Vitamin C for sepsis: from mechanisms to individualized therapy

Sepsis is a critical illness initiated by infection and characterized by a dysregulated inflammatory and oxidative stress response, leading to high mortality rates and impaired long-term quality of life. It is noteworthy that many sepsis patients have insufficient levels of vitamin C, an essential micronutrient. Due to its diverse physiological roles, including antioxidant, anti-inflammatory, immunomodulatory, and antimicrobial-enhancing effects, vitamin C has gained significant attention as a potential adjunctive therapy for sepsis. However, the specific mechanisms by which vitamin C acts in sepsis are still not fully understood. Recent preclinical studies have shown that it can help reduce sepsis-induced organ damage, but clinical trials assessing its effectiveness have produced mixed results. Importantly, vitamin C's pharmacological effects depend on its concentration, and it has complex pharmacokinetics, which makes establishing an appropriate dosage regimen critical for achieving therapeutic outcomes in patients. This review aims to synthesize the current evidence regarding the therapeutic mechanisms of vitamin C in sepsis, identify limitations in the existing clinical research, and highlight future directions for investigation.