The Effect of a Novel Combination of Vitamin D and Probiotic on Clinical Symptoms, Biomarkers of Oxidative Stress and Cardio-Metabolic Risk in Patients with Chronic Schizophrenia: A Randomized, Double-Blinded, Placebo-Controlled Trial

Abstract

Objective: This study determined the effects of a novel combination of vitamin D and probiotic supplementation on clinical and metabolic symptoms in patients with chronic schizophrenia. Methods: A randomized, double-blind, placebo-controlled trial was conducted for 60 patients with chronic schizophrenia. They were randomly allocated into two groups to receive either 50,000 IU vitamin D3 plus 8x109 CFU/day probiotic (n=30) every 2 weeks or placebo (n=30) for 12 weeks. The patients' clinical symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS) and the Brief Psychiatric Rating Scale (BPRS) scores test. Results: Vitamin D and probiotic co-supplementation was associated with a significant improvement in the general (-3.1±4.7 vs. 0.3±3.9, P=0.004) and total PANSS scores (-7.4±8.7 vs. -1.9±7.5, P=0.01), compared with the placebo group. Vitamin D and probiotic co-supplementation also significantly increased total antioxidant capacity ( 51.1±129.7 vs. -20.7±53.3 mmol/L, P=0.007), and decreased malondialdehyde (-0.3±0.9 vs. 0.2±0.4 µmol/L, P=0.01) and serum high sensitivity C-reactive protein levels (-2.3±3.0 vs. -0.3±0.8 mg/L, P=0.001) rather than placebo group. Moreover, taking vitamin D plus probiotic, compared with the placebo, significantly reduced fasting plasma glucose (-7.0±9.9 vs. -0.2±9.9 mg/dL, P=0.01), insulin concentrations (-2.7±2.3 vs. 0.4±2.0 µIU/mL, P<0.001), homeostasis model of assessment-estimated insulin resistance (-0.8±0.7 vs. 0.1±0.7, P<0.001), triglycerides (-7.8±25.2 vs. 10.1±30.8 mg/dL, P=0.01) and total- (-4.9±15.0 vs. 5.9±19.5 mg/dL, P=0.04). Co-supplementation also significantly increased quantitative insulin sensitivity check index ( 0.02±0.01 vs. 0.0003±0.01, P<0.001). Conclusion: Co-supplementation for 12 weeks had beneficial effects on the general and total PANSS score and metabolic profiles in patients with chronic schizophrenia. Trial registration number: This clinical trial was registered by the Iranian registry of clinical trials IRCT2017072333551N2). Funding: The study was supported by a grant from Kashan University of Medical Sciences, Kashan, Iran. Declaration of Interest: None. Ethical Approval: This study followed the principals of the Declaration of Helsinki and the study protocol was approved by the ethics committee at KUMS. Informed consent was obtained from all individual participants included in the study.