Common anti-oxidant vitamin C as an anti-infective agent with remedial role on SARS-CoV-2 infection. An update

Submitted: February 16, 2021
Accepted: May 26, 2021
Published: July 19, 2021
Abstract Views: 1650
PDF: 562
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Authors

Coronavirus disease 2019 (COVID-19) has led to a worldwide multifaceted crisis. The medical world agonizes to contend with the problem, but a string of tested medications has been proven unavailing. Vitamin C is well described as a salutary antioxidant and some trials conclude that it may be a potential antiviral drug. In high doses, vitamin C can alternate crucial steps in the pathogenesis of sepsis and acute respiratory distress syndrome. This dynamic was the driving force behind trials around the world that tried immunonutrition as a weapon against clinical entities. We summarize the mechanisms of action of vitamin C and its role against infections and the current literature referring to the potential role of vitamin C in SARS-CoV-2 infection, also as a contingent treatment agent.

Dimensions

Altmetric

PlumX Metrics

Downloads

Download data is not yet available.

Citations

Cossarizza A, De Biasi S, Guaraldi G, et al. SARS-CoV-2, the virus that causes COVID-19: Cytometry and the new challenge for global health. Cytometry A 2020;97:340-3. DOI: https://doi.org/10.1002/cyto.a.24002
Siemieniuk RA, Bartoszko JJ, Ge L, et al. Drug treatments for covid-19: living systematic review and network meta-analysis. BMJ 2020;370:m2980.
Our World In Data [Internet], Coronavirus (COVID-19) vaccinations. Dec 13, 2020 – Feb 15, 2021. Available from: https://ourworldindata.org/covid-vaccinations
Yuan P, Ai P, Liu Y, et al. Safety, tolerability, and immunogenicity of COVID-19 vaccines: A systematic review and meta-analysis. medRxiv 2020;2020.11.03.20224998. DOI: https://doi.org/10.1101/2020.11.03.20224998
Giamarellos-Bourboulis EJ, Netea MG, Rovina N, et al. Complex immune dysregulation in COVID-19 patients with severe respiratory failure. Cell Host Microbe 2020;27:992-1000.e3. DOI: https://doi.org/10.1016/j.chom.2020.04.009
Huang I, Pranata R, Lim MA, et al. C-reactive protein, procalcitonin, D-dimer, and ferritin in severe coronavirus disease-2019: a meta-analysis. Ther Adv Respir Dis 2020;14. Online ahed of print. DOI: https://doi.org/10.1177/1753466620937175
Alamdari DH, Moghaddam AB, Amini S, et al. Application of methylene blue -vitamin C -N-acetyl cysteine for treatment of critically ill COVID-19 patients, report of a phase-I clinical trial. Eur J Pharmacol 2020;885:173494. DOI: https://doi.org/10.1016/j.ejphar.2020.173494
Zhang J, Rao X, Li Y, et al. Pilot trial of high-dose vitamin C in critically ill COVID-19 patients. Ann Intensive Care 2021;11:5. DOI: https://doi.org/10.1186/s13613-020-00792-3
Hiedra R, Lo KB, Elbashabsheh M, et al. The use of IV vitamin C for patients with COVID-19: a case series. Expert Rev Anti Infect Ther 2020;18:1259-61. DOI: https://doi.org/10.1080/14787210.2020.1794819
Zhao B, Ling Y, Li J, et al. Beneficial aspects of high dose intravenous vitamin C on patients with COVID-19 pneumonia in severe condition: a retrospective case series study. Ann Palliat Med 2021;10:1599-609. DOI: https://doi.org/10.21037/apm-20-1387
JamaliMoghadamSiahkali S, Zarezade B, Koolaji S, et al. Safety and effectiveness of high-dose vitamin C in patients with COVID-19: a randomized open-label clinical trial. Eur J Med Res 2021;26:20. DOI: https://doi.org/10.1186/s40001-021-00490-1
Burugu HR, Kandi V, Kutikuppala LVS, Suvvari TK. Activities of serum ferritin and treatment outcomes among COVID-19 patients treated with vitamin c and dexamethasone: An uncontrolled single-center observational study. Cureus 2020;12:e11442. DOI: https://doi.org/10.7759/cureus.11442
Kumari P, Dembra S, Dembra P, et al. The role of vitamin C as adjuvant therapy in COVID-19. Cureus 2020;12:e11779. DOI: https://doi.org/10.7759/cureus.11779
Thomas S, Patel D, Bittel B, et al. 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. JAMA Netw Open 2021;4:e210369. DOI: https://doi.org/10.1001/jamanetworkopen.2021.0369
Arvinte C, Singh M, Marik PE. 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. Med Drug Discov 2020;8:100064. DOI: https://doi.org/10.1016/j.medidd.2020.100064
Chiscano-Camón L, Ruiz-Rodriguez JC, Ruiz-Sanmartin A, et al. Vitamin C levels in patients with SARS-CoV-2-associated acute respiratory distress syndrome. Crit Care 2020;24:522. DOI: https://doi.org/10.1186/s13054-020-03249-y
Pincemail J, Cavalier E, Charlier C, et al. Oxidative stress status in COVID-19 patients hospitalized in intensive care unit for severe pneumonia. A pilot study. Antioxidants (Basel) 2021;10:257. DOI: https://doi.org/10.3390/antiox10020257
Frei B, England L, Ames BN. Ascorbate is an outstanding antioxidant in human blood plasma. Proc Natl Acad Sci USA 1989;86:6377-81. DOI: https://doi.org/10.1073/pnas.86.16.6377
Tsukaguchi H, Tokui T, Mackenzie B, et al. A family of mammalian Na+-dependent L-ascorbic acid transporters. Nature 1999;399:70-5. DOI: https://doi.org/10.1038/19986
Asard H, May J, Smirnoff N. Vitamin C: Its functions and biochemistry in animals and plants. Chichester Taylor & Francis; 2004. DOI: https://doi.org/10.1201/9780203500002
Jovic TH, Ali SR, Ibrahim N, et al. Could vitamins help in the fight against COVID-19. Nutrients 2020;12:E2550. DOI: https://doi.org/10.3390/nu12092550
Levine M. New concepts in the biology and biochemistry of ascorbic acid. N Engl J Med 1986;314:892-902. DOI: https://doi.org/10.1056/NEJM198604033141407
Infusino F, Marazzato M, Mancone M, et al. Diet supplementation, probiotics, and nutraceuticals in SARS-CoV-2 infection: A scoping review. Nutrients 2020;12:E1718. DOI: https://doi.org/10.3390/nu12061718
Kim HJ, Lee SI, Lee DH, et al. Ascorbic acid synthesis due to L-gulono-1,4-lactone oxidase expression enhances NO production in endothelial cells. Biochem Biophys Res Commun 2006;345:1657-62. DOI: https://doi.org/10.1016/j.bbrc.2006.05.090
Jackson TS, Xu A, Vita JA, Keaney JF. Ascorbate prevents the interaction of superoxide and nitric oxide only at very high physiological concentrations. Circ Res 1998;83:916-22. DOI: https://doi.org/10.1161/01.RES.83.9.916
Carr A, Frei B. Does vitamin C act as a pro-oxidant under physiological conditions. FASEB J 1999;13:1007-24. DOI: https://doi.org/10.1096/fasebj.13.9.1007
Smith AR, Visioli F, Hagen TM. Vitamin C matters: increased oxidative stress in cultured human aortic endothelial cells without supplemental ascorbic acid. FASEB J 2002;16:1102-4. DOI: https://doi.org/10.1096/fj.01-0825fje
Tyml K, Li F, Wilson JX. Septic impairment of capillary blood flow requires nicotinamide adenine dinucleotide phosphate oxidase but not nitric oxide synthase and is rapidly reversed by ascorbate through an endothelial nitric oxide synthase-dependent mechanism. Crit Care Med 2008;36:2355-62. DOI: https://doi.org/10.1097/CCM.0b013e31818024f6
Fisher BJ, Kraskauskas D, Martin EJ, et al. Mechanisms of attenuation of abdominal sepsis induced acute lung injury by ascorbic acid. Am J Physiol Lung Cell Mol Physiol 2012;303:L20-32. DOI: https://doi.org/10.1152/ajplung.00300.2011
Iddir M, Brito A, Dingeo G, et al. Strengthening the immune system and reducing inflammation and oxidative stress through diet and nutrition: considerations during the COVID-19 crisis. Nutrients 2020;12:E1562. DOI: https://doi.org/10.3390/nu12061562
de la Fuente M, Ferrández MD, Burgos MS, et al. Immune function in aged women is improved by ingestion of vitamins C and E. Can J Physiol Pharmacol 1998;76:373-80. DOI: https://doi.org/10.1139/y98-038
Goldschmidt MC, Masin WJ, Brown LR, Wyde PR. The effect of ascorbic acid deficiency on leukocyte phagocytosis and killing of actinomyces viscosus. Int J Vitam Nutr Res 1988;58:326-34.
Nungester WJ, Ames AM. The relationship between ascorbic acid and phagocytic activity. J Infect Dis 1948;83:50-4. DOI: https://doi.org/10.1093/infdis/83.1.50
Johnston CS, Huang SN. Effect of ascorbic acid nutriture on blood histamine and neutrophil chemotaxis in guinea pigs. J Nutr 1991;121:126-30. DOI: https://doi.org/10.1093/jn/121.1.126
Johnston CS, Martin LJ, Cai X. Antihistamine effect of supplemental ascorbic acid and neutrophil chemotaxis. J Am Coll Nutr 1992;11:172-6. DOI: https://doi.org/10.1080/07315724.1992.12098241
Mohammed BM, Fisher BJ, Kraskauskas D, et al. Vitamin C: a novel regulator of neutrophil extracellular trap formation. Nutrients 2013;5:3131-51. DOI: https://doi.org/10.3390/nu5083131
Czaikoski PG, Mota JM, Nascimento DC, et al. Neutrophil extracellular traps induce organ damage during experimental and clinical sepsis. PLoS On. 2016;11:e0148142. DOI: https://doi.org/10.1371/journal.pone.0148142
Prinz W, Bortz R, Bregin B, Hersch M. The effect of ascorbic acid supplementation on some parameters of the human immunological defence system. Int J Vitam Nutr Res 1977;47:248-57.
Heyland DK, Dhaliwal R, Suchner U, Berger MM. Antioxidant nutrients: a systematic review of trace elements and vitamins in the critically ill patient. Intensive Care Med 2005;31:327-37. DOI: https://doi.org/10.1007/s00134-004-2522-z
Cárcamo JM, Bórquez-Ojeda O, Golde DW. Vitamin C inhibits granulocyte macrophage-colony-stimulating factor-induced signaling pathways. Blood 2002;99:3205-12. DOI: https://doi.org/10.1182/blood.V99.9.3205
Gao YL, Lu B, Zhai JH, et al. The parenteral vitamin C improves sepsis and sepsis-induced multiple organ dysfunction syndrome via preventing cellular immunosuppression. Mediators Inflamm 2017;2017:4024672. DOI: https://doi.org/10.1155/2017/4024672
Fisher BJ, Seropian IM, Kraskauskas D, et al. Ascorbic acid attenuates lipopolysaccharide-induced acute lung injury. Crit Care Med 2011;39:1454-60. DOI: https://doi.org/10.1097/CCM.0b013e3182120cb8
Cárcamo JM, Pedraza A, Bórquez-Ojeda O, Golde DW. Vitamin C suppresses TNF alpha-induced NF kappa B activation by inhibiting I kappa B alpha phosphorylation. Biochemistry 2002;41:12995-3002. DOI: https://doi.org/10.1021/bi0263210
Mikirova N, Riordan N, Casciari J. Modulation of Cytokines in Cancer Patients by Intravenous Ascorbate Therapy. Med Sci Monit 2016;22:14-25. DOI: https://doi.org/10.12659/MSM.895368
Ma S, Sun S, Li J, et al. Single-cell transcriptomic atlas of primate cardiopulmonary aging. Cell Res 2021;31:415-32. DOI: https://doi.org/10.1038/s41422-020-00412-6
Anderson TJ, Uehata A, Gerhard MD, et al. Close relation of endothelial function in the human coronary and peripheral circulations. J Am Coll Cardiol 1995;26:1235-41. DOI: https://doi.org/10.1016/0735-1097(95)00327-4
Lykkesfeldt J, Poulsen HE. Is vitamin C supplementation beneficial? Lessons learned from randomised controlled trials. Br J Nutr 2010;103:1251-9. DOI: https://doi.org/10.1017/S0007114509993229
Levine M, Rumsey SC, Daruwala R, et al. Criteria and recommendations for vitamin C intake. JAMA 1999;281:1415-23. DOI: https://doi.org/10.1001/jama.281.15.1415
Gey KF, Moser UK, Jordan P, et al. Increased risk of cardiovascular disease at suboptimal plasma concentrations of essential antioxidants: an epidemiological update with special attention to carotene and vitamin C. Am J Clin Nutr 1993;57:S787-97. DOI: https://doi.org/10.1093/ajcn/57.5.787S
Jacob RA, Skala JH, Omaye ST. Biochemical indices of human vitamin C status. Am J Clin Nutr 1987;46:818-26. DOI: https://doi.org/10.1093/ajcn/46.5.818
Caccialanza R, Laviano A, Lobascio F, et al. Early nutritional supplementation in non-critically ill patients hospitalized for the 2019 novel coronavirus disease (COVID-19): Rationale and feasibility of a shared pragmatic protocol. Nutrition 2020;74:110835. DOI: https://doi.org/10.1016/j.nut.2020.110835
Fowler AA, Syed AA, Knowlson S, et al. Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis. J Transl Med 2014;12:32. DOI: https://doi.org/10.1186/1479-5876-12-32
Hudson EP, Collie JT, Fujii T, et al. Pharmacokinetic data support 6-hourly dosing of intravenous vitamin C to critically ill patients with septic shock. Crit Care Resusc 2019;21:236-42.
de Grooth HJ, Manubulu-Choo WP, Zandvliet AS, et al. Vitamin C pharmacokinetics in critically ill patients: A randomized trial of four IV regimens. Chest 2018;153:1368-77. DOI: https://doi.org/10.1016/j.chest.2018.02.025
Levine M, Conry-Cantilena C, Wang Y, et al. Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Proc Natl Acad Sci USA 1996;93:3704-9. DOI: https://doi.org/10.1073/pnas.93.8.3704
Sasazuki S, Sasaki S, Tsubono Y, et al. Effect of vitamin C on common cold: randomized controlled trial. Eur J Clin Nutr 2006;60:9-17. DOI: https://doi.org/10.1038/sj.ejcn.1602261
Van Straten M, Josling P. Preventing the common cold with a vitamin C supplement: a double-blind, placebo-controlled survey. Adv Ther 2002;19:151-9. DOI: https://doi.org/10.1007/BF02850271
Johnston CS, Barkyoumb GM, Schumacher SS. Vitamin C supplementation slightly improves physical activity levels and reduces cold incidence in men with marginal vitamin C status: a randomized controlled trial. Nutrients 2014;6:2572-83. DOI: https://doi.org/10.3390/nu6072572
Gorton HC, Jarvis K. The effectiveness of vitamin C in preventing and relieving the symptoms of virus-induced respiratory infections. J Manipulative Physiol Ther 1999;22:530-3. DOI: https://doi.org/10.1016/S0161-4754(99)70005-9
Audera C, Patulny RV, Sander BH, Douglas RM. Mega-dose vitamin C in treatment of the common cold: a randomised controlled trial. Med J Aust 2001;175:359-62. DOI: https://doi.org/10.5694/j.1326-5377.2001.tb143618.x
Hemilä H, Chalker E. Vitamin C for preventing and treating the common cold. Cochrane Database Syst Rev 2013;CD000980. DOI: https://doi.org/10.1002/14651858.CD000980.pub4
Lopez BS, Yamamoto M, Utsumi K, et al. A clinical pilot study of lignin--ascorbic acid combination treatment of herpes simplex virus. In Vivo 2009;23:1011-6.
Müller F, Svardal AM, Nordoy I, et al. Virological and immunological effects of antioxidant treatment in patients with HIV infection. Eur J Clin Invest 2000;30:905-14. DOI: https://doi.org/10.1046/j.1365-2362.2000.00727.x
Mikirova N, Hunninghake R. Effect of high dose vitamin C on Epstein-Barr viral infection. Med Sci Monit 2014;20:725-32. DOI: https://doi.org/10.12659/MSM.890423
Galley HF, Howdle PD, Walker BE, Webster NR. The effects of intravenous antioxidants in patients with septic shock. Free Radic Biol Med 1997;23:768-74. DOI: https://doi.org/10.1016/S0891-5849(97)00059-2
Carr AC, Rosengrave PC, Bayer S, et al. Hypovitaminosis C and vitamin C deficiency in critically ill patients despite recommended enteral and parenteral intakes. Crit Care 2017;21:300. DOI: https://doi.org/10.1186/s13054-017-1891-y
Pontes-Arruda A, Aragão AM, Albuquerque JD. Effects of enteral feeding with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants in mechanically ventilated patients with severe sepsis and septic shock. Crit Care Med 2006;34:2325-33. DOI: https://doi.org/10.1097/01.CCM.0000234033.65657.B6
Wani SJ, Mufti SA, Jan RA, et al. Combination of vitamin C, thiamine and hydrocortisone added to standard treatment in the management of sepsis: results from an open label randomised controlled clinical trial and a review of the literature. Infect Dis (Lond) 2020;52:271-8. DOI: https://doi.org/10.1080/23744235.2020.1718200
Fujii T, Luethi N, Young PJ, et al. Effect of vitamin C, hydrocortisone, and thiamine vs hydrocortisone alone on time alive and free of vasopressor support among patients with septic shock: The VITAMINS randomized clinical trial. JAMA. 2020 02 4;323:423-31. DOI: https://doi.org/10.1001/jama.2019.22176
Colunga Biancatelli RML, Berrill M, Catravas JD, Marik PE. Quercetin and vitamin C: An experimental, synergistic therapy for the prevention and treatment of SARS-CoV-2 related disease (COVID-19). Front Immunol 2020;11:1451. DOI: https://doi.org/10.3389/fimmu.2020.01451
Li R, Wu K, Li Y, et al. Integrative pharmacological mechanism of vitamin C combined with glycyrrhizic acid against COVID-19: findings of bioinformatics analyses. Brief Bioinform 2021;22:1161-74. DOI: https://doi.org/10.1093/bib/bbaa141
Fowler AA, Truwit JD, Hite RD, et al. Effect of vitamin C infusion on organ failure and biomarkers of inflammation and vascular injury in patients with sepsis and severe acute respiratory failure: The CITRIS-ALI randomized clinical trial. JAMA 2019322:1261-70.
Li C, Bo L, Liu W, et al. Enteral immunomodulatory diet (omega-3 fatty acid, γ-linolenic acid and antioxidant supplementation) for acute lung injury and acute respiratory distress syndrome: An updated systematic review and meta-analysis. Nutrients 2015;7:5572-85. DOI: https://doi.org/10.3390/nu7075239
Dushianthan A, Cusack R, Burgess VA, et al. Immunonutrition for adults with ARDS: Results from a Cochrane systematic review and meta-analysis. Respir Care 2020;65:99-110. DOI: https://doi.org/10.4187/respcare.06965
Li J. Evidence is stronger than you think: a meta-analysis of vitamin C use in patients with sepsis. Crit Care 2018;22:258. DOI: https://doi.org/10.1186/s13054-018-2191-x
Hemilä H, Chalker E. Vitamin C can shorten the length of stay in the ICU: A meta-analysis. Nutrients 2019;11:E708. DOI: https://doi.org/10.3390/nu11040708
Hemilä H, Chalker E. Vitamin C may reduce the duration of mechanical ventilation in critically ill patients: a meta-regression analysis. J Intensive Care 2020;8:15. DOI: https://doi.org/10.1186/s40560-020-0432-y
Farjana M, Moni A, Sohag AAM, et al. Repositioning vitamin C as a promising option to alleviate complications associated with COVID-19. Infect Chemothe. 2020;52:461-77. DOI: https://doi.org/10.3947/ic.2020.52.4.461
Morelli MB, Gambardella J, Castellanos V, et al. Vitamin C and cardiovascular disease: An update. Antioxidants (Basel) 2020;9:E1227. DOI: https://doi.org/10.3390/antiox9121227
Kashiouris MG, L'Heureux M, Cable CA, et al. The emerging role of vitamin C as a treatment for sepsis. Nutrients 2020;12:E292. DOI: https://doi.org/10.3390/nu12020292
Waqas Khan HM, Parikh N, Megala SM, Predeteanu GS. Unusual early recovery of a critical COVID-19 patient after administration of intravenous vitamin C. Am J Case Rep 2020;21:e925521. DOI: https://doi.org/10.12659/AJCR.925521
Douedi S, Miskoff J. Novel coronavirus 2019 (COVID-19): A case report and review of treatments. Medicine (Baltimore) 2020;99:e20207. DOI: https://doi.org/10.1097/MD.0000000000020207
Cossey LN, Rahim F, Larsen CP. Oxalate nephropathy and intravenous vitamin C. Am J Kidney Dis 2013;61:1032-5. DOI: https://doi.org/10.1053/j.ajkd.2013.01.025
Fontana F, Cazzato S, Giovanella S, et al. Oxalate nephropathy caused by excessive vitamin C administration in 2 patients with COVID-19. Kidney Int Rep 2020;5:1815-22. DOI: https://doi.org/10.1016/j.ekir.2020.07.008
Front Line COVID-19 Critical Care Alliance Group. MATH+ Hospital Treatment Protocol for COVID-19. 2020, Dec 14 update.
Jin YH, Cai L, Cheng ZS, et al. A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version). Mil Med Res 2020;6;7:4.
Shanghai Clinical Treatment Expert Group for COVID-19.Comprehensive treatment and management of corona virus disease 2019: expert consensus statement from Shanghai. Chin J Infect Dis 2020;38:E016. DOI: https://doi.org/10.1142/9789811222078_0027
Vizcaychipi MP, Shovlin CL, McCarthy A, et al. Development and implementation of a COVID-19 near real-time traffic light system in an acute hospital setting. Emerg Med J 2020;37:630-6. DOI: https://doi.org/10.1136/emermed-2020-210199

How to Cite

Michailides, Christos, and Dimitrios Velissaris. 2021. “Common Anti-Oxidant Vitamin C As an Anti-Infective Agent With Remedial Role on SARS-CoV-2 Infection. An Update”. Monaldi Archives for Chest Disease 91 (4). https://doi.org/10.4081/monaldi.2021.1808.