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Background: The role of vitamin C as an antioxidant in guarding against osteoporosis in adults is still debated. This research employs both a cross-sectional study and a two-sample bidirectional Mendelian randomization (MR) analysis to explore how serum vitamin C levels correlate with the incidence of osteoporosis among adults., Methods: In this study, we utilized data from the National Health and Nutrition Examination Survey (NHANES) database for the years 2003-2006, and 2017-2018 to conduct both a cross-sectional analysis and MR to investigate the relationship between serum vitamin C levels and the risk of osteoporosis in adults. We adjusted our analyses for essential demographic and lifestyle variables, and applied logistic regression techniques. Genetic determinants of vitamin C levels were analyzed through MR, using methods like inverse-variance weighted (IVW) and MR-Egger to assess causality. Statistical computations were carried out in R, incorporating visual tools such as restricted cubic spline curves (RCS) and forest plots to clarify the dose-response dynamics and variations across different subgroups. This study was approved by the NCHS Ethics Review Board, and informed consent was obtained from all participants., Results: In our investigation, we analyzed data from 3,940 participants, among whom 291 were diagnosed with osteoporosis. The logistic regression analysis of serum vitamin C quartiles did not indicate a significant trend. The most adjusted model showed a slight, albeit inconsistent, protective effect in the highest quartile (OR = 0.68, 95% CI: 0.47-0.99, P = 0.22). Mendelian randomization, employing methods such as IVW, reinforced the absence of a significant causal relationship between serum vitamin C levels and osteoporosis risk (IVW OR = 1.000, 95% CI: 0.999-1.001, P = 0.601).Subgroup analyses, visualized through forest plots and restricted cubic spline (RCS) curves, supported the primary findings, showing no significant effects or interactions between vitamin C levels and osteoporosis risk across different demographic and lifestyle subgroups. The RCS analysis particularly highlighted a lack of significant non-linear relationships between serum vitamin C concentration and the odds of osteoporosis (P for nonlinear = 0.840)., Conclusions: The cross-sectional study revealed that higher serum vitamin C levels do not consistently correlate with a reduced risk of osteoporosis. Meanwhile, the Mendelian randomization analysis confirmed that there is no genetic evidence to suggest a causal relationship between vitamin C levels and osteoporosis risk. Recent research highlights the polygenic nature of osteoporosis, with genetic predispositions playing a significant role in disease risk. The relationship between serum vitamin C and osteoporosis requires further research. This suggests the need for further investigation into the connection between vitamin C and bone health., (© 2024. The Author(s).)

Background: Assessment for vitamin C deficiency (VCD) is rarely undertaken in an acute hospital setting in high-income countries. However, with growing interest in VCD in community settings, there is emerging evidence investigating the prevalence and impact of VCD during hospitalization., Objectives: In this scoping review, the prevalence of VCD in adult hospitalized patients is explored, patient characteristics are described, and risk factors and clinical outcomes associated with VCD are identified., Methods: A systematic scoping review was conducted in accordance with the PRISMA-ScR framework. The Ovid MEDLINE, Ovid Embase, Scopus, CINAHL Plus, Allied and Complementary Medicine Database, and the Cochrane Library databases were searched for interventional, comparative, and case-series studies that met eligibility criteria, including adult hospital inpatients in high-income countries, as defined by the Organization for Economic Co-operation and Development, that reported VCD prevalence using World Health Organization reference standards. These standards define VCD deficiency as plasma or serum vitamin C level <11.4 µmol/L, wholeblood level <17 µmol/L, or leukocytes <57 nmol/108 cells., Results: Twenty-three articles were included, representing 22 studies. The cumulative prevalence of VCD was 27.7% (n = 2494; 95% confidence interval [CI], 21.3-34.0). High prevalence of VCD was observed in patients with severe acute illness and poor nutritional status. Scurvy was present in 48% to 62% of patients with VCD assessed in 2 studies (n = 71). Being retired (P = 0.015) and using excessive amounts of alcohol and tobacco (P = 0.0003) were independent risk factors for VCD (n = 184). Age was not conclusively associated with VCD (n = 631). Two studies examined nutrition associations (n = 309); results were inconsistent. Clinical outcomes for VCD included increased risk of frailty (adjusted odds ratio, 4.3; 95%CI, 1.33-13.86; P = 0.015) and cognitive impairment (adjusted odds ratio, 2.93; 95%CI, 1.05-8.19, P = 0.031) (n = 160)., Conclusions: VCD is a nutritional challenge facing the healthcare systems of high-income countries. Research focused on early identification and treatment of patients with VCD is warranted., Systematic Review Registration: Open Science Framework ( https://doi.org/10.17605/OSF.IO/AJGHX )., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Life Sciences Institute.)

The primary characteristics of a clinical assay are its accuracy and speed. For alkaline phosphatase (ALP) monitoring in medical treatment, a rapid, reliable surface-enhanced Raman scattering (SERS) detection technique was designed based on the controlled "hot spot" effect caused by the mediation of silver ions (Ag + ). Consisting of functionalized Au nanoparticles (NPs), Ag + , and the enzyme substrate 2-phospho-L-ascorbic acid triso-dium salt (AAP), the fabricated detection technique can achieve a reliable clinical assay for ALP detection in human serum within several minutes. Herein, due to the coordination interaction of Ag + and the cyano group (-CN), Ag + can coordinate with p -mercaptobenzonitrile (MBN) modified on the surface of Au NPs, leading to the connection of adjacent Au NPs in a controllable manner to form a chain structure, in which the SERS signal of MBN at 2228 cm -1 in the Raman silent region would be highly amplified. Under the enzymatic biocatalysis of ALP, AAP was converted into ascorbic acid (AA). AA triggered the reduction of Ag + into Ag 0 , resulting in a decrease in the concentration of Ag + . Meanwhile, the decrease in the SERS intensity of MBN was well-controlled and was recognized with the increased amounts of ALP. Based on this, the SERS detection technique for ALP was established. The limit of detection (LOD) for the detection of ALP was as low as 1.23 pg mL -1 (0.005 U L -1 ). Because of all these characteristics and its ultrahigh stability, this SERS detection technique is an important point-of-care candidate for the reliable, efficacious, and highly sensitive detection of ALP.

Carbon cloth (CC) was electrochemically activated using three electrochemical methods in different electrolytes. The gases released during the activation process etched the surface of the CC, thereby increasing its surface area of the activated CC (FCC). Moreover, functional groups such as oxygen-containing groups and N-doping have been introduced. The quantity and type of functional groups introduced during the activation process were related to the anions in the solution. FCC electrodes were used to construct electrochemical sensors for the simultaneous determination of ascorbic acid (AA), dopamine (DA), and uric acid (UA). The PFCC electrode activated by advanced cyclic voltammetry in (NH 4 ) 2 HPO 4 showed linear ranges for AA, DA, and UA concentrations of 0.1 to 2.1 mM, 0.5 to 11 µM, and 0.5 to 11 µM, respectively. The detection limits are 72.93, 0.22, and 0.42 µM, respectively. The good flexibility the PFCC electrode made it suitable for the preparation of flexible sensors. The simultaneous determination of AA, DA, and UA in fetal bovine serum showed a reliable recovery ratio. This study provides a simple and green approach for activating carbon cloth and constructing flexible electrochemical sensors with the potential to simultaneously detect AA, DA, and UA., (© 2024. The Author(s).)

Cobalt-doped Prussian blue composite nanocubes (Co-PB NCs) were synthesized, which can quickly convert O 2 to O 2 •- and 1 O 2 . Due to the presence of cobalt and iron transition metal redox electron pairs, Co-PB NCs with high oxidase mimetic activity can rapidly oxidize the substrate 3,3',5,5'-tetramethylbenzidine (TMB) to produce blue products (ox-TMB) without the assistance of unstable H 2 O 2 . Using ascorbic acid-2-phosphate trisodium salt (AAP) as a substrate, it can be converted to reduced ascorbic acid (AA) under acid phosphatase (ACP) hydrolysis, resulting in suppression of TMB oxidation. Therefore, an enzyme cascade signal amplification strategy for rapid colorimetric detection of AA/ACP was developed based on the high-efficiency oxidase-like activity of Co-PB NCs combined with the hydrolysis effect of ACP. The color changes at low concentrations of AA and ACP could be observed by the naked eye, and the detection limits of AA and ACP were 1.67 μM and 0.0266 U/L, respectively. The developed colorimetric method was applied to the determination of AA in beverages and ACP in human serum, and the RSDs were less than 3%, showing good reproducibility. This work provides a promising strategy for the use of metal-doped Prussian blue composite material for the construction of rapid colorimetric sensing platforms that avoid the use of unstable hydrogen peroxide., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Aims: The objective of this study was to investigate the associations of dietary and circulating antioxidant vitamins with metabolic syndrome (MetS), and to assess causality using Mendelian randomization (MR)., Methods: This study included 10,308 participants from the National Health and Nutrition Examination Survey. The associations of vitamins A, C, E and carotenoids with MetS were assessed using multivariable weighted logistic regression analysis. Subsequently, the MR approach was employed to test the causal associations, with inverse variance weighted (IVW) serving as the primary analysis., Results: Observationally, dietary vitamin A (OR=0.852, 95%CI: 0.727-0.999), C (OR=0.802, 95%CI: 0.675-0.952), carotene (OR=0.832, 95%CI: 0.706-0.982), and β-carotene (OR=0.838, 95%CI: 0.706-0.995) in quartile 4 had lower incidents of MetS, when compared to quartile 1. Circulating vitamin C and carotene were also present inversely associated with MetS, while the vitamin A and E both increased this risk. IVW-MR confirmed the associations of dietary vitamin A (OR=0.920, 95%CI: 0.861-0.984), vitamin C (OR=0.905, 95%CI: 0.836-0.979) and carotene (OR=0.918, 95%CI: 0.865-0.974) with MetS. However, there was only circulating β-carotene (OR=0.909, 95%CI: 0.857-0.965) was found to be causally associated with MetS., Conclusions: Observational and MR studies have shown that adequate dietary intake of vitamin A, C and carotenoids may help to reduce the risk of MetS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sun, Fan, Yao, Zhao, Jiang, Yang, Mao and Yang.)

Recent advances in mass spectrometry have indicated that the water-soluble antioxidant vitamin C differentially modulates the abundance of various proteins in the hepatic tissue of female and male mice. In this study, we performed LC-MS/MS to identify and quantify proteins that correlate with serum vitamin C concentrations in the whole brain, heart, liver, and spleen tissues in mice deficient for the enzyme L-Gulonolactone oxidase required for vitamin C synthesis in mammals. This work shows for the first time that various biological processes affected by a vitamin C deficiency are not only sex specific dependent but also tissue specific dependent even though many proteins have been identified and quantified in more than three organs. For example, the abundance of several complex III subunits of the mitochondrial electron transport chain correlated positively with the levels of serum vitamin C only in the liver and not in the other tissues examined in this study even though such proteins were identified in all the organs analyzed. Western blot analyses on the Uqcrc1 and Uqcrfs1 complex III subunits validated the mass spectrometry results. Interestingly, the ferritin subunits represented the few quantified protein complexes that correlated positively with serum vitamin C in all the organs examined. Concomitantly, serum ferritin light chain 1 was inversely correlated with vitamin C levels in the serum. Thus, our study provides an initial comprehensive atlas of proteins significantly correlating with vitamin C in four organs in mice that will be a useful resource to the scientific community., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Aumailley, Lebel. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: The objective of this study is to analyze oxidative stress markers Total Oxidant Status (TOS) and total Antioxidant Status (TAS), assess antioxidant levels (vitamin C, E), and evaluate co-factor element profiles zinc (Zn), copper (Cu), iron (Fe) in the serum of Iraqi gastric cancer patients. By elucidating these relationships, the research aims to enhance knowledge on oxidative stress, dietary factors, and potential therapeutic approaches for managing nutritional imbalances in this cohort., Methods: The study included 60 gastric cancer patients and 60 matched controls. Blood samples were collected and serum was extracted for analysis of TOS, TAS, Vitamin C, Vitamin E, copper, zinc, and iron levels. Measurements were conducted using spectrophotometry and ELISA kits from various companies. Statistical analysis was performed with IBM SPSS 25.0, presenting results as means ± SD, and differences between groups were assessed via independent samples t-test at p < 0.05 and p ≤ 0.01., Results: The study results indicated statistically significant differences between gastric cancer patients and controls in various biomarkers, with all comparisons showing p-values less than 0.001. This suggests strong evidence for the observed differences between the two groups in (TOS), (TAS), vitamins C and E, Cu, Zn, and  Fe levels. These relationships underscore the intricate connections among biomarkers in gastric cancer pathophysiology., Conclusion: The study underscores the intricate relationship between oxidative stress, antioxidant depletion, and micronutrient imbalances in gastric cancer. These findings offer valuable insights into the disease's pathophysiology, indicating potential diagnostic biomarkers. Further research is warranted to unravel underlying mechanisms and explore clinical applications for early gastric cancer diagnosis.

This study aimed to investigate the levels of vitamins A, C, and E in patients with Non-Alcoholic Fatty Liver Disease (NAFLD) compared to healthy controls and to explore the correlation between these vitamin levels and various other parameters, including bone mineral density (BMD), adiposity (fat storage), insulin resistance and subclinical inflammation. The study involved 50 participants diagnosed with NAFLD and 50 healthy controls. Blood samples were collected to measure vitamin A, C and E levels, along with other parameters like insulin, inflammatory markers, and liver function tests. Additionally, participants underwent DEXA scans to assess BMD and body composition. Vitamin levels: The study found no significant deficiencies in vitamin A or C levels in either group. However, vitamin E levels were significantly higher in the NAFLD group compared to controls, although only one case of vitamin E deficiency was observed in the NAFLD group. No significant correlations were found between vitamin levels and BMD, adiposity parameters, insulin resistance, or subclinical inflammation markers in either group. The study acknowledges the limited data available on the association between NAFLD, vitamin levels and BMD in the Asian Indian population. The findings regarding vitamin A and C levels are consistent with some previous studies, whereas the higher vitamin E levels in the NAFLD group contradict other research. This discrepancy might be due to factors like sample size, dietary habits, or vitamin fortification programs. The lack of significant correlations between vitamin levels and other parameters suggests that further research is needed to understand the complex interplay between these factors in NAFLD development and progression.

Obesity and diabetes are known to negatively affect vitamin C status. However, whether the presence of diabetes, in addition to obesity, contributes an additional impact on vitamin C status is currently uncertain. In a cohort of 152 adults living with obesity, we assessed metabolic and nutrient parameters in participants without diabetes (n = 92), and with prediabetes (n = 22) and type 2 diabetes mellitus (T2DM; n = 35). Vitamin C concentrations were measured in plasma and leukocytes using HPLC and vitamin C intakes were assessed using 24-hour dietary recall. Metabolic severity scores were derived using gender, ethnicity, height, weight, waist circumference, systolic blood pressure, fasting glucose, HDL, and triglyceride values. In people living with obesity, those with prediabetes and T2DM had increased metabolic dysregulation and decreased vitamin C status relative to those without diabetes (P < .05). Vitamin C deficiency was observed in a high proportion (23%-32%) of participants with prediabetes and T2DM and ≥50% had hypovitaminosis C. However, there was no difference in vitamin C intake between those without diabetes and those with prediabetes or T2DM (P > .05). There was a significant inverse correlation between plasma vitamin C status and metabolic severity score (r = -0.290, P < .001). Linear regression indicated that for every 1-unit increase in metabolic severity score, there was a 6.5 µmol/L decrease in vitamin C status. Thus, the enhanced metabolic dysregulation observed with prediabetes and T2DM is associated with an increased demand for vitamin C in people living with obesity., Competing Interests: Author declarations ACC has received food and supplement industry funding for investigator-led research studies. HL has previously received industry funding for diabetes intervention trials., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Vitamin C deficiency is associated with excess mortality in kidney transplant recipients (KTR). We aim to evaluate plasma vitamin C status at different post-transplantation moments and assess the main characteristics associated with vitamin C deficiency in KTR., Methods: Plasma vitamin C was assessed in 598 KTR at 3-, 6-, 12-, 24-, and 60-months post-transplantation, 374 late KTR with a functioning graft ≥ 1 year, and 395 potential donors. Vitamin C deficiency was defined as plasma vitamin C ≤ 28 µmol/L. Diet was assessed by a 177-item food frequency questionnaire. Data on vitamin C-containing supplements use were extracted from patient records and verified with the patients., Results: Vitamin C deficiency ranged from 46% (6-months post-transplantation) to 30% (≥ 1 year post-transplantation). At all time points, KTR had lower plasma vitamin C than potential donors (30-41 µmol/L vs 58 µmol/L). In cross-sectional analyses of the 953 KTR at their first visit ≥ 12 months after transplantation (55 ± 14 years, 62% male, eGFR 55 ± 19 mL/min/1.73 m 2 ), the characteristics with the strongest association with vitamin C deficiency were diabetes and smoking (OR 2.67 [95% CI 1.84-3.87] and OR 1.84 [95% CI 1.16-2.91], respectively). Dietary vitamin C intake and vitamin C supplementation were associated with lower odds (OR per 100 mg/day 0.38, 95% CI 0.24-0.61 and OR 0.21, 95% CI 0.09-0.44, respectively)., Conclusion: Vitamin C deficiency is frequent among KTR regardless of the time after transplantation, especially among those with diabetes and active smokers. The prevalence of vitamin C deficiency was lower among KTR with higher vitamin C intake, both dietary and supplemented. Further research is warranted to assess whether correcting this modifiable risk factor could improve survival in KTR., (© 2024. The Author(s).)

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.)

Low-cost transition metal vanadate-based electrochemical sensors have attracted a lot of attention recently. A cobalt vanadate and carboxylated multi-walled carbon nanotube composite (CoV/MWCNTs-COOH) was prepared by an ultrasonic-assisted assembly method. The uniform and dense MWCNTs-COOH attached to the surface of CoV not only combines the large surface area and superior conductivity of MWCNTs-COOH with the excellent electrochemical activity of CoV, but also enhances the redox reaction between CoV/MWCNTs-COOH composite and the analyte through synergistic effect of hydrogen bonding and electrostatic interaction. The electrochemical behaviors of CoV/MWCNTs-COOH composite modified glassy carbon electrode (CoV/MWCNTs-COOH/GCE) were investigated by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV). The simultaneous electrochemical sensing of ascorbic acid (AA), dopamine (DA) and uric acid (UA) on CoV/MWCNTs-COOH/GCE possesses good peak current signals with well-defined peak potentials. The linear ranges of AA, DA, and UA at CoV/MWCNTs-COOH/GCE are 1.0-100.0 μM, and the limits of detection (LODs; S/N = 3) are 0.4 μM, 0.03 μM, and 0.1 μM, respectively. The practicality of the designed sensor was further confirmed by the good recoveries obtained in the simultaneous measurement of actual samples including fetal bovine serum, human serum, urine, and Vitamin C tablets. Overall, the developed electrochemical sensor shows potential therapeutic applications for simultaneous determination of AA, DA and UA in biological fluids., 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.)

Introduction: The antioxidant effects of vitamins may attenuate the oxidative stress on organs imposed by ischemia-reperfusion injury during the process of organ transplantation from brain-dead donors. Circulating levels of vitamins A, C, and E-α in donors after brain death and their relationships to donor demographics, management, organ utilization, and recipient outcomes are largely unknown., Methods: An observational, prospective, cohort study of 84 consecutive brain-dead organ donors managed at a single organ procurement recovery center was conducted. Vitamin levels were drawn immediately prior to procurement., Results: Levels of serum vitamins A and E-α and plasma vitamin C were below normal in 80%, 85%, and 92% of donors and deficient in 40%, 62%, and 63%, respectively. Vitamin C deficiency was associated with a longer time between death and specimen collection ( P  = .004). Death from head trauma and stroke were associated with lower levels of vitamin A than from anoxic causes ( P  = .003) and smokers had greater vitamin C deficiency ( P  = .03). During donor management, vitamin C deficiency was associated with longer vasopressor support ( P  = .03) and normal levels of vitamin E-α were associated with reaching a lower alanine transferase compared to those with subnormal levels ( P  < .05). Donors deficient in vitamin E-α were less likely to have a liver recovered for transplantation ( P  = .005). Vitamin levels were not associated with the recipient outcomes examined., Conclusion: Circulating vitamins A, C, and E-α is profoundly low in brain-dead organ donors, associated with relevant demographic features of the donor, and may influence donor management and organ utilization., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Robert S. Ream, MD is a pediatric consultant for Mid-America Transplant and receives compensation for pediatric organ donor management. Dr Ream is also a board director for the Mid-America Transplant Foundation. Gary F. Marklin, MD is the Chief Medical and Research Officer for Mid-America Transplant.

Objective: Diet-derived circulating antioxidants have been associated with functional outcome after ischemic stroke (IS), but the causality remains unclear. The aim of our study is to explore the potential causal effect of diet-derived circulating antioxidants on long-term functional outcome (at 3 months) following IS through the utilization of the Mendelian randomization (MR) approach., Materials and Methods: For this two-sample MR analysis, genetic variants associated with the diet-derived circulating antioxidants, including selenium, zinc, vitamin A (retinol), vitamin C, and vitamin E (α-tocopherol and γ-tocopherol), were identified in a large-scale Genome-Wide Association Studies (GWAS) database and utilized as instrumental variables (IVs). Summary data for long-term functional outcome after IS were obtained from the Genetics of Ischemic Stroke Functional Outcome (GISCOME) network of 6021 patients. Our study used the Inverse-variance weighting method as our primary MR method and also performed a series of sensitivity analyses for pleiotropy and heterogeneity., Results: We observed that selenium (odds ratio (OR)=0.81; 95 % confidence interval (CI): 0.68-0.97; p=0.02) was significantly associated with poor functional outcome (modified Rankin Scale score≥3) after IS. Genetic liabilities to other diet-derived circulating antioxidants were not strongly associated with functional outcome after IS (all p>0.05). Sensitivity analyses confirmed the reliability of these results., Conclusion: This MR study suggested the positive effect of selenium on the long-term functional outcome after IS. Giving a longer period of selenium exposure can be used as a potential treatment to improve recovery after IS., Competing Interests: Declaration of competing interest The authors declare no conflict of interest exits in the submission of this manuscript, and the manuscript has been approved for publication by all authors., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Ascorbic acid (Vitamin C) is crucial for bodily functions, including collagen synthesis, immune system support and antioxidant defense. Despite autism spectrum disorder's multifactorial nature involving genetic, environmental and neurological factors, robust evidence exploring the association between ascorbic acid and this disorder is notably lacking. This study introduces an innovative spectrofluorometric method to quantify ascorbic acid in the plasma of healthy children and those with autism spectrum disorder. The method relies on the interaction of ascorbic acid with the fluorescent dye propidium iodide. In acidic conditions, propidium iodide undergoes protonation and selectively binds to the negatively charged ascorbic acid forming an ion-pair complex. This complex alters the molecular structure of propidium iodide inducing chemical fluorescence quenching, that can be utilized for ascorbic acid quantification. The developed method undergoes rigorous validation following ICH guidelines, demonstrating a linear relationship within a concentration range of 4-40 μg/mL, with high precision and accuracy metrics. Analysis of real plasma samples from autistic and healthy children reveals clinically and statistically elevated levels of ascorbic acid in those with autism spectrum disorder., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relations that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Experimental studies have shown that vitamin C has anti-cancer effects, but previous meta-analyses have indicated that the role of vitamin C in digestive system cancers (DSCs) is controversial. In this study, a systematic review and meta-analysis of the relationship between dietary intake/plasma concentration of vitamin C and the risk of DSC was conducted, evaluating 32 prospective studies with 1 664 498 participants. Dose-response and subgroup analyses were also performed. Systematic literature searches were performed in PubMed, EMBASE and Web of Science databases until 9 th September 2023. Vitamin C intake significantly reduced DSCs risk (RR = 0.88, 95% confidence interval (CI) 0.83 to 0.93). The subgroup analyses showed the risks of oral, pharyngeal, and esophageal (OPE) cancers (0.81, 0.72 to 0.93), gastric cancer (0.81, 0.68 to 0.95), and colorectal cancer (0.89, 0.82 to 0.98) were negatively correlated with vitamin C intake, and the effect of vitamin C was different between colon cancer (0.87, 0.77 to 0.97) and rectal cancer (1.00, 0.84 to 1.19). However, plasma vitamin C concentration was only inversely associated with gastric cancer risk (0.74, 0.59 to 0.92). Dose-response analysis revealed that 250 and 65 mg day -1 vitamin C intakes had the strongest protective effect against OPE and gastric cancers respectively. These estimates suggest that vitamin C intake could significantly reduce gastrointestinal cancer incidence, including OPE, gastric, and colon cancers. Plasma vitamin C has a significant reduction effect on the incidence of gastric cancer only, but additional large-scale clinical studies are needed to determine its impact on the incidence of DSCs.

Outcomes after adjustable gastric banding (AGB) were unsatisfactory and many devices need to be removed for dysphagia. Vitamin C and thiamin deficiency are rare conditions in industrialized countries. Patients undergoing AGB removal (90% for dysphagia) from 2021 to 2023 (laparoscopic 15 and robotic 5) were tested for vitamin C and thiamin levels. Twenty patients (8 m/12 f median aged 56 (range 33.6-79.4) were included. BMI at AGB removal was 39.7 (range 24.4-50.1) kg/m 2 . Only 20% of patients had normal thiamin levels, 30% had low levels, 20% were deficient, and 30% were critically low. Only 25% of patients had normal vitamin C levels, 40% had low levels, 25% were deficient, and 10% were critically low. One third of patients had HbA1c levels between 5.8 and 6.4 and 22% had levels >6.5; 60% of patients had hyperlipidemia. Adjustable gastric banding patients develop concerning rates of vitamin C and thiamin deficiency, and routine testing for levels is recommended., 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.

Background: Evidence on the association between serum vitamin C (sVC) levels and obesity is limited. This study aimed to explore the relationship between sVC and body mass index (BMI) in adolescents aged 12 to 19 years., Methods: We analyzed data from the National Health and Nutrition Examination Survey (NHANES) 2003-2006, with 3952 participants. sVC and BMI were independent variables and dependent variables, respectively. The associations of sVC with BMI were examined using multivariable linear regression models. Age, sex, and race/ethnicity were analyzed as subgroups. Then, we devised smooth curve fittings and saturation threshold analysis to address the nonlinear relationship., Results: sVC had a negative correlation with BMI after adjusting for all covariates (β: -1.020, 95% CI: -1.359, -0.680). In the subgroup analysis by age, sex, and race/ethnicity, there was still a negative correlation between sVC and BMI (p < 0.05). The analysis of saturation effects of sVC and BMI showed the relationship between sVC and BMI in female adolescents followed an N-shaped curve, whereas the relationship between sVC and BMI in adolescents aged 12-15 years and Mexican Americans followed a U-shaped curve., Conclusion: Based on the results, proper vitamin C supplementation may be beneficial to weight loss. However, considering the threshold effect, large-scale and good-quality randomized controlled trials are required to obtain the optimal vitamin C level for weight control., (© 2024. The Author(s).)

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.)

This research aimed to study the long-term effects of soccer training on platelet membrane fatty acid levels and antioxidant vitamins. Forty-four subjects divided into soccer players (SP; n = 22; 20.86 ± 0.36 years) and a control group (CG; n = 22; 21.23 ± 0.49 years) participated in the study. The fatty acids of the platelet membrane, the rates of desaturation, lipid peroxidation indexes and intra-platelet levels of vitamins C and E were assessed. SP obtained lower values in polyunsaturated fatty acids 18:3:3 (alpha-linolenic acid), 20:5:3 (eicosapentaenoic acid) and 22:6:3 (docosahexaenoic acid) ( p < 0.05). The desaturation index ∆5 was higher in SP ( p < 0.05), and they had a higher lipid peroxidation index 20:4:6 (arachidonic acid)/16:0 (palmitic acid) ( p < 0.05). Vitamin E and C platelet values were also higher in SP ( p < 0.01). There were positive correlations in the ω6/ω3 index ( p < 0.05), desaturation index ∆5 ( p < 0.05), lipid peroxidation index 20:4:6/16:0 and intra-platelet vitamins E and C ( p < 0.01) with the level of physical activity. In addition, there were inverse correlations in fatty acids 24:0 (lignoceric acid), 16:1 (palmitoleic acid), 20:3:6 (eicosadienoic acid) and 18:3:3 (alpha-linolenic acid) ( p < 0.05) depending on the degree of physical activity. Regular long-term soccer training could modify the concentration of fatty acids such as 24:0, 16:1, 18:6, 20:3:6, 18:3:3:3, 20:5:3, 26:6:3 and ω3 PUFAs in the platelet membrane.

Background : Oxidative stress plays an important role in the occurrence and pathological process of numerous human diseases. A bidirectional relationship was found between sleep disorders and oxidative stress. However, the association between circulating antioxidant levels and the risk of sleep disorders at the population-scale has yet to be determined. Methods : We used the dataset from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 data release cycle and included 3062 adult participants aged 25-75 years. The circulating antioxidants levels in serum were measured, and the sleep status was assessed by self-reported sleep disorder questionnaire tests. We investigated the association and exposure-response relationship between the 12 main circulating antioxidants and sleep disorders using a generalized additive model (GAM), multiple linear, binary logistic, and restricted cubic spline (RCS) regression models. Multiple sensitivity analyses were conducted to validate the results of our study. Results : Significantly lower serum concentrations of ten antioxidants were observed in the group which had trouble sleeping symptoms compared to the control group. After adjusting for all the covariates, the binary logistic regression models indicated that six of the circulating antioxidants including alpha-carotene, alpha-cryptoxanthin, trans -beta-carotene, beta-cryptoxanthin, lutein and zeaxanthin, and vitamin C, showed a significant association with the risk of overall trouble sleeping symptoms, with odds ratios corresponding to 0.88 (95% CI: 0.80-0.96), 0.74 (95% CI: 0.62-0.87), 0.87 (95% CI: 0.79-0.97), 0.85 (95% CI: 0.75-0.95), 0.72 (95% CI: 0.61-0.84), and 0.83 (95% CI: 0.74-0.93), respectively. The GAM and multiple linear regression revealed similar associations whereas the RCS regression models further confirmed their significant negative exposure-response relationship. Conclusions : The circulating carotenoids and vitamin C levels were negatively correlated with the risk of sleep disorders. Higher circulating antioxidant levels were significantly associated with a lower risk of sleep disorders. The potential health risk of low circulating antioxidants levels was higher in the female population than in the male population.

The development of an ultrasensitive and precise measurement of a breast cancer biomarker (cancer antigen 15-3; CA15-3) in complex human serum is essential for the early diagnosis of cancer in groups of healthy populations and the treatment of patients. However, currently available testing technologies suffer from insufficient sensitivity toward CA15-3, which severely limits early large-scale screening of breast cancer patients. We report a versatile electrochemical immunoassay method based on atomically cobalt-dispersed nitrogen-doped carbon (Co-NC)-modified disposable screen-printed carbon electrode (SPCE) with alkaline phosphatase (ALP) and its metabolite, ascorbic acid 2-phosphate (AAP), as the electrochemical labeling and redox signaling unit for sensitive detection of low-abundance CA15-3. During electrochemical detection by differential pulse voltammetry (DPV), it was found that the Co-NC-SPCE electrode did not have a current signal response to the AAP substrate; however, it had an extremely favorable response current to ascorbic acid (AA). Based on the above principle, the target CA15-3-triggered immunoassay enriched ALP-catalyzed AAP produces a large amount of AA, resulting in a significant change in the system current signal, thereby realizing the highly sensitive detection of CA15-3. Under the optimal AAP substrate concentration and ALP catalysis time, the Co-NC-SPCE-based electrochemical immunoassay demonstrated a good DPV current for CA15-3 in the assay interval of 1.0 mU/mL to 10,000 mU/mL, with a calculated limit of detection of 0.38 mU/mL. Since Co-NC-SPCE has an excellent DPV current response to AA and employs split-type scheme, the constructed electrochemical immunoassay has the merits of high preciseness and anti-interference, and its clinical diagnostic results are comparable to those of commercial kits., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Copper-cobalt bimetallic nitrogen-doped carbon-based nanoenzymatic materials (CuCo@NC) were synthesized using a one-step pyrolysis process. A three-channel colorimetric sensor array was constructed for the detection of seven antioxidants, including cysteine (Cys), uric acid (UA), tea polyphenols (TP), lysine (Lys), ascorbic acid (AA), glutathione (GSH), and dopamine (DA). CuCo@NC with peroxidase activity was used to catalyze the oxidation of TMB by H 2 O 2 at three different ratios of metal sites. The ability of various antioxidants to reduce the oxidation products of TMB (ox TMB) varied, leading to distinct absorbance changes. Linear discriminant analysis (LDA) results showed that the sensor array was capable of detecting seven antioxidants in buffer and serum samples. It could successfully discriminate antioxidants with a minimum concentration of 10 nM. Thus, multifunctional sensor arrays based on CuCo@NC bimetallic nanoenzymes not only offer a promising strategy for identifying various antioxidants but also expand their applications in medical diagnostics and environmental analysis of food., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

The precise regulation of nanoenzyme activity is of great significance for application to biosensing analysis. Herein, the peroxidase-like activity of carbon dots was effectively modulated by doping phosphorus, which was successfully employed for sensitive, selective detection of acid phosphatase (ACP). Phosphorus-doped carbon dots (P-CDs) with excellent peroxidase-like activity were synthesized by a one-pot hydrothermal method, and the catalytic activity could be easily modulated by controlling the additional amount of precursor phytic acid. P-CDs could effectively catalyze the oxidation of colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue TMB oxidation products in the presence of hydrogen peroxide. While ACP was able to catalyze the hydrolysis of L-ascorbyl-2-phosphate trisodium salt (AAP) to produce ascorbic acid (AA), which inhibited the peroxidase-like activity of P-CDs, by combining P-CDs nanoenzymes and ACP-catalyzed hydrolysis the colorimetric method was established for ACP detection. The absorbance variation showed a good linear relationship with ACP concentration in the range of 0.4-4.0 mU/mL with a limit of detection at 0.12 mU/mL. In addition, the method was successfully applied to detect ACP in human serum samples with recoveries in the range of 98.7-101.6%. The work provides an effective strategy for regulating nanoenzymes activity and a low-cost detection technique for ACP., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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.)

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.

The aim of the study was to assess the impact of solarium light therapy on selected biological and biochemical parameters of peripheral blood in recreational horses. The study involved 10 horses divided into two groups of young (aged 5 to 7 years) and old (aged 14 to 19 years) individuals. All animals participated in light therapy sessions every other day. Blood was sampled three times during the study: before the treatment, after five light sessions, and after ten light sessions. Morphological parameters, the activity of antioxidant enzymes, TAS values, and the levels of glutathione (GSH), vitamin D3, vitamin C, and malondialdehyde (MDA) were measured in the whole blood. Light therapy contributed to an increase in MCV, HDW, MCVr, CHr and MPV indices, and simultaneously a decrease in the basophil counts, MCHC, RDW and CHCMr indices in both groups of horses (p ≤ 0.05). At the same time reticulocytes fell in older whereas white blood cells and monocytes counts expanded in younger individuals. The treatment also increased the activity of glutathione reductase (GR) and glutathione peroxidase (GPx) in young but decreased the activity of mentioned enzymes in blood plasma of old horses. The total antioxidant status (TAS) of the blood plasma rose progressively, whereas GSH levels declined in all individuals. Moreover, vitamin D3 levels did not change, whereas vitamin C levels gradually decreased during the experiment. The therapy also helped to reduce levels of MDA in the blood plasma, especially of older horses (p ≤ 0.05). In turn, GPx and GR activities as well as MDA levels significantly declined, whereas GSH levels notably elevated in erythrocytes (p ≤ 0.05). Solarium light therapy appears to have a beneficial impact on the morphological parameters and antioxidant status of blood in recreational horses in the winter season. However, the observed results could in part be attributed to the natural physiological adaptation of each individual organism to the treatment., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Orzołek et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

An ultra-sensitive photoelectrochemical (PEC) sensor based on perovskite composite was developed for the determination of alkaline phosphatase (ALP) in human serum. In contrast to CsPbBr 3 or Y6 that generated anodic current, the heterojunction of CsPbBr 3 /Y6 promoted photocarriers to separate and generated cathodic photocurrent. Ascorbic acid (AA) was produced by ALP hydrolyzing L-ascorbic acid 2-phosphate trisodium salt (AAP), which can combine with the holes on the photoelectrode surface, accelerating the transmission of photogenerated carriers, leading to enhanced photocurrent intensity. Thus, the enhancement of PEC current was linked to ALP activity. The PEC sensor exhibits good sensitivity for detection of ALP owing to the unique photoelectric properties of the CsPbBr 3 /Y6 heterojunction. The detection limit of the sensor was 0.012 U·L -1 with a linear dynamic range of 0.02-2000 U·L -1 . Therefore, this PEC sensing platform shows great potential for the development of different PEC sensors., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Vitamin C is an important micronutrient for human. Association between vitamin C and trouble sleeping was less studied. Therefore, the purpose of this study was to investigate the possible link between vitamin C in serum and trouble sleeping. The cross-sectional data was derived from the National Health and Nutrition Examination Survey (NHANES, 2017-2018). Trouble sleeping was measured by asking participants: "Have you ever told doctor had trouble sleeping". Responses to this question was "yes" or "no". vitamin C in serum was obtained by measuring the serum samples. We used multivariable binary logistic regressions to examine the possible link between vitamin C in serum and trouble sleeping, and then a subgroup analysis was performed. Moreover, the non-linear relationship between vitamin C in serum and trouble sleeping was further detected using a restricted cubic spline (RCS) model. A total of 3227 participants were included in the study. After adjusting all potential confounders, the results of multivariable logistic regression showed the significant negative association between vitamin C in serum and trouble sleeping(OR = 0.816; 95% CI:0.669 ~ 0.995). The significant inverse association was also found in female(OR = 0.713; 95% CI:0.546 ~ 0.931), age ≤ 65 years(OR = 0.773; 95% CI:0.600 ~ 0.996), and in participants with high cholesterol level(OR = 0.738; 95% CI:0.548 ~ 0.994). In addition, the RCS model demonstrated the significant non-linear relationship between vitamin C in serum and trouble sleeping (P value of nonlinear = 0.010). Our study demonstrates the significant negative association between vitamin C in serum and trouble sleeping., (© 2024. The Author(s).)

Herein, efficient red carbon dots (R-CDs) were synthesized by one-step hydrothermal treatment of N-(4-amino phenyl) acetamide and (2,3-difluoro phenyl) boronic acid. The optimal emission peak of R-CDs was at 602 nm (under 520 nm excitation) and the absolute fluorescence quantum yield of R-CDs was 12.9%. Polydopamine, which was formed by the self-polymerization and cyclization of dopamine in alkaline condition, emitted characteristic fluorescence with peak position of 517 nm (under 420 nm excitation) and affected the fluorescence intensity of R-CDs through inner filter effect. L-Ascorbic acid (AA), which was the hydrolysis product of L-ascorbic acid-2-phosphate trisodium salt under the catalytic reaction of alkaline phosphatase (ALP), effectively prevented the polymerization of dopamine. Combined with the ALP-mediated AA production and the AA-mediated polydopamine generation, the ratiometric fluorescence signal of polydopamine with R-CDs was correlated closely with the concentration of both AA and ALP. Under optimal conditions, the detection limits of AA and ALP were 0.28 μM during linear range of 0.5-30 μM and 0.044 U/L with linear range of 0.05-8 U/L, respectively. This ratiometric fluorescence detection platform can efficiently shield the background interference of sophisticated samples by introducing a self-calibration as reference signal in a multi-excitation mode, which can detect AA and ALP in human serum samples with satisfactory results. Such R-CDs/polydopamine nanocomposite provides a steadfast quantitative information and makes R-CDs be excellent candidate for biosensors via combining target recognition strategy., 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 Elsevier B.V. All rights reserved.)

Cardiovascular disease (CVD), as the leading cause of death worldwide, is the collective term named for disorders afflicting the blood vessels and heart. Inflammation and enhanced oxidative stress have been shown as fundamental risk factors in the onset and progression of CVD. Chronic inflammatory conditions attenuate blood levels of antioxidants because of the continuous generation of elevated levels of reactive oxygen species (ROS). A sufficient intake of antioxidants is also suggested to beneficially interfere with CVD by quenching ROS. Antioxidant vitamins and minerals, such as vitamins A, E, and C, and zinc may slow the development and progression of CVD. This study aimed at investigating the association between daily consumption of dietary vitamins A, E, and C, and zinc and the incidence of CVD. Eligible adults (n = 5102) aged ≥ 30 years, were selected from the participants of the Tehran lipid and glucose study with an average follow-up of 5.3 years. Dietary intake was assessed using a valid and reliable semi-quantitative food frequency questionnaire. Anthropometrics and biochemical variables were evaluated at baseline and follow-up examinations. Multivariable Cox proportional hazard regression models were used to estimate the development of CVD associated with total intakes of vitamins A, E, and C, and zinc. This study was conducted on 2253 men and 2849 women aged 47.0 ± 11.6 and 45.6 ± 10.5 years, respectively. The main sources of dietary vitamins A, E, and C and zinc were fruits, vegetables, and legumes. Risk of CVD decreased from quartile 1 to quartile 4 for vitamin E intake (HR 1.00, 0.91, 0.77, and 0.57; P trend  = 0.03). The association between the risk of CVD and quartiles of vitamins A, and C and zinc intake was not statistically significant. Our study suggests an inverse association between vitamin E intake and the risk of CVD, emphasizing the potential protective role of fruit and vegetable in the prevention of CVD., (© 2022. The Author(s).)

Aim: We conducted a two-sample Mendelian randomization (MR) study to assess the associations of genetically predicted circulating vitamin C levels with cardiovascular diseases (CVDs)., Methods and Results: Ten lead single-nucleotide polymorphisms associated with plasma vitamin C levels at the genome-wide significance level were used as instrumental variables. Summary-level data for 15 CVDs were obtained from corresponding genetic consortia, the UK Biobank study, and the FinnGen consortium. The inverse-variance-weighted method was the primary analysis method, supplemented by the weighted median and MR-Egger methods. Estimates for each CVD from different sources were combined. Genetically predicted vitamin C levels were not associated with any CVD after accounting for multiple testing. However, there were suggestive associations of higher genetically predicted vitamin C levels (per 1 standard deviation increase) with lower risk of cardioembolic stroke [odds ratio, 0.79; 95% confidence interval (CI), 0.64, 0.99; P = 0.038] and higher risk of atrial fibrillation (odds ratio, 1.09; 95% CI, 1.00, 1.18; P = 0.049) in the inverse-variance-weighted method and with lower risk of peripheral artery disease (odds ratio, 0.76, 95% CI, 0.62, 0.93; P = 0.009) in the weighted median method., Conclusion: We found limited evidence with MR techniques for an overall protective role of vitamin C in the primary prevention of CVD. The associations of vitamin C levels with cardioembolic stroke, atrial fibrillation, and peripheral artery disease need further study., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

A rapid and facile method is reported for the detection of ascorbic acid using molybdenum disulfide quantum dots (MoS 2 QDs) as a fluorescence sensor. Water-soluble and biocompatible MoS 2 QDs with the maximum fluorescence emission at 506 nm have been successfully synthesized by hydrothermal method and specific detection for ascorbic acid (AA) was constructed to utilize the modulation of metal ion on the fluorescence of MoS 2 QDs and the affinity and specificity between the ligand and the metal ion. The fluorescence of MoS 2 QDs was quenched by the irreversible static quenching of Fe 3+ through the formation of a MoS 2 QDs/Fe 3+ complex, while the pre-existence of AA can retain the fluorescence of MoS 2 QDs through the redox reaction between AA and Fe 3+ . Based on this principle, a good linear relationship was obtained in the AA concentration range 1 to 150 μM with a detection limit of 50 nM. The proposed fluorescent sensing strategy was proven to be highly selective, quite simple, and rapid with a requirement of only 5 min at room temperature (RT), which is particularly useful for rapid and easy analysis. Satisfactory results were obtained when applied to AA determination in fruits, beverages, and serum samples as well as AA imaging in living cells, suggesting its great potential in constructing other fluorescence detection and imaging platforms., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Apolipoprotein E E4 (APOE4) is a risk factor for cognitive decline. A high blood vitamin C (VC) level reduces APOE4-associated risk of developing cognitive decline in women. In the present study, we aimed to examine the effects of functional variants of VC transporter genes expressed in the brain (SLC2A1, SLC2A3, and SLC23A2) on APOE4-associated risk of developing cognitive decline. This case-control study involved 393 Japanese subjects: 252 cognitively normal and 141 cognitively impaired individuals (87 mild cognitive impairment and 54 dementia). Database searches revealed that rs1279683 of SLC23A2, and rs710218 and rs841851 of SLC2A1 are functional variants that are significantly associated with the altered expression of the respective genes and genotyped as three single nucleotide variants (SNVs). When stratified by SNV genotype, we found a significant association between APOE4 and cognitive decline in minor allele carriers of rs1279683 (odds ratio [OR] 2.02, 95% CI, 1.05-3.87, p = 0.035) but not in the homozygote carriers of the major allele. Significant associations between APOE4 and cognitive decline were also observed in participants with major allele homozygotes of rs710218 (OR 2.35, 95% CI, 1.05-5.23, p = 0.037) and rs841851 (OR 3.2, 95% CI, 1.58-6.46, p = 0.0012), but not in minor allele carriers of the respective SNVs. In contrast, the three functional SNVs showed no significant effect on cognitive decline. Our results imply that functional SNVs of VC transporter genes can affect APOE4-associated risk of developing cognitive decline via altered VC levels in the brain., Competing Interests: The authors have declared that no competing interests exist.

Competing Interests: Competing interests The BMJ has judged that there are no disqualifying financial ties to commercial companies. The authors declare the following other interests: none.

The Western-style diet, which is common in developed countries and spreading into developing countries, is unbalanced in many respects. For instance, micronutrients (vitamins A, B complex, C, D, E, and K plus iron, zinc, selenium, and iodine) are generally depleted in Western food (causing what is known as 'hidden hunger'), whereas some others (such as phosphorus) are added beyond the daily allowance. This imbalance in micronutrients can induce cellular damage that can increase the risk of cancer. Interestingly, there is a large body of evidence suggesting a strong correlation between vitamin intake as well as vitamin blood concentrations with the occurrence of certain types of cancer. The direction of association between the concentration of a given vitamin and cancer risk is tumor specific. The present review summarized the literature regarding vitamins and cancer risk to assess whether these could be used as diagnostic or prognostic markers, thus confirming their potential as biomarkers. Despite many studies that highlight the importance of monitoring vitamin blood or tissue concentrations in cancer patients and demonstrate the link between vitamin intake and cancer risk, there is still an urgent need for more data to assess the effectiveness of vitamins as biomarkers in the context of cancer. Therefore, this review aims to provide a solid basis to support further studies on this promising topic.

Vitamin C, well-established in immune function and a key factor in epigenetic inflammatory modifications, is only obtained through consistent dietary intake. Identifying individuals at risk for Vitamin C insufficiency may guide prevention and treatment, however, national surveillance has not been evaluated in the United States since 2006. A descriptive, cross-sectional secondary analysis was performed utilizing data from the 2003-2006 National Health and Nutrition Examination Surveys (NHANES) assessing non-institutionalized adults. Five categories of plasma Vitamin C were delineated: deficiency (<11 μmol/L), hypovitaminosis (11-23 μmol/L), inadequate (23-49 μmol/L), adequate (50-69 μmol/L), and saturating (≥70 μmol/L). Results indicated 41.8% of the population possessed insufficient levels (deficiency, hypovitaminosis, and inadequate) of Vitamin C. Males, adults aged 20-59, Black and Mexican Americans, smokers, individuals with increased BMI, middle and high poverty to income ratio and food insecurity were significantly associated with insufficient Vitamin C plasma levels. Plasma Vitamin C levels reveal a large proportion of the population still at risk for inflammatory driven disease with little to no symptoms of Vitamin C hypovitaminosis. Recognition and regulation of the health impact of Vitamin C support the goal of Nutrition and Healthy Eating as part of the Healthy People 2030.

Background & Aims: Previous observational studies have reported associations between plasma vitamin C levels, and cardiovascular diseases (CVDs) and Alzheimer's disease (AD); however, no conclusive results have been obtained. We conducted a Mendelian randomization (MR) study to investigate the causality of vitamin C on the risk of nine CVDs [including coronary artery disease (CAD), myocardial infarction (MI), atrial fibrillation (AF), heart failure (HF), stroke, ischemic stroke (IS), and IS subtypes] and Alzheimer's disease., Methods: Eleven single-nucleotide polymorphisms (SNPs) identified in a recent genome-wide meta-analysis (N = 52,018) were used as the instrumental variables for plasma vitamin C levels. The summary-level data for CVDs and AD were extracted from consortia and genome-wide association studies (GWAS). We performed MR analyses using the fixed-effects inverse-variance-weighted (IVW) method, weighted median, and MR-Egger approaches., Results: This MR study found suggestive evidence that genetic liability to higher vitamin C levels was associated with a lower risk of cardioembolic stroke [odds ratio (OR, presented per 1 standard deviation increase in plasma vitamin C levels) = 0.773; 95% confidence interval (CI), 0.623-0.959; P = 0.020] and AD (OR = 0.968; 95% CI, 0.946-0.991; P = 0.007) using the fixed-effects IVW method. Sensitivity analysis yielded directionally similar results. A null-association was observed between vitamin C and the other CVDs., Conclusion: Our MR study provided suggestive evidence that higher vitamin C levels were casually associated with a decreased risk of cardioembolic stroke and AD. No evidence was observed to suggest that vitamin C affected the risk of CAD, MI, AF, HF, stroke, IS, large artery stroke, or small vessel stroke. However, well-designed studies are warranted to confirm these results and determine the underlying mechanisms of the causal links., Competing Interests: Conflict of interest The authors declare no conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Lipid panels are a commonly performed test in clinical laboratories. Due to the high prevalence of cardiovascular diseases around the world, it is common to see serum or plasma specimens with high results for one or more components of the lipid panel. Exceedingly low results, however, are rare and may be attributed to certain genetic, infectious, or autoimmune conditions in addition to analytical interference. Here we report a serum specimen from a 58-year-old female with cholesterol and triglyceride values below the detection limit of the assay, which was investigated to identify the cause of the anomaly. Using vitamin C test strips and high-performance liquid chromatography, the presence of high levels of antioxidant vitamin C in the patient specimen was confirmed. Subsequent treatment of the sample with the enzyme ascorbate oxidase inactivated vitamin C, leading to lipid analyte values falling within the expected range upon repeat analysis. Thus, analytical interference by vitamin C should be considered when suspiciously low lipid panel results are encountered., (Copyright © 2021 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2021. Other selected articles can be found online at  https://www.biomedcentral.com/collections/annualupdate2021 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from  https://link.springer.com/bookseries/8901 ., (© 2021. Rozemeijer et al.)

Introduction: Micronutrients are essential minerals and vitamins needed for optimal health. There are however conflicting reports about the roles of micronutrients in severity and outcomes of childhood pneumonia. This study aims to determine the socio-demographic and serum micronutrients - Zinc (Zn), Selenium (Se), Vitamins (Vit) A, C and E status of Nigerian children with or without pneumonia and relate these to pneumonia severity and outcome., Methodology: Children aged two months to 14 years with severe and non-severe pneumonia were recruited with age and sex-matched controls over 12 month period in a Nigerian tertiary health centre. Relevant history and serum micronutrients were compared in the two groups and related to pneumonia severity and length of hospitalisation (LOH)., Results: One hundred and forty-four children (72 for each group) were recruited with median (IQR) age 1.6 (0.6 - 4.0) years and fifty-six (38.8%) had severe pneumonia. Pneumonia incidence was associated with undernutrition, inappropriate immunisation and Zn deficiency (p < 0.05). Hypovitaminosis A [60.8(22.2)µg/dl vs. 89.5(34.7)µg/dl; p < 0.001], low serum Zn [71.6(32.5)µg/dl vs. 92.6(24.6)µg/dl; p=0.019] and indoor air pollution (IAP) were associated with pneumonia severity. However, only IAP (OR = 4.529; 95%CI 1.187-17.284; p=0.027) and Zn deficiency (OR=6.144; 95%CI 1.157-32.617; p=0.033) independently predicted severe pneumonia. No significant correlation between serum micronutrients and LOH., Conclusions: Exposure to IAP and low serum micronutrients particularly Zn and Vit A were associated with pneumonia incidence and severity in Nigerian children. Routine micronutrient supplementation may assist to reduce the burden of childhood pneumonia in developing countries., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2021 Bankole Peter Kuti, Hammed Hassan Adetola, Oyeku Akibu Oyelami.)

Background and Aims: The impact of vitamin C supplementation on the risk of cardiovascular diseases (CVDs) remains uncertain with inconsistent evidence obtained from observational studies and randomized clinical trials (RCTs). We aimed to assess possible causal associations of vitamin C with major CVD events as well as their risk factors using Mendelian randomization (MR) design., Methods and Results: Nine genetic variants associated with vitamin C at genome-wide significance (p < 5 × 10 -8 ) were used as instrumental variables to predict plasma vitamin C levels. The primary outcomes were coronary artery disease (Ncase = 122,733 and Ncontrol = 424,528), atrial fibrillation (Ncase = 60,620 and Ncontrol = 970,216), heart failure (Ncase = 47,309 and Ncontrol = 930,014), and ischemic stroke (Ncase = 40,585 and Ncontrol = 406,111). Several CVD risk factors were also evaluated in secondary analyses. Two-sample MR analyses were performed using the inverse variance weighted method, with several sensitivity analyses. Genetically determined higher levels of plasma vitamin C were not significantly associated with any of the four examined CVD events. Likewise, there is no convincing evidence for the associations between genetically determined vitamin C and CVD risk factors, including higher blood lipids, higher blood pressure, and abnormal body composition. Sensitivity analyses using different analytical approaches yielded consistent results. Additionally, MR assumptions did not seem to be violated., Conclusion: This MR study does not support a causal protective role to circulate vitamin C levels on various types of CVD events. In combination with previous RCT results, our findings suggest that vitamin C supplementation to increase circulating vitamin C levels may not help in CVD prevention., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2021 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.)

There are limited proven therapeutic options for the prevention and treatment of COVID-19. We underwent an observational study with the aim of measure plasma vitamin C levels in a population of critically ill COVID-19 adult patients who met ARDS criteria according to the Berlin definition. This epidemiological study brings to light that up to 82% had low Vitamin C values. Notwithstanding the limitation that this is a single-center study, it nevertheless shows an important issue. Given the potential role of vitamin C in sepsis and ARDS, there is gathering interest of whether supplementation could be beneficial in COVID-19., (© 2021. The Author(s).)

Atherosclerosis is a pro-oxidative and pro-inflammatory disease state, which is the underlying cause of most cardiovascular events, estimated to affect 5.2% of the Australian population. Diet, and specifically vitamin C, through its antioxidant properties can play a role in impeding the development and progression of atherosclerosis. This systematic review conducted comprehensive searches in Medline, Emcare, Scopus, PubMed, and Cochrane using key search terms for vitamin C, plasma vitamin C, supplementation, and cardiovascular disease (CVD). The results demonstrated that vitamin C supplementation resulted in a significant increase in vitamin C levels in populations with or without CVD, except for one study on the CVD population. It was also seen that the healthy population baseline and post-intervention vitamin C levels were high compared to the CVD population. However, further research is indicated for CVD population groups with varying baseline vitamin C levels, such as low baseline vitamin C, within a more representative elderly cohort in order to formulate and update vitamin C repletion guidelines.

The commonly used Chromsystems vitamin C (ascorbate) assay (Munich, Germany) has a sample storage life of five days at -20°C. Stabilizing agents have been successfully used to increase longevity; however, their suitability with this commercial assay is unclear. We investigated the compatibility of a stabilizing agent, perchloric acid/diethylenetriaminepentaacetic acid (PCA/DTPA), with the Chromsystems assay. Plasma was stored at -80°C, with or without PCA/DTPA. Storage up to six months was assessed through baseline and repeat analyses, stability was assessed by comparing paired non-stabilized and PCA/DTPA-stabilized plasma, and performance was assessed using allowable performance specifications of an external quality assurance program. Ascorbate concentration was significantly lower in non-stabilized plasma than in paired PCA/DTPA-stabilized plasma, with a proportional difference of 11% (P=0.01). All storage analysis results were within the allowable performance specifications. Storage at -80°C prevented plasma ascorbate oxidation; however, substantial oxidation occurred during sample processing. In conclusion, PCA/DTPA significantly reduces ascorbate oxidation, and PCA/DTPA-stabilized ascorbate plasma is compatible with the Chromsystems assay and stable for up to six months, when stored at -80°C.

Background: Critically ill patients frequently suffer from vitamin C deficiency. Previous studies showed that high doses of vitamin C administration had conflicting results on clinical outcomes in patients with severe sepsis, burns, and trauma. Because of the high incidence and morbidity/mortality with severe pneumonia, we aimed to investigate the effect of administration of high dose vitamin C in critically ill patients with severe pneumonia., Methods: Eighty critically ill patients with pneumonia were enrolled in this randomized double-blinded clinical trial. Patients with a CURB-65 score > 3, one major criterion, or ≥ 3 minor criteria were considered as severe pneumonia. Patients were randomly assigned to intervention or placebo groups receiving standard treatment plus 60 mg/kg/day vitamin C as a continuous infusion or normal saline in the same volume correspondingly for 96 h. Serum levels of vitamin C were noted at baseline and 48 h after vitamin C administration. Duration of mechanical ventilation, ICU length of stay, PaO 2 /FiO 2 , and mortality rate were noted for all patients till the 28th day. Any complications related to the vitamin C administration were recorded., Results: Duration of mechanical ventilation and vasopressor use were significantly lower in the intervention group (p: < 0.001 and 0.003, respectively). Baseline levels of vitamin C in both groups did not have a significant difference but its levels increased in the intervention group and decreased in the control group during the study period. Mortality rate insignificantly decreased in the intervention group (p = 0.17). Three patients showed hypotension and tachycardia during the administration of vitamin C which was self-limited with decreasing the dose of vitamin C. Our results showed that the intravenous administration of a relatively high dose of vitamin C to critically ill patients with severe pneumonia was safe and could decrease the inflammation, duration of mechanical ventilation, and vasopressor use without any significant effect on mortality., Trial Registration: IRCT registration number: IRCT20190312043030N1, Registration date: 2019-08-26, Seied Hadi Saghaleini.

In October 2016, we received reports of five deaths among prisoners with leg swelling of unknown etiology in southwestern Ethiopia. A descriptive cross-sectional study was conducted to investigate the outbreak. A suspected case was defined as a prisoner with leg swelling of unknown etiology noted between May 15, 2016 and November 29, 2016. A total of 118 suspected cases were identified with unilateral or bilateral leg swelling without an identifiable cause from a total of 2,790 prisoners. Eight of the suspected cases were thoroughly examined, and seven of these suspected cases had clinical findings consistent with scurvy. Three of the clinical cases had undetectable vitamin C levels in the serum. The attack rate for the prison was 4.2% (118/2,790), and 11 deaths were identified, making the case fatality rate 9.3% (11/118). Clinical cases of scurvy had symptoms of fatigue, myalgia, arthralgia, and signs of follicular hyperkeratosis, petechiae, peripheral edema, and oral lesions. All clinical cases had severe anemia with hemoglobin < 6.0 g/dL. The diet provided by the prison excluded fruits and vegetables. Scurvy was determined to be the cause of the outbreak, and vitamin C supplementation was promptly initiated. All symptomatic prisoners improved, and no further cases were identified in a 4-week follow-up period of active surveillance.