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Vitamin C

Last Updated: July 17, 2020

Rationale for Using Vitamin C in Patients With COVID-19

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, there is no compelling reason to use vitamin C in this setting.

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 shown variable efficacy and limited safety concerns (as described below).

Clinical Data on Vitamin C in Critically Ill Patients Without COVID-19

In a small, three-arm, pilot study of two regimens of intravenous (IV) vitamin C versus placebo in 24 critically ill patients with sepsis, there were reductions over the 4-day study period in sequential organ failure assessment (SOFA) scores and levels of proinflammatory markers in patients who received vitamin C 200 mg/kg per day and those who received vitamin C 50 mg/kg per day, compared with patients who received placebo.3

In a randomized, controlled trial in critically ill patients with sepsis-induced ARDS (n = 167), administration of IV vitamin C 200 mg/kg per day for 4 days did not change SOFA scores or levels of inflammatory markers. 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 (ICU).4

Two historically controlled studies found that the combination of vitamin C, thiamine, and hydrocortisone had beneficial effects in patients with sepsis or severe pneumonia.5,6 In response, a randomized controlled trial in critically ill patients with septic shock compared the combination of vitamin C (6 g per day), thiamine (400 mg per day), and hydrocortisone (200 mg per day) to hydrocortisone alone. The study reported that the combination therapy had no effect on the duration of shock. It also had no effect on the mortality rate in the ICU, at 28 days, or at 90 days (90-day mortality was 28.6% in the vitamin C group vs. 24.5% in the placebo group, P = 0.51). Only one of the 10 secondary outcomes differed between the two groups; the change in SOFA score from baseline to Day 3 favored the treatment group (median score change of -2 vs. -1, P = 0.02).7

Other Considerations

  • It is worth noting that high circulating concentrations of vitamin C may affect the accuracy of point-of-care glucometers.8
  • Additional large, randomized clinical trials in severely ill patients with sepsis have completed enrollment. These studies may provide additional data on the safety and efficacy of vitamin C that support its potential use in treating patients with COVID-19.9,10
  • Several trials of oral and IV vitamin C supplementation in people with COVID-19 are ongoing. Please check ClinicalTrials.gov for the latest information.

References

  1. Wei XB, Wang ZH, Liao XL, et al. Efficacy of vitamin C in patients with sepsis: an updated meta-analysis. Eur J Pharmacol. 2020;868:172889. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31870831.
  2. Fisher BJ, Seropian IM, Kraskauskas D, et al. Ascorbic acid attenuates lipopolysaccharide-induced acute lung injury. Crit Care Med. 2011;39(6):1454-1460. Available at: https://www.ncbi.nlm.nih.gov/pubmed/21358394.
  3. Fowler AA III, Syed AA, Knowlson S, et al. Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis. J Transl Med. 2014;12:32. Available at: https://www.ncbi.nlm.nih.gov/pubmed/24484547.
  4. Fowler AA III, Truwit JD, Hite RD, et al. Effect of vitamin C infusion on organ failure and biomarkers of inflammation and vascular injury in patients with sepsis and severe acute respiratory failure: the CITRIS-ALI randomized clinical trial. JAMA. 2019;322(13):1261-1270. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31573637.
  5. Marik PE, Khangoora V, Rivera R, Hooper MH, Catravas J. Hydrocortisone, vitamin C, and thiamine for the treatment of severe sepsis and septic shock: a retrospective before-after study. Chest. 2017;151(6):1229-1238. Available at: https://www.ncbi.nlm.nih.gov/pubmed/27940189.
  6. Kim WY, Jo EJ, Eom JS, et al. Combined vitamin C, hydrocortisone, and thiamine therapy for patients with severe pneumonia who were admitted to the intensive care unit: propensity score-based analysis of a before-after cohort study. J Crit Care. 2018;47:211-218. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30029205.
  7. Fujii T, Luethi N, Young PJ, et al. Effect of vitamin C, hydrocortisone, and thiamine vs hydrocortisone alone on time alive and free of vasopressor support among patients with septic shock: the VITAMINS randomized clinical trial. JAMA. 2020;323(5):423-431. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31950979.
  8. Hager DN, Martin GS, Sevransky JE, Hooper MH. Glucometry when using vitamin C in sepsis: a note of caution. Chest. 2018;154(1):228-229. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30044741.
  9. Hwang SY, Park JE, Jo IJ, et al. Combination therapy of vitamin C and thiamine for septic shock in a multicentre, double-blind, randomized, controlled study (ATESS): study protocol for a randomized controlled trial. Trials. 2019;20(1):420. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31296251.
  10. Hager DN, Hooper MH, Bernard GR, et al. The vitamin C, thiamine and steroids in sepsis (VICTAS) protocol: a prospective, multi-center, double-blind, adaptive sample size, randomized, placebo-controlled, clinical trial. Trials. 2019;20(1):197. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30953543.