Special Issue "Vitamin C: From Bench to Bedside"

A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Micronutrients and Human Health".

Deadline for manuscript submissions: 31 December 2020.

Special Issue Editors

Dr. Anitra Carr
Website
Guest Editor
University of Otgao, Chriscthurch, New Zealand
Interests: vitamin C; pneumonia; sepsis; immune function; diabetes; metabolic health; mood; cognitive health; health-related quality of life; recommended dietary intakes
Special Issues and Collections in MDPI journals
Prof. Dr. Jens Lykkesfeldt
Website
Co-Guest Editor
Experimental Pharmacology & Toxicology, Faculty of Health & Medical Sciences, University of Copenhagen, Ridebanevej 9, DK-1870 Frederiksberg C, Denmark
Interests: vitamin C in health and disease; vitamin C deficiency; oxidative stress and damage; pharmacokinetics; lifestyle diseases; non-alcoholic fatty liver disease; disease animal models
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Vitamin C (ascorbic acid) is a normal liver metabolite in most animals, with humans being a notable exception due to random genetic mutations that have occurred during our evolution. As such, it has become a vitamin (vital to life), with requirements increasing significantly during various illnesses, particularly severe infections. Recent international clinical trials are highlighting the potential for intravenous vitamin C administration to improve clinical outcomes for patients, particularly those with severe respiratory illness and sepsis, and some cancers. Furthermore, there has been an upsurge in new discoveries and new mechanistic insights, particularly around epigenetic regulation by vitamin C, that are providing rationales for future targeted clinical trials. Other areas with potential benefit from vitamin C include metabolic disorders and mental health. The health benefits from increased vitamin C could be dramatic as the prevalence of these conditions continues to rise. What is needed moving forward are well designed observational and interventional studies, which take into account baseline status and the unique pharmacokinetics of vitamin C, to help address the current gaps in our knowledge. Underpinning mechanistic research will also further our ability to inform good clinical practice.

Assoc. Prof. Anitra Carr
Guest Editor

Manuscript Submission Information

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Keywords

  • cancer
  • quality of life
  • epigenetics
  • infection
  • sepsis
  • inflammation
  • immune function
  • metabolic health
  • cognitive function
  • mental health

Published Papers (15 papers)

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Editorial

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Open AccessEditorial
The Emerging Role of Vitamin C in the Prevention and Treatment of COVID-19
Nutrients 2020, 12(11), 3286; https://doi.org/10.3390/nu12113286 - 27 Oct 2020
Abstract
Investigation into the role of vitamin C in the prevention and treatment of pneumonia and sepsis has been underway for many decades. This research has laid a strong foundation for translation of these findings into patients with severe coronavirus disease (COVID-19). Research has [...] Read more.
Investigation into the role of vitamin C in the prevention and treatment of pneumonia and sepsis has been underway for many decades. This research has laid a strong foundation for translation of these findings into patients with severe coronavirus disease (COVID-19). Research has indicated that patients with pneumonia and sepsis have low vitamin C status and elevated oxidative stress. Administration of vitamin C to patients with pneumonia can decrease the severity and duration of the disease. Critically ill patients with sepsis require intravenous administration of gram amounts of the vitamin to normalize plasma levels, an intervention that some studies suggest reduces mortality. The vitamin has pleiotropic physiological functions, many of which are relevant to COVID-19. These include its antioxidant, anti-inflammatory, antithrombotic and immuno-modulatory functions. Preliminary observational studies indicate low vitamin C status in critically ill patients with COVID-19. There are currently a number of randomized controlled trials (RCTs) registered globally that are assessing intravenous vitamin C monotherapy in patients with COVID-19. Since hypovitaminosis C and deficiency are common in low–middle-income settings, and many of the risk factors for vitamin C deficiency overlap with COVID-19 risk factors, it is possible that trials carried out in populations with chronic hypovitaminosis C may show greater efficacy. This is particularly relevant for the global research effort since COVID-19 is disproportionately affecting low–middle-income countries and low-income groups globally. One small trial from China has finished early and the findings are currently under peer review. There was significantly decreased mortality in the more severely ill patients who received vitamin C intervention. The upcoming findings from the larger RCTs currently underway will provide more definitive evidence. Optimization of the intervention protocols in future trials, e.g., earlier and sustained administration, is warranted to potentially improve its efficacy. Due to the excellent safety profile, low cost, and potential for rapid upscaling of production, administration of vitamin C to patients with hypovitaminosis C and severe respiratory infections, e.g., COVID-19, appears warranted. Full article
(This article belongs to the Special Issue Vitamin C: From Bench to Bedside)
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Research

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Open AccessArticle
Low Vitamin C Status in Patients with Cancer Is Associated with Patient and Tumor Characteristics
Nutrients 2020, 12(8), 2338; https://doi.org/10.3390/nu12082338 - 05 Aug 2020
Cited by 1
Abstract
Vitamin C (ascorbate) acts as an antioxidant and enzyme cofactor, and plays a vital role in human health. Vitamin C status can be affected by illness, with low levels being associated with disease due to accelerated turnover. However, robust data on the ascorbate [...] Read more.
Vitamin C (ascorbate) acts as an antioxidant and enzyme cofactor, and plays a vital role in human health. Vitamin C status can be affected by illness, with low levels being associated with disease due to accelerated turnover. However, robust data on the ascorbate status of patients with cancer are sparse. This study aimed to accurately measure ascorbate concentrations in plasma from patients with cancer, and determine associations with patient or tumor characteristics. We recruited 150 fasting patients with cancer (of 199 total recruited) from two cohorts, either prior to cancer surgery or during cancer chemo- or immunotherapy. A significant number of patients with cancer had inadequate plasma ascorbate concentrations. Low plasma status was more prevalent in patients undergoing cancer therapy. Ascorbate status was higher in women than in men, and exercising patients had higher levels than sedentary patients. Our study may prompt increased vigilance of ascorbate status in cancer patients. Full article
(This article belongs to the Special Issue Vitamin C: From Bench to Bedside)
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Open AccessArticle
Patients Undergoing Myeloablative Chemotherapy and Hematopoietic Stem Cell Transplantation Exhibit Depleted Vitamin C Status in Association with Febrile Neutropenia
Nutrients 2020, 12(6), 1879; https://doi.org/10.3390/nu12061879 - 24 Jun 2020
Cited by 1
Abstract
Patients undergoing myeloablative chemotherapy and hematopoietic stem cell transplantation (HSCT) experience profound neutropenia and vulnerability to infection. Previous research has indicated that patients with infections have depleted vitamin C status. In this study, we recruited 38 patients with hematopoietic cancer who were undergoing [...] Read more.
Patients undergoing myeloablative chemotherapy and hematopoietic stem cell transplantation (HSCT) experience profound neutropenia and vulnerability to infection. Previous research has indicated that patients with infections have depleted vitamin C status. In this study, we recruited 38 patients with hematopoietic cancer who were undergoing conditioning chemotherapy and HSCT. Blood samples were collected prior to transplantation, at one week, two weeks and four weeks following transplantation. Vitamin C status and biomarkers of inflammation (C-reactive protein) and oxidative stress (protein carbonyls and thiobarbituric acid reactive substances) were assessed in association with febrile neutropenia. The vitamin C status of the study participants decreased from 44 ± 7 µmol/L to 29 ± 5 µmol/L by week one (p = 0.001) and 19 ± 6 µmol/L by week two (p < 0.001), by which time all of the participants had undergone a febrile episode. By week four, vitamin C status had increased to 37 ± 10 µmol/L (p = 0.1). Pre-transplantation, the cohort comprised 19% with hypovitaminosis C (i.e., <23 µmol/L) and 8% with deficiency (i.e., <11 µmol/L). At week one, those with hypovitaminosis C had increased to 38%, and at week two, 72% had hypovitaminosis C, and 34% had outright deficiency. C-reactive protein concentrations increased from 3.5 ± 1.8 mg/L to 20 ± 11 mg/L at week one (p = 0.002), and 119 ± 25 mg/L at week two (p < 0.001), corresponding to the development of febrile neutropenia in the patients. By week four, these values had dropped to 17 ± 8 mg/L (p < 0.001). There was a significant inverse correlation between C-reactive protein concentrations and vitamin C status (r = −0.424, p < 0.001). Lipid oxidation (thiobarbituric acid reactive substances (TBARS)) increased significantly from 2.0 ± 0.3 µmol/L at baseline to 3.3 ± 0.6 µmol/L by week one (p < 0.001), and remained elevated at week two (p = 0.003), returning to baseline concentrations by week four (p = 0.3). Overall, the lowest mean vitamin C values (recorded at week two) corresponded with the highest mean C-reactive protein values and lowest mean neutrophil counts. Thus, depleted vitamin C status in the HSCT patients coincides with febrile neutropenia and elevated inflammation and oxidative stress. Full article
(This article belongs to the Special Issue Vitamin C: From Bench to Bedside)
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Open AccessArticle
Patients with Community Acquired Pneumonia Exhibit Depleted Vitamin C Status and Elevated Oxidative Stress
Nutrients 2020, 12(5), 1318; https://doi.org/10.3390/nu12051318 - 06 May 2020
Cited by 9
Abstract
Pneumonia is a severe lower respiratory tract infection that is a common complication and a major cause of mortality of the vitamin C-deficiency disease scurvy. This suggests an important link between vitamin C status and lower respiratory tract infections. Due to the paucity [...] Read more.
Pneumonia is a severe lower respiratory tract infection that is a common complication and a major cause of mortality of the vitamin C-deficiency disease scurvy. This suggests an important link between vitamin C status and lower respiratory tract infections. Due to the paucity of information on the vitamin C status of patients with pneumonia, we assessed the vitamin C status of 50 patients with community-acquired pneumonia and compared these with 50 healthy community controls. The pneumonia cohort comprised 44 patients recruited through the Acute Medical Assessment Unit (AMAU) and 6 patients recruited through the Intensive Care Unit (ICU); mean age 68 ± 17 years, 54% male. Clinical, microbiological and hematological parameters were recorded. Blood samples were tested for vitamin C status using HPLC with electrochemical detection and protein carbonyl concentrations, an established marker of oxidative stress, using ELISA. Patients with pneumonia had depleted vitamin C status compared with healthy controls (23 ± 14 µmol/L vs. 56 ± 24 µmol/L, p < 0.001). The more severe patients in the ICU had significantly lower vitamin C status than those recruited through AMAU (11 ± 3 µmol/L vs. 24 ± 14 µmol/L, p = 0.02). The pneumonia cohort comprised 62% with hypovitaminosis C and 22% with deficiency, compared with only 8% hypovitaminosis C and no cases of deficiency in the healthy controls. The pneumonia cohort also exhibited significantly elevated protein carbonyl concentrations compared with the healthy controls (p < 0.001), indicating enhanced oxidative stress in the patients. We were able to collect subsequent samples from 28% of the cohort (mean 2.7 ± 1.7 days; range 1–7 days). These showed no significant differences in vitamin C status or protein carbonyl concentrations compared with baseline values (p = 0.6). Overall, the depleted vitamin C status and elevated oxidative stress observed in the patients with pneumonia indicates an enhanced requirement for the vitamin during their illness. Therefore, these patients would likely benefit from additional vitamin C supplementation to restore their blood and tissue levels to optimal. This may decrease excessive oxidative stress and aid in their recovery. Full article
(This article belongs to the Special Issue Vitamin C: From Bench to Bedside)
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Open AccessArticle
A Cecal Slurry Mouse Model of Sepsis Leads to Acute Consumption of Vitamin C in the Brain
Nutrients 2020, 12(4), 911; https://doi.org/10.3390/nu12040911 - 26 Mar 2020
Cited by 1
Abstract
Vitamin C (ascorbate, ASC) is a critical antioxidant in the body with specific roles in the brain. Despite a recent interest in vitamin C therapies for critical care medicine, little is known about vitamin C regulation during acute inflammation and critical illnesses such [...] Read more.
Vitamin C (ascorbate, ASC) is a critical antioxidant in the body with specific roles in the brain. Despite a recent interest in vitamin C therapies for critical care medicine, little is known about vitamin C regulation during acute inflammation and critical illnesses such as sepsis. Using a cecal slurry (CS) model of sepsis in mice, we determined ASC and inflammatory changes in the brain following the initial treatment. ASC levels in the brain were acutely decreased by approximately 10% at 4 and 24 h post CS treatment. Changes were accompanied by a robust increase in liver ASC levels of up to 50%, indicating upregulation of synthesis beginning at 4 h and persisting up to 7 days post CS treatment. Several key cytokines interleukin 6 (IL-6), interleukin 1β (IL-1β), tumor necrosis factor alpha (TNFα), and chemokine (C-X-C motif) ligand 1 (CXCL1, KC/Gro) were also significantly elevated in the cortex at 4 h post CS treatment, although these levels returned to normal by 48 h. These data strongly suggest that ASC reserves are directly challenged throughout illness and recovery from sepsis. Given the timescale of this response, decreases in cortical ASC are likely driven by hyper-acute neuroinflammatory processes. However, future studies are required to confirm this relationship and to investigate how this deficiency may subsequently impact neuroinflammation. Full article
(This article belongs to the Special Issue Vitamin C: From Bench to Bedside)
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Open AccessArticle
Erythrocyte Ascorbate Is a Potential Indicator of Steady-State Plasma Ascorbate Concentrations in Healthy Non-Fasting Individuals
Nutrients 2020, 12(2), 418; https://doi.org/10.3390/nu12020418 - 06 Feb 2020
Cited by 1
Abstract
Plasma vitamin C concentrations fluctuate in response to recent dietary intake; therefore levels are typically determined in the fasting state. Erythrocyte ascorbate concentrations have been shown to be similar to plasma levels, but little is known about the kinetics of ascorbate accumulation in [...] Read more.
Plasma vitamin C concentrations fluctuate in response to recent dietary intake; therefore levels are typically determined in the fasting state. Erythrocyte ascorbate concentrations have been shown to be similar to plasma levels, but little is known about the kinetics of ascorbate accumulation in these cells. In this study, we investigated ascorbate uptake into erythrocytes after dietary supplementation with vitamin C and compared it to changes in plasma ascorbate concentrations. Seven individuals with baseline fasting plasma vitamin C concentrations ≥ 50 µmol/L were depleted of vitamin C-containing foods and drinks for one week, and then supplemented with 250 mg vitamin C/day in addition to resuming their normal diet. Fasting or steady-state plasma ascorbate concentrations declined to almost half of their baseline concentration over the week of vitamin C depletion, and then returned to saturation within two days of beginning supplementation. Erythrocyte ascorbate concentrations exhibited a very similar profile to plasma levels, with values ~76% of plasma, and a strong linear correlation (r = 0.89, p < 0.0001). Using a pharmacokinetic study design in six individuals with baseline fasting plasma vitamin C concentrations ≥50 µmol/L, we also showed that, unlike plasma, which peaked between 2 and 4 h following ingestion of 200 mg of vitamin C, erythrocyte ascorbate concentrations did not change in the six hours after supplementation. The data from these two intervention studies indicate that erythrocyte ascorbate concentration provides a stable measure of steady-state plasma ascorbate status and could be used to monitor ascorbate status in healthy non-fasting individuals. Full article
(This article belongs to the Special Issue Vitamin C: From Bench to Bedside)
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Open AccessArticle
Vitamin C Inhibits Triple-Negative Breast Cancer Metastasis by Affecting the Expression of YAP1 and Synaptopodin 2
Nutrients 2019, 11(12), 2997; https://doi.org/10.3390/nu11122997 - 06 Dec 2019
Cited by 6
Abstract
Vitamin C supplementation has been shown to decrease triple-negative breast cancer (TNBC) metastasis. However, the molecular mechanism whereby vitamin C inhibits metastasis remains elusive. It has been postulated that vitamin C reduces the levels of HIF-1α, the master regulator of metastasis, by promoting [...] Read more.
Vitamin C supplementation has been shown to decrease triple-negative breast cancer (TNBC) metastasis. However, the molecular mechanism whereby vitamin C inhibits metastasis remains elusive. It has been postulated that vitamin C reduces the levels of HIF-1α, the master regulator of metastasis, by promoting its hydroxylation and degradation. Here, we show that vitamin C at 100 µM, a concentration achievable in the plasma in vivo by oral administration, blocks TNBC cell migration and invasion in vitro. The protein level of HIF-1α remains largely unchanged in cultured TNBC cells and xenografts, partially due to its upregulated transcription by vitamin C, suggesting that HIF-1α unlikely mediates the action of vitamin C on metastasis. Vitamin C treatment upregulates the expression of synaptopodin 2 and downregulates the expression of the transcription coactivator YAP1, both genes in the Hippo pathway. The changes in SYNPO2 and YAP1 expression were subsequently validated at mRNA and protein levels in cultured TNBC cells and xenografts. Further experiments showed that vitamin C treatment inhibits F-actin assembly and lamellipodia formation, which correlates with the changes in SYNPO2 and YAP1 expression. Overall, these results suggest that vitamin C inhibits TNBC metastasis by affecting the expression of SYNPO2 and YAP1. Vitamin C may thus have a potential role in the prevention and treatment of TNBC metastasis. Full article
(This article belongs to the Special Issue Vitamin C: From Bench to Bedside)
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Open AccessArticle
Subphenotypes in Patients with Septic Shock Receiving Vitamin C, Hydrocortisone, and Thiamine: A Retrospective Cohort Analysis
Nutrients 2019, 11(12), 2976; https://doi.org/10.3390/nu11122976 - 05 Dec 2019
Cited by 2
Abstract
This study aimed to identify septic phenotypes in patients receiving vitamin C, hydrocortisone, and thiamine using temperature and white blood cell count. Data were obtained from septic shock patients who were also treated using a vitamin C protocol in a medical intensive care [...] Read more.
This study aimed to identify septic phenotypes in patients receiving vitamin C, hydrocortisone, and thiamine using temperature and white blood cell count. Data were obtained from septic shock patients who were also treated using a vitamin C protocol in a medical intensive care unit. Patients were divided into groups according to the temperature measurements as well as white blood cell counts within 24 h before starting the vitamin C protocol. In the study, 127 patients included who met the inclusion criteria. In the cohort, four groups were identified: “Temperature ≥37.1 °C, white blood cell count ≥15.0 1000/mm3” (group A; n = 27), “≥37.1 °C, <15.0 1000/mm3” (group B; n = 30), “<37.1 °C, ≥15.0 1000/mm3” (group C; n = 35) and “<37.1 °C, <15.0 1000/mm3” (group D; n = 35). The intensive care unit mortality rates were 15% for group A, 33% for group B, 34% for group C, and 49% for group D (p = 0.051). The temporal improvement in organ dysfunction and vasopressor dose seemed more apparent in group A patients. Our results suggest that different subphenotypes exist among sepsis patients treated using a vitamin C protocol, and clinical outcomes might be better for patients with the hyperinflammatory subphenotype. Full article
(This article belongs to the Special Issue Vitamin C: From Bench to Bedside)
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Open AccessArticle
Plasma Vitamin C Levels: Risk Factors for Deficiency and Association with Self-Reported Functional Health in the European Prospective Investigation into Cancer-Norfolk
Nutrients 2019, 11(7), 1552; https://doi.org/10.3390/nu11071552 - 09 Jul 2019
Cited by 6
Abstract
Background: To investigate the demographic and lifestyles factors associated with vitamin C deficiency and to examine the association between plasma vitamin C level and self-reported physical functional health. Methods: A population-based cross-sectional study using the European Prospective Investigation into Cancer-Norfolk study. Plasma vitamin [...] Read more.
Background: To investigate the demographic and lifestyles factors associated with vitamin C deficiency and to examine the association between plasma vitamin C level and self-reported physical functional health. Methods: A population-based cross-sectional study using the European Prospective Investigation into Cancer-Norfolk study. Plasma vitamin C level < 11 µmol/L indicated vitamin C deficiency. Unconditional logistic regression models assessed the association between vitamin C deficiency and potential risk factors. Associations between quartiles of vitamin C and self-reported functional health measured by the 36-item short-form questionnaire (SF-36) were assessed. Results: After adjustment, vitamin C deficiency was associated with older age, being male, lower physical activity, smoking, more socially deprived area (Townsend index) and a lower educational attainment. Compared to the highest, those in the lowest quartile of vitamin C were more likely to score in the lowest decile of physical function (adjusted odds ratio (aOR): 1.43 (95%CI: 1.21–1.70)), bodily pain (aOR: 1.29 (95% CI: 1.07–1.56)), general health (aOR: 1.4 (95%CI: 1.18–1.66)), and vitality (aOR: 1.23 (95%CI: 1.04–1.45)) SF-36 scores. Conclusions: Simple public health interventions should be aimed at populations with risk factors for vitamin C deficiency. Poor self-reported functional health was associated with lower plasma vitamin C levels, which may reflect symptoms of latent scurvy. Full article
(This article belongs to the Special Issue Vitamin C: From Bench to Bedside)
Open AccessArticle
The Role of Physiological Vitamin C Concentrations on Key Functions of Neutrophils Isolated from Healthy Individuals
Nutrients 2019, 11(6), 1363; https://doi.org/10.3390/nu11061363 - 17 Jun 2019
Cited by 11
Abstract
Vitamin C (ascorbate) is important for neutrophil function and immune health. Studies showing improved immune function have primarily used cells from scorbutic animals or from individuals with infectious conditions or immune cell disorders. Few studies have focused on the requirements of neutrophils from [...] Read more.
Vitamin C (ascorbate) is important for neutrophil function and immune health. Studies showing improved immune function have primarily used cells from scorbutic animals or from individuals with infectious conditions or immune cell disorders. Few studies have focused on the requirements of neutrophils from healthy adults. Therefore, we have investigated the role of vitamin C, at concentrations equivalent to those obtained in plasma from oral intakes (i.e., 50–200 µmol/L), on key functions of neutrophils isolated from healthy individuals. Cells were either pre-loaded with dehydroascorbic acid, which is rapidly reduced intracellularly to ascorbate, or the cells were activated in the presence of extracellular ascorbate. We measured the effects of enhanced ascorbate uptake on the essential functions of chemotaxis, oxidant production, programmed cell death and neutrophil extracellular trap (NET) formation. We found that neutrophils isolated from healthy individuals already had replete ascorbate status (0.35 nmol/106 cells), therefore they did not uptake additional ascorbate. However, they readily took up dehydroascorbic acid, thus significantly increasing their intracellular ascorbate concentrations, although this was found to have no additional effect on superoxide production or chemotaxis. Interestingly, extracellular ascorbate appeared to enhance directional mobilityin the presence of the chemoattractant formyl-methionyl-leucyl-phenylalanine (fMLP). Stimulation of the cells in the presence of ascorbate significantly increased intracellular ascorbate concentrations and, although this exhibited a non-significant increase in phosphatidylserine exposure, NET formation was significantly attenuated. Our findings demonstrate the ability of neutrophils to regulate their uptake of ascorbate from the plasma of healthy humans to maintain an optimal level within the cell for proper functioning. Higher oral intakes, however, may help reduce tissue damage and inflammatory pathologies associated with NET formation. Full article
(This article belongs to the Special Issue Vitamin C: From Bench to Bedside)
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Review

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Open AccessReview
The Effect of Perioperative Vitamin C on Postoperative Analgesic Consumption: A Meta-Analysis of Randomized Controlled Trials
Nutrients 2020, 12(10), 3109; https://doi.org/10.3390/nu12103109 - 12 Oct 2020
Abstract
Because the analgesic effect of vitamin C against acute pain remains poorly addressed, this meta-analysis aimed at investigating its effectiveness against acute postoperative pain. A total of seven randomized controlled trials with placebo/normal controls were identified from PubMed, Cochrane Library, Medline, Google Scholar, [...] Read more.
Because the analgesic effect of vitamin C against acute pain remains poorly addressed, this meta-analysis aimed at investigating its effectiveness against acute postoperative pain. A total of seven randomized controlled trials with placebo/normal controls were identified from PubMed, Cochrane Library, Medline, Google Scholar, and Embase databases. Pooled analysis showed a lower pain score (standardized mean difference (SMD) = −0.68, 95% CI: −1.01 to −0.36, p < 0.0001; I2 = 57%) and a lower morphine consumption (weighted mean difference (WMD) = −2.44 mg, 95% CI: −4.03 to −0.86, p = 0.003; I2 = 52%) in the vitamin group than that in the placebo group within postoperative 1–2 h. At postoperative 24 h, a lower pain score (SMD = −0.65, 95% CI: −1.11 to −0.19, p = 0.005; I2 = 81%) and lower morphine consumption (WMD = −6.74 mg, 95% CI: −9.63 to −3.84, p < 0.00001; I2 = 85%) were also noted in the vitamin group. Subgroup analyses demonstrated significant reductions in pain severity and morphine requirement immediately (1–2 h) and 24 h after surgery for patients receiving intravenous vitamin C but not in the oral subgroup. These findings showed significant reductions in pain score and opioid requirement up to postoperative 24 h, respectively, suggesting the effectiveness of perioperative vitamin C use. Further large-scale trials are warranted to elucidate its optimal intravenous dosage and effectiveness against chronic pain in the postoperative pain control setting. Full article
(This article belongs to the Special Issue Vitamin C: From Bench to Bedside)
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Open AccessReview
Vitamin C for Cardiac Protection during Percutaneous Coronary Intervention: A Systematic Review of Randomized Controlled Trials
Nutrients 2020, 12(8), 2199; https://doi.org/10.3390/nu12082199 - 23 Jul 2020
Abstract
Percutaneous coronary intervention (PCI) is the preferred treatment for acute coronary syndrome (ACS) secondary to atherosclerotic coronary artery disease. This nonsurgical procedure is also used for selective patients with stable angina. Although the procedure is essential for restoring blood flow, reperfusion can increase [...] Read more.
Percutaneous coronary intervention (PCI) is the preferred treatment for acute coronary syndrome (ACS) secondary to atherosclerotic coronary artery disease. This nonsurgical procedure is also used for selective patients with stable angina. Although the procedure is essential for restoring blood flow, reperfusion can increase oxidative stress as a side effect. We address whether intravenous infusion of vitamin C (VC) prior to PCI provides a benefit for cardioprotection. A total of eight randomized controlled trials (RCT) reported in the literature were selected from 371 publications through systematic literature searches in six electronic databases. The data of VC effect on cardiac injury biomarkers and cardiac function were extracted from these trials adding up to a total of 1185 patients. VC administration reduced cardiac injury as measured by troponin and CK-MB elevations, along with increased antioxidant reservoir, reduced reactive oxygen species (ROS) and decreased inflammatory markers. Improvement of the left ventricular ejection fraction (LVEF) and telediastolic left ventricular volume (TLVV) showed a trend but inconclusive association with VC. Intravenous infusion of VC before PCI may serve as an effective method for cardioprotection against reperfusion injury. Full article
(This article belongs to the Special Issue Vitamin C: From Bench to Bedside)
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Open AccessReview
The Emerging Role of Vitamin C as a Treatment for Sepsis
Nutrients 2020, 12(2), 292; https://doi.org/10.3390/nu12020292 - 22 Jan 2020
Cited by 18
Abstract
Sepsis, a life-threatening organ dysfunction due to a dysregulated host response to infection, is a leading cause of morbidity and mortality worldwide. Decades of research have failed to identify any specific therapeutic targets outside of antibiotics, infectious source elimination, and supportive care. More [...] Read more.
Sepsis, a life-threatening organ dysfunction due to a dysregulated host response to infection, is a leading cause of morbidity and mortality worldwide. Decades of research have failed to identify any specific therapeutic targets outside of antibiotics, infectious source elimination, and supportive care. More recently, vitamin C has emerged as a potential therapeutic agent to treat sepsis. Vitamin C has been shown to be deficient in septic patients and the administration of high dose intravenous as opposed to oral vitamin C leads to markedly improved and elevated serum levels. Its physiologic role in sepsis includes attenuating oxidative stress and inflammation, improving vasopressor synthesis, enhancing immune cell function, improving endovascular function, and epigenetic immunologic modifications. Multiple clinical trials have demonstrated the safety of vitamin C and two recent studies have shown promising data on mortality improvement. Currently, larger randomized controlled studies are underway to validate these findings. With further study, vitamin C may become standard of care for the treatment of sepsis, but given its safety profile, current treatment can be justified with compassionate use. Full article
(This article belongs to the Special Issue Vitamin C: From Bench to Bedside)
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Open AccessReview
The Pharmacokinetics of Vitamin C
Nutrients 2019, 11(10), 2412; https://doi.org/10.3390/nu11102412 - 09 Oct 2019
Cited by 18
Abstract
The pharmacokinetics of vitamin C (vitC) is indeed complex. Regulated primarily by a family of saturable sodium dependent vitC transporters (SVCTs), the absorption and elimination are highly dose-dependent. Moreover, the tissue specific expression levels and subtypes of these SVCTs result in a compartmentalized [...] Read more.
The pharmacokinetics of vitamin C (vitC) is indeed complex. Regulated primarily by a family of saturable sodium dependent vitC transporters (SVCTs), the absorption and elimination are highly dose-dependent. Moreover, the tissue specific expression levels and subtypes of these SVCTs result in a compartmentalized distribution pattern with a diverse range of organ concentrations of vitC at homeostasis ranging from about 0.2 mM in the muscle and heart, and up to 10 mM in the brain and adrenal gland. The homeostasis of vitC is influenced by several factors, including genetic polymorphisms and environmental and lifestyle factors such as smoking and diet, as well as diseases. Going from physiological to pharmacological doses, vitC pharmacokinetics change from zero to first order, rendering the precise calculation of dosing regimens in, for example, cancer and sepsis treatment possible. Unfortunately, the complex pharmacokinetics of vitC has often been overlooked in the design of intervention studies, giving rise to misinterpretations and erroneous conclusions. The present review outlines the diverse aspects of vitC pharmacokinetics and examines how they affect vitC homeostasis under a variety of conditions. Full article
(This article belongs to the Special Issue Vitamin C: From Bench to Bedside)
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Open AccessReview
Vitamin C and Neutrophil Function: Findings from Randomized Controlled Trials
Nutrients 2019, 11(9), 2102; https://doi.org/10.3390/nu11092102 - 04 Sep 2019
Cited by 8
Abstract
Vitamin C is known to support immune function and is accumulated by neutrophils to millimolar intracellular concentrations suggesting an important role for the vitamin in these cells. In this review, the effects of vitamin C, as a mono- or multi-supplement therapy, on neutrophil [...] Read more.
Vitamin C is known to support immune function and is accumulated by neutrophils to millimolar intracellular concentrations suggesting an important role for the vitamin in these cells. In this review, the effects of vitamin C, as a mono- or multi-supplement therapy, on neutrophil function were assessed by conducting a systematic review of randomized controlled trials (RCTs). Specifically, trials which assessed neutrophil migration (chemotaxis), phagocytosis, oxidative burst, enzyme activity, or cell death (apoptosis) as primary or secondary outcomes were assessed. A systematic literature search was conducted using the Cochrane Central Register of Controlled Trials, EMBASE, Embase Classic, Joanna Briggs Institute EBP, Ovid MEDLINE®, Ovid MEDLINE® In-Process & Other Non-Indexed Citations, Ovid Nursing Database, CINAHL and PubMed database, which identified 16 eligible RCTs. Quality appraisal of the included studies was carried out using the Cochrane Risk of Bias tool. Three of the studies assessed neutrophil chemotaxis in hospitalised patients or outpatients, two of which showed improved neutrophil function following intravenous vitamin C administration. Ten RCTs assessed neutrophil phagocytosis and/or oxidative burst activity; five were exercise studies, one in smokers, one in myocardial infarction patients and three in healthy volunteers. Two of the multi-supplement studies showed a difference between the intervention and control groups: increased oxidative burst activity in athletes post-exercise and decreased oxidant generation in myocardial infarction patients. Two studies assessed neutrophil enzyme activity; one showed deceased antioxidant enzyme activity in divers and the other showed increased antioxidant enzyme activity in athletes. One final study showed decreased neutrophil apoptosis in septic surgical patients following intravenous vitamin C administration. Overall, 44% of the RCTs assessed in this review showed effects of vitamin C supplementation on neutrophil functions. However, the studies were very heterogeneous, comprising different participant cohorts and different dosing regimens. There were also a number of limitations inherent in the design of many of these RCTs. Future RCTs should incorporate prescreening of potential participants for low vitamin C status or utilize cohorts known to have low vitamin status, such as hospitalized patients, and should also comprise appropriate vitamin C dosing for the cohort under investigation. Full article
(This article belongs to the Special Issue Vitamin C: From Bench to Bedside)
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