The Role of Vitamins in Sepsis: A Narrative Review

Abstract

Sepsis remains one of the major challenges in modern intensive care, characterized by high mortality and complex metabolic and immunological disturbances. Given the limited effectiveness of current therapeutic strategies, increasing attention has been directed toward supportive interventions aimed at restoring metabolic homeostasis. Particular interest has been focused on selected vitamins that exhibit pleiotropic biological effects. Thus, we summarized the current evidence on the role of selected vitamins (C, D, B1, B9, B12) in the treatment and supportive management of sepsis, highlighting their mechanisms of action, potential clinical benefits, and limitations derived from available studies. A comprehensive analysis of the literature was performed, including clinical trials and meta-analyses evaluating the efficacy of vitamin supplementation in sepsis, with particular emphasis on combined interventions and randomized controlled trials in severe sepsis and septic shock. Vitamin D might demonstrate the greatest therapeutic potential, particularly in patients with severe sepsis and respiratory failure, with benefits associated with achieving appropriate therapeutic concentrations. Thiamine (vitamin B1) appears to provide potential advantages primarily in deficient patients, improving mitochondrial function and reducing the risk of renal failure. Evidence regarding folic acid (vitamin B9) and cobalamin (vitamin B12) remains inconclusive, as both deficiency and elevated serum levels have been linked to adverse outcomes. Vitamin C, despite its well-documented antioxidant and microcirculatory effects, has not yet shown consistent evidence of mortality reduction. In conclusion, current evidence suggests that vitamin supplementation might represent an adjunct to standard sepsis therapy, particularly within a personalized approach that considers nutritional status and metabolic phenotype. The development of standardized dosing protocols and well-designed clinical trials is essential to determine the efficacy and safety of phenotype-driven individualized approaches in sepsis management.

Keywords: adjunctive treatment; folic acid; immunomodulation; oxidative stress; sepsis; targeted therapy; thiamine; vitamin B12; vitamin C; vitamin D.

Figure 1

Clinical trial procedure of the CEMVIS study. Participants received intravenous vitamin C (VC) diluted in 5% glucose solution (GS) every 12 h (q12h). The study was overseen by the principal investigator (PI) and monitored by the Data and Safety Monitoring Board (DSMB) [15].