Vitamin C: Recommendation For Non-Critically Ill Patients With COVID-19

Vitamin C
Last Updated: November 3, 2020

Vitamin C (ascorbic acid) is a water-soluble vitamin that is
thought to have beneficial effects in patients with severe and
critical illnesses. It is an antioxidant and free radical scavenger
that has anti-inflammatory properties, influences cellular
immunity and vascular integrity, and serves as a cofactor in the
generation of endogenous catecholamines.1,2 Because humans
may require more vitamin C in states of oxidative stress,
vitamin C supplementation has been evaluated in numerous
disease states, including serious infections and sepsis.
Because serious COVID-19 may cause sepsis and acute
respiratory distress syndrome (ARDS), the potential role of high
doses of vitamin C in ameliorating inflammation and vascular
injury in patients with COVID-19 is being studied.
Recommendation for Non-Critically Ill Patients

With COVID-19
• There are insufficient data for the COVID-19
Treatment Guidelines Panel (the Panel) to recommend
either for or against the use of vitamin C for the treatment
of COVID-19 in non-critically ill patients.
Rationale
Because patients who are not critically ill with COVID-19 are
less likely to experience oxidative stress or severe
inflammation, the role of vitamin C in this setting is unknown.
Recommendation for Critically Ill Patients With

COVID-19
• There are insufficient data for the Panel to
recommend either for or against the use of vitamin C for
the treatment of COVID-19 in critically ill patients.
Rationale
There are no completed controlled trials of vitamin C in patients
with COVID-19, and the available observational data are
sparse and inconclusive. Studies of vitamin C in sepsis patients
and ARDS patients have reported variable efficacy and few
safety concerns.
Clinical Data on Vitamin C in Critically Ill

Patients Without COVID-19
Intravenous Vitamin C Alone
A small, three-arm pilot study compared two regimens of
intravenous (IV) vitamin C to placebo in 24 critically ill patients
with sepsis. Over the 4-day study period, patients who received
vitamin C 200 mg/kg per day and those who received vitamin C
50 mg/kg per day had lower sequential organ failure
assessment (SOFA) scores and levels of proinflammatory
markers than patients who received placebo.3
In a randomized controlled trial in critically ill patients with
sepsis-induced ARDS (n = 167), patients who received IV
vitamin C 200 mg/kg per day for 4 days had SOFA scores and
levels of inflammatory markers that were similar to those
observed in patients who received placebo. However, 28-day
mortality was lower in the treatment group (29.8% vs.
46.3%; P = 0.03), coinciding with more days alive and free of
the hospital and the intensive care unit.4 A post hoc analysis of
the study data reported a difference in median SOFA scores
between the treatment group and placebo group at 96 hours;
however, this difference was not present at baseline or 48
hours.5
Intravenous Vitamin C Plus Thiamine With or Without

Hydrocortisone
Two small studies that used historic controls reported favorable
clinical outcomes (i.e., reduced mortality, reduced risk of
progression to organ failure, and improved radiographic
findings) in patients with sepsis or severe pneumonia who
received a combination of vitamin C, thiamine, and
hydrocortisone.6,7
Three recent randomized trials in which patients received
vitamin C and thiamine (with or without hydrocortisone) to treat
sepsis and septic shock showed that this combination
conferred benefits for certain clinical parameters. However, no
survival benefit was reported. Two trials observed reductions in
organ dysfunction (as measured by a SOFA score at Day
3)8,9 or the duration of shock10 without an effect on clinical
outcomes. Two other trials found no differences in any
physiologic or outcome measure between the treatment and
placebo groups.11,12
See ClinicalTrials.gov for a list of clinical trials that are
evaluating the use of vitamin C in patients with COVID-19.
Other Considerations
It is important to note that high circulating concentrations of
vitamin C may affect the accuracy of point-of-care
glucometers.13

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Vitamin C

Last Updated: November 3, 2020

Recommendation for Non-Critically Ill Patients

Recommendation for Critically Ill Patients With

Clinical Data on Vitamin C in Critically Ill

Intravenous Vitamin C Plus Thiamine With or Without

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