A ratiometric fluorescent probe for simultaneous detection of L-ascorbic acid and alkaline phosphatase activity based on red carbon dots/polydopamine nanocomposite.

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.

Genetically predicted circulating vitamin C in relation to cardiovascular disease.

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.

Ascorbic acid detector based on fluorescent molybdenum disulfide quantum dots.

A rapid and facile method is reported for the detection of ascorbic acid using molybdenum disulfide quantum dots (MoS2 QDs) as a fluorescence sensor. Water-soluble and biocompatible MoS2 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 MoS2 QDs and the affinity and specificity between the ligand and the metal ion. The fluorescence of MoS2 QDs was quenched by the irreversible static quenching of Fe3+ through the formation of a MoS2 QDs/Fe3+ complex, while the pre-existence of AA can retain the fluorescence of MoS2 QDs through the redox reaction between AA and Fe3+. 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.

Insufficient Vitamin C Levels among Adults in the United States: Results from the NHANES Surveys, 2003-2006.

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.

Vitamins as Possible Cancer Biomarkers: Significance and Limitations.

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.

Effects of functional variants of vitamin C transporter genes on apolipoprotein E E4-associated risk of cognitive decline: The Nakajima study.

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.

The impact of plasma vitamin C levels on the risk of cardiovascular diseases and Alzheimer's disease: A Mendelian randomization study.

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.

Serum Micronutrients as related to Childhood Pneumonia Severity and Outcome in a Nigerian Health Facility.

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.

Measuring vitamin C in critically ill patients: clinical importance and practical difficulties-Is it time for a surrogate marker?

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 .

Effect of Dietary or Supplemental Vitamin C Intake on Vitamin C Levels in Patients with and without Cardiovascular Disease: A Systematic Review.

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.

COVID-19: Up to 82% critically ill patients had low Vitamin C values.

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.

Excessively low cholesterol and triglyceride levels in an apparently healthy patient.

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.

Effect of Vitamin C on mortality of critically ill patients with severe pneumonia in intensive care unit: a preliminary study.

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, PaO2/FiO2, 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.

An Epidemic of Scurvy, Identified Based on Lower Extremity Swelling, in a Southern Ethiopian Prison.

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.

Circulating vitamin C and the risk of cardiovascular diseases: A Mendelian randomization study.

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.

Vitamin C Deficiency in the Young Brain-Findings from Experimental Animal Models.

Severe and long-term vitamin C deficiency can lead to fatal scurvy, which is fortunately considered rare today. However, a moderate state of vitamin C (vitC) deficiency (hypovitaminosis C)-defined as a plasma concentration below 23 µM-is estimated to affect up to 10% of the population in the Western world, albeit clinical hallmarks in addition to scurvy have not been linked to vitC deficiency. The brain maintains a high vitC content and uniquely high levels during deficiency, supporting vitC's importance in the brain. Actions include both antioxidant and co-factor functions, rendering vitamin C deficiency likely to affect several targets in the brain, and it could be particularly significant during development where a high cellular metabolism and an immature antioxidant system might increase sensitivity. However, investigations of a non-scorbutic state of vitC deficiency and effects on the developing young brain are scarce. This narrative review provides a comprehensive overview of the complex mechanisms that regulate vitC homeostasis in vivo and in the brain in particular. Functions of vitC in the brain and the potential consequences of deficiency during brain development are highlighted, based primarily on findings from experimental animal models. Perspectives for future investigations of vitC are outlined.

Clinical efficacy of Curcuvet and Boswellic acid combined with conventional nutraceutical product: An aid to canine osteoarthritis.

INTRODUCTION: Osteoarthritis is a progressive degenerative joint disease which is high prevalent in dogs. In the late stage of the disease, it determines chronic neuropathic pain which leads to reduced quality-of-life in affected patients. To date it has not yet been identified a specific treatment, but it has been proved that nutraceutical and dietary supplements may play an important role in controlling inflammation and pain. The aim of this study was to evaluate, by the use of force plate gait analysis, the clinical efficacy of Boswellia and Curcuvet® combined with conventional nutraceutical therapy compared with conventional nutraceutical alone in dogs affected by osteoarthritis. MATERIALS AND METHODS: Twenty client-owned dogs, over 12 months old and 20 kg of body-weight, with a confirmed diagnosis of Osteoarthritis, were included in this randomized, double-blinded study. The dogs were randomly divided into two groups: the first group (A) received a conventional nutraceutical (consisted in a preparation of glucosamine, chondroitin sulfate, fish-oil containing 80% of omega 3-fatty acid, vitamin C and E, saccharomyces Cerevisiae) with a combination of acid boswellic and Curcuvet®, while the second group (B) received a conventional nutraceutical. All the enrolled dogs underwent a washout period before starting the treatment with nutraceuticals products which were the only admitted treatment over the study period. A full orthopaedic and neurologic examination, and force plate gait analysis were performed before starting the treatment, at 45, 90, and 60 days post-treatment. Ground reaction forces were recorded and analyzed. RESULTS: Twenty dogs were enrolled in the study. In both groups there was an increasing values of ground reaction forces. These results might indicate that both nutraceutical products determined a better condition in terms of pain feeling but that effect is much more visible after 60 days from the end of the administration in treated group. DISCUSSION: In conclusion Curcuvet in combination with Boswellic acid could be considered a valid aid in a multimodal treatment for canine osteoarthritis.

Lithium cobalt phosphate electrode for the simultaneous determination of ascorbic acid, dopamine, and serum uric acid by differential pulse voltammetry.

Lithium cobalt phosphate (LCP) was prepared and modified on the surface of glassy carbon electrode (GCE) to fabricate the electrochemical sensor (LCP/GCE) for the simultaneous determination of ascorbic acid (AA), dopamine (DA), and serum uric acid (UA). The homogenous incorporation of carbon improved the conductivity of LCP. Benefiting from the small particle size distribution, LCP/GCE has a large active surface and responds to AA, DA, and UA sensitively and rapidly. For the simultaneous detection with differential pulse voltammetry the anodic peaks of AA, DA, and UA were well-separated and appeared at ~0 V, ~0.19 V, and ~ 0.33 V (vs. Ag/AgCl), respectively. The linear responses toward AA, DA, and UA were in the range 10 µM-8.0 mM, 10 nM-10 µM, and 0.020 µM-25 µM; the detection limits were estimated to be 8.10 µM, 7.50 nM, and 22.7 nM (S/N = 3), respectively. The excellent selectivity and reproducibility of LCP/GCE enable serum UA to be detected without the interference of AA and DA. The recoveries of DA and AA in the serum sample were in the range 95 to 111%. The results indicate that LCP has the potential to be developed as the sensing devices to be applied to in vitro diagnosis. The lithium-ion battery cathodic material, LCP with the excellent adsorption and catalytic behavior, was utilized to fabricate the electrochemical sensor for the sensitive and simultaneous detection of AA, DA, and UA, which achieved the low detection limits and the wide concentration ranges. LCP/GCE can be used for the quantitative detection of serum UA without the interference of DA and AA. In addition, the recoveries of DA and AA in human serum were satisfactory, which illustrate the reliability of LCP/GCE to be applied to in vitro diagnosis.