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Life
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Antimicrobial Mechanisms of Vitamin C
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Antimicrobial Mechanisms of Vitamin C

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Pharmaceutical Science".

Deadline for manuscript submissions: closed (20 May 2022) | Viewed by 40009

Special Issue Editors

Dr. Jeanne A Drisko

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Guest Editor
Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA
Interests: translational research in intravenous vitamin C; integrative medicine education; integrative and functional medicine nutrition therapy
Dr. Qi Chen

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Guest Editor
Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160, USA
Interests: cancer medicine; cancer drug development; mechanism studies with small molecules; cancer epithelial-mesenchymal transition; cancer stem cells

Special Issue Information

Dear Colleagues,

Oral vitamin C has well-documented vitamin actions that are known to provide protection against a multitude of disorders including infection. This is in contrast to intravenously administered vitamin C, which retains vitamin-like activity but is also able to treat infection rather than simply provide protection. When vitamin C is given intravenously rather than orally, it is known to become a drug called pharmacologic ascorbic acid. Pharmacologic ascorbic acid or intravenous vitamin C has been used for many decades, with one of its known uses being as an antimicrobial agent. Contrasting intravenous vitamin C with that orally administered, absorption and excretion bypass tight controls with well-documented effects beyond its vitamin effects, such as the formation of ascorbyl radicals and hydrogen peroxide, making it a prooxidative therapy. It is the prooxidative actions of intravenous vitamin C that result in its antimicrobial effects.

In this Special Issue, we will collaborate with colleagues from around the world who are well-known in the field of both oral vitamin C and intravenous vitamin C use. Our goal is to provide a collection of articles describing the benefits of oral vitamin C and, finally, emerging research in the use of intravenous vitamin C as an antimicrobial agent.

Dr. Jeanne A Drisko
Dr. Qi Chen 
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Life is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • vitamin C
  • ascorbic acid
  • oral vitamin C
  • intravenous vitamin C
  • prooxidative actions
  • antimicrobial treatment

Published Papers (7 papers)

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Research

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13 pages, 890 KiB  
Article
Pharmacologic Ascorbic Acid as Early Therapy for Hospitalized Patients with COVID-19: A Randomized Clinical Trial
by Dagan Coppock, Pierre-Christian Violet, Gustavo Vasquez, Katherine Belden, Michael Foster, Bret Mullin, Devon Magee, Isabelle Mikell, Lokesh Shah, Victoria Powers, Brian Curcio, Daniel Monti and Mark Levine
Life 2022, 12(3), 453; https://doi.org/10.3390/life12030453 - 19 Mar 2022
Cited by 13 | Viewed by 5998 | Correction
Abstract
Despite the widespread availability of effective vaccines, new cases of infection with severe acute respiratory syndrome coronavirus-2, the cause of coronavirus disease 2019 (COVID-19), remain a concern in the settings of vaccine hesitancy and vaccine breakthrough. In this randomized, controlled, phase 2 trial, [...] Read more.
Despite the widespread availability of effective vaccines, new cases of infection with severe acute respiratory syndrome coronavirus-2, the cause of coronavirus disease 2019 (COVID-19), remain a concern in the settings of vaccine hesitancy and vaccine breakthrough. In this randomized, controlled, phase 2 trial, we hypothesized that high-dose ascorbic acid delivered intravenously to achieve pharmacologic concentrations may target the high viral phase of COVID-19 and thus improve early clinical outcomes. Sixty-six patients admitted with COVID-19 and requiring supplemental oxygen were randomized to receive either escalating doses of intravenous ascorbic acid plus standard of care or standard of care alone. The demographic and clinical characteristics were well-balanced between the two study arms. The primary outcome evaluated in this study was clinical improvement at 72 h after randomization. While the primary outcome was not achieved, point estimates for the composite outcome and its individual components of decreased use of supplemental oxygen, decreased use of bronchodilators, and the time to discharge were all favorable for the treatment arm. Possible favorable effects of ascorbic acid were most apparent during the first 72 h of hospitalization, although these effects disappeared over the course of the entire hospitalization. Future larger trials of intravenous ascorbic acid should be based on our current understanding of COVID-19 with a focus on the potential early benefits of ascorbic in hospitalized patients. Full article
(This article belongs to the Special Issue Antimicrobial Mechanisms of Vitamin C)
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11 pages, 851 KiB  
Article
Reduced Plasma Ascorbate and Increased Proportion of Dehydroascorbic Acid Levels in Patients Undergoing Hemodialysis
by Yuta Doshida, Mitsuyo Itabashi, Takashi Takei, Yuka Takino, Ayami Sato, Wako Yumura, Naoki Maruyama and Akihito Ishigami
Life 2021, 11(10), 1023; https://doi.org/10.3390/life11101023 - 28 Sep 2021
Cited by 3 | Viewed by 2912
Abstract
Ascorbate functions as an electron donor and scavenges free radicals. Dehydroascorbic acid (DHA), the oxidized form of ascorbate, is generated as a result of these reactions. While low plasma ascorbate levels have been reported in hemodialysis patients worldwide, no studies have measured DHA [...] Read more.
Ascorbate functions as an electron donor and scavenges free radicals. Dehydroascorbic acid (DHA), the oxidized form of ascorbate, is generated as a result of these reactions. While low plasma ascorbate levels have been reported in hemodialysis patients worldwide, no studies have measured DHA because it is not generalized. In this study, we aimed to clarify whether plasma ascorbate levels are low in dialysis patients and whether plasma ascorbate levels fluctuate before and after dialysis. Moreover, we applied our previously established method to measure the plasma ascorbate and DHA levels in chronic kidney disease (CKD) stage G3–G5 non-hemodialysis-dependent patients, and pre- and post-dialysis plasma ascorbate and DHA levels in CKD stage G5D hemodialysis patients. The sample size was calculated using G-power software. The pre-dialysis plasma total ascorbate levels, including DHA, were significantly (56%) lower in hemodialysis patients than in non-hemodialysis-dependent CKD patients. After dialysis, there was a 40% reduction in the plasma total ascorbate levels. Hemodialysis increased the post-dialysis plasma proportions of DHA from 37% to 55%. The study results demonstrated lower plasma total ascorbate levels in hemodialysis patients compared with in non-hemodialysis-dependent CKD patients; these low levels in hemodialysis patients were further reduced by hemodialysis and increased DHA proportion. Full article
(This article belongs to the Special Issue Antimicrobial Mechanisms of Vitamin C)
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Review

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35 pages, 1821 KiB  
Review
Bias against Vitamin C in Mainstream Medicine: Examples from Trials of Vitamin C for Infections
by Harri Hemilä and Elizabeth Chalker
Life 2022, 12(1), 62; https://doi.org/10.3390/life12010062 - 3 Jan 2022
Cited by 6 | Viewed by 5657
Abstract
Evidence has shown unambiguously that, in certain contexts, vitamin C is effective against the common cold. However, in mainstream medicine, the views on vitamin C and infections have been determined by eminence-based medicine rather than evidence-based medicine. The rejection of the demonstrated benefits [...] Read more.
Evidence has shown unambiguously that, in certain contexts, vitamin C is effective against the common cold. However, in mainstream medicine, the views on vitamin C and infections have been determined by eminence-based medicine rather than evidence-based medicine. The rejection of the demonstrated benefits of vitamin C is largely explained by three papers published in 1975—two published in JAMA and one in the American Journal of Medicine—all of which have been standard citations in textbooks of medicine and nutrition and in nutritional recommendations. Two of the papers were authored by Thomas Chalmers, an influential expert in clinical trials, and the third was authored by Paul Meier, a famous medical statistician. In this paper, we summarize several flaws in the three papers. In addition, we describe problems with two recent randomized trial reports published in JAMA which were presented in a way that misled readers. We also discuss shortcomings in three recent JAMA editorials on vitamin C. While most of our examples are from JAMA, it is not the only journal with apparent bias against vitamin C, but it illustrates the general views in mainstream medicine. We also consider potential explanations for the widespread bias against vitamin C. Full article
(This article belongs to the Special Issue Antimicrobial Mechanisms of Vitamin C)
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17 pages, 328 KiB  
Review
The Effects of Vitamin C on the Multiple Pathophysiological Stages of COVID-19
by Jorge R. Miranda-Massari, Alondra P. Toro, Doris Loh, Jose R. Rodriguez, Raul Morales Borges, Victor Marcial-Vega, Jose Olalde, Miguel J. Berdiel, Neil H. Riordan, Juan Manuel Martinez, Armando Gil and Michael J. Gonzalez
Life 2021, 11(12), 1341; https://doi.org/10.3390/life11121341 - 3 Dec 2021
Cited by 7 | Viewed by 9675
Abstract
Currently available anti-viral drugs may be useful in reducing the viral load but are not providing the necessary physiological effects to reduce the SARS-CoV-2 complications efficiently. Treatments that provide better clinical outcomes are urgently needed. Vitamin C (ascorbic acid, AA) is an essential [...] Read more.
Currently available anti-viral drugs may be useful in reducing the viral load but are not providing the necessary physiological effects to reduce the SARS-CoV-2 complications efficiently. Treatments that provide better clinical outcomes are urgently needed. Vitamin C (ascorbic acid, AA) is an essential nutrient with many biological roles that have been proven to play an important part in immune function; it serves as an antioxidant, an anti-viral, and exerts anti-thrombotic effects among many other physiological benefits. Research has proven that AA at pharmacological doses can be beneficial to patients with acute respiratory distress syndrome (ARDS) and other respiratory illnesses, including sepsis. In addition, High-Dose Intravenous Vitamin C (HDIVC) has proven to be effective in patients with different viral diseases, such as influenza, chikungunya, Zika, and dengue. Moreover, HDIVC has been demonstrated to be very safe. Regarding COVID-19, vitamin C can suppress the cytokine storm, reduce thrombotic complications, and diminish alveolar and vascular damage, among other benefits. Due to these reasons, the use of HDIVC should be seriously considered in complicated COVID-19 patients. In this article, we will emphasize vitamin C’s multiple roles in the most prominent pathophysiological processes presented by the COVID-19 disease. Full article
(This article belongs to the Special Issue Antimicrobial Mechanisms of Vitamin C)
12 pages, 278 KiB  
Review
Vitamin C Intervention for Critical COVID-19: A Pragmatic Review of the Current Level of Evidence
by Patrick Holford, Anitra C. Carr, Masuma Zawari and Marcela P. Vizcaychipi
Life 2021, 11(11), 1166; https://doi.org/10.3390/life11111166 - 1 Nov 2021
Cited by 15 | Viewed by 10379
Abstract
Severe respiratory infections are characterized by elevated inflammation and generation of reactive oxygen species (ROS) which may lead to a decrease in antioxidants such as vitamin C and a higher requirement for the vitamin. Administration of intravenous vitamin C to patients with pneumonia [...] Read more.
Severe respiratory infections are characterized by elevated inflammation and generation of reactive oxygen species (ROS) which may lead to a decrease in antioxidants such as vitamin C and a higher requirement for the vitamin. Administration of intravenous vitamin C to patients with pneumonia and sepsis appears to decrease the severity of the disease and potentially improve survival rate. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes pneumonia, sepsis and acute respiratory distress syndrome (ARDS) in severe cases, and is referred to as coronavirus disease 2019 (COVID-19). Patients with COVID-19 infection also appear to have depleted vitamin C status and require additional supplementation of vitamin C during the acute phase of the disease. To date there have been 12 vitamin C and COVID-19 trials published, including five randomised controlled trials (RCTs) and seven retrospective cohort studies. The current level of evidence from the RCTs suggests that intravenous vitamin C intervention may improve oxygenation parameters, reduce inflammatory markers, decrease days in hospital and reduce mortality, particularly in the more severely ill patients. High doses of oral vitamin C supplementation may also improve the rate of recovery in less severe cases. No adverse events have been reported in published vitamin C clinical trials in COVID-19 patients. Upcoming findings from larger RCTs will provide additional evidence on vitamin supplementation in COVID-19 patients. Full article
(This article belongs to the Special Issue Antimicrobial Mechanisms of Vitamin C)

Other

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2 pages, 162 KiB  
Correction
Correction: Coppock et al. Pharmacologic Ascorbic Acid as Early Therapy for Hospitalized Patients with COVID-19: A Randomized Clinical Trial. Life 2022, 12, 453
by Dagan Coppock, Pierre-Christian Violet, Gustavo Vasquez, Katherine Belden, Michael Foster, Bret Mullin, Devon Magee, Isabelle Mikell, Lokesh Shah, Victoria Powers, Brian Curcio, Daniel Monti and Mark Levine
Life 2022, 12(9), 1354; https://doi.org/10.3390/life12091354 - 31 Aug 2022
Cited by 2 | Viewed by 956
Abstract
The authors wish to make a change to the author names (deleting one author—Constantine Daskalakis) for this paper [...] Full article
(This article belongs to the Special Issue Antimicrobial Mechanisms of Vitamin C)
9 pages, 2202 KiB  
Case Report
High Dose Intravenous Vitamin C as Adjunctive Therapy for COVID-19 Patients with Cancer: Two Cases
by Guangling Guo, Qi Chen, Guoshi Luo, Zhongji Meng, Pan Lei, Ping Chen and Jeanne A. Drisko
Life 2022, 12(3), 335; https://doi.org/10.3390/life12030335 - 24 Feb 2022
Viewed by 2691
Abstract
Background: Related to the SARS-CoV-2 pandemic leading to COVID-19 illness, patients with cancer comorbidity are known to have a higher risk of developing severe viral-related events, including death. To date, there are few treatments with proven efficacy for COVID-19. Vitamin C administered intravenously [...] Read more.
Background: Related to the SARS-CoV-2 pandemic leading to COVID-19 illness, patients with cancer comorbidity are known to have a higher risk of developing severe viral-related events, including death. To date, there are few treatments with proven efficacy for COVID-19. Vitamin C administered intravenously (IVC) has been extensively investigated in cancer treatment with a known safety profile and has been proposed to play a role in managing COVID-19. IVC was used to treat COVID-19 patients in hospitals in China, USA, and Europe with reported benefits. We report here unexpected beneficial results from the use of IVC in two severely ill oncology patients with documented COVID-19 lung disease. Case Report: two oncology patients were diagnosed with SARS-CoV-2 infection. Prior to receiving IVC, lung infiltrates and systemic inflammation in both patients were progressing despite multiple anti-viral, antibiotic, and anti-inflammatory treatments with intensive supportive care. Both patients subsequently received 12 g of IVC delivered intravenously over 30 min, given 2 times daily for 7 days. Serial SARS-CoV-2 nucleic acid tests showed that the viral load was negative only after the 7-day IVC treatment. In both patients after receiving IVC infusions, imaging by chest CT or X-ray showed improving lung infiltrates. There were reductions in systematic inflammation by high-sensitivity C-reactive protein (hsCRP), and Interleukin-6 (IL-6) testing. No adverse events were observed related to IVC treatment. Conclusion: the use of high-dose IVC demonstrated unexpected clinical benefits in treating COVID-19 in two cancer patients presenting with complicated severe comorbidities where an unfavorable prognosis was anticipated. Full article
(This article belongs to the Special Issue Antimicrobial Mechanisms of Vitamin C)
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