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Adjunctive treatments for the management of septic shock - a narrative review of the current evidence.
Donovan, K, Shah, A, Day, J, McKechnie, SR
Anaesthesia. 2021;(9):1245-1258
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Abstract
Septic shock is a leading cause of death and morbidity worldwide. The cornerstones of management include prompt identification of sepsis, early initiation of antibiotic therapy, adequate fluid resuscitation and organ support. Over the past two decades, there have been considerable improvements in our understanding of the pathophysiology of sepsis and the host response, including regulation of inflammation, endothelial disruption and impaired immunity. This has offered opportunities for innovative adjunctive treatments such as vitamin C, corticosteroids and beta-blockers. Some of these approaches have shown promising results in early phase trials in humans, while others, such as corticosteroids, have been tested in large, international, multicentre randomised controlled trials. Contemporary guidelines make a weak recommendation for the use of corticosteroids to reduce mortality in sepsis and septic shock. Vitamin C, despite showing initial promise in observational studies, has so far not been shown to be clinically effective in randomised trials. Beta-blocker therapy may have beneficial cardiac and non-cardiac effects in septic shock, but there is currently insufficient evidence to recommend their use for this condition. The results of ongoing randomised trials are awaited. Crucial to reducing heterogeneity in the trials of new sepsis treatments will be the concept of enrichment, which refers to the purposive selection of patients with clinical and biological characteristics that are likely to be responsive to the intervention being tested.
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Clinical efficacy and safety of oral and intravenous vitamin C use in patients with malignant diseases.
Hoppe, C, Freuding, M, Büntzel, J, Münstedt, K, Hübner, J
Journal of cancer research and clinical oncology. 2021;(10):3025-3042
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Abstract
BACKGROUND Vitamin C, also called ascorbic acid, is a water-soluble antioxidant and free radical scavenger. It is required in the body for numerous metabolic functions and is involved in the development of proteins and connective tissue. METHODS In April 2020, a systematic search was carried out on five electronic databases (Medline, Embase, Cochrane, Cinahl, PsycINFO) to find studies on the use, efficacy and safety of a complementary therapy with vitamin C in oncological patients. RESULTS Out of the initial 23,195 search results, 21 studies with 1961 patients were included in this review. Five of the included studies (n = 417) were randomized controlled trials (RCTs). The remaining 16 studies belonged to a lower class of evidence. The patients who were treated with vitamin C suffered from various malignant diseases, some in an advanced and palliative stage. Vitamin C was applied intravenously or orally. It was either the only treatment or was combined with chemo- or radiotherapy. Endpoints included the development of the disease-related symptoms, quality of life, mortality, progression-free survival and safety of vitamin C. The studies were of moderate quality and showed either no effect of vitamin C or a positive trend, although this has rarely been statistically proven in group comparisons. No or only slight side effects with both oral and intravenous administration of vitamin C were reported. CONCLUSION Oral intake of vitamin C does not appear to have any effect in patients with malignancies. Data are heterogeneous for intravenous administration. There are no RCTs with statistical group comparisons.
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New promising developments for potential therapeutic applications of high-dose ascorbate as an anticancer drug.
Testa, U, Pelosi, E, Castelli, G
Hematology/oncology and stem cell therapy. 2021;(3):179-191
Abstract
Vitamin C (ascorbate) is an essential dietary requirement, with fundamental redox, anti-oxidant functions at physiologic concentrations. Vitamin C is a cofactor for Fe2+ and 2-oxoglutarate-dependent dioxygenases, englobing large families of enzymes, including also epigenetic regulators of DNA and histone methylation. Importantly, vitamin C is involved in the control of the activity of TET (ten-eleven translocation) enzymes, key epigenetic regulators. For this spectrum of activities, often involving pathways deregulated in cancer cells, vitamin C possesses some pharmacologic activities that can be exploited in anticancer therapy. In particular, the capacity of pharmacological doses of vitamin C to target redox imbalance and to rescue deregulated epigenetic program observed in some cancer cells represents a consistent therapeutic potentiality. Several recent studies have identified some cancer subsets that could benefit from the pharmacological activities of vitamin C. The identification of these potentially responsive patients will help to carefully define controlled clinical trials aiming to evaluate the anticancer activity of Vitamin C.
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The Role of Vitamin C in Two Distinct Physiological States: Physical Activity and Sleep.
Otocka-Kmiecik, A, Król, A
Nutrients. 2020;(12)
Abstract
This paper is a literature overview of the complex relationship between vitamin C and two opposing physiological states, physical activity and sleep. The evidence suggests a clinically important bidirectional association between these two phenomena mediated by different physiological mechanisms. With this in mind, and knowing that both states share a connection with oxidative stress, we discuss the existing body of evidence to answer the question of whether vitamin C supplementation can be beneficial in the context of sleep health and key aspects of physical activity, such as performance, metabolic changes, and antioxidant function. We analyze the effect of ascorbic acid on the main sleep components, sleep duration and quality, focusing on the most common disorders: insomnia, obstructive sleep apnea, and restless legs syndrome. Deeper understanding of those interactions has implications for both public health and clinical practice.
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Manipulation of Ascorbate Biosynthetic, Recycling, and Regulatory Pathways for Improved Abiotic Stress Tolerance in Plants.
Broad, RC, Bonneau, JP, Hellens, RP, Johnson, AAT
International journal of molecular sciences. 2020;(5)
Abstract
Abiotic stresses, such as drought, salinity, and extreme temperatures, are major limiting factors in global crop productivity and are predicted to be exacerbated by climate change. The overproduction of reactive oxygen species (ROS) is a common consequence of many abiotic stresses. Ascorbate, also known as vitamin C, is the most abundant water-soluble antioxidant in plant cells and can combat oxidative stress directly as a ROS scavenger, or through the ascorbate-glutathione cycle-a major antioxidant system in plant cells. Engineering crops with enhanced ascorbate concentrations therefore has the potential to promote broad abiotic stress tolerance. Three distinct strategies have been utilized to increase ascorbate concentrations in plants: (i) increased biosynthesis, (ii) enhanced recycling, or (iii) modulating regulatory factors. Here, we review the genetic pathways underlying ascorbate biosynthesis, recycling, and regulation in plants, including a summary of all metabolic engineering strategies utilized to date to increase ascorbate concentrations in model and crop species. We then highlight transgene-free strategies utilizing genome editing tools to increase ascorbate concentrations in crops, such as editing the highly conserved upstream open reading frame that controls translation of the GDP-L-galactose phosphorylase gene.
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Possible application of high-dose vitamin C in the prevention and therapy of coronavirus infection.
Hoang, BX, Shaw, G, Fang, W, Han, B
Journal of global antimicrobial resistance. 2020;:256-262
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Abstract
Coronaviruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses increase oxidative stress in the body leading to cellular and tissue damage. To combat this, administration of high-dose vitamin C (ascorbic acid or ascorbate), in addition to standard conventional supportive treatments, has been shown to be a safe and effective therapy for severe cases of respiratory viral infection. Morbidity, mortality, infectiveness and spread of infectious diseases are dependent on the host-pathogen relationship. Given the lack of effective and safe antiviral drugs for coronaviruses, there should be more attention in supporting host immune defence, cytoprotection and immunoregulation. Implementation of high-dose vitamin C therapy could dramatically reduce the need for high doses of corticosteroids, antibacterials and antiviral drugs that may be immunosuppressive, adrenal depressive and toxic, complicating the disease course. In order to effectively fight the novel SARS-CoV-2 virus, medical professionals should explore readily available pharmaceutical and nutritional therapeutic agents with proven antioxidant, anti-inflammatory and immunosupportive properties. Supplemental vitamin C may also provide additional benefits for the prevention of viral infections, shorten the disease course and lessen complications of the disease.
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Vitamin C and coronavirus.
Simonson, W
Geriatric nursing (New York, N.Y.). 2020;(3):331-332
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CEAP clinical classes C0S-C4: differences, similarities and role of Ruscus + HMC + vitamin C in patients with chronic venous disease.
Kakkos, SK, Guex, JJ, Lugli, M, Nicolaides, AN
International angiology : a journal of the International Union of Angiology. 2020;(2):118-124
Abstract
Since the publication of the CEAP classification, new research has enriched our knowledge; notably on the heritability of CVD and the genetic and environmental factors involved in this condition, as well as the symptoms apparent within the spectrum of the CEAP clinical classes and the benefits of medical treatment. Using the CEAP classification as a special theme, a symposium with the same title as the present paper was held at the annual meeting of the 2019 European Venous Forum. The lectures presented much valuable information, from which some key points can be extracted. The influence of environmental factors was demonstrated, and the fact that a large amount of information can be obtained from comprehensive history taking. There is robust evidence for heritability. Many candidate genes/loci have been identified, potentially offering new targets for treatment. More research is needed, notably using genome-wide association studies and also on microbiota, which may play a role in CVD through the inflammation pathway. Ruscus + HMC + vitamin C acts by increasing venous and lymphatic tone, protecting microcirculation, and reducing inflammation. It improves quality of life in C0S to C3 CVD patients, while a review of clinical studies and a meta-analysis have confirmed its clinical efficacy across a wide spectrum of CVD clinical classes: C0S, C1S, C2, C3 and C4. It has been awarded a Grade 1A recommendation by the international guidelines.
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Vitamin C Deficiency and the Risk of Osteoporosis in Patients with an Inflammatory Bowel Disease.
Ratajczak, AE, Szymczak-Tomczak, A, Skrzypczak-Zielińska, M, Rychter, AM, Zawada, A, Dobrowolska, A, Krela-Kaźmierczak, I
Nutrients. 2020;(8)
Abstract
Recent research studies have shown that vitamin C (ascorbic acid) may affect bone mineral density and that a deficiency of ascorbic acid leads to the development of osteoporosis. Patients suffering from an inflammatory bowel disease are at a risk of low bone mineral density. It is vital to notice that patients with Crohn's disease and ulcerative colitis also are at risk of vitamin C deficiency which is due to factors such as reduced consumption of fresh vegetables and fruits, i.e., the main sources of ascorbic acid. Additionally, some patients follow diets which may provide an insufficient amount of vitamin C. Moreover, serum vitamin C level also is dependent on genetic factors, such as SLC23A1 and SLC23A2 genes, encoding sodium-dependent vitamin C transporters and GSTM1, GSTP1 and GSTT1 genes which encode glutathione S-transferases. Furthermore, ascorbic acid may modify the composition of gut microbiota which plays a role in the pathogenesis of an inflammatory bowel disease.
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Treating sepsis with vitamin C, thiamine, and hydrocortisone: Exploring the quest for the magic elixir.
Obi, J, Pastores, SM, Ramanathan, LV, Yang, J, Halpern, NA
Journal of critical care. 2020;:231-239
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Abstract
The administration of ascorbic acid (vitamin C) alone or in combination with thiamine (vitamin B1) and corticosteroids (VCTS) has recently been hypothesized to improve hemodynamics, end-organ function, and may even increase survival in critically ill patients. There are several clinical studies that have investigated the use of vitamin C alone or VCTS in patients with sepsis and septic shock or are ongoing. Some of these studies have demonstrated its safety and potential benefit in septic patients. However, many questions remain regarding the optimal dosing regimens and plasma concentrations, timing of administration, and adverse effects of vitamin C and thiamine. These questions exist because the bulk of research regarding the efficacy of vitamin C alone or in combination with thiamine and corticosteroids in sepsis is limited to a few randomized controlled trials, retrospective before-and-after studies, and case reports. Thus, although the underlying rationale and mechanistic pathways of vitamin C and thiamine in sepsis have been well described, the clinical impact of the VCTS regimen is complex and remains to be determined. This review aims to explore the current evidence and potential benefits and adverse effects of the VCTS regimen for the treatment of sepsis.