The Effect of Folic Acid Supplementation on the Liver Function in Chronic Schizophrenia Patients


  • Alifiati Fitrikasari Departemen Psikiatri, Fakultas Kedokteran, Universitas Diponegoro, Semarang
  • Julianata Asady Departemen Psikiatri, Fakultas Kedokteran, Universitas Diponegoro
  • Innawati Jusup Departemen Psikiatri, Fakultas Kedokteran, Universitas Diponegoro
  • Hang Gunawan Asikin Departemen Psikiatri, Fakultas Kedokteran, Universitas Diponegoro



Antipsychotic agents, Aspartate aminotransferase, Schizophrenia, Folic acid, Liver function


Oxidative stress caused by free radicals and long-term antipsychotic use in chronic schizophrenic patients may result in liver cell damage and impaired liver function. Folic acid is an exogenous antioxidant that can boost the antioxidant defense mechanism (Glutathione Reductase), lowering free radicals and improving liver function. Determine the correlation between adjuvant folic acid and liver function in chronic schizophrenic patients. This was a placebo-controlled, double-blinded randomized control trial. The study sample included 36 patients in the control group and 36 patients in the treatment group. Subjects were patients who had suffered from schizophrenia for at least 2 years and received antipsychotics. Research subjects in the treatment group received folic acid supplementation. The intervention was conducted for 21 days during hospitalization. The level of AST (U/L) and ALT (U/L) was measured before and after supplementation. Following folic acid supplementation, AST levels were significantly improved (26.950 U/L compared to prior to treatment 33.09 U/L, p= <0.001). ALT levels after treatment were increased but there was no significant difference observed (p= 0.835). Folic acid supplementation improves AST levels significantly.

Author Biographies

Innawati Jusup, Departemen Psikiatri, Fakultas Kedokteran, Universitas Diponegoro

Departemen Psikiatri, Fakultas Kedokteran, Universitas Diponegoro

Hang Gunawan Asikin, Departemen Psikiatri, Fakultas Kedokteran, Universitas Diponegoro

Departemen Psikiatri, Fakultas Kedokteran, Universitas Diponegoro


[1]. Charlson FJ, Ferrari AJ, Santomauro DF, Diminic S, Stockings E, Scott JG, et al. Global epidemiology and burden of schizophrenia: Findings from the global burden of disease study 2016. Schizophr Bull. 2018;44(6):1195–203.

[2]. Meesters PD, De Haan L, Comijs HC, Stek ML, Smeets-Janssen MMJ, Weeda MR, et al. Schizophrenia spectrum disorders in later life: Prevalence and distribution of age at onset and sex in a dutch catchment area. American Journal of Geriatric Psychiatry. 2012;20(1):18–28.

[3]. Idaiani S, Yunita I, Tjandrarini DH, Indrawati L, Darmayanti I, Kusumawardani N, et al. Prevalensi Psikosis di Indonesia berdasarkan Riset Kesehatan Dasar 2018. Jurnal Penelitian dan Pengembangan Pelayanan Kesehatan. 2019;3(1):9–16.

[4]. James SL, Abate D, Abate KH, Abay SM, Abbafati C, Abbasi N, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 354 Diseases and Injuries for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017. The Lancet. 2018;392(10159):1789–858.

[5]. Baeza I, De La Serna E, Calvo-Escalona R, Merchán-Naranjo J, Rodríguez-Latorre P, Martínez-Cantarero MC, et al. One-Year Prospective Study of Liver Function Tests in Children and Adolescents on Second-Generation Antipsychotics: Is There a Link with Metabolic Syndrome? J Child Adolesc Psychopharmacol. 2018;28(7):463–73.

[6]. Wang S, Zhang J, Zhu L, Song L, Meng Z, Jia Q, et al. Association between liver function and metabolic syndrome in Chinese men and women. Sci Rep. 2017;7:1–9.

[7]. Erdogan A, Karaman MG, Ozdemir E, Yurteri N, Tufan AE, Kurcer MA. Six months of treatment with risperidone may be associated with nonsignificant abnormalities of liver function tests in children and adolescents: A longitudinal, observational study from Turkey. J Child Adolesc Psychopharmacol. 2010;20(5):407–13.

[8]. Morlán-Coarasa MJ, Arias-Loste MT, Ortiz-García de la Foz V, Martínez-García O, Alonso-Martín C, Crespo J, et al. Incidence of non-alcoholic fatty liver disease and metabolic dysfunction in first episode schizophrenia and related psychotic disorders: a 3-year prospective randomized interventional study. Psychopharmacology (Berl). 2016;233(23–24):3947–52.

[9]. Telles-Correia D, Barbosa A, Cortez-Pinto H, Campos C, Rocha NBF, Machado S. Psychotropic drugs and liver disease: A critical review of pharmacokinetics and liver toxicity. World J Gastrointest Pharmacol Ther. 2017;8(1):26.

[10]. Hepatotoxicity D induced, Lee WM. Drug-Induced Hepatotoxicity. 2003;474–85.

[11]. Faizi M, Salimi A, Rasoulzadeh M, Naserzadeh P, Pourahmad J. Schizophrenia induces oxidative stress and cytochrome c release in isolated rat brain mitochondria: A possible pathway for induction of apoptosis and neurodegeneration. Iranian Journal of Pharmaceutical Research. 2014;13(SUPPL):93–100.

[12]. Tsugawa S, Noda Y, Tarumi R, Mimura Y, Yoshida K, Iwata Y, et al. Glutathione levels and activities of glutathione metabolism enzymes in patients with schizophrenia: A systematic review and meta-analysis. Journal of Psychopharmacology. 2019;33(10):1199–214.

[13]. Iskandar BJ, Nelson A, Resnick D, Skene JHP, Gao P, Johnson C, et al. Folic acid supplementation enhances repair of the adult central nervous system. Ann Neurol. 2004;56(2):221–7.

[14]. Wang D, Zhai JX, Liu DW. Serum folate levels in schizophrenia: A meta-analysis. Psychiatry Res. 2016;235:83–9.

[15]. Asbaghi O, Ashtary-Larky D, Bagheri R, Moosavian P, Nazarian B, Afrisham R, et al. Effects of folic acid supplementation on inflammatory markers: A grade-assessed systematic review and dose–response meta-analysis of randomized controlled trials. Nutrients. 2021;13(7):1–20.

[16]. Hakulinen C, McGrath JJ, Timmerman A, Skipper N, Mortensen PB, Pedersen CB, et al. The association between early-onset schizophrenia with employment, income, education, and cohabitation status: nationwide study with 35 years of follow-up. Soc Psychiatry Psychiatr Epidemiol. 2019;54(11):1343–51.

[17]. Samuel R, Thomas E, Jacob KS. Instrumental Activities of Daily Living Dysfunction among People with Schizophrenia. Indian J Psychol Med. 2018;40.

[18]. De Leon J, Diaz FJ. A meta-analysis of worldwide studies demonstrates an association between schizophrenia and tobacco smoking behaviors. Schizophr Res. 2005;76(2–3):135–57.

[19]. Adebiyi MO, Mosaku SK, Irinoye OO, Oyelade OO. Socio-demographic and clinical factors associated with relapse in mental illness. Int J Afr Nurs Sci. 2018;8(May):149–53.

[20]. Dervaux A, Laqueille X. Smoking and schizophrenia. Handbook of Smoking and Health. 2011;21(3):679–93.




How to Cite

Fitrikasari, A., Asady, J., Jusup, I., & Asikin, H. G. (2023). The Effect of Folic Acid Supplementation on the Liver Function in Chronic Schizophrenia Patients. Jurnal Profesi Medika : Jurnal Kedokteran Dan Kesehatan, 17(2), 142–149.