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Vitamin C—An Adjunctive Therapy for Respiratory Infection, Sepsis and COVID-19

Holford et al., Nutrients, doi:10.3390/nu12123760
Dec 2020  
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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, 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., 7 Dec 2020, peer-reviewed, 7 authors.
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Vitamin C—An Adjunctive Therapy for Respiratory Infection, Sepsis and COVID-19
Patrick Holford, Anitra C Carr, Thomas H Jovic, Stephen R Ali, Iain S Whitaker, Paul E Marik, A David Smith
Nutrients, doi:10.3390/nu12123760
There are limited proven therapies for COVID-19. Vitamin C's antioxidant, anti-inflammatory and immunomodulating effects make it a potential therapeutic candidate, both for the prevention and amelioration of COVID-19 infection, and as an adjunctive therapy in the critical care of COVID-19. This literature review focuses on vitamin C deficiency in respiratory infections, including COVID-19, and the mechanisms of action in infectious disease, including support of the stress response, its role in preventing and treating colds and pneumonia, and its role in treating sepsis and COVID-19. The evidence to date indicates that 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. Further trials are urgently warranted. 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 persons with COVID-19.
Author Contributions: Conceptualisation, P.H.; writing-original draft preparation, P.H., T.H.J., S.R.A, I.S.W., A.C.C.; writing-review and editing, P.E.M., A.D.S.; visualisation, T.H.J., S.R.A. All authors have read and agreed to the published version of the manuscript. Conflicts of Interest: The authors declare no conflict of interest.
Arvinte, Singh, Marik, 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, doi:10.1016/j.medidd.2020.100064
Atherton, Kratzing, Fisher, The effect of ascorbic acid on infection chick-embryo ciliated tracheal organ cultures by coronavirus, Arch. Virol, doi:10.1007/BF01317848
Auer, Auer, Rodgers, The effect of ascorbic acid ingestion on the biochemical and physicochemical risk factors associated with calcium oxalate kidney stone formation, Clin. Chem. Lab. Med, doi:10.1515/CCLM.1998.027
Bakaev, Duntau, Ascorbic acid in blood serum of patients with pulmonary tuberculosis and pneumonia, Int. J. Tuberc. Lung. Dis
Barabutis, Khangoora, Marik, Catravas, Hydrocortisone and ascorbic acid synergistically prevent and repair lipopolysaccharide-induced pulmonary endothelial barrier dysfunction, Chest, doi:10.1016/j.chest.2017.07.014
Bates, Collins, Cox, Nicholson, Page et al., National Diet and Nutrition Survey Years 1 to 9 of the Rolling Programme
Bates, Prentice, Cole, Van Der Pols, Doyle et al., Micronutrients: Highlights and research challenges from the 1994-5 National Diet and Nutrition Survey of people aged 65 years and over, Br. J. Nutr, doi:10.1017/S0007114599001063
Berger, Bischoff-Ferrari, Zimmermann, Herter, Spieldenner et al., White Paper on Nutritional Status in Supporting a Well-Functioning Immune System for Optimal Health with a Recommendation for Switzerland
Biancatelli, Berrill, Marik, The antiviral properties of vitamin C, Expert Rev. Anti Infect. Ther, doi:10.1080/14787210.2020.1706483
Blanco-Melo, Nilsson-Payant, Liu, Uhl, Hoagland et al., Imbalanced host response to SARS-CoV-2 drives development of COVID-19, Cell, doi:10.1016/j.cell.2020.04.026
Bosmann, Ward, The inflammatory response in sepsis, Trends Immunol, doi:10.1016/
Brinkmann, Reichard, Goosmann, Fauler, Uhlemann et al., Neutrophil extracellular traps kill bacteria, Science, doi:10.1126/science.1092385
Calder, Carr, Gombart, Eggersdorfer, Optimal nutritional status for a well-functioning immune system is an important factor to protect against viral infections, Nutrients, doi:10.3390/nu12041181
Calder, Nutrition, immunity and COVID-19, BMJ Nutr. Prev. Health, doi:10.1136/bmjnph-2020-000085
Carr, Is the VITAMINS RCT indicating potential redundancy between corticosteroids and vitamin C?, Crit. Care, doi:10.1186/s13054-020-02853-2
Carr, Maggini, Vitamin C and immune function, Nutrients, doi:10.3390/nu9111211
Carr, Rosengrave, Bayer, Chambers, Mehrtens et al., Hypovitaminosis C and vitamin C deficiency in critically ill patients despite recommended enteral and parenteral intakes, Crit. Care, doi:10.1186/s13054-017-1891-y
Carr, Rowe, Factors affecting vitamin C status and prevalence of deficiency: A global health perspective, Nutrients, doi:10.3390/nu12071963
Carr, Spencer, Dixon, Chambers, Patients with community acquired pneumonia exhibit depleted vitamin C status and elevated oxidative stress, Nutrients, doi:10.3390/nu12051318
Carr, Vitamin C in pneumonia and sepsis
Cathcart, Vitamin C, titrating to bowel tolerance, anascorbemia, and acute induced scurvy, Med. Hypotheses, doi:10.1016/0306-9877(81)90126-2
Chakrabarti, Banerjee, Dehydroascorbic acid level in blood of patients suffering from various infectious diseases, Proc. Soc. Exp. Biol. Med, doi:10.3181/00379727-88-21659
Chen, Luo, Yuan, Wang, Yang et al., Vitamin C mitigates oxidative stress and tumor necrosis factor-alpha in severe community-acquired pneumonia and LPS-induced macrophages, Mediators Inflamm, doi:10.1155/2014/426740
Chen, Vissers, CRC Press/Taylor & Francis
Chiscano-Camón, Ruiz-Rodriguez, Ruiz-Sanmartin, Roca, Ferrer, Vitamin C levels in patients with SARS-CoV-2-associated acute respiratory distress syndrome, Crit. Care, doi:10.1186/s13054-020-03249-y
Curhan, Willett, Speizer, Stampfer, Intake of vitamins B6 and C and the risk of kidney stones in women, J. Am. Soc. Nephrol
Dahl, Degre, The effect of ascorbic acid on production of human interferon and the antiviral activity in vitro, Acta Pathol. Microbiol. Scand. B, doi:10.1111/j.1699-0463.1976.tb01938.x
Davelaar, Bos, Ascorbic acid and infectious bronchitis infections in broilers, Avian Pathol, doi:10.1080/03079459208418879
De Grooth, Manubulu-Choo, Zandvliet, Spoelstra-De Man, Girbes et al., Vitamin-C pharmacokinetics in critically ill patients: A randomized trial of four intravenous regimens, Chest, doi:10.1016/j.chest.2018.02.025
Doise, Aho, Quenot, Guilland, Zeller et al., Plasma antioxidant status in septic critically ill patients: A decrease over time, Fundam. Clin. Pharmacol, doi:10.1111/j.1472-8206.2008.00573.x
Drouin, Godin, Page, The genetics of vitamin C loss in vertebrates, Curr. Genomics
Erol, Saglam, Saglam, Erol, Altun et al., The protection potential of antioxidant vitamins against acute respiratory distress syndrome: A rat trial, Inflammation
Evans-Olders, Eintracht, Hoffer, Metabolic origin of hypovitaminosis C in acutely hospitalized patients, Nutrition, doi:10.1016/j.nut.2009.08.015
Fain, Paries, Jacquart, Le Moel, Kettaneh et al., Hypovitaminosis C in hospitalized patients, Eur. J. Intern. Med, doi:10.1016/j.ejim.2003.08.006
Fisher, Kashiouris, Vitamin C for sepsis and acute respiratory failure-Reply, JAMA, doi:10.1001/jama.2019.21987
Fisher, Kraskauskas, Martin, Farkas, Wegelin et al., Mechanisms of attenuation of abdominal sepsis induced acute lung injury by ascorbic acid, Am. J. Physiol. Lung Cell Mol. Physiol, doi:10.1152/ajplung.00300.2011
Fowler, Iii, None
Fowler, Iii, None
Fowler, Syed, Knowlson, Sculthorpe, Farthing et al., Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis, J. Transl. Med, doi:10.1186/1479-5876-12-32
Fujii, Luethi, Young, Frei, Eastwood 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, doi:10.1001/jama.2019.22176
Gan, Eintracht, Hoffer, Vitamin C deficiency in a university teaching hospital, J. Am. Coll. Nutr, doi:10.1080/07315724.2008.10719721
Gan, Rosoman, Henshaw, Noble, Georgius et al., COVID-19 as a viral functional ACE2 deficiency disorder with ACE2 related multi-organ disease, Med. Hypotheses, doi:10.1016/j.mehy.2020.110024
Gerster, High-dose vitamin C: A risk for persons with high iron stores?, Int. J. Vitam. Nutr. Res, doi:10.1024/0300-9831.69.2.67
Glazebrook, Thomson, The administration of vitamin C in a large institution and its effect on general health and resistance to infection, J. Hyg, doi:10.1017/S0022172400012596
Grommes, Soehnlein, Contribution of neutrophils to acute lung injury, Mol. Med
Habib, Ahmed, Early adjuvant intravenous vitamin C treatment in septic shock may resolve the vasopressor dependence, Int. J. Microbiol. Adv. Immunol
Hemila, Chalker, Vitamin C can shorten the length of stay in the ICU: A meta-analysis, Nutrients, doi:10.3390/nu11040708
Hemila, Chalker, Vitamin C may reduce the duration of mechanical ventilation in critically ill patients: A meta-regression analysis, J. Intensive Care, doi:10.1186/s40560-020-0432-y
Hemila, Vitamin C and infectious diseases
Hemilä, Chalker, Reanalysis of the effect of vitamin C on mortality in the CITRIS-ALI trial: Important findings dismissed in the trial report, Front. Med, doi:10.3389/fmed.2020.590853
Hemilä, Chalker, Vitamin C for preventing and treating the common cold, Cochrane Database Syst. Rev, doi:10.1002/14651858.CD000980.pub4
Hemilä, Louhiala, Vitamin C for preventing and treating pneumonia, Cochrane Database Syst. Rev
Hemilä, Louhiala, Vitamin C may affect lung infections, J. R. Soc. Med, doi:10.1177/014107680710001109
Hemilä, Vitamin C and infections, Nutrients, doi:10.3390/nu9040339
Hiedra, Lo, Elbashabsheh, Gul, Wright et al., The use of IV vitamin C for patients with COVID-19: A case series, Expert Rev. Anti Infect. Ther, doi:10.1080/14787210.2020.1794819
Horby, Lim, Emberson, Mafham, Bell et al., Dexamethasone in hospitalized patients with Covid-19-preliminary report, N. Engl. J. Med, doi:10.1056/NEJMoa2021436
Hornig, Distribution of ascorbic acid, metabolites and analogues in man and animals, Ann. N. Y. Acad. Sci, doi:10.1111/j.1749-6632.1975.tb29271.x
Hume, Weyers, Changes in leucocyte ascorbic acid during the common cold, Scott. Med. J
Hunt, Chakravorty, Annan, Habibzadeh, Schorah, The clinical effects of vitamin C supplementation in elderly hospitalised patients with acute respiratory infections, Int. J. Vitam. Nutr. Res
Jiang, Tang, Liu, Xu, Ye et al., Ascorbic acid supplements and kidney stones incidence among men and women: A systematic review and meta-analysis, Urol. J
Jovic, Ali, Ibrahim, Jessop, Tarassoli et al., Could vitamins help in the fight against COVID-19?, Nutrients, doi:10.3390/nu12092550
Kashiouris, ; L'heureux, Cable, Fisher, Leichtle et al., The emerging role of vitamin C as a treatment for sepsis, Nutrients, doi:10.3390/nu12020292
Kim, Kim, Bae, Choi, Lim et al., Vitamin C is an essential factor on the anti-viral immune responses through the production of interferon-a/b at the initial stage of influenza A virus (H3N2) infection, Immune Netw, doi:10.4110/in.2013.13.2.70
Kimbarowski, Mokrow, Colored precipitation reaction of the urine according to Kimbarowski (FARK) as an index of the effect of ascorbic acid during treatment of viral influenza, Dtsch Gesundheitsw
Klenner, Massive doses of vitamin C and the virus diseases, South Med. Surg
Kodama, Kodama, Murakami, Kodama, Vitamin C infusion treatment enhances cortisol production of the adrenal via the pituitary ACTH route, Vivo
Kory, Kanne, SARS-CoV-2 organising pneumonia: 'Has there been a widespread failure to identify and treat this prevalent condition in COVID-19?, BMJ Open Respir. Res, doi:10.1136/bmjresp-2020-000724
Kumar, Jena, In silico virtual screening-based study of nutraceuticals predicts the therapeutic potentials of folic acid and its derivatives against COVID-19, Res. Square, doi:10.21203/
Levine, Conry-Cantilena, Wang, Welch, Washko et al., Vitamin C pharmacokinetics in healthy volunteers: Evidence for a recommended dietary allowance, doi:10.1073/pnas.93.8.3704
Levine, Wang, Padayatty, Morrow, A new recommended dietary allowance of vitamin C for healthy young women, doi:10.1073/pnas.171318198
Long, Kory, Marik, Vitamin C, hydrocortisone, and thiamine for septic shock, JAMA, doi:10.1001/jama.2020.5844
Long, Maull, Krishnan, Laws, Geiger et al., Ascorbic acid dynamics in the seriously ill and injured, J. Surg. Res
Ma, Sun, Li, Fan, Qu et al., Single-cell transcriptomic atlas of primate cardiopulmonary aging, Cell Res, doi:10.1038/s41422-020-00412-6
Marik, Hooper, Doctor-your septic patients have scurvy!, Crit. Care, doi:10.1186/s13054-018-1950-z
Marik, Is intravenous vitamin C contraindicated in patients with G6PD deficiency?, Crit. Care, doi:10.1186/s13054-019-2397-6
Marik, Kory, Varon, Iglesias, Meduri, MATH+ protocol for the treatment of SARS-CoV-2 infection: The scientific rationale, Expert Rev. Anti Infect. Ther, doi:10.1080/14787210.2020.1808462
Marik, Vitamin C for the treatment of sepsis: The scientific rationale, Pharmacol. Ther
Marik, Vitamin, An essential "stress hormone" during sepsis, J. Thorac. Dis
May, Harrison, Role of vitamin C in the function of the vascular endothelium, Antioxid. Redox Signal, doi:10.1089/ars.2013.5205
May, Qu, Ascorbic acid prevents oxidant-induced increases in endothelial permeability, Biofactors, doi:10.1002/biof.134
Michels, Joisher, Hagen, Age-related decline of sodium-dependent ascorbic acid transport in isolated rat hepatocytes, Arch. Biochem. Biophys, doi:10.1016/S0003-9861(02)00678-1
Milton, Micronutrient intakes of wild primates: Are humans different? Comp, Biochem. Physiol. A Mol. Integr. Physiol, doi:10.1016/S1095-6433(03)00084-9
Milton, Nutritional characteristics of wild primate foods: Do the diets of our closest living relatives have lessons for us?, Nutrition, doi:10.1016/S0899-9007(99)00078-7
Mochalkin, Ascorbic acid in the complex therapy of acute pneumonia, Voen. Med. Zhurnal
Mohammed, Fisher, Kraskauskas, Farkas, Brophy et al., None
Mosdol, Erens, Brunner, Estimated prevalence and predictors of vitamin C deficiency within UK's low-income population, J. Public Health, doi:10.1093/pubmed/fdn076
Myint, Wilson, Clark, Luben, Wareham et al., Plasma vitamin C concentrations and risk of incident respiratory diseases and mortality in the European Prospective Investigation into Cancer-Norfolk population-based cohort study, Eur. J. Clin. Nutr, doi:10.1038/s41430-019-0393-1
Natarajan, Brophy, 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, doi:10.1001/jama.2019.11825
Natarajan, Vitamin C: A novel regulator of neutrophil extracellular trap formation, Nutrients
Ni, Yang, Yang, Bao, Li et al., Role of angiotensin-converting enzyme 2 (ACE2) in COVID-19, Crit. Care
Nualart, Rivas, Montecinos, Godoy, Guaiquil et al., Recycling of vitamin C by a bystander effect, J. Biol. Chem, doi:10.1074/jbc.M210686200
Padayatty, Doppman, Chang, Wang, Gill et al., Human adrenal glands secrete vitamin C in response to adrenocorticotrophic hormone, Am. J. Clin. Nutr
Padayatty, Sun, Chen, Espey, Drisko et al., Vitamin C: Intravenous use by complementary and alternative medicine practitioners and adverse effects, PLoS ONE
Padayatty, Sun, Wang, Riordan, Hewitt et al., Vitamin C pharmacokinetics: Implications for oral and intravenous use, Ann. Intern. Med
Patterson, Isales, Fulzele, Low level of vitamin C and dysregulation of vitamin C transporter might be involved in the severity of COVID-19 Infection, Aging Dis
Pauling, The significance of the evidence about ascorbic acid and the common cold, Proc. Natl. Acad. Sci, doi:10.1073/pnas.68.11.2678
Pauling, Vitamin C the Common Cold and Flu
Pitt, Costrini, Vitamin C prophylaxis in marine recruits, JAMA, doi:10.1001/jama.1979.03290350028016
Ravindran, Wiltshire, Das, Wilson, Vitamin C deficiency in an Australian cohort of metropolitan surgical patients, Pathology, doi:10.1016/j.pathol.2018.07.004
Robitaille, Mamer, Miller, Jr, Levine et al., Oxalic acid excretion after intravenous ascorbic acid administration, Metabolism, doi:10.1016/j.metabol.2008.09.023
Schorah, Downing, Piripitsi, Gallivan, Al-Hazaa et al., Total vitamin C, ascorbic acid, and dehydroascorbic acid concentrations in plasma of critically ill patients, Am. J. Clin. Nutr, doi:10.1093/ajcn/63.5.760
Sen, Packer, Antioxidant and redox regulation of gene transcription, FASEB J
Subramanian, Sabui, Moradi, Marchant, Said, Inhibition of intestinal ascorbic acid uptake by lipopolysaccharide is mediated via transcriptional mechanisms, Biochim. Biophys. Acta Biomembr, doi:10.1016/j.bbamem.2017.10.010
Subramanian, Sabui, Subramenium, Marchant, Said, Tumor Necrosis Factor alpha (TNF-alpha) reduces intestinal vitamin C uptake: A role for NF-kB-mediated signaling, Am. J. Physiol. Gastrointest. Liver Physiol, doi:10.1152/ajpgi.00071.2018
Teixeira, Carrie, Genereau, Herson, Cherin, Vitamin C deficiency in elderly hospitalized patients, Am. J. Med, doi:10.1016/S0002-9343(01)00893-2
Thomas, Holt, Vitamin C and immunity: An assessment of the evidence, Clin. Exp. Immunol
Truwit, Hite, Morris, Dewilde, Priday et al., None
Van Straten, Josling, Preventing the common cold with a vitamin C supplement: A double-blind, placebo-controlled survey, Adv. Ther, doi:10.1007/BF02850271
Vitamin, C. REMAP-CAP: Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia
Vitamin, Fact Sheet for Health Professionals USA
Vizcaychipi, Shovlin, Mccarthy, Howard, Brown et al., Development and implementation of a COVID-19 near real-time traffic light system in an acute hospital setting, Emerg. Med. J, doi:10.1136/emermed-2020-210199
Voigt, Kontush, Stuerenburg, Muench-Harrach, Hansen et al., Decreased plasma and cerebrospinal fluid ascorbate levels in patients with septic encephalopathy, Free Radic. Res, doi:10.1080/10715760290032557
Wang, Russo, Kwon, Chanock, Rumsey et al., Ascorbate recycling in human neutrophils: Induction by bacteria, doi:10.1073/pnas.94.25.13816
Waqas Khan, Parikh, Megala, Predeteanu, Unusual early recovery of a critical COVID-19 patient after administration of intravenous vitamin C, Am. J. Case Rep
Webb, Villamor, Update: Effects of antioxidant and non-antioxidant vitamin supplementation on immune function, Nutr. Rev, doi:10.1111/j.1753-4887.2007.tb00298.x
Zabet, Mohammadi, Ramezani, Khalili, Effect of high-dose ascorbic acid on vasopressor's requirement in septic shock, J. Res. Pharm. Pract
Zhang, Jativa, Vitamin C supplementation in the critically ill: A systematic review and meta-analysis, SAGE Open Med, doi:10.1177/2050312118807615
Zhang, Rao, Li, Zhu, Liu et al., High-dose vitamin C infusion for the treatment of critically ill COVID-19, Res, doi:10.21203/
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