scholarly journals Therapeutic potential of mega-dose vitamin C to reverse organ dysfunction in sepsis and COVID-19

2021 ◽  
Author(s):  
Clive May ◽  
Rinaldo Bellomo ◽  
Yugeesh Lankadeva
Keyword(s):  
Clinical Trials ◽  
Renal Function ◽  
Vitamin C ◽  
Organ Dysfunction ◽  
Therapeutic Potential ◽  
Sodium Ascorbate ◽  
Clinical State ◽  
Reduced Body ◽  
Arterial Blood ◽  
Intravenous Sodium

Sepsis causes multi-organ dysfunction and is a major cause of death in intensive care units, but there are no treatments that reverse the pathophysiological effects of sepsis. Vitamin C has antioxidant, anti-inflammatory, anticoagulant and immune modulatory actions, so is a potential treatment for sepsis. Recent clinical trials of high-doses of intravenous vitamin C (6-16 g/day) had variable effects. Since much higher doses are without side-effects in cancer and burns patients, we studied the effects of a mega-dose of intravenous sodium ascorbate (150 g/40 kg) in a clinically relevant ovine model of sepsis. This treatment dramatically improved the clinical state and over 3-7-h improved cardiovascular, pulmonary, hepatic and renal function and reduced body temperature. In a critically ill COVID-19 patient, intravenous sodium ascorbate (60 g) restored arterial pressure, improved renal function and increased arterial blood oxygen levels. Clinical trials are testing the effectiveness of mega-dose vitamin C in septic patients.

scholarly journals Therapeutic potential of mega-dose vitamin C to reverse organ dysfunction in sepsis and COVID-19

2021 ◽  
Author(s):  
Clive May ◽  
Rinaldo Bellomo ◽  
Yugeesh Lankadeva
Keyword(s):  
Clinical Trials ◽  
Renal Function ◽  
Vitamin C ◽  
Organ Dysfunction ◽  
Therapeutic Potential ◽  
Sodium Ascorbate ◽  
Clinical State ◽  
Reduced Body ◽  
Arterial Blood ◽  
Intravenous Sodium

Sepsis causes multi-organ dysfunction and is a major cause of death in intensive care units, but there are no treatments that reverse the pathophysiological effects of sepsis. Vitamin C has antioxidant, anti-inflammatory, anticoagulant and immune modulatory actions, so is a potential treatment for sepsis. Recent clinical trials of high-doses of intravenous vitamin C (6-16 g/day) had variable effects. Since much higher doses are without side-effects in cancer and burns patients, we studied the effects of a mega-dose of intravenous sodium ascorbate (150 g/40 kg) in a clinically relevant ovine model of sepsis. This treatment dramatically improved the clinical state and over 3-7-h improved cardiovascular, pulmonary, hepatic and renal function and reduced body temperature. In a critically ill COVID-19 patient, intravenous sodium ascorbate (60 g) restored arterial pressure, improved renal function and increased arterial blood oxygen levels. Clinical trials are testing the effectiveness of mega-dose vitamin C in septic patients.

scholarly journals Continuous intravenous vitamin C in the cancer treatment: re-evaluation of a Phase I clinical study

2019 ◽  
Vol 9 (3) ◽  
pp. 180
Author(s):  
Nina Mikirova ◽  
Joseph Casciari ◽  
Ronald Hunninghake
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Vitamin C ◽  
Phase I ◽  
Cancer Patients ◽  
Phase 1 ◽  
Cancer Prognosis ◽  
Sodium Ascorbate ◽  
High Dose ◽  
Treatment Schedule

Background: Intravenous high-dose vitamin C (IVC) therapy is widely used in naturopathic and integrative oncology. A number of Phase I and Phase II clinical trials were launched to prove the benefits of the IVC therapy. Many case studies demonstrated the effectiveness of IVC, with various degrees of success. Clinical trials using IVC to treat cancer have, to date, demonstrated its safety without conclusively proven its efficacy.  One difficulty in administering IVC is determining the optimal treatment schedule.  To this end, data from a previous Phase 1 clinical trial conducted in 1998 using continuous vitamin C infusions was analyzed to examine the effects of this regimen on key prognostic parameters.  Method: Twenty-four subjects were given continuous IVC at doses between 150 and 710 mg/kg/day. Most of the patients had colon cancer with liver and lung metastasis and three patients had pancreatic or liver cancer. All patients had several chemotherapy/radiation treatments before entering the study. Patients were treated by pharmaceutical grade sodium ascorbate diluted in Lactated Ringers solution with the rate of infusion of 20 ml/hr or 10 ml/hr for lower doses. This diluted solution was administered by continuous infusion.Results: Prior to treatment, serum lymphocyte counts and ascorbate concentrations tended to be low while serum levels of lactate dehydrogenase (LDH), neutrophils, and glucose tended to be high.  Improvements were seen during IVC therapy.  In patients with initially elevated neutrophil levels, numbers tended to decrease.  In contrast, increased absolute neutrophil and lymphocyte numbers were seen in patients with initially low counts.  Neutrophil to lymphocyte ratios (NLR) proved to be a good indicator of cancer patients’ survival times (high NLR, low survival).   This was also true of LDH, creatinine, and glucose concentrations.   In patients with the highest pre-treatment NLR, rate of growth of this ratio decreased significantly during therapy.  IVC treatments were also associated with decreases in glucose concentrations, restoration of vitamin C levels, and, in about 40% of cases, reductions in LDH levels. Conclusions: As the result of the study we found that continuous IVC infusions improved several parameters associated with poor cancer prognosis. The data suggests a strategic benefit to using lower IVC doses in continuous infusions: raising the dose above 300 mg/kg/day (20 grams in 70 kg human) increased the frequency of side effects without noticeably increasing plasma ascorbate levels.  Moreover, improvements in lymphocyte counts at low IVC doses tended to decrease at the higher doses.  In conclusion, continuous infusions had benefits to cancer patients and further research in this area is warranted.Keywords: ascorbic acid; continuous infusion; cancer patients; clinical trial; lymphopenia; neutrophil to lymphocyte ratio; hyperglycemia; safety.

scholarly journals Vitamin C in the Treatment of COVID-19

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1172
Author(s):  
Gregorio Paolo Milani ◽  
Marina Macchi ◽  
Anat Guz-Mark
Keyword(s):  
Clinical Trials ◽  
Vitamin C ◽  
Respiratory Infections ◽  
Medical Condition ◽  
Case Reports ◽  
Case Series ◽  
Theoretical Background ◽  
Current Evidence ◽  
Vitamin C Supplementation ◽  
Essential Nutrient

Vitamin C is an essential nutrient that serves as antioxidant and plays a major role as co-factor and modulator of various pathways of the immune system. Its therapeutic effect during infections has been a matter of debate, with conflicting results in studies of respiratory infections and in critically ill patients. This comprehensive review aimed to summarize the current evidence regarding the use of vitamin C in the prevention or treatment of patients with SARS-CoV2 infection, based on available publications between January 2020 and February 2021. Overall, 21 publications were included in this review, consisting of case-reports and case-series, observational studies, and some clinical trials. In many of the publications, data were incomplete, and in most clinical trials the results are still pending. No studies regarding prevention of COVID-19 with vitamin C supplementation were found. Although some clinical observations reported improved medical condition of patients with COVID-19 treated with vitamin C, available data from controlled studies are scarce and inconclusive. Based on the theoretical background presented in this article, and some preliminary encouraging studies, the role of vitamin C in the treatment of patients with SARS-CoV-2 infection should be further investigated.

scholarly journals Therapeutic Features and Updated Clinical Trials of Mesenchymal Stem Cell (MSC)-Derived Exosomes

2021 ◽  
Vol 10 (4) ◽  
pp. 711
Author(s):  
Byung-Chul Lee ◽  
Insung Kang ◽  
Kyung-Rok Yu
Keyword(s):  
Clinical Trials ◽  
Therapeutic Agent ◽  
Therapeutic Potential ◽  
Therapeutic Option ◽  
Treatment Options ◽  
Genetic Material ◽  
Experimental Models ◽  
Attractive Alternative ◽  
Cell Based Therapy ◽  
Cellular Rejection

Identification of the immunomodulatory and regenerative properties of mesenchymal stem cells (MSCs) have made them an attractive alternative therapeutic option for diseases with no effective treatment options. Numerous clinical trials have followed; however, issues such as infusional toxicity and cellular rejection have been reported. To address these problems associated with cell-based therapy, MSC exosome therapy was developed and has shown promising clinical outcomes. MSC exosomes are nanosized vesicles secreted from MSCs and represent a non-cellular therapeutic agent. MSC exosomes retain therapeutic features of the cells from which they originated including genetic material, lipids, and proteins. Similar to MSCs, exosomes can induce cell differentiation, immunoregulation, angiogenesis, and tumor suppression. MSC exosomes have therefore been employed in several experimental models and clinical studies. Here, we review the therapeutic potential of MSC-derived exosomes and summarize currently ongoing clinical trials according to disease type. In addition, we propose several functional enhancement strategies for the effective clinical application of MSC exosome therapy.

scholarly journals The Potency of Seaweed Sulfated Polysaccharides for the Correction of Hemostasis Disorders in COVID-19

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2618
Author(s):  
Tatyana A. Kuznetsova ◽  
Boris G. Andryukov ◽  
Ilona D. Makarenkova ◽  
Tatyana S. Zaporozhets ◽  
Natalya N. Besednova ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Therapeutic Potential ◽  
Low Cost ◽  
Clinical Manifestations ◽  
Optimal Dose ◽  
Monosaccharide Composition ◽  
Structural Features ◽  
Sulfated Polysaccharides ◽  
Clinical Use ◽  
Hemostasis System

Hemostasis disorders play an important role in the pathogenesis, clinical manifestations, and outcome of COVID-19. First of all, the hemostasis system suffers due to a complicated and severe course of COVID-19. A significant number of COVID-19 patients develop signs of hypercoagulability, thrombocytopenia, and hyperfibrinolysis. Patients with severe COVID-19 have a tendency toward thrombotic complications in the venous and arterial systems, which is the leading cause of death in this disease. Despite the success achieved in the treatment of SARS-CoV-2, the search for new effective anticoagulants, thrombolytics, and fibrinolytics, as well as their optimal dose strategies, continues to be relevant. The wide therapeutic potential of seaweed sulfated polysaccharides (PSs), including anticoagulant, thrombolytic, and fibrinolytic activities, opens up new possibilities for their study in experimental and clinical trials. These natural compounds can be important complementary drugs for the recovery from hemostasis disorders due to their natural origin, safety, and low cost compared to synthetic drugs. In this review, the authors analyze possible pathophysiological mechanisms involved in the hemostasis disorders observed in the pathological progression of COVID-19, and also focus the attention of researchers on seaweed PSs as potential drugs aimed to correction these disorders in COVID-19 patients. Modern literature data on the anticoagulant, antithrombotic, and fibrinolytic activities of seaweed PSs are presented, depending on their structural features (content and position of sulfate groups on the main chain of PSs, molecular weight, monosaccharide composition and type of glycosidic bonds, the degree of PS chain branching, etc.). The mechanisms of PS action on the hemostasis system and the issues of oral bioavailability of PSs, important for their clinical use as oral anticoagulant and antithrombotic agents, are considered. The combination of the anticoagulant, thrombolytic, and fibrinolytic properties, along with low toxicity and relative cheapness of production, open up prospects for the clinical use of PSs as alternative sources of new anticoagulant and antithrombotic compounds. However, further investigation and clinical trials are needed to confirm their efficacy.

scholarly journals Targeting the Complement Cascade in the Pathophysiology of COVID-19 Disease

2021 ◽  
Vol 10 (10) ◽  
pp. 2188
Author(s):  
Nicole Ng ◽  
Charles A. Powell
Keyword(s):  
Clinical Trials ◽  
Endothelial Dysfunction ◽  
Severe Acute Respiratory Syndrome ◽  
Disease Progression ◽  
Organ Dysfunction ◽  
Innate Immune ◽  
Complement Cascade ◽  
Significant Morbidity ◽  
Immune Pathways ◽  
Complement Pathways

Severe coronavirus disease 2019 causes multi-organ dysfunction with significant morbidity and mortality. Mounting evidence implicates maladaptive over-activation of innate immune pathways such as the complement cascade as well as endothelial dysfunction as significant contributors to disease progression. We review the complement pathways, the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on these pathways, and promising therapeutic targets in clinical trials.

From mesenchymal stem cells and stromal cells - from bench to bedside

2019 ◽  
Vol 1 (1) ◽  
pp. 36-39
Author(s):  
Bernd Giebel ◽  
Verena Börger ◽  
Mario Gimona ◽  
Eva Rohde
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Stromal Cells ◽  
Therapeutic Agent ◽  
Therapeutic Potential ◽  
Therapeutic Effects ◽  
Cell Replacement ◽  
Beneficial Effects ◽  
Promising Tool

Human mesenchymal stem/stromal cells (MSCs) represent a promising tool in regenerative medicine. Until now, almost one thousand NIH-registered clinical trials investigated their immunomodulatory and pro-regenerative therapeutic potential in various diseases. Despite controversial reports regarding the efficacy of MSC-treatments, MSCs appear to exert their beneficial effects in a paracrine manner rather than by cell replacement. In this context, extracellular vesicles (EVs), such as exosomes and microvesicles, seem to induce the MSCs’ therapeutic effects. Here, we briefly illustrate the potential of MSC-EVs as therapeutic agent of the future.

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