Vitamin C Supports Healthy Immunology

Vitamin C is a wonder for human immunity.

• 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 

The Possible Role of Vitamin D in Suppressing Cytokine Storm and Associated Mortality in COVID-19 Patients

Staff Writer, DL Mullan 
COVID-19 / Corona Virus / Vitamin C
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Abstract

Abstract Objectives To investigate the possible role of Vitamin D (Vit D) deficiency via unregulated inflammation in COVID-19 complications and associated mortality. Design The time-adjusted case mortality ratio (T-CMR) was estimated as the number of deceased patients on day N divided by the number of confirmed cases on day N-8. The adaptive average of T-CMR (A-CMR) was further calculated as a metric of COVID-19 associated mortality in different countries. A model based on positivity change (PC) and an estimated prevalence of COVID-19 was developed to determine countries with similar screening strategies. Mean concentration of 25-hydroxyvitamin D (25(OH)D) in elderly individuals in countries with similar screening strategies were compared to investigate the potential impact of Vit D on A-CMR. We analyzed data showing a possible association between high C-Reactive Protein (CRP) concentration (CRP greater than or equal to 1 mg/dL) and severe COVID-19. We estimated a link between Vit D status and high CRP in healthy subjects (CRP greater than or equal to 0.2 mg/dL) with an adjustment for age and income to explore the possible role of Vit D in reducing complications attributed to unregulated inflammation and cytokine production. Data Sources Daily admission, recovery, and deceased rate data for patients with COVID-19 were collected from Kaggle as of April 20, 2020. Screening data were collected from Our World in Data and official statements from public authorities. The mean concentration of 25(OH)D among the elderly for comparison with A-CMR was collected from previously published studies from different countries. Chronic factor data used in regression analysis was obtained from published articles. The correlation between Vit D and CRP was calculated based on 9,212 subject-level data from NHANES, 2009-2010. Results A link between 25(OH)D and A-CMR in the US, France, Iran and the UK (countries with similar screening status) may exist. We observed an inverse correlation (correlation coefficient ranging from -0.84 to -1) between high CRP and 25(OH)D. Age and the family income status also correlated to high CRP and subjects with higher age and lower family income presented more incidences of high CRP. Our analysis determined a possible link between high CRP and Vit D deficiency and calculated an OR of 1.8 with 95%CI (1.2 to 2.6) among the elderly (age greater than or equal to 60 yo) in low-income families and an OR of 1.9 with 95%CI (1.4 to 2.7) among the elderly (age greater than or equal to 60 yo) in high-income families. COVID-19 patient-level data shows a notable OR of 3.4 with 95%CI (2.15 to 5.4) for high CRP in severe COVID-19 patients. Conclusion Given that CRP is a surrogate marker for cytokine storm and is associated with Vit D deficiency, based on retrospective data and indirect evidence we see a possible role of Vit D in reducing complications attributed to unregulated inflammation and cytokine storm. Further research is needed to account for other factors through direct measurement of Vit D levels in COVID-19 patients.

Read the entire article at Med Rx iv.


Source: Med Rx iv

Efficacy of glutathione therapy in relieving dyspnea associated with COVID-19 pneumonia: A report of 2 cases

Staff Writer, DL Mullan 
COVID-19 / Corona Virus / Vitamin C
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Abstract

Purpose

Infection with COVID-19 potentially can result in severe outcomes and death from “cytokine storm syndrome”, resulting in novel coronavirus pneumonia (NCP) with severe dyspnea, acute respiratory distress syndrome (ARDS), fulminant myocarditis and multiorgan dysfunction with or without disseminated intravascular coagulation. No published treatment to date has been shown to adequately control the inflammation and respiratory symptoms associated with COVID-19, apart from oxygen therapy and assisted ventilation. We evaluated the effects of using high dose oral and/or IV glutathione in the treatment of 2 patients with dyspnea secondary to COVID-19 pneumonia.


Conclusion

Oral and IV glutathione, glutathione precursors (N-acetyl-cysteine) and alpha lipoic acid may represent a novel treatment approach for blocking NF-κB and addressing “cytokine storm syndrome” and respiratory distress in patients with COVID-19 pneumonia.

Read the rest of the report on Science Direct.


Source: Science Direct

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

Staff Writer, DL Mullan 
COVID-19 / Corona Virus / Vitamin C
_______________________________________

Abstract

L-ascorbic acid (vitamin C) is one of the well-known anti-viral agents, especially to influenza virus. Since the in vivo anti-viral effect is still controversial, we investigated whether vitamin C could regulate influenza virus infection in vivo by using Gulo (-/-) mice, which cannot synthesize vitamin C like humans. First, we found that vitamin C-insufficient Gulo (-/-) mice expired within 1 week after intranasal inoculation of influenza virus (H3N2/Hongkong). Viral titers in the lung of vitamin C-insufficient Gulo (-/-) mice were definitely increased but production of anti-viral cytokine, interferon (IFN)-α/β, was decreased. On the contrary, the infiltration of inflammatory cells into the lung and production of pro-inflammatory cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-α/β, were increased in the lung. Taken together, vitamin C shows in vivo anti-viral immune responses at the early time of infection, especially against influenza virus, through increased production of IFN-α/β.

INTRODUCTION

Vitamin C is known as an essential anti-oxidant (1,2) and enzymatic co-factor for physiological reactions such as hormone production, collagen synthesis (3) and immune potentiation (4-6). Naturally, an insufficiency of vitamin C leads to severe injuries to multiple organs, especially to the heart and brain, since they are both highly aerobic organs that produce more oxygen radicals. In fact, studies of in vivo effect on vitamin C are difficult since most animals, except human and some primate, are capable of synthesizing vitamin C endogenously (7). However, Gulo (-/-) mice were recently developed by the L-gulono-γ-lactone oxidase (Gulo) gene deletion like human, thus they should be supplied with dietary vitamin C (8). It already has been reported that vitamin C concentration was decreased by 10~15% in plasma of the Gulo (-/-) mice without supplementation of vitamin C for 2 weeks (8). We also reported that vitamin C level was remarkably decreased in the most organs in the Gulo (-/-) mice without supplementation of vitamin C for 3 weeks (9).

In addition, we found that numbers of T cell was decreased in the spleen of vitamin C-insufficient Gulo (-/-) mice (10). Even though it is thought that vitamin C shows its anti-viral or anti-tumor effects through the up-regulation of the activity of natural killer (NK) cells and tumor specific cytolytic T lymphocytes (CTLs), its related evidences in vivo are still unclear. The reason why it is impossible to investigate in vivo effect of vitamin C is that all of animals could synthesize vitamin C from glucose thorough the action of L-glunolactone-γ-oxidase (Gulo), as described above (7). However, we confirmed that vitamin C up-regulates NK cell activity through the regulation of activating/inhibitory receptors on the surface of NK cell (our unpublished data). Since it is commonly known that vitamin C and NK cells are closely related to the prevention of common cold and the flu (11-13), we evaluated in vivo anti-viral effect of vitamin C and its related mechanism in Gulo (-/-) mice against influenza virus (H3N2/Honkong/1/68). First, wild type, vitamin C-sufficient Gulo (-/-) mice and vitamin C-insufficient Gulo (-/-) mice were subjected to intranasal inoculation of 20 hemagglutination units (HAU) of influenza virus, and then their survival was monitored. Interestingly, we observed that vitamin C-insufficient Gulo (-/-) mice expired within 1 week, but all of wild type and vitamin C-sufficient Gulo (-/-) mice survived (Fig. 1B). However, the supplementation of vitamin C on a day after virus inoculation could not prevent the death of vitamin C-insufficient Gulo (-/-) mice (Fig. 1B). It suggests that a sufficient amount of vitamin C is needed to prevent in vivo pathogenesis of influenza virus. Also, considering that H3N2 influenza virus shows a good circulation in humans and pigs as well as a slow antigenic drift in swine (14), we believe that the antigenic divergence between human and swine influenza virus might be increased. Therefore, our results shown in Fig. 1 suggest that vitamin C may effectively prevent severe or fatal damages in humans by the infection of influenza virus as well. To clarify the underlying mechanisms on the survival by the presence of the sufficient amounts vitamin C in the mice, we examined the viral titers in the lung of each experimental group. As shown in Fig. 2, viral titer in the lung from vitamin C-insufficient Gulo (-/-) mice was 10 to 15-fold increased, when it was compared with viral titer in wild type and vitamin C-sufficient Gulo (-/-) mice. However, when Gulo (-/-) mice were supplemented with vitamin C after virus inoculation, we could not observe a definite suppression of viral replication. This provides the importance of the vitamin C concentration at the initial stage of influenza virus infection. That is to say, damages through the replication of influenza viruses can be effectively prevented, when vitamin C concentration is sufficiently high at the initial stage of viral infection. If it is insufficient, however, the pathogenesis of influenza virus could not be prevented.

Read the entire report on the NIH's website.

Source: NIH

Potentiality of Virus Transmission through Vaccines

Staff Writer, DL Mullan
Vaccines / Virus Transmission

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Investigating Viruses in Cells Used to Make Vaccines; and Evaluating the Potential Threat Posed by Transmission of Viruses to Humans

The emergence of pathogenic virus infections like influenza and HIV have created an urgent need for new vaccines.

Virus-based vaccines are made in living cells (cell substrates). Some manufacturers are investigating the use of new cell lines to make vaccines. The continual growth of cell lines ensures that there is a consistent supply of the same cells that can yield high quantities of the vaccine.

In some cases the cell lines that are used might be tumorigenic, that is, they form tumors when injected into rodents. Some of these tumor-forming cell lines may contain cancer-causing viruses that are not actively reproducing. Such viruses are hard to detect using standard methods. These latent, or "quiet," viruses pose a potential threat, since they might become active under vaccine manufacturing conditions. Therefore, to ensure the safety of vaccines, our laboratory is investigating ways to activate latent viruses in cell lines and to detect the activated viruses, as well as other unknown viruses, using new technologies. We will then adapt our findings to detect viruses in the same types of cell substrates that are used to produce vaccines. We are also trying to identify specific biological processes that reflect virus activity.

These methods will enable FDA scientists to help manufacturers to determine whether their specific cell substrate is safe to use for vaccine production. The methods our laboratory are developing and testing will help to ensure the production of safe and effective vaccines in two ways: 1) FDA will be able to develop testing guidelines for manufacturers who use new cell substrates for producing vaccines; and 2) FDA will publish the new methods it develops in peer-reviewed scientific journals, thus making them readily accessible to all manufacturers.

We are also evaluating the risk of retrovirus infections in humans. (Retroviruses are RNA viruses that use an enzyme called reverse transcriptase (RT) to replicate; RNA is the de-coded form of DNA). Simian foamy virus (SFV) can be transmitted from nonhuman primates (e.g., monkeys) to humans. Although there is no evidence that SFV causes disease, the virus can remain in a lifelong quiet state in the DNA after infection. Moreover, two individuals in Africa were recently found to be infected with both HIV-1 and SFV. Therefore, it is important to determine if SFV poses a threat to human health and to understand how the virus spreads in order to create strategies for controlling human infections. Such work will also help FDA to develop a new policy regarding blood donation by individuals working with nonhuman primates and implementing formal safety guidelines for people working with SFV-infected animals. We are also investigating the consequences of dual SFV and HIV-1 infection in the monkey model.


Source: FDA