Current Insights and Trends in Vitamin C Research

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Natural and Synthetic Antioxidants".

Deadline for manuscript submissions: 20 August 2024 | Viewed by 6317

Special Issue Editors


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Guest Editor
Nutrition in Medicine Research Group, Department of Pathology and Biomedical Science, University of Otgao, Christchurch, New Zealand
Interests: vitamin C; intake recommendations; respiratory infections; immune function; diabetes; metabolic health; mood; cognitive health; health-related quality of life
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Guest Editor
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Interests: vitamin C; recommendations; effects of vitamin deficiency; lifestyle diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Vitamin C research continues apace. New discoveries abound around vitamin C’s pleiotropic mechanisms of action, as well as its complex pharmacokinetics resulting in varying requirements depending on health, lifestyle, different disease states, etc. Many diseases, such as diabetes, cardiovascular disease and cancer, are characterized by accompanying inflammation and oxidative stress, both of which increase requirements for vitamin C. The more recent discovery of vitamin C’s role in epigenetic regulation opens much wider involvement of this micronutrient in genetic expression and general health than previously acknowledged. However, vitamin C analysis is complicated due to the labile nature of the compound, and accepted methods often require specialized techniques. As high-quality data are the underlying foundation of new knowledge in the field, simpler well-validated methodologies would help in increasing the quality of the vitamin C literature.

Ongoing research on vitamin C’s mechanisms of action and optimal intake will help to inform both clinical practice and health authorities on relevant intake recommendations. As increasing amounts of high-quality vitamin-C-related research are published, more healthcare professionals around the world are becoming aware of the important roles that vitamin C plays in both human health and disease, as well as the higher turnover that various diseases induce on the vitamin C pool and the much-increased daily intake needed to compensate for disease in order to maintain the body stores at optimal status. This is particularly apparent for severe respiratory infections and sepsis, as is observed with COVID-19, which generally require intravenous administration of the vitamin to provide sufficient amounts to meet the increased turnover of the vitamin.

Intravenous vitamin C has been administered to cancer patients for many decades, however, basic information documenting clinical efficacy, optimal dosing, dosing frequency and necessary duration of administration is still needed for the different cancer types. Finally, a vast body of epidemiological evidence has long suggested that disease prevention is facilitated by the optimal intake of micronutrients such as vitamin C, but well-designed intervention studies are lacking. Globally, vitamin C intake recommendations vary widely. Further research in this area will provide an evidence base to aid in the harmonization of intake recommendations worldwide.

We invite you to submit your high-quality vitamin-C-focused research for consideration for publication in our Special Issue.

Dr. Anitra Carr
Prof. Dr. Jens Lykkesfeldt
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • vitamin C
  • antioxidant activities
  • analytical methodology
  • enzyme cofactor activities
  • infection
  • immune function
  • diabetes
  • metabolic health
  • cardiovascular health
  • cancer prevention
  • cancer treatment
  • mood
  • cognitive health
  • health-related quality of life
  • epidemiology

Published Papers (4 papers)

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Research

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16 pages, 6560 KiB  
Article
Ascorbate Uptake and Retention by Breast Cancer Cell Lines and the Intracellular Distribution of Sodium-Dependent Vitamin C Transporter 2
by Citra Praditi, Stephanie M. Bozonet, Gabi U. Dachs and Margreet C. M. Vissers
Antioxidants 2023, 12(11), 1929; https://doi.org/10.3390/antiox12111929 - 30 Oct 2023
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Abstract
Ascorbate plays a vital role as a co-factor for a superfamily of enzymes, the 2-oxoglutarate dependent dioxygenases (2-OGDDs), which govern numerous pathways in cancer progression, including the hypoxic response and the epigenetic regulation of gene transcription. Ascorbate uptake into most cells is through [...] Read more.
Ascorbate plays a vital role as a co-factor for a superfamily of enzymes, the 2-oxoglutarate dependent dioxygenases (2-OGDDs), which govern numerous pathways in cancer progression, including the hypoxic response and the epigenetic regulation of gene transcription. Ascorbate uptake into most cells is through active transport by the sodium-dependent vitamin C transporter 2 (SVCT2). The aims of this study were to determine the kinetics of ascorbate uptake and retention by breast cancer cell lines under various oxygen conditions, and to investigate the role of SVCT2 in mediating ascorbate uptake and intracellular trafficking. Human MDA-MB231 cells accumulated up to 5.1 nmol ascorbate/106 cells, human MCF7 cells 4.5 nmol/106 cells, and murine EO771 cells 26.7 nmol/106 cells. Intracellular ascorbate concentrations decreased rapidly after reaching maximum levels unless further ascorbate was supplied to the medium, and there was no difference in the rate of ascorbate loss under normoxia or hypoxia. SVCT2 was localised mainly to subcellular compartments, with the nucleus apparently containing the most SVCT2 protein, followed by the mitochondria. Much less SVCT2 staining was observed on the plasma membrane. Our data showed that careful management of the doses and incubation times with ascorbate in vitro allows for an approximation of in vivo conditions. The localisation of SVCT2 suggests that the distribution of ascorbate to intracellular compartments is closely aligned to the known function of ascorbate in supporting 2-OGDD enzymatic functions in the organelles and with supporting antioxidant protection in the mitochondria. Full article
(This article belongs to the Special Issue Current Insights and Trends in Vitamin C Research)
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15 pages, 2991 KiB  
Article
Pharmacologic Ascorbate and DNMT Inhibitors Increase DUOX Expression and Peroxide-Mediated Toxicity in Pancreatic Cancer
by Garett J. Steers, Brianne R. O’Leary, Juan Du, Brett A. Wagner, Rory S. Carroll, Frederick E. Domann, Prabhat C. Goswami, Garry R. Buettner and Joseph J. Cullen
Antioxidants 2023, 12(9), 1683; https://doi.org/10.3390/antiox12091683 - 29 Aug 2023
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Abstract
Recent studies have demonstrated an important role for vitamin C in the epigenetic regulation of cancer-related genes via DNA demethylation by the ten-eleven translocation (TET) methylcytosine dioxygenase enzymes. DNA methyltransferase (DNMT) reverses this, increasing DNA methylation and decreasing gene expression. Dual oxidase (DUOX) [...] Read more.
Recent studies have demonstrated an important role for vitamin C in the epigenetic regulation of cancer-related genes via DNA demethylation by the ten-eleven translocation (TET) methylcytosine dioxygenase enzymes. DNA methyltransferase (DNMT) reverses this, increasing DNA methylation and decreasing gene expression. Dual oxidase (DUOX) enzymes produce hydrogen peroxide (H2O2) in normal pancreatic tissue but are silenced in pancreatic cancer (PDAC). Treatment of PDAC with pharmacologic ascorbate (P-AscH, intravenous, high dose vitamin C) increases DUOX expression. We hypothesized that inhibiting DNMT may act synergistically with P-AscH to further increase DUOX expression and cytotoxicity of PDAC. PDAC cells demonstrated dose-dependent increases in DUOX mRNA and protein expression when treated with DNMT inhibitors. PDAC cells treated with P-AscH + DNMT inhibitors demonstrated increased DUOX expression, increased intracellular oxidation, and increased cytotoxicity in vitro and in vivo compared to either treatment alone. These findings suggest a potential therapeutic, epigenetic mechanism to treat PDAC. Full article
(This article belongs to the Special Issue Current Insights and Trends in Vitamin C Research)
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15 pages, 2003 KiB  
Article
Inflammation and Vitamin C in Women with Prenatal Depression and Anxiety: Effect of Multinutrient Supplementation
by Anitra C. Carr, Hayley A. Bradley, Emma Vlasiuk, Hayley Pierard, Jessica Beddow and Julia J. Rucklidge
Antioxidants 2023, 12(4), 941; https://doi.org/10.3390/antiox12040941 - 17 Apr 2023
Cited by 2 | Viewed by 1695
Abstract
Elevated inflammation has been associated with adverse mood states, such as depression and anxiety, and antioxidant nutrients, such as vitamin C, have been associated with decreased inflammation and improved mood. In the current study comprising a cohort of pregnant women with depression and [...] Read more.
Elevated inflammation has been associated with adverse mood states, such as depression and anxiety, and antioxidant nutrients, such as vitamin C, have been associated with decreased inflammation and improved mood. In the current study comprising a cohort of pregnant women with depression and anxiety, we hypothesised that elevated inflammation would be associated with adverse mood states and inversely associated with vitamin C status and that multinutrient supplementation would optimise vitamin concentrations and attenuate inflammation. Sixty-one participants from the NUTRIMUM trial had blood samples collected between 12 and 24 weeks gestation (baseline) and following 12 weeks of daily supplementation with a multinutrient formula containing 600 mg of vitamin C or active placebo. The samples were analysed for inflammatory biomarkers (C-reactive protein (CRP) and cytokines) and vitamin C content and were related to scales of depression and anxiety. Positive correlations were observed between interleukin-6 (IL-6) and all of the mood scales administered (p < 0.05), including the Edinburgh Postnatal Depression Scale, the Clinical Global Impressions—Severity Scale, the Montgomery and Åsberg Depression Rating Scale, the Depression Anxiety Stress Scale 21, and the Generalized Anxiety Disorder-7 (GAD-7). CRP correlated weakly with GAD-7 (p = 0.05). There was an inverse correlation between CRP and the vitamin C status of the cohort (p = 0.045), although there was no association of the latter with the mood scales (p > 0.05). Supplementation with the multinutrient formula resulted in a significant increase in the vitamin C status of the cohort (p = 0.007) but did not affect the inflammatory biomarker concentrations (p > 0.05). In conclusion, greater systemic inflammation was associated with worse mood states; however, 12-week multinutrient supplementation did not alter inflammatory biomarker concentrations. Nevertheless, the vitamin C status of the cohort was improved with supplementation, which may aid pregnancy and infant outcomes. Full article
(This article belongs to the Special Issue Current Insights and Trends in Vitamin C Research)
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Review

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15 pages, 7847 KiB  
Review
Vitamin C: Rationale for Its Use in Sepsis-Induced Acute Respiratory Distress Syndrome (ARDS)
by Alpha A. Fowler III
Antioxidants 2024, 13(1), 95; https://doi.org/10.3390/antiox13010095 - 12 Jan 2024
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Abstract
Acute respiratory distress syndrome (ARDS) is a life-threatening event that occurs in patients suffering from bacterial, fungal, or viral sepsis. Research performed over the last five decades showed that ARDS is a consequence of severe unrestrained systemic inflammation, which leads to injury of [...] Read more.
Acute respiratory distress syndrome (ARDS) is a life-threatening event that occurs in patients suffering from bacterial, fungal, or viral sepsis. Research performed over the last five decades showed that ARDS is a consequence of severe unrestrained systemic inflammation, which leads to injury of the lung’s microvasculature and alveolar epithelium. ARDS leads to acute hypoxic/hypercapnic respiratory failure and death in a significant number of patients hospitalized in intensive care units worldwide. Basic and clinical research performed during the time since ARDS was first described has been unable to construct a pharmacological agent that will combat the inflammatory fire leading to ARDS. In-depth studies of the molecular pharmacology of vitamin C indicate that it can serve as a potent anti-inflammatory agent capable of attenuating the pathobiological events that lead to acute injury of the lungs and other body organs. This analysis of vitamin C’s role in the treatment of ARDS includes a focused systematic review of the literature relevant to the molecular physiology of vitamin C and to the past performance of clinical trials using the agent. Full article
(This article belongs to the Special Issue Current Insights and Trends in Vitamin C Research)
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