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PROPUESTA APOYO GUBERNAMENTAL PARA APLICACIÓN VITAMINA C - kwag - 04-17-2020
Al final del post, hay dos enlaces para que puedan descargar los dos PDF originales, con las gráficas y todo.
PROPUESTA APOYO GUBERNAMENTAL PARA APLICACIÓN VITAMINA C INTRAVENOSA EN PACIENTES CON COVID-19 P.R.
17 April 2020
8 de abril de 2020.
HONORABLES:
WANDA VAZQUEZ GARCED, GOBERNADORA
LORENZO GONZALEZ FELICIANO, SECRETARIO DE SALUD
TASK FORCE COVID-19
LEGISLADORES DEL PUEBLO DE P.R.
RE: PROPUESTA APOYO GUBERNAMENTAL PARA APLICACIÓN VITAMINA C
INTRAVENOSA EN PACIENTES CON COVID-19 P.R.
El Puerto Rico Integrative Medicine Association, es una organización profesional sin fines de lucro compuesta por médicos, científicos, naturópatas, nutricionistas y otros profesionales de la salud especializados en Medicina Funcional, Regenerativa y Ortomolecular. Su propósito es empoderar a la comunidad en temas de optimización de la salud y a su vez promover el avance de la medicina mediante la investigación, la educación y el servicio, con énfasis en métodos tradicionales e innovadores, seguros, efectivos y científicamente estudiados y comprobados como son la bioquímica nutricional, la farmacológica, la optimización metabólica y otros ampliamente estudiados y basados en ciencia.
Debido a la situación de emergencia que se encuentran todos los ciudadanos del pueblo de Puerto Rico ante la pandemia del CoVid-19, enfermedad de alta contagiosidad, su seria morbilidad y su alta mortalidad asociada y la ausencia hasta el presente de tratamientos aprobados, proponemos a las autoridades nos apoyen la iniciativa para fomentar y autorizar el uso de emergencia de vitamina C (Ácido Ascórbico) por vía intravenosa para el manejo de pacientes positivos al CoVid-19 hospitalizados con enfermedad severa dentro del contexto de un protocolo de investigación clínica aprobado por el comité de derechos humanos (IRB, Institutional Review Board). Como objetivo adicional, nos proponemos, el apoyar el desarrollo de mecanismos para producir vitamina C de manera industrial y resiliente, y evitar la casi total dependencia de suplidores foráneos los cuales no garantizan alta calidad, y que actualmente apenas pueden suplir la demanda y a su vez esto nos permite desarrollar una industria que puede generar actividad económica. La producción industrial de ingredientes químicos fue una industria importante en Puerto Rico por lo cual la experiencia y la infraestructura está disponible para renovarla por la seguridad nacional de los puertorriqueños.
Debido a la urgencia de la situación del CoVid-19 en Puerto Rico, proponemos que definamos los objetivos por orden de prioridad de la siguiente manera:
1. Autorizar y promover mediante mandato de la Gobernadora, los Legisladores, el Secretario de Salud y el Task Force del CoVid-19, el uso de vitamina C intravenosa en PR Puerto Rico para pacientes con CoVid-19 hospitalizados que sean admitidos en el estudio clínico aprobado por el comité de derechos humanos (IRB) bajo el protocolo establecido en dicho estudio.
2. Autorizar un fondo de emergencia para adquirir vitamina C intravenosa. El proceso de compra debe ser ágil, ético y transparente para poder adquirirla lo más rápido posible y comenzar a dar tratamiento a los pacientes lo antes posible pues lamentablemente ya están muriendo personas. La vitamina en cuestión debe cumplir con todos los parámetros de calidad y seguridad. La vitamina C está escaseando a nivel mundial y puede ser difícil conseguir.
3. Debemos hacer disponible educación e información adecuada sobre el estudio de la vitamina C intravenosa para los profesionales (mini talleres virtuales / información escrita) y para el público general (conferencia/comunicados de prensa).
4. La fabricación farmacéutica local de la vitamina C intravenosa es un proceso que tendría beneficios de salud para nuestros ciudadanos y para nuestra economía. Este proceso es viable ya que tenemos infraestructura y recursos humanos extremadamente competentes. De hecho, conocemos personas de la industria farmacéutica que han estado trabajando en esta dirección y ya se han hecho inversiones considerables. Entendemos que actualmente el factor limitante es lograr atraer más capital para este proyecto. Este tipo de proyecto es importante porque fortalece nuestra economía y nos da herramientas poderosas para mejorar la salud y garantizar la calidad de las drogas que se manufacturan bajo las buenas prácticas de manufactura federal regulados por la FDA.
5. Adjunto se aneja a esta carta un resumen de la información pertinente al uso terapéutico de ácido ascórbico intravenoso para CoVid-19 debidamente referenciado con publicaciones en revistas médicas/científicas arbitradas.
Esperamos su pronta atención a esta propuesta y les expresamos que estamos a su disposición para cualquier información adicional y/o cualquier duda con respecto a lo antes expresado. Así mismo, estamos disponibles para reunirnos de forma virtual y/o a través de televideo, conferencia por Zoom o Skype. Mi número de teléfono es el (787) 354-0758.
Atentamente,
_____________________________________
Raúl H. Morales-Borges, MD / Presidente, PRIMA
[b]Data Summary to Support High Dose Ascorbic Acid Infusion for the Treatment of Severe 2019-nCoV Viral Pneumonia[/b]
Based on Emergency Clinical Research Proposal to be conducted in Puerto Rico
Dr. Víctor A. Marcial-Vega, MD, Adjunct faculty, School of Medicine, UCC, Dr. Jorge R Miranda-Massari,
PharmD, Professor, School of Pharmacy, MSC, UPR and Dr. Michael J González, DSc, NMD, PhD
Professor, School of Public Health, MSC, UPR and others.
Brief Summary:
The new coronavirus (2019-nCoV) and its pulmonary and systemic complications have
caused worldwide concern and emergency. There is a lack of effective targeted antiviral
drugs, and symptomatic supportive treatment is the only therapeutic approach for severe
acute respiratory infection (SARI).
Ascorbic acid (AA) is an essential nutrient with important and diverse physiological effects.
Moreover, at high doses (7,500 and over mg/day), especially when producing high
micromolar or milimolar concentrations it has been shown to exhibit pharmacological
properties. Among its many actions, it plays a role in reducing inflammation, (a
precipitating factor in SARI), supporting various aspects of the immune system and has a
direct antiviral effect.
A number of studies describe an array of mechanisms by which ascorbic acid enhances the
function of leukocytes including chemokinesis and chemotaxis properties
1
, phagocytosis 2 , production of lysosomal enzymes 3 , generation of reactive oxygen species 4 ,
and microbial killing 5 , up-regulation of antibody response 6 and increased interferon 7 .
These effects, as well as enhanced neutrophil chemotactic capacity 8,9 , have also been
documented in humans ingesting gram doses of vitamin C.
In addition, studies have shown clinical benefits which include lowering and reducing the
risk of infection 10 , 11 . Studies in animal models have demonstrated that parenteral ascorbate
improves sepsis and sepsis-induced multiple organ dysfunction syndrome via preventing of
cellular immunosuppression 12 . Studies in septic mice suggest that increased survival occurs
by activation of Nrf2/HO-1 signals 13 .
In-vitro observations with pharmacologic concentrations (millimolar range) suggest a direct
antiviral effect of ascorbate 14 consistent with clinical observations of patients with Epstein-
Barr viral (EBV) infection. There was a significant reduction of the EBV antibodies upon
pharmacologic intravenous ascorbate therapy 15 . Moreover, intravenous ascorbic acid has
demonstrated clinical benefits in different viral infections 16,17,18,19 .
Sepsis is a systemic response of an infection that results in an overwhelming production of
reactive oxygen species (ROS) with widespread injury to multiple tissues, cells and
organelles leading to progressive organ failure. The severe immune reaction in which the
1body releases too many cytokines into the blood too quickly produces an uncontrolled burst
of damaging ROS is known as the cytokine storm and represents an important complication
of covid1-9 infection 20 . In summary, over 500 peer reviewed experimental and clinical
studies have been published, clearly demonstrating the biologic credibility and biological
and pharmacologic mechanisms of vitamin C alone or combined with other agents in the
management of sepsis and other inflammatory disorders 21,22 . Based on these concepts, the
most comprehensive randomized study using intravenous ascorbic acid in 167 patients with
severe acute respiratory failure demonstrated at day 4 and forward significant reduction in
mortality in the ascorbic acid group when compared to placebo (p = 0.023) 23 . (see figure 1)
Figure 1. Patients With Sepsis and Severe Acute Respiratory Failure
Most vertebrates respond to a physiological stress such as sepsiFFigures with a dramatic
increase in the synthesis of ascorbate by converting glucose by means of the enzyme l-
gulono-g-lactone oxidase (GLO). When sufficient ascorbate is present, it helps: control
excess inflammation, support leukocyte function, inhibit microbial pathogen growth and
neutralize harmful ROS. However, since humans lack the GLO enzyme, we are not able to
2synthetize ascorbate and must acquire nutritional or pharmacologic doses according the
particular physiologic demands at hand.
Some recent studies suggest that the use of ascorbic acid as part of a protective protocol
against sars-covid-2 can reduce mortality in patients hospitalized in intensive care units with
sepsis. This ascorbic acid protocol can significantly reduce mortality from sepsis 24 , reduce
ICU stay length 25 and significantly reduce the time to resolution of shock 26 . The use of
ascorbic acid injections also improved the ventricular function (EF) 72 h after surgery and
reduced the length of ICU stay in patients undergoing coronary artery bypass surgery 27 .
The use of ascorbic acid as an effective antiviral has been documented as early as 1949
when Frederick R. Klenner, MD, documented the ability of vitamin C to reliably cure many
different acute infectious diseases and to reliably neutralize any toxin treated, when
sufficiently dosed and administered for a long enough period of time 28 including the cure of
60 out of 60 (100%) patients with polio within 4 days of ascorbic acid administration
intramuscularly and orally 29 . He also reported the cure of advanced polio and its associated
flaccid paralysis with ascorbic acid in 1951 30 .
A paper by Marcial-Vega et al reported on the efficacy and safety of the use of intravenous
25-50 grams of ascorbic acid in the treatment of 56 patients with Chikungunya. These
patients reported clinical improvements with no reported side effects. This protocol showed
that the use of intravenous hydrogen peroxide and ascorbic acid is safe and strongly
associated with a more than 71% post-infusion reduction of pain in patients affected with
Chikungunya virus related arthralgia 31 .
These results are consistent with previous in-vitro research which has shown that ascorbic
acid inactivates the polio 32 , herpes 33 , vaccinia 34,35 , tobacco mosaic 36 , bacteriophage 37,38,39,40 ,
entero 41 , influenza 42 and rabies 43 viruses.
They are also consistent with previous clinical research showing ascorbic acid can resolve
polio 9,10,11,44,45 , its associated flaccid paralysis 10 , acute hepatitis 46,47,48 , viral
encephalitis 49,50,51,52 , measles 53 , mumps 54 , Herpes 55 ,, influenza 56 and rabies in guinea
pigs 57 . Also consistent with human case reports of influenza 18 , mononucleosis 58 ,
chikungunya 59 and Zika 60 in which intravenous vitamin C was utilized successfully as
therapy.
Recently, there is some global movement leaning towards including ascorbic acid as part of
the modalities used for the management of pulmonary failure due to the corona virus. One of
these is a randomized protocol recently approved by the National Institutes of Health using
12 grams of intravenous ascorbic acid for severe infected 2019-nCov pneumonia. This
research is led by Dr. ZhiYong Peng, Zhongnan Hospital in Wuhan, China 61 .
More recently another clinical study using 10 grams of iv AA for hospitalized patients With
COVID-19 started in Italy. This study lead by Salvatore Corrao, MD from the University of
Palermo started on March 13, 2020 62 .
3The Shanghai Expert Consensus on Covid-19 Treatment organized by the Shanghai
Medical Association has included ascorbic acid as a treatment modality for Cov-2019 virus
associated pneumonia 63 .
An International Pulmonologist’s Consensus Group has stated that a moderate dose of IV
vitamin C could be considered (e.g. 1.5 grams IV q6 ascorbic acid plus 200 mg thiamine IV
q12) for treatment of this disease and they consider this dose to be safe 64 .
On a presentation given to us by Dr. Enqian Mao, chief of Emergency Medicine Department
at Ruijin Hospital, Shanghai, affiliated with the Joatong University School of Medicine and a
member of the Senior Expert Team at the Shanghai Public Health Center and co-author of
the Shanghai Guidelines for the Treatment of Covid-19 infection, an official document
endorsed by the Shanghai Medical Association and the Shanghai city government he stated
65
:
In the year 2020, out of the 358 CoVid19 patients, 50 patients were treated with
intravenous ascorbic acid (IVAA)
Dose was 10-20 gm infused over 24 hours
A patient that continued to deteriorate received an increased dose of 50 gm of
ascorbic acid infused over a period of 4 hours and started responding during the
infusion. This patient had a complete recovery and was eventually discharged.
All patients receiving IVAA improved and there was zero mortality
No side effects
Patients who received IVAA had average 5 days shorter stay (from 30 to 25 days)
than untreated patients
Given the track record of safety of intravenous ascorbic acid 66 and the diversity of favorable
actions of ascorbate in the management of viral infections on sepsis and the effects on
diminishing inflammatory complications in the scientific and clinical literature we propose the
evaluation of high dose intravenous ascorbic acid infusions as a therapeutic intervention in
patients with severe acute respiratory infection from covid-19. We propose this study to
evaluate the clinical safety and efficacy of high dose intravenous vitamin C in the clinical
management of severe acute respiratory infection from covid-19.
Currently there are 3 ongoing clinical trials in CoVid19 patients using intravenous ascorbate
as treatment registered in clinicaltrials.gov and several others not registered yet. In addition
there are some that are in the process of being submitted for approval and funding before
starting. The clinical trial to be conducted in Puerto Rico is expected to submitted for IRB
approval very soon. This study will examine as primary outcome measures mortality
(survival), length of stay at the ICU and length of stay at the hospital. Secondary outcomes
will include severity scores, laboratory markers and others.
Here is a summary of the ongoing registered trials:
PI/ Location
Dose
Primary
4
Secondary1
2
3
4
5
6
Amount of patients
ZhiYong Peng, Zhongnan
Hospital of Wuhan
University, Wuhan, Hubei,
China 140 pts CoVid19
François Lamontagne,
Université de Sherbrooke
Quebec, Canada
800 pts CoVid19
Salvatore Corrao, MD,
University of Palermo, Italy
800 pts CoVid19
Wessam Adel El Sayed
Abdel Aziz El Driny, Ain
Shams University. Ventilator
Associated Pneumonia
( VAP) Sepsis
Virginia Commonwealth
University. Richmond,
Virginia, USA, Sepsis
Alcoholic Hepatitis
Emory University, University
of Kentucky, Cleveland
Clinic, NHLBI (CIRIS-ALI)
Acute lung injury (170)
12g Vitamin C/ sterile
water 50ml @ 12ml/h;
infusion 12h x 7 days
50 mg/kg (≈ 3.5 gm)
every 6 hours for 96
hrs.
(Aprox 14 gm/d)
10 gr/d of vitamin C
intravenously in
addition to
conventional therapy
1.5 gm intravenous
(IV) Vitamin C in 100
ml dextrose 5%
outcome
Ventilation-free
days outcome
Mortality, ICU
stay
Mortality at 28
days ICU stay
Mortality at 6
months
Mortality Hospital stay
Incidence of
Ventilator -
Associated
Pneumonia Plasma Vitamin
C level
Vitamin C (14 gm)
200mg/kg/24hours
dextrose 5%
50 mg/kg (≈ 3.5 gm)
every 6 hours for 96
hrs. in dextrose 5%
References
5
mSOFA
Mortality
C-Reactive
ICU stay
Protein
Hospital stay
Thrombomodulin1 .Schwager J1, Bompard A1, Weber P1, Raederstorff D1. Ascorbic acid modulates cell migration in differentiated
HL-60 cells and peripheral blood leukocytes. Mol Nutr Food Res. 2015 Aug;59(8):1513-23.
2 .Shilotri, P.G. Phagocytosis and leukocyte enzymes in ascorbic acid deficient guinea pigs. J. Nutr. 1977, 107,
1513–1516.
3 .Anderson R. Effects of ascorbate on normal and abnormal leucocyte functions. Int J Vitam Nutr Res Suppl.
1982;23:23-34.
4 .Sharma, P.; Raghavan, S.A.; Saini, R.; Dikshit, M. Ascorbate-mediated enhancement of reactive oxygen species
generation from polymorphonuclear leukocytes: Modulatory effect of nitric oxide. J. Leukoc. Biol. 2004, 75, 1070–
1078
5 .Vilchèze C1, Kim J1, Jacobs WR Jr2. Vitamin C Potentiates the Killing of Mycobacterium tuberculosis by the
First-Line Tuberculosis Drugs Isoniazid and Rifampin in Mice. Antimicrob Agents Chemother. 2018 Feb 23;62(3).
pii: e02165-17..
6 .Mitsuzumi H1, Kusamiya M, Kurimoto T, Yamamoto I. Requirement of cytokines for augmentation of the antigen-
specific antibody responses by ascorbate in cultured murine T-cell-depleted splenocytes. Jpn J Pharmacol. 1998
Oct;78(2):169-79.
7 .Kim Y1, Kim H, Bae S, Choi J, Lim SY, Lee N, Kong JM, Hwang YI, Kang JS, Lee WJ. Vitamin C Is an Essential
Factor on the Anti-viral Immune Responses through the Production of Interferon-α/β at the Initial Stage of
Influenza A Virus (H3N2) Infection. Immune Netw. 2013 Apr;13(2):70-4. doi: 10.4110/in.2013.13.2.70. Epub 2013
Apr 30.
8 .Anderson, R.; Oosthuizen, R.; Maritz, R.; Theron, A.; Van Rensburg, A.J. The effects of increasing weekly doses
of ascorbate on certain cellular and humoral immune functions in normal volunteers. Am. J. Clin. Nutr. 1980, 33,
71–76.
9 .Bozonet SM, Carr AC, Pullar JM, Vissers MCM. Enhanced human neutrophil vitamin C status, chemotaxis and
oxidant generation following dietary supplementation with vitamin C-rich SunGold kiwifruit. Nutrients 2015, 7,
2574–2588.
10 .Vorilhon P, Arpajou B, Vaillant Roussel H, Merlin É, Pereira B, Cabaillot A. Efficacy of vitamin C for the prevention
and treatment of upper respiratory tract infection. A meta-analysis in children. Eur J Clin Pharmacol. 2019
Mar;75(3):303-311.
11 .Kim GN, Yoo WS, Park MH, Chung JK, Han YS, Chung IY, Seo SW, Yoo JM, Kim SJ. Clinical Features of
Herpes Simplex Keratitis in a Korean Tertiary Referral Center: Efficacy of Oral Antiviral and Ascorbic Acid on
Recurrence.Korean J Ophthalmol. 2018 Oct;32(5):353-360.
12 .Gao YL, Lu B, Zhai JH, Liu YC, Qi HX, Yao Y, Chai YF, Shou ST. The Parenteral Vitamin C Improves Sepsis
and Sepsis-Induced Multiple Organ Dysfunction Syndrome via Preventing Cellular Immunosuppression.
Mediators Inflamm. 2017;2017:4024672.
13 .Kim SR, Ha YM, Kim YM, Park EJ, Kim JW, Park SW, Kim HJ, Chung HT, Chang KC. Ascorbic acid reduces
HMGB1 secretion in lipopolysaccharide-activated RAW 264.7 cells and improves survival rate in septic mice by
activation of Nrf2/HO-1 signals. Biochem Pharmacol. 2015 Jun 15;95(4):279-89.
14 .Furuya A1, Uozaki M, Yamasaki H, Arakawa T, Arita M, Koyama AH. Antiviral effects of ascorbic and
dehydroascorbic acids in vitro. Int J Mol Med. 2008 Oct;22(4):541-5.
15 Mikirova N, Hunninghake R.Effect of high dose vitamin C on Epstein-Barr viral infection. Med Sci Monit. 2014
May 3;20:725-32.
16 .Schencking M1, Vollbracht C, Weiss G, Lebert J, Biller A, Goyvaerts B, Kraft K. Intravenous vitamin C in the
treatment of shingles: results of a multicenter prospective cohort study. Med Sci Monit. 2012 Apr;18(4):CR215-24.
17 .Chen S, Zhao W, Zhang B, Jia Y, Wu S, Zhong B, Yu X, Wang X, Hao Y, ang H, Zhao Y, Mizuno K, Bu H, Tseng
Y5Clinical Effect of Intravenous Vitamin C on Viral Myocarditis in Children: A Systematic Review and Meta-
Analysis. Evid Based Complement Alternat Med. 2019;23;2019:3082437.
18 . Gonzalez MJ, Berdiel MJ, Duconge J, Levy TE, Alfaro IM, Morales-Borges R, Marcial-Vega V, Olalde J. High
Dose Intravenous Vitamin C and Influenza: A Case Report. J Orthomolec Med 2018;33(3):1-3.
19 .Marcial-Vega V, Gonzalez-Terron I, Levy TE. Intravenous Ascorbic Acid And Hydrogen Peroxide In The
Management Of Patients With Chikungunya. Bol Asoc Med. 2017;107(1):20-24.20 .Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ; HLH Across Speciality Collaboration,
UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020 Mar
28;395(10229):1033-1034.
21 .Marik PE, Vitamin C. for the treatment of sepsis: the scientific rationale. Pharmacol Therapeut 2018;189:63–70.
22 .Marik PE, Hydrocortisone. Ascorbic acid and thiamine (HAT therapy) for the treatment of sepsis. Focus on
ascorbic acid. Nutrients 2018;10:1762.
23 .Fowler AA, Truwit JD, Hite RD, Morris PE, DeWilde C, 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. 2019 Oct 1;322(13):1261-1270. doi:
10.1001/jama.2019.11825.
24 .Marik PE, Khangoora V, Rivera R, Hooper MH, Catravas J. Hydrocortisone, Vitamin C, and Thiamine for the
Treatment of Severe Sepsis and Septic Shock: A Retrospective Before-After Study. Chest. 2017
Jun;151(6):1229-1238.
25 .Mitchell AB, Ryan TE, Gillion AR, Wells LD, Muthiah P. Vitamin C and Thiamine for Sepsis and Septic Shock. Am
J Med. 2019 Aug 28. pii: S0002-9343(19)30699-0.
26 .Iglesias J, Vassallo AV, Patel VV, Sullivan JB, Cavanaugh J, Elbaga Y. Outcomes of Metabolic Resuscitation
Using Ascorbic Acid, Thiamine, and Glucocorticoids in the Early Treatment of Sepsis. Chest. 2020 Mar 16. pii:
S0012-3692(20)30455-4.
27 .Emadi N, Nemati MH, Ghorbani M, Allahyari E. The Effect of High-Dose Vitamin C on Biochemical Markers of
Myocardial Injury in Coronary Artery Bypass Surgery. Braz J Cardiovasc Surg. 2019 Dec 1;34(5):517-524.
28 .Klenner FR.. Observations On the Dose and Administration of Ascorbic Acid When Employed Beyond the Range
Of A Vitamin In Human Pathology Journal of Applied Nutrition 1971;23( 3 & 4).
29 .Klenner FR. The Treatment of Poliomyelitis and Other Viral Diseases with Vitamin C, Southern Medicine and
Surgery, July1949, 209
30 .Klenner, F.R. Massive Doses of Vitamin C and the Virus Diseases, Journal of Southern Medicine and Surgery,
April 1951;113(4): 101-107.
31 . Marcial-Vega V, Idxian Gonzalez-Terron G, Levy TE. Intravenous ascorbic acid and hydrogen peroxide in the
management of patients with chikungunya. Bol Asoc Med P R. 2015 Jan-Mar;107(1):20-4.
32 .Jungeblut, CW, Inactivation of Poliomyelitis virus in vitro by crystalline vitamin C (ascorbic acid): J Exp Med. 1935
Sep 30; 62(4):517- -21.
33 Holden; Molloy: Further experiments on the inactivation of herpes virus by vitamin C (l-ascorbic acid). Journal of
Immunology 1937;33:251-257.
34 . Kligler and Bernkopf: Inactivation of vaccinia virus by ascorbic acid and glutathione. Nature 1937;139:965-966.
35 .Turner G Inactivation of vaccinia virus by ascorbic acid. J Gen Microbiol 1964;35:75-80 [14171261]
36 .Lojkin M. A study of ascorbic acid as an inactivating agent of tobacco mosaic virus. Contr. Boyce Thompson Inst.
Pl. Res. 1936;8, 455.
37 .Lominski () Inactivation du bacteriophage par l’acide delta containing single-stranded DNA by ascorbic acid. J
Nutr Sci Viascorbique. C r Seanc Soc Biol 1936;122:176
38 .Murata A, Oyadomari R, Ohashi T, Kitagawa K. Mechanism of inactivation of bacteriophage deltaA containing
single-stranded DNA by ascorbic acid. J Nutr Sci Vitaminol (Tokyo). 1975;21(4):261-9.
39 .Morgan AR, Cone RL, Elgert TM. The mechanism of DNA strand breakage by vitamin C and superoxide and the
protective roles of catalase and superoxide dismutase. Nucleic Acids Res. 1976 May;3(5):1139-49.
40 .Richter HE, Loewen PC. Rapid inactivation of bacteriophage T7 by ascorbic acid is repairable. Biochim Biophys
Acta. 1982 Apr 26;697(1):25-30.
41 .Salo RJ, Cliver DO. Inactivation of enteroviruses by ascorbic acid and sodium bisulfite. Appl Environ Microbiol.
1978 Jul;36(1):68-75.42 .Cheng LL1, Liu YY, Li B, Li SY, Ran PX. [An in vitro study on the pharmacological ascorbate treatment of
influenza virus]. Zhonghua Jie He He Hu Xi Za Zhi. 2012 Jul;35(7):520-3.
43 .Amato G Azione dell’acido ascorbico sul virus fisso della rabia e sulla tossina tetanica. Giornale di Batteriologia,
Virologia et Immunologia (Torino). 1937;19:843-847 (rabies virus inactivated in vitro)
44 .Greer E. Vitamin C in acute poliomyelitis Med Times. 1955 Nov; 83(11):1160-1.
45 .Baur, H, Poliomyelitis therapy with ascorbic acid: Helv Med Acta., 1952 Oct; 19(4-5):470-4.
46 .Dalton, WL, Massive Doses of Vitamin C in the treatment of Viral Diseases: J Indiana State Med Assoc., 1962
Aug; 55:1151-4.
47 .Orens, S, Hepatitis B—A ten Day “Cure”. A personal History: Bull Phila Cty Dent Socc., 1983; 48(6):4-5.
48 .Klenner F. Significance of high daily intake of ascorbic acid in preventive medicine. Journal of the International
Academy of Preventive Medicine 1:45-69.
49 .Klenner F. The treatment of poliomyelitis and other virus diseases with vitamin C. Southern Medicine & Surgery.
1949;111:209-214
50 .Klenner F. Massive doses of vitamin C and the virus diseases. Southern Medicine & Surgery 1951;103:101-107.
51 .Klenner F. The use of vitamin C as an antibiotic. Journal of Applied Nutrition 1953;6:274-278
52 .Klenner F. Observations of the dose and administration of ascorbic acid when employed beyond the range of a
vitamin in human pathology. Journal of Applied Nutrition 1971;23:61-88
53 .Joffe MI, Sukha NR, Rabson AR. Lymphocyte subsets in measles. Depressed helper/inducer subpopulation
reversed by in vitro treatment with levamisole and ascorbic acid. J Clin Invest. 1983 Sep;72(3):971-80
54 .Karam F. Vitamins B1 and C in the treatment of mumps]. Rev Bras Med. 1953 Apr;10(4):285-6.[
55 .Zureick M. [Therapy of herpes and herpes zoster with intravenous vitamin C]. J Prat Rev Gen Clin Ther. 1950
Nov 30;64(48):586.
56 .Cai Y, Li YF, Tang LP, Tsoi B, Chen M, Chen H, Chen XM, Tan RR, Kurihara H, He RR. A new mechanism of
vitamin C effects on A/FM/1/47(H1N1) virus-induced pneumonia in restraint-stressed mice. Biomed Res Int.
2015;2015:675149.
57 .Banic S. Prevention of rabies by vitamin C. Nature. 1975 Nov 13;258(5531):153-4.
58 .Mikirova N, Hunninghake R. Effect of high dose vitamin C on Epstein-Barr viral infection. Med Sci Monit. 2014
May 3;20:725-32.
59 .Adrover-López PA, Gonzalez MJ, Miranda-Massari JR, Duconge J and Berdiel M. Inflammatory Sequelae After
Chikungunya Virus Infection: Proposed. Journal of Restorative Medicine 2016; 5:39-45.
60 .González MJ, Berdiel MJ, Miranda-Massari JR, Duconge J. Rodríguez-López JL, Adrover-López PA. High Dose
Intravenous Vitamin C Treatment for Zika Fever. J Orthomolec Med 2016;31(1).
61 .Zhiyong Peng (PI), Wuhan University. Vitamin C Infusion for the Treatment of Severe 2019-nCoV Infected
Pneumonia. https://clinicaltrials.gov/ct2/show/NCT04264533.
62 .Salvatore Corrao (PI) University of Palermo. Use of Ascorbic Acid in Patients With COVID 19.
https://www.clinicaltrials.gov/ct2/show/NCT04323514
63 . Shanghai Expert Group on Clinical Treatment of New Coronavirus Disease. Chinese Journal of Infectious
Diseases, 2020, Pre-published Online. DOI: 10.3760/cma.j.issn.1000-6680.2020.0016
64 . International Pulmonologist’s Consensus on COVID-19, Tinku, J and Ashkan,M, editors, 2020, pp.19
65 .Personal communication with Dr. Enqian Mao.
66 .Padayatty SJ, Sun AY, Chen Q, Espey MG, Drisko J, Levine M. Vitamin C: intravenous use by complementary
and alternative medicine practitioners and adverse effects. PLoS One. 2010 Jul 7;5(7):e11414.
Enlaces para descargar estos dos documentos:
Proposal: https://app.blackhole.run/#1cd42591591887zyNBezkEAZjLHE4z1tuzPgQbgdV3su
Data Summary: https://app.blackhole.run/#19d8e70fa916RFFJoKkbRcRpvbx9rhpWJ8R15hpGpn77