Intravenous Vitamin C in Severe Sepsis: A Systematic Review of Evidence From 2020 to 2025

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, with high mortality despite advances in standard care. Intravenous (IV) vitamin C has been proposed as an adjunctive therapy due to its antioxidant, endothelial-stabilizing, and catecholamine-sparing properties, which may improve organ function and reduce vasopressor requirements. This systematic review evaluates evidence from 2020 to 2025 on IV vitamin C in adult patients with sepsis or septic shock. Five studies, including randomized controlled trials, cohort studies, and meta-analyses, were included. Results indicate modest physiological benefits, such as transient reductions in Sequential Organ Failure Assessment (SOFA) scores and vasopressor duration, but consistent improvement in mortality, ICU stay, or hospital length of stay remains unproven. Variability in outcomes is influenced by dosing regimens, timing of administration, patient severity, and cointerventions. Early administration, particularly within 6 h of sepsis recognition, may enhance physiological effects, while delayed therapy appears less effective. Adverse effects, including oxalate nephropathy, highlight the need for careful monitoring. Overall, IV vitamin C may serve as a supportive adjunct in sepsis management, but robust, large-scale trials are needed to clarify its clinical efficacy, optimal dosing, safety, and patient selection.