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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: 25 November 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 studies (6 studies)

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

Study 4 Deficiency of antioxidants and increased oxidative stress in COVID-19 patients: A cross-sectional comparative study in Jigawa, Northwestern Nigeria
Date online 1 February 2021
Location Jigawa, Northwestern Nigeria
Cohort 50 COVID-19 symptomatic patients
21 healthy controls
Findings Patients had 0.33 mg/dL (19 µmol/L) vitamin C
Controls had 0.44 mg/dL (25 µmol/L) vitamin C (p <0.001)
Notes Oxidative stress markers were elevated in the patients relative to controls and correlated with vitamin C in the patients (r = -0.605, p = 0.004)
Reference Muhammad et al. SAGE Open Medicine. 2021 9:1-8. doi/10.1177/2050312121991246

Study 5 Oxidative Stress Status in COVID-19 Patients Hospitalized in Intensive Care Unit for Severe Pneumonia. A Pilot Study
Date online 7 February 2021
Location Liège, Belgium
Cohort 9 ICU patients with severe COVID-19 pneumonia
Findings Patients had 3.9 (3.1–6.1) µg/mL or 22 (18-35) µmol/L vitamin C
Reference rage 6.2–15.2 µg/mL or 35-86 µmol/L (p = 0.004)
Notes These low concentrations were despite the patients receiving 124 (95-172) mg/day of vitamin C in their liquid nutrition
Reference Pincemail et al. Antioxidants. 2021 10(2):257. doi: 10.3390/antiox10020257

Study 6 COVID‑19: Up to 82% critically ill patients had low Vitamin C values
Date online 9 July 2021
Location Barcelona, Spain
Cohort 67 critically ill COVID-19 patients with acute respiratory distress syndrome (ARDS)
Findings Mean vitamin C concentration was 8 ± 3 µmol/L (0.14 ± 0.05 mg/dL);
range of <6 – 61 µmol/L (<0.10 – 1.08 mg/dL)
55 patients (82%) had values <23 µmol/L (<0.40 mg/dL)
12 patients (18%) had values <6 µmol/L (<0.10 mg/dL)
Reference Tomasa‑Irriguible and Bielsa‑Berrocal. Nutr Res. 2021 20(1):66. doi: 10.1186/s12937-021-00727-z.

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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.

Intravenous vitamin C – randomised controlled trials (3 RCTs)

RCT 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)
↑ oxygenation 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 (HR, 0.32 [95% CI 0.10-1.06]; p = 0.07)
No adverse events were reported.

Notes Trial was stopped early due to lack of patients
Reference Zhang et al. Ann Intensive Care, 2021, 11, 5

RCT 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

RCT 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 ↓ body temperature on 3rd day of hospitalization (p = 0.001)
↑ peripheral capillary oxygen saturations (SpO2) on 3rd day of hospitalization (p = 0.014)
Comparable SpO2 levels (oxygen saturation) at discharge
↑ length of hospitalization (8.5 days vs. 6.5 days, p = 0.028).
No difference in length of intensive care unit (ICU) stay or mortality
No adverse events were reported
Reference JamaliMoghadamSiahkali et al. Eur J Med Res. 2021, 26(1):20. doi: 10.1186/s40001-021-00490-1

RCT 4 An investigation into the effects of intravenous vitamin C on pulmonary CT findings and clinical outcomes of patients with COVID 19 pneumonia A Randomized Clinical Trial
Date online 8 November 2021
Location Tehran, Iran
Trial type Randomised controlled trial (open-label)
Cohort 50 patients with moderate to severe COVID-19
Intervention IV vitamin C at 2 g every 6 hours (8 g/day) for 5 days (n = 18)
or standard care (n = 26)
Findings

↑ oxygen saturation (p = 0.02)
↓ respiratory rate (p = 0.03)
↓ lung involvement (p = 0.02)
No difference in C-reactive protein levels (p = 0.1)
No difference in duration of hospitalisation (p = 0.2)
No difference in mortality (0 vs 4 deaths, p = 0.2)

Reference Tehrani et al. Urol J. 2021 doi: 10.22037/uj.v18i.6863

Intravenous vitamin C - retrospective cohort studies (7 studies)

Study 1 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.
Study 2 High Dose Intravenous Vitamin C for Preventing The Disease Aggravation of Moderate COVID-19 Pneumonia. A Retrospective Propensity Matched Before-After Study
Date online 22 April 2021
Location Shanghai, China
Trial type Retrospective propensity matched
Cohort 110 patients with moderate COVID-19 pneumonia (55 per group)
Intervention 100 mg/kg/day IV vitamin C for 7 days vs standard care
Findings ↓ number of patients progressing to severe type (4/55 vs 12/55; RR 0.28 [0.08, 0.93], P = 0.03)
↓ duration (P < 0.001) and ↓ incidence (2/21 vs 10/22, P = 0.08) of systemic inflammation (SIRS)
↓ C-reactive protein levels (P = 0.05), ↓ activated partial thromboplastin (blood clotting) time (P = 0.02), ↑ CD4+ (helper) T cells (P = 0.04)
No Effect on time to negative nucleic acid load
Reference Zhao et al. Frontiers Pharmacol, 2021, 12:638556.
Study 3 Effect of high-dose intravenous vitamin C on prognosis in patients with SARS-CoV-2 pneumonia
Date online 11 May 2021
Location Ankara, Turkey
Trial type Retrospective 
Cohort 232 patients with severe acute respiratory syndrome due to COVID-19 infection
Intervention 2 g/day IV vitamin C initiated within a median duration of 3 days after admission (n=153)
vs no vitamin C (n=170)
Findings Those in the VC group were not significantly different in terms of the length of hospital stay (p=0.05), re-admission rate (p=0.943), admission to intensive care, need for advanced oxygen support (p=0.488), need for advanced medical treatment (p<0.001), and mortality (p=0.52)
No adverse effects associated with the use of IV vitamin C treatment were recorded.
Reference Suna et al. Med Clin (Barc). 2021;S0025-7753(21)00252-9. doi: 10.1016/j.medcli.2021.04.010.
Study 4 Use of Intravenous Vitamin C in Critically Ill Patients With COVID-19 Infection
Date online 8 June 2021
Location New York, United States of America
Trial type Retrospective observational cohort study with propensity score matching
Cohort ICU patients with COVID-19 infection
Intervention 1.5 grams IV vitamin C every 6 hours for up to 4 days (n = 8) vs matched patients (n = 24)
Findings Patients in the IV vitamin C group had higher rates of hospital mortality [7 (88%) vs. 19 (79%), P = 0.049] and mean SOFA scores post-treatment (12.4 ± 2.8 vs. 8.1 ± 3.5, P < 0.005).
There was no difference in the daily vasopressor requirement or in ICU length of stay between the treatment and control groups.
Reference Li et al. J Pharm Pract. 2021;8971900211015052. doi: 10.1177/08971900211015052.
Study 5 High-dose intravenous vitamin C attenuates hyperinflammation in severe coronavirus disease 2019
Date online 26 June 2021
Location Wuhan, China
Trial type Retrospective cohort
Cohort 236 patients with severe COVID-19
Intervention Intravenous vitamin C (IVC) at 100 mg/kg body weight every 6 hours on the first day, then 100 mg/kg body weight every 12 h for the next 5 days (n=85)
or standard therapy group (n=151)
Findings IVC intervention was associated with reduced levels of inflammatory markers (C-reactive protein, interleukin-6, tumor necrosis factor-α)
Reference Xia et al. Nutrition 2021, 91-92:111405. doi: 10.1016/j.nut.2021.111405.g.
Study 6 High-dose vitamin C ameliorates cardiac injury in COVID-19 pandemic: a retrospective cohort study
Date online 9 September 2021
Location Wuhan, China
Trial type Retrospective cohort
Cohort 113 severe and critical COVID-19 patients with cardiac injury
Intervention Intravenous vitamin C (IVC) at 100 mg/kg body weight every 6 hours on the first day, then 100 mg/kg body weight every 12 h for the next 5 days (n = 51)
or standard therapy group (n = 62)
Findings More patients in ameliorated cardiac injury group received IVC (53 vs 33%, p = 0.035)
IVC was associated with ameliorated cardiac injury independent of other medications (OR 2.42 [1.02, 5.73], p = 0.04)
IVC was associated with reduced levels of inflammatory markers (C-reactive protein, interleukin-6, interleukin-8, tumor necrosis factor-α) at day 21 of hospitalisation (p <0.05)
Reference Xia et al. Aging 2021, 13. doi: 10.18632/aging.203503.
Study 7 No significant benefit of moderate-dose vitamin C on severe COVID-19 cases
Date online 22 September 2021
Location Wuhan, China
Trial type Retrospective cohort
Cohort 397 adult patients with severe COVID-19
Intervention Intravenous vitamin C (2-4 g/day; n = 70)
No vitamin C (n = 327)
Findings No difference in mortality between groups
No difference in clinical improvement between groups
Reference Zheng et al. Open Med (Wars) 2021, 16(1):1403-1414. doi: 10.1515/med-2021-0361

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Oral vitamin C - randomised controlled trials (2 RCTs)

RCT 1 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
RCT 2 The effect of vitamin E and vitamin C in patients with COVID-19 pneumonia; a randomized controlled clinical trial
Date online 14 April 2021
Location Isfahan, Iran
Trial type Randomised controlled trial 
Cohort 72 non-serious hospitalized COVID-19 patients
Intervention 1000 mg oral vitamin (plus 400 IU vitamin E) daily (n=38) administered until hospital discharge or ICU admission vs standard care (n=34)
Findings No difference in clinical improvement or duration of hospitalisation.
No patients died in the study.
Reference Hakamifard et al. Immunopathol Persa. 2021;7(2):exx

Oral vitamin C - retrospective cohort studies (1 study)

Study 1 Ascorbic acid as an adjunctive therapy in critically ill patients with COVID-19: a propensity score matched study
Date online 3 September 2021
Location Riyadh, Saudi Arabia
Study type Retrospective propensity score matched
Cohort 296 critically ill patients with COVID-19
Intervention 1000 mg/d oral vitamin C for 11 (7-18) days (n = 148 patients)
Findings vitamin C adjunct therapy graph thumbNo association of low dose oral vitamin C with in hospital or 30-day mortality, or acute kidney injury, liver injury, respiratory failure/mechanical ventilation
Longer ICU and hospital length of stay observed for vitamin C group
Decreased incidence of thrombosis in vitamin C group (6 vs 13%; OR 0.42 [0.18 – 0.94) p = 0.03)
Reference Sulaiman et al. Sci Rep. 2021; 11(1):17648. doi: 10.1038/s41598-021-96703-y.

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Vitamin C intake or status and COVID-19 risk (2 studies)

Study 1 Role of ivermectin in the prevention of SARS-CoV-2 infection among healthcare workers in India: A matched case-control study
Date online 16 February 2021
Location Bhubaneswar, India
Study type Case control
Cohort 372 health-care workers who tested positive (cases) or negative (controls)
Intervention 67 took prophylactic vitamin C at 500 mg/day (or twice daily) vs 305 who did not
Findings Vitamin C prophylaxis was not associated with SARS-CoV-2 infection (OR 0.71, 95% CI, 0.40–1.26)
Reference Behera et al. PLoS ONE 16(2): e0247163.

Genetically predicted circulating levels of vitamin C was not associated with susceptibility to severe COVID-19, COVID-19 hospitalisation, any COVID-19 infection nor pneumonia.

Study 2 The role of vitamin C in pneumonia and COVID-19 infection in adults with European ancestry: a Mendelian randomisation study
Date online 30 August 2021
Location UK Biobank
Study type Genome-wide association study (GWAS)
Cohort 52,018 people of European ancestry
Methodology Used single nucleotide polymorphisms (SNPs) that were associated with circulating levels of vitamin C (note: they did not use measured vitamin C levels)
Findings Genetically predicted circulating levels of vitamin C was not associated with susceptibility to severe COVID-19, COVID-19 hospitalisation, any COVID-19 infection nor pneumonia.
Reference Hui et al. Eur J Clin Nutr 2021 1-4. doi: 10.1038/s41430-021-00993-4

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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 patients.

In vitro (laboratory-based) studies

In vivo (clinical) studies

Intravenous vitamin C administration to COVID-patients:

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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

Meta-analyses

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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/videos

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Feedback

“A useful repository of studies on vitamin C and COVID‑19 is managed by Professor Anita Carr at the University of Otago who has herself has contributed much to research with Vitamin C and both communicable and non-communicable disease.”
Prof R Mithen, Chief Scientist, NZ High Value Nutrition National Science Challenge.

“I live in Canada and I was exposed to COVID‑19 in late December, and fell seriously ill [positive COVID test]. Everyone has a different experience with the virus but what stuck out to me was my constant craving for orange juice, I drank gallons of it, which I usually don’t drink. The sickness passed and I stopped craving it. I really think there is something to these studies.”
B Okojie, Canada.

“I feedback quite a lot of information to our Access and Choice practitioners who are seeing a lot of people in primary care with health anxiety. I have highlighted your page to help explain why there is evidence of the use of vitamin C in the treatment of COVID but not as a preventative in place of vaccination.”
H Gibbs, Nutrition Development Advisor, WellSouth Primary Health Network, NZ

Contact

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

Email anitra.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