Evaluating Vitamin C in Septic Shock: A Randomized Controlled Trial of Vitamin C Monotherapy

David A. Wacker, Susan L. Burton, John P. Berger, A. J. Hegg, Jamie Heisdorffer, Qi Wang, Emily J. Medcraft, Ronald A. Reilkoff

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


OBJECTIVES: To determine whether IV vitamin C therapy reduces 28-day mortality in patients with septic shock.

DESIGN: Multicenter, double-blinded, randomized controlled trial.

SETTING: One academic medical ICU and four community ICUs.

PATIENTS: Of 167 adult patients within 24 hours of vasopressor initiation for septic shock, 126 consented to participation, and 124 received study drug and were included in analysis.

INTERVENTIONS: IV vitamin C (10 mg/mL in normal saline) administered as a 1,000-mg bolus over 30 minutes followed by continuous infusion of 250 mg/hr for 96 hours or placebo of equal volumes of normal saline.

MEASUREMENTS AND MAIN RESULTS: Of 124 subjects receiving study drug and included in analysis, 60 received vitamin C and 64 placebo. The primary outcome of all-cause 28-day mortality (vitamin C, 26.7%; placebo, 40.6%; p = 0.10) was lower in the vitamin C arm but did not reach statistical significance. Initiation of renal replacement therapy was higher in the vitamin C arm (vitamin C, 16.7%; placebo, 3.3%; p = 0.015), as was volume of fluid administration within 6 hours of study drug initiation (vitamin C, 1.07 L; placebo, 0.76 L; p = 0.03). There were no statistically significant differences in other secondary outcomes. In post hoc subgroup analysis, there was a decrease in 28-day mortality in the vitamin C arm among patients requiring positive-pressure ventilation at the time of enrollment (vitamin C, 36.3%; placebo, 60.0%; p = 0.05). This trial is registered at clinicaltrials.gov under identifier NCT03338569.

CONCLUSIONS: Vitamin C monotherapy failed to significantly reduce mortality in septic shock patients as hypothesized. Our findings do not support its routine clinical use for this purpose.

Original languageEnglish (US)
Pages (from-to)e458-e467
JournalCritical care medicine
Issue number5
StatePublished - May 1 2022

Bibliographical note

Funding Information:
Supported, in part, by the University of Minnesota Critical Care Program (grant to Dr. Reilkoff), the University of Minnesota Foundation (grant to Dr. Reilkoff), and the Fairview Foundation (grant to Dr. Reilkoff); and the University of Minnesota Clinical and Translation Science Institute (Grant Number UL1TR002494 from the National Institutes of Health’s National Center for Advancing Translational Sciences) in the form of access to the Research Electronic Data Capture database software.

Funding Information:
Dr. Wacker’s institution received funding from the University of Minnesota Critical Care Program for an unrelated project, the University of Minnesota Foundation, and the Fairview Foundation. Drs. Wacker, Berger, Medcraft, and Reilkoff disclosed the off-label product use of Vitamin C in septic shock. Dr. Hegg’s institution received funding from the Essentia Health DC Foundation; he disclosed he is employed by Essentia Health. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Publisher Copyright:
© 2022 Lippincott Williams and Wilkins. All rights reserved.


  • Adult
  • Ascorbic Acid/therapeutic use
  • Double-Blind Method
  • Humans
  • Saline Solution/therapeutic use
  • Shock, Septic
  • Vasoconstrictor Agents/therapeutic use
  • Vitamins/therapeutic use

PubMed: MeSH publication types

  • Journal Article
  • Randomized Controlled Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural


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