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: 15 February 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
Zhang et al. Ann Intensive Care, 2021, 11, 5
| Study 1 | Pilot trial of high-dose vitamin C in critically ill COVID-19 patients |
| Date online | 9 August 2020 |
| Location | Hubei, China (multicentre) |
| 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 |
| Cohort | 150 severe COVID-19 patients (75 per group) |
| Intervention | 50 mg/kg bodyweight/day IV vitamin C (or standard therapy alone) |
| Findings | Became 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 |
| 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 |
| 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 |
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/
