DOI: https://doi.org/10.1016/j.schres.2008.01.017

Zhang XY, Xiu MH, De Yang F, Wu GY, Lu L, Kosten TA, et al. Nicotine dependence and serum BDNF levels in male patients with schizophrenia. Psychopharmacology. 2010;212(3):301-7. https://doi.org/10.1007/s00213-010-1956-y PMid:20661552 DOI: https://doi.org/10.1007/s00213-010-1956-y

Nasirin C, Lionardo A. Decentralization, public services and neglected children in Mataram City, West Nusa Tenggara. Rese Horiz. 2021;1(2):55-61. https://doi.org/10.54518/rh.1.2.2021.55-61 DOI: https://doi.org/10.54518/rh.1.2.2021.55-61

Tsai G, Coyle JT. Glutamatergic mechanisms in schizophrenia. Ann Rev Pharmacol Toxicol. 2002;42(1):165-79. https://doi.org/10.1146/annurev.pharmtox.42.082701.160735 PMid:11807169 DOI: https://doi.org/10.1146/annurev.pharmtox.42.082701.160735

Tamminga CA. Schizophrenia and glutamatergic transmission. Crit Rev Neurobiol. 1998;12(1-2):21-36. https://doi.org/10.1615/critrevneurobiol.v12.i1-2.20 PMid:9444480 DOI: https://doi.org/10.1615/CritRevNeurobiol.v12.i1-2.20

Menniti FS, Lindsley CW, Conn PJ, Pandit J, Zagouras P, Volkmann RA. Allosteric modulators for the treatment of schizophrenia: targeting glutamatergic networks. Curr Top Med Chem. 2013;13(1):26-54. https://doi.org/10.2174/1568026611313010005 PMid:23409764 DOI: https://doi.org/10.2174/1568026611313010005

Gaspar PA, Bustamante ML, Silva H, Aboitiz F. Molecular mechanisms underlying glutamatergic dysfunction in schizophrenia: Therapeutic implications. J Neurochem. 2009;111(4):891-900. https://doi.org/10.1111/j.1471-4159.2009.06325.x PMid:19686383 DOI: https://doi.org/10.1111/j.1471-4159.2009.06325.x

D’souza B, D’souza V. Oxidative injury and antioxidant Vitamins E and C in schizophrenia. Indian J Clin Biochem. 2003;18(1):87-90. https://doi.org/10.1007/BF02867671 PMid:23105377 DOI: https://doi.org/10.1007/BF02867671




How to Cite

Tanra AJ, Sabaruddin H, Liaury K, Zainuddin AA. Effect of Adjuvant Vitamin C on Brain-Derived Neurotrophic Factor Levels and Improvement of Negative Symptoms in Schizophrenic Patients. Open Access Maced J Med Sci [Internet]. 2021 Nov. 17 [cited 2024 Apr. 21];9(T3):353-7. Available from: https://oamjms.eu/index.php/mjms/article/view/7086

Most read articles by the same author(s)

1 2 > >>