Send to

Choose Destination
JPEN J Parenter Enteral Nutr. 2018 Nov 19. doi: 10.1002/jpen.1471. [Epub ahead of print]

Vitamin C Administration to the Critically Ill: A Systematic Review and Meta-Analysis.

Author information

Department of Anesthesiology and Reanimation, Faculty of Medicine and Health Sciences, Sherbrooke University Hospital, Sherbrooke, Québec, Canada.
Department of Critical Care, Intensive Care Unit, University Hospital, Faculty of Medicine, Universidad de la Republica, Montevideo, Uruguay.
Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada.
Department of Intensive Care Medicine, Faculty of Medicine and Health Sciences, Sherbrooke University Hospital, Sherbrooke, Québec, Canada.
Department of Intensive Care Medicine, University Hospital Rheinisch-Westfälische Technische Hochschule Aachen, Aachen, Germany.
Clinical Evaluation Research Unit, Kingston General Hospital, Kingston, Ontario, Canada and Department of Critical Care, Queen's University, Kingston, Ontario, Canada.


Vitamin C, an enzyme cofactor and antioxidant, could hasten the resolution of inflammation, oxidative stress, and microvascular dysfunction. While observational studies have demonstrated that critical illness is associated with low levels of vitamin C, randomized controlled trials (RCTs) of vitamin C, alone or in combination with other antioxidants, have yielded contradicting results. We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials (inception to December 2017) for RCTs comparing vitamin C, by enteral or parenteral routes, with placebo or none, in intensive care unit (ICU) patients. Two independent reviewers assessed study eligibility without language restrictions and abstracted data. Overall mortality was the primary outcome; secondary outcomes were incident infections, ICU length of stay (LOS), hospital LOS, and duration of mechanical ventilation (MV). We prespecified 5 subgroups hypothesized to benefit more from vitamin C. Eleven randomized trials were included. When 9 RCTs (n = 1322) reporting mortality were pooled, vitamin C was not associated with reduced risk of mortality (risk ratio [RR] 0.72, 95% confidence interval [CI]: 0.43-1.20, P = .21). No effect was found on infections, ICU or hospital LOS, or duration of MV. In multiple subgroup comparison, no statistically significant subgroup effects were observed. However, we did observe a tendency towards a mortality reduction (RR 0.21; 95% CI: 0.04-1.05; P = .06) when intravenous high-dose vitamin C monotherapy was administered. Current evidence does not support supplementing critically ill patients with vitamin C. A moderately large treatment effect may exist, but further studies, particularly of monotherapy administration, are warranted.


antioxidant; ascorbic acid; critical care; meta-analysis; systematic review; vitamin C


Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center