Vitamin C for COVID-19: real-time analysis of all 17 studies

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5/3	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
	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..
5/3	Details Source PDF In Silico 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
	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. Malla et al., 5/3/2021, preprint, 9 authors.
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4/14	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
	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.
4/14	Details Source PDF Late treatment study Late treatment study
	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. 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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4/2	Late	Sulaimen 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
	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..
4/2	Details Source PDF Late treatment study Late treatment study
	Sulaimen 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. Sulaimen et al., 4/2/2021, retrospective, Saudi Arabia, Middle East, preprint, 12 authors.
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3/2	Early	Hemilä et al., Research Square, doi:10.21203/rs.3.rs-289381/v1 (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
	Reanalysis of Thomas et al. showing that vitamin C increased the recovery rate by 70%, p = 0.025.
3/2	Details Source PDF Early treatment study Early treatment study
	Hemilä et al., Research Square, doi:10.21203/rs.3.rs-289381/v1 (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. Hemilä et al., 3/2/2021, preprint, 3 authors.
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2/26	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
	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..
2/26	Details Source PDF Late treatment study Late treatment study
	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. 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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2/12	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
	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].
2/12	Details Source PDF Early treatment study Early treatment study
	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]. [1] pubpeer.com/publications/6DFC3BD2E1DAA79A9BBD1DAF5D9BB4#1 [2] patrickholford.com/blog/vitamin-c-speeds-up-covid-recovery 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.
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2/1	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
	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.
2/1	Details Source PDF Late treatment study Late treatment study
	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. Zhao et al., 2/1/2021, peer-reviewed, 14 authors.
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1/27	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
	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..
1/27	Details Source PDF Late treatment study Late treatment study
	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. Xing et al., 1/27/2021, peer-reviewed, 13 authors.
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1/9	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
	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 ..
1/9	Details Source PDF Late treatment study Late treatment study
	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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12/7	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
	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..
12/7	Details Source PDF Review Review
	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. Holford et al., 12/7/2020, peer-reviewed, 7 authors.
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11/30	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
	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.
11/30	Details Source PDF Late treatment study Late treatment study
	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. 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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11/3	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
	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, ..
11/3	Details Source PDF Pre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study
	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 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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10/1	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
	Retrospective 176 hospitalized patients, 96 treated with oral vitamin C (from 500mg to 1500mg daily), showing lower mortality with treatment.
10/1	Details Source PDF Late treatment study Late treatment study
	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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9/8	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
	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.
9/8	Details Source PDF Levels Analysis of outcomes based on serum 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
	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. Arvinte et al., 9/8/2020, peer-reviewed.
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8/26	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
	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).
8/26	Details Source PDF Levels Analysis of outcomes based on serum 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
	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). Chiscano-Camón et al., 8/26/2020, peer-reviewed, mean age 59.0, 5 authors.
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8/10	Late	Zhang et al., Research Square, doi:10.21203/rs.3.rs-52778/v2 (Preprint)	death, ↓50.0%, p=0.31	Pilot Trial of High-dose vitamin C in critically ill COVID-19 patients
	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.
8/10	Details Source PDF Late treatment study Late treatment study
	Zhang et al., Research Square, doi:10.21203/rs.3.rs-52778/v2 (Preprint)
	Pilot Trial of High-dose vitamin C in critically ill COVID-19 patients
	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. risk of death, 50.0% lower, RR 0.50, p = 0.31, treatment 6 of 27 (22.2%), control 11 of 29 (37.9%), 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, preprint, 11 authors.
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8/1	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
	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 ..
8/1	Details Source PDF Late treatment study Late treatment study
	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. Hiedra et al., 8/1/2020, peer-reviewed, 8 authors.
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7/25	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?
	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-..
7/25	Details Source PDF Review Review
	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. Feyaerts et al., 7/25/2020, peer-reviewed, 2 authors.
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5/27	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
	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.
5/27	Details Source PDF In Silico 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
	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. Kumar et al., 5/27/2020, peer-reviewed, 3 authors.
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