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: 20 July 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 |
| Study 4 | 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. |
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
| 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 |  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 |
| 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 |
|
| 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 |
Intravenous vitamin C - retrospective cohort 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 |  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. |
| 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. |
Oral vitamin C - randomised controlled trials
| 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 |  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 |
| 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 - case control 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. |
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
- High-dose vitamin C intravenous infusion in the treatment of patients with COVID-19: A protocol for systematic review and meta-analysis
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
- Kidney transplant dysfunction in a patient with COVID - 19 infection: role of concurrent Sars-Cov 2 nephropathy, chronic rejection and vitamin C-mediated hyperoxalosis: case report
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
- 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)
- Decreases C-reactive protein (an inflammatory marker), decreases activated partial thromboplastin (blood clotting) time, and increases CD4+ (helper) T cells (Zhao et al. Frontiers Pharmacol, 2021, 12:638556).
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)?
- Vitamin C in the treatment of COVID-19
- Feasibility of vitamin C in the treatment of post viral fatigue with focus on long COVID, based on a systematic review of IV vitamin C on fatigue
- Therapeutic potential of mega-dose vitamin C to reverse organ dysfunction in sepsis and 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
Meta-analyses
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/
