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A randomized feasibility study of the effect of ascorbic acid on post-angioplasty restenosis of hemodialysis vascular access (NCT03524846).
Yang, CW, Wu, CC, Luo, CM, Chuang, SY, Chen, CH, Shen, YF, Tarng, DC
Scientific reports. 2019;(1):11095
Abstract
Restenosis remains a significant problem after angioplasty of hemodialysis vascular access. Both experimental and clinical studies have shown a protective effect of antioxidants against post-angioplasty restenosis. A prospective, randomized, feasibility study was conducted to investigate the effect of ascorbic acid to prevent restenosis. Ninety-three hemodialysis patients were randomized into three groups after angioplasty: placebo (n = 31), 300 mg ascorbic acid (n = 31), and 600 mg ascorbic acid (n = 31), treated intravenously 3 times per week for 3 months. Eighty-nine completed the clinical follow-up, and 81 had angiographic follow-up. In the angiographic follow-up, the mean (stand deviation) late loss of luminal diameter for the placebo, 300 mg, and 600 mg groups were 3.15 (1.68) mm, 2.52 (1.70) mm (P = 0.39 vs. placebo group), and 1.59 (1.67) mm (P = 0.006, vs. placebo group), with corresponding angiographic binary restenosis of 79%, 67% (P = 0.38 vs. placebo group), and 54% (P = 0.08 vs. placebo group). The post-interventional primary patency rates at 3 months were 47%, 55% (P = 0.59 vs. placebo group), and 70% (P = 0.18 vs. placebo group) for placebo, 300 mg, and 600 mg groups. Our results demonstrated that intravenous 600 mg ascorbic acid was a feasible therapy and might attenuate restenosis after angioplasty; however, its effect on post-interventional primary patency was modest.
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Plasma Vitamin C Levels: Risk Factors for Deficiency and Association with Self-Reported Functional Health in the European Prospective Investigation into Cancer-Norfolk.
McCall, SJ, Clark, AB, Luben, RN, Wareham, NJ, Khaw, KT, Myint, PK
Nutrients. 2019;(7)
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 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.
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Vitamin C Administration to the Critically Ill: A Systematic Review and Meta-Analysis.
Langlois, PL, Manzanares, W, Adhikari, NKJ, Lamontagne, F, Stoppe, C, Hill, A, Heyland, DK
JPEN. Journal of parenteral and enteral nutrition. 2019;(3):335-346
Abstract
Vitamin C, an enzyme cofactor and antioxidant, could hasten the resolution of inflammation, oxidative stress, and microvascular dysfunction. While observational studies have demonstrated that critical illness is associated with low levels of vitamin C, randomized controlled trials (RCTs) of vitamin C, alone or in combination with other antioxidants, have yielded contradicting results. We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials (inception to December 2017) for RCTs comparing vitamin C, by enteral or parenteral routes, with placebo or none, in intensive care unit (ICU) patients. Two independent reviewers assessed study eligibility without language restrictions and abstracted data. Overall mortality was the primary outcome; secondary outcomes were incident infections, ICU length of stay (LOS), hospital LOS, and duration of mechanical ventilation (MV). We prespecified 5 subgroups hypothesized to benefit more from vitamin C. Eleven randomized trials were included. When 9 RCTs (n = 1322) reporting mortality were pooled, vitamin C was not associated with reduced risk of mortality (risk ratio [RR] 0.72, 95% confidence interval [CI]: 0.43-1.20, P = .21). No effect was found on infections, ICU or hospital LOS, or duration of MV. In multiple subgroup comparison, no statistically significant subgroup effects were observed. However, we did observe a tendency towards a mortality reduction (RR 0.21; 95% CI: 0.04-1.05; P = .06) when intravenous high-dose vitamin C monotherapy was administered. Current evidence does not support supplementing critically ill patients with vitamin C. A moderately large treatment effect may exist, but further studies, particularly of monotherapy administration, are warranted.
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Role of antioxidant supplementation in oxidant/antioxidant status and hepatotoxic effects due to aflatoxin B1 in wheat miller workers.
Saad-Hussein, A, Moubarz, G, Mohgah, SA, Wafaa, GS, Aya, HM
Journal of complementary & integrative medicine. 2019;(4)
Abstract
Background Aflatoxin B1 (AFB1) is classified as a Group I carcinogen. A Previous study found that oxidative stress from the metabolism of AFB1 induced hepatotoxic effects in wheat miller workers. Zinc and vitamin C may play a significant role in the activation of detoxification and overcoming the oxidative stress of AFB1. Objectives A prospective clinical trial was designed to evaluate the role of zinc and vitamin C oral supplementation on the oxidant-antioxidant status and the hepatotoxic effects of AFB1 in wheat miller workers. Methods Liver enzymes (ALT, AST, ALP, and GGT), P53 protein, malondialdehyde (MDA), glutathione S transferase (GST), Superoxide dismutase (SOD), zinc and vitamin C were estimated in 35 wheat miller workers before and after zinc and vitamin C supplementation for 1 month. Results The results revealed that zinc and vitamin C were significantly increased after the one-month supplementation, while liver enzymes (AST, ALP, and GGT), MDA, and GST of the workers were significantly decreased. SOD and P53 were also decreased but not to a significant level; SOD was decreased in 56% and P53 was decreased in 58% of the total workers. Conclusions Zinc and vitamin C oral supplementation for 1 month had an ameliorative effect on the hepatotoxicity of AFB1 in wheat miller workers, through decreasing MDA, SOD, and GST levels that in turn led to an improvement in their liver enzymes. Further study on a larger scale is needed to confirm these results.
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Dietary and circulating vitamin C, vitamin E, β-carotene and risk of total cardiovascular mortality: a systematic review and dose-response meta-analysis of prospective observational studies.
Jayedi, A, Rashidy-Pour, A, Parohan, M, Zargar, MS, Shab-Bidar, S
Public health nutrition. 2019;(10):1872-1887
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Abstract
OBJECTIVE The present review aimed to quantify the association of dietary intake and circulating concentration of major dietary antioxidants with risk of total CVD mortality. DESIGN Systematic review and meta-analysis. SETTING Systematic search in PubMed and Scopus, up to October 2017.ParticipantsProspective observational studies reporting risk estimates of CVD mortality across three or more categories of dietary intakes and/or circulating concentrations of vitamin C, vitamin E and β-carotene were included. A random-effects meta-analysis was conducted. RESULTS A total of fifteen prospective cohort studies and three prospective evaluations within interventional studies (320 548 participants and 16 974 cases) were analysed. The relative risks of CVD mortality for the highest v. the lowest category of antioxidant intakes were as follows: vitamin C, 0·79 (95 % CI 0·68, 0·89; I 2=46 %, n 10); vitamin E, 0·91 (95 % CI 0·79, 1·03; I 2=51 %, n 8); β-carotene, 0·89 (95 % CI 0·73, 1·05; I 2=34 %, n 4). The relative risks for circulating concentrations were: vitamin C, 0·60 (95 % CI 0·42, 0·78; I 2=65 %, n 6); α-tocopherol, 0·82 (95 % CI 0·76, 0·88; I 2=0 %, n 5); β-carotene, 0·68 (95 % CI 0·52, 0·83; I 2=50 %, n 6). Dose-response meta-analyses demonstrated that the circulating biomarkers of antioxidants were more strongly associated with risk of CVD mortality than dietary intakes. CONCLUSIONS The present meta-analysis demonstrates that higher vitamin C intake and higher circulating concentrations of vitamin C, vitamin E and β-carotene are associated with a lower risk of CVD mortality.
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Pharmacological Ascorbate as a Means of Sensitizing Cancer Cells to Radio-Chemotherapy While Protecting Normal Tissue.
Schoenfeld, JD, Alexander, MS, Waldron, TJ, Sibenaller, ZA, Spitz, DR, Buettner, GR, Allen, BG, Cullen, JJ
Seminars in radiation oncology. 2019;(1):25-32
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Abstract
Chemoradiation has remained the standard of care treatment for many of the most aggressive cancers. However, despite effective toxicity to cancer cells, current chemoradiation regimens are limited in efficacy due to significant normal cell toxicity. Thus, efforts have been made to identify agents demonstrating selective toxicity, whereby treatments simultaneously sensitize cancer cells to protect normal cells from chemoradiation. Pharmacological ascorbate (intravenous infusions of vitamin C resulting in plasma ascorbate concentrations ≥20 mM; P-AscH-) has demonstrated selective toxicity in a variety of preclinical tumor models and is currently being assessed as an adjuvant to standard-of-care therapies in several early phase clinical trials. This review summarizes the most current preclinical and clinical data available demonstrating the multidimensional role of P-AscH- in cancer therapy including: selective toxicity to cancer cells via a hydrogen peroxide (H2O2)-mediated mechanism; action as a sensitizing agent of cancer cells to chemoradiation; a protectant of normal tissues exposed to chemoradiation; and its safety and tolerability in clinical trials.
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A pilot study of the impact of Vitamin C supplementation with neoadjuvant chemoradiation on regulators of inflammation and carcinogenesis in esophageal cancer patients.
Abdel-Latif, MMM, Babar, M, Kelleher, D, Reynolds, JV
Journal of cancer research and therapeutics. 2019;(1):185-191
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AIMS: Vitamin C plays a role in chemoprevention in cancer treatment, and Vitamin C modulates many regulators of inflammation in in vitro studies. The aim of this study is to assess the effect of Vitamin C supplementation with neoadjuvant chemoradiation in esophageal adenocarcinoma on the nuclear factor-kappa B (NF-κB) and associated cytokines. MATERIALS AND METHODS A total of 20 patients undergoing multimodal treatment for esophageal adenocarcinoma were randomized to receive Vitamin C (1000 mg/day) orally for 4 weeks or no supplementation. Pre- and post-Vitamin C endoscopic biopsies were used for the study of NF-κB activity and cytokine analysis. RESULTS NF-κB activity along with cytokines was activated in the cancer tissue pretreatment. Down-regulation in NF-κB activity was observed in 25% of cases, two from the Vitamin C arm posttreatment. There was a significant reduction in cytokines levels in the cancer group, and this effect was more pronounced in the Vitamin C group (P < 0.05). CONCLUSIONS Vitamin C supplementation had a mild protective effect in modulating of regulators of inflammation and carcinogenesis. Further studies with larger numbers of endpoints are needed to evaluate its effect on modulation of chemoradiation responses.
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Effects of Different Vitamin C-Enriched Collagen Derivatives on Collagen Synthesis.
Lis, DM, Baar, K
International journal of sport nutrition and exercise metabolism. 2019;(5):526-531
Abstract
Nutritional strategies to improve connective tissue collagen synthesis have garnered significant interest, although the scientific validity of these interventions lags behind their hype. This study was designed to determine the effects of three forms of collagen on N-terminal peptide of procollagen and serum amino acid levels. A total of 10 recreationally active males completed a randomized double-blinded crossover design study consuming either placebo or 15 g of vitamin C-enriched gelatin or hydrolyzed collagen (HC), or gummy containing equal parts of gelatin and HC. Supplements were consumed 1 hr before 6 min of jump rope. Blood samples were collected immediately prior to supplement consumption and 4 hr after jump rope. A subset of blood samples (n = 4) was collected for amino acid analysis 1 hr after ingestion. Consumption of an equivalent dose of each supplement increased amino acids in the circulation similarly across all interventions. N-terminal peptide of procollagen levels tended to increase ∼20% from baseline in the gelatin and HC interventions but not the placebo or gummy. These results suggest that vitamin C-enriched gelatin and HC supplementation may improve collagen synthesis when taken 1 hr prior to exercise. However, large variability was observed, which precluded significance for any treatment.
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Antitumor Platinium(IV) Prodrugs: A Systematic Computational Exploration of Their Reduction Mechanism by l-Ascorbic Acid.
Dabbish, E, Ponte, F, Russo, N, Sicilia, E
Inorganic chemistry. 2019;(6):3851-3860
Abstract
The reduction mechanism of Pt(IV) anticancer prodrugs, still today a matter of debate, assisted by one of the dominant reductants in human plasma, that is l-ascorbic acid in its monodeprotonated form, has been computationally examined in this work. In order to check what should be the influence on the reduction rate of the identity of the ligands in axial and equatorial position, both cisplatin and oxaliplatin derivatives have been studied, varying the ligands in axial position in connection with the role they should play as bridges, trans leaving species, and proton acceptors. OH, OAc, Cl, and Br ligands have been tested as bridging/leaving ligands, whereas Cl and aspirin have been used as trans labile and less labile ligands, respectively. The most recent theoretical and experimental investigations have demonstrated that the generally adopted grouping of reduction mechanisms into inner- and outer-sphere does not properly take into account all the viable alternatives. Therefore, inner-sphere mechanisms, classified as ligand-bridged, ligand-bridged-H transfer and enolate β-carbon attack, have been explored for all the complexes under investigation. Concerning the outer-sphere mechanism, redox potentials have been calculated adopting a recently proposed procedure based on the separation between electrochemical and chemical events to evaluate their propensity to be reduced. Moreover, according to the hypothesis that the outer-sphere reduction mechanism involves the sequential addition of two electrons causing the formation of a Pt(III) intermediate, the possibility that singlet and triplet pathways can cross for the Pt(IV) cisplatin derivative having two chlorido ligands in axial position has been explored in detail. Results show that the mechanism indicated as base-assisted outer sphere can become competitive with respect to the inner one if two singlet-triplet spin inversions occur. Results presented here are helpful in addressing synthetic strategies as they show that Pt(IV) prodrugs propensity to be reduced can be properly tuned and give indications on how this aim can be accomplished.
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Transporter oligomerisation: roles in structure and function.
Cecchetti, C, Pyle, E, Byrne, B
Biochemical Society transactions. 2019;(1):433-440
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Oligomerisation is a key feature of integral membrane transporters with roles in structure, function and stability. In this review, we cover some very recent advances in our understanding of how oligomerisation affects these key transporter features, with emphasis on a few groups of transporters, including the nucleobase ascorbate transporters, neurotransmitter sodium symporters and major facilitator superfamily members.