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Aging and disease    2021, Vol. 12 Issue (1) : 14-26     DOI: 10.14336/AD.2020.0918
Commentary |
Low level of Vitamin C and dysregulation of Vitamin C transporter might be involved in the severity of COVID-19 Infection
Taylor Patterson1, Carlos M Isales2,3, Sadanand Fulzele1,2,3,*
1Department of Medicine, Augusta University, Augusta, GA 30912, USA.
2Center for Healthy Aging, Augusta University, Augusta, GA 30912, USA
3Department of Cell biology and anatomy, Augusta University, Augusta, GA 30912, USA
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The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been spreading around the world at an exponential pace, leading to millions of individuals developing the associated disease called COVID-19. Due to the novel nature and the lack of immunity within humans, there has been a collective global effort to find effective treatments against the virus. This has led the scientific community to repurpose Food and Drug Administration (FDA) approved drugs with known safety profiles. Of the many possible drugs, vitamin C has been on the shortlist of possible interventions due to its beneficial role as an immune booster and inherent antioxidant properties. Within this manuscript, a detailed discussion regarding the intracellular function and inherent properties of vitamin C is conducted. It also provides a comprehensive review of published research pertaining to the differences in expression of the vitamin C transporter under several pathophysiologic conditions. Finally, we review recently published research investigating the efficacy of vitamin C administration in treating viral infection and life-threatening conditions. Overall, this manuscript aims to present existing information regarding the extent to which vitamin C can be an effective treatment for COVID-19 and possible explanations as to why it may work in some individuals but not in others.

Keywords Vitamin C      Coronavirus      Aging      Immune response     
Corresponding Authors: Fulzele Sadanand   
About author:

Meiqian Xu and Xiaodong Su contributed equally to this work.

Just Accepted Date: 28 September 2020   Issue Date: 11 January 2021
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Patterson Taylor,Isales Carlos M,Fulzele Sadanand. Low level of Vitamin C and dysregulation of Vitamin C transporter might be involved in the severity of COVID-19 Infection[J]. Aging and disease, 2021, 12(1): 14-26.
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AuthorStudy TypePathophysiological conditionVitamin C regulation
Macias et al. 2010Human study on liver biopsieshepatocellular cholestasis, primary biliary cirrhosis, haemochromatosis and non-alcoholic steatohepatitis-Increase SVCT 1 and SVCT 2 expression
Blackburn AJ et al. 2014Human OsteoarthritisOsteoarthritisSVCT2 downregulated in OA grade 3 tissue compared to OA grade 1
Macias et al. 2010Animal studyObstructive Cholestasis-Increase SVCT 2 expression
-Decrease SVCT 1 expression
Miao et al. 2019Animal cell culture studyMelanocyte exposure to excess vitamin-Increase SVCT 2 expression
-No change SVCT 1 expression
Kang et al. 2007Human cell culture studyUVB damaged keratinocytes-No change in SVCT 1 and 2 expression
Subramanian et al. 2016Human cell culture and animal studyChronic alcohol exposureHuman cells: decrease SVCT 2 expression
Animal cells: decrease SVCT2 expression
Wu et al. 2007Animal studyStreptozotocin (STZ)-induced diabetes-Increase SVCT 2 expression in adrenals
-Decrease SVCT 1 expression in kidney
Michels et al. 2003Animal studyAged rats-Decrease in hepatic SVCT 1 expression
-No change in hepatic SVCT 2 expression in aged rats
Bayram et al. 2013Animal studyFast aging phenotypic mice-Increase in hepatic SVCT 1 expression
-No change in hepatic SVCT 2 expression
Sangani et al. 2013Animal ModelDiabeticDecrease SVCT2 in bone and bone marrow
Sangani et al. 2015Cell cultureApoptosis and AutophagySVCT2 regulates Apoptosis and Autophagy
Table 1  Selected studies showing dysregulation of vitamin C transporter (SVCT1 and SVCT2) in different pathological condition or stress.
GenderRelative Serum Vit C ConcentrationRelative Chance of Severe Covid-19
Male+ + [37, 38]+ + + [7, 40]
Female+ + + [37, 38]+ + [7, 40]
Caucasian+ + + [37, 38]+ + [7, 41]
African American+ + [37, 38]+ + + [7, 41]
Underlying Condition
Diabetes+ + [13]+ + + [7]
Hypertension+ + [42, 47]+ + + [7]
COPD+ + [36, 45]+ + + [7, 44]
No Complication+ + + [37, 38]+ [7]
0-44+++ [14, 42]+ [7]
45-64++ [14, 42]++ [7, 44]
≥65+ [14, 42]+++ [7, 44]
“+” = arbitrary unit
Table 2  Risk factors for developing severe covid-19 infections and relationship to serum vitamin C levels.
AuthorViral infectionAgeDoseOutcome
Zabet et al. 2016
Type: RCT
Sepsis18-65 years old-Vitamin C (25mg/kg) every 6 hours-28 day mortality was significantly lower (14.28% vs. 64.28%, respectively; P = 0.009)
Fowler et al. 2019
-Type: double blinded, RCT
Patients with Sepsis or ARDS for less than 24 hoursMean age of 54.8 years old-IV infusion of vitamin C (50 mg/kg in dextrose 5% in water, n=84) every 6 hours-No significant difference in mean modified SOFA score, C-reactive protein or thrombomodulin levels
-HOWEVER, strong indication of lower all-cause mortality in vit C group
Sawyer et al. 1986
Type: RCT
Patients with ARDSN/A-IV injection of vitamin C (1000 mg) every 6 hours-Dramatic reduction in mortality in vit. C group compared with control (37% vs. 71% (p<.01))
Fowler et al. 2014
Type: Double Blinded, RCT
Patients in MICU with severe Sepsis30-70 years old in low dose group
49-92 years old in high dose group 54-68 years old in placebo group
-Low dose group: IV Vitamin C (50 mg/kg/24 h, n=8)
-High dose group: IV Vitamin C (200 mg/kg/24 h, n=8) -Placebo group: IV (5% dextrose/water, n=8)
-SOFA score
-Hi: 10.4±4.4 -Lo: 10.1±2.0 -Placebo: 13.3±2.9 -Vit. C groups decreased levels of C-reactive protein and procalcitonin -No significant difference between thrombomodulin levels between groups
Marik et al. 2017
Type: Retrospective clinical study
Patients diagnosed with severe Sepsis of septic shockStudy group mean age was 58.3 years old
Control group mean age was 62.2 years old
-Patients treated with triple therapy of hydrocortisone, HDIVC, Thiamine
-Mortality rate
-Treatment: 8.5% (4 of 47) - Control: 40.4% (19 of 47) *(P < .001) -72 hr ΔSOFA -Treatment: 4.8 ± 2.4 -Control: 0.9 ± 2.7 *(P<.001)
Fujii et al. 2020
Type: RCT
Patients in ICUs suffering from SepsisMean age 61.7 years old-Intervention group: IV vitamin C (1.5 g every 6 hours), hydrocortisone (50 mg every 6 hours), thiamine (200 mg every 12 hours)
-Control group: IV hydrocortisone (50 mg every 6 hours)
-No difference in time alive and free of vasopressor administration up to 7 days between intervention group and control group (122.1 hours vs. 124.6 hours; respectively)
-ninety-day mortality -28.6% (intervention group) vs. 24.5% (control group)
Hemilä et al. 2013
Type: meta-analysis
Patients suffering from the common coldN/A-First arm: 29 trials with vitamin C supplementation
(>.2 g/day) -Second arm: 31 trials with regular vitamin C intake (>.2 g/day) -Third arm: 7 trials with therapeutic use of IV or oral vitamin C (>.2 g/day)
-First arm
-Risk Ratio of .97 -Second arm -Regular vit C reduced cold duration by 8% in adult population studied -Regular vit C reduced cold duration by 12% in children population studied -Third arm: no consistent effect of therapeutic use of vit C
Fowler et al. 2017
Type: case report
Single patient presenting with enterovirus/rhinovirus induced ARDS20 years old-high does Intravenous vitamin C injections (200 mg/kg per day)-12 hours following initiation of treatment, symptoms dramatically improved
-mechanical ventilation was discontinued 7 days post treatment -No long term ARDS sequelae noted
Table 3  Selected studies pertaining to the efficacy behind Vitamin C supplementation for patients with diseases and/or viral infections.
S.No.Identification NumberCountryParticipantInterventionRegister with
1ChiCTR2000029768Wuhan, Hubei, China60 ParticipantsDiammonium Glycyrrhizinate Enteric-coated Capsules (oral, 150mg, Tid), Oral Vit C tablets (.5 g) every
2ChiCTR2000030135Xi'an, Shaanxi, China39 ParticipantsHigh dose Vit
3NCT04264533Wuhan, Hubei, China140 participantsIV 12g Vit C every 12
4NCT04323514Palermo, Italy500 participantsIV 10g Vit C plus conventional
5NCT03680274Sherbrooke, Quebec, Canada800 participantsIV 50 mg/kg Vit C every 6 hours for 96
6NCT04326725Istanbul, Turkey80 participantsHydroxychloroquine 200mg plus vitamin C and zinc every
7IRCT20190917044805N2Tehran, Iran60 participantsIV 12g Vit C in .5% dextrose (total volume 200ml)
8IRCT20200324046850N5Abadan, Khuzestan Province, Iran40 participantsHydroxychloroquine 200 mg plus oral 500 mg Vit C every 12 hours for 5
9NCT04347889N/A1212 participantsHydroxychloroquine 800 mg followed by once weekly oral hydroxychloroquine 400 mg for 3 months vs. Oral Vitamin C 1,000 mg
10ChiCTR2000032400Huangpu, Shanghai, China120 participantsIV 100mg/kg Vit C every
11NCT04344184Richmond, Virginia, United States200 participantsIV 100 mg/kg Vit C every 8
12NCT04357782Richmond, Virginia, United States20 participantsIV 50mg/kg Vit C every 6 hours for 4
13NCT04370288Mashhad, Razavi Khorasan, Iran20 participantsTreatment with mixture of methylene blue, Vit C, N-acetyl
14ChiCTR2000032717Xi'an, Shaanxi, China60 participantsHigh dose vitamin C plus Chinese medicine for treatment of
15ChiCTR2000032716Shanghai, Shanghai, China12 participantsHigh dose IV vitamin C treatment upon diagnosis of severe
16NCT04363216Philadelphia, Pennsylvania, United States66 participantsEscalating dose of oral Vit C (0.3g/kg, 0.6g/kg, 0.9g/kg) every 6
17ACTRN12620000557932Australia, United States, Germany200 participantsTrial arms:
1)Hydroxychloroquine plus zinc plus Vit D3/B12 plus azithromycin plus IV Vitamin C 2) Hydroxychloroquine plus zinc plus Vit D3/B12 plus azithromycin
18IRCT20200411047025N1Tehran, Iran110 participantsIV 1.5g Vit C 4 times a day plus hydroxychloroquine 400
19IRCT20140305016852N4Sabzevar, Razavi Khorasan, Iran30 participantsTreatments of 500mg Vit C daily for a
20IRCT20200418047121N1Kermanshah, Kermanshah, Iran40 participants250mg Azithromycin once daily, 100 mg of doxycycline twice daily, 1.5g Vit C every 6 hours, and 500mg
21TCTR20200404004Bangkok, Thailand400 participantsTrial arms:
1) Chloroquine 10 mg base/kg once a day
2) Vitamin C 1000 mg once a day
22NCT04334512Ventura, California, United States600 participantsQuintuple therapy consisting of hydroxychloroquine, azithromycin, zinc, vit C and D for 10
23NCT04335084Ventura, California, United States600 participantshydroxychloroquine, Vitamin C, Vitamin D, and Zinc can prevent symptoms of
24NCT04342728Weston, Florida, United States
and Cleveland, Ohio, United States
520 participantsTrial arms:
1)Vit C 8000mg in 2-3 doses
2)Zinc Gluconate 50mg daily
3)Vit C 8000mg plus Zinc gluconate 50mg daily
4)Standard of care
25NCT04328961Various cities throughout the united states2000 participantsTrial arms:
1) Oral 500mg Vit C daily for 3 days then 250mg for 11 days
2) 400mg Hydroxychloroquine for 3 days then 200mg for 11 days
26ChiCTR2000033050Shanghai, China110 participantsHigh dose IV Vitamin C to patients with
27NCT04395768Hawthorn, Victoria, Australia200 participantsIV vitamin C, Hydroxycholorquine, azithromycin, Zinc citrate, Vitamin D3, Vitamin B12 for treating
28NCT04334967Portland, Oregon, United States13 participantsTrial arms:
1) 800mg hydroxychloroquine on day 1, 400mg on days 2-5
2) 2000mg of Vit C on day 1, 1000mg on days 2-5
29NCT04354428Various cities throughout the United States630 participantsTrial arms:
1) Vit C plus folic acid
2) Hydroxychloroquine plus Folic Acid
3) Hydroxychloroquine and Azithromycin
30NCT04401150Sherbrooke, Quebec, Canada800 participantsIV 50 mg/kg Vit C every 6
Table 4  Ongoing clinical trials register for using Vitamin C alone or in combination with other drug for treatment of COVID-19 infections.
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