Vitamin C is essential for proper myogenic differentiation.

There is substantial international variation in recommended vitamin C intake levels. In the USA, the recommendation is 90 mg/d for men and 75 mg/d for women, while in the UK, the current recommendation – established in 1991 – is only 40 mg/d for adults. This UK level was based on the 1953 Sheffield study, which found that 10 mg/d prevents scurvy, with 40 mg/d chosen as the recommended level for yielding somewhat higher plasma levels. In this commentary, we argue that the UK recommendation overlooked key evidence available at the time. Specifically, at least six controlled trials published before 1991 reported benefits from vitamin C supplementation in participants whose baseline vitamin C intake was already 40 mg/d or higher. One randomised controlled trial, published in 1993, found benefits from vitamin C supplementation even at a baseline intake of about 500 mg/d; however, this trial involved ultramarathon runners, and the findings should not be broadly generalised. Nonetheless, such results challenge the assumption that 40 mg/d is universally adequate to maintain full health. We also highlight that the UK recommendations were narrowly focused on preventing dermatological symptoms of scurvy, despite strong evidence – even at the time – that vitaminC deficiency can also cause cardiac dysfunction and greater morbidity due to respiratory infections. We conclude that the current UK vitamin C recommendation should be re-evaluated in light of controlled trial evidence and broader clinical outcomes.

Background: Vitamin C deficiency remains an under-recognized condition in children, especially in Southeast Asia. This study aimed to study the clinical characteristics, dietary risk factors, and outcomes of pediatric vitamin C deficiency in a tertiary hospital in Southern Thailand. Methods: This retrospective study reviewed the medical records of children aged 1 to 15 years diagnosed with vitamin C deficiency from 2004 to 2024. Diagnosis was based on serum ascorbic acid levels below 0.4 mg/dL, or clinical-radiographic findings. Data collected included demographics, developmental status, dietary history, clinical presentations, radiological and laboratory results, treatment, and outcomes. Results: Forty-six children were diagnosed; the median age was 4.8 years, and 60% were male; developmental delay was present in 54.4%. The majority had poor dietary intake, with 73% not consuming adequate fruits and vegetables; no significant differences were observed when classified by developmental status. Common clinical signs included: limb pain (76.1%), refusal to walk (52.2%), and bleeding gums (39.1%). Radiographs showed osteopenia in 73.8% and white line of Frankel in 47.6%. Serum ascorbic acid deficiency was significantly associated with low fruit and vegetable intake and excessive milk consumption over the recommendations (p < 0.05). Treatment with oral vitamin C resulted in clinical improvement; although, residual symptoms persisted in some cases. Conclusions: As pediatric vitamin C deficiency is still of concern, this study highlights the importance of early detection in at-risk children and the critical role of detailed dietary history to identify inadequate nutrition. Prompt recognition and intervention can prevent misdiagnosis and improve clinical outcomes. Hence, strengthening parental education on nutritional intake is essential to reduce future incidences.

The prospect of high-dose vitamin c in improving early survival in patients with hemophagocytic lymphohistiocytosis

Vitamin C deficiency (VCD) is common in adult inpatients in high-income countries and is associated with moderate to severe frailty, cognitive impairment, and scurvy signs and symptoms. However, clinical practice associated with vitamin C status has not been explored in this setting. This study aims to describe current vitamin C clinical practices and explore barriers and enablers that influence nutrition care delivered to adult hospitalized patients within routine clinical practice. This study was conducted across General Medicine units at a tertiary health service in Melbourne, Australia. Using an explanatory, sequential mixed methods design, data across each stage of the Nutrition Care Process (NCP) was triangulated from three phases involving analysis of clinical guidelines, file review data of patients with VCD (n = 100) according to plasma vitamin C levels, and focus groups informed by the Theoretical Domains Framework. Triangulated data revealed that barriers to vitamin C nutrition care include infrequent assessment, influenced by environmental factors, beliefs about consequences, clinical priority, and healthcare professionals' (HCPs') knowledge. Enablers include strong belief in nutrition care capability and belief that vitamin C nutrition care is within HCPs' roles. Low suspected VCD diagnosis and low intervention and discharge planning rates were also observed. The single vitamin C clinical guideline lacked detail across specific stages of the NCP. Limited vitamin C nutrition care potentially occurs in adult inpatients, hindered predominantly by assessment barriers. To achieve improvements in clinical practice, a theoretically driven implementation strategy targeted to healthcare systems, clinician behavior, and national quality standards is required.

Chronic ascorbic acid deficiency as a trigger for pseudoexfoliation syndrome: A hypothesis

Ascorbic acid deficiency promotes metabolic remodeling and pulmonary fibrosis that leads to respiratory failure in Sod1 and Akr1a double-knockout mice

Ascorbic acid (AA) is a ubiquitous and essential, water-soluble electron donor in living organisms which must be obtained from the diet. AA deficiency is closely associated with the pathogenesis and/or progression of various diseases, including diabetes and neurodegenerative disorders affecting hippocampal neurogenesis and cognitive function. Thus, it is beneficial to monitor AA in living cells and real samples. However, few probes have been developed for AA monitoring in both living cells and real samples. Here, we developed an LRET-based nanoprobe for AA detection, leveraging the near-infrared (NIR) excitation properties and spectral tunability of up-conversion nanoparticles (UCNPs). Upon exposure to AA, the MnO2 layer undergoes gradual decomposition, leading to a significant decrease in absorption. The detection limit was determined to be 0.097µg/mL. As the MnO2 layer decomposes, the quenching effect on UCNPs is inhibited, leading to a 5.2-fold enhancement in up-conversion emission. The detection limit for this luminescence-based approach was determined to be 2.48µg/mL. Moreover, UCNP@MnO2 exhibits low cytotoxicity and efficiently enters cells, making it suitable for application in both living cells and real samples. This research demonstrates the dual-sensing capabilities of UCNP@MnO2 to AA, and validates its application in both living cells and real samples.

Background/Objectives: Assessment of vitamin C status rarely occurs in hospital patients within high-income countries on the assumption that vitamin C deficiency (VCD) is rare, and evidence on prevalence, risk factors, and clinical outcomes of VCD is limited. This study aimed to describe the prevalence of VCD, characteristics of patients with VCD, and identify risk factors and clinical outcomes associated with VCD status in adult hospitalised patients. Methods: This retrospective observational study included adult inpatients from five metropolitan hospitals within a single public health service in Australia which provides tertiary, acute, and sub-acute care, over a 3.5-year period. Non-fasting vitamin C levels were examined for the prevalence of VCD, defined as <11.4 µmol/L. Multivariate regression models were used to identify risk factors and clinical outcomes associated with VCD. Results: The prevalence of VCD was 22.9% (n = 1791), comprising 23.2% (n = 1717) and 16.2% (n = 74) within acute and sub-acute settings, respectively. VCD prevalence was high in acute setting subgroups including patients with malnutrition (30%, n = 611) and patients admitted to ICU during hospitalisation (37.3%, n = 327). Malnutrition (OR 1.50, 95% CI 1.19-1.91, p < 0.001) and male gender (OR 1.47, 95% CI 1.17-1.86, p = 0.001) were associated with VCD. VCD was not associated with clinical outcomes including in-hospital death, hospital or intensive care unit LOS, or hospital-acquired complications. Conclusions: VCD exists within adult hospital patients in high-income countries, and early, targeted detection of VCD in this setting is warranted. Further research is needed to explore the impact of VCD on hospital clinical outcomes.

Declining levels of physical activity and fitness in children and youth are linked to negative health outcomes. This study investigates whether maternal exercise can enhance offspring's physical fitness. Our results demonstrate that maternal exercise improves offspring's endurance by changing muscle fiber composition and promoting mitochondrial biogenesis, with benefits lasting across generations. This improvement is associated with changes in DNA methylation, specifically the demethylation of the Slc23a2 gene, which codes for SVCT2, crucial for vitamin C (VC) transport, in F1 and F2 generations. Importantly, VC administration during pregnancy mimics the transgenerational benefits of exercise on offspring fitness, but these benefits are absent in genetic VC deficiency mice. VC supplementation increases TET2 expression in murine and human myogenic cells, regulating DNA methylation, promoting the development of oxidative fibers, and enhancing mitochondrial biogenesis. This study highlights the VC-TET2-SVCT2 pathway as a key mechanism for the transgenerational endurance benefits of maternal exercise, suggesting potential strategies to enhance maternal and child health.

Background Vitamin D is crucial for calcium and phosphorus intestinal absorption, and for bone formation and its deficiency causes nutritional rickets. Many studies, both on animals and cell cultures, showed that vitamin C (VC) is a vital modulator of osteogenic and chondrogenic differentiation. We aimed to determine the effectiveness of VC supplementation as an add-on therapy in the treatment of nutritional rickets. Patients and methods A total of 88 infants and toddlers with nutritional rickets participated in this study, which was a randomized controlled trial. We documented the signs and symptoms of vitamin D and VC deficiency. Initial measurements of serum calcium, phosphorus, and alkaline phosphatase were taken and tracked for one and three months, respectively, while parathyroid hormone and 25-hydroxy vitamin D levels were initially taken. After 3 months of treatment, N-terminal, mid-region Osteocalcin was evaluated. An radiography of the knee was taken and followed for 3 months. Patients were split into two groups: those who received VC in addition to vitamin D and calcium and those who did not. Results Boys were more prone to rickets, especially those who were exclusively breastfed (61.4%). Short stature (16%), macrocephaly (9%), limb deformities (48.9%), delayed dentition (34%), delayed closure of the anterior fontanel (39.8%), delayed motor development (61%), and convulsions (11.4%) are all possible side effects. There was no discernible difference between patients who received VC in daily small doses versus those who did not regard biochemical and radiographic findings (P&gt;0.05). Conclusion VC did not have a beneficial effect on nutritional rickets.

Our study aimed to examine the ascorbic acid (AA) status of the Ukrainian population during wartime conditions. Ascorbic acid is one of the most essential vitamins in human nutrition. It possesses antioxidant properties and plays a vital role in maintaining bodily functions. Materials and methods. A total of 408 individuals were surveyed, including 234 local residents, 66 internally displaced persons (IDPs), and 108 servicemen of the Armed Forces of Ukraine (AFU). AA levels were assessed using a lingual assay with the Tillman's reagent. Statistical methods were employed for data analysis. Results. A statistically significant difference was found in AA saturation levels among local residents with normal AA levels compared to local residents with insufficiency and deficiency, IDPs with insufficiency, IDPs with deficiency, and AFU servicemen with insufficiency and deficiency. Significant differences in AA saturation were also observed between local residents with insufficiency and deficiency, IDPs with normal levels versus those with deficiency, and AFU servicemen with insufficiency and deficiency. The prevalence of AA deficiency among local residents was significantly higher compared to IDPs with normal levels or insufficiency and AFU servicemen with insufficiency. The number of IDPs with normal AA levels was significantly greater compared to those with insufficiency and deficiency, as well as AFU servicemen with insufficiency and deficiency. Significant differences were observed in the frequency of insufficiency among IDPs compared to those with deficiency, AFU servicemen with normal AA levels, and those with deficiency. The AA saturation rate in the IDP group with deficiency was significantly lower compared to the group of AFU servicemen with normal levels or deficiency. The prevalence of normal AA levels in AFU servicemen was considerably higher compared to those with insufficiency or deficiency in this category. Conclusions. The results of our study highlight a predominant deficiency of AA among internally displaced persons compared to local residents and AFU servicemen. The AA status of AFU servicemen did not differ significantly from that of residents in the Poltava region.

Chronic pancreatitis (CP) is characterized by disorders of the exocrine and endocrine functions of the pancreas. One of the manifestations of trophic insufficiency in patients with CP is endogenous and exogenous hypovitaminosis, in particular, ascorbic acid (vitamin C) deficiency. Unlike most animals, humans are unable to synthesize vitamin C endogenously due to the lack of the enzyme L-gulonolactone oxidase, which is necessary for the last step of ascorbic acid biosynthesis. Development of a mathematical prognostic model for predicting hypovitaminosis of ascorbic acid in patients with CP based on established predictive factors is an urgent task today. The objective: to develop a formula for predicting ascorbic acid deficiency in patients with CP based on established predictive factors. Materials and methods. 112 patients with CP and 30 practically healthy individuals were included in the study. During the study, the main clinical indicators affecting the course of CP were determined for the patients. Univariate regression analysis was performed to identify factors that could potentially affect ascorbic acid levels. A multivariate regression analysis was also performed, resulting in a multiple regression formula that identified a cohort of patients potentially with low ascorbic acid levels. Results. During the univariate correlation analysis, such indicators were established as the age of the patient with CP (R=–0.457) (р&lt;0.05), the duration of CP (R=–0.478) (р&lt;0.05), the functional capacity of the pancreas according to the point index of the coprogram (R=–0.372) (р&lt;0.05), as well as the structural and morphological functional state of the pancreas according to ultrasound criteria expressed in points (R=–0.398) (р&lt;0.05), total protein (R=0.370) (р&lt;0.05), erythrocyte level (R=0.377) (р&lt;0.05), ALT (R=–0.403) (р&lt;0.05) and AST (R=–0.391) (p&lt;0.05), which are predictors of vitamin deficiency for patients with CP. A multivariate regression analysis was performed to create a formula for predicting the level of ascorbic acid. Conclusions. The presence of ascorbic acid hypovitaminosis in patients with CP (p&lt;0.001) indicates the need to study the level of this indicator for timely diagnosis and the appointment of appropriate treatment. For the personalized prediction of ascorbic acid deficiency in patients with CP the formulas are proposed that take into account the parameters of the course of CP, available for determination in the practice of primary care doctors: age of patients, duration of the disease, level of erythrocytes, quantitative value of ultrasound criteria, determination of coprogram criteria expressed in points.

Background: Stroke presents a significant global health challenge. Despite its potential for cardiovascular protection, the role of vitamin C (VTMC) in stroke risk remains contentious. Aim: This study aimed to assess VTMC deficiency in stroke patients and its association with stroke risk. Methods: We analyzed data from 13,339 adults aged 20 and above in the National Health and Nutrition Examination Survey (NHANES) between 2003 and 2018, excluding those with missing serum VTMC and stroke status. We assessed the VTMC deficiency (&lt;11.4 µmol/L) and stroke incidence association using multivariate weighted logistic regression, adjusting for demographics, BMI, medical history, smoking, and dietary VTMC intake. Results: Stroke rates in the NHANES cycles 2003–2006 and 2017–2018 were 2.8% (95% CI [2.3–3.4]) and 3.3% (95% CI [2.7–4.2]), respectively. VTMC deficiency was more common in individuals with a history of stroke, with rates of 3.6% (95% CI [2.2–5.8]) and 5.3% (95% CI [3–9.1]) compared to 2.7% (95% CI [2.3–3.3]) and 3.2% (95% CI [2.5–4.1]) in the nonstroke population. Nevertheless, VTMC deficiency was distinctly prevalent across diverse demographic and health-related subgroups. Multivariate analyses invalidated any statistically significant association between VTMC deficiency and stroke risk across all employed analytical models within both time intervals. Conclusions: Our study does not support a link between VTMC deficiency and increased stroke risk in U.S. adults. Substantial uncertainties persist regarding the use of VTMC for stroke-related oxidative stress, dosage, and delivery methods, requiring further clinical trials. Healthcare providers should carefully consider its prevalence in specific subgroups.

Cellulose-based yellow-green emitting carbon dots with large Stokes shift as effective “turn off-on” fluorescence platforms for Cr (VI) and AA dual efficacy detection

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.Graphical

Scurvy, a condition resulting from vitamin C (ascorbic acid) deficiency, was previously thought to be rare in affluent countries, yet its prevalence has increased in recent years even in these regions. This clinical case report of scurvy details

In recent years, there has been growing demand for the monitoring of ascorbic acid levels, especially in underdeveloped populations where ascorbic acid deficiency affects up to 74% of individuals. To facilitate widespread ascorbic acid screening, we have developed a highly scalable conductive polymer nanocomposite with excellent ascorbic acid sensing performance. The material is based on polyaniline, which is deposited in a single step in the presence of polystyrene sulfonate and multi-walled carbon nanotubes onto carbon paper. The modified electrodes take advantage of the electrocatalytic properties of polyaniline toward ascorbic acid, which are boosted by the proton donating polystyrene sulfonate polymer and the high surface area of the multi-walled carbon nanotubes. The morphology and composition of the composite are characterized using field-emission scanning electron microscopy, transmission electron microscopy, Raman spectroscopy, and X-ray photoelectron spectroscopy and the electrochemical characteristics are examined using cyclic voltammetry and electrochemical impedance spectroscopy. The modified electrode shows good ascorbic acid sensing characteristics, with a linear range of 1–400 μM, a sensitivity of 546 μA mM−1 cm−2, and a limit of detection of 0.11 μM. High performance and low cost results in a promising platform to support the widespread, cheap monitoring of ascorbic acid deficiency.

Introduction: This study evaluated nutrient deficiencies in infants and toddlers with inflammatory bowel disease (IBD) and eosinophilic gastrointestinal disorders (EGIDs), whose primary nutritional source is elemental formulas (EFs). Methods: The nutrient status of children with IBD and EGID aged 6 months to 6 years was evaluated. Results: Twenty-one children fed with EFs (EF group) and 25 controls (CL group) were enrolled. The selenium level in the EF group was lower than that in the CL group (2.2 μg/dL vs. 9.3 μg/dL; p < 0.01). Although fat-soluble vitamins were deficient in some EF group participants, no significant differences were observed in their concentration and insufficiency proportion. However, ascorbic acid deficiency was more frequent in the EF group, with significantly lower levels (8.6 μg/mL vs. 12.0 μg/mL; p < 0.01). The triene:tetraene ratio was significantly higher in the EF group (0.046 vs. 0.010; p < 0.01). Asparagine and taurine levels were significantly lower in the EF group (asparagine: p < 0.01; taurine: p < 0.01) and tyrosine and phenylalanine levels were higher in the EF group, resulting in a lower Fisher’s ratio (p < 0.01). Conclusion: Long-term feeding with EFs can cause deficiencies in essential fatty acids, selenium, and ascorbic acid and also carries a risk of amino acid imbalance in infants and toddlers.

It is known that reactive oxygen species cause abnormal immune responses in the gut during inflammatory bowel diseases (IBD). Therefore, oxidative stress has been theorized as an agent of IBD development and antioxidant compounds such as vitamin C (L-ascorbic acid) have been studied as a new tool to treat IBD. Therefore, the potential of vitamin C to treat IBD was reviewed here as a critical discussion about this field and guide future research. Indeed, some preclinical studies have shown the beneficial effects of vitamin C in models of ulcerative colitis in mice and clinical and experimental findings have shown that deficiency in this vitamin is associated with the development of IBD and its worsening. The main mechanisms that may be involved in the activity of ascorbic acid in IBD include its well-established role as an antioxidant, but also others diversified actions. However, some experimental studies employed high doses of vitamin C and most of them did not perform dose-response curves and neither determined the minimum effective dose nor the ED50. Allometric extrapolations were also not made. Also, clinical studies on the subject are still in their infancy. Therefore, it is suggested that the research agenda in this matter covers experimental studies that assess the effective, safe, and translational doses, as well as the appropriate administration route and its action mechanism. After that, robust clinical trials to increase knowledge about the role of ascorbic acid deficiency in IBD patients and the effects of their supplementation in these patients can be encouraged.