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Clinical studies have reported that increased epileptiform and subclinical epileptiform activity can be detected in many patients with an Alzheimer's disease (AD) diagnosis using electroencephalogram (EEG) and this may correlate with poorer cognition. Ascorbate may have a specific role as a neuromodulator in AD as it is released concomitantly with glutamate reuptake following excitatory neurotransmission. Insufficiency may therefore result in an exacerbated excitatory/inhibitory imbalance in neuronal signaling. Using a mouse model of AD that requires dietary ascorbate (Gulo -/- APP swe /PSEN1 dE9 ), EEG was recorded at baseline and during 4 weeks of ascorbate depletion in young (5-month-old) and aged (20-month-old) animals. Data were scored for changes in quantity of spike trains, individual spikes, sleep-wake rhythms, sleep fragmentation, and brainwave power bands during light periods each week. We found an early increase in neuronal spike discharges with age and following ascorbate depletion in AD model mice and not controls, which did not correlate with brain amyloid load. Our data also show more sleep fragmentation with age and with ascorbate depletion. Additionally, changes in brain wave activity were observed within different vigilance states in both young and aged mice, where Gulo -/- APP swe /PSEN1 dE9 mice had shifts towards higher frequency bands (alpha, beta, and gamma) and ascorbate depletion resulted in shifts towards lower frequency bands (delta and theta). Microarray data supported ascorbate insufficiency altering glutamatergic transmission through the decreased expression of glutamate related genes, however no changes in protein expression of glutamate reuptake transporters were observed. These data suggest that maintaining optimal brain ascorbate levels may support normal brain electrical activity and sleep patterns, particularly in AD patient populations where disruptions are observed., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Fiona Harrison reports financial support was provided by National Institutes of Health. James May reports financial support was provided by US Department of Veterans Affairs. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Favipiravir is a nucleoside analogue antiviral drug and inhibits the replication of many RNA viruses, especially influenza viruses. Favipiravir has also been used to treat patients with mild to moderate COVID-19 disease. However, various side effects, including neurological side effects, have been reported related to the use of favipiravir. Therefore, in this study, we aimed to investigate the possible effects of favipiravir alone or in combination with vitamin C on aged rats' brain tissue and the possible mechanisms of these effects. A total of 30 rats used in the study were randomly divided into 5 equal groups and the first group was kept as the control group. High-dose (100 mg/kg) or low-dose (20 mg/kg) favipiravir was administered alone or in combination with vitamin C (150 mg/kg) to other groups. Administration of both high and low doses of favipiravir significantly increased TBARS levels in brain tissue of aged rats. Similarly, both high and low doses of favipiravir led to significant increases in Bcl-2 and caspase-3 relative mRNA expression. However, only low dose favipiravir caused a significant increase in iNOS and IL-1β relative mRNA expression levels. Similar results were also observed in histopathological examinations. However, co-administration of vitamin C with favipiravir attenuated some of the adverse effects of favipiravir. In conclusion, in this study, it was shown that the use of favipiravir caused some adverse effects through oxidative, inflammatory and apoptotic processes in the brain tissue of aged rats, and the potential of vitamin C to alleviate these effects.

Ascorbic acid (AA), a prominent antioxidant commonly found in human blood serum, serves as a biomarker for assessing oxidative stress levels. Therefore, precise detection of AA is crucial for swiftly diagnosing conditions arising from abnormal AA levels. Consequently, the primary aim of this research is to develop a sensitive and selective electrochemical sensor for accurate AA determination. To accomplish this aim, we used a novel nanocomposite comprised of CeO 2 -doped ZnO adorned on biomass-derived carbon (CeO 2 ·ZnO@BC) as the active nanomaterial, effectively fabricating a glassy carbon electrode (GCE). Various analytical techniques were employed to scrutinize the structure and morphology features of the CeO 2 ·ZnO@BC nanocomposite, ensuring its suitability as the sensing nanomaterial. This innovative sensor is capable of quantifying a wide range of AA concentrations, spanning from 0.5 to 1925 μM in a neutral phosphate buffer solution. It exhibits a remarkable sensitivity of 0.2267 μA μM -1 cm -2 and a practical detection limit of 0.022 μM. Thanks to its exceptional sensitivity and selectivity, this sensor enables highly accurate determination of AA concentrations in real samples. Moreover, its superior reproducibility, repeatability, and stability underscore its reliability and robustness for AA quantification., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The exact pathogenesis of melasma is not yet known, and its treatment remains challenging. Mesotherapy with tranexamic acid (TXA) and vitamin C was both reported to have certain effects on melasma. In spite of that several articles have compared the efficacy and safety of the two drugs on melasma, most of them were clinical study with small sample size., Aims: To evaluate the efficacy and safety of mesotherapy with TXA versus vitamin C in treating melasma through meta-analysis and systemic review., Methods: The authors searched PubMed, Web of Science, Springer, and ScienceDirect for studies that compared mesotherapy with TXA versus vitamin C as a treatment for melasma. Primary outcomes were change in melasma area and severity index (MASI) before and after the treatment., Results: Finally, five studies with a total of 127 patients were included in the systematic review. There was no statistic difference in the change in MASI score between the TXA and vitamin C groups (mean difference, 0.16; 95% CI, -0.79 to 1.11)., Conclusions: Mesotherapy with both TXA and vitamin C is safe and effective in the treatment of melasma., (© 2024 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Greenhouses located at high latitudes and in cloudy areas often experience a low quality and quantity of light, especially during autumn and winter. This low daily light integral (DLI) reduces production rate, quality, and nutritional value of many crops. This study was conducted on Sakhiya RZ F1 tomato plants to evaluate the impact of LED lights on the growth and nutritional value of tomatoes in a greenhouse with low daily light due to cloudy weather. The treatments included LED growth lights in three modes: top lighting, intra-canopy lighting, and combined top and intra-canopy lighting. The results showed that although the combined top and intra-canopy lighting reached the maximum increase in tomato yield, exposure to intra-canopy LED lighting alone outperformed in tomato fruit yield increase (28.46%) than exposure to top LED lighting alone (12.12%) when compared to no supplemental lighting during the entire production year. Intra-canopy exposure demonstrated the highest increase in tomato lycopene (31.3%), while top and intra-canopy lighting exhibited the highest increase in vitamin C content (123.4%) compared to the control. The LED light treatment also had a very positive effect on the expression of genes responsible for metabolic cycles, including Psy1, LCY-β, and VTC2 genes, which had collinearity with the increase in tomato fruit production., (© 2024. The Author(s).)

Background: Food allergy has become a global public health problem. This study aimed to explore the possible anti-allergic effect of vitamin C (VC). A rat basophilic leukemia (RBL)-2H3 cell degranulation model was used to assess the effect of VC on degranulation in vitro, and an ovalbumin (OVA)-induced BALB/c mouse allergy model was used to assess the anti-allergy effect of VC in vivo., Results: In vitro, VC significantly attenuated the release of β-hexosaminidase, tryptase and histamine, and also reduced cytokine production (interleukins 4 and 6, tumor necrosis factor α) significantly (P < 0.05), with the inhibitory effect demonstrating a positive correlation with VC dose. In vivo, compared with the OVA group, the levels of serum immunoglobulins E and G 1 of the VC low-dose (VCL) group (50 mg kg -1 ) and high-dose (VCH) group (200 mg·kg -1 ) were significantly reduced (P < 0.05). Furthermore, the plasma histamine level was also significantly decreased (P < 0.05). Moreover, T H 2 cell polarization in mice of the VCL and VCH groups was significantly inhibited (P < 0.05), promoting the T H 1/T H 2 cell polarization balance. Additionally, VC treatment enhanced the expression of CD80 (P < 0.05) in spleen and small intestine tissues, while significantly inhibiting the expression of CD86 (P < 0.05); notably, high-dose VC treatment was more effective., Conclusion: VC exerted an anti-allergic effect through inhibiting degranulation and regulating T H 1/T H 2 cell polarization balance. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Recent research has highlighted potential benefits of vitamin C in managing periodontal diseases, yet systematic reviews to consolidate these findings are scarce. This study aims to evaluate the effectiveness of vitamin C supplementation in preventing and treating periodontal diseases and elucidate the biological mechanisms underlying these effects. We conducted a systematic review following PRISMA guidelines, searching three databases up to 13 April 2024, for studies from 2010 onward. Our selection criteria aimed to capture a wide range of studies regarding vitamin C's impact on periodontal health. After rigorous screening, 16 studies were included in the final analysis. Meta-analysis techniques were employed to synthesize data and evaluate the association between vitamin C intake and periodontal disease outcomes. The meta-analysis included 17,853 participants from studies with diverse geographical and demographic settings. Notable findings indicated that higher vitamin C intake was associated with a reduction in periodontal disease risk, with a pooled odds ratio (OR) of 1.52 (95% CI: 1.49-1.55). The individual studies reported ORs ranging from 0.62 (95% CI: 0.38-0.94) indicating significant protective effects, to 1.66 (95% CI: 1.04-2.64), suggesting increased risks associated with inadequate vitamin C levels. The heterogeneity among the studies was high (I 2 = 95.46%), reflecting variability in study design and population characteristics. This systematic review confirms that vitamin C supplementation has a beneficial effect on periodontal health. The significant variability across studies suggests that individual dietary needs and baseline vitamin C levels might influence the effectiveness of supplementation. These findings underscore the importance of personalized nutritional guidance as part of comprehensive periodontal care. Future research should focus on longitudinal studies to better understand the causal relationships and potential confounding factors affecting the link between vitamin C intake and periodontal health.

The use of cinnamaldehyde and Vitamin C can improve immunity and intestinal health. A two-way factorial design was employed to investigate the main and interactive effects of cinnamaldehyde and vitamin C on the growth, carcass, and intestinal health of broiler chickens. A total of 288 one-day-old female Arbor Acres broiler chicks were randomly distributed among four treatment groups, consisting of six replicate cages with 12 birds each. Four treatments were basal diet or control (CON), supplemental cinnamaldehyde (CA) 300 g/ton (g/t), vitamin C (VC) 300 g/t, and cinnamaldehyde 300 g/t, and vitamin C 300 g/t (CA + VC), respectively. The results showed that supplemental CA did not affect the growth performance or slaughter performance of broilers at 21 days (d), 42 days (d), and 1-42 days (d); however, it could improve intestinal barrier function at 42 d of age and reduce the mRNA expression of inflammatory factors in the intestine at 21 d and 42 d of age. Supplemental VC showed a trend towards increasing body weight gain (BWG) at 21 d ( p = 0.094), increased breast muscle rate (at 21-d 5.33%, p < 0.05 and at 42-d 7.09%, p = 0.097), and decreased the abdominal fat (23.43%, p < 0.05) and drip loss (20.68%, p < 0.05) at 42-d. Moreover, VC improves intestinal morphology and intestinal barrier function and maintains a balanced immune response. The blend of CA and VC significantly upregulated the mRNA expression of myeloid differentiation factor 88 ( MyD-88 ) in the intestine at 21 d of age, the mRNA expression of catalase ( CAT ), Occludin , Claudin-1 , Mucin-2 , nuclear factor-kappa B ( NF-κB ) and toll-like receptor 4 ( TLR-4 ) in the intestine at 42 d of age ( p < 0.01), and downregulated the mRNA expression of interleukin 10 ( IL-10 ), interleukin 6 ( IL-6 ), tumor necrosis factor-alpha ( TNF-α ) in the intestine at 21-d and 42-d of age, and interleukin-1 beta ( IL-1β ) mRNA in intestine at 42 d of age ( p < 0.01). This study suggested that the combination of CA and VC had the potential to regulate intestinal health and result in better carcass character of broilers.

Background: The aim of this study was to evaluate the association between dietary vitamin C intake and depression in adults., Methods: This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) during 2005 to 2020. Logistic regressions and restricted cubic spline (RCS) regression were used to assess the association between dietary vitamin C intake and depression. Additionally, we performed stratified and sensitivity analyses to evaluate the stability of the results., Results: This study included 38,157 participants, with 3448 (9.04 %) of them experiencing depression. The vitamin C intake was negatively associated with depression after adjusting for all covariates (OR = 0.91, 95%CI: 0.88-0.94, P < 0.001). Similar inverse associations were observed when vitamin C intake was transformed into categorical variables. Individuals in higher quartiles of dietary vitamin C intake (Q2, Q3, and Q4) had lower odds ratios (ORs) compared to those in the lowest quartile (Q1), as indicated by adjusted ORs of 0.78 (95 % CI: 0.71-0.87, P < 0.001), 0.74 (95 % CI: 0.67-0.82, P < 0.001), and 0.73 (95 % CI: 0.65-0.81, P < 0.001), respectively. The RCS analysis found an L-shaped nonlinear relationship between dietary vitamin C intake and depression, after adjusting for all covariates (P for non-linearity<0.001). Consumption of vitamin C was inversely associated with depression (OR = 0.994, 95%CI: 0.993-0.996, P < 0.001) for intakes below 93.61 mg, but there was no association between dietary vitamin C intake and depression (P = 0.980) for intakes of 93.61 mg or higher. The inverse associations between vitamin C intake and depression remained robust in stratified and sensitivity analyses., Limitations: This study was a cross-sectional study, and therefore unable to establish a causal relationship between dietary vitamin C intake and depression. We are unable to fully eliminate the confounding effects resulted from other unmeasured or unknown factors., Conclusion: The study revealed a negative association between dietary vitamin C intake and depression, as well as an L-shaped nonlinear relationship between vitamin C intake and depression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Skin photoaging and uneven pigmentation are common dermatological concerns. Tetrahexyldecyl ascorbate (THDA) and acetyl zingerone (AZ) are potent antioxidants that have been shown to have anti-photoaging and anti-pigmentation effects. THDA is a more stable and penetrable form of vitamin C. AZ is an antioxidant derived from ginger which has clinical evidence for improving photoaging. However, no studies have assessed how they may synergistically act on the skin., Aims: This study aims to assess whether a serum containing both THDA and AZ can improve photoaging and the appearance of uneven facial pigmentation., Patients/methods: This open-label study was conducted on 35 healthy individuals aged 21-55. All subjects were instructed to use three to five drops of the topical serum (Power-C Serum, Image Skincare, Lantana, FL) daily for 12 weeks. Videomicroscopy and high-resolution photography and various skin biophysical measurements were taken at baseline, 1, 4, and 12 weeks. Outcomes included skin tone and pigmentation, transepidermal water loss (TEWL), skin smoothness, firmness, and elasticity., Results: Compared to baseline, the results at 12 weeks revealed significant decreases in skin pigmentation (p < 0.0001), decreased fine lines and wrinkles (p < 0.0001), and increased smoothness (p < 0.0001), firmness (p < 0.0001), and elasticity (p < 0.0001). Additionally, transepidermal water loss was significantly decreased at 4 weeks compared to baseline (p = 0.01), indicating an increased epidermal barrier integrity., Conclusions: Overall, these findings provide evidence for the combined use of THDA and AZ to address skin photoaging and dyspigmentation changes., (© 2024 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

The proposed glucosylamine oxidation pathway (GOP) is a two-step, intraerythrocyte, thermodynamically favorable nonenzymatic reaction that first binds glucose to the N-terminal valine of beta globin (βVal1) to form a closed-chain glucosylamine that can spontaneously reduce oxidized vitamin C to its antioxidant form. This review summarizes analytical, biochemical and clinical research supporting the existence of the GOP and the surprising hypothesis that βVal1 glucosylamine is a reducing agent that works cooperatively with reduced glutathione to dynamically regulate vitamin C recycling during naturally occurring periods of transiently or chronically elevated blood glucose and oxidant production. Rationale for the existence of the GOP is presented from the perspective of the hemoglobin glycation index, a clinically practical biomarker of risk for chronic vascular disease that we propose is mechanistically explained by person-to-person variation in GOP activity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Context: Coronavirus disease 2019 (COVID-19) could induce the "cytokine storm" due to overactivation of immune system and accompanied by acute respiratory distress syndrome as a serious complication. Vitamin C has been effective in improving lung function of patients by reducing inflammation., Objective: The aim was to explore the therapeutic effects of high-dose vitamin C supplementation for patients with COVID-19 using meta-analysis., Data Sources: Published studies were searched from PubMed, Cochrane Library, Web of Science, EMBASE, and China National Knowledge Infrastructure databases up to August 2022 using the terms "vitamin C" and "COVID-19". Data analyses were performed independently by 2 researchers using the PRISMA guidelines., Data Extraction: Heterogeneity between the included studies was assessed using I2 statistics. When I2 ≥50%, the random-effects model was used; otherwise, a fixed-effects model was applied. Stata 14.0 software was used to pool data by standardized mean differences (SMDs) with 95% CIs or odds ratios (ORs) with 95% CIs., Data Analysis: The 14 studies had a total of 751 patients and 1583 control participants in 7 randomized controlled trials and 7 retrospective studies. The vitamin C supplement significantly increased ferritin (SMD = 0.272; 95% CI: 0.059 to 0.485; P = 0.012) and lymphocyte count levels (SMD = 0.376; 95% CI: 0.153 to 0.599; P = 0.001) in patients with COVID-19. Patients administered vitamin C in the length of intensive care unit staying (SMD = 0.226; 95% CI: 0.073 to 0.379; P = 0.004). Intake of vitamin C prominently alleviate disease aggravation (OR = 0.344, 95%CI: 0.135 to 0.873, P = 0.025)., Conclusions: High-dose vitamin C supplementation can alleviate inflammatory response and hinder the aggravation of COVID-19., (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Excessive iron intake causes lipid peroxidation and increases oxidative stress. Ascorbic acid is a natural compound with antioxidant and therapeutic properties. In this study, the effect of AA on oxidative stress parameters in fruit flies in the presence of iron was investigated. Third instar larvae were exposed to Fe and/or AA. Antioxidant enzyme activities, MDA, and GSH levels were determined in adult heads developing from the larvae. The mRNA levels of the enzymes were also analyzed. Iron treatment caused inhibition of SOD, CAT, and GPx enzymes, and only a decrease in the mRNA level of CAT. However, AA treatment together with iron prevented the inhibition. In addition, iron treatment increased the MDA level and decreased the GSH level. AA treatment together with iron ameliorated the changes in MDA and GSH levels. The results showed that AA can interfere with the iron-induced changes. Considering the potential of AA to ameliorate iron-induced changes, further studies are needed to elucidate the effect of AA on different mechanisms., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Neuroinflammation is a major characteristic of pathology in several neurodegenerative diseases. Microglia, the brain's resident myeloid cells, shift between activation states under neuroinflammatory conditions, both responding to, but also driving damage in the brain. Vitamin C (ascorbate) is an essential antioxidant for central nervous system function that may have a specific role in the neuroinflammatory response. Uptake of ascorbate throughout the central nervous system is facilitated by the sodium-dependent vitamin C transporter 2 (SVCT2). SVCT2 transports the reduced form of ascorbate into neurons and microglia, however the contribution of altered SVCT2 expression to the neuroinflammatory response in microglia is not well understood. In this study we demonstrate that SVCT2 expression modifies microglial response, as shown through changes in cell morphology and mRNA expression, following a mild traumatic brain injury (mTBI) in mice with decreased or increased expression of SVCT2. Results were supported by in vitro studies in an immortalized microglial cell line and in primary microglial cultures derived from SVCT2-heterozygous and transgenic animals. Overall, this work demonstrates the importance of SVCT2 and ascorbate in modulating the microglial response to mTBI and suggests a potential role for both in response to neuroinflammatory challenges., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This study was conducted to investigate whether optimal vitamin C (VC) levels can enhance non-specific immune response and antioxidant capacity and reduce mortality of Pacific white shrimp (Penaeus vannamei) post-larvae when infected with Vibrio parahaemolyticus. Six experimental diets were formulated to contain six different VC levels of 0, 40, 80, 120, 160 and 320 mg/kg diet (designated as C0, C40, C80, C120, C160 and C320, respectively). Shrimp post-larvae (39.1 ± 0.47 mg) were randomly distributed to 24 tanks with 40 shrimp per tank. Four replicate groups of shrimp were fed one of the diets for 43 days. VC supplemented groups showed significantly higher growth performance than C0 group. Shrimp fed C120 diet had significantly improved feed utilization efficiency than shrimp fed C0 diet. VC concentrations in hepatopancreas and gills were significantly higher with the increase in dietary VC levels. Optimal dietary VC levels significantly upregulated the expressions of growth and digestive enzyme-related genes such as IGF-1, IGF-BP, amylase, trypsin and chymotrypsin, and also upregulated the expressions of innate immunity and antioxidant-related genes such as prophenoloxidase, crustin, penaiedin-3a, superoxide dismutase, glutathione peroxidase and catalase in hepatopancreas. Shrimp fed C80, C120 and C160 diets showed significantly increased resistance to V. parahaemolyticus than shrimp fed C0 diet. The optimum dietary VC level for the shrimp post-larvae was established to be 80.2 mg/kg diet by a broken-line regression analysis based on the growth. The findings from the challenge test indicated that VC levels over 83.0 mg/kg diet could enhance disease resistance of the shrimp against V. parahaemolyticus., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Ten-eleven translocases (TETs) are enzymes responsible for demethylation processes, playing a crucial role in maintaining the body's methylation balance. Dysregulation of TET expression can lead to abnormal methylation levels. Isocitrate dehydrogenases (IDH) are upstream genes involved in Kreb cycle responsible for production of α-ketoglutarate (α-KG). α-KG and vitamin C are cofactors of TET3 enzyme. There is limited data on the relationship between TET3 and its cofactor Vitamin C in head and neck carcinoma (H&NC)., Methods and Results: In this study, we have investigated the expression of the TET3 gene along with IDH1/2 genes involved in the Krebs cycle in the peripheral blood of 32 H&NC patients compared to 32 healthy controls. We estimated serum levels of TET3 protein and vitamin C and 5-hydroxymethylcytosine (5-hmC) percentage in DNA isolated from EDTA blood samples. Our findings revealed that TET3 and IDH1/2 were downregulated in H&NC patients compared to healthy controls. Serum levels of TET3 and Vitamin C were low in H&NC patients compared to healthy controls. Diminished levels of percentage 5-hmC were detected in EDTA blood samples of H&NC patients compared to controls. Spearman correlation analysis revealed a significant positive correlation between TET3 levels, vitamin C levels and 5-hmC percentage., Conclusion: The low levels of Vitamin C are believed to contribute to decreased activity of the TET3 gene and less conversion of 5-methylcytosine (5-mC) to 5-hmC. Dietary supplementation of Vitamin C may increase TET3 activity., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: In the treatment of advanced pancreatic cancer, chemotherapy plays a pivotal role. Despite its effectiveness, this regimen is often marred by side effects such as anemia, neuropathy, fatigue, nausea, and malnutrition, which significantly affect patients' tolerance to the treatment. Some studies have shown that vitamin C could potentially augment chemotherapy's tolerability, notably by boosting iron absorption, ameliorating anemia, and relieving pain and numbness in hands and feet. Nevertheless, the integration of vitamin C with chemotherapy to mitigate toxic side effects and enhance the quality of life for advanced pancreatic cancer patients has not been examined in any randomized controlled trials to date., Methods: A prospective, single-center, open-label, randomized controlled trial will be conducted at Fudan University Shanghai Cancer Center from September 2023 to September 2026. A total of at least 100 patients with advanced pancreatic adenocarcinoma exhibiting distant metastases will be recruited and randomly assigned to the chemotherapy group or the chemotherapy plus vitamin C group. The primary endpoint is the rate of anemia. Secondary endpoints include the rate of grade 3 neuropathy, change of numeric rating scale, quality of life, and overall survival., Discussion: This study aims to assess the impact of low-dose vitamin C on enhancing the quality of life for patients with metastatic pancreatic cancer undergoing gemcitabine and nab-paclitaxel chemotherapy., Trial Registration: The trial was registered with the ClinicalTrials.gov (NCT06018883) on August 31, 2023., (© 2024. The Author(s).)

The efficacy of vitamin C in age-related hearing loss, i.e., presbycusis, remains debatable. On a separate note, inflammation induced by the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is involved in the progression of presbycusis. In this study, we investigated the effect of vitamin C on male C57BL/6 mice's presbycusis and NLRP3 inflammasome. The results showed that vitamin C treatment improved hearing, reduced the production of inflammatory factors, inhibited NLRP3 inflammasome activation, and decreased cytosolic mitochondrial DNA (mtDNA) in the C57BL/6 mouse cochlea, inferior colliculus, and auditory cortex. According to this study, vitamin C protects auditory function in male C57BL/6 presbycusis mice through reducing mtDNA release, inhibiting the NLRP3 inflammasome activation in the auditory pathway. Our study provides a theoretical basis for applying vitamin C to treat presbycusis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The optimal approach for managing partial-thickness rotator cuff tears (PTRCT) remains controversial. Recent studies related to PTRCTs have shown that platelet-rich plasma (PRP) injection might be an effective treatment option. Despite the role of vitamin C in collagen synthesis and its antioxidant properties, the effects of combined PRP and vitamin C treatment on rotator cuff repair are not well understood. This study investigated the effect of combined treatment of PRP and vitamin C treatment on PTRCTs., Methods: One hundred-ten patients with PTRCTs were randomly allocated to two groups and underwent subacromial injections of either (A) normal saline and platelet-rich plasma or (B) vitamin C and platelet-rich plasma. The Constant score, American Shoulder and Elbow Surgeons (ASES) score, and visual analog scale were used to evaluate the outcomes before, 1 month after, and 3 months after injection., Results: At the 3-month follow-up, no statistically significant differences were observed between the two groups in terms of ASES and Constant scores. Although a slight difference favoring group B was noted in functional scores and pain reduction, this difference was not statistically significant. However, both groups demonstrated significant pain reduction over time (p-value < 0.001). Additionally, the enhancement of ASES and Constant scores in both groups was statistically significant (p-value < 0.001)., Conclusions: In conclusion, both PRP injection alone and PRP combined with vitamin C led to significant reductions in pain and enhancements in function scores over time (p < 0.001), suggesting the effectiveness of PRP as a non-surgical treatment for PTRCTs within 3 months. While PRP alone showed significant benefits, further research is required to ascertain if the combination therapy offers statistically significant advantages over PRP alone., Trial Registration: Clinical trial registration code: IRCT20230821059205N1., (© 2024. The Author(s).)

In aquaculture, fish are exposed to many stressors, such as climate changes and infectious diseases that affect their performance, immunity, and welfare. Freshwater fish subjected to salt bath become exhausted and stressed. In this experiment, Nile tilapia were exposed to a salt bath at a dose of 30 ppt for 30 min a day. Vitamin C and vitamin E are well-known antioxidants that are used in aquaculture. Fish received dietary nanoparticles of chitosan-vitamin C and chitosan-vitamin E (CCE-NPs) for different periods (7 and 14 days) pre- (G2) and post-salt treatment (G3). In the control fish (G1), cortisol 5.44 µg/dL and glucose 91.67 mg/dL were significantly up-regulated post-salt treatment by 1 h and 24 h, respectively, whereas those (G2) fed CCE-NPs diet had significantly lower values of 4.72 and 3.25 µg/dL; 86.3 and 84.3 mg/dL, respectively. A rapid decrease of glucose 68.3 and 66.3 mg/dL was noticed in those (G2) fed CCE-NPs diet compared to the control 84.67 mg/dL at 48 h post-stress. Regardless of the supplementation period, fish (G2) could partially restore normal food reflex at 48 h (post-salt bath) and fully restored at 72 h compared to 7 days in the control (G1). After 48 h, fish that received dietary CCE-NPs (G2 and G3) restored normal mucus lysozyme levels, whereas the control did not restore pre-treatment values till the seventh day. Mucus antibacterial activity, fish received rapid dietary CCE-NPs (G2) and partially restored average values (pre-salt bath) at 96 h. The salt treatment could provoke gene expression of pro-inflammatory cytokines interleukin (IL-1β) and tumor necrosis (TNF)-α in the head kidney of fish at 24 h post-salt bath to 5.9-8.35 fold-change, respectively, with a rapid decline in fish (G2) the gene expression. Post-salt bath (24 h), the gene expression of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) was higher in fish (G2) than in the control group (G1) regardless of the supplementation period (7 and 14 days). Bacterial infection S. agalactiae (OL471408), a significantly lower MR was recorded in G2 at 40% and 33.3% compared to the control G1 MR (53.3%), with an RPL of 24.95% and 37.5%. In conclusion, Nile tilapia treated with a 30 ppt salt became more vulnerable to S. agalactiae. Adding CCE-NPs to the Nile tilapia diet for 7- and 14-day pre-salt bath could increase immune and antioxidant-related gene expression to counteract S. agalactiae infection., (© 2024. The Author(s).)

Vitamin C (VC) serves as a pivotal nutrient for anti-oxidation process, metabolic responses, and stem cell differentiation. However, its precise contribution to placenta development and gestation remains obscure. Here, we demonstrated that physiological levels of VC act to stabilize Hand1, a key bHLH transcription factor vital for the development trajectory of trophoblast giant cell (TGC) lineages, thereby promoting the differentiation of trophoblast stem cells into TGC. Specifically, VC administration inactivated c-Jun N-terminal kinase (JNK) signaling, which directly phosphorylates Hand1 at Ser48, triggering the proteasomal degradation of Hand1. Conversely, a loss-of-function mutation at Ser48 on Hand1 not only significantly diminished both intrinsic and VC-induced stabilization of Hand1 but also underscored the indispensability of this residue. Noteworthy, the insufficiency of VC led to severe defects in the differentiation of diverse TGC subtypes and the formation of labyrinth's vascular network in rodent placentas, resulting in failure of maintenance of pregnancy. Importantly, VC deficiency, lentiviral knockdown of JNK or overexpression of Hand1 mutants in trophectoderm substantially affected the differentiation of primary and secondary TGC in E8.5 mouse placentas. Thus, these findings uncover the significance of JNK inactivation and consequential stabilization of Hand1 as a hitherto uncharacterized mechanism controlling VC-mediated placentation and perhaps maintenance of pregnancy., (© 2024. The Author(s).)

Background: Exposure to heavy metals has been suggested to increase the risk of gestational diabetes mellitus (GDM) through the oxidative stress pathway. The study is aimed at examining whether vitamin C could modify the association between exposure to heavy metals and risk of GDM. Methods: We conducted a case-control study in Taiyuan, China, with 776 GDM cases and 776 controls. Data on vitamin C intake from diet and supplements were collected through questionnaires. Concentrations of metals in participants' blood were measured using inductively coupled plasma-mass spectrometry (ICP-MS). Unconditional logistic regression models were applied to estimate effect modification of vitamin C on the association between heavy metals and GDM. Results: Women with higher blood levels of mercury (Hg) (odds ratio (OR) = 2.36, 95% confidence interval (CI): 1.43, 3.92 and 2.04, 95% CI: 1.20, 3.46 for the second and third vs. the first tertile) and arsenic (As) (OR = 2.46, 95% CI: 1.37, 4.43 and 2.16, 95% CI: 1.12, 4.17 for the second and third vs. the first tertile) exposure were associated with increased risk of GDM among women without vitamin C supplement use and having dietary vitamin C intake < 85 mg/day. We found no significant association with metals among women who took vitamin C supplements and/or dietary vitamin C ≥ 85 mg/day. Significant interactions were observed between vitamin C and exposures to metals (i.e., Hg and As) on the risk of GDM ( P interaction Our study, for the first time, suggests that vitamin C supplement use or higher dietary vitamin C intake during preconception and early pregnancy could alleviate the risk of GDM associated with exposure to As and Hg. The results warrant further investigation.Conclusions: Our study, for the first time, suggests that vitamin C supplement use or higher dietary vitamin C intake during preconception and early pregnancy could alleviate the risk of GDM associated with exposure to As and Hg. The results warrant further investigation., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Ying Wang et al.)

Vitamin C is extensively used in cosmetic formulation, howbeit stability is the supreme demerit that limits its use in beautifying products. Numerous techniques are being employed to inhibit the degradation of vitamin C caused by formulation components to facilitate the use in skin rejuvenating products. Diverse materials are being exercised in formulation to stabilize the ascorbic acid and ingredients selected in this formulation composition help for stabilization. The initial stable prototype is developed and further optimization is accomplished by applying the design of experiment tools. The stable pharmaceutical formulations were evaluated for the evaluation parameters and designated as two optimized formulations. The analytical method for the assay of ascorbic acid from the United States pharmacopeia and the related substance method from European pharmacopeia has been modified to be used for cream formulation. The DoE design exhibited that the stability of formulation is impacted by citric acid and tartaric acid but not by propylene glycol and glycerin. The analysis results of topical formulations for the evaluation parameter exhibited satisfactory results. The in-vitro release study method has been developed, optimized, and validated to fit the analysis. The in-vitro studies have been performed for selected compositions and both the formulation has similar kinds of release patterns. The stability study as per ICH guidelines exhibited that the product is stable for accelerated, intermediate, and room-temperature storage conditions. The optimized formulation shows constant release and permeation of ascorbic acid through the skin. The formulation with the combinations of citric acid, tartaric acid, and tocopherol is more stable and the degradation of vitamin C has been reduced significantly. The beaucoup strategies in the unique composition help to protect the degradation by inhibiting the multitudinous degradation pathways., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

The role of food constituents as pharmacological agents is an important consideration in health and obesity. Vitamin C acts as a small molecule antioxidant but is also a co-factor for numerous transition metal-dependent enzymes involved in healthy weight and energy metabolism. Vitamin C cannot be manufactured by humans and is mainly obtained from the dietary intake of fresh fruit and vegetables. There is great variability between different nutritional guidelines in the recommended daily allowance of vitamin C. Vitamin C deficiency results from an inadequate intake of vitamin C-containing foods and also increased utilization by oxidative and carbonyl stress. Risk factors for vitamin C deficiency include cigarette smoking, malnutrition, obesity, type 2 diabetes mellitus, age, race, sex, social isolation, major surgery, and Western-type diets. Despite the common belief that vitamin C deficiency is rare in affluent countries, surveys of large populations and specific patient groups suggest otherwise. Patients with obesity typically consume highly processed, energy-dense foods which contain inadequate micronutrients. As obesity increases, larger amounts of oral vitamin C are required to achieve adequate plasma and tissue concentrations, as compared to persons with a healthy weight. This is important in the control of oxidative stress and the maintenance of homeostasis and organ function. In this narrative review, the dosage, absorption, distribution, excretion, and catabolism of vitamin C are reviewed, together with the latest findings on vitamin C pharmacology in patients with obesity.

Nowadays, nanomaterials enter high numbers of daily used products and drug manufacture. A nanocomposite of vitamins C (VC) and vitamin E (VE) with chitosan as a vehicle and protector was used in a comparative eight-week feeding study, Nile tilapia weighing 31.2 ± 0.36 g distributed in seven groups and fed (G1) basal diet, (G2) bulk VC, (G3) VC- nanoparticles (NPs), (G4) bulk VE, (G5) VE-NPs, bulk VCE (G6), and (G7) VC plus VE (VCE)-NPs, respectively. The Nile tilapia-fed nanocomposite vitamins had significantly higher growth performance compared to the control; VCE-NPs had the superiority among tested supplementations where total weight gain (63.6 g), daily weight gain (1.13 g), relative growth rate (206.1%) with lower feed conversion rate (1.6) and insignificant feed intake (101.5 g). Overall, the level of liver enzymes was significantly decreased in fish serum after eight-week nanocomposite supplementation, and dietary VCE-NPs caused a significant reduction of serum AST (18.45 IU/L) and ALT (14.77 IU/L) compared to the control 25.5 IU/L and 17.6 IU/L, respectively. Fish fed dietary VCE-NPs, VC-NPs, and VE-NPs had significant enhancement of RBCs 4.2 × 10 6 /μL, 3.8 × 10 6 /μL, and 3.55 × 10 6 /μL; WBCs 46.15 × 10 3 , 42.9 × 10 3 , and 44 × 10 3 /μL, respectively, Also TP was significantly higher 6.38 g/dL in VCE-NPs group compared to the control and the other treatments. Over all, the dietary nanocomposite vitamins boost the innate immunity of the experimental Nile tilapia, the oxidative burst activity (OBA), phagocytic activity (PA), phagocytic index (PI), and serum antibacterial (SAA) were significantly increased compared to those received bulk vitamins and the control. The activity of antioxidant biomarkers in fish serum including glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (TAC), glutathione reductase (GR), and myeloperoxidase (MPO) showed a rise in the serum of Nile tilapia received nano- and bulk-form of VC and VCE compared to the control and both forms of VE. Furthermore, the level of malondialdehyde (MDA), reduced glutathione (GSH), and oxidized glutathione (GSSG) were significantly increased in the fish serum following the trend of antioxidants enzymes. In conclusion, a dietary nanocomposite of vitamin C and vitamin E enhanced Nile tilapia's growth performance and feed utilization. It could also improve health status and immune response. The values of antioxidant biomarkers indicated that the nanocomposite could help the fish body scavenge the generated reactive oxidative species (ROS)., (© 2024. The Author(s).)

Vitamin C is a water-soluble vitamin introduced through the diet with anti-inflammatory, immunoregulatory, and antioxidant activities. Today, this vitamin is integrated into the treatment of many inflammatory pathologies. However, there is increasing evidence of possible use in treating autoimmune and neoplastic diseases. We reviewed the literature to delve deeper into the rationale for using vitamin C in treating this type of pathology. There is much evidence in the literature regarding the beneficial effects of vitamin C supplementation for treating autoimmune diseases such as Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA) and neoplasms, particularly hematological neoplastic diseases. Vitamin C integration regulates the cytokines microenvironment, modulates immune response to autoantigens and cancer cells, and regulates oxidative stress. Moreover, integration therapy has an enhanced effect on chemotherapies, ionizing radiation, and target therapy used in treating hematological neoplasm. In the future, integrative therapy will have an increasingly important role in preventing pathologies and as an adjuvant to standard treatments.

Vitamin C (ascorbic acid) is a potent antioxidant and a cofactor for various enzymes including histone demethylases and methylcytosine dioxygenases. Vitamin C also exerts direct cytotoxicity toward selected tumor cells including colorectal carcinoma. Moreover, vitamin C has been shown to impact immune cell differentiation at various levels including maturation and/or functionality of T cells and their progenitors, dendritic cells, B cells, and NK cells. γδ T cells have recently attracted great interest as effector cells for cell-based cancer immunotherapy, due to their HLA-independent recognition of a large variety of tumor cells. While γδ T cells can thus be also applied as an allogeneic off-the-shelf product, it is obvious that the effector function of γδ T cells needs to be optimized to ensure the best possible clinical efficacy. Here we review the immunomodulatory mechanisms of vitamin C with a special focus on how vitamin C enhances the effector function of γδ T cells. We also discuss future directions of how vitamin C can be used in the clinical setting to boost the efficacy of adoptive cell therapies., (© 2024 The Authors. European Journal of Immunology published by Wiley‐VCH GmbH.)

Although vitamin C is one of the most important antioxidants, its effect on muscle quality is not fully understood. Therefore, we hypothesized that low dietary vitamin C intake is associated with low muscle strength. To test the hypothesis, a single 24-h dietary recall and handgrip strength test of 10,883 younger adults 19-64 y and 3,961 older adults ≥65 y from the seventh Korea National Health and Examination Survey (KNHANES VII 2016-2018) was analyzed by multivariable linear and logistic regression models, and low muscle strength was defined as handgrip strength <28 kg for men and <18 kg for women. Approximately 15.5% of Korean adults met the recommended intake of dietary vitamin C, and those with higher dietary vitamin C intake had higher total energy and protein intake. After adjusting for confounding variables, including age, body mass index, total energy intake, household income, alcohol consumption, smoking, resistance exercise, medical condition, and dietary intake of protein, vitamin E, and β-carotene, dietary vitamin C was correlated with maximal handgrip strength in younger women 19-64 y (β = 0.002; SE = 0.001; P-value = .026) and older women ≥65 y (β = 0.005; SE = 0.002; P-value = .013). Among older women ≥65 y, those in the lowest quartile of dietary vitamin C intake had a higher risk of low muscle strength compared to those in the highest quartile after adjustment of confounding factors (odds ratio, 2.16; 95% confidence interval, 1.49-3.15). These results imply that adequate dietary vitamin C intake may reduce the risk of sarcopenia in older Korean women., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Tetrahexydecyl ascorbate (THDA) is a lipophilic precursor to ascorbic acid that may be stabilized by acetyl zingerone (AZ). Studies have shown that the topical application of THDA may have photoprotective effects. Similarly, AZ has been shown to mitigate oxidative and inflammatory stress, thereby improving the appearance of photoaging., Aims: To examine the effects of THDA and AZ (THDA-AZ) on skin photoaging compared to THDA alone., Patients/methods: In this double-blind, randomized controlled trial, healthy individuals aged 30 to 65 were included and 44 participants were randomized to receive either THDA-AZ (THDA 5% + AZ 1%) or THDA only (THDA 5%) for 8 weeks. Facial photographs were taken at 0, 4, and 8 weeks to analyze wrinkle severity, pigment intensity, and redness intensity. A skin colorimeter was used to assess infraorbital pigmentation and erythema. Self-perception of skin and tolerability were assessed through questionnaires., Results: Average wrinkle severity was significantly decreased in the THDA-AZ group at Weeks 4 and 8 by 0.75% (p = 0.023) and 3.72% (p = 0.048), respectively, compared to the THDA group where wrinkle severity at Weeks 4 and 8 was increased by 7.88% and 4.48%, respectively. Facial pigment intensity was significantly decreased in the THDA-AZ group by 4.10% (p = 0.0002) at Week 8 compared to a 0.69% decrease in the THDA group. Facial redness intensity was decreased in the THDA-AZ group at Weeks 4 and 8 by 3.73% (p = 0.0162) and 14.25% (p = 0.045), respectively, compared to the THDA group where at Weeks 4 and 8 erythema increased by 27.5% and 8.34%, respectively. There were no significant differences in either group for infraorbital pigmentation or erythema., Conclusions: Daily use of combined THDA and AZ may improve facial wrinkle severity, pigment intensity, and erythema to a greater extent than THDA. While THDA alone increases facial wrinkle severity and erythema, the addition of AZ reduces both., (© 2024 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background and Objectives: There is no evidence on antioxidant-rich diets in preventing hypertension in heat-exposed workers. We aimed to evaluate the effects of formula supplemented with vitamin C (Vit C) and hawthorn beverage on reducing blood pressure (BP) and oxidative stress levels in heat-exposed workers., Methods and Study Design: In the 40-day cluster-randomized controlled trial, four heat-exposed shift-teams were enrolled and randomly assigned to the intervention and control groups. The intervention group was given one Vit C tablet (130 mg) and a 500 mL hawthorn beverage containing 278.7 mg flavonoids daily whereas the control group was given 500 mL of slightly salted water daily; both groups were provided education on a healthy diet. BP and creatinine-corrected urinary 8-isoprostane-prostaglandin F2α (8-iso-PGF2α/Cr) concentrations were assessed at baseline, Day 17 (only BP) and Day 41, respectively., Results: Compared with the control group, the systolic BP (SBP), diastolic BP (DBP), and log10-transformed 8-iso-PGF2α/Cr in the inter-vention group decreased by 7.41 mmHg, 7.93 mmHg and 0.232, respectively, from baseline to day 41 (all p<0.05). When comparing BP levels at baseline, DBP in the intervention group was reduced by 5.46 mmHg when compared to control (p<0.05) among participants with lower baseline BP; SBP and DBP experienced reductions of 9.74 and 9.22 mmHg among participants with higher baseline BP (both p<0.05)., Conclusions: Supplementation of Vit C and flavonoids rich hawthorn beverage to heat-exposed workers prevented elevated BP caused by heat exposure which may be attributed to its oxidative stress inhibition effects., Competing Interests: The authors declare no conflicts of interest

The objective of this work was to prepare and characterize liposomes containing co-encapsulated ascorbic acid (AA) and ascorbyl palmitate (AP), as well as to evaluate their stability, cytotoxicity, antioxidant, and antimicrobial activity. Through the pre-formulation studies, it was possible to improve the formulation, as leaving it more stable and with a greater antioxidant activity, resulting in a formulation designated LIP-AAP, with 161 nm vesicle size, 0.215 polydispersity index, -31.7 mV zeta potential, and pH of 3.34. Encapsulation efficiencies were 37% for AA and 79% for AP, and the content was 1 mg/mL for each compound. The optimized liposomes demonstrated stability under refrigeration for 60 days, significant antioxidant activity (31.4 μMol of TE/mL), and non-toxicity, but no antimicrobial effects against bacteria and fungi were observed. These findings confirm that the co-encapsulated liposomes are potent, stable antioxidants that maintain their physical and chemical properties under optimal storage conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Deregulation of ten-eleven Translocation protein 1 (TET1) is commonly reported to induce imbalances in gene expression and subsequently to colorectal cancer development (CRC). On the other hand, vitamin C (VitC) improves the prognosis of colorectal cancer by reprogramming the cancer epigenome and limiting chemotherapeutic drug resistance events. In this study, we aimed to characterize TET1-specific subcellular compartments and evaluate the effect of VitC on TET1 compartmentalization in colonic tumour cells. We demonstrated that TET1 is concentrated in coarse nuclear bodies (NB) and 5-hydroxymethylcytosine (5hmC) in foci in colorectal cancer cells (HCT116, Caco-2, and HT-29). To our knowledge, this is the first report of a novel intracellular localization profile of TET1 and its demethylation marker, 5hmC, in CRC cells. Interestingly, we found that TET1-NBs frequently interacted with Cajal bodies, but not with promyelocytic leukaemia (PML) bodies. In addition, we report that VitC treatment of HCT116 cells induces 5hmC foci biogenesis and triggers 5hmC marks to form active complexes with nuclear body components, including both Cajal and PML proteins. Our data highlight novel NB-concentrating TET1 in CRC cells and demonstrate that VitC modulates TET1-NBs' interactions with other nuclear structures. These findings reveal novel TET1-dependent cellular functions and potentially provide new insights for CRC management.

Electrospraying for Vitamin C (VC) encapsulation in Chitosan (Cs) nanoparticles was investigated and particle size, zeta potential, loading capacity (LC%) and encapsulation efficiency (EE%) were examined. Cs concentration (1-2% w/v) and voltage (21-25 kV) were varied with VC (0.25-0.75 w/w Cs). Twenty experiments in a face-centered CCD-RSM design were evaluated. ANOVA suggested voltage and Cs concentration as significant factors for particle size and VC content affected zeta, LC and EE%. RSM proposed optimum processing parameter at 2% Cs, 0.746 VC: Cs mass ratio and 21 kV voltage with 251.1 ± 59.03 nm particle size, 36.6% LC and an EE of 85.42%. Encapsulated particles were subjected to release behaviour, antioxidant property and analyzed through FTIR, DSC and XRD. Encapsulated VC had better antibacterial properties than Cs nanoparticles, and comparable VC retention in apple juice showed its effectiveness. Overall, nanoencapsulation of VC using electrospraying was successfully developed to be used in numerous food processing applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Mammalian embryos often suffer from oxidative stress in vitro, as the oxygen in the atmosphere is higher than that in the oviductal environment. Vitamin C (Vc) has been proven to enhance early embryonic development in vitro , but the underlying mechanism remains unclear. In this study, we investigated the pathways of action by which Vc promotes the in vitro development of porcine embryos. Comparative analysis of in vitro and in vivo gene expression profiles of morula found that most of the differentially expressed genes were enriched in pathways related to mitochondrial function. The addition of 12.5 μg/mL Vc to the culture medium significantly increased blastocyst production in a dose- and duration-dependent manner. Moreover, ROS levels were significantly higher in embryos cultured in the air (21% oxygen) than cultured in a hypoxic condition (5% oxygen) and were reduced by Vc supplementation. Vc also significantly increased the mitochondrial membrane potential levels and the expression levels of mitochondrial function-related genes ( MFN1 and OPA1 ) and TCA cycle-related genes ( PDHA1 and OGDH ) in embryos cultured in vitro . These results suggest that the addition of Vc to the in vitro culture medium can increase the developmental potential and improve the mitochondrial function of early porcine embryos.

Rosa roxburghii Tratt (RRT), a traditional Chinese plant known as the 'King of Vitamin C (VitC; ascorbic acid, AsA)', contains a wealth of nutrients and functional components, including polysaccharides, organic acids, flavonoids, triterpenes, and high superoxide dismutase (SOD) activity. The various functional components of RRT suggest that it may theoretically have a stronger potential for alleviating colitis compared to VitC. This study aims to verify whether RRT has a stronger ability to alleviate colitis than equimolar doses of VitC and to explore the mechanisms underlying this improvement. Results showed that RRT significantly mitigated body weight loss, intestinal damage, elevated inflammation levels, and compromised barriers in mice induced by Dextran sulfate sodium (DSS). Additionally, RRT enhanced the diversity and composition of intestinal microbiota in these DSS-induced mice. Colon RNA sequencing analysis revealed that compared to VitC, RRT further downregulated multiple immune-related signaling pathways, particularly the B cell receptor (BCR) pathway, which is centered around genes like Btk and its downstream PI3K-AKT, NF-κB, and MAPK signaling pathways. Correlation analysis between microbiota and genes demonstrated a significant relationship between the taxa improved by RRT and the key genes in the BCR and its downstream signaling pathways. Overall, RRT exhibited superior capabilities in alleviating DSS-induced colitis compared to VitC by decreasing intestinal inflammation and modulating BCR and its downstream signaling pathways, potentially regulated by the improved intestinal microbiota., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

A validated silver nanoparticle assay (SNaP-C) for quantitation of Vitamin C, as ascorbic acid (AA) and total AA (TAA), was applied to 31 beverages. SNaP-C assay results (LOD of 2.2 mg/L AA) were compared to AA and TAA determined by high-performance liquid chromatography with UV/Vis (LOD = 0.4 mg/L AA), and two well-known assays. All approaches were calibrated using meta-phosphoric acid stabilized AA, where the reducing agent tris(2-carboxyethyl) phosphine hydrochloride was added to convert dehydroascorbic acid to AA for determination of TAA. Statistical comparisons of these four resulting datasets were completed. SNaP-C and HPLC were not statistically significantly different (P > 0.05) for comparison of AA and TAA (mg/L) in these samples, whereas the CUPRAC and Folin-Ciocalteu assays statistically significantly overestimated values of AA and TAA content, respectively. The SNaP-C method is a novel assay that has high specificity for AA capable of quantifying TAA with addition of TCEP., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

This experiment was conducted to explore the effects of dietary vitamin C supplementation on non-specific immune defense, antioxidant capacity and resistance to low-temperature stress of juvenile mud crab (Scylla paramamosain). Mud crabs with an initial weight of 14.67 ± 0.13 g were randomly divided into 6 treatments and fed diets with 0.86 (control), 44.79, 98.45, 133.94, 186.36 and 364.28 mg/kg vitamin C, respectively. The experiment consisted of 6 treatments, each treatment was designed with 4 replicates and each replicate was stocked with 8 crabs. After 42 days of feeding experiment, 2 crabs were randomly selected from each replicate, and a total of 8 crabs in each treatment were carried out 72 h low-temperature challenge experiment. The results showed that crabs fed diets with 186.36 and 364.28 mg/kg vitamin C significantly improved the activities of alkaline phosphatase (AKP) and acid phosphatase (ACP) in hemolymph and hepatopancreas (P < 0.05). Crabs fed diet with 133.94 mg/kg vitamin C significantly decreased the concentration of nitric oxide (NO) and the activity of nitric oxide synthase (NOS) in hemolymph (P < 0.05). Diet with 133.94 mg/kg vitamin C was improved the activity of polyphenol oxidase (PPO) and the concentration of albumin (ALB) in hemolymph. Crabs fed diet with 133.94 mg/kg vitamin C showed lower concentration of malondialdehyde (MDA) in hemolymph and hepatopancreas than those fed the other diets. Meanwhile, crabs fed diet with 98.45 mg/kg vitamin C showed higher activity of total superoxide dismutase (T-SOD) in hemolymph, and crabs fed diet with 133.94 mg/kg vitamin C showed higher activity of T-SOD in hepatopancreas. Crabs fed diet with 186.36 mg/kg vitamin C significantly decreased the concentration of reduced glutathione (GSH) and the activity of glutathione peroxidase (GSH-PX) in hepatopancreas (P < 0.05). In normal temperature, crabs fed diets with 133.94 mg/kg vitamin C significantly up-regulated the expression levels of gpx (glutathione peroxidase) and trx (thioredoxin) in hepatopancreas compared with the control treatment (P < 0.05). The highest expression levels of relish, il16 (interleukin 16), caspase 2 (caspase 2), p38 mapk (p38 mitogen-activated protein kinases) and bax (bcl-2 associated x protein) in hepatopancreas were found at crabs fed control diet (P < 0.05). Moreover, crabs fed diet with 133.94 mg/kg vitamin C showed higher expression levels of alf-3 (anti-lipopolysaccharide factor 3) and bcl-2 (B-cell lymphoma 2) in hepatopancreas than those fed the other diets (P < 0.05). Under low-temperature stress, crabs fed diet with 133.94 mg/kg vitamin C significantly improved the expression levels of hsp90 (heat shock protein 90), cat (catalase), gpx, prx (thioredoxin peroxidase) and trx in hepatopancreas (P < 0.05). In addition, dietary with 133.94 vitamin C significantly up-regulated the expression levels of alf-3 and bcl-2 (P < 0.05). Based on two slope broken-line regression analysis of activity of PPO against the dietary vitamin C level, the optimal dietary vitamin C requirement was estimated to be 144.81 mg/kg for juvenile mud crab. In conclusion, dietary 133.94-144.81 mg/kg vitamin C significantly improved the non-specific immune defense, antioxidant capacity and resistance to low-temperature stress of juvenile mud crab., Competing Interests: Declaration of competing interest The authors confirm that they have no known financial conflicts of interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Vitamin C (Ascorbic acid, AA), as vital micro-nutrient, plays an essential role for male animal reproduction. Previously, we showed that vitamin C reprogrammed the transcriptome and proteome to change phenotypes of porcine immature Sertoli cells (iSCs). Here, we used LC-MS-based non-targeted metabolomics to further investigate the metabolic effects of vitamin C on porcine iSCs. The results identified 43 significantly differential metabolites (DMs) (16 up and 27 down) as induced by vitamin C (L-ascorbic acid 2-phosphate sesquimagnesium salt hydrate, AA2P) treatment of porcine iSCs, which were mainly enriched in steroid related and protein related metabolic pathways. ELISA (Enzyme-Linked ImmunoSorbent Assay) showed that significantly differential metabolites of Dehydroepiandrosterone (DHEA) (involved in steroid hormone biosynthesis) and Desmosterol (involved in steroid degradation) were significantly increased, which were partially consistent with metabolomic results. Further integrative analysis of metabolomics, transcriptomics and proteomics data identified the strong correlation between the key differential metabolite of Dehydroepiandrosterone and 6 differentially expressed genes (DEGs)/proteins (DEPs) (HMGCS1, P4HA1, STON2, LOXL2, EMILIN2 and CCN3). Further experiments validated that HMGCS1 could positively regulate Dehydroepiandrosterone level. These data indicate that vitamin C could modulate the metabolism profile, and HMGCS1-DHEA could be the pathway to mediate effects exerted by vitamin C on porcine iSCs., Competing Interests: Conflict of interest The authors declare that there are no conflicts of interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic and symmetric in-flammation. Our previous research revealed an imbalance in the gut flora of RA patients and showed that certain gut microbiota can accelerate RA progression by enhancing vitamin C degradation. However, it is unclear whether vitamin C supplementation could improve the gut microbiota to prevent the development of arthritis by interfering with the gut-joint axis. In this work, we aimed to evaluate the effects of vitamin C in regulating the gut microbiota and to elucidate its potential role in the onset and progression of RA in a mouse model, thus providing a basis for the development of new intervention strategies and treatments for RA. In this study, collagen-induced arthritis (CIA) mouse models, biochemical, histological and 16S rRNA microbiological methods were used to investigate the role and possible mechanism of vitamin C in rheumatoid arthritis. The results showed that treatment of CIA mice with vitamin C effectively rescued the gut mi-crobiota imbalance and suppressed the inflammatory response associated with RA, and effectively alleviated arthritis symptoms in mice in which levels of the pro-inflammatory cytokines IL-6 and TNF-α were specifi-cally reduced. In conclusion, our results demonstrate the potential of vitamin C as a potential therapeutic choice for RA.

In recent years, the utilization of natural components has become crucial across various industries, including medicine. Particularly in biomedical contexts, hydrogel materials are of significant importance. Therefore, the objective of this research was to develop and analyze hydrogel materials infused with vitamin C. A key focus of this study was to conduct multiple syntheses with varying levels of vitamin C to explore the feasibility of creating materials with adjustable properties. The produced hydrogels underwent comprehensive physicochemical evaluation. The findings of this examination verified the correlation between the vitamin C content and the specific characteristics of the hydrogels. It was determined from these results that the samples displayed both sorptive and antioxidative capabilities, enabling their potential application in wound dressings or other biomedical uses. A notable benefit of these hydrogels is their adaptability, allowing for modifications to achieve desired attributes tailored to particular applications.

Background and Aims: The associations between dietary vitamin C (VC), vitamin E (VE) intake and aortic aneurysm and dissection (AAD) remain unclear. This study aimed to prospectively investigate the associations between dietary VC and VE with the incident risk of AAD., Methods and Results: A total of 139 477 participants of UK Biobank cohort were included in the analysis. Dietary VC and VE consumptions were acquired through a 24-h recall questionnaire. Cox proportional regression models were used to examine the associations between VC, VE intake and the risk of AAD. Incident AAD was ascertained through hospital inpatient records and death registers. During a median follow-up of 12.5 years, 962 incident AAD events were documented. Both dietary VC [adjusted hazard ratio (HR), 0.77; 95 % confidence intervals (CI), 0.63-0.93; P-trend = 0.008] and VE (adjusted HR, 0.70; 95 % CI, 0.57-0.87; P-trend = 0.002) were inversely associated with incident AAD when comparing the participants in the highest quartile with those in the lowest. In subgroup analyses, the associations were more pronounced in participants who were over 60 years old, participants with smoking history, hypertension or hyperlipidemia, who were under the high risk of AAD., Conclusion: Higher dietary VC and VE intakes are associated with reduced risk of AAD. Our study emphasizes the importance of diet adjustment strategies targeted on VC and VE to lower the incidence rate of AAD especially in the high-risk population., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Co-administration of vitamin C and inorganic nitrate ([Formula: see text]) may reduce oxidative stress, boost the conversion of nitrite ([Formula: see text]) into NO and elicit positive vascular effects. Background: We aimed to test the effects of oral inorganic [Formula: see text] and vitamin C co-supplementation on vascular function, muscular strength, and on concentrations of urinary [Formula: see text], vitamin C, 8-isoprostanes and salivary [Formula: see text] in healthy young adults. Aims: Ten young healthy participants were enrolled in a randomised, double-blind (only for the [Formula: see text] intervention) crossover clinical trial. Participants consumed in random order: 1) nitrate-rich beetroot juice and vitamin C (N+VC), 2) nitrate-rich beetroot juice alone (N) or 3) nitrate-depleted beetroot juice alone (ND). Resting blood pressure (BP) was measured at the research centre and at home. Non-invasive, continuous measurements of BP and cardiac function parameters were performed using a Finometer device. Free-living physical activity and hand-grip strength were assessed. Salivary [Formula: see text] and [Formula: see text] and urinary [Formula: see text], 8-isoprostanes and vitamin C concentrations were measured. Methods: There were no significant differences for any of the vascular outcomes between the three interventions groups. However, analyses of within-intervention changes showed a significant lower daily systolic BP in the [Formula: see text]+vitamin C (N+VC) group only (P=0.04). Urinary [Formula: see text] (P=0.002) and salivary [Formula: see text] (P=0.001) were significantly higher in the N+VC group compared to the N and ND groups. Results: These preliminary findings suggest that combining dietary [Formula: see text] with vitamin C could have protective effects on vascular function in young adults and could represent an effective strategy for the maintenance of healthy cardiovascular trajectories.Conclusion: These preliminary findings suggest that combining dietary [Formula: see text] with vitamin C could have protective effects on vascular function in young adults and could represent an effective strategy for the maintenance of healthy cardiovascular trajectories.

The aim of this study was to determine whether ascorbic acid (AA) supplementation can lower plasma levels of Cortisol and dehydroepiandrosterone-sulphate (DHEA-S) in patients diagnosed with functional hypercortisolemia due to unspecified chronic stress. Study includes data from 69 female with elevations in the cortisol and DHEA-S levels. Duration of follow-up was 2 months. Patients were divided into 3 groups. Group I included patients 23 with elevated cortisol, Group II-patients 24 with elevated levels of both hormones, Group III- patients 22 with normal cortisol and increased DHEA-S. Each group was randomly divided into two subgroups. The first subgroup was prescribed 1000 mg daily oral dose of AA. The diet of the second subgroup were left unaltered. All patients have their hormones levels re-examined 2 months later. After 2 months of AA supplementation the mean levels of elevated plasma cortisol and DHEA-S decreased. In Group I the level of cortisol fell from 780 ± 57-446 ± 26 nmol/L, p = 0.000065 in Group II from 657 ± 47-515 ± 29 nmol/L, p = 0.005. The elevated levels of DHEA-S have also declined in patients from AA-treated subgroups (from 13.9 ± 1.6-9.9 ± 1.2, p = 0.0007 in Group II, and from 12.8 ± 1.0-7.8 ± 1.4, p = 0.003 in Group III). In untreated subgroups changes in hormone levels were insignificant. The study shows that female patients with functional hypercortisolemia or elevated levels of DHEA-S can be treated with AA to bring level of these hormones closer to a normal range., (© 2023 John Wiley & Sons Ltd.)

Objective: With rising rates of complementary and alternative medicine (CAM) use, the exploration of CAM integration into oncology treatments is becoming increasingly prevalent. Antioxidants have been proposed as potentially beneficial to prevent or treat cancer. However, evidence summaries are limited, and the United States Preventive Services Task Force has recently recommended the use of Vitamin C and E supplementation for cancer prevention. Thus, the objective of this systematic review is to evaluate the existing literature on the safety and efficacy of antioxidant supplementation in oncology patients., Methods: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, using prespecified search terms in PubMed and CINAHL. Two reviewers independently reviewed titles, abstracts, and full-text articles, with a third reviewer resolving conflicts, before the included articles underwent data extraction and quality appraisal., Results: Twenty-four articles met the inclusion criteria. Of the included studies, nine evaluated selenium, eight evaluated Vitamin C, four evaluated Vitamin E, and three of these studies included a combination of two or more of these agents. The most frequently evaluated cancer types included colorectal cancer ( n  = 4), leukemias ( n  = 4), breast cancer ( n  = 3), and genitourinary cancers ( n  = 3). Most of the studies focused on the antioxidants' therapeutic efficacy ( n  = 15) or their use in protecting against chemotherapy- or radiation-induced side effects ( n  = 8), and one study evaluated the role of an antioxidant in protection against cancer. Findings were generally favorable among the studies, and adverse effects of supplementation were limited. Furthermore, the average score for all the included articles on the Mixed Methods Appraisal Tool was 4.2, indicating the high quality of the studies., Conclusions: Antioxidant supplements may provide benefits in reducing incidence or severity of treatment-induced side effects with limited risk for adverse effects. Large, randomized controlled trials are needed to confirm these findings among various cancer diagnoses and stages. Healthcare providers should understand the safety and efficacy of these therapies to address questions that arise in caring for those with cancer., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The relation of vitamin C with Alzheimer's disease (AD) is equivocal. The aim of this study was to assess the relation of serum vitamin C levels with AD-related mortality, and to evaluate the threshold beyond which the potential benefits of higher serum concentrations of vitamin C for AD mortality ceases. The cohort consisted of 4504 adults aged ≥60 years enrolled in the National Health and Nutrition Examination Survey who had serum measures of vitamin C and no cognitive impairment at baseline (1988-1994) and were followed-up for mortality until 2019. Vitamin C was assayed from fasting blood samples using isocratic high-performance liquid chromatography. At baseline, the mean age of participants was 70 years, with 42.7% being men. At the end of follow-up (median: 15 years), the AD mortality rate was 2.4 per 1000 person-years. In the Cox regression models, compared to participants in the lowest tertile of serum vitamin C (<0.56 mg/dL), those in the highest tertile (>0.98 mg/dL) had a lower risk of AD mortality (hazard ratio: 0.44, 95% confidence intervals: 0.25-0.77) after adjusting for sociodemographic factors, behavior/lifestyle factors, prevalent health conditions, and dietary vitamin C intake. In dose-response analysis using restricted cubic splines, vitamin C concentrations beyond 2.3 mg/dL were associated with the elevated risk of AD-related mortality. The findings from this national sample of community-dwelling elderly adults suggest that higher levels of serum vitamin C are associated with slower AD disease progression, although levels beyond the normal reference values were associated with a higher risk of AD mortality.

Vitamin C (VC), also known as ascorbic acid, plays a crucial role as a water-soluble nutrient within the human body, contributing to a variety of metabolic processes. Research findings suggest that increased doses of VC demonstrate potential anti-tumor capabilities. This review delves into the mechanisms of VC absorption and its implications for cancer management. Building upon these foundational insights, we explore modern delivery systems for VC, evaluating its use in diverse cancer treatment methods. These include starvation therapy, chemodynamic therapy (CDT), photothermal/photodynamic therapy (PTT/PDT), electrothermal therapy, immunotherapy, cellular reprogramming, chemotherapy, radiotherapy, and various combination therapies.

Background: Vitamin C (ascorbate) is a water-soluble antioxidant and an important cofactor for various biosynthetic and regulatory enzymes. Mice can synthesize vitamin C thanks to the key enzyme gulonolactone oxidase (Gulo) unlike humans. In the current investigation, we used Gulo -/- mice, which cannot synthesize their own ascorbate to determine the impact of this vitamin on both the transcriptomics and proteomics profiles in the whole liver. The study included Gulo -/- mouse groups treated with either sub-optimal or optimal ascorbate concentrations in drinking water. Liver tissues of females and males were collected at the age of four months and divided for transcriptomics and proteomics analysis. Immunoblotting, quantitative RT-PCR, and polysome profiling experiments were also conducted to complement our combined omics studies., Results: Principal component analyses revealed distinctive differences in the mRNA and protein profiles as a function of sex between all the mouse cohorts. Despite such sexual dimorphism, Spearman analyses of transcriptomics data from females and males revealed correlations of hepatic ascorbate levels with transcripts encoding a wide array of biological processes involved in glucose and lipid metabolisms as well as in the acute-phase immune response. Moreover, integration of the proteomics data showed that ascorbate modulates the abundance of various enzymes involved in lipid, xenobiotic, organic acid, acetyl-CoA, and steroid metabolism mainly at the transcriptional level, especially in females. However, several proteins of the mitochondrial complex III significantly correlated with ascorbate concentrations in both males and females unlike their corresponding transcripts. Finally, poly(ribo)some profiling did not reveal significant enrichment difference for these mitochondrial complex III mRNAs between Gulo -/- mice treated with sub-optimal and optimal ascorbate levels., Conclusions: Thus, the abundance of several subunits of the mitochondrial complex III are regulated by ascorbate at the post-transcriptional levels. Our extensive omics analyses provide a novel resource of altered gene expression patterns at the transcriptional and post-transcriptional levels under ascorbate deficiency., (© 2024. The Author(s).)

L-Ascorbic acid, commonly known as vitamin C, has been used not only for disease prevention and in complementary and alternative medicine, but also for anti-aging purposes. However, the scientific evidence is not yet sufficient. Here, we review the physiological functions of vitamin C and its relationship with various pathological conditions, including our previous findings, and discuss the prospects of its application in healthy longevity. In summary, vitamin C levels are associated with lifespan in several animal models. Furthermore, clinical studies have shown that the blood vitamin C levels are lower in middle-aged and older adults than in younger adults. Lower blood vitamin C levels have also been observed in various pathological conditions such as chronic kidney disease and chronic obstructive pulmonary disease in the elderly. These observations suggest the implications of vitamin C in age-related pathological mechanisms owing to its physiological functions., (© 2024. The Author(s).)

Background: Retinal pigment epithelial cells (RPECs) are a type of retinal cells that structurally and physiologically support photoreceptors. However, hyperglycemia has been shown to play a critical role in the progression of diabetic retinopathy (DR), which is one of the leading causes of vision impairment. In the diabetic eye, the high glucose environment damages RPECs via the induction of oxidative stress, leading to the release of excess reactive oxygen species (ROS) and triggering apoptosis. In this study, we aim to investigate the antioxidant mechanism of Vitamin C in reducing hyperglycemia-induced stress and whether this mechanism can preserve the function of RPECs., Methods and Results: ARPE-19 cells were treated with high glucose in the presence or absence of Vitamin C. Cell viability was measured by MTT assay. Cleaved poly ADP-ribose polymerase (PARP) was used to identify apoptosis in the cells. ROS were detected by the DCFH-DA reaction. The accumulation of sorbitol in the aldose reductase (AR) polyol pathway was determined using the sorbitol detection assay. Primary mouse RPECs were isolated from adult mice and identified by Rpe65 expression. The mitochondrial damage was measured by mitochondrial membrane depolarization. Our results showed that high glucose conditions reduce cell viability in RPECs while Vitamin C can restore cell viability, compared to the vehicle treatment. We also demonstrated that Vitamin C reduces hyperglycemia-induced ROS production and prevents cell apoptosis in RPECs in an AR-independent pathway., Conclusions: These results suggest that Vitamin C is not only a nutritional necessity but also an adjuvant that can be combined with AR inhibitors for alleviating hyperglycemic stress in RPECs., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

l-Ascorbic acid (AsA, vitamin C) is a pivotal dietary nutrient with multifaceted importance in living organisms. In plants, the Smirnoff-Wheeler pathway is the primary route for AsA biosynthesis, and understanding the mechanistic details behind its component enzymes has implications for plant biology, nutritional science, and biotechnology. As part of an initiative to determine the structures of all six core enzymes of the pathway, the present study focuses on three of them in the model species Myrciaria dubia (camu-camu): GDP-d-mannose 3',5'-epimerase (GME), l-galactose dehydrogenase (l-GalDH), and l-galactono-1,4-lactone dehydrogenase (l-GalLDH). We provide insights into substrate and cofactor binding and the conformational changes they induce. The MdGME structure reveals a distorted substrate in the active site, pertinent to the catalytic mechanism. Mdl-GalDH shows that the way in which NAD+ association affects loop structure over the active site is not conserved when compared with its homologue in spinach. Finally, the structure of Mdl-GalLDH is described for the first time. This allows for the rationalization of previously identified residues which play important roles in the active site or in the formation of the covalent bond with FAD. In conclusion, this study enhances our understanding of AsA biosynthesis in plants, and the information provided should prove useful for biotechnological applications., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)