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 |  Total 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 |  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 |
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 |  no 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 |
|
| 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 |  Trial 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 |  Risk 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 |  Mortality 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).  |
| Reference | Gao et al. Aging. 2021:13. doi: 10.18632/aging.202557. |
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
- Lessening Organ Dysfunction with VITamin C—COVID-19 (LOVIT-COVID; Canada; n = 800; NCT04401150), also an arm of REMAP-CAP (Randomized Embedded Multifactorial Adaptive Platform for Community-Acquired Pneumonia; NCT02735707)
- Use of Ascorbic Acid in Patients With COVID-19 (Italy; n = 500; NCT04323514)
- Early Infusion of Vitamin C for Treatment of Novel COVID-19 Acute Lung Injury (EVICT-CORONA-ALI; USA; n = 200; NCT04344184)
- Coronavirus 2019 (COVID-19)- Using Ascorbic Acid and Zinc Supplementation (COVIDAtoZ; USA; n = 520; NCT04342728)
Published study protocols
- Intravenous high-dose vitamin C for the treatment of severe COVID-19: study protocol for a multicentre randomised controlled trial.
- Impact of vitamins A, B, C, D, and E supplementation on improvement and mortality rate in ICU patients with coronavirus-19: a structured summary of a study protocol for a randomized controlled trial
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
- MATH+ Hospital Treatment Protocol for Covid-19. See also review by Marik, Expert Rev Anti Infect Ther, 2020.(doi: 10.1080/14787210.2020.1808462)
- I-MASK+ Prophylaxis & Early Outpatient Treatment Protocol for COVID-19
- Development and implementation of a COVID-19 near real-time traffic light system in an acute hospital setting (page 4)
- Expert consensus on comprehensive treatment of COVID-19 in Shanghai
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
- Unusual early recovery of a critical COVID-19 patient after administration of intravenous vitamin C
- The use of IV vitamin C for patients with COVID-19: a case series doi: 10.1080/14787210.2020.1794819
- Beneficial aspects of high dose intravenous vitamin C on patients with COVID-19 pneumonia in severe condition: a retrospective case series study
- Reversal of the pathophysiological responses to gram-negative sepsis by megadose vitamin C
Case reports with negative outcomes
- Novel coronavirus 2019 (COVID-19): A case report and review of treatments
- Oxalate nephropathy caused by excessive vitamin C administration in 2 patients with COVID-19
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
- Vitamin C (in the form of magnesium ascorbate) binds to a key protease in the virus, Mpro (Kumar et al. ResearchSquare preprint, 2020)
In vivo (clinical) studies
- Intravenous vitamin C administration to COVID-patients decreases interleukin-6 (IL-6), an inflammatory biomarker (Zhang et al. Ann Intensive Care, 2021)
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
- Vitamin C—An adjunctive therapy for respiratory infection, sepsis and COVID-19
- Overview of the possible role of vitamin C in management of COVID-19
- Repositioning vitamin C as a promising option to alleviate complications associated with COVID-19
- The emerging role of vitamin C in the prevention and treatment of COVID-19
- The long history of vitamin C: From prevention of the common cold to potential aid in the treatment of COVID-19
- Efficacy and safety of vitamin C in the management of acute respiratory infection and disease
- Low level of vitamin C and dysregulation of vitamin C transporter might be involved in the severity of COVID-19 Infection
- A possible application of high dose vitamin C in the prevention and therapy for coronavirus infections
- Vitamin C as prophylaxis and adjunctive medical treatment for COVID-19?
- Ascorbate as prophylaxis and therapy for COVID-19 - Update from Shanghai and U.S. medical institutions
- Vitamin C for COVID-19: A living systematic review
- Is vitamin C an effective agent for the prevention of COVID-19 and treatment of severe infection in the ICU?
- Can early and high intravenous dose of vitamin C prevent and treat coronavirus disease 2019 (COVID-19)?
Published commentaries
- Vitamin C and COVID-19: should clinical trials be prioritized for low-income settings and vitamin C deficient populations?
- Vitamin C as a Possible Therapy for COVID-19
- High-dose intravenous vitamin C may help in cytokine storm in severe SARS-CoV-2 infection
- Role of vitamin C in critically ill patients with COVID-19: is it effective?
- Micronutrient status of COVID-19 patients: a critical consideration
- A new clinical trial to test high-dose vitamin C in patients with COVID-19
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
- Vitamin C could be the secret weapon in the fight against coronavirus
- Vitamin C trials in China podcast
Clinical practice in the media
- Holistic approaches may have reduced coronavirus deaths at this London hospital
- New York hospitals treating coronavirus patients with vitamin C
Case reports in the media
- 'Unusual' IV High-Dose Vitamin C Success Story in COVID-19
- COVID patient with sepsis makes 'remarkable' recovery following megadose of vitamin C
- Richmond doctor shares story of COVID-19 infection, survival
- Emergency room doctor, near death with coronavirus, saved with experimental treatment
Reviews/overviews in the media
- Coronavirus update: Vitamin C could save the lives of those severely affected by COVID-19
- Vitamin C can help severe Covid-19 cases, NZ-led review finds
- Vitamin C and COVID-19: A Review
- Vitamin C and COVID-19: Researchers call for status testing and intravenous / oral supplementation
- Vitamin C's effectiveness against COVID may hinge on vitamin's natural transporter levels
- This vitamin may help treat COVID, study finds
- Coronavirus: Vitamin C treatment 'encouraging' says NZ researcher
- Big vote of confidence for Vitamin C as viral fighter. Now being tested
- Is it ethical to keep ignoring the potential of vitamin C to fight the virus?
- Grassroots clinicians pick up on Vitamin C treatment for coronavirus
Podcasts
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/
