Examining the links between vitamin C and schizophrenia spectrum disorders: a systematic review and meta-analysis on circulating levels and supplementation outcomes.

Introduction: Schizophrenia (SCZ) is a debilitating psychiatric condition characterized by psychotic symptoms such as hallucinations, delusions, and disorganized thought. Recent evidence suggests its association with deficiency of various micronutrients. Vitamin C (vitC) is a key endogenous metabolite with potent antioxidant and neuroprotectant actions. However, the relationship between vitC deficiency and SCZ remains inconclusively established, both at the epidemiological and clinical levels, hindering its potential utility as a biomarker and a supplementary therapeutic. The purpose of this systematic review and meta-analysis was to investigate whether circulating levels of endogenous vitC are altered in SCZ subjects, and to examine the effect of exogenous vitC supplements on disease outcomes. Methods: Systematic searches for pertinent primary peer-reviewed studies on scholarly databases identified 19 studies. Newcastle-Ottawa scale and Methodological Index for Non-Randomized Studies were applied to judge the quality of studies of the case-control and supplementation trials, respectively. Random-effects restricted maximum likelihood meta-analysis models were employed for addressing the two specific aims of the study using standardized mean difference (SMD) as the point estimate. Results: SCZ patients showed significantly lowered vitC levels compared to the controls, with the pooled SMD being -1.046 [-1.459, -0.632]. Further, vitC supplementation was found to significantly reduce psychotic symptoms by -1.632 [-2.473, -0.791] units across a total of 6 datasets. Discussion: VitC deficiency appears to be a consistent feature of SCZ across diverse populations and its supplementation may be considered as a safe, inexpensive adjunct to antipsychotic therapy.