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Late |
Xia et al., Aging, doi:10.18632/aging.203503 (Peer Reviewed) |
High-dose vitamin C ameliorates cardiac injury in COVID-19 pandemic: a retrospective cohort study |
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Details
Retrospective 113 severe and critical patients in China with cardiac injury, 51 treated with high dose vitamin C, showing treatment associated with improvement of myocardial injury. |
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Late treatment study
Late treatment study
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| Xia et al., Aging, doi:10.18632/aging.203503 (Peer Reviewed) |
| High-dose vitamin C ameliorates cardiac injury in COVID-19 pandemic: a retrospective cohort study |
Retrospective 113 severe and critical patients in China with cardiac injury, 51 treated with high dose vitamin C, showing treatment associated with improvement of myocardial injury.
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Xia et al., 9/7/2021, China, Asia, peer-reviewed, 5 authors.
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Late |
Tan et al., QJM, doi:10.1093/qjmed/hcab184 (Peer Reviewed) |
int./death, ↓24.5%, p=0.74 |
Efficacy of diammonium glycyrrhizinate combined with vitamin C for treating hospitalized COVID-19 patients: a retrospective, observational stud |
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Details
PSM retrospective 207 hospitalized patients in China, 46 treated with diammonium glycyrrhizinate and vitamin C, showing lower risk of ARDS with treatment. |
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Details
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Late treatment study
Late treatment study
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| Tan et al., QJM, doi:10.1093/qjmed/hcab184 (Peer Reviewed) |
| Efficacy of diammonium glycyrrhizinate combined with vitamin C for treating hospitalized COVID-19 patients: a retrospective, observational stud |
PSM retrospective 207 hospitalized patients in China, 46 treated with diammonium glycyrrhizinate and vitamin C, showing lower risk of ARDS with treatment.
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risk of combined intubation/death, 24.5% lower, RR 0.75, p = 0.74, treatment 1 of 46 (2.2%), control 14 of 115 (12.2%), OR converted to RR.
risk of ARDS, 73.3% lower, RR 0.27, p = 0.002, treatment 7 of 46 (15.2%), control 41 of 115 (35.7%), OR converted to RR.
Tan et al., 7/26/2021, retrospective, China, Asia, peer-reviewed, 7 authors, this trial uses multiple treatments in the treatment arm (combined with diammonium glycyrrhizinate) - results of individual treatments may vary.
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PrEP |
Margolin et al., Journal of Evidence-Based Integrative Medicine, doi:10.1177/2515690X211026193 (Peer Reviewed) |
cases, ↓94.4%, p=0.003 |
20-Week Study of Clinical Outcomes of Over-the-Counter COVID-19 Prophylaxis and Treatment |
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Details
Retrospective 113 outpatients, 53 (patient choice) treated with zinc, quercetin, vitamin C/D/E, l-lysine, and Quina, showing lower cases with treatment. |
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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| Margolin et al., Journal of Evidence-Based Integrative Medicine, doi:10.1177/2515690X211026193 (Peer Reviewed) |
| 20-Week Study of Clinical Outcomes of Over-the-Counter COVID-19 Prophylaxis and Treatment |
Retrospective 113 outpatients, 53 (patient choice) treated with zinc, quercetin, vitamin C/D/E, l-lysine, and Quina, showing lower cases with treatment.
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risk of COVID-19 case, 94.4% lower, RR 0.06, p = 0.003, treatment 0 of 53 (0.0%), control 9 of 60 (15.0%), continuity correction due to zero event.
risk of COVID-19 or flu-like illness, 81.1% lower, RR 0.19, p = 0.01, treatment 2 of 53 (3.8%), control 12 of 60 (20.0%).
Margolin et al., 7/6/2021, retrospective, USA, North America, peer-reviewed, 5 authors, this trial uses multiple treatments in the treatment arm (combined with zinc, quercetin, vitamin D/E, l-lysine, and Quina) - results of individual treatments may vary.
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Late |
Özgünay et al., The European Research Journal, doi:10.18621/eurj.938778 (Peer Reviewed) |
death, ↓9.3%, p=0.69 |
The use of vitamin C in the intensive care unit during the COVID-19 pandemic |
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Details
Retrospective 160 ICU patients, 32 with raised neutrophil/lymphocyte ratio treated with vitamin C, showing no significant differences. |
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Late treatment study
Late treatment study
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| Özgünay et al., The European Research Journal, doi:10.18621/eurj.938778 (Peer Reviewed) |
| The use of vitamin C in the intensive care unit during the COVID-19 pandemic |
Retrospective 160 ICU patients, 32 with raised neutrophil/lymphocyte ratio treated with vitamin C, showing no significant differences.
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risk of death, 9.3% lower, RR 0.91, p = 0.69, treatment 17 of 32 (53.1%), control 75 of 128 (58.6%).
risk of mechanical ventilation, 1.1% higher, RR 1.01, p = 1.00, treatment 23 of 32 (71.9%), control 91 of 128 (71.1%).
Özgünay et al., 7/4/2021, retrospective, Turkey, Europe, peer-reviewed, 7 authors.
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Late |
Vishnuram et al., Indian Journal of Basic and Applied Medical Research, doi:10.36848/IJBAMR/2020/29215.55599 (Peer Reviewed) |
death, ↓54.2%, p=0.03 |
Role of high dose oral liposomal vitamin C in reducing mortality in patients with COVID-19 |
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Details
Retrospective 8,634 hospitalized patients in India, showing lower mortality with high-dose vitamin C in unadjusted results. No group details are provided, the text and table appear to show different results, and some numbers do not match. |
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Late treatment study
Late treatment study
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| Vishnuram et al., Indian Journal of Basic and Applied Medical Research, doi:10.36848/IJBAMR/2020/29215.55599 (Peer Reviewed) |
| Role of high dose oral liposomal vitamin C in reducing mortality in patients with COVID-19 |
Retrospective 8,634 hospitalized patients in India, showing lower mortality with high-dose vitamin C in unadjusted results. No group details are provided, the text and table appear to show different results, and some numbers do not match.
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risk of death, 54.2% lower, RR 0.46, p = 0.03, treatment 164 of 8634 (1.9%), control 10 of 241 (4.1%).
Vishnuram et al., 6/30/2021, retrospective, India, South Asia, peer-reviewed, 5 authors.
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Late |
Li et al., Journal of Pharmacy Practice, doi:10.1177/08971900211015052 (Peer Reviewed) |
death, ↑10.5%, p=1.00 |
Use of Intravenous Vitamin C in Critically Ill Patients With COVID-19 Infection |
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Details
PSM retrospective 8 ICU patients treated with vitamin C and 24 matched controls, showing no significant difference. Authors note that "it is possible for the delayed timing of IV vitamin C to have blunted the beneficial effects as th.. |
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Late treatment study
Late treatment study
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| Li et al., Journal of Pharmacy Practice, doi:10.1177/08971900211015052 (Peer Reviewed) |
| Use of Intravenous Vitamin C in Critically Ill Patients With COVID-19 Infection |
PSM retrospective 8 ICU patients treated with vitamin C and 24 matched controls, showing no significant difference. Authors note that "it is possible for the delayed timing of IV vitamin C to have blunted the beneficial effects as these patients may have already progressed to the late fibroproliferative phase or ARDS". IV vitamin C 1.5 grams every 6 hours.
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risk of death, 10.5% higher, RR 1.11, p = 1.00, treatment 7 of 8 (87.5%), control 19 of 24 (79.2%), PSM.
Li et al., 6/8/2021, retrospective, propensity score matching, USA, North America, peer-reviewed, 6 authors.
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Review |
May et al., British Journal of Pharmacology, doi:10.1111/bph.15579 (Review) (Peer Reviewed) |
review |
Therapeutic potential of megadose vitamin C to reverse organ dysfunction in sepsis and COVID-19 |
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Review of data supporting the use of megadose vitamin C as a treatment for sepsis and COVID-19. |
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Review
Review
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| May et al., British Journal of Pharmacology, doi:10.1111/bph.15579 (Review) (Peer Reviewed) |
| Therapeutic potential of megadose vitamin C to reverse organ dysfunction in sepsis and COVID-19 |
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Review of data supporting the use of megadose vitamin C as a treatment for sepsis and COVID-19.
May et al., 6/1/2021, peer-reviewed, 3 authors.
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Submit Corrections or Comments
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Late |
Suna et al., Med. Clin. (Barc.), doi:10.1016/j.medcli.2021.04.010 (Peer Reviewed) |
death, ↓21.3%, p=0.52 |
Effect of high-dose intravenous vitamin C on prognosis in patients with SARS-CoV-2 pneumonia |
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Details
Retrospective 323 hospitalized patients, 153 treated with vitamin C, showing no significant differences. Patients in each group were in different time periods, with the vitamin C group first. Time based confounding is possible due to impr.. |
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Late treatment study
Late treatment study
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| Suna et al., Med. Clin. (Barc.), doi:10.1016/j.medcli.2021.04.010 (Peer Reviewed) |
| Effect of high-dose intravenous vitamin C on prognosis in patients with SARS-CoV-2 pneumonia |
Retrospective 323 hospitalized patients, 153 treated with vitamin C, showing no significant differences. Patients in each group were in different time periods, with the vitamin C group first. Time based confounding is possible due to improvements in SOC.
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risk of death, 21.3% lower, RR 0.79, p = 0.52, treatment 17 of 153 (11.1%), control 24 of 170 (14.1%).
risk of ICU admission, 1.9% higher, RR 1.02, p = 1.00, treatment 11 of 153 (7.2%), control 12 of 170 (7.1%).
Suna et al., 5/11/2021, retrospective, Turkey, Europe, peer-reviewed, 5 authors.
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In Silico |
Malla et al., bioRxiv, doi:10.1101/2021.05.02.442358 (Preprint) |
Vitamin C inhibits SARS coronavirus-2 main protease essential for viral replication |
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Details
In Vitro study showing that vitamin C inhibits SARS-CoV-2 3CLpro. Authors note that the different clinical results may be explained in part by the widely varying dosages used, and they conclude that vitamin C and/or derivatives may become.. |
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In Silico
In Silico
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| Malla et al., bioRxiv, doi:10.1101/2021.05.02.442358 (Preprint) |
| Vitamin C inhibits SARS coronavirus-2 main protease essential for viral replication |
In Vitro study showing that vitamin C inhibits SARS-CoV-2 3CLpro. Authors note that the different clinical results may be explained in part by the widely varying dosages used, and they conclude that vitamin C and/or derivatives may become an important treatment for COVID-19 and other viral infections.
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Malla et al., 5/3/2021, preprint, 9 authors.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
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Early |
Zhao et al., Frontiers in Pharmacology, doi:10.3389/fphar.2021.638556 (Peer Reviewed) |
progression, ↓72.0%, p=0.03 |
High Dose Intravenous Vitamin C for Preventing The Disease Aggravation of Moderate COVID-19 Pneumonia. A Retrospective Propensity Matched Before-After Study |
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Details
PSM retrospective 110 patients, 55 treated with high-dose IV vitamin C, showing lower progression to severe disease with treatment. Patients in each group were in different time periods, time based confounding is likely due to SOC improvi.. |
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Details
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Early treatment study
Early treatment study
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| Zhao et al., Frontiers in Pharmacology, doi:10.3389/fphar.2021.638556 (Peer Reviewed) |
| High Dose Intravenous Vitamin C for Preventing The Disease Aggravation of Moderate COVID-19 Pneumonia. A Retrospective Propensity Matched Before-After Study |
PSM retrospective 110 patients, 55 treated with high-dose IV vitamin C, showing lower progression to severe disease with treatment. Patients in each group were in different time periods, time based confounding is likely due to SOC improving over time. ChiCTR2000033050.
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risk of disease progression, 72.0% lower, RR 0.28, p = 0.03, treatment 4 of 55 (7.3%), control 12 of 55 (21.8%), adjusted, PSM.
time to viral-, 7.7% higher, relative time 1.08, p = 0.79, treatment 55, control 55, PSM.
Zhao et al., 4/22/2021, retrospective, propensity score matching, China, Asia, peer-reviewed, 15 authors.
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Submit Corrections or Comments
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Late |
Hakamifard et al., Immunopathologia Persa, doi:10.34172/ipp.2021.xx (Peer Reviewed) |
ICU, ↓46.3%, p=0.46 |
The effect of vitamin E and vitamin C in patients with COVID-19 pneumonia; a randomized controlled clinical trial |
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Details
RCT with 38 patients treated with vitamin C and vitamin E, and 34 control patients, showing lower ICU admission with treatment, but not statistically significant. |
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Details
Source
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Late treatment study
Late treatment study
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| Hakamifard et al., Immunopathologia Persa, doi:10.34172/ipp.2021.xx (Peer Reviewed) |
| The effect of vitamin E and vitamin C in patients with COVID-19 pneumonia; a randomized controlled clinical trial |
RCT with 38 patients treated with vitamin C and vitamin E, and 34 control patients, showing lower ICU admission with treatment, but not statistically significant.
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risk of ICU admission, 46.3% lower, RR 0.54, p = 0.46, treatment 3 of 38 (7.9%), control 5 of 34 (14.7%).
hospitalization time, 1.0% lower, relative time 0.99, p = 0.82, treatment 38, control 34.
Hakamifard et al., 4/14/2021, Randomized Controlled Trial, Iran, Middle East, peer-reviewed, 8 authors, this trial uses multiple treatments in the treatment arm (combined with vitamin E) - results of individual treatments may vary.
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Late |
Gadhiya et al., BMJ Open, doi:10.1136/bmjopen-2020-042549 (Peer Reviewed) |
death, ↑0.7%, p=0.98 |
Clinical characteristics of hospitalised patients with COVID-19 and the impact on mortality: a single-network, retrospective cohort study from Pennsylvania state |
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Details
Retrospective 283 patients in the USA showing higher mortality with all treatments (not statistically significant). Confounding by indication is likely. In the supplementary appendix, authors note that the treatments were usually given fo.. |
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Details
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Late treatment study
Late treatment study
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| Gadhiya et al., BMJ Open, doi:10.1136/bmjopen-2020-042549 (Peer Reviewed) |
| Clinical characteristics of hospitalised patients with COVID-19 and the impact on mortality: a single-network, retrospective cohort study from Pennsylvania state |
Retrospective 283 patients in the USA showing higher mortality with all treatments (not statistically significant). Confounding by indication is likely. In the supplementary appendix, authors note that the treatments were usually given for patients that required oxygen therapy. Oxygen therapy and ICU admission (possibly, the paper includes ICU admission for model 2 in some places but not others) were the only variables indicating severity used in adjustments.
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risk of death, 0.7% higher, RR 1.01, p = 0.98, treatment 19 of 55 (34.5%), control 36 of 226 (15.9%), adjusted, OR converted to RR, multivariate logistic regression.
Gadhiya et al., 4/8/2021, retrospective, USA, North America, peer-reviewed, 4 authors.
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Late |
Mulhem et al., BMJ Open, doi:10.1136/bmjopen-2020-042042 (Peer Reviewed) |
death, ↑32.2%, p=0.01 |
3219 hospitalised patients with COVID-19 in Southeast Michigan: a retrospective case cohort study |
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Details
Retrospective database analysis of 3,219 hospitalized patients in the USA. Very different results in the time period analysis (Table S2), and results significantly different to other studies for the same medications (e.g., heparin OR 3.06.. |
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Details
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Late treatment study
Late treatment study
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| Mulhem et al., BMJ Open, doi:10.1136/bmjopen-2020-042042 (Peer Reviewed) |
| 3219 hospitalised patients with COVID-19 in Southeast Michigan: a retrospective case cohort study |
Retrospective database analysis of 3,219 hospitalized patients in the USA. Very different results in the time period analysis (Table S2), and results significantly different to other studies for the same medications (e.g., heparin OR 3.06 [2.44-3.83]) suggest significant confounding by indication and confounding by time.
risk of death, 32.2% higher, RR 1.32, p = 0.01, treatment 157 of 794 (19.8%), control 359 of 2425 (14.8%), adjusted, OR converted to RR, logistic regression.
Mulhem et al., 4/7/2021, retrospective, database analysis, USA, North America, peer-reviewed, 3 authors.
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Late |
Al Sulaiman et al., Research Square, doi:10.21203/rs.3.rs-354711/v1 (Preprint) |
death, ↓14.9%, p=0.27 |
Ascorbic Acid as an Adjunctive Therapy in Critically Ill Patients with COVID-19: A Multicenter Propensity Score Matched Study |
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Details
Retrospective 158 critically ill patients receiving vitamin C and propensity matched controls, showing mortality OR 0.77 [0.48-1.23], and statistically significantly lower thrombosis, OR 0.42 [0.18-0.94]. 1000mg of vitamin C was given dai.. |
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Details
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Late treatment study
Late treatment study
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| Al Sulaiman et al., Research Square, doi:10.21203/rs.3.rs-354711/v1 (Preprint) |
| Ascorbic Acid as an Adjunctive Therapy in Critically Ill Patients with COVID-19: A Multicenter Propensity Score Matched Study |
Retrospective 158 critically ill patients receiving vitamin C and propensity matched controls, showing mortality OR 0.77 [0.48-1.23], and statistically significantly lower thrombosis, OR 0.42 [0.18-0.94]. 1000mg of vitamin C was given daily.
risk of death, 14.9% lower, RR 0.85, p = 0.27, treatment 46 of 142 (32.4%), control 59 of 142 (41.5%), OR converted to RR, PSM.
Al Sulaiman et al., 4/2/2021, retrospective, propensity score matching, Saudi Arabia, Middle East, preprint, 12 authors.
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Submit Corrections or Comments
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Late |
Hamidi-Alamdari et al., Clinical and Translational Investigation, doi:10.24875/RIC.21000028 (Peer Reviewed) |
death, ↓44.4%, p=0.38 |
Methylene blue for treatment of hospitalized COVID-19 patients: a randomized, controlled, open-label clinical trial, phase 2 |
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Details
RCT 80 hospitalized patients with severe COVID-19, 40 treated with methylene blue + vitamin C + N-acetyl cysteine, showing lower mortality, shorter hospitalization, and significantly improved SpO2 and respiratory distress with treatment. .. |
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Details
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Late treatment study
Late treatment study
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| Hamidi-Alamdari et al., Clinical and Translational Investigation, doi:10.24875/RIC.21000028 (Peer Reviewed) |
| Methylene blue for treatment of hospitalized COVID-19 patients: a randomized, controlled, open-label clinical trial, phase 2 |
RCT 80 hospitalized patients with severe COVID-19, 40 treated with methylene blue + vitamin C + N-acetyl cysteine, showing lower mortality, shorter hospitalization, and significantly improved SpO2 and respiratory distress with treatment. NCT04370288.
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risk of death, 44.4% lower, RR 0.56, p = 0.38, treatment 5 of 40 (12.5%), control 9 of 40 (22.5%).
hospitalization time, 37.6% lower, relative time 0.62, p = 0.004, treatment 40, control 40.
Hamidi-Alamdari et al., 3/8/2021, Randomized Controlled Trial, Iran, Middle East, peer-reviewed, 23 authors, this trial uses multiple treatments in the treatment arm (combined with methylene blue and N-acetyl cysteine) - results of individual treatments may vary.
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Submit Corrections or Comments
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Early |
Hemilä et al., Research Square, doi:10.21203/rs.3.rs-289381/v1 (Preprint) (meta analysis) |
meta-analysis |
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 |
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Details
Reanalysis of Thomas et al. showing that vitamin C increased the recovery rate by 70%, p = 0.025. |
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Details
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Early treatment study
Early treatment study
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| Hemilä et al., Research Square, doi:10.21203/rs.3.rs-289381/v1 (Preprint) (meta analysis) |
| 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 |
Reanalysis of Thomas et al. showing that vitamin C increased the recovery rate by 70%, p = 0.025.
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Hemilä et al., 3/2/2021, preprint, 3 authors.
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Submit Corrections or Comments
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Late |
Gao et al., Aging, doi:10.18632/aging.202557 (Peer Reviewed) |
death, ↓86.0%, p=0.04 |
The efficiency and safety of high-dose vitamin C in patients with COVID-19: a retrospective cohort study |
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Details
Retrospective 76 COVID-19 patients, 46 treated with intravenous high-dose vitamin C, showing lower mortality and improved oxygen requirements with treatment. Dosage was 6g intravenous infusion per 12hr on the first day, and 6g once for th.. |
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Details
Source
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Late treatment study
Late treatment study
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| Gao et al., Aging, doi:10.18632/aging.202557 (Peer Reviewed) |
| The efficiency and safety of high-dose vitamin C in patients with COVID-19: a retrospective cohort study |
Retrospective 76 COVID-19 patients, 46 treated with intravenous high-dose vitamin C, showing lower mortality and improved oxygen requirements with treatment. Dosage was 6g intravenous infusion per 12hr on the first day, and 6g once for the following 4 days.
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risk of death, 86.0% lower, RR 0.14, p = 0.04, treatment 1 of 46 (2.2%), control 5 of 30 (16.7%), adjusted, KM.
Gao et al., 2/26/2021, retrospective, China, Asia, peer-reviewed, 14 authors.
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Submit Corrections or Comments
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Early |
Thomas et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2021.0369 (Peer Reviewed) |
recov. time, ↓17.9%, p=0.38 |
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 |
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Details
Small 214 low-risk outpatient RCT showing non-statistically significant faster recovery with zinc and with vitamin C. NCT04342728.
A secondary analysis concludes that vitamin C increases recovery rate by 71% (p = 0.036) [1]. See also [2]. |
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Early treatment study
Early treatment study
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| Thomas et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2021.0369 (Peer Reviewed) |
| 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 |
Small 214 low-risk outpatient RCT showing non-statistically significant faster recovery with zinc and with vitamin C. NCT04342728.A secondary analysis concludes that vitamin C increases recovery rate by 71% (p = 0.036) [1]. See also [2].
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recovery time, 17.9% lower, relative time 0.82, p = 0.38, treatment 48, control 50, mean time to a 50% reduction in symptoms, p value approximated with combined p value in study.
Thomas et al., 2/12/2021, Randomized Controlled Trial, USA, North America, peer-reviewed, 11 authors, this trial uses multiple treatments in the treatment arm (combined with zinc) - results of individual treatments may vary.
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Submit Corrections or Comments
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PrEP |
Hancock et al., SSRN, doi:10.2139/ssrn.3779211 (Preprint) |
Case Cluster of RT-PCR COVID-19 Positive Patients with an Unexpected Benign Clinical Course With Vitamin D, Melatonin, Vitamin C, and Viscum Album |
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Details
Case series of 24 COVID-19 patients (12 confirmed PCR+) treated with vitamin D, vitamin C, and melatonin, showing positive outcomes with no patient having worse than a mild case, including 7 high risk patients. |
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Details
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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| Hancock et al., SSRN, doi:10.2139/ssrn.3779211 (Preprint) |
| Case Cluster of RT-PCR COVID-19 Positive Patients with an Unexpected Benign Clinical Course With Vitamin D, Melatonin, Vitamin C, and Viscum Album |
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Case series of 24 COVID-19 patients (12 confirmed PCR+) treated with vitamin D, vitamin C, and melatonin, showing positive outcomes with no patient having worse than a mild case, including 7 high risk patients.
Hancock et al., 2/9/2021, preprint, 4 authors.
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Submit Corrections or Comments
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Late |
Zhao et al., Ann. Palliat. Med., doi:10.21037/apm-20-1387 (Peer Reviewed) |
Beneficial aspects of high dose intravenous vitamin C on patients with COVID-19 pneumonia in severe condition: a retrospective case series study |
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Details
Retrospective case study of 12 severe/critical COVID-19 patients finding that high dose IV vitamin C improved inflammatory response, immune and organ function. There was no control group. |
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Details
Source
PDF
Late treatment study
Late treatment study
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| Zhao et al., Ann. Palliat. Med., doi:10.21037/apm-20-1387 (Peer Reviewed) |
| Beneficial aspects of high dose intravenous vitamin C on patients with COVID-19 pneumonia in severe condition: a retrospective case series study |
Retrospective case study of 12 severe/critical COVID-19 patients finding that high dose IV vitamin C improved inflammatory response, immune and organ function. There was no control group.
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Zhao et al., 2/1/2021, peer-reviewed, 14 authors.
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Submit Corrections or Comments
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Late |
Xing et al., Journal of Pharmaceutical and Biomedical Analysis, doi:10.1016/j.jpba.2021.113927 (Peer Reviewed) |
Vitamin C supplementation is necessary for patients with coronavirus disease: An ultra-high-performance liquid chromatography-tandem mass spectrometry finding |
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Details
Prospective study with 31 COVID-19 patients and 60 controls reporting on a new method to assess plasma vitamin C concentrations. Vitamin C was deficient (11.4µmol/l vs. 52µmol/l for healthy controls), and returned to a normal range (76µmo.. |
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Late treatment study
Late treatment study
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| Xing et al., Journal of Pharmaceutical and Biomedical Analysis, doi:10.1016/j.jpba.2021.113927 (Peer Reviewed) |
| Vitamin C supplementation is necessary for patients with coronavirus disease: An ultra-high-performance liquid chromatography-tandem mass spectrometry finding |
Prospective study with 31 COVID-19 patients and 60 controls reporting on a new method to assess plasma vitamin C concentrations. Vitamin C was deficient (11.4µmol/l vs. 52µmol/l for healthy controls), and returned to a normal range (76µmol/l) with intravenous vitamin C. Authors recommend high dose intravenous vitamin C for COVID-19 patients at a dose of 100mg/kg/day.
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Xing et al., 1/27/2021, peer-reviewed, 13 authors.
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Submit Corrections or Comments
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Late |
JamaliMoghadamSiahkali et al., Research Square, doi:10.21203/rs.3.rs-139942/v1 (Preprint) |
death, 0.0%, p=1.00 |
Safety and Effectiveness of High-Dose Vitamin C in Patients with COVID-19; A Randomized Controlled open-label Clinical Trial |
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Details
Small late stage RCT for the addition of vitamin C to HCQ and lopinavir/ritonavir, with 30 treatment and 30 control patients, finding a significant reduction in temperature and a significant improvement in oxygenation after 3 days in the .. |
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Details
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Late treatment study
Late treatment study
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| JamaliMoghadamSiahkali et al., Research Square, doi:10.21203/rs.3.rs-139942/v1 (Preprint) |
| Safety and Effectiveness of High-Dose Vitamin C in Patients with COVID-19; A Randomized Controlled open-label Clinical Trial |
Small late stage RCT for the addition of vitamin C to HCQ and lopinavir/ritonavir, with 30 treatment and 30 control patients, finding a significant reduction in temperature and a significant improvement in oxygenation after 3 days in the vitamin C group. However, hospitalization time was longer and there was no significant difference in mortality.
risk of death, no change, RR 1.00, p = 1.00, treatment 3 of 30 (10.0%), control 3 of 30 (10.0%).
risk of mechanical ventilation, 25.0% higher, RR 1.25, p = 1.00, treatment 5 of 30 (16.7%), control 4 of 30 (13.3%).
hospitalization time, 30.8% higher, relative time 1.31, p = 0.03, treatment 30, control 30.
JamaliMoghadamSiahkali et al., 1/9/2021, Randomized Controlled Trial, Iran, Middle East, preprint, 17 authors.
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Late |
Darban et al., Journal of Cellular & Molecular Anesthesia, doi:10.22037/jcma.v6i2.32182 (Peer Reviewed) |
progression, ↓33.3%, p=1.00 |
Efficacy of High Dose Vitamin C, Melatonin and Zinc in Iranian Patients with Acute Respiratory Syndrome due to Coronavirus Infection: A Pilot Randomized Trial |
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Small RCT in Iran with 20 ICU patients, 10 treated with high-dose vitamin C, melatonin, and zinc, not showing significant differences. IRCT20151228025732N52. |
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Late treatment study
Late treatment study
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| Darban et al., Journal of Cellular & Molecular Anesthesia, doi:10.22037/jcma.v6i2.32182 (Peer Reviewed) |
| Efficacy of High Dose Vitamin C, Melatonin and Zinc in Iranian Patients with Acute Respiratory Syndrome due to Coronavirus Infection: A Pilot Randomized Trial |
Small RCT in Iran with 20 ICU patients, 10 treated with high-dose vitamin C, melatonin, and zinc, not showing significant differences. IRCT20151228025732N52.
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risk of disease progression, 33.3% lower, RR 0.67, p = 1.00, treatment 2 of 10 (20.0%), control 3 of 10 (30.0%).
ICU time, 6.0% lower, relative time 0.94, p = 0.30, treatment 10, control 10.
Darban et al., 12/15/2020, Randomized Controlled Trial, Iran, Middle East, peer-reviewed, 8 authors, this trial uses multiple treatments in the treatment arm (combined with melatonin and zinc) - results of individual treatments may vary.
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Review |
Holford et al., Nutrients, doi:10.3390/nu12123760 (Review) (Peer Reviewed) |
review |
Vitamin C—An Adjunctive Therapy for Respiratory Infection, Sepsis and COVID-19 |
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Review of vitamin C use for respiratory infections including COVID-19 and the mechanisms of action. Authors note that evidence to date indicates oral vitamin C (2–8 g/day) may reduce the incidence and duration of respiratory infections, a.. |
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Review
Review
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| Holford et al., Nutrients, doi:10.3390/nu12123760 (Review) (Peer Reviewed) |
| Vitamin C—An Adjunctive Therapy for Respiratory Infection, Sepsis and COVID-19 |
Review of vitamin C use for respiratory infections including COVID-19 and the mechanisms of action. Authors note that evidence to date indicates oral vitamin C (2–8 g/day) may reduce the incidence and duration of respiratory infections, and intravenous vitamin C (6–24 g/day) has been shown to reduce mortality, intensive care unit (ICU) and hospital stays, and time on mechanical ventilation for severe respiratory infections. Authors conclude that given the favourable safety profile and low cost of vitamin C, and the frequency of vitamin C deficiency in respiratory infections, it may be worthwhile testing patients’ vitamin C status and treating them accordingly with intravenous administration within ICUs and oral administration in hospitalised COVID-19 patients.
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Holford et al., 12/7/2020, peer-reviewed, 7 authors.
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Late |
Kumari et al., Cureus 12(11): e11779, doi:10.7759/cureus.11779 (Peer Reviewed) |
death, ↓36.4%, p=0.45 |
The Role of Vitamin C as Adjuvant Therapy in COVID-19 |
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RCT 150 hospitalized patients in Pakistan showing 26% faster recovery, p < 0.0001. 36% lower mortality, not statistically significant due to the small number of events. Dosage was 50 mg/kg/day of intravenous vitamin C. |
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Late treatment study
Late treatment study
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| Kumari et al., Cureus 12(11): e11779, doi:10.7759/cureus.11779 (Peer Reviewed) |
| The Role of Vitamin C as Adjuvant Therapy in COVID-19 |
RCT 150 hospitalized patients in Pakistan showing 26% faster recovery, p < 0.0001. 36% lower mortality, not statistically significant due to the small number of events. Dosage was 50 mg/kg/day of intravenous vitamin C.
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risk of death, 36.4% lower, RR 0.64, p = 0.45, treatment 7 of 75 (9.3%), control 11 of 75 (14.7%).
risk of mechanical ventilation, 20.0% lower, RR 0.80, p = 0.67, treatment 12 of 75 (16.0%), control 15 of 75 (20.0%).
recovery time, 26.0% lower, relative time 0.74, p < 0.001, treatment 75, control 75, days to symptom-free.
hospitalization time, 24.3% lower, relative time 0.76, p < 0.001, treatment 75, control 75, days spent in hospital.
Kumari et al., 11/30/2020, Randomized Controlled Trial, Pakistan, South Asia, peer-reviewed, 10 authors.
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PrEP |
Louca et al., BMJ Nutrition, Prevention & Health, doi:10.1136/bmjnph-2021-000250 (preprint 11/30/20) (Peer Reviewed) |
cases, 0.0%, p=1.00 |
Modest effects of dietary supplements during the COVID-19 pandemic: insights from 445 850 users of the COVID-19 Symptom Study app |
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Survey analysis of dietary supplements showing no significant difference in PCR+ cases with vitamin C usage in the UK, however significant reductions were found in the US and Sweden. These results are for PCR+ cases only, they do not refl.. |
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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| Louca et al., BMJ Nutrition, Prevention & Health, doi:10.1136/bmjnph-2021-000250 (preprint 11/30/20) (Peer Reviewed) |
| Modest effects of dietary supplements during the COVID-19 pandemic: insights from 445 850 users of the COVID-19 Symptom Study app |
Survey analysis of dietary supplements showing no significant difference in PCR+ cases with vitamin C usage in the UK, however significant reductions were found in the US and Sweden. These results are for PCR+ cases only, they do not reflect potential benefits for reducing the severity of cases. A number of biases could affect the results, for example users of the app may not be representative of the general population, and people experiencing symptoms may be more likely to install and use the app.
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risk of COVID-19 case, no change, RR 1.00, p = 1.00, OR converted to RR, United Kingdom, all adjustment model.
Louca et al., 11/30/2020, retrospective, United Kingdom, Europe, peer-reviewed, 26 authors.
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PrEP |
Behera et al., PLoS ONE, doi:10.1371/journal.pone.0247163 (preprint 11/3) (Peer Reviewed) |
cases, ↓9.6%, p=0.58 |
Role of ivermectin in the prevention of SARS-CoV-2 infection among healthcare workers in India: A matched case-control study |
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Retrospective matched case-control prophylaxis study for HCQ, ivermectin, and vitamin C with 372 healthcare workers, showing lower COVID-19 incidence for all treatments, with statistical significance reached for ivermectin.
HCQ OR 0.56, .. |
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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| Behera et al., PLoS ONE, doi:10.1371/journal.pone.0247163 (preprint 11/3) (Peer Reviewed) |
| Role of ivermectin in the prevention of SARS-CoV-2 infection among healthcare workers in India: A matched case-control study |
Retrospective matched case-control prophylaxis study for HCQ, ivermectin, and vitamin C with 372 healthcare workers, showing lower COVID-19 incidence for all treatments, with statistical significance reached for ivermectin.HCQ OR 0.56, p = 0.29
Ivermectin OR 0.27, p < 0.001
Vitamin C OR 0.82, p = 0.58
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risk of COVID-19 case, 9.6% lower, RR 0.90, p = 0.58, treatment 29 of 67 (43.3%), control 157 of 305 (51.5%), adjusted, OR converted to RR, model 2 conditional logistic regression.
risk of COVID-19 case, 16.5% lower, RR 0.83, p = 0.04, treatment 29 of 67 (43.3%), control 157 of 305 (51.5%), adjusted, OR converted to RR, matched pair analysis.
Behera et al., 11/3/2020, retrospective, India, South Asia, peer-reviewed, 13 authors.
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Late |
Patel et al., Chest Infections, doi:10.1016/j.chest.2020.08.322 (Peer Reviewed) |
death, ↓29.5%, p=0.18 |
The significance of oral ascorbic acid in patients with COVID-19 |
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Retrospective 176 hospitalized patients, 96 treated with oral vitamin C (from 500mg to 1500mg daily), showing lower mortality with treatment. |
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Late treatment study
Late treatment study
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| Patel et al., Chest Infections, doi:10.1016/j.chest.2020.08.322 (Peer Reviewed) |
| The significance of oral ascorbic acid in patients with COVID-19 |
Retrospective 176 hospitalized patients, 96 treated with oral vitamin C (from 500mg to 1500mg daily), showing lower mortality with treatment.
risk of death, 29.5% lower, RR 0.71, p = 0.18, treatment 22 of 96 (22.9%), control 26 of 80 (32.5%).
risk of death, 15.6% lower, RR 0.84, p = 0.60, treatment 15 of 30 (50.0%), control 16 of 27 (59.3%), ICU patients.
Patel et al., 10/1/2020, retrospective, USA, North America, peer-reviewed, 8 authors.
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Levels |
Arvinte et al., Med. Drug Discov, doi:10.1016/j.medidd.2020.100064
(Peer Reviewed) |
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 |
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Pilot study with 21 ICU patients finding low serum levels of vitamin C and vitamin D in most patients. Older age and low vitamin C level appeared to be co-dependent risk factors for mortality. |
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Levels
Analysis of outcomes based on serum levels
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| Arvinte et al., Med. Drug Discov, doi:10.1016/j.medidd.2020.100064
(Peer Reviewed) |
| 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 |
Pilot study with 21 ICU patients finding low serum levels of vitamin C and vitamin D in most patients. Older age and low vitamin C level appeared to be co-dependent risk factors for mortality.
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Arvinte et al., 9/8/2020, peer-reviewed.
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Levels |
Chiscano-Camón et al., Critical Care, doi:10.1186/s13054-020-03249-y (Peer Reviewed) |
Vitamin C levels in patients with SARS-CoV-2-associated acute respiratory distress syndrome |
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Small study of 18 COVID-19 ARDS patients showing that vitamin C levels were very low - 17 patients had undetectable levels and one had a low level (2.4 mg/L). |
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Levels
Analysis of outcomes based on serum levels
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| Chiscano-Camón et al., Critical Care, doi:10.1186/s13054-020-03249-y (Peer Reviewed) |
| Vitamin C levels in patients with SARS-CoV-2-associated acute respiratory distress syndrome |
Small study of 18 COVID-19 ARDS patients showing that vitamin C levels were very low - 17 patients had undetectable levels and one had a low level (2.4 mg/L).
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Chiscano-Camón et al., 8/26/2020, peer-reviewed, mean age 59.0, 5 authors.
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Late |
Zhang et al., Annals of Intensive Care, doi:10.1186/s13613-020-00792-3 (Peer Reviewed) |
death, ↓50.0%, p=0.20 |
Pilot Trial of High-dose vitamin C in critically ill COVID-19 patients (preprint 8/10/2020) |
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Small RCT for high dose vitamin C for ICU patients showing reduced (but not statistically significant) mortality. Dosage was 12g of vitamin C/50ml every 12 hours for 7 days at a rate of 12ml/hour. |
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Late treatment study
Late treatment study
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| Zhang et al., Annals of Intensive Care, doi:10.1186/s13613-020-00792-3 (Peer Reviewed) |
| Pilot Trial of High-dose vitamin C in critically ill COVID-19 patients (preprint 8/10/2020) |
Small RCT for high dose vitamin C for ICU patients showing reduced (but not statistically significant) mortality. Dosage was 12g of vitamin C/50ml every 12 hours for 7 days at a rate of 12ml/hour.
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risk of death, 50.0% lower, RR 0.50, p = 0.20, treatment 6 of 27 (22.2%), control 11 of 29 (37.9%), adjusted, ICU mortality.
risk of death, 80.0% lower, RR 0.20, p = 0.04, treatment 5 of 27 (18.5%), control 11 of 29 (37.9%), adjusted, ICU mortality for SOFA>=3.
risk of death, 50.0% lower, RR 0.50, p = 0.31, treatment 6 of 27 (22.2%), control 10 of 29 (34.5%), adjusted, 28 day mortality.
risk of death, 70.0% lower, RR 0.30, p = 0.07, treatment 5 of 27 (18.5%), control 10 of 29 (34.5%), adjusted, 28 day mortality for SOFA>=3.
Zhang et al., 8/10/2020, Randomized Controlled Trial, China, Asia, peer-reviewed, 11 authors.
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Late |
Hiedra et al., Expert Review of Anti-infective Therapy, doi:10.1080/14787210.2020.1794819 (Peer Reviewed) |
The use of IV vitamin C for patients with COVID-19: a case series |
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Case study of 17 patients receiving IV vitamin C for COVID-19, finding a significant decrease in inflammatory markers, including ferritin and D-dimer, and a trend to decreasing FiO2 requirements, after vitamin C administration. There was .. |
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Late treatment study
Late treatment study
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| Hiedra et al., Expert Review of Anti-infective Therapy, doi:10.1080/14787210.2020.1794819 (Peer Reviewed) |
| The use of IV vitamin C for patients with COVID-19: a case series |
Case study of 17 patients receiving IV vitamin C for COVID-19, finding a significant decrease in inflammatory markers, including ferritin and D-dimer, and a trend to decreasing FiO2 requirements, after vitamin C administration. There was no control group.
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Hiedra et al., 8/1/2020, peer-reviewed, 8 authors.
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Review |
Feyaerts et al., Nutrition, doi:10.1016/j.nut.2020.110948 (Review) (Peer Reviewed) |
review |
Vitamin C as prophylaxis and adjunctive medical treatment for COVID-19? |
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Review concluding that there is clear evidence that vitamin C in high doses can reduce interleukin-6 and endothelin-1 mediators. Authors suggest a relatively low dose as prophylaxis, and in cases of severe COVID-19, an (intravenous) high-.. |
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Review
Review
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| Feyaerts et al., Nutrition, doi:10.1016/j.nut.2020.110948 (Review) (Peer Reviewed) |
| Vitamin C as prophylaxis and adjunctive medical treatment for COVID-19? |
Review concluding that there is clear evidence that vitamin C in high doses can reduce interleukin-6 and endothelin-1 mediators. Authors suggest a relatively low dose as prophylaxis, and in cases of severe COVID-19, an (intravenous) high-dose regimen may be beneficial.
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Feyaerts et al., 7/25/2020, peer-reviewed, 2 authors.
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Late |
Krishnan et al., J Clin Anesth., doi:10.1016/j.jclinane.2020.110005 (Peer Reviewed) |
death, ↓30.7%, p<0.0001 |
Clinical comorbidities, characteristics, and outcomes of mechanically ventilated patients in the State of Michigan with SARS-CoV-2 pneumonia |
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Retrospective 152 mechanically ventilated patients in the USA showing unadjusted lower mortality with vitamin C, vitamin D, HCQ, and zinc treatment, statistically significant only for vitamin C. |
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Late treatment study
Late treatment study
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| Krishnan et al., J Clin Anesth., doi:10.1016/j.jclinane.2020.110005 (Peer Reviewed) |
| Clinical comorbidities, characteristics, and outcomes of mechanically ventilated patients in the State of Michigan with SARS-CoV-2 pneumonia |
Retrospective 152 mechanically ventilated patients in the USA showing unadjusted lower mortality with vitamin C, vitamin D, HCQ, and zinc treatment, statistically significant only for vitamin C.
risk of death, 30.7% lower, RR 0.69, p < 0.001, treatment 40 of 79 (50.6%), control 52 of 73 (71.2%), adjusted, OR converted to RR.
Krishnan et al., 7/20/2020, retrospective, USA, North America, peer-reviewed, 13 authors.
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Review |
Biancatelli et al., Frontiers in Immunology, doi:10.3389/fimmu.2020.01451 (Review) (Peer Reviewed) |
review |
Quercetin and Vitamin C: An Experimental, Synergistic Therapy for the Prevention and Treatment of SARS-CoV-2 Related Disease (COVID-19) |
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Review of the evidence for the use of vitamin C and quercetin both for prophylaxis in high-risk populations and for the treatment of COVID-19 patients. |
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Review
Review
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| Biancatelli et al., Frontiers in Immunology, doi:10.3389/fimmu.2020.01451 (Review) (Peer Reviewed) |
| Quercetin and Vitamin C: An Experimental, Synergistic Therapy for the Prevention and Treatment of SARS-CoV-2 Related Disease (COVID-19) |
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Review of the evidence for the use of vitamin C and quercetin both for prophylaxis in high-risk populations and for the treatment of COVID-19 patients.
Biancatelli et al., 6/19/2020, peer-reviewed, 4 authors.
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In Silico |
Kumar et al., VirusDisease, doi:10.1007/s13337-020-00643-6 (preprint 5/27) (Peer Reviewed) |
In silico virtual screening-based study of nutraceuticals predicts the therapeutic potentials of folic acid and its derivatives against COVID-19 |
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In Silico analysis finding that magnesium ascorbate, a form of Vitamin C, was found to be the top compound among 106 nutraceuticals for binding to Mpro of SARS-CoV-2. |
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In Silico
In Silico
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| Kumar et al., VirusDisease, doi:10.1007/s13337-020-00643-6 (preprint 5/27) (Peer Reviewed) |
| In silico virtual screening-based study of nutraceuticals predicts the therapeutic potentials of folic acid and its derivatives against COVID-19 |
In Silico analysis finding that magnesium ascorbate, a form of Vitamin C, was found to be the top compound among 106 nutraceuticals for binding to Mpro of SARS-CoV-2.
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Kumar et al., 5/27/2020, peer-reviewed, 3 authors.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
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