Vitamin C in Sepsis: Evidence-Based Recommendations

Guideline-Based Recommendations

The Surviving Sepsis Campaign pediatric guidelines (2020) recommend against the use of ascorbic acid (vitamin C) in the treatment of children with septic shock or other sepsis-associated organ dysfunction (weak recommendation, very low quality of evidence) 1
The ESPEN guidelines (2022) provide context-specific recommendations, including a higher vitamin C repletion dose of 2-3 g per day IV during the acute phase of inflammation (Grade B recommendation, 84% consensus) 2

Do NOT routinely administer vitamin C for sepsis treatment based on current evidence 1
Consider vitamin C only in the context of documented severe vitamin C deficiency with clinical suspicion of scurvy 2
Consider vitamin C only in the context of research protocol participation with appropriate informed consent 3
Consider vitamin C only in the context of refractory septic shock after exhausting all guideline-recommended therapies, understanding this is not evidence-based 4

The most commonly studied regimen is 1.5 g IV every 6 hours for 4 days (total 6 g/day), often combined with thiamine and hydrocortisone
Alternative protocols include 2-3 g/day IV during acute inflammation 2

Avoid vitamin C supplementation in patients with hemochromatosis, G6PD deficiency, renal dysfunction, or history of oxalate kidney stones 2
Screen for contraindications before administration 3
Monitor for edema if using doses above 1 g daily
Be aware that plasma vitamin C levels decline rapidly with inflammation (CRP >10 mg/L), making interpretation difficult 2

Do not delay standard sepsis care (antibiotics, source control, fluid resuscitation, vasopressors) to administer vitamin C 4, 3, 5
Do not measure plasma vitamin C levels in acute sepsis - inflammation makes interpretation unreliable 2

The ESPEN guidelines suggest specific dosages for critical illness in general, including 2-3 g/day IV during the acute phase of inflammation, 2-3 g/day IV for continuous renal replacement therapy, and 1-2 g/day for 5-7 days IV for perioperative cardiac surgery, with a Grade B recommendation and 84% consensus, although this is not specific to sepsis 6

The C-EASIE 2025 trial used a dosage of 1.5 g every 6 hours for 4 days (total 6 g/day) and found no significant reduction in the mean SOFA score post-baseline (ratio 0.91, 95% CI 0.77-1.08, P=0.30) 7
The ESPEN guidelines mention a dosage range of 50-200 mg/kg/day in various protocols, although this is not specific to sepsis 8
A dosage of 66 mg/kg/hour for 24 hours has been studied in the context of burns, which is different from sepsis 8

High-dose vitamin C is relatively safe, but precautions should be taken in patients with hemochromatosis, G6PD deficiency, renal dysfunction, and those at risk of oxalate stone formation, with a recommendation against monotherapy antioxidant use in high doses without proven deficiency (Grade B, 96% consensus) 9
The use of high-dose vitamin C should be avoided in patients without proven deficiency, with dosages exceeding 10 times the dietary reference intake not recommended in clinical settings without severe proven deficiency 8

Proposed mechanisms of vitamin C in sepsis include prevention of microcirculatory flow deterioration, inhibition of platelet aggregation, restoration of vascular response to vasoconstrictors, preservation of the endothelial barrier, and enhancement of antibacterial defenses, although these have not translated to significant clinical benefits in rigorous trials 7