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Vitamin C and Human Health

A special issue of Nutrients (ISSN 2072-6643).

Deadline for manuscript submissions: closed (31 July 2013) | Viewed by 190543

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Special Issue Editors

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
Special Issues, Collections and Topics in MDPI journals
Centre for Free Radical Research, Department of Pathology, University of Otago, Christchurch, 2 Riccarton Ave, P.O. Box 4345, Christchurch 8140, New Zealand
Interests: vitamin C in cancer and inflammation; oxidative stress; antioxidants; human bioavailability studies

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Keywords

  • human status
  • bioavailability
  • vitamin C-dependent enzymes
  • gene regulation
  • cancer
  • cardiovascular disease
  • neurological effects
  • inflammation

Published Papers (12 papers)

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Research

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2102 KiB  
Article
Orally Administrated Ascorbic Acid Suppresses Neuronal Damage and Modifies Expression of SVCT2 and GLUT1 in the Brain of Diabetic Rats with Cerebral Ischemia-Reperfusion
by Naohiro Iwata, Mari Okazaki, Meiyan Xuan, Shinya Kamiuchi, Hirokazu Matsuzaki and Yasuhide Hibino
Nutrients 2014, 6(4), 1554-1577; https://doi.org/10.3390/nu6041554 - 15 Apr 2014
Cited by 43 | Viewed by 9543
Abstract
Diabetes mellitus is known to exacerbate cerebral ischemic injury. In the present study, we investigated antiapoptotic and anti-inflammatory effects of oral supplementation of ascorbic acid (AA) on cerebral injury caused by middle cerebral artery occlusion and reperfusion (MCAO/Re) in rats with streptozotocin-induced diabetes. [...] Read more.
Diabetes mellitus is known to exacerbate cerebral ischemic injury. In the present study, we investigated antiapoptotic and anti-inflammatory effects of oral supplementation of ascorbic acid (AA) on cerebral injury caused by middle cerebral artery occlusion and reperfusion (MCAO/Re) in rats with streptozotocin-induced diabetes. We also evaluated the effects of AA on expression of sodium-dependent vitamin C transporter 2 (SVCT2) and glucose transporter 1 (GLUT1) after MCAO/Re in the brain. The diabetic state markedly aggravated MCAO/Re-induced cerebral damage, as assessed by infarct volume and edema. Pretreatment with AA (100 mg/kg, p.o.) for two weeks significantly suppressed the exacerbation of damage in the brain of diabetic rats. AA also suppressed the production of superoxide radical, activation of caspase-3, and expression of proinflammatory cytokines (tumor necrosis factor-α and interleukin-1β) in the ischemic penumbra. Immunohistochemical staining revealed that expression of SVCT2 was upregulated primarily in neurons and capillary endothelial cells after MCAO/Re in the nondiabetic cortex, accompanied by an increase in total AA (AA + dehydroascorbic acid) in the tissue, and that these responses were suppressed in the diabetic rats. AA supplementation to the diabetic rats restored these responses to the levels of the nondiabetic rats. Furthermore, AA markedly upregulated the basal expression of GLUT1 in endothelial cells of nondiabetic and diabetic cortex, which did not affect total AA levels in the cortex. These results suggest that daily intake of AA attenuates the exacerbation of cerebral ischemic injury in a diabetic state, which may be attributed to anti-apoptotic and anti-inflammatory effects via the improvement of augmented oxidative stress in the brain. AA supplementation may protect endothelial function against the exacerbated ischemic oxidative injury in the diabetic state and improve AA transport through SVCT2 in the cortex. Full article
(This article belongs to the Special Issue Vitamin C and Human Health)
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299 KiB  
Article
A Randomised Cross-Over Pharmacokinetic Bioavailability Study of Synthetic versus Kiwifruit-Derived Vitamin C
by Anitra C. Carr, Stephanie M. Bozonet and Margreet C. M. Vissers
Nutrients 2013, 5(11), 4451-4461; https://doi.org/10.3390/nu5114451 - 11 Nov 2013
Cited by 22 | Viewed by 10307
Abstract
Kiwifruit are a rich source of vitamin C and also contain numerous phytochemicals, such as flavonoids, which may influence the bioavailability of kiwifruit-derived vitamin C. The aim of this study was to compare the relative bioavailability of synthetic versus kiwifruit-derived vitamin C using [...] Read more.
Kiwifruit are a rich source of vitamin C and also contain numerous phytochemicals, such as flavonoids, which may influence the bioavailability of kiwifruit-derived vitamin C. The aim of this study was to compare the relative bioavailability of synthetic versus kiwifruit-derived vitamin C using a randomised cross-over pharmacokinetic study design. Nine non-smoking males (aged 18–35 years) received either a chewable tablet (200 mg vitamin C) or the equivalent dose from gold kiwifruit (Actinidia chinensis var. Sungold). Fasting blood and urine were collected half hourly to hourly over the eight hours following intervention. The ascorbate content of the plasma and urine was determined using HPLC with electrochemical detection. Plasma ascorbate levels increased from 0.5 h after the intervention (P = 0.008). No significant differences in the plasma time-concentration curves were observed between the two interventions (P = 0.645). An estimate of the total increase in plasma ascorbate indicated complete uptake of the ingested vitamin C tablet and kiwifruit-derived vitamin C. There was an increase in urinary ascorbate excretion, relative to urinary creatinine, from two hours post intervention (P < 0.001). There was also a significant difference between the two interventions, with enhanced ascorbate excretion observed in the kiwifruit group (P = 0.016). Urinary excretion was calculated as ~40% and ~50% of the ingested dose from the vitamin C tablet and kiwifruit arms, respectively. Overall, our pharmacokinetic study has shown comparable relative bioavailability of kiwifruit-derived vitamin C and synthetic vitamin C. Full article
(This article belongs to the Special Issue Vitamin C and Human Health)
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284 KiB  
Article
A Randomized Steady-State Bioavailability Study of Synthetic versus Natural (Kiwifruit-Derived) Vitamin C
by Anitra C. Carr, Stephanie M. Bozonet, Juliet M. Pullar, Jeremy W. Simcock and Margreet C. M. Vissers
Nutrients 2013, 5(9), 3684-3695; https://doi.org/10.3390/nu5093684 - 17 Sep 2013
Cited by 32 | Viewed by 18745
Abstract
Whether vitamin C from wholefoods has equivalent bioavailability to a purified supplement remains unclear. We have previously showed that kiwifruit provided significantly higher serum and tissue ascorbate levels than synthetic vitamin C in a genetically vitamin C-deficient mouse model, suggesting a synergistic activity [...] Read more.
Whether vitamin C from wholefoods has equivalent bioavailability to a purified supplement remains unclear. We have previously showed that kiwifruit provided significantly higher serum and tissue ascorbate levels than synthetic vitamin C in a genetically vitamin C-deficient mouse model, suggesting a synergistic activity of the whole fruit. To determine if these results are translatable to humans, we carried out a randomized human study comparing the bioavailability of vitamin C from kiwifruit with that of a vitamin C tablet of equivalent dosage. Thirty-six young non-smoking adult males were randomized to receive either half a gold kiwifruit (Actinidia Chinensis var. Hort 16A) per day or a comparable vitamin C dose (50 mg) in a chewable tablet for six weeks. Ascorbate was monitored weekly in fasting venous blood and in urine, semen, leukocytes, and skeletal muscle (vastus lateralis) pre- and post-intervention. Dietary intake of vitamin C was monitored using seven day food and beverage records. Participant ascorbate levels increased in plasma (P < 0.001), urine (P < 0.05), mononuclear cells (P < 0.01), neutrophils (P < 0.01) and muscle tissue (P < 0.001) post intervention. There were no significant differences in vitamin C bioavailability between the two intervention groups in any of the fluid, cell or tissue samples tested. Overall, our study showed comparable bioavailability of synthetic and kiwifruit-derived vitamin C. Full article
(This article belongs to the Special Issue Vitamin C and Human Health)
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191 KiB  
Article
Genetic Aspects of Scurvy and the European Famine of 1845–1848
by Joris R. Delanghe, Marc L. De Buyzere, Marijn M. Speeckaert and Michel R. Langlois
Nutrients 2013, 5(9), 3582-3588; https://doi.org/10.3390/nu5093582 - 12 Sep 2013
Cited by 12 | Viewed by 8660
Abstract
The view of scurvy being exclusively a nutritional disorder needs to be updated. Genetic polymorphisms of HFE and haptoglobin (Hp) may explain the geographic variability of mortality caused by the European famine of the mid-19th century. In this period, potatoes had fallen victim [...] Read more.
The view of scurvy being exclusively a nutritional disorder needs to be updated. Genetic polymorphisms of HFE and haptoglobin (Hp) may explain the geographic variability of mortality caused by the European famine of the mid-19th century. In this period, potatoes had fallen victim to the potato blight and Ireland was more severely hit than continental Europe. Hereditary hemochromatosis is a genetic disorder with mutations in the HFE gene, characterized by iron overload (with a reduced vitamin C stability) and with a predominance of affected men. The Irish have the world’s highest frequency of the C282Y mutation and the particular iron metabolism of the Irish helps to understand the size of the catastrophe and the observed overrepresentation of male skeletons showing scurvy. Hp is a plasma α2-glycoprotein characterized by 3 common phenotypes (Hp 1-1, Hp 2-1 and Hp 2-2). When the antioxidant capacity of Hp is insufficient, its role is taken over by hemopexin and vitamin C. The relative number of scurvy victims corresponds with the Hp 2-2 frequency, which is associated with iron conservation and has an impact on vitamin C stability. As iron is more abundant in males, males are overrepresented in the group of skeletons showing scurvy signs. Full article
(This article belongs to the Special Issue Vitamin C and Human Health)
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897 KiB  
Article
Vitamin C: A Novel Regulator of Neutrophil Extracellular Trap Formation
by Bassem M. Mohammed, Bernard J. Fisher, Donatas Kraskauskas, Daniela Farkas, Donald F. Brophy, Alpha A. Fowler and Ramesh Natarajan
Nutrients 2013, 5(8), 3131-3150; https://doi.org/10.3390/nu5083131 - 09 Aug 2013
Cited by 127 | Viewed by 14210
Abstract
Introduction: Neutrophil extracellular trap (NET) formation was recently identified as a novel mechanism to kill pathogens. However, excessive NET formation in sepsis can injure host tissues. We have recently shown that parenteral vitamin C (VitC) is protective in sepsis. Whether VitC alters [...] Read more.
Introduction: Neutrophil extracellular trap (NET) formation was recently identified as a novel mechanism to kill pathogens. However, excessive NET formation in sepsis can injure host tissues. We have recently shown that parenteral vitamin C (VitC) is protective in sepsis. Whether VitC alters NETosis is unknown. Methods: We used Gulo−/− mice as they lack the ability to synthesize VitC. Sepsis was induced by intraperitoneal infusion of a fecal stem solution (abdominal peritonitis, FIP). Some VitC deficient Gulo−/− mice received an infusion of ascorbic acid (AscA, 200 mg/kg) 30 min after induction of FIP. NETosis was assessed histologically and by quantification for circulating free DNA (cf-DNA) in serum. Autophagy, histone citrullination, endoplasmic reticulum (ER) stress, NFκB activation and apoptosis were investigated in peritoneal PMNs. Results: Sepsis produced significant NETs in the lungs of VitC deficient Gulo−/− mice and increased circulating cf-DNA. This was attenuated in the VitC sufficient Gulo−/− mice and in VitC deficient Gulo−/− mice infused with AscA. Polymorphonuclear neutrophils (PMNs) from VitC deficient Gulo−/− mice demonstrated increased activation of ER stress, autophagy, histone citrullination, and NFκB activation, while apoptosis was inhibited. VitC also significantly attenuated PMA induced NETosis in PMNs from healthy human volunteers. Full article
(This article belongs to the Special Issue Vitamin C and Human Health)
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1159 KiB  
Article
Vitamin C in Cultured Human (HeLa) Cells: Lack of Effect on DNA Protection and Repair
by Amaya Azqueta, Solange Costa, Yolanda Lorenzo, Nasser E. Bastani and Andrew R. Collins
Nutrients 2013, 5(4), 1200-1217; https://doi.org/10.3390/nu5041200 - 09 Apr 2013
Cited by 17 | Viewed by 9442
Abstract
Aims: Dietary antioxidants, including vitamin C, may be in part responsible for the cancer-preventive effects of fruits and vegetables. Human intervention trials with clinical endpoints have failed to confirm their protective effects, and mechanistic studies have given inconsistent results. Our aim was to [...] Read more.
Aims: Dietary antioxidants, including vitamin C, may be in part responsible for the cancer-preventive effects of fruits and vegetables. Human intervention trials with clinical endpoints have failed to confirm their protective effects, and mechanistic studies have given inconsistent results. Our aim was to investigate antioxidant/ pro-oxidant effects of vitamin C at the cellular level. Experimental approach: We have used the comet assay to investigate effects of vitamin C on DNA damage, antioxidant status, and DNA repair, in HeLa (human tumor) cells, and HPLC to measure uptake of vitamin C into cells. Results: Even at concentrations in the medium as high as 200 μM, vitamin C did not increase the background level of strand breaks or of oxidized purines in nuclear DNA. Vitamin C is taken up by HeLa cells and accumulates to mM levels. Preincubation of cells with vitamin C did not render them resistant to strand breakage induced by H2O2 or to purine oxidation by photosensitizer plus light. Vitamin C had no effect on the rate of repair of strand breaks or oxidized bases by HeLa cells. However, vitamin C at a concentration of less than 1 μM, or extract from cells preincubated for 6 h with vitamin C, was able to induce damage (strand breaks) in lysed, histone-depleted nuclei (nucleoids). Conclusion: In these cultured human cells, vitamin C displays neither antioxidant nor pro-oxidant properties; nor does it affect DNA strand break or base excision repair. Full article
(This article belongs to the Special Issue Vitamin C and Human Health)
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Review

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1038 KiB  
Review
Ascorbic Acid and the Brain: Rationale for the Use against Cognitive Decline
by Fiona E. Harrison, Gene L. Bowman and Maria Cristina Polidori
Nutrients 2014, 6(4), 1752-1781; https://doi.org/10.3390/nu6041752 - 24 Apr 2014
Cited by 74 | Viewed by 12909
Abstract
This review is focused upon the role of ascorbic acid (AA, vitamin C) in the promotion of healthy brain aging. Particular attention is attributed to the biochemistry and neuronal metabolism interface, transport across tissues, animal models that are useful for this area of [...] Read more.
This review is focused upon the role of ascorbic acid (AA, vitamin C) in the promotion of healthy brain aging. Particular attention is attributed to the biochemistry and neuronal metabolism interface, transport across tissues, animal models that are useful for this area of research, and the human studies that implicate AA in the continuum between normal cognitive aging and age-related cognitive decline up to Alzheimer’s disease. Vascular risk factors and comorbidity relationships with cognitive decline and AA are discussed to facilitate strategies for advancing AA research in the area of brain health and neurodegeneration. Full article
(This article belongs to the Special Issue Vitamin C and Human Health)
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915 KiB  
Review
Myths, Artifacts, and Fatal Flaws: Identifying Limitations and Opportunities in Vitamin C Research
by Alexander J. Michels and Balz Frei
Nutrients 2013, 5(12), 5161-5192; https://doi.org/10.3390/nu5125161 - 16 Dec 2013
Cited by 78 | Viewed by 32086
Abstract
Research progress to understand the role of vitamin C (ascorbic acid) in human health has been slow in coming. This is predominantly the result of several flawed approaches to study design, often lacking a full appreciation of the redox chemistry and biology of [...] Read more.
Research progress to understand the role of vitamin C (ascorbic acid) in human health has been slow in coming. This is predominantly the result of several flawed approaches to study design, often lacking a full appreciation of the redox chemistry and biology of ascorbic acid. In this review, we summarize our knowledge surrounding the limitations of common approaches used in vitamin C research. In human cell culture, the primary issues are the high oxygen environment, presence of redox-active transition metal ions in culture media, and the use of immortalized cell lines grown in the absence of supplemental ascorbic acid. Studies in animal models are also limited due to the presence of endogenous ascorbic acid synthesis. Despite the use of genetically altered rodent strains lacking synthesis capacity, there are additional concerns that these models do not adequately recapitulate the effects of vitamin C deprivation and supplementation observed in humans. Lastly, several flaws in study design endemic to randomized controlled trials and other human studies greatly limit their conclusions and impact. There also is anecdotal evidence of positive and negative health effects of vitamin C that are widely accepted but have not been substantiated. Only with careful attention to study design and experimental detail can we further our understanding of the possible roles of vitamin C in promoting human health and preventing or treating disease. Full article
(This article belongs to the Special Issue Vitamin C and Human Health)
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324 KiB  
Review
Synthetic or Food-Derived Vitamin C—Are They Equally Bioavailable?
by Anitra C. Carr and Margreet C. M. Vissers
Nutrients 2013, 5(11), 4284-4304; https://doi.org/10.3390/nu5114284 - 28 Oct 2013
Cited by 80 | Viewed by 28494
Abstract
Vitamin C (ascorbate) is an essential water-soluble micronutrient in humans and is obtained through the diet, primarily from fruits and vegetables. In vivo, vitamin C acts as a cofactor for numerous biosynthetic enzymes required for the synthesis of amino acid-derived macromolecules, neurotransmitters, [...] Read more.
Vitamin C (ascorbate) is an essential water-soluble micronutrient in humans and is obtained through the diet, primarily from fruits and vegetables. In vivo, vitamin C acts as a cofactor for numerous biosynthetic enzymes required for the synthesis of amino acid-derived macromolecules, neurotransmitters, and neuropeptide hormones, and is also a cofactor for various hydroxylases involved in the regulation of gene transcription and epigenetics. Vitamin C was first chemically synthesized in the early 1930s and since then researchers have been investigating the comparative bioavailability of synthetic versus natural, food-derived vitamin C. Although synthetic and food-derived vitamin C is chemically identical, fruit and vegetables are rich in numerous nutrients and phytochemicals which may influence its bioavailability. The physiological interactions of vitamin C with various bioflavonoids have been the most intensively studied to date. Here, we review animal and human studies, comprising both pharmacokinetic and steady-state designs, which have been carried out to investigate the comparative bioavailability of synthetic and food-derived vitamin C, or vitamin C in the presence of isolated bioflavonoids. Overall, a majority of animal studies have shown differences in the comparative bioavailability of synthetic versus natural vitamin C, although the results varied depending on the animal model, study design and body compartments measured. In contrast, all steady state comparative bioavailability studies in humans have shown no differences between synthetic and natural vitamin C, regardless of the subject population, study design or intervention used. Some pharmacokinetic studies in humans have shown transient and small comparative differences between synthetic and natural vitamin C, although these differences are likely to have minimal physiological impact. Study design issues and future research directions are discussed. Full article
(This article belongs to the Special Issue Vitamin C and Human Health)
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229 KiB  
Review
The Effects of High Concentrations of Vitamin C on Cancer Cells
by Seyeon Park
Nutrients 2013, 5(9), 3496-3505; https://doi.org/10.3390/nu5093496 - 09 Sep 2013
Cited by 54 | Viewed by 12463
Abstract
The effect of high doses of vitamin C for the treatment of cancer has been controversial. Our previous studies, and studies by others, have reported that vitamin C at concentrations of 0.25–1.0 mM induced a dose- and time-dependent inhibition of proliferation in acute [...] Read more.
The effect of high doses of vitamin C for the treatment of cancer has been controversial. Our previous studies, and studies by others, have reported that vitamin C at concentrations of 0.25–1.0 mM induced a dose- and time-dependent inhibition of proliferation in acute myeloid leukemia (AML) cell lines and in leukemic cells from peripheral blood specimens obtained from patients with AML. Treatment of cells with high doses of vitamin C resulted in an immediate increase in intracellular total glutathione content and glutathione-S transferase activity that was accompanied by the uptake of cysteine. These results suggest a new role for high concentrations of vitamin C in modulation of intracellular sulfur containing compounds, such as glutathione and cysteine. This review, discussing biochemical pharmacologic studies, including pharmacogenomic and pharmacoproteomic studies, presents the different pharmacological effects of vitamin C currently under investigation. Full article
(This article belongs to the Special Issue Vitamin C and Human Health)
591 KiB  
Review
Increasing Vitamin C Content in Plant Foods to Improve Their Nutritional Value—Successes and Challenges
by Daniel R. Gallie
Nutrients 2013, 5(9), 3424-3446; https://doi.org/10.3390/nu5093424 - 30 Aug 2013
Cited by 41 | Viewed by 11348
Abstract
Vitamin C serves as a cofactor in the synthesis of collagen needed to support cardiovascular function, maintenance of cartilage, bones, and teeth, as well as being required in wound healing. Although vitamin C is essential, humans are one of the few mammalian species [...] Read more.
Vitamin C serves as a cofactor in the synthesis of collagen needed to support cardiovascular function, maintenance of cartilage, bones, and teeth, as well as being required in wound healing. Although vitamin C is essential, humans are one of the few mammalian species unable to synthesize the vitamin and must obtain it through dietary sources. Only low levels of the vitamin are required to prevent scurvy but subclinical vitamin C deficiency can cause less obvious symptoms such as cardiovascular impairment. Up to a third of the adult population in the U.S. obtains less than the recommended amount of vitamin C from dietary sources of which plant-based foods constitute the major source. Consequently, strategies to increase vitamin C content in plants have been developed over the last decade and include increasing its synthesis as well as its recycling, i.e., the reduction of the oxidized form of ascorbic acid that is produced in reactions back into its reduced form. Increasing vitamin C levels in plants, however, is not without consequences. This review provides an overview of the approaches used to increase vitamin C content in plants and the successes achieved. Also discussed are some of the potential limitations of increasing vitamin C and how these may be overcome. Full article
(This article belongs to the Special Issue Vitamin C and Human Health)
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756 KiB  
Review
Regulation of Vitamin C Homeostasis during Deficiency
by Maiken Lindblad, Pernille Tveden-Nyborg and Jens Lykkesfeldt
Nutrients 2013, 5(8), 2860-2879; https://doi.org/10.3390/nu5082860 - 25 Jul 2013
Cited by 104 | Viewed by 20921
Abstract
Large cross-sectional population studies confirm that vitamin C deficiency is common in humans, affecting 5%–10% of adults in the industrialized world. Moreover, significant associations between poor vitamin C status and increased morbidity and mortality have consistently been observed. However, the absorption, distribution and [...] Read more.
Large cross-sectional population studies confirm that vitamin C deficiency is common in humans, affecting 5%–10% of adults in the industrialized world. Moreover, significant associations between poor vitamin C status and increased morbidity and mortality have consistently been observed. However, the absorption, distribution and elimination kinetics of vitamin C in vivo are highly complex, due to dose-dependent non-linearity, and the specific regulatory mechanisms are not fully understood. Particularly, little is known about how adaptive mechanisms during states of deficiency affect the overall regulation of vitamin C transport in the body. This review discusses mechanisms of vitamin C transport and potential means of regulation with special emphasis on capacity and functional properties, such as differences in the Km of vitamin C transporters in different target tissues, in some instances demonstrating a tissue-specific distribution. Full article
(This article belongs to the Special Issue Vitamin C and Human Health)
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