ascorbic-acid and Pulmonary-Disease--Chronic-Obstructive

Vitamin C is used in modern medicine supplements for treatment of various disorders associated with oxidative stress, inflammation and immune dysregulation. In this review article, experimental and clinical results regarding the effects of vitamin C on respiratory immunologic, and allergic diseases are reviewed. Various databases and appropriate keywords are used to search the effect of vitamin C on respiratory diseases until the end of May 2022. Books, theses and articles were included. These studies assessed the effects of vitamin C on respiratory disorders including asthma, chronic obstructive pulmonary disease (COPD), lung infection and lung cancer. Vitamin C showed relaxant effect on tracheal smooth muscle via various mechanisms. The preventive effects of vitamin C were mediated by antioxidant, immunomodulatory and anti-inflammatory mechanisms in the experimental animal models of different respiratory diseases. Some clinical studies also indicated the effect of vitamin C on lung cancer and lung infections. Therefore, vitamin C could be used a preventive and/or relieving therapy in respiratory diseases.

Topics: Animals; Ascorbic Acid; Asthma; Lung Neoplasms; Pneumonia; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Diseases; Vitamins

Currently, an increasing amount of evidence supports the notion that vitamins C, D and E, carotenoids, and omega-3 fatty acids may protect against the progression of chronic respiratory diseases. Although chronic obstructive pulmonary disease (COPD) primarily affects the lung, it is often accompanied by extrapulmonary manifestations such as weight loss and malnutrition, skeletal muscle dysfunction, and an excess of harmful oxidants, which can lead to a decline in quality of life and possible death. Recently, the role of various vitamins, minerals, and antioxidants in mitigating the effects of environmental pollution and smoking has received significant attention. Therefore, this review evaluates the most relevant and up-to-date evidence on this topic. We conducted a literature review between 15 May 2018 and 15 May 2023, using the electronic database PubMed. Our search keywords included COPD, chronic obstructive pulmonary disease, FEV

Topics: Antioxidants; Ascorbic Acid; Dietary Supplements; Humans; Minerals; Pulmonary Disease, Chronic Obstructive; Vitamin A; Vitamin B Complex; Vitamin K

The development of effective nutritional supports for patients with chronic obstructive pulmonary diseases (COPD) is still challenging. This study was conducted to investigate the efficacy of daily consumption of fortified whey on inflammation, muscle mass, functionality, and quality of life in patients with moderate-to-severe COPD.. A single-blind, randomized trial study was performed on patients with COPD (n = 46). Participants in the intervention group (n = 23) daily received 250 ml of whey beverage fortified with magnesium and vitamin C for 8 weeks. Any changes in inflammatory cytokines (including interleukin- 6 (IL-6) and tumor necrosis factor (TNFα)) were the primary outcomes and the secondary outcomes were fat-free mass, handgrip strength, malnutrition, glutathione and malondialdehyde serum concentrations, and health-related quality of life (HRQoL). Body composition and muscle strength were measured by Bioelectrical Impedance Analysis (BIA) and hydraulic hand dynamometer, respectively. Fat-free mass index (FFMI) was also calculated.. At the end of the study, 44 patients were analyzed. There were significant decreases in IL-6 concentrations in the intervention group compared to the control group. Also, FFMI, body protein, and handgrip strength increased significantly in the intervention group with significant changes between two groups. Moreover, improvement in health-related quality of life was observed in the intervention group compared to the control group. There were no significant changes in other study variables.. This novel nutritional intervention decreased inflammatory cytokines levels, improved indices of skeletal muscle mass and muscle strength, and ultimately, increased HRQoL in patients with moderate-to-severe COPD. Thus, it is suggested to do further studies to assess the effects of nutrition intervention on COPD progression.. IR.SUMS.REC.1396.85 ( https://www.irct.ir/ ).

Topics: Aged; Ascorbic Acid; Beverages; Female; Food, Fortified; Hand Strength; Humans; Magnesium; Male; Middle Aged; Muscle Strength; Muscle, Skeletal; Pulmonary Disease, Chronic Obstructive; Single-Blind Method; Whey

Antioxidant therapy has a potential to be introduced as therapeutic modality for chronic obstructive pulmonary disease (COPD) patients. This study aimed to determine the effect of antioxidant supplementation [ascorbic acid and N-Acetylcysteine (NAC)] on nutritional and antioxidant status in male COPD patients. A parallel and single blind randomised controlled clinical trial (RCT) was conducted at two medical centers in Kuala Lumpur, Malaysia. Seventy-nine subjects were recruited and randomly divided into four trial arms (i.e., NAC, vitamin C, NAC+vitamin C and control groups) for six mo. The primary outcome was changes in body mass index by estimating power of 90% and significance level of p<0.05. Repeated Measure ANOVA showed that there was a significant interaction effect on BMI (p=0.046) and carbohydrate intake (p=0.030), especially in the NAC group. Plasma glutathione (GSH) increased significantly in all intervention groups, especially in vitamin C (p=0.005). A single supplementation of NAC or vitamin C improved nutritional and antioxidant status of subjects.

Topics: Acetylcysteine; Adult; Aged; Antioxidants; Ascorbic Acid; Body Mass Index; Dietary Carbohydrates; Dietary Supplements; Glutathione; Humans; Malaysia; Male; Middle Aged; Nutritional Status; Pulmonary Disease, Chronic Obstructive; Single-Blind Method; Treatment Outcome; Vitamin A

Acute hypoxia increases cerebral blood flow (CBF) and ventilation (V̇e). It is unknown if these responses are impacted with normal aging, or in patients with enhanced oxidative stress, such as (COPD). The purpose of the study was to 1) investigate the effects of aging and COPD on the cerebrovascular and ventilatory responses to acute hypoxia, and 2) to assess the effect of vitamin C on these responses during hypoxia. In 12 Younger, 14 Older, and 12 COPD, we measured peak cerebral blood flow velocity (V̄p; index of CBF), and V̇e during two 5-min periods of acute isocapnic hypoxia, under conditions of 1) saline-sham; and 2) intravenous vitamin C. Antioxidants [vitamin C, superoxide dismutase (SOD), glutathione peroxidase, and catalase], oxidative stress [malondialdehyde (MDA) and advanced protein oxidation product], and nitric oxide metabolism end products (NOx) were measured in plasma. Following the administration of vitamin C, vitamin C, SOD, catalase, and MDA increased, while NOx decreased. V̄p and V̇e sensitivity to hypoxia was reduced in Older by ∼60% (P < 0.02). COPD patients exhibited similar V̄p and V̇e responses to Older (P > 0.05). Vitamin C did not have an effect on the hypoxic V̇e response but selectively decreased the V̄p sensitivity in Younger only. These findings suggest a reduced integrative reflex (i.e., cerebrovascular and ventilatory) during acute hypoxemia in healthy older adults. Vitamin C does not appear to have a large influence on the cerebrovascular or ventilatory responses during acute hypoxia.

Topics: Adaptation, Physiological; Administration, Intravenous; Adult; Age Factors; Aged; Aging; Alberta; Antioxidants; Ascorbic Acid; Biomarkers; Blood Flow Velocity; Cerebrovascular Circulation; Female; Humans; Hypoxia; Lung; Male; Middle Aged; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Pulmonary Ventilation; Reactive Oxygen Species; Time Factors; Treatment Outcome; Young Adult

Oxidative stress may contribute to exercise intolerance in patients with chronic obstructive pulmonary disease (COPD). This study sought to determine the effect of an acute oral antioxidant cocktail (AOC, vitamins C and E, and alpha-lipoic acid) on skeletal muscle function during dynamic quadriceps exercise in COPD.. Ten patients with COPD performed knee extensor exercise to exhaustion and isotime trials after either the AOC or placebo (PL). Pre- to postexercise changes in quadriceps maximal voluntary contractions and potentiated twitch forces (Q(tw,pot)) quantified quadriceps fatigue.. Under PL conditions, the plasma electron paramagnetic resonance (EPR) spectroscopy signal was inversely correlated with the forced expiratory volume in 1 s to forced vital capacity ratio (FEV1/FVC), an index of lung dysfunction (r = -0.61, P = 0.02), and maximal voluntary contraction force (r = -0.56, P = 0.04). AOC consumption increased plasma ascorbate levels (10.1 ± 2.2 to 24.1 ± 3.8 μg · mL(-1), P < 0.05) and attenuated the area under the curve of the EPR spectroscopy free radical signal (11.6 ± 3.7 to 4.8 ± 2.2 AU, P < 0.05), but it did not alter the endurance time or quadriceps fatigue. The ability of the AOC to decrease the EPR spectroscopy signal, however, was prominent in those with high basal free radicals (n = 5, PL, 19.7 ± 5.8, to AOC, 5.8 ± 4.5 AU; P < 0.05) with minimal effects in those with low levels (n = 5, PL, 1.6 ± 0.5, to AOC, 3.4 ± 1.1 AU).. These data document a relation between directly measured free radicals and lung dysfunction and the ability of the AOC to decrease oxidative stress in COPD. Acute amelioration of free radicals, however, does not appear to affect dynamic quadriceps exercise performance.

Topics: Administration, Oral; Aged; Antioxidants; Ascorbic Acid; Biomarkers; Drug Administration Schedule; Drug Combinations; Electromyography; Electron Spin Resonance Spectroscopy; Exercise Test; Female; Free Radicals; Humans; Male; Middle Aged; Muscle Fatigue; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Quadriceps Muscle; Respiratory Function Tests; Single-Blind Method; Thioctic Acid; Treatment Outcome; Vitamin E

Upper respiratory tract infections (URTI) frequently cause exacerbations of chronic-obstructive pulmonary disease (COPD). Stimulation of the innate immune system may provide an early defence against such infections. The objective of this study was to determine whether Echinacea purpurea (EP) along with micronutrients may alleviate COPD exacerbations caused by acute URTI.. This was a double-blind, randomized, placebo-controlled trial in COPD patients with acute URTI. Patients were given ciprofloxacin for 7 days and additionally one tablet per day of EP, of EP along with zinc, selenium and ascorbic acid (EP+), or of placebo until day 14. Serum levels of TNF α and interleukins 1β, 6 and 10 were measured before and after treatment. Until week 4 post-end of treatment, all patients had to daily report on COPD symptoms in diaries.. In total, 108 mostly male patients with a mean age of 65·8 years (40-81 years) were enrolled. Patients of the three treatment arms did not vary significantly in baseline characteristics. EP+, but not EP resulted in significantly less severe and shorter exacerbation episodes following URTI as compared with placebo suggesting a synergistic effect of Echinacea and micronutrients. Large variations in biomarkers in-between and within groups were unrelated to treatment. Study medication was safe and well tolerated with overall 15 adverse events one of which was serious. Among those, sleeping disorders were most frequent and likely related to the underlying disease.. The combination of EP, zinc, selenium and vitamin C may alleviate exacerbation symptoms caused by URTI in COPD. Further studies are warranted to investigate the interactions among Echinacea, zinc, selenium and vitamin C.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Ascorbic Acid; Ciprofloxacin; Disease Progression; Double-Blind Method; Drug Synergism; Echinacea; Female; Herb-Drug Interactions; Humans; Immunity, Innate; Male; Micronutrients; Middle Aged; Phytotherapy; Placebos; Plant Extracts; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections; Selenium; Treatment Outcome; Vitamins; Zinc

The purpose of this study was to determine whether vitamin E or vitamin C supplementation alters the DNA damage of whole blood white blood cells (WBC) in patients with chronic obstructive pulmonary disease (COPD). Thirty-five patients with stable COPD were recruited in this randomized and placebo-controlled study. Patients were randomly assigned to placebo (n = 8), 400 mg/day vitamin E (E400, n = 9), 200 mg/day vitamin E (E200, n = 9), or 250 mg/day vitamin C (C250, n = 9) for 12 weeks. The results showed that vitamin E or C supplementation did not significantly change the mean level of endogenous DNA breakages. Whereas, after 12 weeks of vitamin supplementation, the H2O2-induced DNA breakages were significantly suppressed by 45%, 59%, and 52%, respectively, in E400, E250 and C250 groups (p < 0.05). In addition, neither the level of thiobarbituric acid-reactive substances (TBARS) nor spirometric parameters were significantly changed after 12 weeks of supplementation. In conclusion, vitamin E or C supplementation for 12 weeks may improve the resistance of DNA in whole blood WBC against oxidative challenge, although more research is needed to demonstrate the beneficial effect on slowing the decline of lung function in patients with COPD.

Topics: Aged; Aged, 80 and over; Ascorbic Acid; Comet Assay; Dietary Supplements; DNA Damage; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Statistics, Nonparametric; Thiobarbituric Acid Reactive Substances; Vital Capacity; Vitamin E

People with chronic obstructive pulmonary disease (COPD) undergo oxidative damage during exacerbations that continues in stable periods, gradually contributing to pathogenesis. Since serum concentrations of antioxidant vitamins in COPD patients have been little investigated, we studied antioxidant vitamin and lipid peroxidation concentrations in patients during acute exacerbations and stable periods.. We prospectively recruited 24 patients with COPD (mean age 51.8 yr, standard deviation [SD] 6.7 yr) in acute exacerbation. Serum concentrations of vitamins A, C and E and malondialdehyde (MDA) were determined before treatment and during stable periods with high-performance liquid chromatography, and in 23 healthy controls (mean age 48.0 yr; SD 5.9 yr) with established methods.. The mean vitamin A level in patients during acute exacerbation was 0.8 (SD 0.2) microg/mL, rising to 1.0 (SD 0.2) microg/mL during stable periods, both significantly less than that of controls (1.0 [SD 0.2] microg/mL; p <0.01); vitamin C, 5.0 (SD 2.2) microg/mL acute and 7.5 (SD 2.7) stable, neither significantly differing from the mean level in controls (8.6 [SD 1.8] microg/mL; p > 0.05); vitamin E, 10.0 (SD 2.4) microg/mL acute and 11.1 (SD 2.6) stable, both lower than in controls (11.0 [SD 2.86] microg/mL; p <0.01); and MDA, 2.4 (SD 0.7) nmol/mL acute and 1.2 (SD 0.4) stable, both higher than in controls (0.9 [SD 0.2] nmol/mL; p< 0.01).. Whereas patients with COPD undergo increased oxidative stress during exacerbations and in stable periods, their serum concentrations of antioxidant vitamins A and E decrease during exacerbations. Our findings suggest that the administration of vitamins A and E may be beneficial in the prevention and treatment of the harmful effects of COPD.

Topics: Antioxidants; Ascorbic Acid; Biomarkers; Blood Gas Analysis; Female; Humans; Lung Volume Measurements; Male; Malondialdehyde; Middle Aged; Pulmonary Disease, Chronic Obstructive; Vitamin A; Vitamin E

Several nutrients have been suggested to protect against airway destruction

Topics: Adult; Age Factors; Aged; Ascorbic Acid; Diet; Dietary Carbohydrates; Dietary Fiber; Dietary Proteins; Female; Forced Expiratory Volume; Humans; Linear Models; Male; Middle Aged; Multivariate Analysis; Niacin; Pulmonary Disease, Chronic Obstructive; Republic of Korea; Riboflavin; Severity of Illness Index; Sex Factors; Thiamine; Vitamin A; Vitamins

The increased oxidative stress in chronic obstructive pulmonary disease (COPD) patients is the result of increased inhaled oxidants, generated by various cells of the airways.. The investigation included measurements of malondiadehyde (MDA), uric acid, ascorbic acid, and matrix metalloproteinase-12 (MMP-12) in COPD patient. We also performed genetic analysis for protein-protein interaction (PPI) network.. The study was conducted on healthy subjects with normal lung function (NS, 14 subjects) and 28 patients (Global Initiative for Chronic Obstructive Lung Disease (Gold) 1 and Gold 2) with COPD.. There was significant (p < .001) increase in MMP-12, MDA and uric acid levels as compared to healthy controls. A significant (p < .001) decline in ascorbic acid level was observed in COPD patients. The PPI was found to be 0.833 which indicated that proteins present in COPD are linked.. This study suggests oxidative stress plays an important role in COPD and the PPI provide indication that proteins present in COPD are linked.

Topics: Ascorbic Acid; Case-Control Studies; Female; Gene Expression Regulation, Enzymologic; Humans; Male; Malondialdehyde; Matrix Metalloproteinase 12; Middle Aged; Oxidative Stress; Protein Interaction Maps; Pulmonary Disease, Chronic Obstructive; Uric Acid

The proteolytic autophagy pathway is enhanced in the lower limb muscles of patients with chronic obstructive pulmonary disease (COPD). Reactive oxygen species (ROS) have been shown to regulate autophagy in the skeletal muscles, but the role of oxidative stress in the muscle autophagy of patients with COPD is unknown. We used cultured myoblasts and myotubes from the quadriceps of eight healthy subjects and twelve patients with COPD (FEV1% predicted: 102.0% and 32.0%, respectively; p < 0.0001). We compared the autophagosome formation, the expression of autophagy markers, and the autophagic flux in healthy subjects and the patients with COPD, and we evaluated the effects of the 3-methyladenine (3-MA) autophagy inhibitor on the atrophy of COPD myotubes. Autophagy was also assessed in COPD myotubes treated with an antioxidant molecule, ascorbic acid. Autophagosome formation was increased in COPD myoblasts and myotubes (p = 0.011; p < 0.001), and the LC3 2/LC3 1 ratio (p = 0.002), SQSTM1 mRNA and protein expression (p = 0.023; p = 0.007), BNIP3 expression (p = 0.031), and autophagic flux (p = 0.002) were higher in COPD myoblasts. Inhibition of autophagy with 3-MA increased the COPD myotube diameter (p < 0.001) to a level similar to the diameter of healthy subject myotubes. Treatment of COPD myotubes with ascorbic acid decreased ROS concentration (p < 0.001), ROS-induced protein carbonylation (p = 0.019), the LC3 2/LC3 1 ratio (p = 0.037), the expression of SQSTM1 (p < 0.001) and BNIP3 (p < 0.001), and increased the COPD myotube diameter (p < 0.001). Thus, autophagy signaling is enhanced in cultured COPD muscle cells. Furthermore, the oxidative stress level contributes to the regulation of autophagy, which is involved in the atrophy of COPD myotubes in vitro.

Topics: Adenine; Aged; Ascorbic Acid; Autophagy; Biomarkers; Cells, Cultured; Female; Humans; Male; Microtubule-Associated Proteins; Middle Aged; Muscle Cells; Muscle Fibers, Skeletal; Muscular Atrophy; Myoblasts; Oxidative Stress; Phagosomes; Pulmonary Disease, Chronic Obstructive

Few studies to date have investigated the antioxidant nutrients such as vitamin C (ascorbic acid), vitamin E (α-tocopherol), retinol and carotenoids in plasma from patients with pulmonary disease in Japan. To clarify the role of antioxidant nutrients such as vitamin C, vitamin E, retinol and various carotenoids in plasma of Japanese patients with chronic obstructive lung diseases (COPD), asthma-COPD overlap syndrome (ACOS) and/or bronchial asthma (BA), we compared to healthy elderly controls.. Ascorbic acid (AA), carotenoids (lutein, zeaxanthin, β-cryptoxanthin, α-carotene, β-carotene and lycopene), retinol and α-tocopherol levels in plasma were determined by using a high performance liquid chromatography. Reduced glutathione (GSH), oxidised glutathione (GSSG) in whole blood and urinary 8-OHdG were also determined.. Plasma AA level of COPD subjects was significantly lower than that of healthy elderly people. Conversely, ACOS and BA subjects showed no significant difference from healthy elderly people. Moreover, plasma lycopene and total carotenoid levels and GSH content in blood were significantly lower in COPD subjects than these in healthy elderly people. However, other redox markers such as GSSG, GSH/GSSG ratio and urinary 8-OHdG found no significant differences between COPD, ACOS and BA compared to healthy elderly people.. These results suggested that COPD of Japanese patients may develop partly because of oxidative stress derived from a shortage of antioxidant nutrients, especially of AA and lycopene, as well as GSH while this may not be the case in both ACOS and BA.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Asthma; Biomarkers; Carotenoids; Chromatography, Liquid; Female; Food; Glutathione; Humans; Japan; Lycopene; Male; Middle Aged; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Smoking

Chronic obstructive pulmonary disease (COPD) is associated with vascular dysfunction, possibly related to increased oxidative stress. Exercise hyperemia may similarly be impaired, which could have implications for exercise limitations in COPD. We tested if brachial blood flow (BBF) was reduced during handgrip exercise in COPD and if this response would be improved after vitamin C infusion.. Doppler ultrasound was used to measure brachial blood flow and vascular conductance (BBF and BVC, respectively) during mild, rhythmic handgrip exercise (EX) under conditions of sham-saline and vitamin C. Measures of flow-mediated dilation (FMD) and nitroglycerine-mediated dilation were used to assess endothelial-dependent and independent dilation, respectively. Biomarkers of antioxidants (vitamin C, superoxide dismutase [SOD], catalase), oxidative stress (malondialdehyde [MDA], advanced oxidation protein products [AOPP]), and nitric oxide metabolism (NOx) were measured in blood plasma.. Ten COPD patients with moderate COPD and 10 healthy age-matched controls participated. COPD patients had similar increases in BBF and BVC during EX, compared with controls. Vitamin C was not found to have an effect on blood flow parameters during exercise (P > 0.05). Markers of endothelial-dependent dilation (FMD) and nitroglycerin-mediated dilation were similar between groups at baseline; FMD improved similarly in both groups after vitamin C.. Moderate COPD patients have a preserved BBF response during handgrip exercise and do not exhibit endothelial dysfunction. Despite an increase in endothelial-dependent dilation after vitamin C, BBF remained unchanged, suggesting a limited impact of endothelial-derived NO in determining the blood flow response to handgrip exercise in older individuals. COPD patients of moderate severity, screened for cardiovascular disease, do not exhibit endothelial dysfunction and have similar exercise blood flow responses to healthy controls.

Topics: Aged; Antioxidants; Ascorbic Acid; Brachial Artery; Endothelium, Vascular; Exercise; Female; Hand Strength; Humans; Male; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Regional Blood Flow; Ultrasonography; Vasodilation

Chronic obstructive pulmonary disease (COPD) is one of the most important and prevalent diseases suffered by the elderly. Evidence exists that its onset and severity might be conditioned by antioxidant status. The aim of the present study was to investigate the relationship between antioxidant status and COPD in institutionalised elderly people. In all, 183 elderly people aged >65 years (twenty-one had COPD and 160 healthy controls) were studied. The subjects' diets were investigated via the use of precise individual weighing for 7 d. Body weight, height, and biceps and triceps skinfold thickness were measured, and body fat (kg) and BMI (kg/m2) were calculated. Serum retinol, α-tocopherol, β-carotene and vitamin C levels were determined. Subjects with COPD ate less fruits than healthy controls (117 (sd 52) v. 192 (sd 161) g/d), their coverage of the recommended intake of vitamin C was smaller (150 (sd 45) v. 191 (sd 88) %; note that both exceeded 100 %) and their diets had a lower antioxidant capacity (6558 (sd 2381) v. 9328 (sd 5367) mmol trolox equivalent/d). Those with COPD had lower serum vitamin C and α-tocopherol concentrations than healthy controls (32·4 (sd 15·3) v. 41·5 (sd 14·8) µmol/l and 12·1 (sd 3·2) v. 13·9 (sd 2·8) µmol/l, respectively). In addition, subjects with α-tocopherol <14·1µmol/l (50th percentile) were at 6·43 times greater risk of having COPD than those subjects with ≥14·1µmol/l (OR 6·43; 95 % CI 1·17, 35·24; P<0·05), taking sex, age, use of tobacco, body fat and vitamin E intake as covariables. Subjects with COPD had diets of poorer antioxidant quality, especially with respect to vitamins C and E, compared with healthy controls.

Topics: Aged; Aged, 80 and over; alpha-Tocopherol; Antioxidants; Ascorbic Acid; beta Carotene; Biomarkers; Body Mass Index; Body Weight; Case-Control Studies; Diet; Female; Fruit; Humans; Male; Pulmonary Disease, Chronic Obstructive; Vitamin E

Oxidative stress is thought to be one of the most important mechanisms implicated in the muscle wasting of chronic obstructive pulmonary disease (COPD) patients, but its role has never been demonstrated. We therefore assessed the effects of both pro-oxidant and antioxidant treatments on the oxidative stress levels and atrophic signaling pathway of cultured COPD myotubes. Treatment of cultured COPD myotubes with the pro-oxidant molecule H2O2 resulted in increased ROS production (P = 0.002) and protein carbonylation (P = 0.050), in association with a more pronounced atrophy of the myotubes, as reflected by a reduced diameter (P = 0.003), and the activated expression of atrophic markers MuRF1 and FoxO1 (P = 0.022 and P = 0.030, respectively). Conversely, the antioxidant molecule ascorbic acid induced a reduction in ROS production (P<0.001) and protein carbonylation (P = 0.019), and an increase in the myotube diameter (P<0.001) to a level similar to the diameter of healthy subject myotubes, in association with decreased expression levels of MuRF1, atrogin-1 and FoxO1 (P<0.001, P = 0.002 and P = 0.042, respectively). A significant negative correlation was observed between the variations in myotube diameter and the variations in the expression of MuRF1 after antioxidant treatment (P = 0.047). Moreover, ascorbic acid was able to prevent the H2O2-induced atrophy of COPD myotubes. Last, the proteasome inhibitor MG132 restored the basal atrophy level of the COPD myotubes and also suppressed the H2O2-induced myotube atrophy. These findings demonstrate for the first time the involvement of oxidative stress in the atrophy of COPD peripheral muscle cells in vitro, via the FoxO1/MuRF1/atrogin-1 signaling pathway of the ubiquitin/proteasome system.

Topics: Aged; Antioxidants; Ascorbic Acid; Female; Forkhead Box Protein O1; Humans; Hydrogen Peroxide; Leupeptins; Male; Middle Aged; Muscle Fibers, Skeletal; Muscle Proteins; Muscular Atrophy; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Signal Transduction; SKP Cullin F-Box Protein Ligases; Tripartite Motif Proteins; Ubiquitin-Protein Ligases

Vitamin C, as an antioxidant, has recently been suggested to provide protection against COPD; however, only few national cohort studies have investigated these effects. We aimed to confirm the protective effects of vitamin C against COPD in Korean patients.. We analyzed the data of 3,283 adults aged ≥40 years (representing 23,541,704 subjects) who underwent pulmonary function tests and responded to questionnaires on smoking history and vitamin C intake, with stratification variables and sampling weight designated by the Korea 2012 National Health and Nutrition Examination Survey.. Among all the subjects, 512 (representing 3,459,679 subjects; 15.6%) were diagnosed as having COPD based on pulmonary function test results. Male gender, old age, residence in suburban/rural regions, low household income, low educational level, an occupation in agriculture or fisheries, and heavy smoking were significantly associated with COPD. Low intake of nutrients, including potassium, vitamin A, carotene, retinol, and vitamin C, was significantly associated with COPD. The prevalence of COPD in heavy smokers with the lowest quartile (Q1, <48.50 mg; 63.0%) and low-middle quartile (Q2, 48.50-84.38 mg; 56.4%) of vitamin C intake was significantly higher than that in subjects with the high-middle quartile (Q3, 84.38-141.63 mg; 29.5%) and highest quartile (Q4, >141.63 mg; 32.6%) of vitamin C intake (. This large-scale national study suggests that dietary vitamin C provides protection against COPD, independent of smoking history, in the general Korean population.

Topics: Adult; Aged; Ascorbic Acid; Chi-Square Distribution; Diet; Female; Health Status; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Nutrition Surveys; Odds Ratio; Prevalence; Protective Factors; Pulmonary Disease, Chronic Obstructive; Republic of Korea; Risk Assessment; Risk Factors; Smoking; Time Factors

Oxidative stress (OS) plays a key role in the muscle impairment and exercise capacity of COPD patients. However, the literature reveals that systemic OS markers show great heterogeneity, which may hinder the prescription of effective antioxidant supplementation. This study therefore aimed to identify OS markers imbalance of COPD patients, relative to validated normal reference values, and to investigate the possibility of systemic OS profiles. We measured systemic enzymatic/nonenzymatic antioxidant and lipid peroxidation (LP) levels in 54 stable COPD patients referred for a rehabilitation program. The main systemic antioxidant deficits in these patients concerned vitamins and trace elements. Fully 89% of the COPD patients showed a systemic antioxidant imbalance which may have caused the elevated systemic LP levels in 69% of them. Interestingly, two patient profiles (clusters 3 and 4) had a more elevated increase in LP combined with increased copper and/or decreased vitamin C, GSH, and GPx. Further analysis revealed that the systemic LP level was higher in COPD women and associated with exercise capacity. Our present data therefore support future supplementations with antioxidant vitamins and trace elements to improve exercise capacity, but COPD patients will probably show different positive responses.

Topics: Aged; Ascorbic Acid; Biomarkers; Copper; Exercise; Female; Glutathione; Glutathione Peroxidase; Humans; Lipid Peroxidation; Male; Middle Aged; Oxidative Stress; Principal Component Analysis; Pulmonary Disease, Chronic Obstructive; Sex Factors

Vitamin C (VC) is a potent antioxidant and is essential for collagen synthesis. We investigated whether VC treatment prevents and cures smoke-induced emphysema in senescence marker protein-30 knockout (SMP30-KO) mice, which cannot synthesize VC. Two smoke-exposure experiments using SMP30-KO mice were conducted. In the first one (a preventive study), 4-month-old mice received minimal VC (0.0375 g/l) [VC(L)] or physiologically sufficient VC (1.5 g/l) [VC(S)] and exposed to cigarette smoke or smoke-free air for 2 months. Pulmonary evaluations followed when the mice were 6 months of age. The second study began after the establishment of smoke-induced emphysema (a treatment study). These mice no longer underwent smoke exposure but received VC(S) or VC(L) treatment for 2 months. Morphometric analysis was performed, and measurements of oxidative stress, collagen synthesis, and vascular endothelial growth factor in the lungs were evaluated. Chronic smoke exposure caused emphysema (29.6% increases of mean linear intercepts [MLI] and 106.5% increases of destructive index compared with the air-only group) in 6-month-old SMP30-KO mice, and this emphysema closely resembled human chronic obstructive pulmonary disease. Smoke-induced emphysema persisted in the VC(L) group after smoking cessation, whereas VC treatment provided pulmonary restoration (18.5% decrease of MLI and 41.3% decrease of destructive index compared with VC(L) group). VC treatment diminished oxidative stress, increased collagen synthesis, and improved vascular endothelial growth factor levels in the lungs. Our results suggest that VC not only prevents smoke-induced emphysema in SMP30-KO mice but also restores emphysematous lungs. Therefore, VC may provide a new therapeutic strategy for treating chronic obstructive pulmonary disease in humans.

Topics: Animals; Ascorbic Acid; Calcium-Binding Proteins; Disease Models, Animal; Intracellular Signaling Peptides and Proteins; Mice; Mice, Knockout; Nicotiana; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Smoke

Chronic obstructive pulmonary disease is characterised by oxidative stress, but little is known about the associations between antioxidant status and all-cause mortality in adults with this disease. The objective of the present study was to examine the prospective associations between concentrations of α- and β-carotene, β-cryptoxanthin, lutein/zeaxanthin, lycopene, Se, vitamin C and α-tocopherol and all-cause mortality among US adults with obstructive lung function. Data collected from 1492 adults aged 20-79 years with obstructive lung function in the National Health and Nutrition Examination Survey III (1988-94) were used. Through 2006, 629 deaths were identified during a median follow-up period of 14 years. After adjustment for demographic variables, the concentrations of the following antioxidants modelled as continuous variables were found to be inversely associated with all-cause mortality among adults with obstructive lung function: α-carotene (P= 0·037); β-carotene (P= 0·022); cryptoxanthin (P= 0·022); lutein/zeaxanthin (P= 0·004); total carotenoids (P= 0·001); vitamin C (P< 0·001). In maximally adjusted models, only the concentrations of lycopene (P= 0·013) and vitamin C (P= 0·046) were found to be significantly and inversely associated with all-cause mortality. No effect modification by sex was detected, but the association between lutein/zeaxanthin concentrations and all-cause mortality varied by smoking status (P interaction= 0·048). The concentrations of lycopene and vitamin C were inversely associated with all-cause mortality in this cohort of adults with obstructive lung function.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Carotenoids; Cause of Death; Female; Humans; Lung; Male; Middle Aged; Oxidative Stress; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Smoking; United States; Young Adult

Chronic obstructive pulmonary disease (COPD) is associated with systemic oxidative stress and skeletal muscle dysfunction. The purpose of this study was to examine the impact of intravenous ascorbate administration (AO) on biological markers of antioxidant capacity and oxidative stress, and subsequently skeletal muscle function during dynamic, small muscle mass exercise in patients with COPD. Ten patients with spirometric evidence of COPD performed single-leg knee extensor (KE) trials matched for intensity and time (isotime) following intravenous ascorbate (2 g) or saline infusion (PL). Quadriceps fatigue was quantified by changes in force elicited by maximal voluntary contraction (MVC) and magnetic femoral nerve stimulation (Qtw,pot). AO administration significantly increased antioxidant capacity, as measured by the ferric-reducing ability of plasma (PL: 1 ± 0.1 vs. AO: 5 ± 0.2 mM), and significantly reduced malondialdehyde levels (PL: 1.16 ± 0.1 vs. AO: 0.97 ± 0.1 mmol). Additionally, resting blood pressure was significantly reduced (PL: 104 ± 4 vs. AO: 93 ± 6 mmHg) and resting femoral vascular conductance was significantly elevated after AO (PL: 2.4 ± 0.2 vs. AO: 3.6 ± 0.4 ml·min(-1)·mmHg(-1)). During isotime exercise, the AO significantly attenuated both the ventilatory and metabolic responses, and patients accumulated significantly less peripheral quadriceps fatigue, as illustrated by less of a fall in MVC (PL: -11 ± 2% vs. AO: -5 ± 1%) and Qtw,pot (PL: -37 ± 1% vs. AO: -30 ± 2%). These data demonstrate a beneficial role of AO administration on skeletal muscle fatigue in patients with COPD and further implicate systemic oxidative stress as a causative factor in the skeletal muscle dysfunction observed in this population.

Topics: Aged; Antioxidants; Ascorbic Acid; Blood Pressure; Electromyography; Female; Humans; Male; Middle Aged; Muscle Fatigue; Oxidative Stress; Pulmonary Disease, Chronic Obstructive

Imbalance between antioxidant and oxidative stress is a major risk factor for pathogenesis of some chronic diseases such as chronic obstructive pulmonary disease (COPD). This study aimed to determine antioxidant and oxidative stress status, and also theirs association with respiratory function of male COPD patients to find the antioxidant predictors' factors. A total of 149 subjects were involved in a cross-sectional study. The study was conducted at two medical centers in Kuala Lumpur, Malaysia. Results of the study showed that plasma vitamin C was low in most of the subjects (86.6%). Total antioxidant capacity was the lowest in COPD stage IV compare to other stages (p < 0.05). Level of plasma vitamin A (p= 0.012) and vitamin C (p= 0.007) were low in malnourished subjects. The predictors for total antioxidant capacity were forced vital capacity (FVC) % predicted and intake of ?-carotene (R2= 0.104, p= 0.002). Number of cigarette (pack/ year) and smoking index (number/ year) were not associated with total antioxidant capacity of this COPD population. Plasma oxidative stress as assessed plasma lipid peroxidation (LPO) was only positively correlated with plasma glutathione (p= 0.002). It might be a need to evaluate antioxidant status especially in older COPD patients to treat antioxidant deficiency which is leading to prevent COPD progression.

Topics: Adult; Antioxidants; Ascorbic Acid; Cross-Sectional Studies; Disease Progression; Forced Expiratory Volume; Humans; Malaysia; Male; Nutritional Status; Outpatients; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Vitamin A; Vitamin E; Vitamins

Low molecule weight antioxidants such as uric acid (UA), glutathione (GSH), and ascorbate (ASC) counter the effects of oxidants produced by cigarette smoke. Although dietary intake of foods rich in antioxidants has been associated with a reduced risk of smokers developing chronic obstructive pulmonary disease (COPD), the association between plasma antioxidants and COPD is less clear. In this cross-sectional study we investigated the relationship among plasma antioxidants and COPD phenotypes (severity of airflow obstruction on spirometry and history of exacerbations) in 136 smokers with normal lung function and 367 smokers with COPD. In the multivariate analysis, a lower plasma UA was associated with more severe COPD (P < 0.002) and a lower GSH was associated with a history of COPD exacerbations (P = 0.03); ASC was not associated with any COPD phenotypes. This suggests that antioxidant balance is impaired in smokers with obstruction on spirometry or a history of COPD exacerbations.

Topics: Aged; Antioxidants; Ascorbic Acid; Chromatography, High Pressure Liquid; Colorado; Colorimetry; Cross-Sectional Studies; Female; Glutathione; Humans; Male; Middle Aged; Multivariate Analysis; Phenotype; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Smoking; Uric Acid

The imbalance of oxidant/antioxidant plays an important role in the development of chronic obstructive pulmonary disease (COPD). There is increasing evidence that individuals with high antioxidative nutrient levels in the diet or in blood tend to maintain better lung function. This study was conducted to determine whether COPD patients in Taiwan have lower plasma concentrations of antioxidative nutrients than do healthy people, and whether the dietary habits of COPD patients in Taiwan affect their intake of vitamin C and carotenoids. Thirty-four COPD patients and 43 healthy persons (with normal lung function) aged 50 years or older were recruited. Fasting venous blood was collected to measure concentrations of vitamins A, C, and E and carotenoids. Endogenous and H2O2-induced additional DNA damage (markers of oxidative stress) in white blood cells were assayed. Dietary intakes of vitamin C and carotenoids were assessed by a food-frequency questionnaire. Compare to the healthy controls, COPD patients had significantly lower plasma concentrations of vitamins A, C, and E; alpha- and beta-carotene; and total carotenoids but significantly higher endogenous and H2O2-induced white blood cell DNA damage. Intakes of vitamin C and several carotenoids were lower in the COPD group, and COPD patients consumed significantly fewer vegetables and fruits than did the healthy controls. In conclusion, COPD patients in Taiwan have lower levels of antioxidative nutrients in their plasma and diet than do healthy people. Intakes of vitamin C and carotenoids are correlated with dietary habits.

Topics: Aged; Antioxidants; Ascorbic Acid; Carotenoids; Case-Control Studies; Diet; DNA Damage; Female; Fruit; Humans; Hydrogen Peroxide; Leukocytes; Male; Middle Aged; Odds Ratio; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Taiwan; Vegetables; Vitamin A; Vitamin E

To investigate the prevalence and type of dietary supplements taken by Japanese patients with chronic obstructive pulmonary disease (COPD) and factors affecting their use.. Cross-sectional study by face-to-face interviews.. Six hospitals in central Japan.. Of the 300 referred COPD patients aged between 50 and 75 years, 278 eligible participants (244 men and 34 women) with complete data were available for analysis.. Prevalence of supplement use, dietary supplement categories (multivitamin, beta-carotene, vitamin C, vitamin E, and miscellaneous).. Overall, 42% of participants were dietary supplement users taking at least one category of supplements weekly; the prevalence being higher for female (47%) than male patients (41%). The most common supplements consumed were energy drink for men (11.1%), and multivitamin (11.8%) and vinegar (11.8%) for women. Dietary supplementation was found to be affected by age (p=0.04), COPD severity (p=0.03) and presence of co-morbidity (p=0.03). Older patients over 60 years were more likely to take dietary supplements (odds ratio (OR) 2.44, 95% CI 1.03-5.80), whereas severe COPD patients (OR 0.41, 95% CI 0.18-0.95) and those with a co-morbidity (OR 0.54, 95% CI 0.32-0.94) tended not to use.. Dietary supplements are popular for patients with COPD especially among older patients. The findings are important to clinical trials and experimental interventions advocating nutritional supplementation therapy for pulmonary rehabilitation.

Topics: Acetic Acid; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Cross-Sectional Studies; Dietary Supplements; Female; Forced Expiratory Volume; Health Behavior; Humans; Japan; Logistic Models; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Vitamins

Topics: Adult; Aged; Ascorbic Acid; Asthma; beta Carotene; Clinical Trials as Topic; Clinical Trials, Phase I as Topic; Coronary Disease; Disease; Disease Susceptibility; Epidemiologic Factors; Female; Heart Transplantation; Humans; Incidence; Male; Men; Middle Aged; Neoplasms; Pregnancy; Prognosis; Pulmonary Disease, Chronic Obstructive; Risk Factors; Sex Factors

In healthy subjects, hypoxemia and exercise represent independent stressors promoting the exercise-induced cytokine response and oxidative stress. We hypothesized that hypoxemia in patients with chronic obstructive pulmonary disease (COPD) may affect the cytokine production and/or the changes in oxidant-antioxidant status in response to maximal exercise. Exercise-induced changes in PaO2 allowed to transiently increase or decrease baseline hypoxemia and to point out its specific action on muscle metabolism. COPD patients with severe to moderate hypoxemia (56 < PaO2 < 72 mmHg) performed an incremental cycling exercise until volitional exhaustion. Two cytokines [interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha] and three blood indices of oxidative stress [plasma thiobarbituric acid reactive substances (TBARS) and two antioxidants, reduced erythrocyte glutathione (GSH), and reduced plasma ascorbic acid, RAA] were measured at rest, then during and after exercise. The changes in the cytokine levels and oxidant-antioxidant status were analysed in relation with the baseline PaO2 and its exercise-induced variations. Data were compared with those obtained in an age- and body mass index-matched group of healthy subjects. Compared with healthy subjects, COPD patients presented a marked accentuation of exercise-induced increase in IL-6 level and earlier changes in their oxidant-antioxidant status. Resting levels of IL-6 and TNF-alpha and exercise-induced peak variations of TBARS, IL-6 and TNF-alpha were negatively correlated with the baseline PaO2. In COPD patients, the peak increases in IL-6 and TBARS were attenuated when exercise hyperventilation reduced the baseline hypoxemia. Our study indicates that the PaO2 level affects both the exercise-induced oxidative stress and cytokine response in hypoxemic COPD patients.

Topics: Adult; Ascorbic Acid; Biomarkers; Case-Control Studies; Exercise; Female; Glutathione; Humans; Hypoxia; Interleukin-6; Male; Middle Aged; Oxidative Stress; Oxygen; Pulmonary Disease, Chronic Obstructive; Thiobarbituric Acid Reactive Substances; Time Factors; Tumor Necrosis Factor-alpha

Smoking-induced oxidative stress contributes to chronic obstructive pulmonary disease, a lung disease characterized by low lung function and increasing mortality worldwide. The counterbalance for this effect may be provided by, for example, increased intake of the antioxidant vitamin C or endogenously acting antioxidant enzymes like glutamate-cysteine ligase (GCL), which is responsible for glutathione biosynthesis.. To investigate associations of functional polymorphisms in GCL subunits (GCLM and GCLC) with lung function level and its longitudinal course, with vitamin C and smoking habits as potential interactive factors.. Two independent general population samples (Doetinchem, n = 1,152, and Vlagtwedde-Vlaardingen, n = 1,390) with multiple lung function (FEV(1), VC) measurements were genotyped for three polymorphisms (C[-129]T, C[-588]T, and a trinucleotide GAG repeat [TNR]) in the subunits of GCL. Genetic effects on lung function level and decline were estimated using linear regression and linear mixed effect models adjusted for confounders. Findings were further investigated for interactions with vitamin C intake in the Doetinchem cohort.. GCLC polymorphisms were significantly associated with lower lung function levels in interaction with pack-years smoked in both cohorts. TNR variants in GCLC were associated with accelerated FEV(1) decline in both cohorts in interaction with pack-years. All significant effects were specifically present in subjects within the lowest tertile of vitamin C intake.. GCLC is a novel susceptibility gene for low level of lung function in two independent populations. We provide suggestive evidence that this occurs due to an interaction between GCLC polymorphisms, smoking, and low vitamin C intake, which all contribute to the oxidative burden.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Cohort Studies; Female; Forced Expiratory Volume; Genetic Predisposition to Disease; Glutamate-Cysteine Ligase; Humans; Lung; Male; Middle Aged; Oxidative Stress; Polymorphism, Single Nucleotide; Pulmonary Disease, Chronic Obstructive; Smoking; Trinucleotide Repeats

The aim of this study was to test the hypothesis that pulmonary inflammation and emphysema induced by cadmium (Cd) inhalation are associated with pulmonary oxidative stress. Two groups of Sprague Dawley rats were used: one vehicle-exposed group undergoing inhalation of NaCl (0.9%, n = 24) and one Cd-exposed group undergoing inhalation of CdCl(2) (0.1%, n = 24). The animals in the vehicle-and Cd-exposed groups were divided into 4 subgroups (n = 6 per group), which underwent either a single exposure (D2) of 1H or repeated exposures 3 times/week for 1H for a period of 3 weeks (3W), 5 weeks (5W) or 5 weeks followed by 2 weeks without exposure (5W + 2). At sacrifice, the left lung was fixed for histomorphometric analysis (median inter-wall distance, MIWD), whilst bronchoalveolar lavage fluid (BALF) was collected from the right lung. Cytological analysis of BALF was performed and BALF was analysed for oxidant markers 8-iso-PGF(2a), uric acid (UA), reduced (AA) and oxidised ascorbic acid (DHA) and reduced (GSH) and oxidised glutathione (GSSG). Cd-exposure induced a significant increase of BALF macrophages and neutrophils. 8-iso-PGF(2a), UA, GSH and GSSG were significantly increased at D2. At 5W and 5W + 2, AA and GSH were significantly lower in Cd-exposed rats, indicating antioxidant depletion. MIWD significantly increased in all repeatedly Cd-exposed groups, suggesting development of pulmonary emphysema. 8-iso-PGF(2a) and UA were positively correlated with macrophage and neutrophil counts. GSH, GSSG and 8-iso-PGF(2a) were negatively correlated with MIWD, indicating that Cd-induced emphysema could be associated with pulmonary oxidative stress.

Topics: Animals; Antioxidants; Ascorbic Acid; Bronchoalveolar Lavage Fluid; Cadmium; Dinoprost; Glutathione; Inflammation; Lung; Macrophages; Male; Neutrophils; Oxidation-Reduction; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Rats; Rats, Sprague-Dawley; Uric Acid

There is an increasing interest in the concept that oxidant/antioxidant imbalance plays a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, most of the studies are concentrated on the local antioxidant/oxidant balance. In this study, we investigated the oxidant/antioxidant balance in systemic circulation of patients with COPD. Serum malonyldialdehyde (MDA), vitamin C and erythrocyte reduced glutathione (GSH) were determined in patients during acute exacerbation and during the stable phase of the disease, and compared with age- and sex-matched healthy controls. The levels of serum MDA, vitamin C and erythrocyte GSH were determined according to Yagi, Beutler and Bauer et al., respectively. Serum MDA levels were significantly higher in patients compared to controls, and during acute exacerbation compared to the stable phase. MDA levels in patients with acute exacerbation and in those in stable phase were also higher than in controls. We found significantly decreased levels of erythrocyte GSH and serum vitamin C in patients with acute exacerbation and stable COPD compared to controls. Although smoking caused an increase in oxidative stress in controls, the measured parameters were not affected by smoking in the patient group. In conclusion, there is a systemic oxidant/antioxidant imbalance in COPD, and this imbalance is probably independent of smoking.

Topics: Ascorbic Acid; Erythrocytes; Female; Glutathione; Humans; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Smoking