ascorbic-acid and Stroke

For decades, there has been epidemiologic evidence linking chronic toxic metal exposure with cardiovascular disease, suggesting a therapeutic role for metal chelation. Given the lack of compelling scientific evidence, however, the indications for metal chelation were never clearly defined. To determine the safety and efficacy of chelation therapy, the National Institutes of Health funded the Trial to Assess Chelation Therapy (TACT). TACT was the first double-blind, randomized, controlled trial to demonstrate an improvement in cardiovascular outcomes with edetate disodium therapy in patients with prior myocardial infarction. The therapeutic benefit was striking among the prespecified subgroup of patients with diabetes.. We review the published literature focusing on the atherogenic nature of diabetes, as well as available evidence from clinical trials, complete and in progress, of metal chelation with edetate disodium therapy in patients with diabetes.. The TACT results support the concept that ubiquitous toxic metals such as lead and cadmium may be modifiable risk factors for cardiovascular disease, particularly in patients with diabetes.. The purpose of this review is to discuss the potential mechanisms unifying the pathogenesis of atherogenic factors in diabetes with toxic metal exposure, and the potential role of metal chelation.

Topics: Antioxidants; Arsenic; Ascorbic Acid; Atherosclerosis; Cadmium; Calcium Chelating Agents; Cardiovascular Diseases; Chelating Agents; Chelation Therapy; Copper; Diabetes Complications; Diabetes Mellitus; Edetic Acid; Glycation End Products, Advanced; Hospitalization; Humans; Iron; Lead; Lipid Metabolism; Mercury; Myocardial Infarction; Myocardial Revascularization; Oxidative Stress; Randomized Controlled Trials as Topic; Stroke

Tissue plasminogen activator (t-PA) is the only FDA-approved drug for acute ischemic stroke treatment, but its clinical use is limited due to the narrow therapeutic time window and severe adverse effects, including hemorrhagic transformation (HT) and neurotoxicity. One of the potential resolutions is to use adjunct therapies to reduce the side effects and extend t-PA's therapeutic time window. However, therapies modulating single target seem not to be satisfied, and a multitarget strategy is warranted to resolve such complex disease. Recently, large amount of efforts have been made to explore the active compounds from herbal supplements to treat ischemic stroke. Some natural compounds revealed both neuro- and bloodbrain- barrier (BBB)-protective effects by concurrently targeting multiple cellular signaling pathways in cerebral ischemia-reperfusion injury. Thus, those compounds are potential to be one-drug-multi-target agents as combined therapy with t-PA for ischemic stroke. In this review article, we summarize current progress about molecular targets involving in t-PA-mediated HT and neurotoxicity in ischemic brain injury. Based on these targets, we select 23 promising compounds from currently available literature with the bioactivities simultaneously targeting several important molecular targets. We propose that those compounds merit further investigation as combined therapy with t-PA. Finally, we discuss the potential drawbacks of the natural compounds' studies and raise several important issues to be addressed in the future for the development of natural compound as an adjunct therapy.

Topics: Animals; Ascorbic Acid; Biological Products; Brain Ischemia; Drug Therapy, Combination; Flavonoids; Humans; Stroke; Thrombolytic Therapy; Tissue Plasminogen Activator; Treatment Outcome

Vitamin C is an essential micronutrient and powerful antioxidant. Observational studies have shown an inverse relationship between vitamin C intake and major cardiovascular events and cardiovascular disease (CVD) risk factors. Results from clinical trials are less consistent.. To determine the effectiveness of vitamin C supplementation as a single supplement for the primary prevention of CVD.. We searched the following electronic databases on 11 May 2016: the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library; MEDLINE (Ovid); Embase Classic and Embase (Ovid); Web of Science Core Collection (Thomson Reuters); Database of Abstracts of Reviews of Effects (DARE); Health Technology Assessment Database and Health Economics Evaluations Database in the Cochrane Library. We searched trial registers on 13 April 2016 and reference lists of reviews for further studies. We applied no language restrictions.. Randomised controlled trials of vitamin C supplementation as a single nutrient supplement lasting at least three months and involving healthy adults or adults at moderate and high risk of CVD were included. The comparison group was no intervention or placebo. The outcomes of interest were CVD clinical events and CVD risk factors.. Two review authors independently selected trials for inclusion, abstracted the data and assessed the risk of bias.. We included eight trials with 15,445 participants randomised. The largest trial with 14,641 participants provided data on our primary outcomes. Seven trials reported on CVD risk factors. Three of the eight trials were regarded at high risk of bias for either reporting or attrition bias, most of the 'Risk of bias' domains for the remaining trials were judged as unclear, with the exception of the largest trial where most domains were judged to be at low risk of bias.The composite endpoint, major CVD events was not different between the vitamin C and placebo group (hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.89 to 1.10; 1 study; 14,641 participants; low-quality evidence) in the Physicians Health Study II over eight years of follow-up. Similar results were obtained for all-cause mortality HR 1.07, 95% CI 0.97 to 1.18; 1 study; 14,641 participants; very low-quality evidence, total myocardial infarction (MI) (fatal and non-fatal) HR 1.04 (95% CI 0.87 to 1.24); 1 study; 14,641 participants; low-quality evidence, total stroke (fatal and non-fatal) HR 0.89 (95% CI 0.74 to 1.07); 1 study; 14,641 participants; low-quality evidence, CVD mortality HR 1.02 (95% 0.85 to 1.22); 1 study; 14,641 participants; very low-quality evidence, self-reported coronary artery bypass grafting (CABG)/percutaneous transluminal coronary angioplasty (PTCA) HR 0.96 (95% CI 0.86 to 1.07); 1 study; 14,641 participants; low-quality evidence, self-reported angina HR 0.93 (95% CI 0.84 to 1.03); 1 study; 14,641 participants; low-quality evidence.The evidence for the majority of primary outcomes was downgraded (low quality) because of indirectness and imprecision. For all-cause mortality and CVD mortality, the evidence was very low because more factors affected the directness of the evidence and because of inconsistency.Four studies did not state sources of funding, two studies declared non-commercial funding and two studies declared both commercial and non-commercial funding.. Currently, there is no evidence to suggest that vitamin C supplementation reduces the risk of CVD in healthy participants and those at increased risk of CVD, but current evidence is limited to one trial of middle-aged and older male physicians from the USA. There is limited low- and very low-quality evidence currently on the effect of vitamin C supplementation and risk of CVD risk factors.

Topics: Angioplasty, Balloon, Coronary; Ascorbic Acid; Cardiovascular Diseases; Coronary Artery Bypass; Dietary Supplements; Humans; Male; Middle Aged; Myocardial Infarction; Physicians; Primary Prevention; Publication Bias; Randomized Controlled Trials as Topic; Stroke; Vitamins

Vitamin C is a pivotal antioxidant in the brain and has been reported to have numerous functions, including reactive oxygen species scavenging, neuromodulation, and involvement in angiogenesis. Absence of vitamin C in the brain has been shown to be detrimental to survival in newborn SVCT2(-/-) mice and perinatal deficiency have shown to reduce hippocampal volume and neuron number and cause decreased spatial cognition in guinea pigs, suggesting that maternal vitamin C deficiency could have severe consequences for the offspring. Furthermore, vitamin C deficiency has been proposed to play a role in age-related cognitive decline and in stroke risk and severity. The present review discusses the available literature on effects of vitamin C deficiency on the developing and aging brain with particular focus on in vivo experimentation and clinical studies.

Topics: Aging; Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Brain; Cognition; Cognition Disorders; Female; Humans; Pregnancy; Prenatal Nutritional Physiological Phenomena; Stroke; Vitamins

Though vitamin C supplementation has shown no observed effects on stroke prevention in several clinical trials, uncertainty remains as to whether long-term, low-dose intake influences the development of stroke among general populations. Furthermore, the association between circulating vitamin C and the risk of stroke is also unclear. For further clarification of these issues, we conducted a meta-analysis of prospective studies.. PubMed and EMBASE databases were searched, and the bibliographies of the retrieved articles were also reviewed to identify eligible studies. Summary relative risk (RRs) with corresponding 95% confidence intervals (CIs) were computed with a random-effects model. The summary RR for the high-versus-low categories was 0.81 (95% CI: 0.74 to 0.90) for dietary vitamin C intake (11 studies), and 0.62 (95% CI: 0.49 to 0.79) for circulating vitamin C (6 studies). The summary RR for each 100 mg/day increment in dietary vitamin C was 0.83 (95% CI: 0.75 to 0.93) (10 studies), and for each 20 μmol/L increment in circulating vitamin C was 0.81 (95% CI: 0.75 to 0.88) (5 studies). Few studies reported results for vitamin C supplements (RR for high-versus-low intake=0.83, 95% CI: 0.62 to 1.10, 3 studies).. This meta-analysis suggests significant inverse relationships between dietary vitamin C intake, circulating vitamin C, and risk of stroke.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Biomarkers; Dietary Supplements; Humans; Prognosis; Prospective Studies; Risk Factors; Stroke; Time Factors

Acute ischemic stroke is a leading cause of death and severe disability in industrialised countries and also in many developing countries. An excessive amount of free radicals is generated during cerebral ischemia, which significantly contributes to brain damage. Therefore, an increasing interest has been devoted to the potential benefits of antioxidant compounds in ischemic stroke patients. In this review, we examined the most relevant observational studies concerning the relationship between dietary antioxidants and ischemic stroke as well as clinical trials investigating the effects of single or multiple antioxidant supplementation in the prevention or treatment of acute ischemic stroke. Furthermore, we reviewed the most promising antioxidant compounds, i.e. dehydroascorbic acid, alpha-tocotrienol, gamma-tocopherol, flavonoids, resveratrol and gingko biloba, tested in animal models of acute ischemic stroke. Finally, we carefully evaluated the reasons for the discrepancy between experimental and clinical studies, and provided recommendations to improve the translation of the results obtained in animal models to patients with acute ischemic stroke.

Topics: Animals; Antioxidants; Ascorbic Acid; Brain; Brain Ischemia; Diet; Fruit; Humans; Oxidative Stress; Risk; Stroke; Vegetables; Vitamin A; Vitamin E

Free radical production is increased in ischemic and hemorrhagic stroke, leading to oxidative stress that contributes to brain damage. The measurement of oxidative stress in stroke would be extremely important for a better understanding of its pathophysiology and for identifying subgroups of patients that might receive targeted therapeutic intervention. Since direct measurement of free radicals and oxidized molecules in the brain is difficult in humans, several biological substances have been investigated as potential peripheral markers. Among lipid peroxidation products, malondialdehyde, despite its relevant methodological limitations, is correlated with the size of ischemic stroke and clinical outcome, while F2-isoprostanes appear to be promising, but they have not been adequately evaluated. 8-Hydroxy-2-deoxyguanosine has been extensively investigated as markers of oxidative DNA damage but no study has been done in stroke patients. Also enzymatic and nonenzymatic antioxidants have been proposed as indirect markers. Among them ascorbic acid, alpha-tocopherol, uric acid, and superoxide dismutase are related to brain damage and clinical outcome. After a critical evaluation of the literature, we conclude that, while an ideal biomarker is not yet available, the balance between antioxidants and by-products of oxidative stress in the organism might be the best approach for the evaluation of oxidative stress in stroke patients.

Topics: Aldehydes; Animals; Antioxidants; Ascorbic Acid; Biomarkers; DNA Damage; Free Radicals; Humans; Lipid Peroxidation; Malondialdehyde; Oxidation-Reduction; Oxidative Stress; Prognosis; Reactive Oxygen Species; Stroke; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Uric Acid

Topics: Animals; Antioxidants; Ascorbic Acid; Brain Ischemia; Dehydroascorbic Acid; Humans; Stroke

In a recent prospective observational study, vitamins C and E and beta-carotene did not elicit protective effects on stroke risk. Lutein, however, may elicit such protection. Nevertheless, these nutrients may be important modulators of the outcome after the occurrence of a stroke. At present, optimal control of the classic stroke risk factors in combination with increased consumption of fruits, vegetables, and antioxidant nutrients may represent the safest and most efficient strategy to control stroke risk.

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Fruit; Humans; Lutein; Risk Factors; Stroke; Vegetables; Vitamin E

Stroke is a clinical syndrome of localized or global brain dysfunction caused by cerebrovascular disease.. The aim of this study was to explore the effect of vitamin C acid stimulation on the rehabilitation process, Nourishment State Index and immune function indicators of stroke patients with dysphagia.. This is a prospective cohort study.. This study was conducted at our hospital.. We analyzed stroke patients with dysphagia.. A total of 120 stroke patients with dysphagia were randomly divided into a routine group and a test group, with 60 cases in each group. Routine swallowing training was performed in the routine group, and the test group was stimulated with vitamin C acid. The water swallow test (WST) and video fluoroscopic swallowing study (VFSS) were used to compare the rehabilitation of dysphagia in the two groups. Nourishment State Index was evaluated by BMI, serum albumin, total serum protein and hemoglobin. Immune Function Index was evaluated by IgA, IgM and IgG.. Compared with the control group, the WST level of patients treated with vitamin C acid stimulation intervention were significantly reduced, and the VFSS score were significantly increased. Serum levels of hemoglobin, albumin, total protein, IgA, IgM and IgG in the vitamin C acid stimulation group were remarkably increased than those in the control group.. Vitamin C acid stimulation exhibits a good application effect in patients with dysphagia after stroke. Moreover, vitamin C acid stimulation can further improve the nutritional status and immune function after stroke and promote postoperative recovery of patients. Therefore, we believe that vitamin C stimulation therapy can be widely used in stroke rehabilitation management.. Vitamin C acid stimulation significantly improves rehabilitation of stroke patients with dysphagia and ameliorates the nutritional status and immune function of patients.

Topics: Ascorbic Acid; Deglutition; Deglutition Disorders; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Prospective Studies; Stroke; Stroke Rehabilitation; Treatment Outcome

Patients at nutritional risk are particularly vulnerable to adverse outcomes of acute stroke. We previously found that increased energy- and protein intervention improved short-term survival among stroke patients with the highest baseline antioxidant capacity. We now examined survival of these patients after 5-7 years.. We studied 165 patients >65 years admitted to hospital for acute stroke and enrolled in a randomized nutritional intervention study in 2005-2007. Cox regression analysis was used to estimate the associations between all-cause mortality (through 2011) and baseline plasma levels of antioxidant markers (glutathione reducing capacity, alpha-tocopherol, vitamin C and total carotenoids).. We found no significant difference (P = 0.86) in survival between the intervention and control group. Among the tested antioxidant markers, plasma levels above the median for total carotenoids were associated with reduced risk of death in the intervention group (adjusted hazard ratio, 0.29; 95% confidence interval, 0.12-0.71).. Hospitalized patients that received enhanced dietary energy- and protein after acute stroke and with baseline plasma total carotenoids above median level, had reduced risk of death after 5-7 years. Further trials testing intervention with diets rich in antioxidants are warranted.

Topics: Aged; Aged, 80 and over; alpha-Tocopherol; Antioxidants; Ascorbic Acid; Biomarkers; Cardiovascular Diseases; Carotenoids; Diet; Dietary Proteins; Energy Intake; Female; Follow-Up Studies; Hospitalization; Humans; Male; Middle Aged; Oxidative Stress; Proportional Hazards Models; Stroke

In the multicenter randomized clinical-instrumental prospective study 185 patients aged 55-75 years (mean age 68 years) with 94 men and 91 women with cerebral infarction were included. All the patients were hospitalized in the period from 6 to 24 hours from the time of the debut of clinical symptoms, 42,2% of patients scored 14 and above on NIH scale on admission. Patients were randomized into 3 groups: 1st group consisted of 64 patients treated as an antioxidant by 5% solution of ascorbic acid 2 times a day the recommended dose (20 ml/day) for 20 days; 2nd group consisted of 72 patients who received energy monitor Cytoflavin in a daily dose of 20 ml (10.0 ml/drip 2 times a day for 10 days); 3rd group consisted of 49 patients with Cytoflavin therapy extended to 20 days, moreover from 11th to 20th day the dose was 10 ml/day. Cytoflavin treatment was more efficient than ascorbic acid, which can be explained by different pharmacologic mechanisms. Treatment with Cytoflavin for 10 days resulted in a significant decrease of ischemia zone volume by 25% in average, treatment with Cytoflavin for 20 days--by 29%, which manifested in better outcomes in neurologic and functional status. Ascorbic acid demonstrated no effect on morphologic parameters. Patients having at the time of admission 18-20 points according to the NIH and treated with Cytoflavin for 20 days demonstrated significant trend towards improvement of the parameters of the neurological status.

Topics: Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Energy Metabolism; Female; Flavin Mononucleotide; Homeostasis; Humans; Inosine Diphosphate; Male; Middle Aged; Niacinamide; Prospective Studies; Severity of Illness Index; Stroke; Succinates; Treatment Outcome

The importance of dietary modification for disease prevention is widely accepted. The difficulty of implementing and sustaining long-term changes is also well documented. Nevertheless, a few studies have attempted to achieve significant dietary change for extended periods.. The Hiraka Dietary Intervention Study was a community-based randomized cross-over trial designed to develop an effective dietary modification tool and system in an area with high mortality for stomach cancer and stroke in 1998-2000. The main study subjects were 550 healthy volunteers, who were randomized into two groups and given tailored dietary education aimed at decreasing the intake of sodium and increasing that of carotene and vitamin C in either the first or second year. Four (first intervention group) and three (second intervention group) years after the intervention ended, 308 subjects were selected for this follow-up dietary survey.. The low-sodium, high-vitamin C and -carotene diet was maintained with only a small, nonsignificant reversal from post-intervention to follow-up (P = 0.082-0.824). Significant changes from pre-intervention to follow-up were also maintained (P < 0.01).. This dietary intervention program was maintained well over 4 years after the termination of the intervention sessions.

Topics: Ascorbic Acid; Carotenoids; Cross-Over Studies; Feeding Behavior; Follow-Up Studies; Humans; Sodium, Dietary; Stomach Neoplasms; Stroke; Surveys and Questionnaires

A condition of oxidative stress is known to occur in ischemic stroke, the current therapeutic intervention of which is largely limited to thrombolysis. To assess the effect of vitamin C - in conjunction to aspirin - in ischemic stroke-related lipid peroxidation, we measured plasma levels of ascorbate, of 8,12-isoprostanes F2alpha-VI (8,12-iPF2alpha-VI) and activities and levels of a broad spectrum of antioxidant enzymes and micronutrients in stroke patients randomized to receive, from stroke onset and up to three months, either vitamin C (200 mg/day) plus aspirin (300 mg/day) or only aspirin (300 mg/day). By the end of the first week, patients treated with vitamin C plus aspirin had higher vitamin C levels (p = 0.02) and lower 8,12-iPF2alpha-VI levels (p = 0.01) than patients treated with aspirin alone. The significance was maintained for the increase of vitamin C after three months of therapy (p < 0.01). The clinical functional outcome for both groups of patients similarly ameliorated after three months of treatment. We conclude that vitamin C, at the dose of 200 mg/day and in conjunction with aspirin, significantly decreases ischemic stroke-related lipid peroxidation in humans. Further studies are warranted to clarify whether the use of vitamin C may add clinical long-term beneficial effects in patients with stroke.

Topics: Ascorbic Acid; Aspirin; Carotenoids; Dinoprost; Humans; Kinetics; Lipid Peroxidation; Oxidative Stress; Stroke; Superoxide Dismutase; Uric Acid; Vitamin A; Vitamin E

Inflammatory response is a critical component of the complex pathophysiological response to stroke. Vitamin C has been shown to have important roles in cell performance and vascular function. In this study, we compared the nutritional status and levels of inflammatory markers between stroke cases and controls and assessed which antioxidant was associated with levels of inflammatory markers and oxidative stress among cases and controls.. We evaluated the nutritional status and measured plasma levels of vitamins C and E, uric acid, serum levels of C-reactive protein (CRP), the cytokines tumor necrosis factor-alpha and interleukin-1beta, intercellular adhesion molecule-1 (ICAM-1) and chemokine monocyte chemoattractant protein-1 (MCP-1), prostaglandins PGE2 and PGI2, and 8-isoprostanes (8-epiPGF2alpha) for 15 patients with ischemic stroke within 2 to 5 days after stroke onset and for 24 control subjects.. Stroke patients had significantly lower plasma levels of vitamin C than did controls. Among stroke patients, CRP was significantly elevated, as were the ICAM-1, MCP-1, and 8-epiPGF2alpha, but the prostaglandins PGE2 and PGI2 were significantly reduced. Interestingly, vitamin C concentration was significantly inversely correlated with the levels of CRP and 8-epiPGF2alpha among stroke patients, and 8-epiPGF2alpha was significantly associated with the levels of CRP. Uric acid was also elevated among stroke patients.. Lower vitamin C concentration, higher serum levels of inflammatory (CRP, ICAM-1, MCP-1) and oxidative stress (8-epiPGF2alpha) markers, and lower PGI2 and PGE2 concentrations among stroke patients indicate the presence of an inflammatory response associated with stroke.

Topics: Aged; Antioxidants; Ascorbic Acid; Biomarkers; Brain Ischemia; C-Reactive Protein; Chemokine CCL2; Cytokines; Diet; Dinoprost; Humans; Inflammation Mediators; Intercellular Adhesion Molecule-1; Middle Aged; Neuropsychological Tests; Nutritional Status; Oxidative Stress; Prostaglandins; Reference Values; Stroke; Time Factors; Uric Acid; Vitamin E

It has been suggested that increased intake of various antioxidant vitamins reduces the incidence rates of vascular disease, cancer, and other adverse outcomes.. 20,536 UK adults (aged 40-80) with coronary disease, other occlusive arterial disease, or diabetes were randomly allocated to receive antioxidant vitamin supplementation (600 mg vitamin E, 250 mg vitamin C, and 20 mg beta-carotene daily) or matching placebo. Intention-to-treat comparisons of outcome were conducted between all vitamin-allocated and all placebo-allocated participants. An average of 83% of participants in each treatment group remained compliant during the scheduled 5-year treatment period. Allocation to this vitamin regimen approximately doubled the plasma concentration of alpha-tocopherol, increased that of vitamin C by one-third, and quadrupled that of beta-carotene. Primary outcomes were major coronary events (for overall analyses) and fatal or non-fatal vascular events (for subcategory analyses), with subsidiary assessments of cancer and of other major morbidity.. There were no significant differences in all-cause mortality (1446 [14.1%] vitamin-allocated vs 1389 [13.5%] placebo-allocated), or in deaths due to vascular (878 [8.6%] vs 840 [8.2%]) or non-vascular (568 [5.5%] vs 549 [5.3%]) causes. Nor were there any significant differences in the numbers of participants having non-fatal myocardial infarction or coronary death (1063 [10.4%] vs 1047 [10.2%]), non-fatal or fatal stroke (511 [5.0%] vs 518 [5.0%]), or coronary or non-coronary revascularisation (1058 [10.3%] vs 1086 [10.6%]). For the first occurrence of any of these "major vascular events", there were no material differences either overall (2306 [22.5%] vs 2312 [22.5%]; event rate ratio 1.00 [95% CI 0.94-1.06]) or in any of the various subcategories considered. There were no significant effects on cancer incidence or on hospitalisation for any other non-vascular cause.. Among the high-risk individuals that were studied, these antioxidant vitamins appeared to be safe. But, although this regimen increased blood vitamin concentrations substantially, it did not produce any significant reductions in the 5-year mortality from, or incidence of, any type of vascular disease, cancer, or other major outcome.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Cause of Death; Cholesterol; Coronary Disease; Diabetes Mellitus; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasms; Severity of Illness Index; Stroke; United Kingdom; Vitamin E

Topics: Aged; Aged, 80 and over; Aging; Ascorbic Acid; Chromatography, High Pressure Liquid; Female; Folic Acid; Humans; Hyperhomocysteinemia; Lipid Peroxides; Male; Nitric Oxide; Oxidative Stress; Predictive Value of Tests; Stroke; Vitamin B 12

Experimental studies provide evidence of an association between ischemic stroke and increased oxidative stress, but data in humans are still limited and controversial. The purpose of this study was to investigate the time course of plasma antioxidant changes in ischemic stroke patients.. Plasma antioxidants, including water-soluble (vitamin C and uric acid) and lipid-soluble (vitamins A and E) compounds as well as antioxidant enzyme activities in plasma (superoxide dismutase [SOD] and glutathione peroxidase) and erythrocytes (SOD), were measured by high-performance liquid chromatography (antioxidant vitamins) and by spectrophotometry (antioxidant enzymes) in 38 subjects (25 men and 13 women aged 77.2+/-7.9 years) with acute ischemic stroke of recent onset (<24 hours) on admission, after 6 and 24 hours, and on days 3, 5, and 7. Antioxidant levels in patients on admission were compared with those of age- and sex-matched controls.. Mean antioxidant levels and activities in patients on admission were lower than those of controls and showed a gradual increase over time. Patients with the worst early outcome (death or functional decline) had higher vitamin A and uric acid plasma levels and lower vitamin C levels and erythrocyte SOD activity than those who remained functionally stable.. These results suggest that the majority of antioxidants are reduced immediately after an acute ischemic stroke, possibly as a consequence of increased oxidative stress. A specific antioxidant profile is associated with a poor early outcome.

Topics: Aged; Analysis of Variance; Antioxidants; Ascorbic Acid; Brain Ischemia; Chromatography, High Pressure Liquid; Disease Progression; Erythrocytes; Female; Glutathione Peroxidase; Humans; Longitudinal Studies; Male; Oxidative Stress; Severity of Illness Index; Spectrophotometry; Stroke; Superoxide Dismutase; Treatment Outcome; Uric Acid; Vitamin A; Vitamin E

Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is the most common subtype of mitochondrial encephalopathy. In the past, it was believed that most hereditary white matter lesions were lysosome storage disorders or peroxisome diseases. However, in recent years, white matter lesions have been increasingly regarded as a common feature of patients with mitochondrial diseases. In addition to stroke-like lesions, about half of the patients with MELAS reported white matter lesions in the brain.. Herein, we provide a case of A 48-year-old female who presented with episodic loss of consciousness with twitching of extremities. Previous medical history revealed 10 years of history of epilepsy, 10 years of history of diabetes, a history of hearing loss, and unknown etiology. Ancillary findings included brain magnetic fluid-attenuated inversion recovery showed symmetrical lesions in the bilateral parietal lobe with high signal intensity at the edge, and high signal intensity in the bilateral occipital lobe, paraventricular white matter, corona radiata, and the center of semiovale.. Mitochondrial deoxyribonucleic acid gene sequencing returned A3243G point mutation and it supports the diagnosis of intracranial hypertension.. Considered the diagnosis of symptomatic epilepsy, the patient was treated with mechanical ventilation, midazolam, and levetiracetam, and the limb twitching symptoms were controlled. The patient was comatose, chronically bedridden, with gastrointestinal dysfunction, and was treated prophylactically with antibiotics against infection, parenteral nutrition, and other supportive measures. B vitamins, vitamin C, vitamin E, coenzyme Q10, and idebenone were given, and mechanical ventilation and midazolam were stopped after 8 days. He was discharged from the hospital on 30 days and continued symptomatic treatment with B-vitamins, vitamin C, vitamin E, coenzyme Q10, and idebenone, and antiepileptic treatment with levetiracetam, with outpatient follow-up.. No further seizures were recorded and the patient recovered well.. MELAS syndrome without stroke-like episodes of diffuse posterior cerebral white matter lesions is rare in clinical practice, and the possibility of MELAS syndrome should be considered in symmetric posterior cerebral white matter lesions.

Topics: Acidosis, Lactic; Ascorbic Acid; Female; Humans; Leukoencephalopathies; Levetiracetam; Male; MELAS Syndrome; Midazolam; Middle Aged; Stroke; Vitamin E; Vitamins

Vitamin C has recently been identified as an epigenetic regulator by activating ten-eleven translocases (TETs), enzymes involved in generating DNA hydroxymethylcytosine (5hmC). Currently, we investigated whether high-dose vitamin C promotes neuroprotection through epigenetic modulation of 5hmC, if there are sex-specific differences in outcome, and the therapeutic potential of vitamin C in stroke-related comorbidities in adult mice. Post-stroke treatment with ascorbate (reduced form), but not dehydroascorbate (oxidized form), increased TET3 activity and 5hmC levels and reduced infarct following focal ischemia. Hydroxymethylation DNA immunoprecipitation sequencing showed that ascorbate increased 5hmC across the genome and specifically in promoters of several stroke pathophysiology-related genes, particularly anti-inflammatory genes. Ascorbate also decreased markers of oxidative stress, mitochondrial fragmentation, and apoptosis in cortical peri-infarct neurons and promoted motor and cognitive functional recovery in both sexes via TET3. Furthermore, post-stroke ascorbate treatment reduced infarct volume and improved motor function recovery in aged, hypertensive and diabetic male and female mice. Delayed ascorbate treatment at 6 h of reperfusion was still effective at reducing infarct volume and motor impairments in adult mice. Collectively, this study shows that post-stroke treatment with high-dose ascorbate protects the brain through epigenetic reprogramming and may function as a robust therapeutic against stroke injury.

Topics: 5-Methylcytosine; Animals; Ascorbic Acid; Brain; Brain Injuries; Brain Ischemia; DNA; Epigenesis, Genetic; Female; Infarction; Male; Mice; Neuroprotection; Stroke

Stroke is a major public health problem and ranks third most common cause of death in adults worldwide. Thrombolysis with recombinant tissue plasminogen activator and endovascular thrombectomy are the main revascularization therapies for acute ischemic stroke. However, ischemia-reperfusion injury, mainly caused by oxidative/nitrosative stress injury, after revascularization therapy can result in worsening outcomes. For better clinical prognosis, more and more studies have focused on the pharmaceutical neuroprotective therapies against free radical damage. The impact of vitamin C (ascorbic acid) on oxidative stress-related diseases is moderate because of its limited oral bioavailability and rapid clearance. However, recent evidence of the clinical benefit of parenteral vitamin C administration has emerged, especially in critical care. In this study we demonstrated that parenteral administration of vitamin C significantly improved neurological deficits and reduced brain infarction and brain edema by attenuating the transient middle cerebral artery occlusion (tMCAO)-induced nitrosative stress, inflammatory responses, and the resultant disruptions of blood brain barrier and cerebral neuronal apoptosis. These results suggest that parenteral administration of vitamin C has potential as an adjuvant agent with intravenous thrombolysis or endovascular thrombectomy in acute treatment of ischemic stroke.

Topics: Animals; Apoptosis; Ascorbic Acid; Blood-Brain Barrier; Brain; Brain Ischemia; Infarction, Middle Cerebral Artery; Neuroprotective Agents; Rats; Stroke; Tissue Plasminogen Activator

As a promising therapeutic treatment, ischemic postconditioning has recently received considerable attention. Although the neuroprotection effect of postconditioning has been observed, a reliable approach that can evaluate the neuroprotective efficiency of postconditioning treatment during the acute period after ischemia remains to be developed. This study investigates the dynamics of cortex ascorbic acid during the acute period of cerebral ischemia before and after ischemic postconditioning with an online electrochemical system (OECS). The cerebral ischemia/reperfusion injury and the neuronal functional outcome are evaluated with triphenyltetrazolium chloride staining, immunohistochemistry, and electrophysiological recording techniques. Electrochemical recording results show that cortex ascorbic acid sharply increases 10 min after middle cerebral artery occlusion and then reaches a plateau. After direct reperfusion following ischemia (i.e., without ischemic postconditioning), the cortex ascorbic acid further increases and then starts to decrease slowly at a time point of about 40 min after reperfusion. In striking contrast, the cortex ascorbic acid drops and recovers to its basal level after ischemic postconditioning followed by reperfusion. With the recovery of cortex ascorbic acid, ischemic postconditioning concomitantly promotes the recovery of neural function and reduces the oxidative damage. These results demonstrate that our OECS for monitoring cortex ascorbic acid can be used as a platform for evaluating the neuroprotective efficiency of ischemic postconditioning in the acute phase of cerebral ischemia, which is of great importance for screening proper postconditioning parameters for preventing ischemic damages.

Topics: Acute Disease; Animals; Ascorbic Acid; Brain Ischemia; Cerebral Cortex; Disease Models, Animal; Electrophysiological Phenomena; Infarction, Middle Cerebral Artery; Ischemic Postconditioning; Male; Monitoring, Physiologic; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Stroke

Epidemiological studies have demonstrated that vitamin C decreases the risk of stroke, which has generally been ascribed to its function as antioxidant and free radical scavenger. However, whether there is a defined molecular target for vitamin C on stroke is unknown. Utilizing middle cerebral artery occlusion (MCAO) in rats as a model for ischemic stroke, we demonstrated that long-term, low-dose administration of vitamin C prior to MCAO could exert significant neuroprotective effect on the brain damage. The long-term, low-dose vitamin C pretreated rats had decreased brain infarct size and decreased neurological deficit score compared with the vehicle or single high dose pretreated MCAO rats. Furthermore, electrophysiological experiments using patch clamp technique showed that vitamin C increased the whole-cell current of the large-conductance Ca

Topics: Animals; Ascorbic Acid; Brain Infarction; CHO Cells; Cricetulus; Disease Models, Animal; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; Male; Rats; Rats, Sprague-Dawley; Stroke

Epidemiologic evidence on the relationship between antioxidant vitamin intake and stroke is limited. We aimed to investigate the association between dietary intake of antioxidant vitamins and the incidence of total stroke and ischemic stroke.. The subjects were 82 044 Japanese men and women aged 45-74 years under the Japan Public Health Center-based Prospective Cohort Study. Between 1995 and 1997, dietary assessment was done using a food frequency questionnaire. During 983 857 person-years of follow-up until the end of 2009 we documented 3541 incident total strokes and 2138 ischemic strokes.. Dietary intakes of α-carotene, β-carotene, α-tocopherol and vitamin C were not inversely associated with the incidence of total stroke and ischemic stroke adjustment for cardiovascular risk factors and selected lifestyle variables. When stratified by current smoking status, the inverse association between dietary vitamin C intake and incidence of total stroke observed among non-smokers but not smokers, with respective multivariable hazard ratios for the highest versus lowest quintiles of vitamin C of 0.81 (95% confidence interval (CI), 0.68-0.96; P-trend=0.03) among non-smokers; and 1.03 (0.84-1.25; P-trend=0.55) among smokers. As for ischemic stroke, the corresponding multivariable hazard ratios were 0.76 (0.60-0.96; P-trend=0.02) among non-smokers; and 1.00 (0.78-1.28; P-trend=0.61) among smokers.. Dietary vitamin C intake was inversely associated with the incidence of total stroke and ischemic stroke among non-smokers.

Topics: Aged; Antioxidants; Ascorbic Acid; Cohort Studies; Dietary Supplements; Female; Health Services for the Aged; Humans; Incidence; Japan; Male; Middle Aged; Nutrition Surveys; Prospective Studies; Risk Factors; Stroke; Surveys and Questionnaires

Topics: Anticoagulants; Antioxidants; Ascorbic Acid; Atrial Fibrillation; Humans; Postoperative Complications; Sample Size; Stroke

In animal models of acute ischemic stroke, intravenous dehydroascorbic acid (DHAA), unlike ascorbic acid (AA), readily enters brain and is converted in both normal and ischemic brain into protective ascorbic acid. When given parenterally DHAA minimizes infarct volume and facilitates functional recovery. I hypothesize the same effect will occur in humans with acute ischemic stroke. Efficacy in reducing infarct volume is demonstrable in mice and rats even when DHAA is infused three hours after the experimental infarct. Moreover, there is fivefold mechanistic rational for DHA beside excellent pharmacokinetics and rapid penetration of brain and conversion to protective AA: (1) in ischemic brain, there is a precipitous decline in AA which can be reversed by intravenous DHAA; (2) after reduction of DHAA to AA in both normal and ischemic brain, AA can reduce oxidized vitamin E and glutathione, other protectors of brain against damaging reactive oxygen species which build up in ischemic brain; (3) AA itself can protect brain against damaging reactive oxygen species; (4) AA is an essential cofactor for several enzymes in brain including ten-eleven translocase-2 which upregulates production of protective molecules like brain-derived neurotrophic factor; and (5) DHAA after conversion to AA prevents both lipid oxidation and presumably oxidation of other labile substances (e.g., dopamine) in ischemic brain. In terms of safety, based on all available animal information, DHAA is safe in the proposed dosing regimen. For human clinical trials, the methodology for conducting the proposed animal safety, clinical pharmacology and phase II efficacy studies is straightforward. Finally, if DHAA preserved brain substance and function in humans, it could be employed in pre-hospital stroke patients.

Topics: Animals; Ascorbic Acid; Brain; Dehydroascorbic Acid; Evidence-Based Medicine; Humans; Models, Neurological; Stroke; Treatment Outcome; Vitamins

Less than 8.5% of ischemic stroke patients receive clot-busting drugs within the narrow time needed to reduce injury. Thus, there is need for an easily-accessible delayed post-stroke drug treatment to improve functional recovery. Various combinations of fluoxetine, simvastatin, and ascorbic acid were given to healthy rats to assess impact on neurogenesis versus controls. Fluoxetine combined with simvastatin and ascorbic acid produced a 19-fold increase in neurogenesis versus controls in healthy rats; fluoxetine alone produced 10-fold increase. We next tried a couple of drug combinations versus control in endothelin-induced stroked rats. Combined fluoxetine/ simvastatin/ascorbic acid treatment, given to stroked rats 20-26 hours after stroke induction and continued for 31 days, produced strong recovery as measured by Montoya staircase test (mean recovery to 85% of pre-stroke function) and Forelimb Asymmetry test (mean recovery to 90% of pre-stroke function). Fluoxetine and ascorbic acid without simvastatin only produced ~50% of recovery produced by the 3-drug combination. Our results indicate that combined treatment of Fluoxetine, simvastatin and ascorbic acid represents a promising delayed stroke treatment that greatly improves functional recovery in rats and warrants further study in human patient populations. This work formed the basis for a patent submission (US20130065924A1) Composition and method for treatment of neurodegeneration.

Topics: Animals; Ascorbic Acid; Brain; Brain Ischemia; Drug Therapy, Combination; Female; Fluoxetine; Male; Neurogenesis; Rats; Rats, Long-Evans; Rats, Wistar; Recovery of Function; Simvastatin; Stroke

To examine the association between plasma concentrations of antioxidative micronutrients and leukocyte telomere length (LTL) in elderly adults.. Cross-sectional cohort study.. Austrian Stroke Prevention Study, a population-based cohort study on brain aging.. Individuals with a mean age of 66 ± 7 (n = 786; 58% female).. Concentrations of vitamin C, lutein, zeaxanthin, β-cryptoxanthin, canthaxanthin, lycopene, α- and γ-tocopherol, α- and β-carotene, and retinol in plasma, advanced oxidation protein products as a measure of oxidative stress in serum, and LTL were measured. Vitamins and carotenoids were measured using high-performance liquid chromatography, advanced oxidation protein products using spectrophotometry, and telomere length using quantitative real-time polymerase chain reaction.. Multiple linear regression analyses with adjustment for age and sex demonstrated that higher lutein, zeaxanthin, and vitamin C concentrations were strongly associated with longer telomere length. The associations were independent of body mass index, maximum oxygen uptake, and vascular risk factors and were not mediated by advanced oxidation protein products content.. This study provides first evidence that higher lutein, zeaxanthin, and vitamin C concentrations in plasma are associated with longer LTL in normal elderly persons and suggest a protective role of these vitamins in telomere maintenance.

Topics: Aged; Aged, 80 and over; Aging; Antioxidants; Ascorbic Acid; Austria; Chromatography, High Pressure Liquid; Cross-Sectional Studies; DNA; Female; Follow-Up Studies; Humans; Incidence; Leukocytes; Lutein; Male; Middle Aged; Oxidative Stress; Real-Time Polymerase Chain Reaction; Retrospective Studies; Spectrophotometry; Stroke; Telomere Homeostasis; Xanthophylls; Zeaxanthins

Consuming a variety of fruit and vegetables provides many different micronutrients and bioactive compounds. Whether this contributes to the beneficial association between fruit and vegetables and incident CHD and stroke is unknown.. Prospective population-based cohort study.. The Netherlands.. Men and women (n 20 069) aged 20-65 years. Participants completed a validated 178-item FFQ, including nine fruit and thirteen vegetable items. Variety in fruit and vegetables was defined as the sum of different items consumed at least once per 2 weeks over the previous year. Hazard ratios (HR) for variety in relation to incident CHD and stroke were calculated using multivariable Cox proportional hazards models additionally adjusted for quantity of fruit and vegetables.. Variety and quantity in fruit and vegetables were highly correlated (r = 0.81). Variety was not associated with total energy intake (r = -0.01) and positively associated with nutrient intakes, particularly vitamin C (r = 0.70). During 10 years of follow-up, 245 cases of CHD and 233 cases of stroke occurred. Variety in vegetables (HR per 2 items = 1.05; 95 % CI 0.94, 1.17) and in fruit (HR per 2 items = 1.00; 95 % CI 0.87, 1.15) were not related to incident CHD. Variety in vegetables (HR per 2 items = 0.93; 95 % CI 0.83, 1.04) and in fruit (HR per 2 items = 1.03; 95 % CI 0.89, 1.18) were also not related to incident stroke.. More variety in fruit and vegetable consumption was associated with higher intakes of fruit and vegetables and micronutrients. Independently of quantity, variety in fruit and vegetables was related neither to incident CHD nor to incident stroke.

Topics: Adult; Aged; Ascorbic Acid; Coronary Disease; Diet; Diet Surveys; Energy Intake; Feeding Behavior; Female; Fruit; Humans; Incidence; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Stroke; Surveys and Questionnaires; Vegetables; Young Adult

Topics: Adiponectin; Antioxidants; Ascorbic Acid; Humans; Scurvy; Stroke

We compared ascorbic acid (AA) levels in the blood and TPA- and fMLP-stimulated superoxide (O(2)(•-)) production in neutrophils of pre-, early, and late hypertensive stroke-prone spontaneously hypertensive rats (SHRSP) with those of age-matched Wistar Kyoto rats (WKY), or two other normotensive strains of rats. Plasma and lymphocyte AA levels were about two-fold higher in SHRSP as early as 4 weeks old compared to WKY, and also higher than those of Wistar and Sprague-Dawley (SD) rats. Levels of AA were high in the liver and adrenal glands of SHRSP, indicating congenitally high AA levels. The production of O(2)(•-) in neutrophils was about two-fold higher in SHRSP than in WKY even at 4 weeks of age, and increased with age in both strains. Among SHRSP, AA levels in lymphocytes decreased at the late hypertensive stages with a decrease in hepatic l-gulono-γ-lactone oxidase (GLO) activities. These data suggest that bi-phasic AA levels in the blood of SHRSP comprise congenitally high levels and a decrease after persistent hypertension due to enhanced O(2)(•-) production and a decrease in de novo AA synthesis through GLO.

Topics: Adrenal Glands; Aging; Animals; Ascorbic Acid; Disease Models, Animal; Glucose; Hypertension; L-Gulonolactone Oxidase; Liver; Male; Neutrophils; Rats; Rats, Inbred SHR; Rats, Sprague-Dawley; Rats, Wistar; Risk Factors; Stroke; Superoxides

To examine the role of increased oxidative stress in the pathogenesis of cerebral infarction in stroke in stroke-prone spontaneously hypertensive rats (SHR-SP).. The differentially expressed brain protein profile was examined in spontaneously hypertensive rats (SHR) (control group) and SHR-SP using two-dimensional fluorescent difference gel electrophoresis (2D-DIGE). In addition, oxidative stress indicators including total antioxidation capacity (TAC), glutathione peroxidase (GPx) activity, and maleic dialdehyde (MDA) were also measured. Lastly, SHR-SP were randomly divided into untreated and treated (vitamins C (200 mg/kg/day) and E (100 mg/kg/day)) groups. After treatment for 4 weeks, half of the animals were sacrificed for detection of TAC, GPx, and MDA. The remaining rats underwent middle cerebral artery occlusion (MCAO) and the infarct areas were measured.. Compared with SHR, the infarct area of SHR-SP was larger (P < 0.01), and the antioxidative proteins including glutathione S-transferase (GST) Pi2 and GST A5 were lower; TAC and GPx activities were decreased and MDA levels. Treatment with vitamins C and E decreased MDA, and increased TAC and GPx activity significantly in SHR-SP, while also decreasing the infarct area (P < 0.01).. Our findings indicate that oxidative stress plays an important role in the pathogenesis of cerebral ischemia.

Topics: Aldehydes; Amino Acid Sequence; Animals; Antioxidants; Ascorbic Acid; Blotting, Western; Cerebral Infarction; Electrophoresis, Gel, Two-Dimensional; Glutathione Peroxidase; Image Processing, Computer-Assisted; Infarction, Middle Cerebral Artery; Lipid Peroxidation; Male; Mass Spectrometry; Molecular Sequence Data; Nerve Tissue Proteins; Oxidative Stress; Rats; Rats, Inbred SHR; Stroke; Vitamin E; Vitamins

Underlying cardiovascular disease (CVD) is a risk factor for the exacerbation of air pollution health effects. Pulmonary oxidative stress, inflammation, and altered iron (Fe) homeostasis secondary to CVD may influence mammalian susceptibility to air pollutants. Rodent models of CVD are increasingly used to examine mechanisms of variation in susceptibility. Baseline cardiac and pulmonary disease was characterized in healthy normotensive Wistar Kyoto (WKY) rats, cardiovascular compromised spontaneously hypertensive rats (SHR), and spontaneously hypertensive heart failure (SHHF) rats. Blood pressure, heart rate, and breathing frequencies were measured in rats 11 to 12 wk of age, followed by necropsy at 14 to 15 wk of age. Blood pressure and heart rate were increased in SHR and SHHF relative to WKY rats (SHR > SHHF > WKY). Increased breathing frequency in SHHF and SHR (SHR > SHHF > WKY) resulted in greater minute volume relative to WKY. Bronchoalveolar lavage fluid (BALF) protein and neutrophils were higher in SHHF and SHR relative to WKY (SHHF >> SHR > WKY). Lung ascorbate and glutathione levels were low in SHHF rats. BALF Fe-binding capacity was decreased in SHHF relative to WKY rats and was associated with increased transferrin (Trf) and ferritin. However, lung ferritin was lower and Trf was higher in SHHF relative to WKY or SHR rats. mRNA for markers of inflammation and oxidative stress (macrophage inflammatory protein [MIP]-2, interleukin [IL]-1alpha, and heme oxygenase [HO]-1) were greater in SHHF and SHR relative to WKY rats. Trf mRNA rose in SHR but not SHHF relative to WKY rats, whereas transferrin receptors 1 and 2 mRNA was lower in SHHF rats. Four of 12 WKY rats exhibited cardiac hypertrophy despite normal blood pressure, while demonstrating some of the pulmonary complications noted earlier. This study demonstrates that SHHF rats display greater underlying pulmonary complications such as oxidative stress, inflammation, and impaired Fe homeostasis than WKY or SHR rats, which may play a role in SHHF rats' increased susceptibility to air pollution.

Topics: Animals; Ascorbic Acid; Biomarkers; Bronchoalveolar Lavage Fluid; Cardiovascular Diseases; Disease Models, Animal; Ferritins; Gene Expression; Glutathione; Heart Failure; Hemodynamics; Homeostasis; Hypertension; Inflammation; Iron; Lung; Lung Diseases; Male; Obesity; Oxidative Stress; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Respiratory Function Tests; Stroke; Transferrin

In humans, growth hormone deficiency (GHD) and low circulating levels of insulin-like growth factor 1 (IGF-1) significantly increase the risk for cerebrovascular disease. Genetic growth hormone (GH)/IGF-1 deficiency in Lewis dwarf rats significantly increases the incidence of late-life strokes, similar to the effects of GHD in elderly humans. Peripubertal treatment of Lewis dwarf rats with GH delays the occurrence of late-life stroke, which results in a significant extension of life span. The present study was designed to characterize the vascular effects of life span-extending peripubertal GH replacement in Lewis dwarf rats. Here, we report, based on measurements of dihydroethidium fluorescence, tissue isoprostane, GSH, and ascorbate content, that peripubertal GH/IGF-1 deficiency in Lewis dwarf rats increases vascular oxidative stress, which is prevented by GH replacement. Peripubertal GHD did not alter superoxide dismutase or catalase activities in the aorta nor the expression of Cu-Zn-SOD, Mn-SOD, and catalase in the cerebral arteries of dwarf rats. In contrast, cerebrovascular expression of glutathione peroxidase 1 was significantly decreased in dwarf vessels, and this effect was reversed by GH treatment. Peripubertal GHD significantly decreases expression of the Nrf2 target genes NQO1 and GCLC in the cerebral arteries, whereas it does not affect expression and activity of endothelial nitric oxide synthase and vascular expression of IGF-1, IGF-binding proteins, and inflammatory markers (tumor necrosis factor alpha, interluekin-6, interluekin-1β, inducible nitric oxide synthase, intercellular adhesion molecule 1, and monocyte chemotactic protein-1). In conclusion, peripubertal GH/IGF-1 deficiency confers pro-oxidative cellular effects, which likely promote an adverse functional and structural phenotype in the vasculature, and results in accelerated vascular impairments later in life.

Topics: Animals; Ascorbic Acid; Biomarkers; Blood Vessels; Body Weight; Chromatography, High Pressure Liquid; Dwarfism; Endothelium, Vascular; Glutamate-Cysteine Ligase; Glutathione Peroxidase; Growth Hormone; Insulin-Like Growth Factor I; Longevity; NAD(P)H Dehydrogenase (Quinone); Nitric Oxide Synthase; Oxidative Stress; Phenotype; Rats; Rats, Inbred Lew; Reverse Transcriptase Polymerase Chain Reaction; Stroke

Ischemic stroke results from brain blood vessel blockage by thrombus, and produces neuronal cell damage and death. While thrombolytic therapy with tPA has achieved some success in clinic, the strategy of using neuroprotective agents to treat ischemic stroke has been disappointing thus far. In the present work, we synthesized TBN, a derivative of the clinically useful stroke drug TMP armed with a powerful free radical-scavenging nitrone moiety. TBN retains the thrombolytic activity of the parent TMP and possesses strong antioxidative properties. TBN demonstrates significant activity in the rat MCAo stroke model. The results suggest that design of molecules possessing both thrombolytic and neuroprotective properties may be a novel strategy for effective stroke therapeutics.

Topics: Animals; Antioxidants; Brain Ischemia; Fibrinolytic Agents; Nitrogen Oxides; Pyrazines; Rats; Stroke; Thrombolytic Therapy

Experimental stroke studies indicate that oxidative stress is a major contributing factor to ischemic cerebral injury. Oxidative stress is also implicated in activation of matrix metalloproteinases (MMPs) and blood-brain barrier injury after ischemia-reperfusion. Plasma biomarkers of oxidative stress may have utility as early indicators of efficacy in Phase 2 trials of antioxidant therapies in human stroke. To date, a valid biomarker has been unavailable. We measured F2-isoprostanes (F2IPs), free-radical induced products of neuronal arachadonic acid peroxidation, in acute ischemic stroke. We aimed to determine the change in plasma F2IP levels over time and relationship with plasma MMP-9 in tPA-treated and tPA-untreated stroke patients.. We performed a case-control study of consecutive ischemic stroke patients (25 tPA-treated and 27 tPA-untreated) presenting within 8 hours of stroke onset. Controls were individuals without prior stroke from a primary care clinic network serving the source population from which cases were derived. Infarct volume was determined on acute diffusion-weighted MRI (DWI) performed within 48 hours using a semi-automated computerized segmentation algorithm. Phlebotomy was performed at <8 hours, 24 hours, 2 to 5 days, and 4 to 6 weeks. F2IPs were measured by gas chromatography/mass spectrometry and MMP-9 by ELISA. Prestroke antioxidant dietary intake was measured by the 24-hour recall method.. In 52 cases and 27 controls, early (median 6 hours postonset) F2IPs were elevated in stroke cases compared with controls (medians 0. 041 versus 0.0295 pg/mL, P=0.012). No difference in F2IPSs was present at later time points. Early plasma F2IPs correlated with MMP-9 in all patients (P=0.01) and the tPA-treated subgroup (P=0.02). No correlation was found with NIHSS, DWI infarct volume, 90-day Rankin score, or C-reactive protein (P>0.05 for all).. In early human stroke we found evidence of increased oxidative stress and a relationship with MMP-9 expression, supporting findings from experimental studies.

Topics: Aged; Aged, 80 and over; alpha-Tocopherol; Antioxidants; Ascorbic Acid; Biomarkers; Brain Ischemia; Case-Control Studies; Cerebral Infarction; Diffusion Magnetic Resonance Imaging; F2-Isoprostanes; Female; Fibrinolytic Agents; Humans; Male; Matrix Metalloproteinase 9; Middle Aged; Oxidative Stress; Severity of Illness Index; Stroke; Tissue Plasminogen Activator; Treatment Outcome

Topics: Ascorbic Acid; Biomarkers; Cardiovascular Diseases; Confounding Factors, Epidemiologic; Evidence-Based Medicine; Food, Organic; Fruit; Humans; Stroke; Vegetables

The relation between plasma vitamin C and risk of stroke remains unclear. Although clinical trials showed no significant benefit of vitamin C supplementation in reducing stroke risk, they were not able to examine the relation between plasma vitamin C concentrations and stroke risk in a general population.. The objective was to examine the relation between baseline plasma vitamin C concentrations and risk of incident stroke in a British population.. A population-based prospective study was conducted in 20,649 men and women aged 40-79 y without prevalent stroke at baseline and participating in the European Prospective Investigation into Cancer-Norfolk prospective population study. The participants completed a health questionnaire and attended a clinic during 1993-1997 and were followed up for incident strokes through March 2005.. Over 196,713 total person-years (average follow-up: 9.5 y), 448 incident strokes occurred. In a Cox proportional hazards model, persons in the top quartiles of baseline plasma vitamin C concentrations had a 42% lower risk (relative risk: 0.58; 95% CI: 0.43, 0.78) than did those in the bottom quartile, independently of age, sex, smoking, body mass index, systolic blood pressure, cholesterol, physical activity, prevalent diabetes and myocardial infarction, social class, alcohol consumption, and any supplement use. Similar results were obtained after exclusion of persons with illnesses, users of ascorbic acid-containing supplements, and persons with a history of early strokes during the initial 2 y of follow-up.. Plasma vitamin C concentrations may serve as a biological marker of lifestyle or other factors associated with reduced stroke risk and may be useful in identifying those at high risk of stroke.

Topics: Adult; Age Factors; Aged; Antioxidants; Ascorbic Acid; Body Mass Index; Cohort Studies; Dietary Supplements; Female; Health Status Indicators; Health Surveys; Humans; Incidence; Longitudinal Studies; Male; Middle Aged; Predictive Value of Tests; Proportional Hazards Models; Prospective Studies; Risk Factors; Sex Factors; Smoking; Stroke; United Kingdom

Epidemiological studies have associated increased dietary intake of antioxidants (vitamin C, E, and beta-carotene) in preventing and decreasing the extent of ischemic brain injury. The effect of vitamin C supplementation on functional recovery after stroke has not been studied.. In this retrospective, case-control study of 23 patients with ischemic stroke taking vitamin C were identified and matched for age, sex, onset to admission, and admission total functional independence measure (TFIM) with 23 patients with ischemic stroke not taking Vitamin C supplementation. Vitamin C 1000 mg daily was prescribed on admission to our unit mainly to patients who were undernourished (defined as significant weight loss and/or 90% or less ideal body weight for age and sex) and those with pressure sores. The outcome measures were: change in the TFIM, FIM-Cognition (FIM-Cog), and FIM-Motor sub-scores, discharge disposition, and length of stay (LOS).. The change in TFIM (20 +/- 13 standard deviation [SD] vs. 26 +/- 6, p = 0.20), FIM-Cog (3 +/- 3 SD vs. 4 +/- 5, p = 0.41), FIM-Motor (15 +/- 11 SD vs. 20 +/- 13, p = 0.21) sub-scores were less in the vitamin C treated group, but these differences did not reach statistical significance. Similarly, no significant differences were found in LOS (21 +/- 9 SD vs. 23 +/- 9, p = 0.59), and discharge disposition (home/institution) (9/10 vs. 13/9, p = 0.60) between the vitamin C and the control groups.. This study suggests vitamin C supplementation did not enhance functional recovery in undernourished ischemic stroke patients.

Topics: Aged; Ascorbic Acid; Case-Control Studies; Convalescence; Dietary Supplements; Female; Humans; Male; Stroke

Topics: Ascorbic Acid; Humans; Nutrition Policy; Risk; Stroke

In the Rotterdam Study, the authors investigated whether high intake of antioxidants from food is associated with the risk of stroke. Among 5,197 participants who were followed on average for 6.4 years, 227 ischemic strokes occurred. Higher intake of antioxidants was associated with a lower risk of stroke. The relationship was dose-dependent, significant for vitamin C, and most pronounced in smokers. These results agree with the view that high dietary intake of antioxidants, in particular vitamin C and--in smokers--vitamin E, reduces the risk of stroke.

Topics: Aged; Antioxidants; Ascorbic Acid; Brain Ischemia; Cohort Studies; Comorbidity; Diet; Female; Follow-Up Studies; Fruit; Humans; Male; Netherlands; Risk; Risk Reduction Behavior; Stroke; Vegetables; Vitamin E

There are no prospective studies to determine whether plasma vitamin C modifies the risk of stroke among hypertensive and overweight individuals. We sought to examine whether plasma vitamin C modifies the association between overweight and hypertension and the risk of stroke in middle-aged men from eastern Finland.. We conducted a 10.4-year prospective population-based cohort study of 2419 randomly selected middle-aged men (42 to 60 years) with no history of stroke at baseline examination. A total of 120 men developed a stroke, of which 96 were ischemic and 24 hemorrhagic strokes.. Men with the lowest levels of plasma vitamin C (<28.4 micromol/L, lowest quarter) had a 2.4-fold (95% CI, 1.4 to 4.3; P=0.002) risk of any stroke compared with men with highest levels of plasma vitamin C (>64.96 micromol/L, highest quarter) after adjustment for age and examination months. An additional adjustment for body mass index, systolic blood pressure, smoking, alcohol consumption, serum total cholesterol, diabetes, and exercise-induced myocardial ischemia attenuated the association marginally (relative risk, 2.1; 95% CI, 1.2 to 3.8; P=0.01). Adjustment for prevalent coronary heart disease and atrial fibrillation did not attenuate the association any further. Furthermore, hypertensive men with the lowest vitamin C levels (<28.4 micromol/L) had a 2.6-fold risk (95% CI, 1.52 to 4.48; P<0.001), and overweight men (> or =25 kg/m2) with low plasma vitamin C had a 2.7-fold risk (95% CI, 1.48 to 4.90; P=0.001) for any stroke after adjustment for age, examination months, and other risk factors.. Low plasma vitamin C was associated with increased risk of stroke, especially among hypertensive and overweight men.

Topics: Adult; Ascorbic Acid; Body Mass Index; Brain Ischemia; Cerebral Hemorrhage; Cohort Studies; Demography; Finland; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged; Obesity; Prospective Studies; Risk; Risk Assessment; Risk Factors; Stroke

An association between ischemic stroke and increased oxidative stress has been suggested from animal studies. However, there is a lack of evidence with respect to this association in humans. Here, the time course of plasma levels of six carotenoids, which are lipophilic micronutrients with antioxidant properties, as well as of malondialdehyde (MDA), a marker of lipid peroxidation, was followed in ischemic stroke patients. Plasma levels of lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha- and beta-carotene, as well as MDA were measured by high-performance liquid chromatography in 28 subjects (19 men and nine women aged 76.9+/-8.7 years) with an acute ischemic stroke of recent onset (<24h) on admission, after 6 and 24 h, and on days 3, 5, and 7. Carotenoid and MDA levels in patients on admission were compared with those of age- and sex-matched controls. Plasma levels of lutein, lycopene, alpha- and beta-carotene were significantly lower and levels of MDA were significantly higher in patients in comparison with controls. Significantly higher levels of MDA and lower levels of lutein were found in patients with a poor early-outcome (functional decline) after ischemic stroke as compared to patients who remained functionally stable. These findings suggest that the majority of plasma carotenoids are lowered immediately after an ischemic stroke, perhaps as a result of increased oxidative stress, as indicated by a concomitant rise in MDA concentrations. Among the carotenoids, only lutein plasma changes are associated with a poor early-outcome.

Topics: Aged; Ascorbic Acid; beta Carotene; Brain Ischemia; Carotenoids; Chromatography, High Pressure Liquid; Disease Progression; Female; Humans; Lipid Peroxidation; Lutein; Lycopene; Male; Malondialdehyde; Oxidative Stress; Stroke; Vitamin A; Vitamin E; Xanthophylls; Zeaxanthins

Of particular physiological interest, ascorbate, the ionized form of ascorbic acid, possesses strong reducing properties. However, it has been shown to induce oxidative stress and lead to apoptosis under certain experimental conditions. Ascorbate in the brain is released during hypoxia, including stroke, and is subsequently oxidized in plasma. The oxidized product (dehydroascorbate) is transported into neurons via a glucose transporter (GLUT) during a reperfusion period. The dehydroascorbate taken up by cells is reduced to ascorbate by both enzymatic and non-enzymatic processes, and the ascorbate is stored in cells. This reduction process causes an oxidative stress, due to coupling of redox reactions, which can induce cellular damage and trigger apoptosis. Ascorbate treatment decreased cellular glutathione (GSH) content, and increased the rates of lipid peroxide production in rat cortical slices. Wortmannin, a specific inhibitor of phosphatidylinositol (PI)-3-kinase (a key enzyme in GLUT translocation), prevented the ascorbate induced-decrease of GSH content, and suppressed ascorbate-induced lipid peroxide production. However, wortmannin was ineffective in reducing hydrogen peroxide (H(2)O(2))-induced oxidative stress. The oxidative stress caused ceramide accumulation, which was proportionally changed with lipid peroxides when the cortical slices were treated with ascorbate. These differential effects support the hypothesis that GLUT efficiently transports the dehydroascorbate into neurons, causing oxidative stress.

Topics: Androstadienes; Animals; Apoptosis; Ascorbic Acid; Brain; Ceramides; Dehydroascorbic Acid; Dose-Response Relationship, Drug; Enzyme Inhibitors; Glutathione; Hypoxia-Ischemia, Brain; Lipid Peroxides; Male; Monosaccharide Transport Proteins; Nerve Degeneration; Organ Culture Techniques; Oxidative Stress; Rats; Rats, Sprague-Dawley; Rotenone; Signal Transduction; Sphingomyelins; Stroke; Uncoupling Agents; Wortmannin

To assess whether systemic oxidative stress can predict the risk of first myocardial infarction, ischemic stroke, and congestive heart failure.. A longitudinal study started in 1992 and completed in 1997.. Community-based, outpatient.. 102 apparently healthy, community-dwelling subjects age 80 and older from the Vibrata valley, Teramo, Italy.. Plasma vitamin E, beta-carotene, vitamin C, fluorescent products of lipid peroxidation (FPLPs), and serum lipids were determined at enrollment.. Thirty-two cardiovascular events were recorded in 47.4 months of follow-up. The subjects with vitamin E levels in the highest quartile had a risk of cardiovascular events one-sixth those with vitamin E levels in the lowest quartile (relative risk (RR) = 0.16; 95% confidence interval (CI) = 0.04-0.55). The subjects with FPLPs in the highest quartile had a risk seven times greater than those with FPLPs in the lowest quartile (RR = 7.61; 95% CI = 2.23-25.96). No association was observed for vitamin C, beta-carotene, or total cholesterol. Multivariate adjustment for known risk factors did not significantly change the results.. Our results suggest that in apparently healthy, community-dwelling very old subjects, base-line plasma concentration of vitamin E and FPLPs predicts the risk of future cardiovascular events. We confirm previous data showing that total cholesterol is not a predictor of cardiovascular disease in people age 80 and older.

Topics: Age Distribution; Age Factors; Aged; Aged, 80 and over; Ascorbic Acid; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Female; Heart Failure; Humans; Incidence; Italy; Lipid Peroxides; Longitudinal Studies; Male; Multivariate Analysis; Myocardial Infarction; Oxidative Stress; Predictive Value of Tests; Risk Factors; Stroke; Triglycerides; Vitamin E

Neuronal injury in ischemic stroke is partly mediated by cytotoxic reactive oxygen species. Although the antioxidant ascorbic acid (AA) or vitamin C does not penetrate the blood-brain barrier (BBB), its oxidized form, dehydroascorbic acid (DHA), enters the brain by means of facilitative transport. We hypothesized that i.v. DHA would improve outcome after stroke because of its ability to cross the BBB and augment brain antioxidant levels. Reversible or permanent focal cerebral ischemia was created by intraluminal middle cerebral artery occlusion in mice treated with vehicle, AA, or DHA (40, 250, or 500 mg/kg), either before or after ischemia. Given before ischemia, DHA caused dose-dependent increases in postreperfusion cerebral blood flow, with reductions in neurological deficit and mortality. In reperfused cerebral ischemia, mean infarct volume was reduced from 53% and 59% in vehicle- and AA-treated animals, respectively, to 15% in 250 mg/kg DHA-treated animals (P < 0.05). Similar significant reductions occurred in nonreperfused cerebral ischemia. Delayed postischemic DHA administration after 15 min or 3 h also mediated improved outcomes. DHA (250 mg/kg or 500 mg/kg) administered at 3 h postischemia reduced infarct volume by 6- to 9-fold, to only 5% with the highest DHA dose (P < 0.05). In contrast, AA had no effect on infarct volumes, mortality, or neurological deficits. No differences in the incidence of intracerebral hemorrhage occurred. Unlike exogenous AA, DHA confers in vivo, dose-dependent neuroprotection in reperfused and nonreperfused cerebral ischemia at clinically relevant times. As a naturally occurring interconvertible form of AA with BBB permeability, DHA represents a promising pharmacological therapy for stroke based on its effects in this model of cerebral ischemia.

Topics: Animals; Antioxidants; Ascorbic Acid; Biological Transport; Brain; Cerebrovascular Circulation; Dehydroascorbic Acid; Dose-Response Relationship, Drug; Mice; Middle Cerebral Artery; Neuroprotective Agents; Reperfusion; Stroke; Time Factors; Treatment Outcome

To study the relation between intake of the antioxidant flavonoid quercetin and subsequent incidence of cerebrovascular disease (CVA).. A cohort study carried out among 9208 Finnish men and women 15 y or more of age and initially free from cardiovascular disease. During a 28 y follow-up period in 1967-1994, a total of 824 cases with CVA were diagnosed.. Food consumption data were collected using a dietary history interview method covering the total habitual diet during the previous year.. Quercetin intake was not associated with CVA incidence. The relative risk of CVA adjusted for age, serum cholesterol, body mass index, smoking, hypertension, diabetes, geographical area, occupation and intake of beta-carotene, vitamin E, vitamin C, fibre, various fatty acids, and energy between the highest and lowest quartiles of quercetin intake was 0.99 (95% confidence interval (CI)=0.71-1.38) for men and 0.85 (CI=0.60-1.21) for women. In contrast, apples, the major source of quercetin in the study population, showed a significant inverse association both in men and women, mainly due to an association with thrombotic or embolic stroke. The relative risks of thrombotic stroke after further adjustment for quercetin intake were 0.59 (CI=0.35-0.99; P=0.45) and 0.61 (CI=0.33-1.12: P for trend=0.02) for men and women, respectively.. The results suggest that the intake of apples is related to a decreased risk of thrombotic stroke. This association apparently is not due to the presence of the antioxidant flavonoid quercetin.

Topics: Aging; Antioxidants; Ascorbic Acid; Body Mass Index; Cholesterol; Cohort Studies; Diet; Dietary Fiber; Energy Intake; Fatty Acids; Female; Fruit; Humans; Hypertension; Intracranial Thrombosis; Male; Quercetin; Risk Factors; Smoking; Stroke; Vitamin E

Topics: Antioxidants; Ascorbic Acid; Dementia, Vascular; Humans; Male; Stroke; Vitamin E

To determine the relation between multivitamin use and death from heart disease, cerebrovascular disease, and cancer, the authors examined a prospective cohort of 1,063,023 adult Americans in 1982-1989 and compared the mortality of users of multivitamins alone; vitamin A, C, or E alone; and multivitamin and vitamin A, C, or E in combination with that of vitamin nonusers by using multivariate Cox proportional hazard models. Multivitamin users had heart disease and cerebrovascular disease mortality risks similar to those of nonusers, whereas combination users had mortality risks that were 15% lower than those of nonusers. Multivitamin and combination use had minimal effect on cancer mortality overall, although mortality from all cancers combined was increased among male current smokers who used multivitamins alone (relative risk (RR) = 1.13, 95% confidence interval (CI): 1.05, 1.23) or in combination with vitamin A, C, or E (RR = 1.16, 95% CI: 1.06, 1.26), but decreased in male combination users who had never (RR = 0.86, 95% CI: 0.74, 0.99) or had formerly (RR = 0.90, 95% CI: 0.82, 0.98) smoked. No such associations were seen in women. These observational data provide limited support for the hypothesis that multivitamin use in combination with vitamin A, C, or E may reduce heart disease and cardiovascular disease mortality, but add to concerns raised by randomized studies that some vitamin supplements may adversely affect male smokers.

Topics: Aged; Ascorbic Acid; Coronary Disease; Female; Humans; Male; Middle Aged; Mortality; Neoplasms; Proportional Hazards Models; Prospective Studies; Risk Factors; Smoking; Stroke; Vitamin A; Vitamin E; Vitamins

Epidemiological evidence suggests that vitamin C may decrease the risk of stroke. The purpose of the present study was to examine the association of serum vitamin C concentration with the subsequent incidence of stroke.. In a Japanese rural community, a cohort of 880 men and 1241 women aged 40 years and older who were initially free of stroke was examined in 1977 and followed until 1997. The baseline examination included a measurement of serum vitamin C concentration. The incidence of stroke was determined by annual follow-up examinations and registry.. During the 20-year observation period, 196 incident cases of all stroke, including 109 cerebral infarctions and 54 hemorrhagic strokes, were documented. Strong inverse associations were observed between serum vitamin C concentration and all stroke (sex- and age-adjusted hazard ratios were 0.93, 0.72, and 0.59, respectively, for the second, third, and fourth quartiles compared with the first quartile; P for trend=0.002), cerebral infarction (0.71, 0.59, and 0.51; P for trend=0.015), and hemorrhagic stroke (0.89, 0.75, and 0. 45; P for trend=0.013). Additional adjustments for blood pressure, serum total cholesterol, body mass index, physical activity, smoking, alcohol drinking, antihypertensive medication, atrial fibrillation, and history of ischemic heart disease did not attenuate these associations markedly.. Serum vitamin C concentration was inversely related to the subsequent incidence of stroke. This relationship was significant for both cerebral infarction and hemorrhagic stroke. Additional mechanistic hypotheses may be required to explain our findings.

Topics: Adult; Age Distribution; Aged; Ascorbic Acid; Cerebral Hemorrhage; Cerebral Infarction; Cohort Studies; Comorbidity; Diet; Female; Follow-Up Studies; Humans; Incidence; Japan; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Risk Factors; Rural Population; Sex Distribution; Stroke

Antioxidants may protect against atherosclerosis and thus prevent cerebrovascular disease. We studied the association between dietary antioxidants and subtypes of stroke.. The study cohort consisted of 26 593 male smokers, aged 50 to 69 years, without a history of stroke. They were participants of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study in Finland. The men completed a validated dietary questionnaire at baseline. Incident cases were identified through national registers.. During a 6.1-year follow-up, 736 cerebral infarctions, 83 subarachnoid hemorrhages, and 95 intracerebral hemorrhages occurred. Neither dietary flavonols and flavones nor vitamin E were associated with risk for stroke. The dietary intake of beta-carotene was inversely associated with the risk for cerebral infarction (relative risk [RR] of highest versus lowest quartile 0.74, 95% CI 0.60 to 0. 91), lutein plus zeaxanthin with risk for subarachnoid hemorrhage (RR 0.47, 95% CI 0.24 to 0.93), and lycopene with risks of cerebral infarction (RR 0.74, 95% CI 0.59 to 0.92) and intracerebral hemorrhage (RR 0.45, 95% CI 0.24 to 0.86). Vitamin C intake was inversely associated with the risk for intracerebral hemorrhage (RR 0.39, 95% CI 0.21 to 0.74). After simultaneous modeling of the antioxidants, a significant association remained only between beta-carotene intake and risk for cerebral infarction (RR 0.77, 95% CI 0.61 to 0.99).. Dietary intake of beta-carotene was inversely associated with the risk for cerebral infarction. No association was detected between other dietary antioxidants and risk for stroke.

Topics: Aged; Ascorbic Acid; beta Carotene; Carotenoids; Cerebral Hemorrhage; Cerebral Infarction; Cohort Studies; Comorbidity; Diet; Finland; Flavonoids; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Risk; Risk Assessment; Smoking; Stroke; Subarachnoid Hemorrhage; Vitamin E; Vitamins

Topics: Ascorbic Acid; Blood Chemical Analysis; Coal Mining; Glucose; Heat Exhaustion; Heat Stroke; Hot Temperature; Humans; Japan; Occupational Diseases; Potassium; Sodium; Statistics as Topic; Stroke; Thiamine

Topics: Ascorbic Acid; Cerebrovascular Disorders; Flavonoids; Nutrition Therapy; Stroke; Vitamins

Topics: Ascorbic Acid; Capillary Permeability; Flavonoids; Nutrition Therapy; Stroke; Vitamins

Topics: Aminophylline; Ascorbic Acid; Cerebral Hemorrhage; Ethylenediamines; Flavonoids; Humans; Rutin; Stroke; Theophylline; Vitamins