Intravenous vitamin C for reduction of cytokines storm in acute respiratory distress syndrome

Alberto Boretti, Bimal Krishna Banik, Alberto Boretti, Bimal Krishna Banik

Abstract

The recent outbreak of Covid19 has required urgent treatments for numerous patients. No suitable vaccines or antivirals are available for Covid19. The efficiency against Covid19 of WHO therapies of choice, that are two antivirals developed for other pathologies, is controversial. Therefore, alternative approaches are required. Intravenous (IV) Vitamin C (Vit-C) has emerged as one of the other alternatives for this purpose. Here we review the effects of IV Vit-C on the immune system response, the antiviral properties of IV Vit-C, and finally the antioxidant properties of IV Vit-C to specifically address the cytokines' storm characteristic of the Acute Respiratory Distress Syndrome (ARDS) that occur in the later cycle of the Covid19 infectious disease.

Keywords: Antiviral agents; Covid19; Cytokines; Severe acute respiratory syndrome coronavirus; Vitamin C.

Conflict of interest statement

The authors received no funding and have no conflict of interest to declare.

© 2020 Elsevier B.V. All rights reserved.

Figures

Fig. 1
Fig. 1
Top, novel Coronavirus SARS-CoV-2. This transmission electron microscope image shows SARS-CoV-2—also known as 2019-nCoV, the virus that causes COVID-19. isolated from a patient in the U.S., emerging from the surface of cells cultured in the lab. Credit: NIAID-RML.CC BY 2.0. sv.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2#/media/Fil:SARS-CoV_with_corona.jpg. Middle, Novel Coronavirus SARS-CoV-2 This scanning electron microscope image shows SARS-CoV-2 (yellow)—also known as 2019-nCoV, the virus that causes COVID-19—isolated from a patient in the U.S., emerging from the surface of cells (pink) cultured in the lab. Credit: NIAID-RML. CC BY 2.0. sv.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2#/media/Fil:SARS-CoV-2.jpg Bottom, 3D medical animation still shot showing the structure of a coronavirus. CC BY-SA 4.0. sv.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2#/media/Fil:3D_medical_animation_coronavirus_structure.jpg.

References

    1. Hunt C. Even small supplemental amounts of vitamin C can keep severely ill patients from dying. Int. J. Vitam. Nutr. Res. 1994;64:212–219.
    1. Shiguang Ren. Infants with viral pneumonia treated with vitamin C had reduced mortality. Hebei Med. 1978;4:1–3.
    1. Hemilä H., Chalker E. 17,000 mg/day vitamin C given intravenously shortened intensive care unit stay by 44% Nutrients. 2019;11(4)
    1. Khan I.M. 200 mg of vitamin C reduced duration of severe pneumonia in children. Oxygen saturation was improved in less than one day. J. Rawalpindi Med. Coll. (JRMC) 2014;18(1):55–57.
    1. Jungeblut C.W. Inactivation of poliomyelitis virus by crystalline vitamin C (ascorbic acid) J. Exp. Med. 1935;62:317–321.
    1. Jungeblut C.W. Vitamin C therapy and prophylaxis in experimental poliomyelitis. J. Exp. Med. 1937;65:127–146.
    1. Jungeblut C.W. Further observations on vitamin C therapy in experimental poliomyelitis. J. Exp. Med. 1937;66:459–477.
    1. Jungeblut C.W., Feiner R.R. Vitamin C content of monkey tissues in experimental poliomyelitis. J. Exp. Med. 1937;66:479–491.
    1. Jungeblut C.W. A further contribution to vitamin C therapy in experimental poliomyelitis. J. Exp. Med. 1939;70:315–332.
    1. Klenner F.R. Virus pneumonia and its treatment with vitamin C. South. Med. Surg. 1948;110(2):36.
    1. Kline A.B., Eheart M.S. Variations in the ascorbic acid requirements for saturation of nine normal young women. J. Nutr. 1944;28:413.
    1. Joliffe N. Preventive and therapeutic use of vitamins. JAMA. 1945;129:613.
    1. Crandon J.H., Lund C.C., Dill D.B. Experimental human scurvy. N. Eng. J. Med. 1940;223:353.
    1. Baker A.B., Noran J.A. Changes in the central nervous system associated with encephalitis complicating pneumonia. Arch. Intern. Med. 1945;76:146–153.
    1. Krumholz S., Luhan J.A. Encephalitis associated with herpes zoster. Arch. Neur. Psych. 1945;53:59–67.
    1. Chambers R., Zweifach B.W. Intercellular cement and capillary permeability. Physiol. Rev. 1947;27:436–463.
    1. Hawley E.E., Frazer J.P., Button L.L., Stevens D.J. The effect of the administration of sodium bicarbonate and of ammonium chloride on the amount of ascorbic acid found in the urine. J. Nutr. 1936;12:215.
    1. Klenner F.R. Significance of high daily intake of ascorbic acid in preventive medicine. J. Int. Acad. Prev. Med. 1974;1:45–69.
    1. Klenner F.R. Use of vitamin C as an antibiotic. J. Appl. Nutr. 1953;6
    1. Klenner F.R. Massive doses of vitamin C and the virus diseases. J. South Med. Surg. 1951;113:4.
    1. Shaw Acute and chronic ascorbic deficiencies in Rhesus monkeys. J. Nutr. 1945;29:365.
    1. Klenner F.R. The treatment of poliomyelitis and other virus diseases with vitamin C. South Med. Surg. 1949;111:7.
    1. Klenner F.R. The vitamin and massage treatment for acute poliomyelitis. South Med. Surg. 1952;114:8.
    1. Sabin A.B. Vitamin C in relation to experimental poliomyelitis. J. Exp. Med. 1939;69:507.
    1. Jungeblut C.W. Vitamin C therapy and prophylaxis in experimental poliomyelitis. J. Exp. Med. 1937;65:127.
    1. Jungeblut C.W. Further observations on vitamin C therapy in experimental poliomyelitis. J. Exp. Med. 1937;66:450.
    1. Ginter E.L. Cholesterol and vitamin C. Am. J. Clin. Nutr. 1971;24:1238–1245.
    1. Spittle C. Atherosclerosis and vitamin C. Lancet II. 1971:1280–1281.
    1. Ginter E. Effects of dietary cholesterol on vitamin C metabolism in laboratory animals. Acta Med. Acad. Sci. Hungary. 1970;27:23–29.
    1. Ginter E. The effects of ascorbic acid on cholesterolemia in healthy subjects with seasonal deficit of vitamin C. Nutr. Metabol. 1970;12:76–86.
    1. Willis G.C. An experimental study of the intimal ground substance in atherosclerosis. Can. Med. Assoc. J. 1953;69:17–22.
    1. Shafer J. Ascorbic acid and atherosclerosis. Am. J. Clin. Nutr. 1970;23:27.
    1. Dannenburg A.M. Ascorbic acid in the treatment of chronic lead poisoning. JAMA. 1940;114:1439–1440.
    1. Greenwood J. Optimum vitamin C intake as a factor in the preservation of disc integrity. Med. Ann. DC. 1964;33:6.
    1. Kyhos E.D. Large doses of ascorbic acid in treatment of vitamin C deficiencies. Arch. Int. Med. 1945;75:407.
    1. . 2020. High-Dose Vitamin C (PDQ®)–Health Professional Version. “n.d.”.
    1. Naidu K.A. Vitamin C in human health and disease is still a mystery? An overview. Nutr. J. 2003;2:7.
    1. Padayatty S., Espey M.G., Levine M. Vitamin C. In: Coates P.M., Betz J.M., Blackman M.R., editors. Encyclopedia of Dietary Supplements. 2nd ed. Informa Healthcare; New York, NY: 2010. pp. 821–831.
    1. McCormick W.J. Cancer: a collagen disease, secondary to a nutritional deficiency. Arch. Pediatr. 1959;76(4):166–171.
    1. Cameron E., Pauling L. The orthomolecular treatment of cancer. I. The role of ascorbic acid in host resistance. Chem. Biol. Interact. 1974;9(4):273–283.
    1. Cameron E., Campbell A. The orthomolecular treatment of cancer. II. Clinical trial of high-dose ascorbic acid supplements in advanced human cancer. Chem. Biol. Interact. 1974;9(4):285–315.
    1. Cameron E., Pauling L. Supplemental ascorbate in the supportive treatment of cancer: prolongation of survival times in terminal human cancer. Proc. Natl. Acad. Sci. U. S. A. 1976;73(10):3685–3689.
    1. Cameron E., Pauling L. Supplemental ascorbate in the supportive treatment of cancer: reevaluation of prolongation of survival times in terminal human cancer. Proc. Natl. Acad. Sci. U. S. A. 1978;75(9):4538–4542.
    1. Creagan E.T., Moertel C.G., O’Fallon J.R. Failure of high-dose vitamin C (ascorbic acid) therapy to benefit patients with advanced cancer. A controlled trial. N. Engl. J. Med. 1979;301(13):687–690.
    1. Moertel C.G., Fleming T.R., Creagan E.T. High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy. A randomized double-blind comparison. N. Engl. J. Med. 1985;312(3):137–141.
    1. Padayatty S.J., Sun H., Wang Y. Vitamin C pharmacokinetics: implications for oral and intravenous use. Ann. Intern. Med. 2004;140(7):533–537.
    1. Hoffer L.J., Levine M., Assouline S. Phase I clinical trial of i.v. ascorbic acid in advanced malignancy. Ann. Oncol. 2008;19(11):1969–1974.
    1. Verrax J., Calderon P.B. Pharmacologic concentrations of ascorbate are achieved by parenteral administration and exhibit antitumoral effects. Free Radic. Biol. Med. 2009;47(1):32–40.
    1. Padayatty S.J., Sun A.Y., Chen Q. Vitamin C: intravenous use by complementary and alternative medicine practitioners and adverse effects. PLoS One. 2010;5(7)
    1. Campbell G.D., Steinberg M.H., Bower J.D. Letter: ascorbic acid-induced hemolysis in G-6-PD deficiency. Ann. Intern. Med. 1975;82(6):810.
    1. Mehta J.B., Singhal S.B., Mehta J.B.C. Ascorbic-acid-induced haemolysis in G-6-PD deficiency. Lancet. 1990;336(8720):944.
    1. Rees D.C., Kelsey H., Richards J.D. Acute haemolysis induced by high dose ascorbic acid in glucose-6-phosphate dehydrogenase deficiency. BMJ. 1993;306(6881):841–842.
    1. Barton J.C., McDonnell S.M., Adams P.C. Management of hemochromatosis. Hemochromatosis management working group. Ann. Intern. Med. 1998;129(11):932–939.
    1. Welsh J.L., Wagner B.A., van’t Erve T.J. Pharmacological ascorbate with gemcitabine for the control of metastatic and node-positive pancreatic cancer (PACMAN): results from a phase I clinical trial. Cancer Chemother. Pharmacol. 2013;71(3):765–775.
    1. Zou W., Yue P., Lin N. Vitamin C inactivates the proteasome inhibitor PS-341 in human cancer cells. Clin. Cancer Res. 2006;12(1):273–280.
    1. Llobet D., Eritja N., Encinas M. Antioxidants block proteasome inhibitor function in endometrial carcinoma cells. Anticancer Drugs. 2008;19(2):115–124.
    1. Perrone G., Hideshima T., Ikeda H. Ascorbic acid inhibits antitumor activity of bortezomib in vivo. Leukemia. 2009;23(9):1679–1686.
    1. Bannerman B., Xu L., Jones M. Preclinical evaluation of the antitumor activity of bortezomib in combination with vitamin C or with epigallocatechin gallate, a component of green tea. Cancer Chemother. Pharmacol. 2011;68(5):1145–1154.
    1. Heaney M.L., Gardner J.R., Karasavvas N. Vitamin C antagonizes the cytotoxic effects of antineoplastic drugs. Cancer Res. 2008;68(19):8031–8038.
    1. Cameron E., Campbell A., Jack T. The orthomolecular treatment of cancer. III. Reticulum cell sarcoma: double complete regression induced by high-dose ascorbic acid therapy. Chem. Biol. Interact. 1975;11(5):387–393.
    1. Padayatty S.J., Riordan H.D., Hewitt S.M. Intravenously administered vitamin C as cancer therapy: three cases. CMAJ. 2006;174(7):937–942.
    1. Vollbracht C., Schneider B., Leendert V. Intravenous vitamin C administration improves quality of life in breast cancer patients during chemo-/radiotherapy and aftercare: results of a retrospective, multicentre, epidemiological cohort study in Germany. In Vivo. 2011;25(6):983–990.
    1. Yeom C.H., Jung G.C., Song K.J. Changes of terminal cancer patients’ health-related quality of life after high dose vitamin C administration. J. Korean Med. Sci. 2007;22(1):7–11.
    1. Monti D.A., Mitchell E., Bazzan A.J. Phase I evaluation of intravenous ascorbic acid in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. PLoS One. 2012;7(1)
    1. Ma Y., Chapman J., Levine M. High-dose parenteral ascorbate enhanced chemosensitivity of ovarian cancer and reduced toxicity of chemotherapy. Sci. Transl. Med. 2014;6(222)
    1. Hoffer L.J., Robitaille L., Zakarian R. High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial. PLoS One. 2015;10(4)
    1. Wang F., He M.M., Wang Z.X. Phase I study of high-dose ascorbic acid with mFOLFOX6 or FOLFIRI in patients with metastatic colorectal cancer or gastric cancer. BMC Cancer. 2019;19(1):460.
    1. Qazilbash M.H., Saliba R.M., Nieto Y., Parikh G., Pelosini M., Khan F.B., Jones R.B., Hosing C., Mendoza F., Weber D.M., Wang M. Arsenic trioxide with ascorbic acid and high-dose melphalan: results of a phase II randomized trial. Biol. Blood Marrow Transplant. 2008;14(12):1401–1407.
    1. Berenson J.R., Boccia R., Siegel D., Bozdech M., Bessudo A., Stadtmauer E., Talisman Pomeroy J., Steis R., Flam M., Lutzky J., Jilani S. Efficacy and safety of melphalan, arsenic trioxide and ascorbic acid combination therapy in patients with relapsed or refractory multiple myeloma: a prospective, multicentre, phase II, single‐arm study. Br. J. Haematol. 2006;135(2):174–183.
    1. Sharma M., Khan H., Thall P.F., Orlowski R.Z., Bassett R.L., Jr, Shah N., Bashir Q., Parmar S., Wang M., Shah J.J., Hosing C.M. A randomized phase 2 trial of a preparative regimen of bortezomib, high‐dose melphalan, arsenic trioxide, and ascorbic acid. Cancer. 2012;118(9):2507–2515.
    1. Berenson J.R., Matous J., Swift R.A. A phase I/II study of arsenic trioxide/bortezomib/ascorbic acid combination therapy for the treatment of relapsed or refractory multiple myeloma. Clin. Cancer Res. 2007;13(6):1762–1768.
    1. Campbell R.A., Sanchez E., Steinberg J.A. Antimyeloma effects of arsenic trioxide are enhanced by melphalan, bortezomib and ascorbic acid. Br. J. Haematol. 2007;138(4):467–478.
    1. Qazilbash M.H., Saliba R.M., Nieto Y. Arsenic trioxide with ascorbic acid and high-dose melphalan: results of a phase II randomized trial. Biol. Blood Marrow Transplant. 2008;14(12):1401–1407.
    1. Abou-Jawde R.M., Reed J., Kelly M. Efficacy and safety results with the combination therapy of arsenic trioxide, dexamethasone, and ascorbic acid in multiple myeloma patients: a phase 2 trial. Med. Oncol. 2006;23(2):263–272.
    1. Berenson J.R., Boccia R., Siegel D. Efficacy and safety of melphalan, arsenic trioxide and ascorbic acid combination therapy in patients with relapsed or refractory multiple myeloma: a prospective, multicentre, phase II, single-arm study. Br. J. Haematol. 2006;135(2):174–183.
    1. Subbarayan P.R., Lima M., Ardalan B. Arsenic trioxide/ascorbic acid therapy in patients with refractory metastatic colorectal carcinoma: a clinical experience. Acta Oncol. 2007;46(4):557–561.
    1. Schoenfeld J.D., Sibenaller Z.A., Mapuskar K.A. O2⋅- and H2O2-mediated disruption of Fe metabolism causes the differential susceptibility of NSCLC and GBM cancer cells to pharmacological ascorbate. Cancer Cell. 2017;32(2):268.
    1. Chen Q., Espey M.G., Sun A.Y. Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice. Proc. Natl. Acad. Sci. U. S. A. 2008;105(32):11105–11109.
    1. Magrì A., Germano G., Lorenzato A., Lamba S., Chilà R., Montone M., Amodio V., Ceruti T., Sassi F., Arena S., Abrignani S. High-dose vitamin C enhances cancer immunotherapy. Sci. Transl. Med. 2020;12(532)
    1. Colunga Biancatelli R.M.L., Berrill M., Marik P.E. The antiviral properties of vitamin C. Expert Rev. Anti. Ther. 2020;18(2):99–101.
    1. Marik P.E., Khangoora V., Rivera R. Hydrocortisone, vitamin C and thiamine for the treatment of severe sepsis and septic shock: a retrospective before-after study. Chest. 2017;151:1229–1238.
    1. Hemila H., Chalker E. Vitamin C for preventing and treating the common cold. Cochrane Database Syst. Rev. 2013;1
    1. Pauling L. The significance of the evidence about ascorbic acid and the common cold. Proc. Natl. Acad. Sci. U. S. A. 1971;68:2678–2681.
    1. Pauling L., Rath M. An orthomolecular theory of human health and disease. J. Orthomol. Med. 1991;6:135–138.
    1. Oudemans-van Straaten H.M., Spoelstra-de Man A.M.`, de Waard M.C., Vitamin C revisited, Crit. Care 18 (2014) 460.
    1. McNamara R., Deane A.M., Anstey J. Understanding the rationale for parenteral ascorbate (vitamin C) during an acute inflammatory reaction: a biochemical perspective. Crit. Care Resusc. 2018;20:174–179.
    1. While L.A., Freeman C.Y., Forrester B.D. In vitro effect of ascorbic acid on infectivity of herpesviruses and paramyxoviruses. J. Clin. Microbiol. 1986;24:527–531.
    1. Klein M. The mechanism of the virucidal action of ascorbic acid. Science. 1945;101:587–589.
    1. Marik P.E. Hydrocortisone, ascorbic acid and thiamine (HAT therapy) for the treatment of sepsis. Focus on ascorbic acid. Nutrients. 2018;10:1762.
    1. Avci P., Freire F., Banvolgi A. Sodium ascorbate kills Candida albicans in vitro via iron-catalyzed fenton reaction: importance of oxygenation and metabolism. Future Microbiol. 2016;11:1535–1547.
    1. Uesato S., Kitagawa Y., Kaijima T. Inhibitory effects of 6-O-acylated L-ascorbic acids possessing a straight- or branched-acyl chain on epstein-barr virus activation. Cancer Lett. 2001;166:143–146.
    1. Cinatl J., Cinatl J., Weber B. In vitro inhibition of human cytomegalovirus replication in human foreskin fibroblasts and endothelial cells by ascorbic acid 2-phosphate. Antiviral Res. 1995;27:405–418.
    1. Carr A.C. Vitamin C and immune function. Nutrients. 2017;9:1211.
    1. May J.M., Harrison F.E. Role of vitamin C in the function of the vascular endothelium. Antioxid. Redox Signal. 2013;19:2068–2083.
    1. Leibovitz B., Siegel B.V. Ascorbic acid and the immune response. Adv. Exp. Med. Biol. 1981;135:1–25.
    1. Dey S., Bishayi B. Killing of S. aureus in murine peritoneal macrophages by ascorbic acid along with antibiotics chloramphenicol or ofloxacin: correlation with inflammation. Microb. Pathog. 2018;115:239–250.
    1. Kim Y., Kim H., Bae S. Vitamin C is an essential factor on the anti-viral immune response through the production of interferon-alpha/beta at the initial stage of influenza A virus (H3N2) infection. Immune Netw. 2013;13:70–74.
    1. Li W., Maeda N., Beck M.A. Vitamin C deficiency increases the lung pathology of influenza virus-infected gulo-/- mice. J. Nutr. 2006;136:2611–2616.
    1. Cai Y., Li Y.F., Tang L.P. A new mechanism of vitamin C effects on A/FM/1/47(H1N1) virus-induced pneumonia in restraint-stressed mice. Biomed Res. Int. 2015;2015
    1. Valero N., Mosquera J., Alcocer S. Melatonin, minocycline and ascorbic acid reduce oxidative stress and viral titers and increase survival rate in experimental venezuelan equine encephalitis. Brain Res. 2015;1622:368–376.
    1. Lallement A. Persistent parvovirus B19 viremia with chronic arthralgia treated with ascorbic acid: a case report. J. Med. Case Rep. 2015;9:1.
    1. Moens B., Decanine D., Menezes S.M. Ascorbic acid has superior ex vivo antiproliferative, cell death-inducing and immunomodulatory effects over IFN-alpha in HTLV-1-associated myelopathy. PLoS Negl. Trop. Dis. 2012;6:e1729.
    1. Kataoka A., Imai H., Inayoshi S. Intermittent high-dose vitamin C therapy in patients with HTLV-I associated myelopathy. J. Neurol. Neurosurg. Psy. 1993;56:1213–1216.
    1. Harakeh S. NF-kappa B-independent suppression of HIV expression by ascorbic acid. AIDS Res. Hum. Retroviruses. 1997;13:235–239.
    1. Rawal B.D., Bartolini F., Vyas G.N. In vitro inactivation of human immunodeficiency virus by ascorbic acid. Biologicals. 1995;23:75–81.
    1. Harakeh S., Jariwalla R.J., Pauling L. Suppression of human immunodeficiency virus replication by ascorbate in chronically and acutely infected cells. Proc. Natl. Acad. Sci. U. S. A. 1990;87:7245–7249.
    1. Banic S. Prevention of rabies by vitamin C. Nature. 1975;258:153–154.
    1. Hosakote Y.M., Jantzi P.D., Esham D.L. Viral-mediated in hibition of antioxidant enzymes contributes to the pathogenesis of severe respiratory syncytial virus bronchiolitis. Am. J. Respir. Crit. Care Med. 2011;183:1550–1560.
    1. Castro S.M., Guerrero-Plata A., Suarez-Real G. Antioxidant treatment ameliorates respiratory syncytial virus-induced disease and lung inflammation. Am. J. Respir. Crit. Care Med. 2006;174:1361–1369.
    1. Marik P.E. Vitamin C for the treatment of sepsis: the scientific rationale. Pharmacol. Therapeut. 2018;189:63–70.
    1. Chen J.Y., Chang C.Y., Feng P.H. Plasma vitamin C is lower in postherpetic neuralgia patients and administration of vitamin C reduces spontaneous pain but not brush-evoked pain. Clin. J. Pain. 2009;25:562–569.
    1. Kim M.S., Kim D.J., Na C.H. A study of intravenous administration of vitamin C in the treatment of acute herpetic pain and postherpetic neuralgia. Ann. Dermatol. 2016;28:677–683.
    1. Lansbury L.E. Corticosteroids as adjunctive therapy in the treatment of influenza: an updated cochrane systematic review and meta-analysis. Crit. Care Med. 2019;1 doi: 10.1097/CCM.0000000000004093. ePub.
    1. Rodrigo C. Effect of corticosteroid therapy on influenza-related mortality: a systematic review and meta-analysis. J. Infect. Dis. 2015;212:183–194.
    1. . 2020. Early Large Dose Intravenous Vitamin C is the Treatment of Choice for 2019-nCov Pneumonia.
    1. Wang D., Hu B., Hu C., Zhu F., Liu X., Zhang J., Wang B., Xiang H., Cheng Z., Xiong Y., Zhao Y., Li Y., Wang X., Peng Z. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020 doi: 10.1001/jama.2020.1585.
    1. Chen N., Zhou M., Dong X., Qu J., Gong F., Han Y., Qiu Y., Wang J., Liu Y., Wei Y., Xia J., Yu T., Zhang X., Zhang L. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507–513.
    1. Fowler III A.A., Kim C., Lepler L., Malhotra R., Debesa O., Natarajan R., Fisher B.J., Syed A., DeWilde C., Priday A., Kasirajan V. Intravenous vitamin C as adjunctive therapy for enterovirus/rhinovirus induced acute respiratory distress syndrome. World J. Crit. Care Med. 2017;6(1):85–90.
    1. Meng L., Zhao X., Zhang H. HIPK1 interference attenuates inflammation and oxidative stress of acute lung injury via autophagy. Med. Sci. Monit. Int. Med. J. Exp. Clin. Res. 2019;25:827–835.
    1. Yan X., Fu X., Jia Y., Ma X., Tao J., Yang T., Ma H., Liang X., Liu X., Yang J., Wei J. Nrf2/Keap1/ARE signaling mediated an antioxidative protection of human placental mesenchymal stem cells of fetal origin in alveolar epithelial cells. Oxid. Med. Cell. Longev. 2019;2019
    1. Hecker L. Mechanisms and consequences of oxidative stress in lung disease: therapeutic implications for an aging populace. Am. J. Physiol. Lung Cell Mol. Physiol. 2018;314(4):L642–653.
    1. Chen L., Liu H.G., Liu W., Liu J., Liu K., Shang J., Deng Y., Wei S. [Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia]. Zhonghua Jie He He Hu Xi Za Zhi Zhonghua Jiehe He Huxi Zazhi. Chin. J. Tuberc. Respir. Dis. 2020;43(0):E005. doi: 10.3760/cma.j.issn.1001-0939.2020.0005.
    1. Liu Q., Gao Y., Ci X. Role of Nrf2 and its activators in respiratory diseases. Oxid. Med. Cell. Longev. 2019;2019
    1. Nabzdyk C.S., Bittner E.A. Vitamin C in the critically ill - indications and controversies. World J. Crit. Care Med. 2018;7(5):52–61.
    1. Gonzalez M.J. High dose vitamin C and influenza: a case report. J. Orthomol. Med. 2018;33(3)
    1. Zarubaeva V.V., Slitaa A.V., Lavrentyevaa I.N., Smirnovb V.S. Protective activity of ascorbic acid at influenza infection. Russ. J. Infect. Immun. 2017;7(4):319–326.
    1. Levy T.E. MedFox Publishing; Henderson, NV, USA: 2012. Primal Panacea. 350 p.
    1. Hemilä H., Chalker E. Vitamin C can shorten the length of stay in the ICU: a meta-analysis. Nutrients. 2019;11(4)
    1. Marik P.E., Khangoora V., Rivera R., Hooper M.H., Catravas J. Hydrocortisone, vitamin C, and thiamine for the treatment of severe sepsis and septic shock: a retrospective before-after study. Chest. 2017;151(6):1229–1238.
    1. Patel V., Dial K., Wu J., Gauthier A.G., Wu W., Lin M., Espey M.G., Thomas D.D., Jr C.R.A., Mantell L.L. Dietary antioxidants significantly attenuate hyperoxia-induced acute inflammatory lung injury by enhancing macrophage function via reducing the accumulation of airway HMGB1. Int. J. Mol. Sci. 2020;21(3)
    1. Zhang B., Swamy S., Balijepalli S., Panicker S., Mooliyil J., Sherman M.A., Parkkinen J., Raghavendran K., Suresh M.V. Direct pulmonary delivery of solubilized curcumin reduces severity of lethal pneumonia. FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol. 2019;33(12):13294–13309.
    1. Ngo B., Van Riper J.M., Cantley L.C., Yun J. Targeting cancer vulnerabilities with high-dose vitamin C. Nat. Rev. Cancer. 2019;19(5):271–282.
    1. Ma E. Pharmacologic ascorbate induces neuroblastoma cell death by hydrogen peroxide mediated DNA damage and reduction in cancer cell glycolysis. Free Radic. Biol. Med. 2017;113:36–47.
    1. Rychtarcikova Z. Tumor-initiating cells of breast and prostate origin show alterations in the expression of genes related to iron metabolism. Oncotarget. 2017;8:6376–6398.
    1. Shenoy N. Upregulation of TET activity with ascorbic acid induces epigenetic modulation of lymphoma cells. Blood Cancer J. 2017;7:e587.
    1. Xia J. Multiple myeloma tumor cells are selectively killed by pharmacologically-dosed ascorbic acid. EBioMedicine. 2017;18:41–49.
    1. Lu Y.-X. Pharmacological ascorbate suppresses growth of gastric cancer cells with GLUT1 overexpression and enhances the efficacy of oxaliplatin through redox modulation. Theranostics. 2018;8:1312–1326.
    1. Quinn J. Effect of high-dose vitamin C infusion in a glucose-6-phosphate dehydrogenase-deficient patient. Case Rep. Med. 2017;2017
    1. Cimmino L. Restoration of TET2 function blocks aberrant self-renewal and leukemia progression. Cell. 2017;170:1079–1095.
    1. Mingay M. Vitamin C-induced epigenomic remodelling in IDH1 mutant acute myeloid leukaemia. Leukemia. 2018;32:11–20.
    1. Peng D. Vitamin C increases 5-hydroxymethylcytosine level and inhibits the growth of bladder cancer. Clin. Epigenetics. 2018;10:94.
    1. Agathocleous M. Ascorbate regulates haematopoietic stem cell function and leukaemogenesis. Nature. 2017;549:476–481.
    1. Wilkes J.G. Pharmacologic ascorbate (P-AscH-) suppresses hypoxia-inducible Factor-1α (HIF-1α) in pancreatic adenocarcinoma. Clin. Exp. Metastasis. 2018;35:37–51.
    1. Wohlrab C. The association between ascorbate and the hypoxia-inducible factors in human renal cell carcinoma requires a functional Von Hippel-Lindau protein. Front. Oncol. 2018;8:574.
    1. Mustafi S. Vitamin C sensitizes melanoma to BET inhibitors. Cancer Res. 2018;78:572–583.
    1. Erol A. OSF Preprints; 2020. High-dose Intravenous Vitamin C Treatment for COVID-19.
    1. Fauci A.S., Lane H.C., Redfield R.R. Covid-19—navigating the uncharted. N. Engl. J. Med. 2020 doi: 10.1056/NEJMe2002387.
    1. Zhang L., Liu Y. Potential interventions for novel coronavirus in China: a systematic review. J. Med. Virol. 2020 doi: 10.1002/jmv.25707.
    1. Zhang G., Hu C., Luo L., Fang F., Chen Y., Li J., Peng Z., Pan H. Clinical features and outcomes of 221 patients with COVID-19 in Wuhan, China. medRxiv. 2020 doi: 10.1101/2020.03.02.20030452.
    1. Qiu R., Wei X., Zhao M., Zhong C., Zhao C., Hu J., Li M., Huang Y., Han S., He T., Chen J. Outcome reporting from protocols of clinical trials of Coronavirus Disease 2019 (COVID-19): a review. medRxiv. 2020 doi: 10.1101/2020.03.04.20031401.

Source: PubMed

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