The Role and Efficacy of Vitamin C in Sepsis: A Systematic Review and Meta-Analysis

HIGHLIGHTS: Sepsis is a significant global healthcare burden and the leading cause of in-patient mortality. Our analysis showed that vitamin C adjunct therapy was linked to a significant decrease in mortality, duration of vasopressor used, and SOFA scores in septic patients. There is a further need for a large, randomized control trial to define a clearer role of vitamin C in the care of septic patients. ABSTRACT: Clinical rationale for study: Despite advancements in critical care, the mortality rate of sepsis remains high, with an overall poor prognosis. There is a complex pathophysiology of a lethal cascade of cytokines and inflammatory proteins underlying sepsis. The use of vitamin C can theoretically suppress the inflammatory cascade but remains a questionable practice due to a lack of conclusive evidence. Aims of the study: To appraise the therapeutic role of vitamin C in sepsis. Materials and methods: A systematic review was conducted on PubMed, Embase, and the Central Cochrane Registry. The study included randomized clinical trials (RCTs) with vitamin C as an intervention arm in the septic patient population. For continuous variables, the difference in means (MD) and for discrete variables, the odds ratio (OR) was used. For effect sizes, a confidence interval of 95% was used. A p-value of less than 0.05 was used for statistical significance. The analysis was performed using a random-effects model irrespective of heterogeneity. Heterogeneity was evaluated using the I(2) statistic. Results: 23 studies were included with the total sample size of 2712 patients. In patients treated with vitamin C, there was a statistically significant reduction in the mortality: OR = 0.778 (0.635 to 0.954), p = 0.016; the sequential organ failure assessment score (SOFA): MD = −0.749 (−1.115 to −0.383), p < 0.001; and the duration of vasopressor requirement: MD = −1.034 days (−1.622 to −0.445), p = 0.001. No significant difference was found in the hospital or ICU length of stay. Conclusions and clinical implications: Vitamin C treatment regimens were associated with reduced mortality, SOFA score, and vasopressor requirement compared to the control in sepsis. Given its low cost and minimal adverse effects, we strongly encourage further large, randomized trials to establish vitamin C as a standard of care in sepsis management.