Recent large randomized trials led by BIO-MICRO partners have raised important safety concerns about high-dose intravenous vitamin C in critically ill patients. Across different populations, out-of-hospital cardiac arrest and severe burn injury, vitamin C failed to improve organ function or survival and, in several analyses, was associated with signals of harm. Below we highlight the key findings from the VITaCCA trial in Intensive Care Medicine and the VICTORY trial in JAMA.
The VITaCCA trial
Amsterdam UMC researchers, working in the team of intensivist Angelique de Man, have published the VITaCCA randomized clinical trial in Intensive Care Medicine. This multi-center study investigated whether early intravenous vitamin C could improve outcomes in 273 comatose patients after out-of-hospital cardiac arrest with a shockable rhythm.
Key findings:
- Both a supplementation dose (3 g/day) and a high pharmacological dose (10 g/day) did not reduce organ dysfunction.
- The 10 g/day regimen led to less improvement in R-SOFA scores at 96 hours than placebo.
- High-dose vitamin C was associated with higher troponin T levels, more renal replacement therapy, worse neurological outcomes, and more serious adverse events, raising important safety concerns and challenging routine vitamin C supplementation in the ICU.
The publication is accompanied by an editorial in Intensive Care Medicine that reinforces these safety signals and recommends against using vitamin C after cardiac arrest outside of clinical trials.
Read the full paper here: Early high-dose vitamin C for out-of-hospital cardiac arrest: the VITaCCA randomized clinical trial | Intensive Care Medicine | Springer Nature Link
The VICTORY trial
An international team led by Christian Stoppe and coordinated by Queen’s University and University Hospital Würzburg has published the VICTORY randomized clinical trial in JAMA, evaluating high-dose intravenous vitamin C in adults with severe burn injury. In this phase 3, double-blind, multicenter study across 24 burn centers worldwide, 238 patients with deep second- or third-degree burns affecting ≥20% of total body surface area were randomized to receive high-dose vitamin C or placebo for 96 hours.
Key findings:
- The primary composite outcome of 28-day mortality and persistent organ dysfunction (ongoing need for mechanical ventilation, kidney replacement therapy, or vasopressors) was higher in the vitamin C group (40.8% vs 29.7%; adjusted RR 1.28).
- 28-day mortality and hospital mortality were both increased in the vitamin C arm (28-day mortality 15.0% vs 7.6%; hospital mortality 23.3% vs 16.1%).
- High-dose vitamin C did not improve time to discharge alive, organ support–free days, or longer-term outcomes, and the trial was stopped early at the first interim analysis for futility/harm.
Read the full paper here: High-Dose Intravenous Vitamin C and Mortality and Organ Dysfunction in Severe Burn Injury: The VICTORY Randomized Clinical Trial | Trials | JAMA | JAMA Network
These new trials in cardiac arrest (VITaCCA) and severe burn injury (VICTORY) demonstrate that “one‑size‑fits‑all” high‑dose vitamin C not only fails to deliver benefit, but may even harm critically ill patients, despite biologically plausible mechanisms. They underscore how little we currently understand about functional micronutrient status, the right dose, the right timing and, crucially, which patients (and subphenotypes) might truly benefit from specific micronutrient interventions.
This is exactly why the BIO‑MICRO project is so important: by training a new generation of interdisciplinary research fellows to develop advanced analytics for assessing functional micronutrient status, to identify responsive patient subgroups, to guide individualized timing and combinations of MN therapies, and to explore their role in rehabilitation after ICU, BIO‑MICRO aims to move the field from empiric, high‑dose supplementation towards evidence‑based, personalized micronutrient medicine in critical care, so that future interventions will be safer, more targeted and more effective than the undifferentiated approaches tested in these trials.
