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Vitamin C and COVID-19 Research Resource

This online resource is an up-to-date repository of published and ongoing vitamin C and COVID-19 research studies and related resources. Contact: Associate Professor Anitra Carr (anitra.carr@otago.ac.nz) if you wish to provide relevant resources or receive further information.
Page last updated: 8 April 2021

In March 2020, the World Health Organization (WHO) published a ‘Coordinated Global Research Roadmap for the 2019 Novel Coronavirus’. In this document vitamin C was highlighted as an adjunctive intervention with biological plausibility to improve the outcome of COVID-19 infected patients (pages 36-7).

Vitamin C and COVID-19 observational studies

Low vitamin C levels can predispose people to viral infections. In addition, viral infections can further decrease vitamin C levels due to enhanced requirements for the vitamin during infections. Below is a summary of COVID-19 and vitamin C observational studies which indicate that patients with COVID-19 have depleted vitamin C status. Definitions: vitamin C deficiency ≤11 µmol/L (<0.2 mg/dL); hypovitaminosis C ≤23 µmol/L (<0.4 mg/dL).

Observational study summaries

Study 1 Vitamin C levels in patients with SARS-CoV-2-associated acute respiratory distress syndrome
Date online 26 August 2020
Location Barcelona Spain
Cohort 18 patients with SARS-CoV-2-associated acute respiratory distress syndrome (ARDS)
Findings 17 patients had <1.5 mg/L (<8.5 µmol/L) vitamin C
1 patient had 2.4 mg/L (14 µmol/L) vitamin C
Reference Chiscano-Camón et al. Crit Care. 2020 24(1):522. doi:10.1186/s13054-020-03249-y

Study 2 Serum levels of vitamin C and vitamin D in a cohort of critically Ill COVID-19 patients of a North American community hospital intensive care unit in May 2020: A pilot study
Date online 18 September 2020
Location Thornton, Colorado, USA
Cohort 21 critically ill COVID-19 patients
Findings Plasma Vitamin C graphTotal cohort (n = 21) mean vitamin C status 22 ± 4 µmol/L (45% deficient, 70% hypovitC)
Survivors (n = 11) mean vitamin C status 29 ± 7 µmol/L (40% deficient, 50% hypovitC)
Non-survivors (n = 10) mean vitamin C status 15 ± 2 µmol/L (50% deficient, 90% hypovitC)
Reference Arvinte et al. Med Drug Discov. 2020 8:100064. doi:10.1016/j.medidd.2020.100064

Study 3 Vitamin C supplementation is necessary for patients with coronavirusdisease: An ultra-high-performance liquid chromatography-tandemmass spectrometry findingYaru
Date online 27 January 2021
Location Shanghai, China
Cohort 31 COVID-19 patients (+/- IV vitamin C) and 51 healthy controls
Findings Plasma Vitamin C graph.6 COVID-19 patients (no IV vitamin C): mean plasma vitamin C level 2 mg/dl (11 µmol/L)
25 COVID-19 patients given 100 mg/kg/d IV vitamin C: mean plasma vitamin C level 13.5 mg/L (76 µmol/L)
51 healthy controls: mean plasma vitamin C level 9.2 mg/L (52 µmol/L)
Reference Xing et al. J Pharm Biomed Anal. 2021, 196:113927. doi: 10.1016/j.jpba.2021.113927

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Vitamin C and COVID-19 intervention trials

Randomised controlled trials (RCTs) of patients with respiratory infections, pneumonia and sepsis have indicated that vitamin C administration may be able to improve some patient outcomes. Critically ill patients with sepsis require intravenous administration of gram doses of vitamin C to normalise their plasma vitamin C levels. Below is a summary of vitamin C and COVID-19 intervention trials which indicate that some symptoms of COVID-19 patients may be improved with vitamin C administration.

Intervention study summaries

Study 1 Pilot trial of high-dose vitamin C in critically ill COVID-19 patients
Date online 9 August 2020
Location Hubei, China (multicentre)
Trial type Randomised placebo-controlled trial
Cohort 54 critically ill COVID-19 patients (27 and 29 per group)
Intervention 24 g/day IV vitamin C (12 g/12 hours) for 7 days (or placebo)
Findings Fig 3 thumbno difference in ventilation-free days (26.5 vs 10.5 days, p = 0.560)
↑ PaO2/FiO2 (229 vs 151 mmHg, p = 0.01)
↓ Interleukin-6 (19.4 vs 158 pg/ml, p = 0.04)
↓ ICU and hospital mortality in patients with SOFA scores ≥3 (4 vs 10 days, p = 0.03)
Notes Trial was stopped early due to lack of patients
Reference Zhang et al. Ann Intensive Care, 2021, 11, 5

Study 2 The role of vitamin C as adjuvant therapy in COVID-19
Date online 30 November 2020
Location Karachi, Pakistan
Trial type Randomised controlled trial (open label)
Cohort 150 severe COVID-19 patients (75 per group)
Intervention 50 mg/kg bodyweight/day IV vitamin C (or standard therapy alone)
Findings

Fig 4 thumbBecame symptom-free earlier (7.1 vs 9.6 days, p <0.0001)
Spent fewer days in the hospital (8.1 vs 10.7 days, p <0.0001)
No difference regarding need for mechanical ventilation (16% vs 20%, p = 0.4)
No difference regarding mortality (9.3% vs 14.6%, p = 0.3)

Reference Kumari et al. Cureus 2020 12(11): e11779. doi:10.7759/cureus.11779

Study 3 Safety and effectiveness of high‑dose vitamin C in patients with COVID‑19: a randomized open‑label clinical trial
Date online 11 February 2021
Location Tehran, Iran
Trial type Randomised controlled trial (open-label)
Cohort 60 patients with COVID-19 (30 per group)
Intervention 6 g/d IV vitamin C (or standard care) for 5 days
Findings There was no significant difference in SpO2 levels (oxygen saturation) at discharge, the length of intensive care unit (ICU) stay, and mortality between the two groups.
There were no adverse events reported
Reference JamaliMoghadamSiahkali et al. Eur J Med Res. 2021, 26(1):20. doi: 10.1186/s40001-021-00490-1

Study 4 Effect of High-Dose Zinc and Ascorbic Acid Supplementation vs Usual Care on Symptom Length and Reduction Among Ambulatory Patients With SARS-CoV-2 Infection: The COVID A to Z Randomized Clinical Trial
Date online 12 February 2021
Location Ohio and Florida, USA
Trial type Randomised controlled trial (open-label)
Cohort 214 patients with SARS-CoV-2 infection (48 - 58 per group)
Intervention 8 g/d oral vitamin C
or 50 mg/d zinc gluconate
or both vitamin C and zinc gluconate
or standard care for 10 days
Findings Non-significant decrease in number of days to reach 50% reduction in symptoms of approx. one day for treatment groups compared with standard care:
Standard care group 6.7 (± 4.4) days
Vitamin C group 5.5 (± 3.7) days
Zinc gluconate group 5.9 (± 4.9) days
Both vitamin C and zinc gluconate group 5.5 (± 3.4) days
Notes Fig 5 thumbTrial was stopped early as interventions assumed to be ineffective (although the difference between the vitamin C and standard care groups was greater than originally anticipated by the authors).
Independent statistical analysis of the data has indicated that vitamin C increased the rate of recovery by 71% (P = 0.036)
Reference Thomas et al. JAMA Network Open 2021 4(2):e210369. doi:10.1001/jamanetworkopen.2021.0369
Study 5 The efficiency and safety of high-dose vitamin C in patients with COVID-19: a retrospective cohort study
Date online 26 February 2021
Location Xi'an, Shaanxi, China
Trial type Retrospective cohort
Cohort 76 patients with COVID-19
Intervention Loading dose of 6 g intravenous infusion per 12 hr on the first day, and 6 g once for the following 4 days (n=46)
or standard therapy group (n=30)
Findings Fig 6 thumbRisk of 28-day mortality was reduced (HR=0.14, 95% CI, 0.03-0.72)
Oxygen support status was improved compared with standard therapy (64% vs 36%)
No adverse safety events were associated with high-dose vitamin C therapy
Notes Fig 7 thumbMortality differences were even more pronounced for (A) those with severe COVID-19 (HR= 9.91, 95% CI, 1.82-54.00) and (B) those aged >60 years (HR=7.98, 95% CI, 1.24-51.22).

Fig 8 thumb

Reference Gao et al. Aging. 2021:13. doi: 10.18632/aging.202557.

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Registered vitamin C and COVID-19 clinical trials

Registered vitamin C and COVID-19 clinical trials can be found at clinicaltrials.gov.

Some of these trials are testing vitamin C as a prophylactic (preventative), while others are testing it as an adjunctive therapy/treatment (i.e. in addition to standard care). Some of these trials are using vitamin C alone (monotherapy), while others are using combination therapies. Some are using oral vitamin C and others intravenous vitamin C administration (summarised in Carr and Rowe, Nutrients, 2020. doi: 10.3390/nu12113286)

Largest vitamin C and COVID-19 trials

Published study protocols

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Vitamin C and COVID-19 in clinical practice

Many clinicians and clinical teams worldwide are administering vitamin C to their COVID-19 patients. Some protocols use vitamin C monotherapy in addition to standard care, others as part of combination therapies, for both prophylaxis and treatment.

Clinical protocols

Vitamin C and COVID-19 in case reports

Case reports do not have untreated patients as comparators so cannot provide definitive evidence that vitamin C is exerting any additional benefit over standard therapy alone.

Case reports with positive outcomes

Case reports with negative outcomes

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Evidence for mechanisms of action

Many mechanisms of action have been proposed for vitamin C against SARS-CoV-2 and COVID-19, based on previous research with similar viruses and respiratory infections, e.g. anti-viral, anti-inflammatory, anti-oxidant, and immunomodulatory. Below are in vitro (laboratory-based) and in vivo (clinical) studies that have been carried out with SARS-CoV-2 and COVID-19.

In vitro (laboratory-based) studies

In vivo (clinical) studies

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Vitamin C and COVID-19 review articles

Many review articles and commentaries have been written about vitamin C and COVID-19. Published articles that have specifically focused on vitamin C are shown below.

Published review articles

Published commentaries

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Vitamin C and COVID-19 in the media

There are many articles in the global media regarding vitamin C and COVID-19. Some of the posts directly related to this topic are shown below.

Clinical studies in the media

Clinical practice in the media

Case reports in the media

Reviews/overviews in the media

Podcasts

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Contact

Contact Associate Professor Anitra Carr if you wish to provide relevant resources of receive further information.

Email: antira.carr@otago.ac.nz
Tel: +64 3 364 0649

How to cite this resource

Carr, A.C. Vitamin C and COVID-19 Research Resource, otago.ac.nz/christchurch/research/nutrition-in-medicine/vitamin-c/