Plasma Ascorbic Acid Concentrations Research Articles

Ascorbic Acid Supplementation and Immune Response in Healthy Women during High-intensity Exercise

Introduction the benefits of consuming extra Ascorbic Acid (AA) while exercising are not well understood. Aim This study aims to explore the effects of AA supplementation on oxidative stress, the immunological response, and inflammation in healthy women after a single bout of high-intensity exercise. Materials and Methods In a crossover design, 20 sedentary women (aged 18-22) underwent 30 minutes of vigorous cycling. They were divided into two groups: one receiving daily 1,000 mg ascorbic acid supplementation (1,000AA) and the other without supplementation (0AA). This regimen was maintained for one week. Blood samples obtained pre-exercise, immediately post-exercise, and 24 hours post-exercise underwent analysis for oxidative stress, inflammatory markers, CD4+ and CD8+ lymphocytes, and neutrophil phagocytic activity. Results An AA supplement significantly increased plasma concentrations of AA (p<0.05) and reduced post-exercise plasma MDA levels (p<0.05) but did not affect creatine kinase activity. White blood cells, CD8+ T cells, and IL-6 increased significantly after exercise but remained unchanged in the 1,000AA group compared to the 0AA group, while the neutrophil count increased (p<0.05) after exercise with no change in phagocytic function. A slight drop in phagocytic function was observed 24 hours after exercise in the 1,000AA group. Exercise and AA supplements had no effect on CD4+ T cells. Conclusion a single session of high-intensity exercise caused oxidative stress, muscle injury, and inflammation, as well as a transient increase in CD8+ T cells. A short administration of AA attenuated the exercise-induced oxidative stress and reduced inflammation by limiting the increase in IL-6 and CD8+ T cells.

Effects of intravenous administration of ascorbic acid (vitamin C) on oxidative status in healthy adult horses.

Ascorbic acid (AA) is an antioxidant that might be beneficial for adjunctive treatment of sepsis in horses. The optimal dose and effects on oxidative status are unknown. Ascorbic acid administration will increase plasma AA concentrations and decrease determinants of reactive oxygen metabolites (dROM), basal and stimulant-induced intraerythrocytic reactive oxygen species (ROS) concentrations, and stimulant-induced neutrophil ROS production, and increase plasma antioxidant capacity (PAC) in a dose-dependent manner. Eight healthy horses. Randomized placebo-controlled crossover study. Each horse received 4 single-dose IV treatments including AA at 25, 50, and 100 mg/kg and saline (placebo) with each treatment separated by ≥1 week. Blood was collected at baseline, 2 and 6 hours for assessment of plasma dROM and PAC via photometer, intraerythrocytic ROS by flow cytometry, and stimulant-induced neutrophil ROS by a fluorometric assay. Plasma AA concentrations were measured by high-performance liquid chromatography/electrochemical detection. Ascorbic acid at 100 mg/kg resulted in decreased dROM 2 hours after treatment (P = .03, 95% CI 5.51-121.2, point estimate 63.3). There was no effect of AA on basal or stimulant-induced intraerythrocytic ROS (P = .88, 95% CI -0.156 to 0.081, point estimate -0.037; P = .93, 95% CI -0.123 to 0.112, point estimate -0.006, respectively), basal or stimulant-induced neutrophil ROS (P ≥ .12, 95% CI -644.9 to 56.2, point estimate -294.4), or PAC (P ≥ .64, 95% CI -1567 to 463.4, point estimate -552.0) at any dose or timepoint. Plasma AA concentrations increased in a dose-dependent manner. High-dose administration of AA might provide antioxidant benefits in horses.

Oxidative stress-related impairment of endothelial function in uncomplicated obesity

Purpose: Visceral obesity is associated with vascular oxidative stress and development of hypertension. Therefore, we tested the hypothesis that suppression of vascular oxidative stress in adults with visceral obesity would improve endothelium-dependent dilation. Methods: IV infusion of a water-soluble antioxidant (ascorbic acid) was performed in 15 middle-age obese adults (3 men/12 women) without diabetes or hypertension in a placebo-controlled, double-blinded, crossover study design. Ascorbic acid was infused at 0.06g/kg fat free mass in 100 ml saline at 5 mL/min over 20 min (bolus) followed by a drip infusion at 0.02 g/kg fat-free mass in 30 ml saline at 0.5 mL/min over 60 min. Endothelium-dependent dilation was assessed via brachial artery flow-mediated dilation (FMD) and expressed as % increase in diameter from baseline before forearm occlusion. Results: Android fat distribution in the visceral cavity (VAT%) was 39 ± 10% and body mass index (BMI) was 37 ± 6 kg/m2. IV infusion significantly increased plasma ascorbic acid concentrations (Baseline: 42 ± 2 vs. Bolus: 66 ± 6 vs. End: 62 ± 4 μmol/L, P<0.001). Compared with baseline, bolus infusion of ascorbic acid significantly increased FMD (Baseline: 5.8 ± 2.5 vs. Bolus: 9.0 ± 4.0 vs. End: 8.0 ± 4.2 %, P=0.01), which remained after statistically adjusting for the stimulus (shear rate area under the curve) via analysis of covariance (P=0.04). No significant change in FMD was observed following placebo (saline) during a separate study visit (Baseline: 8.0 ± 4.4 vs. Bolus: 8.3 ± 3.9 vs. End: 8.6 ± 2.9 %, P=0.86). Conclusions: These preliminary findings suggest that acute elevations in plasma ascorbic acid concentrations improve endothelium-dependent dilation in middle-aged adults with visceral obesity. Future studies should target mechanisms by which mediators of oxidative stress in obesity (e.g., hyperlipidemia, hyperinsulinemia) inhibit nitric oxide-mediated vasodilation. Funding and support: R01HL159370-01 (S.W.H.). This work was also supported by a CTSA grant from NCATS awarded to the University of Kansas for Frontiers: University of Kansas Clinical and Translational Science Institute (# UL1TR002366). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or CTSA. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Microvascular constriction via fatty acid-mediated oxidative stress in humans

Purpose: Excess plasma lipids promote oxidative stress and impair vascular function. Herein, we examined microcirculatory blood flow and tested the hypothesis that a co-infusion of a water-soluble antioxidant (ascorbic acid, AA) would attenuate reductions in retinal arteriole lumen diameter and increase resistance resulting from acutely elevated plasma lipids in healthy adults. Methods: A 20% IV fat emulsion (Intralipid) was administered for 2 hours to 8 healthy, middle-aged adults (2 men/6 women) with and without co-infusion of ascorbic acid (separate visits) in a double-blinded, crossover study design. Co-infusion of AA was administered at 0.06g/kg fat free mass in 100 ml saline at 5 mL/min over 20 min (bolus) followed by a drip infusion at 0.02 g/kg fat-free mass in 30 ml saline at 0.33 mL/min over 90 min. Retinal arteriole lumen diameter and resistance were assessed via Laser Speckle Flowgraphy at baseline and after infusion. Results: Lipid infusion significantly increase plasma fatty acid concentrations (lipid w/o AA: +36 ± 18 vs. lipid with AA: +41 ± 13 vs. μmol/L, P=0.84). AA infusion significantly increased plasma ascorbic acid concentrations (lipid w/o AA: -1 ± 7 vs. lipid with AA: +26 ± 11 μmol/L, P=0.04). A significant increase in retinal arteriole resistance was observed following lipid infusion (lipid w/o AA: +20 ± 8 %, vs. lipid with AA: +17 ± 8 %, P=0.40). In accordance, lipid infusion significantly reduced retinal arteriole lumen diameter; however, co-infusion of AA reversed the lipid-mediated decrease in retinal arteriole diameter (lipid w/o AA: -3 ± 1 % vs. lipid with AA: +3 ± 2 %, P=0.01). Conclusions: Although microvascular resistance was increased, co-infusion of the antioxidant (ascorbic acid) reversed the fatty acid-mediated reduction in arteriole lumen diameter. Therefore, these preliminary findings suggest that acute elevations in plasma fatty acids induce microvascular constriction via an oxidative stress pathway. Funding and support: R01HL159370-01 (S.W.H.). This work was also supported by a CTSA grant from NCATS awarded to the University of Kansas for Frontiers: University of Kansas Clinical and Translational Science Institute (# UL1TR002366). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or CTSA. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Impaired endothelial function via fatty acids and the potential role of oxidative stress

Purpose: Excess plasma lipids promote oxidative stress and impaired vascular function. Therefore, we tested the hypothesis that a water-soluble antioxidant (ascorbic acid, AA) would attenuate reductions in endothelium-dependent dilation resulting from acutely elevated plasma fatty acids. Methods: A 20% IV fat emulsion (Intralipid) was administered for 2 hours to 8 healthy, middle-aged adults (2 men/6 women) with and without co-infusion of ascorbic acid (separate visits) in a double-blinded, crossover study design. Co-infusion of AA was administered at 0.06g/kg fat free mass in 100 ml saline at 5 mL/min over 20 min (bolus) followed by a drip infusion at 0.02 g/kg fat-free mass in 30 ml saline at 0.33 mL/min over 90 min. Endothelium-dependent dilation was assessed via brachial artery flow-mediated dilation (FMD) and expressed as % increase in diameter from baseline before forearm occlusion. Results: Lipid infusion significantly increase plasma fatty acid concentrations (w/o AA: +36 ± 18 vs. with AA: +41 ± 13 vs. μmol/L, P=0.84). AA infusion significantly increased plasma ascorbic acid concentrations (w/o AA: -1 ± 7 vs. with AA: +26 ± 11 μmol/L, P=0.04). Compared with baseline, FMD was significantly reduced following lipid infusion at (Baseline: 9.3 ± 1.1 vs. 20 min: 4.4 ± 1.3 vs. End: 5.3 ± 2.9 %, P=0.03), and when statistically adjusting for the stimulus (shear rate area under the curve) via analysis of covariance (P=0.02). FMD was also significantly reduced following lipid infusion with co-infusion of AA (Baseline: 8.9 ± 1.0 vs. 20 min: 5.3 ± 1.0 vs. End: 6.4 ± 3.8 %, P=0.02), but not when statistically adjusting for shear rate under the curve (P=0.08). Conclusions: Elevated plasma fatty acids impair endothelium-dependent dilation in healthy adults. However, co-administration of an antioxidant (ascorbic acid) limited the reduction in FMD when correcting for shear rate. Therefore, these preliminary data suggest that fatty acids may reduce endothelium-dependent dilation via an oxidative stress mechanism. Funding and support: R01HL159370-01 (S.W.H.). This work was also supported by a CTSA grant from NCATS awarded to the University of Kansas for Frontiers: University of Kansas Clinical and Translational Science Institute (# UL1TR002366). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or CTSA. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects of vitamin C supplementation on oxidative stress and serum paraoxonase/arylesterase activities in patients on long-term hemodialysis

BackgroundOxidative stress increases oxidizability of apolipoprotein-B containing lipoproteins and decreases paraoxonase (PON) activity in hemodialysis (HD) patients and plays an important part in the development of atherosclerotic cardiovascular diseases. In HD patients, plasma ascorbic acid (AA) levels are decreased either due to the loss by hemodialysis membranes or due to malnutrition and contribute to the imbalance of antioxidant defense mechanisms. We hypothesized that long-term ascorbic acid (AA) supplementation recovers oxidizability of lipoproteins in HD patients by reinforcing PON activity. MethodsTwenty-nine adult patients were treated with 100mg and 500mg AA at the end of each HD session thrice a week for two consecutive 16 weeks-periods, respectively. Blood samples were obtained before the first HD session and prior to the first HD sessions following the 100mg AA-supplemented and the 500mg AA-supplemented periods. ResultsPON activities were significantly increased after 100mg (p<0.05) and 500mg AA (p<0.001) supplementation periods compared to the basal level. Apo-B lipoprotein oxidizability (Δ-MDA) was significantly decreased after 500mg AA supplementation compared to both basal (p<0.05) and 100mg AA supplementation periods (p<0.05). Plasma AA concentrations were negatively correlated with Δ-MDA levels (R=−0.327; p<0.01). ConclusionOur results suggest that long-term parenteral 500mg AA supplementation improves PON activity alleviating apo B-containing lipoproteins oxidizability in HD patients.

α-Tocopherol Pharmacokinetics in Adults with Cystic Fibrosis: Benefits of Supplemental Vitamin C Administration.

Background: Numerous abnormalities in cystic fibrosis (CF) could influence tocopherol absorption, transportation, storage, metabolism and excretion. We hypothesized that the oxidative distress due to inflammation in CF increases vitamin E utilization, which could be positively influenced by supplemental vitamin C administration. Methods: Immediately before and after receiving vitamin C (500 mg) twice daily for 3.5 weeks, adult CF patients (n = 6) with moderately advanced respiratory tract (RT) disease consumed a standardized breakfast with 30% fat and a capsule containing 50 mg each hexadeuterium (d6)-α- and dideuterium (d2)-γ-tocopheryl acetates. Blood samples were taken frequently up to 72 h; plasma tocopherol pharmacokinetics were determined. During both trials, d6-α- and d2-γ-tocopherols were similarly absorbed and reached similar maximal plasma concentrations ~18–20 h. As predicted, during vitamin C supplementation, the rates of plasma d6-α-tocopherol decline were significantly slower. Conclusions: The vitamin C-induced decrease in the plasma disappearance rate of α-tocopherol suggests that vitamin C recycled α-tocopherol, thereby augmenting its concentrations. We conclude that some attention should be paid to plasma ascorbic acid concentrations in CF patients, particularly to those individuals with more advanced RT inflammatory disease and including those with severe exacerbations.

Plasma ascorbic acid, antioxidant capacity, and reactive oxygen species in healthy foals.

To describe ascorbic acid (AA) concentrations, plasma antioxidant capacity (PAC) and markers of oxidative stress, as measured by derivatives of reactive oxygen metabolites (dROMs), in healthy foals at birth and during the first month of life. Venous blood samples were collected from healthy Standardbred (n = 13) and Quarter Horse (n = 10) foals. Plasma AA, PAC, and dROMs were assessed at 3 to 12 hours, 3 days, and 1, 2, and 4 weeks of age. AA was measured via high-performance liquid chromatography. PAC and dROMs were measured with a free radical analytical system. Comparisons of AA, PAC, and dROMs at different time points were assessed. Mean ± standard deviation AA concentrations at 3 to 12 hours (44.7 ± 19.6 μmol/L; P ≤ .01), 1 (48.6 ± 22.5 μmol/L; P ≤ .001), and 2 weeks (41.8 ± 15.8 μmol/L; P ≤ .001) were higher than at 4 weeks of age (28.5 ± 12.7 μmol/L). Both PAC and dROMs significantly increased at different time points compared to 3 to 12 hours of age. Healthy foals have higher plasma AA concentrations shortly after birth, which then gradually decrease throughout the first month of life, suggesting that AA may represent a key antioxidant in the postnatal period. The concurrent increase in PAC and dROMs suggests that dynamic development of oxidative balance occurs after birth in foals. Development of AA, PAC, and dROM reference ranges in healthy foals could be used to guide therapeutic interventions and monitor during disease states characterized by increased oxidative stress.

Easy-to-Use HPLC Method to Measure Intracellular Ascorbic Acid Levels in Human Peripheral Blood Mononuclear Cells and in Plasma

Given the growing interest in ascorbic acid (AA), there is a need for a reliable and reproducible method to measure AA status in the human body. Serum AA concentrations do not correlate well with tissue levels, but AA levels in leukocytes do. However, a standard method for clinical application is lacking. This present study describes a method to measure AA in the peripheral blood mononuclear cells (PBMCs) with hydrophilic interaction liquid chromatography (HILIC). The method can also be used in plasma and other leukocyte subsets. The measurements of AA in PBMCs and plasma were performed with HPLC with HILIC separation and UV detection. The sample preparation involved the isolation of PBMCs and lysis and precipitation with acetonitrile. European Medicine Agency guidelines for bioanalytic method validation were followed for the evaluation. A highly precise execution of the method was found with intra- and inter-assay variations at a maximum of 7.8%. In 40 healthy donors, a mean intracellular AA concentration of 7.9 microgram/108 cells was found in PBMCs. A correlation between plasma and PBMC AA concentration was not present (r = 0.22). In conclusion, we developed a convenient, reliable, and reproducible method for the quantitative determination of AA within PBMCs and plasma from human blood.

Effects of vitamin C supplementation on oxidative stress and serum paraoxonase/arylesterase activities in patients on long-term hemodialysis

BackgroundOxidative stress increases oxidizability of apolipoprotein-B containing lipoproteins and decreases paraoxonase (PON) activity in hemodialysis (HD) patients and plays an important part in the development of atherosclerotic cardiovascular diseases. In HD patients, plasma ascorbic acid (AA) levels are decreased either due to the loss by hemodialysis membranes or due to malnutrition and contribute to the imbalance of antioxidant defense mechanisms. We hypothesized that long-term ascorbic acid (AA) supplementation recovers oxidizability of lipoproteins in HD patients by reinforcing PON activity. MethodsTwenty-nine adult patients were treated with 100mg and 500mg AA at the end of each HD session thrice a week for two consecutive 16 weeks-periods, respectively. Blood samples were obtained before the first HD session and prior to the first HD sessions following the 100mg AA-supplemented and the 500mg AA-supplemented periods. ResultsPON activities were significantly increased after 100mg (p<0.05) and 500mg AA (p<0.001) supplementation periods compared to the basal level. Apo-B lipoprotein oxidizability (Δ-MDA) was significantly decreased after 500mg AA supplementation compared to both basal (p<0.05) and 100mg AA supplementation periods (p<0.05). Plasma AA concentrations were negatively correlated with Δ-MDA levels (R=−0.327; p<0.01). ConclusionOur results suggest that long-term parenteral 500mg AA supplementation improves PON activity alleviating apo B-containing lipoproteins oxidizability in HD patients.

Two Faces of Vitamin C in Hemodialysis Patients: Relation to Oxidative Stress and Inflammation.

Hemodialysis (HD) is the most common method of renal replacement therapy. Besides toxins, it eliminates nutrients from the circulation, such as ascorbic acid (AA). HD-patients present AA deficiency more often than representatives of the general population, also due to dietary restrictions. This condition aggravates oxidative stress and inflammation related to uremia and extracorporeal circulation and increases cardiovascular risk followed by mortality. Supplementation of AA seems to be a promising approach in the treatment of hemodialysis patients. Many successful interventions restored plasma AA concentration in HD patients by enteral or intravenous supplementation, concomitantly inhibiting oxidative stress and inflammation. A significant number of studies reported opposite, serious pro-oxidant effects of AA. In this narrative review, we present studies, commenting on their limitations; on AA plasma or serum concentration and the influence of its supplementation on protein and lipid peroxidation, DNA damage, reactive oxygen species generation, paraoxonase activity, advanced glycation endproducts, and C-reactive protein (CRP) concentration. Moreover, in terms of safety, the possible development of oxalosis in HD patients regarding the intravenous or enteral route of AA administration is discussed. Unequivocal clinical results of recent studies on hemodialysis patients are displayed.

Effects of administration of ascorbic acid and low-dose hydrocortisone after infusion of sublethal doses of lipopolysaccharide to horses.

BackgroundSepsis is associated with ascorbic acid (AA) depletion and critical illness‐related corticosteroid insufficiency (CIRCI) in humans.HypothesesIntravenous infusion of lipopolysaccharide (LPS) would (a) decrease endogneous AA concentrations, (b) induce CIRCI and (c) administration of a combination of AA and hydrocortisone (HC) would have decreased indices of inflammation compared to either drug alone.AnimalsThirty‐two healthy horses.MethodsRandomized placebo‐controlled experimental trial. Horses were assigned to 1 of 4 groups (saline, AA and HC, AA only, or HC only). Treatments were administered 1 hour after completion of LPS infusion. Clinical signs, clinicopathological variables, pro‐inflammatory cytokine gene expression and production, and plasma AA concentrations were assessed at various time points. Serum cortisol concentrations and ACTH stimulation tests were used to detect CIRCI.ResultsThere was no effect of drug on clinical signs or pro‐inflammatory cytokine gene expression or production compared to controls at any time point. Administration of AA was associated with higher blood neutrophil counts 6 hours after LPS infusion (11.01 ± 1.02 K/μl) compared to other groups (8.99 ± 0.94 K/μL; P < .009). Adminstration of HC was associated with higher blood neutrophil counts 12 hours after LPS infusion (10.40 ± 0.75 K/μl) compared to other groups (6.88 ± 0.68 K/μl; P < .001). Serum cortisol increased from 5.11 ± 1.48 μg/dL before LPS administration to 9.59 ± 1.83 μg/dL 1 h after completion of LPS infusion (T1) without an effect of treatment (P = 0.59).Conclusions and Clinical ImportanceAscorbic acid and HC appeared to protect against LPS‐induced neutrophil depletion and could be considered as adjunctive therapy in horses with endotoxemia.

Plasma Cortisol, Aldosterone, and Ascorbic Acid Concentrations in Patients with Septic Shock Do Not Predict Treatment Effect of Hydrocortisone on Mortality. A Nested Cohort Study.

Rationale: Whether biomarkers can identify subgroups of patients with septic shock with differential treatment responses to hydrocortisone is unknown.Objectives: To determine if there is heterogeneity in effect for hydrocortisone on mortality, shock resolution, and other clinical outcomes based on baseline cortisol, aldosterone, and ascorbic acid concentrations.Methods: From May 2014 to April 2017, we obtained serum samples from 529 patients with septic shock from 22 ICUs in Australia and New Zealand.Measurements and Main Results: There were no significant interactions between the association with 90-day mortality and treatment with either hydrocortisone or placebo for total cortisol (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.02-1.16 vs. OR, 1.07; 95% CI, 1.00-1.13; P = 0.70), free cortisol (OR, 1.20; 95% CI, 1.04-1.38 vs. OR, 1.16; 95% CI, 1.02-1.32; P = 0.75), aldosterone (OR, 1.01; 95% CI, 0.97-1.05 vs. OR, 1.01; 95% CI, 0.98-1.04; P = 0.99), or ascorbic acid (OR, 1.11; 95% CI, 0.89-1.39 vs. OR, 1.05; 95% CI, 0.91-1.22; P = 0.70), respectively. Similar results were observed for the association with shock resolution. Elevated free cortisol was significantly associated with 90-day mortality (OR, 1.13; 95% CI, 1.00-1.27; P = 0.04), but total cortisol, aldosterone, and ascorbic acid were not.Conclusions: In patients with septic shock, there was no heterogeneity in effect of adjunctive hydrocortisone on mortality, shock resolution, or other clinical outcomes based on cortisol, aldosterone, and ascorbic acid concentrations. Plasma aldosterone and ascorbic acid concentrations are not associated with outcome.

Quantification of Plasma and Leukocyte Vitamin C by High Performance Liquid Chromatography with Mass Spectrometric Detection

In the present study a high performance liquid chromatographic–mass spectrometric (LC–MS) method was developed for the measurement of ascorbic acid in human plasma and white blood cells. Special attention was paid to the known difficulties of ascorbic acid stability, and a plasma sample preparation method was developed, accordingly. The novel objective of this work was to focus on the determination of plasma ascorbic acid concentrations considering the necessity of accurate determination for further clinical studies related to scurvy induced by various pathological conditions. The presented study describes in detail a validated LC–MS method with adequate accuracy and precision for quantitative determination of ascorbic acid in human plasma. The method was tested on human plasma and leukocyte samples.

Post-transplantation plasma malondialdehyde is associated with cardiovascular mortality in renal transplant recipients: a prospective cohort study.

BackgroundIn renal transplant recipients (RTRs), cardiovascular mortality is the most common cause of long-term renal graft loss. Oxidative stress (OS) has been associated with cardiovascular disease and is known to be enhanced in RTRs. We aimed to prospectively investigate whether the concentration of the OS biomarker malondialdehyde (MDA) is associated with long-term risk of cardiovascular mortality in a large cohort of RTRs.MethodsThe plasma MDA concentration was measured using the thiobarbituric acid reaction assay in 604 extensively phenotyped RTRs with a functioning allograft for ≥1 year. The association between MDA and cardiovascular mortality was assessed using Cox proportional hazard regression analyses in the overall cohort and within subgroups according to significant effect modifiers.ResultsMedian circulating MDA concentration at baseline was 5.38 [interquartile range (IQR) 4.31–6.45] μmol/L. During a follow-up period of 6.4 (IQR 5.6–6.8) years, 110 (18%) RTRs died, with 40% of deaths due to cardiovascular causes. MDA concentration was significantly associated with the risk for cardiovascular mortality {hazard ratio [HR] 1.31 [95% confidence interval (CI) 1.03–1.67] per 1-SD increment}, independent of adjustment for potential confounders, including renal function, immunosuppressive therapy, smoking status and blood pressure. The association between MDA concentration and the risk for cardiovascular mortality was stronger in RTRs with relatively lower plasma ascorbic acid concentrations [≤42.5 µmol/L; HR 1.79 (95% CI 1.30–2.48) per 1-SD increment] or relatively lower estimated glomerular filtration rates [≤45 mL/min/1.73 m2; HR 2.09 (95% CI 1.45–3.00) per 1-SD increment].ConclusionsCirculating MDA concentration is independently associated with long-term risk for cardiovascular mortality, particularly in RTRs with relatively lower ascorbic acid concentrations or renal function. Further studies are warranted to elucidate whether OS-targeted interventions could decrease cardiovascular mortality in RTRs.

Influence of Ascorbic Acid on the Structure and Function of Alpha-2- macroglobulin: Investigations using Spectroscopic and Thermodynamic Techniques.

Ascorbic acid is a classic dietary antioxidant which plays an important role in the body of human beings. It is commonly found in various foods as well as taken as dietary supplement. The plasma ascorbic acid concentration may range from low, as in chronic or acute oxidative stress to high if delivered intravenously during cancer treatment. Sheep alpha-2- macroglobulin (α2M), a human α2M homologue is a large tetrameric glycoprotein of 630 kDa with antiproteinase activity, found in sheep's blood. In the present study, the interaction of ascorbic acid with alpha-2-macroglobulin was explored in the presence of visible light by utilizing various spectroscopic techniques and isothermal titration calorimetry (ITC). UV-vis and fluorescence spectroscopy suggests the formation of a complex between ascorbic acid and α2M apparent by increased absorbance and decreased fluorescence. Secondary structural changes in the α2M were investigated by CD and FT-IR spectroscopy. Our findings suggest the induction of subtle conformational changes in α2M induced by ascorbic acid. Thermodynamics signatures of ascorbic acid and α2M interaction indicate that the binding is an enthalpy-driven process. It is possible that ascorbic acid binds and compromises antiproteinase activity of α2M by inducing changes in the secondary structure of the protein.

Plasma ascorbic acid and the risk of islet autoimmunity and type 1 diabetes: the TEDDY study

Aims/hypothesisWe studied the association of plasma ascorbic acid with the risk of developing islet autoimmunity and type 1 diabetes and examined whether SNPs in vitamin C transport genes modify these associations. Furthermore, we aimed to determine whether the SNPs themselves are associated with the risk of islet autoimmunity or type 1 diabetes.MethodsWe used a risk set sampled nested case–control design within an ongoing international multicentre observational study: The Environmental Determinants of Diabetes in the Young (TEDDY). The TEDDY study followed children with increased genetic risk from birth to endpoints of islet autoantibodies (350 cases, 974 controls) and type 1 diabetes (102 cases, 282 controls) in six clinical centres. Control participants were matched for family history of type 1 diabetes, clinical centre and sex. Plasma ascorbic acid concentration was measured at ages 6 and 12 months and then annually up to age 6 years. SNPs in vitamin C transport genes were genotyped using the ImmunoChip custom microarray. Comparisons were adjusted for HLA genotypes and for background population stratification.ResultsChildhood plasma ascorbic acid (mean ± SD 10.76 ± 3.54 mg/l in controls) was inversely associated with islet autoimmunity risk (adjusted OR 0.96 [95% CI 0.92, 0.99] per +1 mg/l), particularly islet autoimmunity, starting with insulin autoantibodies (OR 0.94 [95% CI 0.88, 0.99]), but not with type 1 diabetes risk (OR 0.93 [95% Cl 0.86, 1.02]). The SLC2A2 rs5400 SNP was associated with increased risk of type 1 diabetes (OR 1.77 [95% CI 1.12, 2.80]), independent of plasma ascorbic acid (OR 0.92 [95% CI 0.84, 1.00]).Conclusions/interpretationHigher plasma ascorbic acid levels may protect against islet autoimmunity in children genetically at risk for type 1 diabetes. Further studies are warranted to confirm these findings.Data availabilityThe datasets generated and analysed during the current study will be made available in the NIDDK Central Repository at https://www.niddkrepository.org/studies/teddy.

High dietary vitamin C intake reduces glucocorticoid-induced immunosuppression and measures of oxidative stress in vitamin C-deficient senescence marker protein 30 knockout mice.

Vitamin C (VC) is a vital micronutrient for humans and some other mammals and also has antioxidant activity. Stress-induced elevation of glucocorticoid production is well known to cause immunosuppression. The present study evaluated the effect of high VC intake on glucocorticoid-induced immune changes in mice. Senescence marker protein 30 knockout mice with genetic VC deficiency were fed a diet containing the recommended VC content (20 mg/kg per d; 0·02 %VC group) or a high VC content (200 mg/kg per d; 0·2 %VC group) for 2 months, then dexamethasone was given by intraperitoneal injection. After administration of dexamethasone, the plasma ascorbic acid concentration decreased significantly in the 0·02 %VC group and was unchanged in wild-type C57BL/6 mice on a VC-deficient diet (wild-type group), while it was significantly higher in the 0·2 %VC group compared with the other two groups. In the 0·02 %VC and wild-type groups, dexamethasone caused a significant decrease in the cluster of differentiation (CD)4+ and CD8+ T cells among splenocytes as well as a significant decrease in IL-2, IL-12p40 and interferon-γ protein production by splenocytes and a significant decrease in T-cell proliferation among splenocytes. In the 0·2 %VC group, these dexamethasone-induced immunosuppression improved when compared with the other two groups. In addition, reduction in the intracellular levels of ascorbic acid, superoxide dismutase and glutathione in splenocytes by dexamethasone as well as elevation in thiobarbituric acid-reactive substances were significantly suppressed in the 0·2 %VC group. These findings suggest that high dietary VC intake reduces glucocorticoid-induced T-cell dysfunction by maintaining intracellular antioxidant activity.

Changes in the Selected Antioxidant Defense Parameters in the Blood of Patients after High Resolution Computed Tomography.

Ionizing radiation generated during high resolution computed tomography (HRCT) scanning may have an indirect effect on the mechanisms regulating the oxidative-antioxidant balance in the human body, which is one of the necessary factors ensuring the maintenance of its homeostasis. The aim of the study was to analyze the response of antioxidant systems through the determination of the antioxidant markers in the blood of patients exposed to oxidative stress resulting from the routine HRCT examination of the chest. Blood of 35 people aged 60.77 ± 10.81 taken before and at four time points after the examination constituted the test material. The determination of the total antioxidant capacity expressed as ferric reducing ability of plasma (FRAP) and ferric reducing antioxidant activity and ascorbic acid concentration (FRASC) were performed together with an examination of catalase activity and the concentration of the reduced glutathione. The organism’s response to ionizing radiation was associated with a significant decrease in the antioxidant markers’ levels at all time-points and showed a significant negative correlation depending on the radiation dose. Visible down-regulation of these markers is a response to increased oxidative stress. In light of the obtained results, the measurement of the selected markers of antioxidant defense may be a useful parameter of oxidative stress caused by ionizing radiation.

Reduced aqueous humour ascorbic-acid concentration in women with smaller anterior chamber depth

Short anterior chamber depth (ACD) is considered a risk factor of endothelial-cell loss after phacoemulsification. However, whether it is an independent risk factor or not remains controversial. We investigated the relationship between ascorbic acid (AA) concentrations in the aqueous humour (AqH) and ACD. We analysed 165 AqH samples of 97 patients (42 men and 55 women) who underwent small incision cataract surgery. AqH and plasma AA concentrations were measured using a high-performance liquid chromatography - electrochemical detection method. Patient characteristics were compared between and within the sexes. As a result, age and ACD were significantly correlated with AqH AA concentrations (r = −0.206, P = 0.045; r = 0.339, P < 0.001) only in women. Moreover, plasma AA concentrations were significantly correlated with AqH AA concentrations (r = 0.420, P < 0.001; r = 0.316, P = 0.002) both in men and women. After adjusting for confounding factors (age and plasma AA concentrations), ACD was significantly and positively correlated with AqH AA concentrations (partial.r = 0.275, P = 0.009) only in women. In conclusion, AqH AA concentrations were reduced in women with smaller ACD. This may suggest that women with short ACD could be more susceptible to oxidative damage.