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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 July 2022

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 (7 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 coronavirus disease: An ultra-high-performance liquid chromatography-tandemmass spectrometry finding
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 Evaluation of nutritional status in pediatric patients diagnosed with Covid-19 infection
Date online 11 May 2021
Location Ankara, Turkey
Cohort 49 paediatric patients (aged 1 month to 18 years),
diagnosed with COVID-19 then hospitalized
Findings 17% of the patients had vitamin C deficiency
Reference Molla et al. Clin Nutr ESPEN. 2021. doi: 10.1016/j.clnesp.2021.04.022.
Study 7 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 (7 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

RCT 5 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
Date online 25 November 2021
Location Turkey (7 hospitals)
Trial type Multicenter, randomised, open-label study
Cohort 237 hospitalised patients with COVID-19
Intervention IV vitamin C (50 mg/kg every six hours on day 1, followed by
100 mg/kg every six hours (average: 28 g/day) for seven days
+ hydroxychloroquine, azithromycin, zinc, and vitamin D3 (n = 162)
vs hydroxychloroquine, azithromycin, zinc, and vitamin D3 (n = 75)
Findings

IVC therapy contributed to a quicker recovery
(57% vs 39% symptom free and discharged by day 15; p = 0.007)

Reference Ried et al. Cureus. 2021. doi: 10.7759/cureus.19902

RCT 6 Pharmacologic Ascorbic Acid as Early Therapy for Hospitalized Patients with COVID-19: A Randomized Clinical Trial
Date online 19 March 2022
Location Philadelphia, USA
Trial type Randomised controlled trial
Cohort 66 patients with COVID-19 requiring supplemental oxygen
Intervention Escalating doses of IV vitamin C plus standard of care (n = 44)
vs standard of care alone (n = 22)
Findings

Overall clinical improvement at 72 h was not achieved, however, point estimates for the composite outcome and its individual components of decreased use of supplemental oxygen, decreased use of bronchodilators, and the time to discharge were all favourable for the treatment arm, particularly at earlier time points (see figures).

Reference Coppock et al. Life (Basel). 2022;12(3):453. doi: 10.3390/life12030453

RCT 7 Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit
Date online 15 June 2022
Location Canada, France, New Zealand
Trial type Randomised placebo-controlled trial
Cohort 63 patients with SARS-CoV-2 infection (within a total cohort of 872 patients with sepsis)
Intervention IV vitamin C (50 mg/kg body weight) every 6 hours for up to 96 hours (n = 37)
vs matched placebo (n = 26)
Findings

A non-significant decrease in risk of death or persistent organ dysfunction in the vitamin C group (RR 0.81, 95% CI 0.57–1.16).

Reference Lamontagne et al. N Engl J Med. 2022;386(25):2387-2398. doi: 10.1056/NEJMoa2200644.

Intravenous vitamin C - retrospective cohort studies (10 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 The use of vitamin C in the intensive care unit during the COVID-19 pandemic
Date online July 2021
Location Bursa, Turkey
Trial type Retrospective cohort
Cohort 160 ICU patients with COVID-19
Intervention IV vitamin C at 3x 2g (n=32)
or no vitamin C (n=128)
Findings No differences observed between groups for inflammatory parameters (e.g. C-reactive protein, procalcitonin, D dimer), length of stay or mortality.
Reference Özgünay et al. Eur Res J 2021. doi:10.18621/eurj.938778
Study 7 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 8 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

Study 9 High-dose intravenous vitamin C decreases rates of mechanical ventilation and cardiac arrest in severe COVID-19
Date online 29 March 2022
Location Missouri, USA
Trial type Retrospective cohort
Cohort 100 patients with severe COVID-19
Intervention Intravenous vitamin C (3 g every 6 h for 7 days; n = 25)
Control - no vitamin C (n = 75)
Findings

Average time to death was significantly longer for HDIVC patients (22.9 days versus 13.7 days for control patients; P = 0.0139).
Patients who received HDIVC had significantly lower rates of mechanical ventilation (52.93% vs. 73.14%; P = 0.0499) and cardiac arrest (2.46% vs. 9.06%; P = 0.0439).

Reference Hess et al. Intern Emerg Med. 2022;1-10. doi: 10.1007/s11739-022-02954-6.

Study 10 Effect of high-dose intravenous vitamin C on prognosis in patients with SARS-CoV-2 pneumonia
Date online 22 April 2022
Location Ankara, Turkey
Trial type Retrospective cohort
Cohort 323 patients with severe COVID-19
Intervention Intravenous vitamin C (2 g/day; n = 153)
Control - no vitamin C (n = 170)
Findings Vitamin C group relative to control group: length of hospital stay (p = 0.05), re-admission rate (p = 0.9), admission to intensive care (ns), need for advanced oxygen support (p = 0.5), need for advanced medical treatment (p < 0.001), and mortality (p = 0.5)
Notes V vitamin C was relatively low dose (2 g/day) and was administered a median of 3 days after admission. Duration of vitamin C administration was not stated.
Reference Suna et al. Med Clin. 2022;158(8):356-360. doi: 10.1016/j.medcle.2021.04.027 2022;1-10.

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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
RCT 3 The Effect of Vitamin C on Pathological Parameters and Survival Duration of Critically Ill Coronavirus Disease 2019 Patients: A Randomized Clinical Trial
Date online 15 December 2021
Location Rasht, Iran
Trial type Double blind randomised controlled trial
Cohort 120 critically ill patients infected with COVID-19 (31 intervention group, 69 control group)
Intervention 500 mg/day oral vitamin C
for 14 days
Findings Higher mean survival duration compared with control group (8 vs. 4 days, p < 0.01)
Linear association between the number of days of vitamin C intake and survival duration
Lower serum potassium levels, but no difference in other blood parameters
Reference Majidi et al. Front Immunol. 2021;12:717816. doi: 10.3389/fimmu.2021.717816.

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 (3 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.

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 Chinese study
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.
Comments There are significant issues with using genetically predicted vitamin C concentrations – see commentary by Hemilä and Chalker, Eur J Clin Nutr. 2022. 1-2. doi: 10.1038/s41430-022-01091-9
Reference Hui et al. Eur J Clin Nutr 2021 1-4. doi: 10.1038/s41430-021-00993-4

Study 3 Relationship Between Plasma Vitamin C and COVID-19 Susceptibility and Severity: A Two-Sample Mendelian Randomization Study
Date online 9 March 2022
Location Chinese study
Study type Genome-wide association study (GWAS)
Cohort 52,018 people of European ancestry
Methodology Mendelian randomization analysis was conducted to examine the effect of selected single nucleotide polymorphisms and COVID-19 susceptibility, hospitalization, disease severity (note: they did not use measured vitamin C levels)
Findings Genetic predisposition to the levels of plasma Vitamin C was not associated with COVID-19 susceptibility, hospitalization and severity.
Comments There are significant issues with using genetically predicted vitamin C concentrations – see commentary by Hemilä and Chalker, Eur J Clin Nutr. 2022. 1-2. doi: 10.1038/s41430-022-01091-9
Reference Chen et al. Front Med (Lausanne). 2022;9:844228. doi: 10.3389/fmed.2022.844228

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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. Meta-analyses, which combine the outcomes from multiple studies, are now also becoming available.

Meta-analyses

Published review articles

Published commentaries

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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