This online resource is an up-to-date repository of published and ongoing vitamin C and COVID-19 research studies and related resources.
If you wish to provide relevant resources or receive further information, contact:
Research Professor Anitra Carr
Email anitra.carr@otago.ac.nz
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
- Vitamin C levels in patients with SARS-CoV-2-associated acute respiratory distress syndrome
- 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
- Vitamin C supplementation is necessary for patients with coronavirus disease: An ultra-high-performance liquid chromatography-tandem mass spectrometry finding
- Deficiency of antioxidants and increased oxidative stress in COVID-19 patients: A cross-sectional comparative study in Jigawa, Northwestern Nigeria
- Oxidative Stress Status in COVID-19 Patients Hospitalized in Intensive Care Unit for Severe Pneumonia. A Pilot Study
- Evaluation of nutritional status in pediatric patients diagnosed with Covid-19 infection
- COVID 19: Up to 82% critically ill patients had low Vitamin C values
- Vitamin C Deficiency in Blood Samples of COVID-19 Patients
- Correlation Between Plasma Vitamin C Concentration and COVID-19 Outcomes among Patients Seen at a Major Hospital in the United Arab Emirates
- Vitamin C as a Potential Interplaying Factor between Obesity and COVID-19 Outcome
- Baseline serum vitamin A and vitamin C levels and their association with disease severity in COVID-19 patients
- Low Levels of Serum and Intracellular Vitamin C in Hospitalized COVID-19 Patients
- Vitamin C deficiency in critically ill COVID-19 patients admitted to intensive care unit
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 (RCTs)
Intravenous vitamin C administration provides higher blood concentrations of the vitamin than oral supplementation. RCTs are considered the gold standard design for drug trials, however, for nutrient trials there is never a true control group as the nutrient (vitamin C) is generally being obtained through dietary intake, including in the control group.
- Pilot trial of high-dose vitamin C in critically ill COVID-19 patients
- The role of vitamin C as adjuvant therapy in COVID-19
- Safety and effectiveness of high dose vitamin C in patients with COVID 19: a randomized open label clinical trial
- 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
- Therapies to prevent progression of COVID-19, including hydroxychloroquine, azithromycin, zinc, and vitamin D3 with or without intravenous vitamin C: An international, multicenter, randomized trial
- Pharmacologic Ascorbic Acid as Early Therapy for Hospitalized Patients with COVID-19: A Randomized Clinical Trial
- Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit
- Efficacy of intravenous vitamin C in management of moderate and severe COVID-19: A double blind randomized placebo controlled trial
- High-dose Intravenous Vitamin C in Early Stages of Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Double-blind, Randomized, Controlled Clinical Trial
- Intravenous Vitamin C for Patients Hospitalized With COVID-19: Two Harmonized Randomized Clinical Trials
Intravenous vitamin C – retrospective cohort studies
Retrospective cohort studies are not as robust as RCTs as the two study groups are retrospectively (historically) identified and then compared, e.g. those who received vitamin C versus those who didn’t. These studies can be prone to various underlying biases.
- The efficiency and safety of high-dose vitamin C in patients with COVID-19: a retrospective cohort study
- High Dose Intravenous Vitamin C for Preventing The Disease Aggravation of Moderate COVID-19 Pneumonia. A Retrospective Propensity Matched Before-After Study
- Effect of high-dose intravenous vitamin C on prognosis in patients with SARS-CoV-2 pneumonia
- Use of Intravenous Vitamin C in Critically Ill Patients With COVID-19 Infection
- High-dose intravenous vitamin C attenuates hyperinflammation in severe coronavirus disease 2019
- The use of vitamin C in the intensive care unit during the COVID-19 pandemic
- High-dose vitamin C ameliorates cardiac injury in COVID-19 pandemic: a retrospective cohort study
- Effect of Vitamin C on Clinical Outcomes of Critically Ill Patients With COVID-19: An Observational Study and Subsequent Meta-Analysis
- No significant benefit of moderate-dose vitamin C on severe COVID-19 cases
Oral vitamin C – randomised controlled trials
Oral vitamin C supplementation does not provide as high blood concentrations as intravenous vitamin C. Also note issues with nutrient RCTs outlined above.
- 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
- (Vitamin C May Increase the Recovery Rate of Outpatient Cases of SARS-CoV-2 Infection by 70%: Reanalysis of the COVID A to Z Randomized Clinical Trial)
- The Effect of Vitamin C on Pathological Parameters and Survival Duration of Critically Ill Coronavirus Disease 2019 Patients: A Randomized Clinical Trial
- A Pilot of a Randomized Control Trial of Melatonin and Vitamin C for Mild-to-Moderate COVID-19
Oral vitamin C – retrospective cohort studies
Note issues discussed above regarding oral versus intravenous vitamin C and retrospective cohort versus RCT study design.
Vitamin C intake or status and COVID-19 risk
These are observational studies only so cannot confirm cause and effect relationships as the studies are prone to various confounding factors. There are also issues with Mendelian randomization studies as outlined in commentary below.
- Role of ivermectin in the prevention of SARS-CoV-2 infection among healthcare workers in India: A matched case-control study
- The role of vitamin C in pneumonia and COVID-19 infection in adults with European ancestry: a Mendelian randomisation study
- (Assessment of vitamin C effects on pneumonia and COVID-19 using Mendelian randomization: analysis may be misleading)
- Relationship Between Plasma Vitamin C and COVID-19 Susceptibility and Severity: A Two-Sample Mendelian Randomization Study
- Impact of Zinc, Vitamins C and D on Disease Prognosis among Patients with COVID-19 in Bangladesh: A Cross-Sectional Study
- The association between dietary intakes of zinc, vitamin C and COVID-19 severity and related symptoms: A cross-sectional study
- The impact of vitamin D, vitamin C, and zinc supplements on immune status among Jordanian adults during COVID-19: cross-sectional study finding
Registered vitamin C and COVID-19 clinical trials
Registered vitamin C and COVID-19 clinical trials can be found at clinicaltrials.gov and the International Clinical Trials Registry Platform. 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.
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), and J Clin Med Res, 2022 (doi: 10.14740/jocmr4658).
- 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
- Vitamin C and COVID-19: An Orthomolecular Perspective on Physiological Mechanisms
- Intravenous Vitamin C and an Orthomolecular Protocol as Therapy for COVID19: A Case Report
- High Dose Intravenous Vitamin C as Adjunctive Therapy for COVID-19 Patients with Cancer: Two Cases
- 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 seriesdoi: 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
- In silico virtual screening-based study of nutraceuticals predicts the therapeutic potentials of folic acid and its derivatives against COVID-19
- Prenol, but Not Vitamin C, of Fruit Binds to SARS-CoV-2 Spike S1 to Inhibit Viral Entry: Implications for COVID-19
In vivo (clinical) studies
Intravenous vitamin C administration to COVID-patients:
- Pilot trial of high-dose vitamin C in critically ill COVID-19 patients
- High Dose Intravenous Vitamin C for Preventing The Disease Aggravation of Moderate COVID-19 Pneumonia. A Retrospective Propensity Matched Before-After Study
- High-dose intravenous vitamin C attenuates hyperinflammation in severe coronavirus disease 2019
- High-dose vitamin C ameliorates cardiac injury in COVID-19 pandemic: a retrospective cohort study
Meta-analyses and 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. Meta-analyses, which combine the outcomes from multiple studies, are now also becoming available.
Published meta-analyses
- Association of Vitamin C Treatment with Clinical Outcomes for COVID-19 Patients: A Systematic Review and Meta-Analysis
- Vitamin C Supplementation for the Treatment of COVID-19: A Systematic Review and Meta-Analysis
- Impact of high-dose vitamin C on the mortality, severity, and duration of hospital stay in COVID-19 patients: A meta-analysis
- Effect of Vitamin C on Clinical Outcomes of Critically Ill Patients With COVID-19: An Observational Study and Subsequent Meta-Analysis
- The effectiveness of high-dose intravenous vitamin C for patients with coronavirus disease 2019: A systematic review and meta-analysis
- Vitamin C and COVID-19 treatment: A systematic review and meta-analysis of randomized controlled trials
- Outcomes in vitamin C studies (online meta-analysis)
- Intravenous vitamin C use and risk of severity and mortality in COVID-19: A systematic review and meta-analysis
- The effect of vitamin C on the risk of mortality in patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials
- Therapeutic effects of high-dose vitamin C supplementation in patients with COVID-19: a meta-analysis
Published review articles
- The Role of Vitamin C in Human Immunity and Its Treatment Potential Against COVID-19: A Review Article
- Unwinding the potentials of vitamin C in COVID-19 and other diseases: An updated review
- The Role of Vitamin C: From Prevention of Pneumonia to Treatment of Covid-19
- Role of high dose vitamin C in management of hospitalised COVID-19 patients: A minireview
- Intravenous Ascorbic Acid and Lung Function in Severely Ill COVID-19 Patients
- The Variable Nature of Vitamin C-Does It Help When Dealing with Coronavirus?
- Vitamin C and its therapeutic potential in the management of COVID19
- A possible role for ascorbic acid in COVID-19
- Oxidative Stress and Hyper-Inflammation as Major Drivers of Severe COVID-19 and Long COVID: Implications for the Benefit of High-Dose Intravenous Vitamin C
- Role of vitamin C in preventing of COVID-19 infection, progression and severity
- High-Dose Vitamin C Supplementation as a Legitimate Anti-SARS-CoV-2 Prophylaxis in Healthy Subjects-Yes or No?
- COVID-19, oxidative stress, and male reproductive dysfunctions: Vitamin C as a potential remedy?
- The effects of vitamin C on the multiple pathophysiological stages of COVID-19
- The protective role of vitamin C in the management of COVID
- Vitamin C intervention for critical COVID-19: A pragmatic review of the current level of evidence
- 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
- The Potential Use of Vitamin C to Prevent Kidney Injury in Patients with COVID-19
- Common anti-oxidant vitamin C as an anti-infective agent with remedial role on SARS-CoV-2 infection. An update
- Does COVID-19 Trigger the Risk for the Development of Parkinson's Disease? Therapeutic Potential of Vitamin C
Published commentaries
- Vitamin C for COVID-19 Treatment: Have We Got Enough Evidence?
- Potential benefit of high-dose intravenous vitamin C for coronavirus disease 2019 pneumonia
- Effect of high-dose intravenous vitamin C on prognosis in patients with SARS-CoV-2 pneumonia
- A Debate on Vitamin C: Supplementation on the Hotline for Critically Ill Patients with COVID-19
- 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
- Multi-level immune support by vitamins C and D during the SARS-CoV-2 pandemic
- Vitamin C for Patients With COVID-19: More Evidence of Lack of Efficacy in Patients With Sepsis
- Vitamin C and COVID-19: should clinical trials be prioritised for low income settings and vitamin C-deficient populations?
- Vitamin C for Patients Hospitalized With COVID-19
- Vitamin C for Patients Hospitalized With COVID-19-Reply
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
- Vitamin C can 'help to prevent severe Covid and speed up recovery'
- 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/videos
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
Please contact Professor Anitra Carr if you wish to highlight 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