Vitamin C

Vitamin C plays a multifaceted role in the surgical stress response, providing critical antioxidant, anti-inflammatory, and endothelial-protective functions. Surgery induces a substantial rise in oxidative stress and systemic inflammation, contributing to postoperative complications and organ dysfunction. Vitamin C levels consistently decline following surgery, with a meta-analysis showing an average 39% reduction in plasma concentrations during the first postoperative week, with levels remaining suppressed for months, indicating heightened perioperative requirements [1,2].

Vitamin C supplementation has been explored for its potential to support immune function, reduce oxidative injury, and mitigate postoperative complications in both cardiac and noncardiac surgical populations.

Mechanisms of Action and Benefits

Oxidative Stress Mitigation and Antioxidant Support
Vitamin C neutralizes reactive oxygen species (ROS) and reduces lipid peroxidation triggered by surgical trauma. This antioxidant action preserves cellular integrity and reduces the burden of oxidative injury during the critical perioperative period [1,2].

Inflammation Modulation
Through its influence on cytokine signaling, vitamin C modulates the inflammatory response associated with surgery. This includes downregulation of pro-inflammatory mediators, which may support a more controlled recovery environment and reduce risk of organ dysfunction [2,3].

Support for Endothelial and Immune Function
Vitamin C helps maintain vascular endothelial integrity, an essential function for regulating capillary permeability and microcirculatory flow following trauma. Additionally, it enhances leukocyte activity, chemotaxis, and lymphocyte proliferation, contributing to immune surveillance and wound healing [2,3].

Perioperative and Clinical Effects

Noncardiac Surgery
In patients undergoing noncardiac procedures, perioperative vitamin C administration has not demonstrated significant effects on length of stay or mortality, but is associated with reduced postoperative pain and lower opioid requirements. Adverse effects are rare, though not comprehensively assessed [3].

Cardiac Surgery
Vitamin C shows greater promise in cardiac surgical settings. Supplementation has been associated with reduced incidence of postoperative atrial fibrillation, shorter ICU and hospital stays, and decreased ventilation duration. However, effects on mortality and organ dysfunction remain unclear due to study heterogeneity [4].

High-Dose Intravenous Administration
Randomized controlled trials using high-dose intravenous vitamin C (e.g., 200 mg/kg/day) report reduced postoperative pulmonary complications, improved renal function, and favorable short-term safety profiles. These findings underscore vitamin C’s therapeutic potential in high-risk surgical patients [5].

Clinical Implications

Surgical patients experience rapid vitamin C depletion, increasing their risk for oxidative injury and delayed recovery. While the routine use of vitamin C remains under investigation, targeted perioperative supplementation—particularly in cardiac surgery or high-risk populations—may help reduce complications, optimize recovery, and improve patient outcomes.

References

1. Travica N, Ried K, Hudson I, et al. The effects of surgery on plasma/serum vitamin C concentrations: a systematic review and meta-analysis. Br J Nutr. 2022;127(2):233–247.
2. Fukushima R, Yamazaki E. Vitamin C requirement in surgical patients. Curr Opin Clin Nutr Metab Care. 2010;13(6):669–676.
3. Suter M, Bollen Pinto B, Belletti A, Putzu A. Efficacy and safety of perioperative vitamin C in patients undergoing noncardiac surgery: a systematic review and meta-analysis of randomised trials. Br J Anaesth. 2022;128(4):664–678.
4. Hill A, Clasen KC, Wendt S, et al. Effects of vitamin C on organ function in cardiac surgery patients: a systematic review and meta-analysis. Nutrients. 2019;11(9):2103.
5. Karadžić Kočica M, Ristić A, Soldatović I, et al. The influence of high-dose parenteral vitamin C on the incidence and severity of postoperative pulmonary complications in cardiac surgery with extracorporeal circulation: a randomized controlled trial. Nutrients. 2024;16(6):761.