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
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.
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.
-Increase SVCT 2 expression in adrenals -Decrease SVCT 1 expression in kidney
Michels et al. 2003
-Decrease in hepatic SVCT 1 expression -No change in hepatic SVCT 2 expression in aged rats
Bayram et al. 2013
Fast aging phenotypic mice
-Increase in hepatic SVCT 1 expression -No change in hepatic SVCT 2 expression
Sangani et al. 2013
Decrease SVCT2 in bone and bone marrow
Sangani et al. 2015
Apoptosis and Autophagy
SVCT2 regulates Apoptosis and Autophagy
Table 1 Selected studies showing dysregulation of vitamin C transporter (SVCT1 and SVCT2) in different pathological condition or stress.
Relative Serum Vit C Concentration
Relative Chance of Severe Covid-19
+ + [37, 38]
+ + + [7, 40]
+ + + [37, 38]
+ + [7, 40]
+ + + [37, 38]
+ + [7, 41]
+ + [37, 38]
+ + + [7, 41]
+ + 
+ + + 
+ + [42, 47]
+ + + 
+ + [36, 45]
+ + + [7, 44]
+ + + [37, 38]
+++ [14, 42]
++ [14, 42]
++ [7, 44]
+ [14, 42]
+++ [7, 44]
“+” = arbitrary unit
Table 2 Risk factors for developing severe covid-19 infections and relationship to serum vitamin C levels.
Zabet et al. 2016 Type: RCT
18-65 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 hours
Mean 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 ARDS
-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 Sepsis
30-70 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 shock
Study 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
-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 cold
-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 ARDS
20 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.
Wuhan, Hubei, China
Diammonium Glycyrrhizinate Enteric-coated Capsules (oral, 150mg, Tid), Oral Vit C tablets (.5 g) every day
Xi'an, Shaanxi, China
High dose Vit C
Wuhan, Hubei, China
IV 12g Vit C every 12 hours
IV 10g Vit C plus conventional therapy
Sherbrooke, Quebec, Canada
IV 50 mg/kg Vit C every 6 hours for 96 hours
Hydroxychloroquine 200mg plus vitamin C and zinc every day
IV 12g Vit C in .5% dextrose (total volume 200ml)
Abadan, Khuzestan Province, Iran
Hydroxychloroquine 200 mg plus oral 500 mg Vit C every 12 hours for 5 days
Hydroxychloroquine 800 mg followed by once weekly oral hydroxychloroquine 400 mg for 3 months vs. Oral Vitamin C 1,000 mg daily
Huangpu, Shanghai, China
IV 100mg/kg Vit C every day
Richmond, Virginia, United States
IV 100 mg/kg Vit C every 8 hours
Richmond, Virginia, United States
IV 50mg/kg Vit C every 6 hours for 4 days
Mashhad, Razavi Khorasan, Iran
Treatment with mixture of methylene blue, Vit C, N-acetyl cysteine
Xi'an, Shaanxi, China
High dose vitamin C plus Chinese medicine for treatment of COVID-19
Shanghai, Shanghai, China
High dose IV vitamin C treatment upon diagnosis of severe COVID-19
Philadelphia, Pennsylvania, United States
Escalating dose of oral Vit C (0.3g/kg, 0.6g/kg, 0.9g/kg) every 6 hours
Australia, United States, Germany
Trial 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
IV 1.5g Vit C 4 times a day plus hydroxychloroquine 400 mg
Sabzevar, Razavi Khorasan, Iran
Treatments of 500mg Vit C daily for a week
Kermanshah, Kermanshah, Iran
250mg Azithromycin once daily, 100 mg of doxycycline twice daily, 1.5g Vit C every 6 hours, and 500mg metformin
Trial arms: 1) Chloroquine 10 mg base/kg once a day 2) Vitamin C 1000 mg once a day
Ventura, California, United States
Quintuple therapy consisting of hydroxychloroquine, azithromycin, zinc, vit C and D for 10 days
Ventura, California, United States
hydroxychloroquine, Vitamin C, Vitamin D, and Zinc can prevent symptoms of COVID-19
Weston, Florida, United States and Cleveland, Ohio, United States
Trial 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
Various cities throughout the united states
Trial 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
High dose IV Vitamin C to patients with COVID-19
Hawthorn, Victoria, Australia
IV vitamin C, Hydroxycholorquine, azithromycin, Zinc citrate, Vitamin D3, Vitamin B12 for treating COVID-19
Portland, Oregon, United States
Trial 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
Various cities throughout the United States
Trial arms: 1) Vit C plus folic acid 2) Hydroxychloroquine plus Folic Acid 3) Hydroxychloroquine and Azithromycin
Sherbrooke, Quebec, Canada
IV 50 mg/kg Vit C every 6 hours
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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