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

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 I2 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.

Efficacy of Marik Protocol in the Treatment of Septic Shock (Hydrocortisone, Ascorbic Acid and Thiamine)

“…SOFA score was reduced in the treatment group, and none of patients developed severe organ failure. In the same line, Muhammad and his colleagues (10) have displayed that in patients received vitamin C, a significant decrease in mortality (p = 0.016), SOFA (p < 0.001), and duration of vasopressors need (p = 0.001). Non-significant differences existed in the hospital and ICU length of stay.…”

“…While, Marik and his colleagues (4) have recorded that SOFA score reduced in treatment group, and none developed serious organ failure including AKI. In addition, Muhammad and his colleagues (10) have demonstrated that vitamin C treatment reduced SOFA score in comparison with controls. Moreover, pooled results from randomized clinical trials showed that hydrocortisone, vitamin C, and thiamine significantly decreased SOFA (p<0.00) (17) .…”

Subclinical Vitamin C Plasma Levels Associated with Increased Risk of CAD Diagnosis via Inflammation: Results from the NHANES 2003–2006 Surveys

“…With COVID-19 infections and pandemic stressors, such as quarantines, food insecurity, school closures, and supply chain issues, it is unclear how the nutritional status, including plasma vitamin C, of the population has been affected. Because of its inflammatory advantages in both acute and chronic inflammation [ 37 , 38 , 39 ], the benefits of a consistent sufficient plasma status may be realized in many disease processes, and an insufficiency of vitamin C explored.…”

The Outcome of IV Vitamin C Therapy in Patients with Sepsis or Septic Shock: A Meta-Analysis of Randomized Controlled Trials

“…Early studies con rmed IV vitamin C (IVVC) is associated with decreased in ammatory response and ameliorated outcomes in sepsis [7][8]. In addition, favorable outcomes in the vitamin C group was reported in some meta-analysis [9][10]. However, the available evidence remains inconsistent.…”