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

Author(s):  
Clive N. May ◽  
Rinaldo Bellomo ◽  
Yugeesh R. Lankadeva
Author(s):  
Clive May ◽  
Rinaldo Bellomo ◽  
Yugeesh Lankadeva

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.


Author(s):  
Clive May ◽  
Rinaldo Bellomo ◽  
Yugeesh Lankadeva

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.


Biomolecules ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. 161 ◽  
Author(s):  
Sharma ◽  
Martins ◽  
Kuca ◽  
Chaudhary ◽  
Kabra ◽  
...  

Chyawanprash (CP) is an Ayurvedic health supplement which is made up of a super-concentrated blend of nutrient-rich herbs and minerals. It is meant to restore drained reserves of life force (ojas) and to preserve strength, stamina, and vitality, while stalling the course of aging. Chyawanprash is formulated by processing around 50 medicinal herbs and their extracts, including the prime ingredient, Amla (Indian gooseberry), which is the world’s richest source of vitamin C. Chyawanprash preparation involves preparing a decoction of herbs, followed by dried extract preparation, subsequent mixture with honey, and addition of aromatic herb powders (namely clove, cardamom, and cinnamon) as standard. The finished product has a fruit jam-like consistency, and a sweet, sour, and spicy flavor. Scientific exploration of CP is warranted to understand its therapeutic efficacy. Scattered information exploring the therapeutic potential of CP is available, and there is a need to assemble it. Thus, an effort was made to compile the scattered information from ancient Ayurvedic texts and treatises, along with ethnobotanical, ethnopharmacological, and scientifically validated literature, that highlight the role of CP in therapeutics. Citations relevant to the topic were screened.


Inflammasome ◽  
2016 ◽  
Vol 2 (1) ◽  
Author(s):  
Xuesong Sang ◽  
Hongbin Wang ◽  
Yihui Chen ◽  
Qiuhong Guo ◽  
Ailing Lu ◽  
...  

AbstractInflammasomes are intracellular protein complexes that mediate maturation and secretion of the pro-inflammatory cytokines IL-1β and IL-18. Inflammasomes have been connected with various diseases, therefore the regulation of inflammasome activation is important for the development of novel therapies for many inflammatory syndromes. Vitamin C is an essential nutrient and has regulatory effects on immune cells. Here we report that vitamin C has an inhibitory effect on the activation of the NLRP3 inflammasome in vitro and in vivo. Mechanistically, this inhibition is through scavenging mitochondrial ROS but not through NF-κB inhibition. Moreover, specificity tests show that the AIM2 inflammasome and the NLRC4 inflammasome can also be inhibited by vitamin C. Our results have thus identified a new inflammasome regulator and provide therapeutic potential for inflammasome-associated diseases.


2018 ◽  
Author(s):  
Jack Sharkey ◽  
Lorenzo Ressel ◽  
Nathalie Brillant ◽  
Bettina Wilm ◽  
B. Kevin Park ◽  
...  

AbstractCell-based regenerative medicine therapies require robust preclinical safety, efficacy, biodistribution and engraftment data prior to clinical testing. To address these challenges, we have developed an imaging toolbox comprising multi-spectral optoacoustic tomography and ultrasonography, which allows the degree of kidney, liver and cardiac injury and the extent of functional recovery to be assessed non-invasively in a mouse model of multi-organ dysfunction. This toolbox allowed us to determine the therapeutic effects of adoptively transferred M2 macrophages. Using bioluminescence imaging, we could then investigate the association between amelioration and biodistribution. Macrophage therapy improved kidney and liver function to a limited extent, but did not ameliorate histological damage. No improvement in cardiac function was observed. Biodistribution analysis showed that macrophages homed and persisted in the injured kidneys and liver, but did not populate the heart. Our data suggest that the limited improvement observed in kidney and liver function could be mediated by M2 macrophages.


2021 ◽  
Vol 25 (1) ◽  
pp. 1-14
Author(s):  
Uchechi Bliss Onyedikachi ◽  
Favour Matthew Awah ◽  
Charles Nnanna Chukwu ◽  
Emmanuel Ejiofor

Abstract The essential oils of Cymbopogon citratus (EOCC) has found use in medicine, food and chemical industry. This study attempts to provide evidence of its suitability for antioxidant and anti-inflammatory therapy. Total phenol and total flavonoid of EOCC was 49.83±0.39mg GAE/g of extract and 352.82±3.45 µg QEC/g of extract respectively. Gas chromatography-mass spectrometry (GC-MS) analysis of its essential oil (EOCC) showed 25 peaks with myrcenyl acetate (9.703%), caryophyllene (8.997%), citronella (6.383%) been the most abundant. The in vitro anti-inflammatory assay using human red blood cell (HRBC) membrane stabilization shows that at 200µg/mL, the percentage inhibition of EOCC was significantly higher compared to diclofenac both for heat-induced and hypotonic induced haemolysis. 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays showed a comparable and dose-dependent increase from 50 to 400 μg/mL in relation to vitamin C. Half maximal inhibitory concentration (IC50) of EOCC (73.16±12.89 μg/mL and 656.01±0.01 μmol Fe (II)/L) was remarkably higher compared to that of vitamin C (69.09±4.52 μg/mL and 246.79±0.01 μmol Fe (II)/L) both for DPPH and FRAP assays respectively. In conclusion, results from this study establish preliminary evidence on the therapeutic potential of EOCC in managing inflammation and oxidative stress caused by free radicals.


2019 ◽  
Vol 3 (24) ◽  
pp. 4187-4201 ◽  
Author(s):  
Supinya Iamsawat ◽  
Linlu Tian ◽  
Anusara Daenthanasanmak ◽  
Yongxia Wu ◽  
Hung D. Nguyen ◽  
...  

Key Points Vit C promotes the generation and stability of CD8+ iTregs. Vit C–stabilized CD8+ iTregs have an increased potential to suppress GVHD while preserving the GVL effect.


Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2157
Author(s):  
Aileen Hill ◽  
Christina Borgs ◽  
Christina Fitzner ◽  
Christian Stoppe

Background: Oxidative stress contributes to organ dysfunction after cardiac surgery and still represents a major problem. Antioxidants, such as vitamins C and E might be organ protective. Methods: The primary objective of this prospective observational study was the description to evaluate the perioperative vitamin C and E levels in 56 patients undergoing cardiac surgery with the use of cardiopulmonary bypass. The association of vitamin C with inflammatory reaction, oxidative stress, organ dysfunctions, and clinical outcomes were evaluated in an explorative approach. Results: Vitamin C levels decreased significantly from 6.5 (3.5–11.5) mg/L before surgery to 2.8 (2.0–3.9) mg/L 48 h after surgery (p < 0.0001). Fifty-six percent of patients had a suboptimal vitamin C status even before surgery. In protein-denaturized probes, significantly higher vitamin C concentrations were detected (p = 0.0008). Vitamin E levels decreased significantly from preoperative level 11.6 (9.5–13.2) mg/L to 7.1 (5.5–7.4) mg/L, (p = 0.0002) at the end of cardiopulmonary bypass, remained low during the first day on ICU and recovered to 8.2 (7.1–9.3) mg/L 48 h after surgery. No patient was vitamin E deficient before surgery. Analysis showed no statistically significant association of vitamin C with inflammation, oxidative stress or organ dysfunction levels in patients with previously suboptimal vitamin C status or patients with a perioperative decrease of ≥50% vitamin C after surgery. Patients with higher vitamin C levels had a shorter ICU stay than those who were vitamin C depleted, which was not statistically significant (72 versus 135 h, p = 0.1990). Conclusion: Vitamin C and E levels significantly declined intraoperatively and remained significantly reduced low for 2 days after cardiac surgery. The influence of reduced serum levels on the inflammatory reaction and clinical outcome of the patients remain unclear in this small observational study and need to be investigated further. Given vitamin C´s pleiotropic role in the human defense mechanisms, further trials are encouraged to evaluate the clinical significance of Vitamin C in cardiac surgery patients.


2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Yu-Lei Gao ◽  
Bin Lu ◽  
Jian-Hua Zhai ◽  
Yan-Cun Liu ◽  
Hai-Xia Qi ◽  
...  

Cellular immunosuppression appears to be involved in sepsis and sepsis-induced multiple organ dysfunction syndrome (MODS). Recent evidence showed that parenteral vitamin C (Vit C) had the ability to attenuate sepsis and sepsis-induced MODS. Herein, we investigated the impact of parenteral Vit C on cellular immunosuppression and the therapeutic value in sepsis. Using cecal ligation and puncture (CLP), sepsis was induced in WT and Gulo−/− mice followed with 200 mg/Kg parenteral Vit C administration. The immunologic functions of CD4+CD25+ regulatory T cells (Tregs) and CD4+CD25− T cells, as well as the organ functions, were determined. Administration of parenteral Vit C per se markedly improved the outcome of sepsis and sepsis-induced MODS of WT and Gulo−/− mice. The negative immunoregulation of Tregs was inhibited, mainly including inhibiting the expression of forkhead helix transcription factor- (Foxp-) 3, cytotoxic T lymphocyte associated antigen- (CTLA-) 4, membrane associated transforming growth factor-β (TGF-βm+), and the secretion of inhibitory cytokines [including TGF-β and interleukin- (IL-) 10], as well as CD4+ T cells-mediated cellular immunosuppression which was improved by parenteral Vit C in WT and Gulo−/− septic mice. These results suggested that parenteral Vit C has the ability to improve the outcome of sepsis and sepsis-induced MODS and is associated with improvement in cellular immunosuppression.


Sign in / Sign up

Export Citation Format

Share Document