ascorbic-acid and Coronary-Disease

Atherosclerotic cardiovascular diseases (CVD) are a major source of mortality and morbidity in general population. Oxidative modification of low density lipoprotein (LDL) represent the most important determinant factor in the development and progression of atherosclerotic lesions. Oxidative damage and the production of free radicals (FRs) in the endothelium are some of the main factors involved in the pathogenesis of the atherosclerotic process which causes CVD. Appropriate nutritional practices are of central importance in managing risk and treatment of CVD; indeed, many current guidelines contain nutritional recommendations to reduce the risk of these diseases. In observational studies vitamin C and E, the most prevalent natural antioxidant vitamins, have suggested that supplemental users have lower rate of coronary events. Despite these data, several large randomized controlled trials (RCTs) have failed to confirm the benefits for vitamin C and E in cardiovascular (CV) prevention. The aim of this review is to examine the studies published in literature which report the effect of supplementation with antioxidant vitamins (C,E) in the primary and secondary prevention of CVD in men due to atherosclerotic process.

Topics: Ascorbic Acid; Coronary Disease; Humans; Male; Vitamin E

Many epidemiological studies have reported that antioxidant vitamin intake from diet or supplements are associated with a lower risk of coronary heart disease (CHD), the findings are, however, inconsistent. We undertook a meta-analysis of cohort studies to examine the relations between antioxidant vitamins (vitamins C, E, and beta-carotene) and CHD risk.. We included all the relevant cohort studies if they provided a relative risk and corresponding 95% confidence interval (CI) of CHD in relation to antioxidant vitamins intake from diet or supplement. Fifteen cohort studies were identified involving a total of 7415 incident CHD cases and 374,488 participants with a median follow-up of approximately 10, 8.5, and 15 years for vitamins C, E, and beta-carotene, respectively. Pooled estimates across studies were obtained by random-effects model. The potential sources of heterogeneity and publication bias were also estimated. For vitamins C, E, and beta-carotene, a comparison of individuals in the top third with those in the bottom third of baseline value yielded a combined relative risk of 0.84 (95% CI, 0.73-0.95), 0.76 (95% CI, 0.63-0.89), and 0.78 (95% CI, 0.53-1.04), respectively. Subgroup analyses show that dietary intake of vitamins C and E and supplement use of vitamin E have an inverse association with CHD risk, but supplement use of vitamin C has no significant association with CHD risk. In the dose-response meta-analysis, each 30 mg/day increase in vitamin C, 30 IU/day increase in vitamin E, and 1 mg/day increase in beta-carotene yielded the estimated overall relative risk for CHD of 1.01 (95% CI, 0.99-1.02), 0.96 (95% CI, 0.94-0.99), and 1.00 (95% CI, 0.88-1.14), respectively.. Our findings in this meta-analysis suggest that an increase in dietary intake of antioxidant vitamins has encouraging prospects for possible CHD prevention.

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Cohort Studies; Coronary Disease; Humans; Incidence; Vitamin E

Epidemiologic studies have suggested a lower risk of coronary heart disease (CHD) at higher intakes of fruit, vegetables, and whole grain. Whether this association is due to antioxidant vitamins or some other factors remains unclear.. We studied the relation between the intake of antioxidant vitamins and CHD risk.. A cohort study pooling 9 prospective studies that included information on intakes of vitamin E, carotenoids, and vitamin C and that met specific criteria was carried out. During a 10-y follow-up, 4647 major incident CHD events occurred in 293 172 subjects who were free of CHD at baseline.. Dietary intake of antioxidant vitamins was only weakly related to a reduced CHD risk after adjustment for potential nondietary and dietary confounding factors. Compared with subjects in the lowest dietary intake quintiles for vitamins E and C, those in the highest intake quintiles had relative risks of CHD incidence of 0.84 (95% CI: 0.71, 1.00; P=0.17) and 1.23 (1.04, 1.45; P=0.07), respectively, and the relative risks for subjects in the highest intake quintiles for the various carotenoids varied from 0.90 to 0.99. Subjects with higher supplemental vitamin C intake had a lower CHD incidence. Compared with subjects who did not take supplemental vitamin C, those who took >700 mg supplemental vitamin C/d had a relative risk of CHD incidence of 0.75 (0.60, 0.93; P for trend <0.001). Supplemental vitamin E intake was not significantly related to reduced CHD risk.. The results suggest a reduced incidence of major CHD events at high supplemental vitamin C intakes. The risk reductions at high vitamin E or carotenoid intakes appear small.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Carotenoids; Cohort Studies; Coronary Disease; Diet Surveys; Dietary Supplements; Female; Follow-Up Studies; Fruit; Humans; Incidence; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Risk; Risk Factors; Vegetables; Vitamin E

Topics: Antioxidants; Ascorbic Acid; Chemoprevention; Coronary Disease; Dietary Supplements; Endothelium, Vascular; Evidence-Based Medicine; Humans; Incidence; Nutrition Surveys; Risk Factors; United States; Women's Health

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; beta Carotene; Clinical Trials as Topic; Cohort Studies; Coronary Disease; Dietary Supplements; Female; Humans; Male; Middle Aged; Oxidants; Oxidative Stress; Randomized Controlled Trials as Topic; Reactive Oxygen Species; Vitamin E; Vitamins

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antioxidants; Ascorbic Acid; Coronary Disease; Endothelium, Vascular; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Losartan; Nitric Oxide; Oxidative Stress; Ramipril; Receptor, Angiotensin, Type 1; Superoxide Dismutase; Vitamins

Antioxidants, trace minerals, and certain amino acids enhance antioxidant defense of the body by improving intracellular redox status, vascular endothelial function, and nitric oxide secretion. Antioxidant supplementation has been suggested for primary and secondary prevention of coronary heart disease.

Topics: Animals; Antioxidants; Ascorbic Acid; Coronary Disease; Diet; Humans; Lipoproteins, LDL; Vitamin E

Although vitamin deficiency is encountered infrequently in developed countries, inadequate intake of several vitamins is associated with chronic disease.. To review the clinically important vitamins with regard to their biological effects, food sources, deficiency syndromes, potential for toxicity, and relationship to chronic disease.. We searched MEDLINE for English-language articles about vitamins in relation to chronic diseases and their references published from 1966 through January 11, 2002.. We reviewed articles jointly for the most clinically important information, emphasizing randomized trials where available.. Our review of 9 vitamins showed that elderly people, vegans, alcohol-dependent individuals, and patients with malabsorption are at higher risk of inadequate intake or absorption of several vitamins. Excessive doses of vitamin A during early pregnancy and fat-soluble vitamins taken anytime may result in adverse outcomes. Inadequate folate status is associated with neural tube defect and some cancers. Folate and vitamins B(6) and B(12) are required for homocysteine metabolism and are associated with coronary heart disease risk. Vitamin E and lycopene may decrease the risk of prostate cancer. Vitamin D is associated with decreased occurrence of fractures when taken with calcium.. Some groups of patients are at higher risk for vitamin deficiency and suboptimal vitamin status. Many physicians may be unaware of common food sources of vitamins or unsure which vitamins they should recommend for their patients. Vitamin excess is possible with supplementation, particularly for fat-soluble vitamins. Inadequate intake of several vitamins has been linked to chronic diseases, including coronary heart disease, cancer, and osteoporosis

Topics: Ascorbic Acid; Avitaminosis; Blood Coagulation; Breast Neoplasms; Carotenoids; Chronic Disease; Colorectal Neoplasms; Coronary Disease; Dietary Supplements; Female; Folic Acid; Fractures, Bone; Humans; Lung Neoplasms; Male; Neoplasms; Neural Tube Defects; Prostatic Neoplasms; Risk Factors; Vitamin A; Vitamin B 12; Vitamin B 6; Vitamin D; Vitamin E; Vitamin K; Vitamins

Topics: Antioxidants; Ascorbic Acid; Carotenoids; Chronic Disease; Coronary Disease; Cross-Cultural Comparison; Epidemiologic Methods; Humans; Neoplasms; Observation; Risk Factors; Vitamin E

Topics: Animals; Antioxidants; Arteriosclerosis; Ascorbic Acid; Carotenoids; Clinical Trials as Topic; Coronary Disease; Fatty Acids, Monounsaturated; Flavonoids; Fluvastatin; Humans; Indoles; Oxidative Stress; Phenols; Polymers; Polyphenols; Probucol; Vitamin E

Endothelium-derived nitric oxide (EDNO) is a pivotal molecule in the regulation of vascular tone via the stimulation of vascular smooth muscle cell relaxation and concomitant vasodilation. In addition, EDNO exerts a number of other potent antiatherogenic effects, including inhibition of leukocyte-endothelial interactions, smooth muscle cell proliferation, and platelet aggregation. Endothelial vasodilator dysfunction has been observed in patients with CAD or coronary risk factors such as hypercholesterolemia, hyperhomocysteinemia, essential hypertension, diabetes mellitus, smoking, and aging. Most of these conditions are associated with increased oxidative stress, particularly increased production of superoxide radicals and elevated levels of oxidized LDL, both of which can attenuate the biological activity of EDNO. The levels of superoxide and oxidized LDL can be decreased by administering the small molecule antioxidants vitamins E and C. Vitamin C also spares intracellular thiols, which in turn can stabilize EDNO through the formation of biologically active S-nitrosothiols. Here we review the role that vitamins E and C and thiol compounds play in endothelium-dependent vasodilation. Understanding the mechanisms of the reversal of endothelial dysfunction by natural antioxidants will lead to successful therapeutic interventions of CAD and its clinical sequelae.

Topics: Animals; Antioxidants; Ascorbic Acid; Coronary Disease; Endothelium, Vascular; Humans; Muscle, Smooth, Vascular; Nitric Oxide; Nitroso Compounds; Rabbits; Rats; Sulfhydryl Compounds; Vasodilation; Vitamin E

Flavonoids are nearly ubiquitous in plants and are recognized as the pigments responsible for the colors of leaves, especially in autumn. They are rich in seeds, citrus fruits, olive oil, tea, and red wine. They are low molecular weight compounds composed of a three-ring structure with various substitutions. This basic structure is shared by tocopherols (vitamin E). Flavonoids can be subdivided according to the presence of an oxy group at position 4, a double bond between carbon atoms 2 and 3, or a hydroxyl group in position 3 of the C (middle) ring. These characteristics appear to also be required for best activity, especially antioxidant and antiproliferative, in the systems studied. The particular hydroxylation pattern of the B ring of the flavonoles increases their activities, especially in inhibition of mast cell secretion. Certain plants and spices containing flavonoids have been used for thousands of years in traditional Eastern medicine. In spite of the voluminous literature available, however, Western medicine has not yet used flavonoids therapeutically, even though their safety record is exceptional. Suggestions are made where such possibilities may be worth pursuing.

Topics: Animals; Antioxidants; Antiviral Agents; Ascorbic Acid; Blood Platelets; Coronary Disease; Cytoprotection; Enzyme Inhibitors; Flavonoids; Heart Diseases; Humans; Immune System; Inflammation; Lymphocytes; Mast Cells; Neoplasms; Xenobiotics

Topics: American Heart Association; Antioxidants; Ascorbic Acid; beta Carotene; Clinical Trials as Topic; Coronary Disease; Diet; Health Personnel; Humans; Risk; Treatment Outcome; Vitamin E

The vascular endothelium plays a key role in the local regulation of vascular tone by the release of vasodilator substances (i.e. endothelium-derived relaxing factor (EDRF = nitric oxide, NO) and prostacyclin) and vasoconstrictor substances (i.e. thromboxane A2, free radicals, or endothelin). Using either agents like acetylcholine or changes in flow to stimulate the release of EDRF (NO), clinical studies have revealed the importance of EDRF in both basal and stimulated control of vascular tone in large epicardial coronary arteries and in the coronary microcirculation. The regulatory function of the endothelium is altered by cardiovascular risk factors or disorders such as hypercholesterolemia, chronic smoking, hypertension or chronic heart failure. Endothelial dysfunction appears to have detrimental functional consequences as well as adverse longterm effects, including vascular remodelling. Endothelial dysfunction is associated with impaired tissue perfusion particularly during stress and paradoxical vasoconstriction of large conduit vessels including the coronary arteries. These effects may cause or contribute to myocardial ischemia. Several mechanisms may be involved in the development of endothelial dysfunction, such as reduced synthesis and release of EDRF or enhanced inactivation of EDRF after its release from endothelial cells by radicals or oxidized low-density lipoprotein (LDL). Increased plasma levels of oxidized LDL have been noted in chronic smokers and are related to the extent endothelial dysfunction, raising the possibility that chronic smoking potentiates endothelial dysfunction by increasing circulating and tissue levels of oxidized LDL. In heart failure, cytokines and/or reduced flow (reflecting reduced shear stress) may be involved in the development of endothelial dysfunction and can be reversed by physical training. Other mechanisms include an activated renin-angiotensin system (i.e. postmyocardial infarction) with increased breakdown of bradykinin by enhanced angiotensin converting enzyme (ACE) activity. There is evidence that endogenous bradykinin is involved in coronary vasomotor control both in coronary conduit and resistance vessels. ACE inhibitors enhance endothelial function by a bradykinin-dependent mechanism and probably also by blunting the generation of superoxide anion. Endothelial dysfunction appears to be reversible by administering L-arginine, the precursor of nitric oxide, lowering cholesterol levels, physical training,

Topics: Acetylcholine; Ascorbic Acid; Cardiac Output, Low; Coronary Disease; Dose-Response Relationship, Drug; Endothelium, Vascular; Enzyme Inhibitors; Humans; Hypercholesterolemia; Hyperemia; Lipoproteins, LDL; omega-N-Methylarginine; Radial Artery

Most species of plants and animals synthesize ascorbic acid, but human subjects cannot, making vitamin C an essential component of our diet. Relationships between vitamin C intake and status, and between status and health are not yet clear. There is evidence, however, that higher intake of vitamin C is associated with lower risk of disease, supporting the concept that optimal intake is needed for optimal vitamin C status, and that both factors are required for optimal health. Vitamin C has low toxicity in healthy subjects, but a clear definition of optimal status and the dietary intake required to meet and maintain this status is needed before a change in the current recommended intake can be considered. Available evidence suggests that intake of 200 mg vitamin C/d saturates tissues and maintains fasting plasma levels above the proposed threshold (50 mumol/l) for minimum risk of CHD. However, the issue of whether or not these levels produce 'optimal vitamin C status' awaits the clear and accepted definition of the term. This definition in turn awaits the development of reliable functional markers capable of assessing the effects of varying levels of vitamin C nutriture. In the present paper the relationship between intake and body stores of vitamin C and the role of vitamin C in human health are reviewed briefly. The requirements of a reliable functional marker of human vitamin C status are defined, three classes of functional markers (molecular, biochemical and physiological) are described, and possible candidate markers are examined.

Topics: Ascorbic Acid; Biomarkers; Coronary Disease; Health Promotion; Humans; Nutritional Requirements; Nutritional Status; Reference Values

Clinical use of antioxidant vitamin supplementation may help to prevent coronary heart disease (CHD). Epidemiologic studies find lower CHD morbidity and mortality in persons who consume larger quantities of antioxidants in foods or supplements. Clinical trials indicate that supplementation with certain nutrients is beneficial in reducing the incidence of CHD events. Recent studies show that supplementation with antioxidant vitamins E and C have benefits in CHD prevention; however, supplementation with beta-carotene may have deleterious effects and is not recommended. Current evidence suggests that patients with CHD would probably benefit from taking vitamin E in a dosage of 400 IU per day and vitamin C in a dosage of 500 to 1,000 mg per day. Clinicians may also want to consider vitamin supplementation for CHD prevention in high-risk patients. Folate lowers elevated homocysteine levels, but evidence for routine supplemental use does not yet exist. Other nutritional supplements are currently under investigation.

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Coronary Disease; Humans; Patient Education as Topic; Randomized Controlled Trials as Topic; Teaching Materials; Vitamin E; Vitamins

Topics: Ascorbic Acid; beta Carotene; Clinical Trials as Topic; Coronary Disease; Female; Humans; Male; Sri Lanka; Vitamin A; Vitamin E; Vitamins

Topics: Antioxidants; Ascorbic Acid; Coronary Disease; Drug Tolerance; Free Radicals; Heart Failure; Humans; Muscle, Smooth, Vascular; Nitrates; Reactive Oxygen Species; Vitamin E

Vitamin C, carotenoids, and vitamin E, the three main dietary sources of antioxidants, each effect lipid peroxidation and may reduce atherogenesis and lower the risk of coronary heart disease (CHD). Crosscultural studies of antioxidants find that regions with relatively low dietary intake tend to have higher rates of CHD, but in these studies it is difficult to account for other important cardiovascular risk factors. Evidence from observational studies with more detailed information do not support a cardiovascular benefit for vitamin C, although the cardiovascular effect of vitamin C supplementation among populations with marginal vitamin C deficiency is not known. Results from recent clinical trials of beta-carotene supplementation show no cardiovascular benefit, although several observational studies have found an inverse association between carotenoid intake or plasma levels and risk of CHD. The benefit reported in the observational studies may be due to consumption in foods rich in beta-carotene rather than the beta-carotene itself. The evidence for a cardiovascular benefit of antioxidants is strongest for vitamin E. Three large prospective studies find that vitamin E supplement users have approximately 40% lower rates of CHD. Short durations and doses of less than 100 IU/d (when data were available) have no significant effect. The effect of dietary vitamin E may be more modest but still associated with lower risk of CHD in populations in which vitamin E supplementation is infrequent. In a large randomized trial, a nonsignificant reduction in CHD risk was reported for 50 IU/d, although the dose may have been insufficient. A secondary prevention trial of 400 and 800 IU/day reported a strong reduction in nonfatal myocardial infarction, further supporting the large body of evidence that suggests that high doses of vitamin E reduce risk of CHD.

Topics: Antioxidants; Ascorbic Acid; Cardiology; Carotenoids; Coronary Disease; Food, Fortified; Humans; Primary Prevention; Risk Factors; Vitamin E

This review summarizes the scientific evidence for a possible role of antioxidants in the prevention of coronary heart disease (CHD). Dietary antioxidants include vitamin E, vitamin C and beta-carotene, whereas selenium is an integral part of the antioxidant enzyme glutathione peroxidase. Experimental studies suggest that the oxidation of low-density lipoproteins (LDL) in the vessel wall plays an important role in the development of atherosclerotic lesions. The resistance of LDL to oxidation is increased by antioxidant supplementation, at least in vitro. Epidemiological studies have not demonstrated unequivocally that a high intake of antioxidants leads to a decreased risk of CHD. Studies on dietary intake and serum levels of antioxidants do point in the direction of a preventive effect of antioxidants, whereas the results of intervention studies are less conclusive. Beta-carotene supplementation is not associated with any decrease in CHD; high doses of vitamin E may be beneficial, but results from large trials are to be awaited. General preventive measures based on antioxidant supplementation are not yet justifiable.

Topics: Animals; Antioxidants; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Coronary Disease; Diet; Female; Free Radicals; Humans; Lipoproteins, LDL; Male; Oxidation-Reduction; Prospective Studies; Risk Factors; Selenium; Vitamin E

Topics: Antioxidants; Ascorbic Acid; Clinical Trials as Topic; Coronary Artery Disease; Coronary Disease; Diet; Dietary Fats; Food, Fortified; Humans; Vitamin E

Evidence is increasing that oxidation of low-density lipoprotein cholesterol may be instrumental in atherogenesis. As a result, a number of studies have been undertaken to evaluate the effects of antioxidant vitamins, beta carotene, selenium, and monounsaturated fat on coronary artery disease. Results in many instances have been promising, particularly in the case of vitamin E supplements. Studies of pro-oxidants, such as iron and copper, are inconclusive at this time, and a trial to assess the value of probucol in hypercholesterolemic patients is currently under way.

Topics: Adult; Aged; Antioxidants; Arteriosclerosis; Ascorbic Acid; beta Carotene; Carotenoids; Cholesterol, LDL; Coronary Disease; Female; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Vitamin E

Topics: Antineoplastic Agents; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Coronary Disease; Fruit; Humans; Incidence; Neoplasms; Vegetables; Vitamin E

Topics: Antioxidants; Ascorbic Acid; Carotenoids; Coronary Disease; Diet; Female; Humans; Male; United Kingdom; Vitamin E; Vitamins

This review briefly summarizes the scientific evidence for a possible role of antioxidants in the prevention of coronary heart disease (CHD). Antioxidants in our diet include vitamins E, C, and beta-carotene, whereas selenium is an integral part of the antioxidant enzyme glutathione peroxidase (GSHPx). Experimental evidence suggests that free-radical damage and antioxidant defence may play an important role in the development of coronary heart disease. Epidemiological studies have produced some intriguing results, but have not indicated unequivocally that a high intake of antioxidants leads to a decreased cardiovascular disease risk. We conclude that the antioxidant atherosclerosis hypothesis is promising, but that the results of long-term intervention studies are still to be awaited. Preventive action based on antioxidant supplementation is therefore not justifiable as yet. Nevertheless, the findings so far certainly do support the recommendations for a varied diet rich in vegetables and fruit.

Topics: Animals; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Coronary Disease; Diet; Fruit; Humans; Selenium; Vegetables; Vitamin E

Topics: Animals; Antioxidants; Ascorbic Acid; Coronary Disease; Drug Interactions; Flavonoids; Free Radical Scavengers; Free Radicals; Humans; Lipid Peroxidation; Molecular Structure; Myocardial Ischemia; Myocardial Reperfusion; Oxidation-Reduction; Phagocytes; Plants; Reactive Oxygen Species

Coronary artery disease (CAD) remains by far the leading killer of men and women in the United States, despite a 2% per year decline over the past 2 decades. While CAD becomes the leading cause of death in U.S. women after 60, it becomes so in men after age 40. Heart disease is responsible for one of every three deaths in women as well as men. Thus, any intervention that can reduce CAD risks could have a tremendous public health impact among U.S. adults. Over the past several decades, the atherogenic potential of low density lipoprotein (LDL) cholesterol has been clearly identified. Recent evidence suggests that oxidation of LDL may enhance its atherogenicity, raising the possibility that antioxidant vitamins, which inhibit the oxidation of LDL, may reduce the risk of CAD. Although antioxidants can preserve endothelial function, inhibit platelet aggregability, and reduce atherosclerotic plaque progression in animals, whether supplementation with antioxidant vitamins will reduce the risk of CAD in humans remains unclear. The epidemiologic studies that have explored the antioxidant vitamin hypothesis in humans have included descriptive and cross-sectional studies, analytic investigation using case-control and prospective cohort study designs, as well as a few small trials in secondary prevention. The findings from these studies are not totally consistent, but generally support the hypothesis that antioxidant vitamins may reduce risk of CAD. At present, therefore, antioxidant vitamins represent a promising, but as yet unproven, means to decrease risks of CAD. Several large-scale randomized trials will provide reliable evidence on this question over the next several years. In primary prevention, the recently begun Women's Health Study of 40,000 female health professionals is testing alternate-day doses of beta-carotene (50 mg) and vitamin E (600 mg), and the ongoing Physicians' Health Study of > 22,000 male physicians is also testing a 50 mg combination of beta-carotene, vitamin E, and vitamin C among approximately 8,000 women not eligible for the Women's Health Study due to a prior history of cardiovascular disease. These and other trials will provide reliable, direct evidence concerning the role of antioxidant vitamins in the primary and secondary prevention of cardiovascular disease in women. Such data are crucial both for individual clinical decision making as well as for formulating rational public health policies.

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Coronary Disease; Female; Humans; Male; Randomized Controlled Trials as Topic; United States; Vitamin E; Vitamins

Topics: Ascorbic Acid; Coronary Disease; Fish Oils; Humans; Hyperlipidemias; Lipid Metabolism; Male; Risk Factors; Smoking; Vitamin E

The concept that ascorbic acid (vitamin C) supplementation protects against coronary heart disease developed in the late 1970s when vitamin C intakes in industrialized nations were lower than at present. Supplementation was then shown to lower plasma total cholesterol and, among some elderly men, to raise high-density lipoprotein cholesterol. However, among people in initially good vitamin C nutriture, these effects are usually not seen. In five populations of essentially healthy people, blood pressure has been found to correlate negatively with vitamin C status. Recently, in a placebo-controlled, double-blinded study, extra ascorbic acid for 6 wk was observed to lower systolic and pulse pressure in a small group of borderline hypertensive subjects.

Topics: Age Factors; Ascorbic Acid; Blood Pressure; Cholesterol; Cholesterol, HDL; Coronary Disease; Diabetes Mellitus; Humans; Risk Factors; Sex Factors; Smoking

Topics: Antioxidants; Ascorbic Acid; Coronary Disease; Dietary Fats, Unsaturated; Humans; Linoleic Acid; Linoleic Acids; Risk Factors; Vitamin E

Topics: Adult; Aminoisobutyric Acids; Ascorbic Acid; Biological Transport, Active; Coronary Disease; Female; Genetic Variation; Hartnup Disease; Humans; Male; Nutritional Physiological Phenomena; Phenotype

There is a growing body of evidence for the role of free radicals in mediating myocardial tissue injury during myocardial ischemia and in particular during the phase of myocardial reoxygenation. Associated with myocardial ischemia and reperfusion is the generation of oxygen-derived free radicals from a variety of sources that include the mitochondrial electron transport chain; the biosynthesis of prostaglandins; the enzyme xanthine oxidase; and circulating elements in the blood, with the polymorphonuclear neutrophil assuming a primary focus of attention. Experimental studies have shown that free radical scavengers (e.g., N-[2-mercaptopropionyl]glycine) and enzymes that scavenge or degrade reactive species of oxygen (superoxide dismutase or catalase) can reduce the mass of myocardial tissue that undergoes irreversible injury. Additionally allopurinol, which inhibits the enzyme xanthine oxidase, reduces ultimate infarct size, putatively by reducing the xanthine oxidase generation of superoxide anion. Neutrophils that enter the ischemically injured myocardium under the influence of chemotactic attraction and activation of the complement system generate and release highly reactive and cytotoxic oxygen derivatives that are destructive to the vascular endothelium and to the cardiac myocytes. Studies have documented that neutrophil depletion or suppression of neutrophil function (ibuprofen, nafazatrom, BW 755C, or more recently with prostacyclin or iloprost) results in a significant salvage of myocardial tissue that is subjected to a period of regional ischemia followed by reperfusion. Our current understanding of the events associated with myocardial ischemia suggests that within the ischemic myocardial region or area at risk, there is a population of cells that are reversibly injured and that reperfusion within a specified period (less than 3 hours) of time is capable of restoring the majority of the jeopardized cells to a normal status, but that the act of reperfusion itself will lead to the sudden demise of a fraction of the cells because of the cytotoxic effects of reactive species of oxygen derived from one or more of the sources indicated above. The efforts to minimize the amount of tissue that undergoes cell death as a result of myocardial ischemia demand that early reperfusion be established. However, the reintroduction of molecular oxygen and the circulating elements of the blood will be associated with an "explosive" and self-limited destruction of so

Topics: Antioxidants; Ascorbic Acid; Cell Adhesion; Coronary Disease; Free Radicals; Glycoproteins; Humans; Lysosomes; Myocardial Infarction; Myocardium; Necrosis; Neutrophils; Oxygen; Superoxide Dismutase; Xanthine Oxidase

Topics: Aging; Animals; Arteriosclerosis; Ascorbic Acid; Chondroitin; Connective Tissue; Coronary Disease; Diet, Atherogenic; Glycoproteins; Glycosaminoglycans; Heparin; Heparitin Sulfate; Hexosamines; Hexoses; Histamine; Humans; Hyaluronic Acid; Hyaluronoglucosaminidase; Lipid Metabolism; Lipoproteins, LDL; Mucoproteins; Neuraminic Acids; Rabbits; Rats

Topics: Adipose Tissue; Adult; Ascorbic Acid; Cholesterol; Cholesterol, Dietary; Coronary Disease; Diet Therapy; Dietary Carbohydrates; Dietary Fats; Fatty Acids; Fatty Acids, Unsaturated; Finland; Humans; Hypercholesterolemia; Lipid Metabolism; Male; Middle Aged; Oils; Time Factors; United States

Restenosis remains a significant problem after angioplasty of hemodialysis vascular access. Both experimental and clinical studies have shown a protective effect of antioxidants against post-angioplasty restenosis. A prospective, randomized, feasibility study was conducted to investigate the effect of ascorbic acid to prevent restenosis. Ninety-three hemodialysis patients were randomized into three groups after angioplasty: placebo (n = 31), 300 mg ascorbic acid (n = 31), and 600 mg ascorbic acid (n = 31), treated intravenously 3 times per week for 3 months. Eighty-nine completed the clinical follow-up, and 81 had angiographic follow-up. In the angiographic follow-up, the mean (stand deviation) late loss of luminal diameter for the placebo, 300 mg, and 600 mg groups were 3.15 (1.68) mm, 2.52 (1.70) mm (P = 0.39 vs. placebo group), and 1.59 (1.67) mm (P = 0.006, vs. placebo group), with corresponding angiographic binary restenosis of 79%, 67% (P = 0.38 vs. placebo group), and 54% (P = 0.08 vs. placebo group). The post-interventional primary patency rates at 3 months were 47%, 55% (P = 0.59 vs. placebo group), and 70% (P = 0.18 vs. placebo group) for placebo, 300 mg, and 600 mg groups. Our results demonstrated that intravenous 600 mg ascorbic acid was a feasible therapy and might attenuate restenosis after angioplasty; however, its effect on post-interventional primary patency was modest.

Topics: Aged; Angioplasty, Balloon, Coronary; Antioxidants; Ascorbic Acid; Coronary Angiography; Coronary Disease; Feasibility Studies; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prospective Studies; Renal Dialysis; Treatment Outcome

Atrial fibrillation (AF) is a common arrhythmia that occurs postoperatively in cardiac surgery. There is evidence for the role of oxidative stress in the etiology of AF. In our study, we examined whether antioxidant ascorbic acid (vitamin C), could help in the reduction of the incidence of postoperative AF. Patients who were scheduled to undergo elective isolated on-pump coronary artery bypass grafting (CABG) were included in our study. One hundred and seventy patients were randomly divided in two groups: Group A (n=85) received vitamin C preoperatively and postoperatively whereas Group B (n=85) did not receive any (control group). The incidence of AF was 44.7% in the vitamin C group and 61.2% in the control group (P=0.041). The hospitalization time, the intensive care unit stay and the time interval for the conversion of AF into sinus rhythm was significantly shorter in the vitamin C group. Patients that developed AF also had longer hospital length of stay (9.5±2.8 days vs. 6.7±1.9, P=0.034). Supplementation of vitamin C reduces the incidence of postCABG AF, and decreases the time needed for rhythm restoration and length of hospital stay.

Topics: Aged; Analysis of Variance; Ascorbic Acid; Atrial Fibrillation; Coronary Artery Bypass; Coronary Disease; Elective Surgical Procedures; Female; Follow-Up Studies; Humans; Length of Stay; Male; Myocardial Revascularization; Pilot Projects; Postoperative Care; Postoperative Complications; Preoperative Care; Prospective Studies; Risk Assessment; Statistics, Nonparametric; Survival Rate; Treatment Outcome

Interindividual variability of platelet inhibition after aspirin administration has been described. Additionally, aspirin resistance occurs in some individuals, but the mechanism for aspirin resistance is still unknown. The aim of the present study was to examine the role of endothelial dysfunction in aspirin resistance.. The antiplatelet effect of aspirin was studied prospectively in 54 consecutive patients with stable coronary heart disease. Platelet aggregation rate was measured and aspirin resistance was defined by a relative inhibition of adenosine diphosphate (5 micromol/L)-induced platelet aggregation of >or=70%. Thrombomodulin (TM) and free tissue factor pathway inhibitor (TFPI) were measured as endothelial dysfunction markers. Erythrocyte superoxide dismutase activity, plasma level of vitamin C, vitamin E and lipoperoxide were measured to estimate the oxidative stress.. Platelet aggregation was positively correlated with TM (r = 0.277, P < 0.05) and TFPI (r = 0.288, P < 0.05) respectively. The TFPI level in aspirin-resistant patients (119.5 +/- 13.5 ng/mL) was significantly higher than that in aspirin-sensitive patients (107.8 +/- 18.9 ng/mL; P < 0.05). There were no statistically significant differences on any indicator of oxidative stress between two groups.. Endothelial dysfunction is one of the mechanisms for aspirin resistance, whereas oxidative stress may not involve in the process of aspirin resistance.

Topics: Adenosine Diphosphate; Aged; Aged, 80 and over; Ascorbic Acid; Aspirin; Biomarkers; Coronary Disease; Drug Resistance; Endothelium, Vascular; Erythrocytes; Female; Humans; Lipid Peroxides; Lipoproteins; Male; Middle Aged; Oxidative Stress; Platelet Aggregation; Platelet Aggregation Inhibitors; Prospective Studies; Superoxide Dismutase; Thrombomodulin; Vitamin E

In humans with cardiovascular risk factors, increased vascular production of superoxide anion may contribute to endothelial dysfunction by its reacting with nitric oxide and reducing its biological activity. High concentrations of ascorbic acid scavenge superoxide anion and restore normal endothelium-dependent vasodilation in humans with cardiovascular risk factors. To investigate the contribution of increased superoxide anion to endothelial dysfunction in atherosclerotic coronary arteries, we examined the effect of sequential infusions of ascorbic acid (final concentration 0.1, 1.0, and 10 mmol/L) or placebo on coronary endothelial function in 26 subjects referred for cardiac catheterization to evaluate coronary artery disease. Coronary vasomotor function was evaluated using intracoronary agonist infusion, quantitative angiography, and intracoronary Doppler measurements. At baseline, endothelium-dependent vasodilation of epicardial arteries and coronary microvessels was impaired to an equivalent extent in the ascorbic acid and placebo groups. Sequential ascorbic acid infusions had no effect on the acetylcholine-induced change in coronary artery diameter (-11+/-8, -12+/-10, and -9+/-9%) compared with the effect of placebo (-14+/-13, -16+/-10, and -13+/-9%) infusions (p=0.98). Similarly, the changes in coronary blood flow during acetylcholine infusions were equivalent during ascorbic acid (51+/-44, 67+/-66, and 62+/-52%) and placebo (61+/-104, 55+/-93, and 50+/-69%) infusions (p=0.63). Ascorbic acid also had no effect on the dilator response to intracoronary nitroglycerin (p=0.19). These data argue against an important role for superoxide-mediated "inactivation" of nitric oxide or another rapidly reversible form of oxidative stress as a mechanism of coronary endothelial dysfunction in patients with coronary atherosclerosis.

Topics: Acetylcholine; Ascorbic Acid; Coronary Disease; Coronary Vessels; Endothelium, Vascular; Female; Humans; Male; Middle Aged; Vasomotor System

We tested whether long-term administration of antioxidant vitamins C and E improves coronary and brachial artery endothelial function in patients with coronary artery disease (CAD).. Endothelial function is a sensitive indicator of vascular health. Oxidant stress and oxidized low-density lipoprotein (LDL) impair endothelial function by reducing nitric oxide bioavailability in the artery wall.. We randomly assigned 30 subjects with CAD to combined vitamin E (800 IU per day) and C (1000 mg per day) or to placebos in a double-blind trial. Coronary artery endothelial function was measured as the change in coronary artery diameter to acetylcholine infusions (n = 18 patients), and brachial artery endothelial function was assessed by flow-mediated dilation (n = 25 patients) at baseline and six months. Plasma markers of oxidant stress (oxidized LDL and autoantibodies) were also measured.. Plasma alpha-tocopherol (p < 0.001) and ascorbic acid (p < 0.02) increased with active therapy. Compared to placebo, there was no improvement in coronary and brachial endothelial vasomotor function over six months. Although vitamins C and E tended to reduce F2-isoprostanes (p = 0.065), they failed to alter oxidized LDL or autoantibodies to oxidized LDL.. Long-term oral vitamins C and E do not improve key mechanisms in the biology of atherosclerosis or endothelial dysfunction, or reduce LDL oxidation in vivo.

Topics: Antioxidants; Ascorbic Acid; Brachial Artery; Coronary Disease; Coronary Vessels; Double-Blind Method; Drug Therapy, Combination; Endothelium, Vascular; Female; Humans; Male; Middle Aged; Oxidative Stress; Time Factors; Vasodilation; Vitamin E

To study an antioxidant action of antioxidant vitamins (vitamins C, E and provitamin A) in vitro and in vivo.. The study was made of kinetic parameters of copper-initiated free radical oxidation (FRO) of low density lipoproteins (HDLP) in human blood plasm, antioxidant potential of rat liver and myocardium, the level of FRO products in HDLP and activity of glutathione peroxidase in erythrocytes of 31 males aged 40-64 years with coronary heart disease (CHD).. An antioxidant action of the combinations alpha-tocopherol+ascorbic acid and alpha-tocopherol+beta-carotin was much more potent than that of each of the component alone. The whole complex of the antioxidants completely suppressed FRO of HDLP in the model system. Feeding rats for 30 days with a complex of antioxidant vitamins and selenium produced a sharp enhancement of the antioxidant potential of the liver and a complete suppression of free radical processes in the myocardium. If this complex was given to CHD patients for 2 months, it sharply reduced the amount of FRO primary and secondary products in blood plasm LDLP in growing activity of erythrocytic selenium-containing glutathione peroxidase.. The scheme is proposed for objective experimental assessment of antioxidant efficacy of multicomponent antioxidant medication in laboratory and clinical trials.

Topics: Adult; Animals; Antioxidants; Ascorbic Acid; beta Carotene; Copper; Coronary Disease; Drug Combinations; Free Radicals; Glutathione Peroxidase; Heart; Humans; Lipoproteins, LDL; Liver; Male; Middle Aged; Myocardium; Oxidation-Reduction; Rats; Rats, Wistar; Vitamin E; Vitamins

We aimed to measure the vasodilating effects of vitamin C on the radial arteries of healthy subjects and to assess whether vitamin C is superior in this regard to diltiazem, a commonly used vasodilator in coronary artery bypass using radial conduits.. In a case-control study (study 1) oral single-dose vitamin C (2 g) was given to 15 healthy nonsmokers and 15 matched otherwise healthy smokers. In a randomized double-blind study (study 2) oral single-dose vitamin C (2 g, n = 15) and diltiazem (180 mg, n = 15) were compared in preoperative patients with coronary artery disease. We examined the dilation of the radial artery with high-resolution ultrasonography and measurement of the lumen surface and color Doppler images of the nondominant radial artery just before and 2 hours after drug administration.. In study 1 both smokers and nonsmokers showed a significant increase in the lumen surface at 2 hours compared with at baseline (P <.001 and P =.013, respectively). The increase was larger in smokers (median, 37.5% vs 14.3%; P =.004). In study 2 both groups showed statistically significant increases in the lumen surface at 2 hours compared with at baseline (P <.001 and P =.008 for vitamin C and diltiazem, respectively). Vitamin C achieved a larger increase than diltiazem (median, 33.3% vs 18.2%; P =.016). In multivariate modeling the increase in lumen surface was independently predicted by use of vitamin C over diltiazem (+21.2%, P =.007), diabetes mellitus (+14.5%, P =.085), increased cholesterol (+26.2%, P =.001), and smoking history (+20.8%, P =.017).. Vitamin C is a potent acute vasodilator in both smokers and nonsmokers and is superior to diltiazem in preoperative coronary patients who need protection from vasospasm of the radial conduit.

Topics: Adult; Aged; Ascorbic Acid; Case-Control Studies; Coronary Artery Bypass; Coronary Disease; Diabetes Complications; Diltiazem; Double-Blind Method; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Multivariate Analysis; Pilot Projects; Predictive Value of Tests; Radial Artery; Smoking; Ultrasonography, Doppler, Color; Vasodilation; Vasodilator Agents

We sought to determine whether abnormal myocardial blood flow (MBF) responses to the cold pressor test (CPT) in patients with various risk factors may involve different mechanisms that could lead to varying responses of short- and long-term administration of antioxidants.. There is a growing body of evidence that increased vascular production of reactive oxygen species markedly reduces the bioavailability of endothelium-derived nitric oxide, leading to impaired vasodilator function. It is unknown whether increased oxidative stress is the prevalent mechanism underlying endothelial dysfunction in patients with different coronary risk factors.. Fifty patients with normal coronary angiograms were studied. The MBF responses to CPT was determined by means of positron emission tomography before and after intravenous infusion of 3 g vitamin C or saline (placebo), as well as after 3 months and 2 years of 2 g vitamin C or placebo supplementation daily.. In hypertensive patients, the change in MBF (DeltaMBF) was not modified significantly by short-term vitamin C administration challenges (0.20 +/- 0.20 ml/g/min; p = NS) but was significantly increased after three months and two years of treatment with vitamin C versus baseline (0.58 +/- 0.27 and 0.63 +/- 0.17 vs. 0.14 +/- 0.18 ml/g/min; both p < or = 0.001). In smokers, DeltaMBF in response to CPT was significantly increased after short-term vitamin C infusion and long-term vitamin C treatment (0.52 +/- 0.10, 0.54 +/- 0.13, 0.50 +/- 0.07 vs. -0.08 +/- 0.10 ml/g/min; all p < or = 0.001). In hypercholesterolemic patients, no improvement in DeltaMBF during CPT was observed after short- and long-term vitamin C treatment (0.05 +/- 0.14, 0.08 +/- 0.18, 0.02 +/- 0.19 vs. 0.08 +/- 0.16 ml/g/min; p = NS). The CPT-induced DeltaMBF in hypertensive patients and smokers after follow-up was significant as compared with placebo and control subjects (p < or = 0.001).. The present study revealed marked heterogeneous responses in MBF changes to short- and long-term vitamin C treatment in patients with various risk factors, which highlights the quite complex nature underlying abnormal coronary vasomotion.

Topics: Antioxidants; Ascorbic Acid; Coronary Angiography; Coronary Circulation; Coronary Disease; Coronary Vessels; Female; Follow-Up Studies; Humans; Hypercholesterolemia; Hypertension; Infusions, Intravenous; Male; Middle Aged; Oxidative Stress; Reactive Oxygen Species; Risk Factors; Smoking; Tomography, Emission-Computed; Treatment Outcome; Vasoconstriction; Vasodilation

The purpose of this study was to compare the short-term effects of an intensive lifestyle modification (ILM) program on lipid peroxidation and antioxidant systems in patients with coronary artery disease (CAD). Twenty-two patients in the control group continued to receive their conventional treatment with lipid-lowering drugs, whereas 22 patients in the experimental group were assigned to intensive lifestyle modification (ILM) without taking any lipid-lowering agent. The ILM program comprised dietary advice on low-fat diets, high antioxidants and high fiber intakes, yoga exercise, stress management and smoking cessation. After 4 months of intervention, patients in the experimental group revealed a statistically significant increase in plasma total antioxidants, plasma vitamin E and erythrocyte glutathione (GSH) compared to patients in the control group. There was no significant change in plasma malondialdehyde (MDA), a circulating product of lipid peroxidation, in either group. We concluded that the ILM program increased circulating antioxidants and reduced oxidative stress in patients with CAD.

Topics: Aged; Antioxidants; Ascorbic Acid; Coronary Disease; Diet, Fat-Restricted; Dietary Fiber; Exercise Therapy; Female; Glutathione; Humans; Imagery, Psychotherapy; Life Style; Lipid Peroxidation; Lipids; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Relaxation Therapy; Smoking Cessation; Stress, Psychological; Vitamin E; Yoga

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

Epidemiologic studies have shown a correlation between antioxidant intake and coronary artery disease (CAD); however, the results of clinical trials have been inconsistent. We evaluated the effect of combined antioxidant supplementation on endothelial function and its correlation with change in low-density lipoprotein cholesterol (LDLC) oxidation in patients with established CAD. In a double-blind, placebo-controlled 12-week trial, 18 nonsmoking, nondiabetic patients (mean age 62.4 +/- 8.1 years) were randomized to receive placebo or antioxidant supplementation consisting of (a) 400 IU of vitamin E, 500 mg of vitamin C, and 12 mg of beta-carotene; or (b) 800 IU of vitamin E, 1000 mg of vitamin C, and 24 mg of beta-carotene daily. Endothelial function was evaluated on the basis of percent and absolute changes in brachial artery diameter in response to reactive hyperemia induced by occlusion-release. Baseline and 12-week values of LDL oxidation (measured on the basis of lag phase), endothelial function, dietary composition, serum antioxidants, and lipids were measured. We noted a significant between-group difference at 12 weeks for change in plasma concentrations of alpha-tocopherol, vitamin C, and beta-carotene between the placebo and antioxidant groups (p <.05). Both placebo and treatment groups demonstrated a significant improvement in lag phase; however, the treatment group achieved a greater, although nonsignificant, magnitude of change compared with the placebo group (181.3 +/- 177.8 minutes vs 80.6 +/- 63.0 minutes, P =.06). Within-group change in brachial reactivity from baseline to follow-up in the treatment group did not reach statistical significance (1.7% +/- 3.2% and 0.07 mm +/- 0.13 mm, P =.08 and P =.09, respectively), whereas an improved change in brachial reactivity was observed in the placebo group (2.2% +/- 1.9%, 0.09 mm +/- 0.06 mm, P <.05). No significant correlation was found between change in lag phase and change in endothelial function. On adjustment for confounders, antioxidant supplementation was found not to be a significant predictor of brachial reactivity. We conclude that antioxidant supplementation did not significantly alter brachial reactivity, despite significantly increased plasma levels of antioxidants and improved lag phase. These data should be confirmed in larger-scale trials and examined in studies evaluating individual dietary antioxidant supplementation.

Topics: alpha-Tocopherol; Antioxidants; Ascorbic Acid; beta Carotene; Brachial Artery; Constriction; Coronary Disease; Diet; Dietary Supplements; Double-Blind Method; Endothelium, Vascular; Hemorheology; Humans; Lipid Peroxidation; Lipids; Lipoproteins, LDL; Placebos; Vasodilation; Vitamin E

Epidemiologic studies suggest a protective effect of regular intake of vitamin C and vitamin E as antioxidant in the manifestation of coronary heart disease. Cigarette smoke contains a large amount of radicals and reactive oxygen-derived substances enhancing aggregation of platelets. We investigated the effect of vitamin C as an important antioxidant in human plasma on the aggregation of human platelets in smokers and nonsmokers. TEST PERSONS AND METHOD: Overall 40 persons (mean age: 28 +/- 9 years) were randomized. The groups of chronic smokers (21 +/- 9 "packyears") and nonsmokers consisted of 20 persons, respectively. In each group ten persons were treated with intravenous infusion of 3 g vitamin C or 100 ml 0.9% saline solution (placebo). The maximal aggregation was measured with an aggregometer after 0, 3, 6, and 24 hours with collagen concentrations of 0.5 microgram/ml and 1.0 microgram/ml, respectively.. In smokers with vitamin C application the group comparison by Wilcoxon's rank test demonstrated a significant decrease of platelet aggregation after 6 hours for both collagen concentrations (0.5 microgram/ml and 1.0 microgram/ml) compared to the placebo group (p < or = 0.05), whereas nonsmokers with vitamin C application revealed a significant decrease of platelet aggregation after 3 and 6 hours for both collagen concentrations (0.5 microgram/ml and 1.0 microgram/ml) compared to the placebo group (p < or = 0.03). The comparison between smokers and nonsmokers regarding the effect of vitamin C on platelet aggregation for both collagen concentrations demonstrated no significant difference (3 hours: p = 0.84 and p = 0.97; 6 hours: p = 0.81 and p = 0.59; and 24 hours p = 0.57 and p = 0.06, not significant, respectively).. These findings suggest that vitamin C exerts an unknown inhibitory effect on collagen-induced platelets aggregation. These observations may represent a further protective effect of vitamin C in the development of coronary heart disease.

Topics: Adult; Ascorbic Acid; Coronary Disease; Female; Humans; Infusions, Intravenous; Male; Platelet Aggregation; Risk Factors; Smoking

Flow-dependent, endothelium-mediated vasodilation (FDD) and activity of extracellular superoxide dismutase (EC-SOD), the major antioxidative enzyme of the arterial wall, are severely impaired in patients with coronary artery disease (CAD). We hypothesized that both ACE inhibitor (ACEI) and angiotensin II type 1 receptor antagonist (AT(1)-A) increase bioavailability of nitric oxide (NO) by reducing oxidative stress in the vessel wall, possibly by increasing EC-SOD activity.. Thirty-five patients with CAD were randomized to 4 weeks of ACEI (ramipril 10 mg/d) or AT(1)-A (losartan 100 mg/d). FDD of the radial artery was determined by high-resolution ultrasound before and after intra-arterial N-monomethyl-L-arginine (L-NMMA) to inhibit NO synthase and before and after intra-arterial vitamin C to determine the portion of FDD inhibited by oxygen free radicals. EC-SOD activity was determined after release from endothelium by heparin bolus injection. FDD was improved after ramipril and losartan (each group P<0.01), and in particular, the portion of FDD mediated by NO, ie, inhibited by L-NMMA, was increased by >75% (each group P<0.01). Vitamin C improved FDD initially, an effect that was lost after ramipril or losartan. After therapy, EC-SOD activity was increased by >200% in both groups (ACEI, 14.4+/-1.1 versus 3.8+/-0.9 and AT(1)-A, 13.5+/-1.0 versus 3.9+/-0.9 U. mL(-1). min(-1); each P<0.01). CONCLUSIONS-Four weeks of therapy with ramipril or losartan improves endothelial function to similar extents in patients with CAD by increasing the bioavailability of NO. Our results suggest that beneficial long-term effects of interference with the renin-angiotensin system may be related to reduction of oxidative stress within the arterial wall, mediated in part by increased EC-SOD activity.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antioxidants; Ascorbic Acid; Biological Availability; Coronary Disease; Endothelium, Vascular; Enzyme Activation; Humans; Losartan; Middle Aged; Nitric Oxide; Nitric Oxide Synthase; omega-N-Methylarginine; Oxidative Stress; Radial Artery; Ramipril; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Regional Blood Flow; Superoxide Dismutase; Time Factors; Vasodilation

We studied the effect of an antioxidant, the intracoronary infusion of vitamin C, on basal and dobutamine-stimulated left ventricular (LV) contractility.. Nineteen patients with normal ventricular function participated in this study. A micromanometer-tipped catheter was inserted into the LV. In the experimental group (n=10), an infusion catheter was positioned in the left main coronary artery. LV peak +dP/dt (LV +dP/dt) was measured in response to the intravenous infusion of dobutamine before (Dob) and during (Dob+vit C) the intracoronary infusion of vitamin C. The intracoronary infusion of vitamin C had no effect on basal LV +dP/dt or any other hemodynamic parameter. The infusion of vitamin C augmented the LV +dP/dt response to dobutamine by 22+/-4% (Dob, 1680+/-76 mm Hg/s; Dob+vit C, 1814+/-97 mm Hg/s, P<0.01). In the control group (n=9), LV +dP/dt was measured in response to sequential infusions of dobutamine (Dob, Dob-2) given at the same time intervals as in the experimental group but without the intracoronary infusion of vitamin C. In contrast to the experimental group, no difference in LV +dP/dt was observed between the 2 infusions of dobutamine (Dob, 1706+/-131 mm Hg/s; Dob-2, 1709+/-138 mm Hg/s, P=NS).. The administration of the antioxidant vitamin C augments the inotropic response to dobutamine in humans. This suggests that redox environment contributes to the adrenergic regulation of ventricular contractility.

Topics: Adrenergic beta-Agonists; Antioxidants; Ascorbic Acid; Cardiac Catheterization; Cardiotonic Agents; Coronary Disease; Coronary Vessels; Diabetes Mellitus, Type 2; Dobutamine; Drug Synergism; Female; Hemodynamics; Humans; Hypertension; Infusions, Intra-Arterial; Male; Middle Aged; Myocardial Contraction; Oxidation-Reduction; Ventricular Function, Left

To determine the efficacy of various antioxidant vitamins and a major dietary source of antioxidants (fruits) we performed a randomized controlled trial.. 175 successive patients with coronary heart disease (CHD) presenting to our centre were recruited and using a Latin-square design divided into five groups of 35 each. The groups were matched for age, lifestyle and dietary variables, clinical diagnosis and drug treatment status. None of the patients was on lipid-lowering drugs. Supplemental vitamins were stopped for one month before study began and American Heart Association Step II dietary advice was given to all. At baseline, total cholesterol, triglycerides, HDL and LDL cholesterol and lipid peroxide measured as thiobarbaturic acid reactive substances (TBARS) were determined. Group I received placebo capsules; Group II vitamin E 400 units/day; Group III vitamin C 1,000 mg; Group IV vitamin A 25,000 IU; Group V received 400 gm of fruit daily. Lipids and lipid peroxide levels were determined at 30 days follow-up.. Response rate in various groups varied form 86% to 91%. No significant changes in total, HDL, LDL cholesterol and triglyceride levels were seen in Groups I, II, III and IV (paired t-test p > 0.05). In Group V there was a significant decrease in total cholesterol (-7.8 +/- 11.1%), and LDL cholesterol (-11.2 +/- 25.4%) and increase in HDL cholesterol (+12.9 +/- 20.1%) (paired t-test p < 0.01). Lipid peroxide levels decreased significantly in all the treatment groups (p < 0.01). This decrease was the highest in Group II (vitamin E; -36.4 +/- 17.7%) as compared to Group III (vitamin C -19.8 -/+ 10.8%); Group IV (vitamin A -5.4 +/- 17%) and Group V (fruits -13.1 +/- 12.0%).. All the antioxidant vitamins and fruits significantly decrease lipid peroxide levels and oxidant load in CHD patients. However, fruits are the best choice as they also favourably modify the lipid profile.

Topics: Antioxidants; Ascorbic Acid; Cholesterol; Coronary Disease; Dietary Supplements; Female; Fruit; Humans; Lipid Peroxides; Male; Middle Aged; Phytotherapy; Treatment Outcome; Triglycerides; Vitamin A; Vitamin E; Vitamins

One strategy for treating coronary artery disease (CAD) patients with low HDL cholesterol (HDL-C) is to maximally increase the HDL-C to LDL-C ratio by combining lifestyle changes with niacin (N) plus a statin. Because HDL can prevent LDL oxidation, the low-HDL state also may benefit clinically from supplemental antioxidants. Lipoprotein changes over 12 months were studied in 153 CAD subjects with low HDL-C randomized to take simvastatin and niacin (S-N), antioxidants (vitamins E and C, beta-carotene, and selenium), S-N plus antioxidants (S-N+A), or placebo. Mean baseline plasma cholesterol, triglyceride, LDL-C, and HDL-C levels of the 153 subjects were 196, 207, 127, and 32 mg/dL, respectively. Without S-N, lipid changes were minor. The S-N and S-N+A groups had comparably significant reductions (P

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Cholesterol, HDL; Cholesterol, LDL; Coronary Disease; Dietary Supplements; Drug Interactions; Female; Humans; Hypolipidemic Agents; Male; Middle Aged; Niacin; Particle Size; Selenium; Simvastatin; Vitamin E

Both lipid-modifying therapy and antioxidant vitamins are thought to have benefit in patients with coronary disease. We studied simvastatin-niacin and antioxidant-vitamin therapy, alone and together, for cardiovascular protection in patients with coronary disease and low plasma levels of HDL.. In a three-year, double-blind trial, 160 patients with coronary disease, low HDL cholesterol levels and normal LDL cholesterol levels were randomly assigned to receive one of four regimens: simvastatin plus niacin, vitamins, simvastatin-niacin plus antioxidants; or placebos. The end points were arteriographic evidence of a change in coronary stenosis and the occurrence of a first cardiovascular event (death, myocardial infarction, stroke, or revascularization).. The mean levels of LDL and HDL cholesterol were unaltered in the antioxidant group and the placebo group; these levels changed substantially (by -42 percent and +26 percent, respectively) in the simvastatin-niacin group. The protective increase in HDL2 with simvastatin plus niacin was attenuated by concurrent therapy with antioxidants. The average stenosis progressed by 3.9 percent with placebos, 1.8 percent with antioxidants (P=0.16 for the comparison with the placebo group), and 0.7 percent with simvastatin-niacin plus antioxidants (P=0.004) and regressed by 0.4 percent with simvastatin-niacin alone (P<0.001). The frequency of the clinical end point was 24 percent with placebos; 3 percent with simvastatin-niacin alone; 21 percent in the antioxidant-therapy group; and 14 percent in the simvastatin-niacin-plus-antioxidants group.. Simvastatin plus niacin provides marked clinical and angiographically measurable benefits in patients with coronary disease and low HDL levels. The use of antioxidant vitamins in this setting must be questioned.

Topics: alpha-Tocopherol; Antioxidants; Apolipoproteins; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Coronary Angiography; Coronary Disease; Coronary Stenosis; Double-Blind Method; Drug Interactions; Drug Therapy, Combination; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypolipidemic Agents; Lipids; Male; Middle Aged; Niacin; Selenium; Simvastatin; Vitamin E

The purpose of this study was to determine the effect of vitamin E and/or vitamin C supplementation on low-density lipoprotein (LDL) oxidizability and neutrophil (PMN) superoxide anion production in young smokers.. Thirty smokers with a <5 pack-year history were randomly assigned to take placebo; vitamin C (1 g/day); vitamin E (400 IU/day), or both vitamins in a double-blind fashion. Subjects took the supplements for 8 weeks. At weeks 0 and 8, blood was collected for isolation of LDL and PMN, and for antioxidant vitamin analysis. LDL was oxidized with a copper (Cu) catalyst, and oxidation was measured by formation of conjugated dienes over a 5-hour time course. Lag times and maximum oxidation rates were calculated from the time course data. PMN superoxide anion release was assessed by respiratory burst after stimulation with phorbol ester and opsonized zymosan, and their ability to oxidize autologous LDL following treatment with the above stimuli was measured with the conjugated diene assay.. Subjects who received vitamin E alone had a significant increase in the lag phase of Cu-catalyzed LDL oxidation (week 0, 118+/-31 min vs. week 8, 193+/-80 min, mean +/- SD, p < 0.05), whereas the vitamin C and placebo groups had no changes in LDL oxidation kinetics. The group receiving both vitamins E and C had a significant reduction in oxidation rate (week 0. 7.4+/-2.3 vs. week 8, 5.1+/-2.1, p < 0.05). There were no significant changes for any group in PMN superoxide anion production or PMN LDL oxidation after stimulation with either phorbol ester or opsonized zymosan. Plasma and LDL vitamin E concentrations were significantly increased in both groups that received vitamin E. The subjects who received vitamin C alone had no significant change in plasma vitamin C concentrations; however, when data were pooled from both groups who received vitamin C, the increases were significant.. Vitamin E supplementation of young smokers was effective in reducing Cu-catalyzed LDL oxidizability; however, vitamin E and/or C supplementation showed few significant effects on the more physiologically relevant PMN function. This casts doubt on the ability of antioxidant supplementation to reduce oxidative stress in smokers in vivo. Therefore, smoking cessation remains the only means by which young smokers can prevent premature coronary heart disease.

Topics: Adolescent; Adult; Ascorbic Acid; Coronary Disease; Dietary Supplements; Double-Blind Method; Endothelium, Vascular; Female; Humans; Lipoproteins, LDL; Male; Neutrophils; Oxidation-Reduction; Respiratory Burst; Smoking; Vitamin E

The purpose of this study was to determine whether lowering homocysteine levels with folic acid, with or without antioxidants, will improve endothelial dysfunction in patients with coronary artery disease (CAD).. Elevated plasma homocysteine levels are a risk factor for atherosclerosis. Homocysteine may promote atherogenesis through endothelial dysfunction and oxidative stress.. In a double-blind, placebo-controlled, randomized trial, we used vascular ultrasound to assess the effect of folic acid alone or with antioxidants on brachial artery endothelium-dependent flow-mediated dilation (FMD). Seventy-five patients with CAD (screening homocysteine level > or =9 micromol/liter) were randomized equally to one of three groups: placebo, folic acid alone or folic acid plus antioxidant vitamins C and E. Patients were treated for four months. Plasma folate, homocysteine, FMD and nitroglycerin-mediated dilation were measured before and after four months of treatment.. Plasma folate, homocysteine and FMD were unchanged in the placebo group. Compared with placebo, folic acid alone increased plasma folate by 475% (p < 0.001), reduced plasma homocysteine by 11% (p = 0.23) and significantly improved FMD from 3.2 +/- 3.6% to 5.2 +/- 3.9% (p = 0.04). The improvement in FMD correlated with the reduction in homocysteine (r = 0.5, p = 0.01). Folic acid plus antioxidants increased plasma folate by 438% (p < 0.001), reduced plasma homocysteine by 9% (p = 0.56) and insignificantly improved FMD from 2.6 +/- 2.4% to 4.0 +/- 3.7% (p = 0.45), as compared with placebo. Nitroglycerin-mediated dilation did not change significantly in any group.. Folic acid supplementation significantly improved endothelial dysfunction in patients with coronary atherosclerosis. Further clinical trials are required to determine whether folic acid supplementation may reduce cardiovascular events.

Topics: Aged; Antioxidants; Ascorbic Acid; Blood Circulation; Coronary Disease; Double-Blind Method; Endothelium, Vascular; Female; Folic Acid; Homocysteine; Humans; Lipids; Male; Malondialdehyde; Middle Aged; Nitroglycerin; Vasodilation; Vasodilator Agents; Vitamin B 12; Vitamin E

Loss of endothelium-derived nitric oxide (EDNO) contributes to the clinical expression of coronary artery disease (CAD). Increased oxidative stress has been linked to impaired endothelial vasomotor function in atherosclerosis, and recent studies demonstrated that short-term ascorbic acid treatment improves endothelial function.. In a randomized, double-blind, placebo-controlled study, we examined the effects of single-dose (2 g PO) and long-term (500 mg/d) ascorbic acid treatment on EDNO-dependent flow-mediated dilation of the brachial artery in patients with angiographically established CAD. Flow-mediated dilation was examined by high-resolution vascular ultrasound at baseline, 2 hours after the single dose, and 30 days after long-term treatment in 46 patients with CAD. Flow-mediated dilation improved from 6.6+/-3.5% to 10.1+/-5.2% after single-dose treatment, and the effect was sustained after long-term treatment (9. 0+/-3.7%), whereas flow-mediated dilation was 8.6+/-4.7% at baseline and remained unchanged after single-dose (7.8+/-4.4%) and long-term (7.9+/-4.5%) treatment with placebo (P=0.005 by repeated-measures ANOVA). Plasma ascorbic acid concentrations increased from 41.4+/-12. 9 to 115.9+/-34.2 micromol/L after single-dose treatment and to 95. 0+/-36.1 micromol/L after long-term treatment (P<0.001).. In patients with CAD, long-term ascorbic acid treatment has a sustained beneficial effect on EDNO action. Because endothelial dysfunction may contribute to the pathogenesis of cardiovascular events, this study indicates that ascorbic acid treatment may benefit patients with CAD.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Biomarkers; Blood Glucose; Coronary Disease; Double-Blind Method; Endothelium, Vascular; Female; Free Radical Scavengers; Glutathione; Hemodynamics; Humans; Lipids; Male; Middle Aged; Nitric Oxide; Time Factors; Treatment Outcome

The SUpplementation en VItamines et Minéraux AntioXydants (SU.VI.MAX) Study is a randomized, double-blind, placebo-controlled, primary-prevention trial designed to test the efficacy of daily supplementation with antioxidant vitamins (vitamin C, 120 mg; vitamin E, 30 mg; and beta-carotene, 6 mg) and minerals (selenium, 100 microg; and zinc, 20 mg) at nutrition-level doses (one to three times the daily recommended dietary allowances) in reducing several major health problems in industrialized countries, especially the main causes of premature death, cancers and cardiovascular diseases. The present report describes the design, implementation, and baseline characteristics of participants in this 8-year cohort study, which started in 1994 in France; 12,735 eligible subjects (women aged 35-60, and men aged 45-60) were included in 1994 and will be followed for 8 years. Participants undergo a yearly visit consisting, every other year, of either biological sampling or clinical examination. They also regularly provide information on health events and dietary intake by filling out computerized questionnaires using the Minitel Telematic Network. Data on baseline characteristics of the participants suggest that the present sample is close to the national population in terms of geographic density, socioeconomic status, and the distribution of various major risk factors for the diseases under study. The choice of the study population should allow the results of this trial to apply to adult populations of both sexes in France and other industrialized countries.

Topics: Adult; Ascorbic Acid; beta Carotene; Coronary Disease; Double-Blind Method; Drug Therapy, Combination; Female; France; Humans; Male; Middle Aged; Mortality; Neoplasms; Selenium; Vitamin E; Zinc

We have investigated the effects of supplementation of the diet with the antioxidant vitamins C and E on several functions of the immune response of aged women. Ten healthy women and 20 women (72 +/- 6 years old) suffering two diseases often associated with age (10 with major depression disorders, MDD, and 10 with coronary heart disease, CHD) were administered 1 g of vitamin C and 200 mg of vitamin E daily for 16 weeks. Blood samples were collected before and after treatment for measurement of several immunological functions, namely proliferative response of lymphocytes to the mitogen phytohemagglutinin (20 mg/L) and phagocytic functions of polymorphonuclear (PMN) neutrophils, i.e., adherence to vascular endothelium, chemotaxis, phagocytosis of latex beads, and superoxide anion production. In addition, we also determined the levels of serum cortisol and lipid peroxides. Intake of vitamins resulted in a significant increase in the lymphoproliferative capacity and in the phagocytic functions of PMN neutrophils as well as in a significant decrease of serum levels of lipid peroxides and cortisol, both in the healthy aged women and in the aged women with MDD or CHD. These findings suggest an important role of antioxidant supplementation in the improvement of immune function in aged females as well as in the prevention and treatment of specific diseases associated with age that are quite prevalent in the developed countries.

Topics: Aged; Antioxidants; Ascorbic Acid; Chemotaxis; Coronary Disease; Depressive Disorder; Female; Humans; Hydrocortisone; Immune System; Lipid Peroxidation; Lymphocyte Activation; Lymphocytes; Neutrophils; Phagocytosis; Superoxides; Vitamin E

The aims of this study were to investigate the effect of ascorbic acid (AA) supplementation on the oxidisability of low density lipoprotein (LDL) in vitro and on plasma lipoproteins under controlled dietary conditions.. Randomised single-blind cross-over trial.. Free living subjects.. Eight male smokers (age: 25 +/- 2.4 y, BMI: 20.7 +/- 0.5, cigarettes per day: 19.1 +/- 2.4; means +/- s.e.).. Dietary intake was determined in all subjects were advised to achieve an intake as close as possible to the recommended dietary intake of AA (40 mg). After two weeks on the baseline diet, subjects were asked to consume 1 g AA per day for two weeks followed by two weeks of placebo supplementation, or vice versa. In view of the carry-over effects of plasma AA, a wash-out period was incorporated between treatments. Duplicate venous blood samples were collected before and after supplementation and the plasma concentrations of AA, lipids and lipoproteins were determined. The in vitro copper-induced oxidisability of LDL was assessed by monitoring of the absorbance of 234 nm.. No changes in the plasma lipids or the oxidisability of LDL were found after AA supplementation compared to placebo. Plasma AA concentrations doubled on average after supplementation indicating that the lack of effect was not a result of poor compliance.. AA supplementation at this dose did not alter plasma lipids of LDL oxidisability in male smokers.

Topics: Adult; Ascorbic Acid; Cholesterol, LDL; Coronary Disease; Food, Fortified; Humans; Lipids; Male; Oxidation-Reduction; Risk Factors; Smoking

Oxidizing metabolites generated at the site of coronary angioplasty can induce chain reactions that may lead to restenosis. Antioxidants may counter oxidative stress and modify neointimal formation and vascular remodeling. Experimental data and small clinical studies have suggested that antioxidants may prevent restenosis after angioplasty. In a double-blind, randomized trial, we studied whether drugs with antioxidant properties decrease the incidence and severity of restenosis after angioplasty.. One month before angioplasty, 317 patients were randomly assigned to receive one of four treatments: placebo, probucol (500 mg), multivitamins (30,000 IU of beta carotene, 500 mg of vitamin C, and 700 IU of vitamin E), or both probucol and multivitamins-all given twice daily. Patients were treated for four weeks before and six months after angioplasty. Patients received an extra 1000 mg of probucol, 2000 IU of vitamin E, both probucol and vitamin E, or placebo 12 hours before angioplasty, according to their treatment assignments. Base-line and follow-up angiograms were interpreted by blinded investigators using a quantitative approach.. The mean (+/-SD) reduction in luminal diameter six months after angioplasty was 0.12 +/- 0.41 mm in the probucol group, 0.22 +/- 0.46 mm in the combined-treatment group, 0.33 +/- 0.51 in the multivitamin group, and 0.38 +/- 0.50 mm in the placebo group (P = 0.006 for those receiving vs. those not receiving probucol, and P = 0.70 for those receiving vs. those not receiving vitamins. Restenosis rates per segment were 20.7 percent in the probucol group, 28.9 percent in the combined-treatment group, 40.3 percent in the multivitamin group, and 38.9 percent in the placebo group (P = 0.003 for probucol vs. no probucol). The rates of repeat angioplasty were 11.2 percent. 16.2 percent, 24.4 percent, and 26.6 percent, respectively (P = 0.009 for probucol vs. no probucol).. The antioxidant probucol is effective in reducing the rate of restenosis after balloon coronary angioplasty.

Topics: Angioplasty, Balloon, Coronary; Antioxidants; Ascorbic Acid; beta Carotene; Coronary Angiography; Coronary Disease; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Probucol; Recurrence; Treatment Outcome; Vitamin E

This study sought to determine the effect of antioxidant supplementation on the susceptibility of low density lipoprotein (LDL) to oxidation in patients with established cardiovascular disease (CVD).. Data are inconsistent regarding the role of antioxidant nutrients in the prevention of CVD.. The study design was a 12-week, double-blind, placebo-controlled clinical trial. Patients with CVD (n = 45) were randomized to 1) placebo control; 2) 400 IU of vitamin E, 500 mg of vitamin C, 12 mg of beta-carotene (mid-dose); or 3) 800 IU of vitamin E, 1,000 mg of vitamin C, 24 mg of beta-carotene (high dose) daily. Reduced susceptibility of LDL to oxidation was estimated by an increase in lag phase (minutes). Baseline and 6- and 12-week measurements of lipoproteins and lag phase were obtained. Plasma levels of antioxidants were measured at baseline and 12 weeks.. Concentrations of alpha-tocopherol, vitamin C and beta-carotene significantly increased in the mid- and high dose groups during the trial. Lag phase significantly increased from baseline (190.1 +/- 63.8 min [mean +/- SD]) to 12 weeks (391.1 +/- 153.0 min) in the high dose group (p < 0.01). A nonsignificant increase in lag phase in the mid-dose group was observed during the same time interval. A dose response was found for mean percent change from baseline to 12 weeks for lag phase for the placebo, mid- and high dose groups (p = 0.004 for trend).. A high dose combination of antioxidant nutrients reduces the susceptibility of LDL to oxidation in patients with CVD and may be useful in secondary prevention.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; beta Carotene; Coronary Disease; Double-Blind Method; Female; Food, Fortified; Humans; Lipoproteins, LDL; Male; Middle Aged; Oxidation-Reduction; Vitamin E

In the setting of atherosclerosis, endothelial vasomotor function is abnormal. Increased oxidative stress has been implicated as one potential mechanism for this observation. We therefore hypothesized that an antioxidant, ascorbic acid, would improve endothelium-dependent arterial dilation in patients with coronary artery disease.. Brachial artery endothelium-dependent dilation in response to hyperemia was assessed by high-resolution vascular ultrasound before and 2 hours after oral administration of either 2 g ascorbic acid or placebo in a total of 46 patients with documented coronary artery disease. Plasma ascorbic acid concentration increased 2.5-fold 2 hours after treatment (46+/-8 to 114+/-11 micromol/L, P=.001). In the prospectively defined group of patients with an abnormal baseline response (<5% dilation), ascorbic acid produced marked improvement in dilation (2.0+/-0.6% to 9.7+/-2.0%), whereas placebo had no effect (1.1+/-1.5% to 1.7+/-1.5%, P=.003 for ascorbic acid versus placebo). Ascorbic acid had no effect on hyperemic flow or arterial dilation to sublingual nitroglycerin.. Ascorbic acid reverses endothelial vasomotor dysfunction in the brachial circulation of patients with coronary artery disease. These findings suggest that increased oxidative stress contributes to endothelial dysfunction in patients with atherosclerosis and that endothelial dysfunction may respond to antioxidant therapy.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Coronary Circulation; Coronary Disease; Endothelium, Vascular; Female; Humans; Male; Middle Aged; Nitric Oxide; Vasodilation

In this preliminary study to assess the possibility of using ascorbic acid to prevent post-percutaneous transluminal coronary angiography (PTCA) restenosis, the incidence of restenosis was significantly less in 50 patients receiving 500 mg/day of oral ascorbic acid than in 51 control patients. Thus, ascorbic acid, a potent natural antioxidant, appeared to be possibly effective in attenuating post-PTCA restenosis.

Topics: Adult; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Ascorbic Acid; Cineangiography; Coronary Angiography; Coronary Disease; Diagnosis, Computer-Assisted; Female; Follow-Up Studies; Humans; Male; Middle Aged; Recurrence

In the Western Electric Company Study, carried out in Chicago, Illinois, data on diet and other factors were obtained in 1958 and 1959 for a cohort of 1,556 employed, middle-aged men. Nutrients included vitamin C and beta-carotene. An index that summarized combined intake of both nutrients was constructed. Mean intakes of vitamin C in the lowest and highest tertiles of the index were 66 and 138 mg/day; corresponding values for beta-carotene were 2.3 and 5.3 mg/day. A total of 522 of 1,556 men died during 32,935 person-years of follow-up, 231 from coronary heart disease and 155 from cancer. After adjustment for potentially confounding factors, relative risks (95% confidence intervals) associated with an increment of 19 points in the index (difference between means of the lowest and highest tertiles) were 0.60 (0.39-0.93) for cancer mortality, 0.70 (0.49-0.98) for coronary disease mortality, and 0.69 (0.55-0.87) for all-cause mortality. These results support the hypothesis that consumption of foods rich in vitamin C and beta-carotene reduces risk of death in middle-aged men.

Topics: Adult; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Chicago; Confidence Intervals; Confounding Factors, Epidemiologic; Coronary Disease; Diet; Humans; Male; Middle Aged; Mortality; Neoplasms; Pilot Projects; Risk Factors; Telephone

The objective of the study was to evaluate the contribution of dietary factors to variation of plasma levels of lipids, apoproteins and lipoparticles in the Northern Ireland population. This study was part of a larger case-control study of the genetic and environmental determinants of myocardial infarction in France and Northern Ireland. A random sample of 175 middle aged men was drawn from the population covered by the Belfast MONICA project register. Habitual diet was assessed by a questionnaire. A blood sample was obtained after an over-night fast for determination of plasma levels of lipids, apoproteins and lipoparticles. All participants had a medical examination and completed a lifestyle questionnaire. In a stepwise regression, after adjusting for co-factors (i) vitamin C and (ii) alcohol consumption were the only nutrients which contributed significantly to the variation in, respectively, (i) Total Cholesterol, LDL Cholesterol and Apolipoprotein B (inverse correlation) and (ii) HDL Cholesterol and LpAI (positive correlation). The amount of variation explained by the final models was modest, ranging from 4% to 15%. In conclusion, in this Northern Ireland population, habitual diet contributes to little of the variation in plasma levels of lipids, apoproteins and lipoparticles.

Topics: Adult; Alcohol Drinking; Apoproteins; Ascorbic Acid; Case-Control Studies; Coronary Disease; Diet; Energy Intake; France; Humans; Life Style; Lipids; Male; Middle Aged; Myocardial Infarction; Northern Ireland; Risk Factors; Surveys and Questionnaires

Pharmacologic doses of folate, in the absence of clinical folate deficiency, can reduce plasma levels of the putatively atherothrombotic amino acid, homocysteine (H(e)). Data suggesting that H(e) may accumulate in experimental scurvy prompted us to explore the efficacy of high dose ascorbate supplementation as a H(e)-lowering treatment, in the absence of clinical ascorbate deficiency. A randomized, placebo-controlled trial of 12 weeks of high dose (4.5 g/day) ascorbate supplementation was completed by 44 patients with established coronary heart disease. No significant change in mean fasting total plasma H(e) levels was demonstrable despite a marked increase in mean fasting plasma ascorbate levels amongst those patients randomized to active treatment. Ascorbate supplementation to prevent the development of fasting hyperhomocysteinemia may only be relevant at scorbutic levels of plasma ascorbate.

Topics: Ascorbic Acid; Coronary Disease; Homocysteine; Humans

Forty patients with past history myocardial infarction were divided into three groups. Group I served as controls, while Groups II and III were given respectively, 1 g and 2 g vitamin C daily, divided in two doses. Samples were collected initially, and then every 2 months during the 6-month period of vitamin C administration and finally 2 months after stopping vitamin C. Vitamin C, 0.5 g twice daily (Group II), increased serum ascorbic acid by about 22% (P less than 0.05). However, no significant changes were observed in fibrinolytic activity or blood lipids. When the dose of vitamin C was doubled, serum ascorbic acid increased by about 96% and fibrinolytic activity increased by 45% (P less than 0.01), while the platelet adhesive index decreased by 27% (P less than 0.01). The serum cholesterol level dropped by 12% (P less than 0.05) and a significant decrease in serum beta lipoproteins and an increase in the alpha fraction was also seen. A further 40 patients with acute myocardial infarction were divided into two groups; one received 2 g vitamin C daily for the first 20 days and the other received a placebo. Blood samples were collected every 10th day during the 40-day follow up. Vitamin C administration increased fibrinolytic activity by 62.5%, while serum ascorbic acid rose by 94%.

Topics: Acute Disease; Adult; Arteriosclerosis; Ascorbic Acid; Coronary Disease; Fibrinolysis; Humans; Lipids; Male; Middle Aged; Myocardial Infarction; Platelet Adhesiveness; Time Factors

Topics: Adult; Ascorbic Acid; Cholesterol; Clinical Trials as Topic; Coronary Disease; Humans; Male; Middle Aged

Topics: Ascorbic Acid; Bioethical Issues; Child; Child Health Services; Clinical Trials as Topic; Common Cold; Compensation and Redress; Control Groups; Coronary Care Units; Coronary Disease; Disclosure; Epidemiologic Methods; Ethics Committees, Clinical; Ethics Committees, Research; Ethics, Medical; Federal Government; Female; Glomerulonephritis; Government Regulation; Human Experimentation; Humans; Informed Consent; Insurance, Liability; Jurisprudence; Male; Maternal Health Services; Moral Obligations; Nontherapeutic Human Experimentation; Penicillin G Benzathine; Placebos; Professional Staff Committees; Respiratory Tract Infections; Rheumatic Fever; Risk Assessment; Streptococcal Infections; Therapeutic Human Experimentation; United States; Withholding Treatment

Topics: Ascorbic Acid; Blood Vessels; Cholesterol; Clinical Trials as Topic; Coronary Disease; Humans

Cardiac rehabilitation (CR) improves exercise tolerance and general function. However, its effects on blood plasma in cardiac patients remain uncertain. Our aim was to examine the effect of comprehensive CR on the oxidative stress parameters and antioxidant plasma status in patients with coronary artery disease (CAD) after cardiac interventions. Exercise-based rehabilitation was established as ergometer training, adjusted for individual patients' physical efficiency. Training was repeated three times a week for two months. The standard biochemical (total cholesterol, HDL, LDL, triglycerides and erythrocyte sedimentation rate) and metabolic parameters (peak oxygen uptake [VO

Topics: Antioxidants; Ascorbic Acid; Blood Pressure; Blood Proteins; Blood Viscosity; Cardiac Rehabilitation; Coronary Disease; Exercise; Exercise Therapy; Humans; Male; Middle Aged; Oxidative Stress; Peroxides

Dietary guidelines recommend increasing fruit and vegetable intake and, most recently, have also suggested increasing variety.. We prospectively examined the independent roles of quantity and variety in fruit and vegetable intake in relation to incident coronary heart disease (CHD).. We prospectively followed 71,141 women from the Nurses' Health Study (1984-2008) and 42,135 men from the Health Professionals Follow-Up Study (1986-2008) who were free of diabetes, cardiovascular diseases, and cancer at baseline. Diet was assessed by using a validated questionnaire and updated every 4 y. Variety was defined as the number of unique fruit and vegetables consumed at least once per week. Potatoes, legumes, and fruit juices were not included in our definition of fruit and vegetables.. During follow-up, we documented 2582 CHD cases in women and 3607 cases in men. In multivariable analyses, after adjustment for dietary and nondietary covariates, those in the highest quintile of fruit and vegetable intake had a 17% lower risk (95% CI: 9%, 24%) of CHD. A higher consumption of citrus fruit, green leafy vegetables, and β-carotene- and vitamin C-rich fruit and vegetables was associated with a lower CHD risk. Conversely, quantity-adjusted variety was not associated with CHD.. Our data suggest that absolute quantity, rather than variety, in fruit and vegetable intake is associated with a significantly lower risk of CHD. Nevertheless, consumption of specific fruit and vegetable subgroups was associated with a lower CHD risk.

Topics: Adult; Aged; Ascorbic Acid; beta Carotene; Citrus; Cohort Studies; Coronary Disease; Diet; Feeding Behavior; Female; Follow-Up Studies; Fruit; Health Personnel; Humans; Male; Middle Aged; Nurses; Plant Leaves; Prospective Studies; Risk Factors; United States; Vegetables

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

The aim of this study was to investigate anthropometric measurements, body composition, and serum antioxidant vitamin levels in men with coronary heart disease (CHD). Thirty-five men with CHD and 31 men without CHD, aged 40 - 65 years, were included this study. Dietary records and anthropometric measurements of each participant were recorded by researchers and serum antioxidant vitamin levels and lipid profiles were analyzed. Fat mass (FM) and the percentage of fat mass (FM%) in men with CHD was higher than in men without CHD (p < 0.05). Lipid profiles were found to be similar in both groups, with the exception of high-density lipoprotein cholesterol (HDL-C). Men with CHD had lower HDL-C levels than men without CHD (p < 0.05). When the antioxidant vitamin intake of participants was investigated, vitamin E intake in men without CHD was found to be less than in men with CHD (p < 0.05). However, serum vitamin A, vitamin E, and vitamin C levels in men with CHD were found to be lower than in men without CHD (p < 0.05). Based on the results of this study, we propose that high FM, low HDL-C, and low serum antioxidant vitamin levels could be important risk factors for CHD.

Topics: Adipose Tissue; Adiposity; Adult; Aged; Antioxidants; Ascorbic Acid; Body Mass Index; Cholesterol, HDL; Coronary Disease; Diet; Diet Records; Humans; Male; Middle Aged; Overweight; Risk Factors; Turkey; Vitamin A; Vitamin E

To examine whether socioeconomic status (SES) (education, occupation, income), is associated both cross sectionally and prospectively with circulating concentrations of a) two correlates of oxidative damage, F(2)-isoprostanes (F(2)-IsoPs) and gamma-glutamyltransferase (GGT); and b) antioxidant nutrients (ascorbic acid and carotenoids). We also examine whether the proposed associations are mediated by smoking, alcohol consumption, and depression. Risk for chronic disease increases with decreasing SES. One pathway by which low SES might influence disease risk is by promoting oxidative stress.. Data from 1278 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study were used to examine the association of SES with oxidation correlates and antioxidant nutrients. Education, occupation, health behaviors, and body mass index (BMI) were assessed during Years 0, 10, and 15 of the study; income and depression were evaluated at Years 10 and 15. F(2)-isoprostanes were measured at Year 15, gamma-glutamyltransferase (GGT) at Years 0 and 10, carotenoids at Years 0 and 15, and ascorbic acid at Years 10 and 15.. Cross sectionally, oxidation correlates decreased and antioxidant nutrients increased with increasing SES, estimated in several ways, independent of age, sex, race, and BMI. Prospectively, lower Year 0 education and occupation predicted greater increases in GGT and greater decreases in carotenoids over 10 to 15 years. Prospective associations of Year 0 SES with Year 15 carotenoids were independent of Year 15 SES. Smoking, drinking, and depression symptoms partially mediated these effects.. Circulating oxidation correlates increase and antioxidant nutrients decrease with decreasing SES, both cross sectionally and prospectively.

Topics: Adolescent; Alcohol Drinking; Antioxidants; Ascorbic Acid; Biomarkers; Body Mass Index; Carotenoids; Coronary Disease; Coronary Vessels; Cross-Sectional Studies; Educational Status; Female; gamma-Glutamyltransferase; Humans; Income; Longitudinal Studies; Male; Micronutrients; Oxidative Stress; Prospective Studies; Risk Factors; Smoking; Social Class; Young Adult

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

Serum CRP concentrations are elevated in subjects at risk of coronary events and in subjects with metabolic syndrome. Although dietary fat and antioxidants are known for their immune-modulating actions, their reported effects on CRP concentrations have been inconsistent. In the present study we have investigated whether dietary constituents are associated with serum CRP concentrations in healthy subjects and patients with dyslipidaemic. Dyslipidaemic subjects (n=238) were recruited from Hospital Outpatient Clinics in Guilford, UK. Apparently healthy subjects (n=188) were recruited from amongst adjacent University and Hospital employees. A validated food frequency questionnaire was used to estimate dietary intake. Dyslipidaemic patients had higher serum CRP [1.25 (0.42-3.26) mg/L] than control subjects [0.50 (0.17-1.42) mg/L] (p<0.001). In the dyslipidaemic patients, approximately 4% of the variation in serum CRP could be explained by dietary cholesterol intake (p = 0.015, 2.8%), and weakly by dietary vitamin C intake (p = 0.06, 1.2%). No relationship between dietary constituents and serum CRP concentrations was found among the healthy subjects. Hence the present study shows that serum CRP concentrations are increased in patients with classical coronary risk factors, and that they may be modulated by dietary cholesterol.

Topics: Ascorbic Acid; C-Reactive Protein; Case-Control Studies; Cholesterol, Dietary; Coronary Disease; Diet; Dyslipidemias; Exercise; Female; Humans; Male; Multivariate Analysis; Risk Factors; Smoking; Surveys and Questionnaires; United Kingdom; Vitamins

Topics: Administration, Oral; Antioxidants; Ascorbic Acid; Blood Flow Velocity; Coronary Circulation; Coronary Disease; Endothelium, Vascular; Homocysteine; Humans; Hyperhomocysteinemia; Methionine

Topics: Antioxidants; Ascorbic Acid; Atorvastatin; Calcinosis; Cardiovascular Diseases; Coronary Disease; Drug Therapy, Combination; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pyrroles; Vitamin E

We have compared the biokinetics of deuterated natural (RRR) and synthetic (all rac) alpha-tocopherol in male apoE4-carrying smokers and nonsmokers. In a randomized, crossover study subjects underwent two 4-week treatments (400 mg/day) with undeuterated RRR- and all rac-alpha-tocopheryl acetate around a 12-week washout. Before and after each supplementation period subjects underwent a biokinetic protocol (48 h) with 150 mg deuterated RRR- or all rac-alpha-tocopheryl acetate. During the biokinetic protocols, the elimination of endogenous plasma alpha-tocopherol was significantly faster in smokers (P < 0.05). However, smokers had a lower uptake of deuterated RRR than nonsmokers, but there was no difference in uptake of deuterated all rac. The supplementation regimes significantly raised plasma alpha-tocopherol (P < 0.001) with no differences in response between smokers and nonsmokers or between alpha-tocopherol forms. Smokers had significantly lower excretion of alpha-carboxyethyl-hydroxychroman than nonsmokers following supplementation (P < 0.05). Nonsmokers excreted more alpha-carboxyethyl-hydroxychroman following RRR than all rac; however, smokers did not differ in excretion between forms. At baseline, smokers had significantly lower ascorbate (P < 0.01) and higher F(2)-isoprostanes (P < 0.05). F(2)-isoprostanes in smokers remained unchanged during the study, but increased in nonsmokers following alpha-tocopherol supplementation. These data suggest that apoE4-carrying smokers and nonsmokers differ in their handling of natural and synthetic alpha-tocopherol.

Topics: Adult; alpha-Tocopherol; Alzheimer Disease; Apolipoprotein E4; Apolipoproteins E; Ascorbic Acid; Chromans; Coronary Disease; F2-Isoprostanes; Genetic Predisposition to Disease; Humans; Hyperlipoproteinemia Type V; Male; Middle Aged; Smoking; Tocopherols

Cardiovascular disease is the main cause of increased mortality in diabetes patients. Myocardial infraction and stroke is in 60% to 80% causes reason of death in patients with type 2 diabetes mellitus. The main risk factor of cardiovascular disease is hyper-glycemia, hyperinsulinaemia and hypertension. The other arteriosclerosis risk factors are for example smoking. We measure the concentration of ascorbic acid in smokers' diabetes patients with type 2 diabetes mellitus with stable coronary disease scheduled for coronary artery bypass grafting (CABG). Vitamin C is assumed to be a basic antioxidant although its role in pathological conditions is controversial. However, it seems that the complexity of the oxidant-antioxidant system makes the question of participation of ascorbic acid in pathogenesis of diseases still open. Determination of the role of ascorbic acid concentration in pathogenesis of diabetic angiopathy may be of significant importance in the their effective therapy.

Topics: Aged; Ascorbic Acid; Comorbidity; Convalescence; Coronary Artery Bypass; Coronary Disease; Diabetes Mellitus, Type 2; Humans; Middle Aged; Postoperative Period; Preoperative Care; Retrospective Studies; Smoking

Topics: Aged; Ascorbic Acid; Coronary Disease; Female; Humans; Middle Aged; Proportional Hazards Models; Prospective Studies; Risk Factors; Socioeconomic Factors; United Kingdom

We compared plasma biomarkers of antioxidant status, oxidative stress, inflammation, and risk for coronary heart disease in long-term vegetarians and age- and sex-matched omnivores.. Thirty vegetarians (mean age +/- standard deviation: 44.2 +/- 9.0 y) were recruited. The subjects had been vegetarian for 5 to 55 y (21.8 +/- 12.2 y). The control group comprised 30 adults selected by age-stratified sampling from a community health project (mean age: 44.0 +/- 9.2 y). Fasting plasma total antioxidant status (ferric-reducing antioxidant power), ascorbic acid (AA), alpha-tocopherol (total and lipid standardized), malondialdehyde, total cholesterol, triacylglycerol, uric acid (UA), and high-sensitivity C-reactive protein (hsCRP) were measured.. Plasma AA was significantly higher in the vegetarians than in the omnivores (90.5 +/- 21.0 and 61.8 +/- 17.0 microM; P < 0.001). The vegetarians had lower concentrations of triacylglycerol, UA, and hsCRP. Plasma total and lipid-standardized alpha-tocopherol concentrations were also lower in the vegetarians: 22.0 +/- 5.9 and 27.0 +/- 7.9 microM versus 3.76 +/- 0.57 and 4.23 +/- 0.58 microM per millimoles per liter of total cholesterol plus triacylglycerol, respectively. There was a significant inverse correlation between AA and UA (r = -0.343, P < 0.01; n = 60) and between AA and hsCRP (r = -0.306, P < 0.05; n = 55). Plasma ferric-reducing antioxidant power and malondialdehyde did not differ significantly between groups; however, the contribution of AA to the total antioxidant capacity of plasma was approximately 50% greater in the vegetarians.. A long-term vegetarian diet is associated with markedly higher fasting plasma AA concentrations and lower concentrations of TAG, UA, and hsCRP. Long-term vegetarians have a better antioxidant status and coronary heart disease risk profile than do apparently healthy omnivores. Plasma AA may act a useful marker of overall health status.

Topics: Adult; Antioxidants; Ascorbic Acid; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Case-Control Studies; Coronary Disease; Diet, Vegetarian; Female; Health Status; Humans; Male; Oxidative Stress; Risk Factors; Triglycerides; Uric Acid

Fruit and vegetable consumption is associated with low CHD risk in the USA and Northern Europe. There is, in contrast, little information about these associations in other regions of Europe. The goal of the present study was to assess the relationship between frequency of fruit and vegetable intake and CHD risk in two European populations with contrasting cardiovascular incidence rates; France and Northern Ireland. The present prospective study was in men aged 50-59 years, free of CHD, who were recruited in France (n 5982) and Northern Ireland (n 2105). Fruit and vegetable intake was assessed by a food-frequency questionnaire. Incident cases of acute coronary events and angina were recorded over a 5-year follow-up. During follow-up there was a total of 249 ischaemic events. After adjustment on education level, smoking, physical activity, alcohol consumption, employment status, BMI, blood pressure, serum total and HDL-cholesterol, the relative risks (RR) of acute coronary events were 0.67 (95% CI 0.44, 1.03) and 0.64 (95% CI 0.41, 0.99) in the 2nd and 3rd tertiles of citrus fruit consumption, respectively (P for trend <0.03). Similar results were observed in France and Northern Ireland. In contrast, the RR of acute coronary events for 'other fruit' consumption were 0.70 (95% CI 0.31, 1.56) and 0.52 (95% CI 0.24, 1.14) respectively in Northern Ireland (trend P<0.05) and 1.29 (95% CI 0.69, 2.4) and 1.15 (95% CI 0.68, 1.94) in France (trend P=0.5; interaction P<0.04). There was no evidence for any association between vegetable intake and total CHD events. In conclusion, frequency of citrus fruit, but not other fruits, intake is associated with lower rates of acute coronary events in both France and Northern Ireland, suggesting that geographical or related factors might affect the relationship between fruit consumption and CHD risk.

Topics: Acute Disease; Anticarcinogenic Agents; Ascorbic Acid; beta Carotene; Citrus; Coronary Disease; Cryptoxanthins; Diet; Eating; France; Fruit; Humans; Incidence; Life Style; Male; Middle Aged; Northern Ireland; Prospective Studies; Risk Factors; Vegetables; Xanthophylls

Topics: Aged; Ascorbic Acid; Coronary Disease; Estrogen Replacement Therapy; Estrogens, Conjugated (USP); Female; Humans; Middle Aged; Postmenopause; Risk Factors; Vitamin E

Our objective was to prospectively examine the relation between vitamin C intake and risk of coronary heart disease (CHD) in women.. Results from prospective investigations of the relation between vitamin C intake and risk of CHD have been inconsistent. The lack of clear evidence for a protective association despite a plausible mechanism indicates the need to evaluate further the association between vitamin C intake and risk of CHD.. In 1980, 85,118 female nurses completed a detailed semiquantitative food-frequency questionnaire that assessed their consumption of vitamin C and other nutrients. Nurses were followed up for 16 years for the development of incident CHD (nonfatal myocardial infarction and fatal CHD).. During 16 years of follow-up (1,240,566 person-years), we identified 1,356 incident cases of CHD. After adjustment for age, smoking, and a variety of other coronary risk factors, we observed a modest significant inverse association between total intake of vitamin C and risk of CHD (relative risk [RR] = 0.73; 95% confidence interval [CI] 0.57 to 0.94). Among women who did not use vitamin C supplements or multivitamins, the association between intake of vitamin C from diet alone and incidence of CHD was weak and not significant (RR = 0.86; 95% CI 0.59 to 1.26). In multivariate models adjusting for age, smoking, and a variety of other coronary risk factors, vitamin C supplement use was associated with a significantly lower risk of CHD (RR = 0.72; 95% CI 0.61 to 0.86).. Users of vitamin C supplements appear to be at lower risk for CHD.

Topics: Adult; Age Factors; Antioxidants; Ascorbic Acid; Chemoprevention; Coronary Disease; Diabetes Complications; Dietary Supplements; Female; Humans; Hypercholesterolemia; Hypertension; Incidence; Life Style; Logistic Models; Middle Aged; Multivariate Analysis; Nutrition Surveys; Proportional Hazards Models; Prospective Studies; Risk Factors; Smoking; Surveys and Questionnaires; United States; Women's Health

Topics: Administration, Oral; Ascorbic Acid; Case-Control Studies; Coronary Disease; Dose-Response Relationship, Drug; Female; Humans; Male; Radial Artery; Risk Assessment; Treatment Failure; Vasodilator Agents

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Coronary Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Prognosis; Randomized Controlled Trials as Topic; Reference Values; Severity of Illness Index; Survival Analysis; Treatment Outcome; Vitamin E

Indians or South Asians have been found to be particularly susceptible to coronary heart disease (CHD) in many countries. A novel risk factor for CHD may be coenzyme Q10 (CoQ10). In this study, plasma CoQ10 (including ubiquinol-10, CoQ10H2, and total CoQ10), various lipid parameters, and antioxidant levels were determined in a random sample of Indians and Chinese from the general population of Singapore. The reduced form of coenzyme Q10, CoQ10H2, and total Q10 concentrations in plasma were significantly lower in Indian males than Chinese males. Although no significant differences were found in plasma concentrations of total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL) between the two ethnic groups, the ratios of ubiquinol and total CoQ10 to triglycerides, total cholesterol, and LDL were significantly lower in Indian males than Chinese males. There were no significant ethnic differences in other antioxidant levels, including trans-retinol, alpha-tocopherol, and ascorbic acid. The consistently lower values of coenzyme Q10, especially its reduced form, in Indian males may contribute to the higher susceptibility of this ethnic group to coronary heart disease.

Topics: Adult; Aged; alpha-Tocopherol; Ascorbic Acid; Cholesterol; Cholesterol, LDL; Coenzymes; Coronary Disease; Disease Susceptibility; Humans; Male; Middle Aged; Oxidation-Reduction; Risk Factors; Singapore; Tretinoin; Triglycerides; Ubiquinone

Although carvedilol attenuates left ventricular (LV) remodeling in coronary occlusion-reperfusion, it is not known whether it attenuates ischemic LV remodeling because of coronary stenosis (CS) or permanent coronary occlusion (CO).. We administered a vehicle, carvedilol, propranolol (2, 10, and 30 mg/kg per day, each), metoprolol (6, 30, and 90 mg/kg per day), or bunazosin (0.2 and 1 mg/kg per day), orally for 12 weeks to a total of 608 rats with CS or CO. In these groups and the sham (n=40), we assessed LV function by echocardiography, CS severity, myocardial blood flow and coronary flow reserve, serum ascorbyl free radical, and vitamin C. Both CS and CO increased LV end-diastolic and end-systolic diameters and decreased ejection fraction. The 4 agents failed to attenuate LV remodeling caused by CO. In contrast, the 3 beta-blockers attenuated (P<0.01) or tended to attenuate the increase in LV end-diastolic diameters caused by CS. With similar blood pressure and heart rate lowering by 3 beta-blockers, carvedilol additionally attenuated the increase in end-systolic diameters and improved ejection fraction. The CS reduced myocardial blood flow and coronary flow reserve, which was reversed by carvedilol without modifying the CS severity. Among the 4 agents, only carvedilol decreased ascorbyl free radical and increased vitamin C.. The effects of beta blockade on ischemic cardiac dysfunction seem to depend on the different properties of the beta-blockers and the doses used. Among the beta-blockers tested, carvedilol provided potent cardioprotection for compromised ischemic but viable myocardium rather than for infarcted myocardium.

Topics: Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Animals; Ascorbic Acid; Carbazoles; Cardiac Catheterization; Carvedilol; Coronary Disease; Coronary Stenosis; Disease Models, Animal; Dose-Response Relationship, Drug; Echocardiography; Hemodynamics; Male; Metoprolol; Norepinephrine; Propanolamines; Propranolol; Quinazolines; Rats; Rats, Sprague-Dawley; Severity of Illness Index; Stroke Volume; Survival Rate; Thiobarbituric Acid Reactive Substances; Ventricular Function, Left; Ventricular Remodeling

It has been suggested that an oxidative mechanism is involved with the impaired endothelium-dependent vasodilatation that occurs after a high-fat meal.. The study was undertaken to evaluate the effect of a single oral dose of vitamin C (2 g) on postprandially impaired endothelium-dependent vasodilatation in patients with coronary heart disease (CHD).. This study included 74 patients with CHD and 50 subjects without CHD with risk factors. The two groups were divided into two subgroups that did or did not receive 2 g of vitamin C (CHD/VitC and CHD/control, n = 37; non-CHD/VitC and non-CHD/control, n = 25) after a high-fat meal (800 calories, 50 g fat). Serum levels of triglyceride, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol in the fasting state and at 2, 4, 5, and 7 h after the high-fat meal were measured. Endothelial function was assessed in the brachial artery by high-resolution ultrasound at baseline and at 4 h postprandially.. The postprandial serum triglyceride concentration increased significantly at 2-5 h after the high-fat meal in all groups. The fasting flow-mediated dilatation (FMD) (p < 0.02) and nitroglycerin-induced dilatation (NID) (p < 0.05) of patients with CHD were impaired compared with those of non-CHD subjects. Postprandial FMD was significantly aggravated in the non-CHD/control group (p < 0.01) and the CHD/control group (p < 0.001), but the postprandial FMD in patients and subjects taking vitamin C showed no significant change, although the CHD/VitC group had a mild tendency toward improvement (p = 0.064) and non-CHD/VitC group had a mild tendency toward aggravation (p = 0.852). The change of NID after a high-fat meal did not reach statistical significance in the four groups. The decrement of postprandial FMD correlated positively with the increment of 2-h serum triglyceride concentration in the patients without vitamin C (n = 62, r = 0.545, p < 0.001).. The postprandial state after a high-fat meal is critical in atherogenesis, as it induces endothelial dysfunction through an oxidative stress mechanism. Vitamin C treatment has a promising benefit for patients with CHD.

Topics: Administration, Oral; Analysis of Variance; Antioxidants; Ascorbic Acid; Brachial Artery; Case-Control Studies; Chi-Square Distribution; Coronary Disease; Dietary Fats; Endothelium, Vascular; Female; Humans; Lipids; Male; Middle Aged; Oxidative Stress; Postprandial Period; Risk Factors; Vasodilation

Topics: Administration, Oral; Antioxidants; Ascorbic Acid; Biological Availability; Coronary Circulation; Coronary Disease; Dose-Response Relationship, Drug; Heart; Humans; Injections, Intravenous; Microcirculation; Research Design; Smoking; Tomography, Emission-Computed

Topics: Antioxidants; Ascorbic Acid; Coronary Disease; Dose-Response Relationship, Drug; Fruit; Humans; Nutritive Value; Vegetables

The possible involvement of oxidative damage in the progression of atherosclerosis has been suggested. There is some evidence that antioxidant therapy may be beneficial for the prevention of coronary heart disease. In this study, we investigated the relationship between coronary artery disease (CAD) and serum antioxidative status by measuring the total antioxidant status (TAS). Other relevant antioxidants, such as retinol, alpha, gamma-tocopherol, ascorbic acid, alpha, beta-carotenoids, erythrocyte glutathione peroxidase (GSH-Px) and oxidative products, were also determined in 31 male CAD patients with angiographically defined CAD and 66 male controls, aged 40-70 years, in a case-control study. The TAS levels, ratio and the concentrations of retinol, albumin, total protein and HDL cholesterol were significantly lower in the CAD patients than in the controls (p<0.01), and alpha-tocopherol and alpha/gamma-tocopherol were significantly higher in the CAD patients than in the controls. The TAS level correlated positively with gamma-GTP, GPT, GOT and uric acid (p<0.01). A multiple regression analysis in the CAD patients revealed that the TAS levels correlated most negatively with the number of diseased vessels. The concentrations of carotenoids and GSH-Px, as well as the alpha/gamma-tocopherol ratio were also significantly associated. Although conditional logistic regression analysis suggested low levels of HDL-cholesterol to be a significant coronary risk factor (OR=5.1, 95% CI=1.09-24.3), the TAS level showed no significant independent contribution to CAD. This study demonstrated an association of antioxidant parameters with the atherosclerosis progression, however, it did not confirm antioxidants as an independent risk factor for CAD event.

Topics: Adult; Aged; alpha-Tocopherol; Antioxidants; Ascorbic Acid; Carotenoids; Case-Control Studies; Coronary Artery Disease; Coronary Disease; gamma-Tocopherol; Glutathione Peroxidase; Humans; Middle Aged; Oxidative Stress; Regression Analysis; Vitamin A

Hyperhomocysteinemia is an important cardiovascular risk factor. Serum homocysteine levels are specially dependent on folate nutritional status. In addition, the oxidative modification of low-density lipoproteins (LDLs) in the endothelial microenvironment is a damaging factor that can be modified with fat-soluble antioxidant vitamins. The present study was done to assess the effect of a supplementation of folic acid and antioxidant vitamins on homocysteine levels and in vitro LDL oxidation in patients with coronary artery disease. Twenty-three patients with angiographically proven coronary artery disease were given supplements for 15 d consisting of one capsule twice a day of a multivitamin preparation containing 0.65 mg folic acid, 150 mg alpha-tocopherol, 150 mg ascorbic acid, 12.5 mg beta-carotene, and 0.4 microgram vitamin B12. Serum lipids, vitamin and homocysteine levels, and in vitro LDL oxidation were measured before and after the supplementation period. During the supplementation period, serum folate levels increased from 5.0 +/- 1.5 to 10.8 +/- 3.8 ng/mL (P < 0.001), vitamin B12 increased from 317.4 +/- 130.4 to 334.5 +/- 123.8 pg/mL (P < 0.05), and alpha-tocopherol increased from 8.2 +/- 5.1 to 13.7 +/- 7.9 mg/L (P < 0.001). Serum homocysteine levels decreased from 8.7 +/- 4.3 to 6.3 +/- 2.2 mumol/L (P < 0.001). In vitro LDL oxidation decreased from 2.6 +/- 1.1 to 1.6 +/- 1.1 nmol malondialdehyde/mg protein (P < 0.001). In comparing patients with healthy controls, basal levels of folate were lower in the patients, whereas vitamin B12, alpha-tocopherol, and homocysteine levels were similar. No changes in serum lipid levels or body weight were observed. In conclusion, a short-term supplementation with folic acid and antioxidant vitamins can reduce serum homocysteine levels and in vitro LDL oxidation in patients with coronary artery disease.

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Coronary Disease; Dietary Supplements; Folic Acid; Homocysteine; Humans; Lipid Peroxidation; Lipids; Lipoproteins, LDL; Vitamin B 12; Vitamin E; Vitamins

Increased inactivation of nitric oxide by oxygen free radicals contributes to endothelial dysfunction in patients with coronary artery disease (CAD). We therefore determined the activity of extracellular superoxide dismutase (EC-SOD), the major antioxidant enzyme system of the vessel wall, and its relation to flow-dependent, endothelium-mediated dilation (FDD) in patients with CAD.. SOD isoenzyme activity was determined in coronary arteries from 10 patients with CAD and 10 control subjects. In addition, endothelium-bound EC-SOD activity (eEC-SOD), released by heparin bolus injection, and FDD of the radial artery were measured in 35 patients with CAD and 15 control subjects. FDD, determined by high-resolution ultrasound, was assessed at baseline, after intra-arterial infusion of vitamin C, N-monomethyl-L-arginine, and combination of both. EC-SOD activity in coronary arteries (control subjects: 126+/-14; CAD: 63+/-11 U/mg protein; P<0.01) and eEC-SOD activity in vivo (control subjects: 14.5+/-1.1; CAD: 3.8+/-1.1 U. mL(-1). min(-1); P<0.01) were reduced in patients with CAD. Activity of eEC-SOD was positively correlated with FDD (r=0.47; P<0. 01) and negatively with the effect of the antioxidant vitamin C on FDD (r=-0.59; P<0.01). In young individuals with hypercholesterolemia, however, eEC-SOD activity was increased (21. 0+/-1.2 U. mL(-1). min(-1); n=10; P<0.05).. In patients with CAD, vascular EC-SOD activity is substantially reduced. The close relation between endothelium-bound EC-SOD activity and FDD suggests that reduced EC-SOD activity contributes to endothelial dysfunction in patients with CAD. In young hypercholesterolemic individuals, however, endothelium-bound EC-SOD activity is increased and may, in part, counteract impairment of endothelial function as the result of increased formation of oxygen free radicals.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Coronary Disease; Coronary Vessels; Drug Combinations; Endothelium, Vascular; Enzyme Inhibitors; Extracellular Space; Humans; Hypercholesterolemia; Male; Middle Aged; omega-N-Methylarginine; Radial Artery; Reactive Oxygen Species; Superoxide Dismutase; Vasodilation

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

Rates of vitamin-mineral supplement use by US female physicians are unknown but are of particular interest for several epidemiologic and clinical reasons.. The objective was to determine rates of and variations in vitamin-mineral supplement use among US female physicians.. We used data from the Women Physicians' Health Study, a large (n = 4501) national, randomly sampled mail survey of female physicians aged 30-70 y.. Half of the physicians took a multivitamin-mineral supplement; 35.5% of these did so regularly. However,

Topics: Adult; Aged; Ascorbic Acid; Calcium; Cohort Studies; Coronary Disease; Diabetes Mellitus; Dietary Supplements; Female; Humans; Marital Status; Middle Aged; Minerals; Neoplasms; Osteoporosis; Physicians, Women; Social Class; Surveys and Questionnaires; Vitamin A; Vitamin E; Vitamins

Topics: Antioxidants; Ascorbic Acid; Coronary Disease; Endothelium, Vascular; Folic Acid; Humans; Vitamin E

Topics: Ascorbic Acid; Coronary Disease; Diet; Dietary Supplements; Humans

Environmental tobacco smoke (ETS) is a pervasive contaminant in the workplace. Our objective was to determine the oxidative stress effects of ETS on employees who are exposed. The results provide information that is useful to the resolution of risk assessment questions associated with ETS. We analyzed two blood draws from volunteers in our control and exposed groups. The level of exposure to ETS was determined through plasma cotinine measurements, which showed a 65% increase from the control group to the exposed group. Exposure to ETS resulted in a statistically significant increase of 63% of the oxidative DNA mutagen 8-hydroxy-2'-deoxyguanosine in the blood of exposed subjects. This oxidative DNA damage has been linked to an increased risk of developing several degenerative chronic diseases, including coronary heart disease and cancer. The exposed subjects also had increased levels of superoxide dismutase, catalase, glutathione peroxidase (GPOX), and glutathione reductase. However, these increases were only statistically significant in catalase and GPOX. Catalase levels were 13% higher in the exposed group, and GPOX levels were 37% higher in exposed volunteers. The biochemical evidence suggests that exposure to ETS causes oxidative stress, resulting in DNA damage that may increase the risk of certain diseases.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Air Pollution, Indoor; Ascorbic Acid; beta Carotene; Catalase; Coronary Disease; Cotinine; Deoxyguanosine; Female; Glutathione Reductase; Humans; Male; Middle Aged; Neoplasms; Oxidative Stress; Risk Factors; Superoxide Dismutase; Tobacco Smoke Pollution; Vitamin E; Workplace

This study sought to investigate the relations between plasma antioxidant status, extent of atherosclerosis and activity of coronary artery disease.. Previous studies indicate that increased antioxidant intake is associated with decreased coronary disease risk, but the underlying mechanisms remain controversial.. Plasma samples were obtained from 149 patients undergoing cardiac catheterization (65 with stable angina, 84 with unstable angina or a myocardial infarction within 2 weeks). Twelve plasma antioxidant/oxidant markers were measured and correlated with the extent of atherosclerosis and the presence of an unstable coronary syndrome.. By multiple linear regression analysis, age (p < 0.001), diabetes mellitus (p < 0.001), male gender (p < 0.001) and hypercholesterolemia (p = 0.02) were independent predictors of the extent of atherosclerosis. No antioxidant/oxidant marker correlated with the extent of atherosclerosis. However, lower plasma ascorbic acid concentration predicted the presence of an unstable coronary syndrome by multiple logistic regression (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.40 to 0.89, p = 0.01). The severity of atherosclerosis also predicted the presence of an unstable coronary syndrome (OR 1.7, 95% CI 1.14 to 2.47, p = 0.008) when all patients were considered. When only patients with significant coronary disease were considered (at least one stenosis >50%), ascorbic acid concentration (OR 0.56, 95% CI 0.37 to 0.85, p = 0.008) and total plasma thiols (OR 0.52, 95% CI 0.34 to 0.80, p = 0.004) predicted the presence of an unstable coronary syndrome, whereas the extent of atherosclerosis did not.. These data are consistent with the hypothesis that the beneficial effects of antioxidants in coronary artery disease may result, in part, by an influence on lesion activity rather than a reduction in the overall extent of fixed disease.

Topics: Aged; Angina Pectoris; Angina, Unstable; Antioxidants; Arteriosclerosis; Ascorbic Acid; Biomarkers; Coronary Disease; Female; Humans; Linear Models; Lipid Peroxidation; Logistic Models; Male; Middle Aged; Myocardial Infarction

1. The ability of EPC-K1 to improve myocardial infarction was evaluated in a rat model with coronary artery occlusion and reperfusion. 2. The myocardial infarct size was 30.5 +/- 1.7% by intravenous (i.v.) administration and 28.8 +/- 2.7% by intraduodenal (i.d.) administration of the saline EPC-K1 at doses between 1 and 10 mg/kg, i.v. and at doses between 50 and 200 mg/kg, i.d., reduced myocardial infarct size dose dependently. Significant reduction in myocardial infarct size was found at a dose of 10 mg/kg, i.v., and 200 mg/kg, i.d.

Topics: Animals; Antioxidants; Arterial Occlusive Diseases; Ascorbic Acid; Combined Modality Therapy; Coronary Disease; Disease Models, Animal; Free Radical Scavengers; Male; Myocardial Infarction; Myocardial Reperfusion Injury; Rats; Rats, Wistar; Vitamin E

To examine the hypothesis that the higher rates of coronary heart disease (CHD) in Indians (South Asians) compared with Malays and Chinese is partly because of differences in antioxidants (vitamins A, C, and E, and selenium) and pro-oxidants (iron).. Cross sectional study of the general population.. Singapore.. Random sample of 941 persons aged 30 to 69 years.. There were moderate correlations between vitamin A and vitamin E, and between these vitamins and selenium. Mean plasma vitamins A and E were similar by ethnic group. Vitamin A concentration for Indians were (men 0.66 and women 0.51 mg/l), Malays (men 0.67 and women 0.54 mg/l), and Chinese (men 0.68 and women 0.52 mg/l). Vitamin E concentrations for Indians were (men 12.9 and women 12.8 mg/l), Malays (men 13.6 and women 13.3 mg/l), and Chinese (men 12.6 and women 12.6 mg/l). In contrast, mean plasma vitamin C concentrations were lower in Indians (men 5.7 and women 6.9 mg/l) and Malays (men 5.1 and women 6.4 mg/l) than Chinese (men 6.3 and women 8.4 mg/l). Mean serum selenium was lower in Indians (men 117 and women 115 micrograms/l) than Malays (men 122 and women 122 micrograms/l) and Chinese (men 126 and women 119 micrograms/l). Mean serum ferritin was much lower in Indians (men 132 and women 50 micrograms/l) than Malays (men 175 and women 85 micrograms/l) and Chinese (men 236 and women 92 micrograms/l).. Lower vitamin C and selenium in Indians, particularly in combination, could play a part in their increased risk of CHD. Vitamins A and E, and ferritin (iron) have no such role. Lower vitamin C in Indians and Malays is probably because of its destruction by more prolonged cooking. In Indians, lower selenium is probably because of a lower dietary intake and the much lower ferritin to a lower dietary intake of iron and its binding by phytates.

Topics: Adult; Ascorbic Acid; China; Coronary Disease; Cross-Sectional Studies; Female; Ferritins; Humans; India; Malaysia; Male; Middle Aged; Risk Factors; Selenium; Singapore; Vitamin A; Vitamin E

The National University of Singapore Heart Study measured cardiovascular risk factors, including selected plasma vitamins, on a random sample of the general population aged 30 to 69 years. Plasma vitamins A and E were normal and similar by ethnic group. Mean plasma vitamin A levels were: Chinese (males 0.68 and females 0.52 mg/L), Malays (males 0.67 and females 0.54 mg/L), and Indians (males 0.66 and females 0.51 mg/L). Mean plasma vitamin E levels were: Chinese (males 12.6 and females 12.6 mg/L), Malays (males 13.6 and females 13.3 mg/L), and Indians (males 12.9 and females 12.8 mg/L). No person had plasma vitamin A deficiency (< 0.01 mg/L) and only 0.1% had vitamin E deficiency (< 5.0 mg/L). In contrast, plasma vitamin C was on the low side and higher in Chinese than Malays and Indians. Mean plasma vitamin C levels were: Chinese (males 6.3 and females 8.4 mg/L), Malays (males 5.1 and females 6.4 mg/L), and Indians (males 5.7 and females 6.9 mg/L). Likewise, the proportions with plasma vitamin C deficiency (< 2.0 mg/L) were lower in Chinese (males 14.4 and females 0.7%), than Malays (males 19.7 and females 7.2%), and Indians (males 17.8 and females 11.0%). Relatively low levels of plasma vitamin C may contribute to the high rates of coronary heart disease and cancer in Singapore. In particular, lower plasma vitamin C in Malays and Indians than Chinese may contribute to their higher rates of coronary heart disease. However, plasma vitamin C does not seem to be involved in the higher rates of cancer in Chinese than Malays and Indians. The findings suggest a relatively low intake of fresh fruits and a higher intake is recommended. Also, food sources of vitamin C may be destroyed by the high cooking temperatures of local cuisines, especially the Malay and Indian ones.

Topics: Adult; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; China; Cooking; Coronary Disease; Ethnicity; Feeding Behavior; Female; Fruit; Heart Diseases; Humans; India; Malaysia; Male; Middle Aged; Neoplasms; Risk Factors; Singapore; Smoking; Vitamin A; Vitamin E; Vitamin E Deficiency

This study demonstrated that magnesium (Mg) reduces free radicals after a brief coronary occlusion-reperfusion sequence.. Magnesium has been shown to reduce infarct size in patients with acute myocardial infarction. We hypothesized that this action of Mg occurs through its action on free radicals.. Eighteen mongrel dogs were studied (nine control, nine receiving Mg). Catheters were placed into the coronary sinus for continuous blood withdrawal. A Varian E-4 electron paramagnetic resonance spectrometer was used to monitor the ascorbate free radical (AFR) signal in the coronary sinus blood; AFR is a measure of total oxidative stress. Occlusion of the left anterior descending coronary artery for 20 min was followed by reperfusion. The study animals received 4 g Mg intravenously starting at 15 min of occlusion (5 min before reperfusion) and continuing during reperfusion.. Results are presented as percent change from baseline +/- SEM. Magnesium blunted the peak AFR increase: at 4 min of reperfusion there was a 4.7 +/- 3.3% increase in AFR signal in the dogs receiving Mg versus an 18.2 +/- 3.3% increase in the control animals (p < 0.05). Total radical flux was reduced during reperfusion by 53% in the Mg dogs compared with controls (p < 0.05).. Magnesium attenuates AFR increase after an occlusion-reperfusion sequence. To our knowledge this is the first in vivo real-time demonstration of Mg's impact on free radicals.

Topics: Animals; Ascorbic Acid; Cardiac Catheterization; Coronary Disease; Coronary Vessels; Dogs; Electron Spin Resonance Spectroscopy; Free Radical Scavengers; Free Radicals; Infusions, Intravenous; Magnesium; Myocardial Infarction; Myocardial Reperfusion; Oxidative Stress

Impaired endothelium-dependent vasodilation has been reported to play an important role in the pathogenesis of cardiovascular diseases such as coronary artery disease (CAD) and congestive heart failure (CHF). However, the precise mechanism of endothelial dysfunction has not been elucidated in these conditions. To evaluate the role of oxidative stress in endothelial dysfunction, the effect of antioxidant ascorbic acid on brachial flow-mediated, endothelium-dependent vasodilation during reactive hyperemia and nitroglycerin-induced endothelium-independent vasodilation was examined with high resolution ultrasound in 12 patients with CHF caused by idiopathic dilated cardiomyopathy without established coronary atherosclerosis and in 10 patients with CAD. Flow-mediated vasodilation in CHF (4.4+/-0.5%) and CAD (4.0 - 0.8%) was significantly (p <0.05) attenuated compared with that in 10 control subjects (9.6+/-0.9%). However, nitroglycerin-induced vasodilation was similar in 3 groups (13.7+/-1.3% in control, 13.9+/-1.1% in CHF, 12.7+/-1.4% in CAD). Ascorbic acid could significantly improve flow-mediated vasodilation only in patients with CAD (9.1+/-0.9%) but not with CHF (5.6+/-0.6%), and had no influence on nitroglycerin-induced vasodilation (13.6+/-1.1% in CHF, 14.0+/-1.3% in CAD). These results suggest that, in brachial circulation, augmented oxidative stress mainly leads to endothelial dysfunction in CAD but not in CHF caused by idiopathic dilated cardiomyopathy.

Topics: Adult; Aged; Angina Pectoris; Ascorbic Acid; Blood Flow Velocity; Brachial Artery; Cardiomyopathy, Dilated; Coronary Disease; Endothelium, Vascular; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Nitroglycerin; Reproducibility of Results; Ultrasonography, Doppler; Vasodilation; Vasodilator Agents

Topics: Antioxidants; Arteriosclerosis; Ascorbic Acid; beta Carotene; Coronary Disease; Humans; Neoplasms; Risk Factors; Treatment Outcome; Vitamin E

Oxidative stress may be an important pathogenetic factor in the development of diabetic vascular complications. The total antioxidative potential of plasma reflects the ability of an individual to resist oxidative stress. We measured the plasma total peroxyl radical-trapping potential (TRAP) and the concentrations of four plasma chain-breaking antioxidants in 81 patients with non-insulin-dependent diabetes mellitus (NIDDM) nine years after diagnosis and in 102 well-matched non-diabetic control subjects. The association between the total antioxidative potential and the presence of coronary heart disease (CHD) and diabetic kidney disease were also studied. There were no significant differences in plasma TRAP between NIDDM patients and control subjects (1250+/-199 vs. 1224+/-198 microM). Nor were there any significant differences in the concentrations of plasma uric acid, ascorbic acid, alpha-tocopherol, and protein thiols between NIDDM patients and control subjects. Patients with a low glomerular filtration rate and/or high urinary albumin excretion had elevated plasma uric acid. Plasma TRAP was not, however, associated with renal dysfunction. The plasma of NIDDM patients with CHD had a significantly higher value of unidentified antioxidative potential than that of patients without CHD. This relation was strongly dependent upon smoking. In conclusion, these data demonstrate that there are no major defects in the antioxidative potential of plasma caused by NIDDM per se. CHD and diabetic renal dysfunction were not associated with changes in plasma TRAP.

Topics: Aged; Antioxidants; Ascorbic Acid; Biomarkers; Chromatography, High Pressure Liquid; Coronary Disease; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Humans; Male; Matched-Pair Analysis; Middle Aged; Oxidative Stress; Smoking; Statistics as Topic; Sulfhydryl Compounds; Uric Acid; Vitamin E

Topics: Antioxidants; Ascorbic Acid; Coronary Disease; Humans; Lipoproteins, LDL; Vitamin E

The Food and Drug Administration (FDA) is issuing an interim final rule to prohibit the use on foods of a claim relating to the relationship between antioxidant vitamins C and E and the risk in adults of atherosclerosis, coronary heart disease, certain cancers, and cataracts. This rule is in response to a notification of a health claim submitted under section 303 of the FDA Modernization Act of 1997 (FDAMA). FDA has reviewed statements that the petitioner submitted in that notification, and, in conformity with the requirements of FDAMA, the agency is prohibiting the claim because the statements submitted as the basis of the claim are not "authoritative statements" of a scientific body, as required by FDAMA; therefore, section 303 of FDAMA does not authorize use of this claim. As provided for in section 301 of FDAMA, this rule is effective immediately upon publication.

Topics: Adult; Arteriosclerosis; Ascorbic Acid; Cataract; Coronary Disease; Drug Approval; Food Labeling; Humans; Neoplasms; Risk Factors; United States; United States Food and Drug Administration; Vitamin E

Topics: Administration, Oral; Aged; Aged, 80 and over; Ascorbic Acid; beta Carotene; Chromatography, High Pressure Liquid; Coronary Disease; Diet; Eating; Female; Humans; Male; Middle Aged; Multivariate Analysis; Vitamin E

There is increasing experimental evidence that oxidation of LDL plays a major role in the pathogenesis of coronary artery disease (CAD). However, results from clinical studies on LDL oxidation and CAD are not consistent. In most studies only single plasma factors of LDL oxidation have been determined. We studied 207 patients who underwent coronary angiography. They were divided into subjects with CAD (n = 137) and those without CAD (n = 70). We determined the susceptibility of LDL to in vitro oxidation (lag phase), potential prooxidative and antioxidative plasma factors (plasma vitamin E, LDL vitamin E, ascorbate, iron, copper, ferritin, and ceruloplasmin), and markers of in vivo LDL oxidation (autoantibodies to malondialdehyde-modified LDL, oxidized LDL, and thiobarbituric acid-reactive substances), plasma lipids and lipoproteins, smoking habits, and other coronary risk factors in both groups. The lag phase was significantly shorter in patients with CAD than in patients without CAD (101 +/- 38.6 versus 119 +/- 40.6 minutes, P < .01). There was no correlation between the lag phase and the other oxidation parameters or the coronary risk factors. In multivariate regression analyses the lag phase remained significant in all tested models. Our data suggest that a short lag phase of LDL oxidation might be an independent risk factor of CAD.

Topics: Aged; Ascorbic Acid; Coronary Disease; Female; Humans; Lipid Metabolism; Lipoproteins; Lipoproteins, LDL; Male; Middle Aged; Multivariate Analysis; Oxidation-Reduction; Time Factors; Vitamin E

The role of dietary antioxidant vitamins in preventing coronary heart disease has aroused considerable interest because of the knowledge that oxidative modification of low-density lipoprotein may promote atherosclerosis.. We studied 34,486 postmenopausal women with no cardiovascular disease who in early 1986 completed a questionnaire that assessed, among other factors, their intake of vitamins A, E, and C from food sources and supplements. During approximately seven years of follow-up (ending December 31, 1992), 242 of the women died of coronary heart disease.. In analyses adjusted for age and dietary energy intake, vitamin E consumption appeared to be inversely associated with the risk of death from coronary heart disease. This association was particularly striking in the subgroup of 21,809 women who did not consume vitamin supplements (relative risks from lowest to highest quintile of vitamin E intake, 1.0, 0.68, 0.71, 0.42, and 0.42; P for trend 0.008). After adjustment for possible confounding variables, this inverse association remained (relative risks from lowest to highest quintile, 1.0, 0.70, 0.76, 0.32, and 0.38; P for trend, 0.004). There was little evidence that the intake of vitamin E from supplements was associated with a decreased risk of death from coronary heart disease, but the effects of high-dose supplementation and the duration of supplement use could not be definitely addressed. Intake of vitamins A and C did not appear to be associated with the risk of death form coronary heart disease.. These results suggest that in postmenopausal women the intake of vitamin E from food is inversely associated with the risk of death from coronary heart disease and that such women can lower their risk without using vitamin supplements. By contrast, the intake of vitamins A and C was not associated with lower risks of dying from coronary disease.

Topics: Aged; Antioxidants; Ascorbic Acid; Coronary Disease; Diet; Female; Food, Fortified; Humans; Middle Aged; Postmenopause; Prospective Studies; Risk; Risk Factors; Vitamin A; Vitamin E

We examined vitamin E and vitamin C supplement use in relation to mortality risk and whether vitamin C enhanced the effects of vitamin E in 11,178 persons aged 67-105 y who participated in the Established Populations for Epidemiologic Studies of the Elderly in 1984-1993. Participants were asked to report all nonprescription drugs currently used, including vitamin supplements. Persons were defined as users of these supplements if they reported individual vitamin E and/or vitamin C use, not part of a multivitamin. During the follow-up period there were 3490 deaths. Use of vitamin E reduced the risk of all-cause mortality [relative risk (RR) = 0.66; 95% CI: 0.53, 0.83] and risk of coronary disease mortality (RR = 0.53; 95% CI: 0.34, 0.84). Use of vitamin E at two points in time was also associated with reduced risk of total mortality compared with that in persons who did not use any vitamin supplements. Effects were strongest for coronary heart disease mortality (RR = 0.37; 95% CI: 0.15, 0.90). The RR for cancer mortality was 0.41 (95% CI: 0.15, 1.08). Simultaneous use of vitamins E and C was associated with a lower risk of total mortality (RR = 0.58; 95% CI: 0.42, 0.79) and coronary mortality (RR = 0.47; 95% CI: 0.25, 0.87). Adjustment for alcohol use, smoking history, aspirin use, and medical conditions did not substantially alter these findings. These findings are consistent with those for younger persons and suggest protective effects of vitamin E supplements in the elderly.

Topics: Aged; Aged, 80 and over; Aging; Ascorbic Acid; Coronary Disease; Female; Humans; Male; Mortality; Neoplasms; Risk; Vitamin E

In the present study, erythrocyte membrane lipid peroxidation, erythrocyte superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and serum vitamin C levels of subjects with and without coronary artery disease (CAD) documented by coronary angiography have been determined. Patients consisted of 42 subjects (31 male, 11 female) aged between 41 and 77 years and controls consisted of 35 subjects (21 male, 14 female) aged between 40 and 69 years. Erythrocyte lipid peroxidation of the patients was significantly higher (P < 0.005) whereas erythrocyte SOD, GSH-Px activities and serum vitamin C levels were lower than those of controls. Our results show significant alteration in erythrocyte membranes and antioxidant status of patients with CAD. However, whether such alterations are a primary cause or consequence of CAD and whether these alterations can be used in the diagnosis and management of the disease needs further investigation.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Coronary Angiography; Coronary Disease; Erythrocyte Membrane; Erythrocytes; Female; Glutathione Peroxidase; Humans; Lipid Peroxidation; Male; Membrane Lipids; Middle Aged; Reference Values; Superoxide Dismutase; Triglycerides

Vitamin C has been suggested to be protective for coronary heart disease but the evidence from epidemiological studies is inconclusive and most studies have been conducted in men. We examined the cross-sectional relationship between vitamin C status and previously undiagnosed angina in women.. Women aged 45-74 years were recruited from general practices. They completed a health and lifestyle questionnaire and attended for a health check and a blood test. Non-fasting plasma vitamin C was used to define vitamin status and a self-completed Rose angina questionnaire was used to identify cases.. Forty-two women with previously undiagnosed angina (cases) were compared with 877 women with no reported angina (controls). The mean plasma vitamin C was 50.2 mumol/l in cases and 58.3 mumol/l in controls. The age-adjusted odds ratio for a 50 mumol/l increase in plasma vitamin C was 0.34 (95% confidence interval 0.15-0.79). The odds ratio was unaltered after adjustment for body mass index, smoking and established coronary risk factors, and after stratification by smoking, vitamin supplementation and hormone replacement.. This cross-sectional analysis showed an association in women between lower plasma levels of vitamin C and previously undiagnosed angina. Although we are unable to exclude the possibility that symptomatic prevalent disease modifies plasma vitamin C levels, these data are consistent with a protective effect of vitamin C for coronary heart disease. This relationship requires confirmation in further prospective studies and trials of vitamin C supplementation.

Topics: Aged; Angina Pectoris; Ascorbic Acid; Confidence Intervals; Coronary Disease; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Odds Ratio; Reference Values; Risk Factors; Sensitivity and Specificity; Surveys and Questionnaires

Our purpose was to determine whether prolonged myocardial ischemia attenuates free radical production after early reperfusion. Twenty-two mongrel dogs underwent left anterior descending coronary artery occlusion for 20, 40, or 60 minutes followed by 30 minutes of reperfusion. Electron paramagnetic resonance spectroscopy was used to measure ascorbate free radical in the coronary vein effluent. Ascorbate free radical production during reperfusion was significantly (p < 0.05) reduced in the dogs undergoing 60 minutes of coronary artery occlusion compared with the dogs undergoing 40 and 20 minutes of occlusion. We conclude that prolonged myocardial ischemia results in less free radical production on reperfusion than do shorter periods of ischemia followed by reperfusion.

Topics: Animals; Ascorbic Acid; Coronary Disease; Dogs; Echocardiography; Electron Spin Resonance Spectroscopy; Female; Free Radicals; Male; Myocardial Reperfusion; Myocardium; Time Factors

Copper mediated oxidative modification of high density lipoprotein (HDL) diminishes its capacity to promote cholesterol efflux from cells in culture. In the present study, HDL was isolated from eight subjects before and after a 10 day administration of the antioxidant vitamins C and E. After incubation HDL (1.25 mg protein/ml) with 10 microM copper for 0-4 h or with 0-20 microM copper for 4 h, thiobarbituric acid reactive substances (TBARS) production was significantly decreased following vitamin administration suggesting that the vitamins decreased the susceptibility of HDL to oxidation. However, two other assays of lipoprotein oxidation, trinitrobenzene sulfonic acid reactivity and conjugated diene formation, did not show a consistent effect of vitamin administration. To study cholesterol efflux, J774 macrophages were labeled with 3H cholesterol (0.1 microCi/ml, 50 micrograms/ml) and incubated with HDL or oxidized HDL (100 micrograms protein/ml) for 24 h. HDL isolated before vitamins and oxidized in vitro was 39% less effective in mediating efflux compared to unmodified HDL, while HDL isolated after vitamins and oxidized was 22% less effective (before vs. after vitamins, P < 0.015). HDL oxidation determined by measuring TBARS production correlated with decreased cholesterol efflux (r = 0.37, P < 0.050). These data suggest that oxidation of HDL interferes with its role in reverse cholesterol transport and that antioxidant vitamins have a protective effect.

Topics: Adult; Animals; Ascorbic Acid; Cells, Cultured; Cholesterol; Copper; Coronary Disease; Female; Food, Fortified; Humans; Lipoproteins, HDL; Macrophages; Male; Mice; Middle Aged; Oxidation-Reduction; Peritoneum; Reference Values; Thiobarbituric Acid Reactive Substances; Trinitrobenzenesulfonic Acid; Vitamin E

The prevalence of coronary artery disease (CAD) in the urban population of India is similar to that in developed countries; Indian immigrants in industrialized countries have the highest prevalence of CAD. This is a cross-sectional survey within a random sample of a single urban setting in India. The relation between risk of CAD and plasma levels of vitamins A, C, E, and beta-carotene was examined in 72 of 595 elderly subjects (12.1%) with CAD (aged 50 to 84 years). Plasma levels of vitamins A, C, E, and beta-carotene were significantly related to risk of CAD. Smoking (n = 145) and diabetes (n = 70) were the confounding factors. Lipid peroxides were higher in patients with CAD and diabetes, and in those who smoked. The inverse relation between CAD and low plasma vitamin C was substantially reduced after adjustment for smoking and diabetes. Vitamin A and E levels remained independently and inversely related to the risk of CAD after adjustment for age, smoking, diabetes, blood pressure, blood lipoproteins, and relative weight and body mass index. The adjusted odds ratios for CAD between the lowest and highest quintiles of vitamin E levels were 2.53 (95% confidence interval [CI] 1.11 to 5.31), vitamin C, 2.21 (95% CI 1.12 to 3.15), and beta-carotene, 1.72 (95% CI 0.88 to 3.62). The fatty acid composition of the diet, blood lipid levels, central obesity (waist-hip ratio), smoking habits, blood pressure, and plasma insulin levels do not appear to account for high rates of CAD among elderly Indians.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Coronary Disease; Cross-Sectional Studies; Diet; Female; Humans; India; Male; Middle Aged; Oxidative Stress; Risk Factors; Smoking; Vitamin E

To determine whether vitamin C status, as measured by dietary intake and plasma ascorbic acid concentration, is related to mortality from stroke and coronary heart disease in people aged 65 and over.. A 20 year follow up study of a cohort of randomly selected elderly people living in the community who had taken part in the 1973-4 Department of Health and Social Security nutritional survey and for whom dietary and other data had been recorded.. Eight areas in Britain (five in England, two in Scotland, and one in Wales).. 730 men and women who had completed a seven day dietary record and who had no history or symptoms of stroke, cerebral arteriosclerosis, or coronary heart disease when examined by a geriatrician in 1973-4.. Mortality from stroke was highest in those with the lowest vitamin C status. Those in the highest third of the distribution of vitamin C intake had a relative risk of 0.5 (95% confidence interval 0.3 to 0.8) compared with those in the lowest third, after adjustment for age, sex, and established cardiovascular risk factors. The relation between vitamin C intake and stroke was independent of social class and other dietary variables. A similar gradient in risk was present for plasma ascorbic acid concentrations. No association was found between vitamin C status and risk of death from coronary heart disease.. In elderly people vitamin C concentration, whether measured by dietary intake or plasma concentration of ascorbic acid, is strongly related to subsequent risk of death from stroke but not from coronary heart disease.

Topics: Aged; Aged, 80 and over; Ascorbic Acid; Cerebrovascular Disorders; Cohort Studies; Coronary Disease; Female; Humans; Male; Nutrition Surveys; Proportional Hazards Models; Risk Factors; Socioeconomic Factors

Topics: Anticholesteremic Agents; Arteriosclerosis; Ascorbic Acid; Clinical Trials as Topic; Coronary Disease; Female; Humans; Hypercholesterolemia; Lipoproteins, LDL; Male; Meta-Analysis as Topic; Risk Factors

The prevalence of coronary artery (CAD) disease in the Indian urban population is comparable to British population. Dietary intakes, antioxidant vitamins, prevalence of risk factors and CAD, were studied in a random sample of 152 adult urban subjects between 26-65 years of age (80 males, 72 females) from Peerzada street, Moradabad and compared with Indian immigrants to U.K. and a British comparison group. There was no significant relation with vitamin A. Smoking and diabetes were the confounding factors. Plasma antioxidant vitamin C (21.6 +/- 3.3 vs 42.5 +/- 4.5 mumol/L), vitamin E (15.2 +/- 2.8 vs 21.4 +/- 3.2 mumol/L) and beta-carotene (0.33 +/- 0.6 vs 0.55 +/- 0.08 mumol/L) were significantly lowered and lipid peroxides higher (2.82 +/- 0.22 vs 1.3 +/- 0.20 nmol/ml) in patients with CAD compared to subjects without any risk factors. The relation between low plasma level of vitamin C and E levels and carotene remained independently and inversely related after adjustment for smoking, diabetes and other risk factors. Regression analysis showed that after adjustment. Odd's ratio for carotene (1.82, 95% C.I. 0.50 to 3.72), vitamin C (2.23, 95% C.I. 1.14 to 5.26) and vitamin E (2.35, 95% C.I. 1.29 to 5.30) were significantly related to CAD. Underlying these changes, dietary intake of vitamin A, E, C and beta-carotene was significantly less in patients with CAD. Vitamin C and beta-carotene intake were less in smokers and diabetes. Compared with British population, the Indian urbans consumed less total and saturated fat and cholesterol and more polyunsaturated fat and complex carbohydrates. The plasma total and low density lipoprotein cholesterol levels were less in Indian urbans compared to Britons and so were mean body weight, body mass index and waist-hip ratio. Plasma insulin levels were comparable. The fatty acid composition of the diet, blood lipids, central obesity and insulin levels do not appear to account for high rates of CAD among Indians. The findings suggest that urban population in India may benefit from eating diets rich in antioxidant vitamin C, E and beta-carotene.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Coronary Disease; Diet; Dietary Fats; Emigration and Immigration; Female; Humans; India; Male; Middle Aged; Oxidative Stress; Prospective Studies; Risk Factors; United Kingdom; Urban Health; Vitamin A; Vitamin E; Vitamins

Oxidation of lipoproteins is hypothesized to promote atherosclerosis and, thus, a high intake of antioxidant nutrients may protect against coronary heart disease. The relation between the intakes of dietary carotene, vitamin C, and vitamin E and the subsequent coronary mortality was studied in a cohort of 5,133 Finnish men and women aged 30-69 years and initially free from heart disease. Food consumption was estimated by the dietary history method covering the total habitual diet during the previous year. Altogether, 244 new fatal coronary heart disease cases occurred during a mean follow-up of 14 years beginning in 1966-1972. An inverse association was observed between dietary vitamin E intake and coronary mortality in both men and women with relative risks of 0.68 (p for trend = 0.01) and 0.35 (p for trend < 0.01), respectively, between the highest and lowest tertiles of the intake. Similar associations were observed for the dietary intake of vitamin C and carotenoids among women and for the intake of important food sources of these micronutrients, i.e., of vegetables and fruits, among both men and women. The associations were not attributable to confounding by major nondietary risk factors of coronary heart disease, i.e., age, smoking, serum cholesterol, hypertension, or relative weight. The results support the hypothesis that antioxidant vitamins protect against coronary heart disease, but it cannot be excluded that foods rich in these micronutrients also contain other constituents that provide the protection.

Topics: Adult; Aged; Ascorbic Acid; Carotenoids; Coronary Disease; Diet; Female; Humans; Longitudinal Studies; Male; Middle Aged; Risk Factors; Vitamin E

Plasma lipid and apolipoprotein (apo) A-I and B concentrations and habitual dietary intakes were determined in 306 free-living elderly individuals (119 men and 187 women, age range 60-100 y). Plasma lipid and apo A-I concentrations were significantly higher in women than in men. In older men, plasma triglyceride, total cholesterol, and apo B concentrations were significantly lower than in younger men, whereas a significant trend towards lower LDL-cholesterol concentrations was observed in older women. Energy intake and percent macronutrient intake were not influenced by age. Higher carbohydrate intake was associated with lower HDL cholesterol and apo A-I concentrations, whereas higher total fat intake was associated with higher apo A-I concentrations. Higher vitamin A intake was associated with higher plasma concentrations of HDL cholesterol and apo A-I. Our data indicate that both dietary and plasma concentrations of vitamin A, body mass index, age, and sex are important determinants of plasma lipid concentrations in the elderly.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Apolipoproteins; Ascorbic Acid; Body Mass Index; Body Weight; Coronary Disease; Diabetes Mellitus; Diet; Diet Surveys; Female; Humans; Hypertension; Lipids; Lipoproteins; Male; Middle Aged; Vitamin A

The oxidation states of intracellular myoglobin and cytochrome oxidase aa3 were monitored by reflectance spectrophotometry in isolated perfused rat hearts subjected to an acutely magnesium deficient environment. After exposure to low extracellular [Mg2+]o (i.e., 0.3 mM) for 30 min, more than 80% of the oxymyoglobin converted to its deoxygenated form. The level of reduced cytochrome oxidase aa3 also increased about 80% in low [Mg2+]o. The deoxymyoglobin was converted further to a species identified as ferrylmyoglobin by its reaction with Na2S to form ferrous sulfmyoglobin which was optically visible. This process, set into motion by acute Mg deficiency, resulted from a direct accessibility of the exogenous peroxide to the cytosolic protein. The results suggest that a pathway leading to cardiac tissue damage, induced by magnesium deficiency, is probably involved in the generation of a ferrylmyoglobin radical which could be prevented by addition of ascorbate, which is known to be a one-electron reductant of this hypervalent form of myoglobin. In further studies, we also investigated whether addition of different concentrations of ascorbic acid (AA) to the perfusate could enhance myocardial function after exposure to low [Mg2+]o perfusion. Four concentrations of AA (0.5, 1, 5, 10 mM) were tested, and the results indicate that they exert their effects in a concentration-dependent manner; 1 mM AA was the most effective dose in improving aortic output in a Mg-deficient heart. Ferrylmyoglobin formation was found to be formed considerably before intracellular release of either creatine phosphokinase or lactic dehydrogenase. These studies may have wide implications as a new mechanism by which low extracellular Mg2+ can induce myocardial injury and subsequent cardiac failure.

Topics: Animals; Ascorbic Acid; Coronary Disease; Electron Transport Complex IV; Magnesium Deficiency; Male; Metmyoglobin; Mitochondria, Heart; Myocardium; Myoglobin; Perfusion; Rats; Rats, Wistar; Spectrophotometry

The mechanism(s) through which smoking influences the progression of atherosclerosis is poorly understood. Recent evidence suggests that oxidants present in the gas phase of cigarette smoke are involved. We exposed human plasma to the filtered gas phase of cigarette smoke to assess its effects on plasma components involved in the antiatherogenic reverse cholesterol transport pathway. In our model, freshly isolated plasma (24 mL) was exposed to filtered air or gas-phase cigarette smoke for up to 6 hours at 37 degrees C. Lecithin-cholesterol acyltransferase (LCAT) activity was dramatically inhibited by cigarette smoke. A single 15-minute exposure to the smoke from an eighth of a cigarette was sufficient to reduce LCAT activity by 7%; additional exposures resulted in further decreases in activity. At 6 hours, only 22% of control LCAT activity remained in plasma exposed to smoke. Compared with control, gas-phase cigarette smoke-exposed plasma possessed high-density lipoprotein (HDL) with increased (16%) negative charge and with cross-linked apolipoproteins AI and AII. These data demonstrate that gas-phase cigarette smoke can inhibit a key enzyme (LCAT) and modify an integral lipid transport particle (HDL) that are essential components for the normal function of the reverse cholesterol transport pathway. Gas-phase cigarette smoke-induced modification of the reverse cholesterol transport pathway may provide a new mechanistic link between cigarette smoke and coronary heart disease risk.

Topics: Adult; Apolipoproteins; Ascorbic Acid; Coronary Disease; Electrophoresis, Polyacrylamide Gel; Female; Glutathione; Humans; Lipoproteins; Lipoproteins, HDL; Male; Nicotiana; Phosphatidylcholine-Sterol O-Acyltransferase; Plants, Toxic; Risk Factors; Smoke; Uric Acid; Vitamin E

The oxidative modification of low-density lipoproteins increases their incorporation into the arterial intima, an essential step in atherogenesis. Although dietary antioxidants, such as vitamin C, carotene, and vitamin E, have been hypothesized to prevent coronary heart disease, prospective epidemiologic data are sparse.. In 1986, 39,910 U.S. male health professionals 40 to 75 years of age who were free of diagnosed coronary heart disease, diabetes, and hypercholesterolemia completed detailed dietary questionnaires that assessed their usual intake of vitamin C, carotene, and vitamin E in addition to other nutrients. During four years of follow-up, we documented 667 cases of coronary disease.. After controlling for age and several coronary risk factors, we observed a lower risk of coronary disease among men with higher intakes of vitamin E (P for trend = 0.003). For men consuming more than 60 IU per day of vitamin E, the multivariate relative risk was 0.64 (95 percent confidence interval, 0.49 to 0.83) as compared with those consuming less than 7.5 IU per day. As compared with men who did not take vitamin E supplements, men who took at least 100 IU per day for at least two years had a multivariate relative risk of coronary disease of 0.63 (95 percent confidence interval, 0.47 to 0.84). Carotene intake was not associated with a lower risk of coronary disease among those who had never smoked, but it was inversely associated with the risk among current smokers (relative risk, 0.30; 95 percent confidence interval, 0.11 to 0.82) and former smokers (relative risk, 0.60; 95 percent confidence interval, 0.38 to 0.94). In contrast, a high intake of vitamin C was not associated with a lower risk of coronary disease.. These data do not prove a causal relation, but they provide evidence of an association between a high intake of vitamin E and a lower risk of coronary heart disease in men. Public policy recommendations with regard to the use of vitamin E supplements should await the results of additional studies.

Topics: Adult; Ascorbic Acid; Carotenoids; Confidence Intervals; Coronary Disease; Diet; Follow-Up Studies; Humans; Male; Middle Aged; Prospective Studies; Risk Factors; Vitamin E

Topics: Aged; Analysis of Variance; Antioxidants; Ascorbic Acid; Ceruloplasmin; Cholesterol; Coronary Disease; Diet; Glutathione Peroxidase; Humans; Lipid Peroxidation; Male; Middle Aged; Random Allocation; Risk Factors; Sex Factors; Smoking; Thiobarbituric Acid Reactive Substances; Uric Acid; Vitamin E

The cardioprotective effects of a high dose of ascorbate on ischemia-reperfusion-induced myocardial damage were investigated using open chest anesthetized dogs. Two-hour occlusion of the left anterior descending coronary artery (LAD) induced mitochondrial dysfunction with a depletion of mitochondrial glutathione (GSH) concentration. Two-hour LAD occlusion followed by 1-h reperfusion worsened the ischemia-induced mitochondrial dysfunction together with a marked depletion of mitochondrial GSH concentration. Ascorbate reduced the mitochondrial dysfunction and prevented the depletion of mitochondrial GSH concentration after 2-h LAD occlusion and 1-h reperfusion. Activities of mitochondrial glutathione peroxidase and glutathione reductase did not change significantly in each group. Administration of ascorbate also prevented reperfusion arrhythmias without affecting blood pressure or heart rate. These results suggest that coronary reperfusion induces mitochondrial dysfunction and a depletion of mitochondrial GSH concentration, and that a high dose of ascorbate prevents reperfusion damage.

Topics: Animals; Arrhythmias, Cardiac; Ascorbic Acid; Coronary Disease; Dogs; Dose-Response Relationship, Drug; Energy Metabolism; Female; Free Radicals; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Male; Mitochondria, Heart; Myocardial Reperfusion Injury

Oxygen-derived free radicals are thought to injure the ischemic heart during coronary microvascular embolization.. To test this idea, microspheres (15 microns in diameter) were repetitively administered into the left anterior descending coronary artery to cause microvascular embolization in dogs. Myocardial contractile and metabolic dysfunctions were significantly attenuated after treatments with recombinant human superoxide dismutase, an acyl derivative of ascorbic acid (CV3611, 2-O-octadecylascorbic acid), and xanthine oxidase inhibitor (allopurinol). The free radical scavengers and inhibitor enhanced the coronary hyperemic flow response during embolization, and the total number of microspheres causing maximal embolization was increased by these drugs. When 8-phenyltheophylline was additionally administered with superoxide dismutase, these beneficial effects were abolished, indicating that coronary effects of these drugs may be due to increased release of adenosine during coronary microvascular embolization.. We conclude that oxygen radicals worsen the ischemic injury in coronary microembolization.

Topics: Allopurinol; Animals; Ascorbic Acid; Body Water; Cardiomyopathies; Coronary Disease; Dogs; Edema; Embolism; Free Radical Scavengers; Free Radicals; Microcirculation; Microspheres; Oxygen; Superoxide Dismutase; Theophylline

Topics: Ascorbic Acid; Coronary Disease; Humans; Nursing Assessment; Nutrition Assessment

The effects of pretreatment with 2-O-octadecylascorbic acid (CV-3611), a novel liposoluble free radical scavenger, on reperfusion-induced arrhythmias were studied in isolated perfused rat hearts (n = 15 per group). The hearts were subjected to 10 min of coronary artery occlusion and 3 min of reperfusion. Pretreatment with CV-3611 (5 and 20 mg/kg) reduced the incidence of ventricular fibrillation (VF; reversible plus sustained) from its control value of 93% to 47% (p less than 0.05). Furthermore, CV-3611 reduced the incidence of sustained VF in a dose-dependent manner, from 67% in the control group to 13% in the CV-3611, 20 mg/kg treated group (p less than 0.01). CV-3611 (5 and 20 mg/kg) reduced the incidence of ventricular tachycardia (VT) from its control value of 93% to 73%. Pretreatment with ascorbic acid (5 mg/kg) had no effect on VF and VT. The myocardial content of CV-3611 was proportional to the dosage. We concluded that CV-3611 could reduce significantly the susceptibility to reperfusion-induced arrhythmias, especially VF, and that its effect may be due to the elimination of oxygen-derived free radicals by CV-3611 present in the membrane and the capture of lipid radicals, thereby inhibiting lipid peroxidation.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Ascorbic Acid; Coronary Circulation; Coronary Disease; Coronary Vessels; Electrocardiography; Free Radical Scavengers; Heart; Heart Rate; In Vitro Techniques; Male; Myocardial Reperfusion; Myocardium; Perfusion; Rats; Rats, Inbred Strains

Reflectance spectroscopy was utilized to monitor the oxidation states of myoglobin (Mb) in isolated, buffer-perfused rat hearts. Hearts were subjected to 30 min global, no-flow ischemia, followed by reperfusion under anoxic conditions. The addition of Na2S to the buffer at reperfusion permitted the detection of ferryl myoglobin (MbIV) as its sulfmyoglobin derivative. The accumulation of MbIV was prevented by addition of ascorbic acid (1 mM), ergothioneine (2 mM), or desferal (1 mM) to the buffer prior to ischemia. Ascorbate and other agents have been previously shown to serve as one-electron reductants of MbIV. We propose that during the early phases of ischemia, deoxymyoglobin is oxidized to MbIV by residual H2O2. It also seems reasonable that the peroxidative activity of Mb(IV), during oxygenated reperfusion, might lead to cellular damage if this hypervalent form of Mb is not reduced.

Topics: Animals; Ascorbic Acid; Coronary Disease; Free Radicals; Hydrogen Peroxide; Myoglobin; Oxidation-Reduction; Rats; Spectrophotometry

The possibility of a relation between plasma antioxidants such as vitamins C and E and selenium, and mortality from coronary heart disease (CHD) was examined. A cross-sectional survey was undertaken of random population samples of apparently healthy middle-aged men in four European regions with differing mortalities from CHD [rate/100,000 for men aged 40-49]: north Karelia (eastern Finland) (n = 99) [212/100,000]; south-west Finland (n = 85) [146/100,000]; Scotland (n = 131) [140/100,000]; and south Italy (n = 80) [43/100,000]. Median (5th-95th percentile) plasma vitamin C concentrations were lower in Scotland: 18.2 (5.7-61.3) microM than in other regions: north Karelia 28.4 (6.2-85.2); south-west Finland 33.5 (5.7-76.6); south Italy 38.0 (10.2-69.8) microM (P less than 0.001). The median levels in the four areas did not however reflect the regional CHD mortality rates. Regional differences in plasma vitamin E levels were also observed: Scottish levels were low 20.0 (12.1-29.3) microM (P less than 0.001) and did not differ between the other areas: 23.0 (16.7-35.1), 22.5 (13.7-31.6) and 23.9 (15.6-41.3) microM respectively. The vitamin E gradient could be explained in part by differences in serum cholesterol. However, cholesterol-adjusted vitamin E levels were low in the three high CHD areas: Scotland 3.41 (2.41-4.62); north Karelia 3.53 (2.67-5.18); south-west Finland 3.53 (2.58-4.92); Italy 4.81 (3.25-5.99) mumol/mmol cholesterol (P less than 0.001). Cholesterol-adjusted vitamin E was not lower in north Karelia, the higher CHD mortality area in Finland. Serum selenium values also varied with the area examined and reported low levels in Finland were confirmed. Nevertheless, selenium levels did not correlate with the reported mortality rates of CHD. Thus in our small cross-cultural study the evidence did not support our hypothesis that plasma antioxidants explain regional differences in CHD mortality.

Topics: Adipose Tissue; Adult; Antioxidants; Ascorbic Acid; Coronary Disease; Cross-Cultural Comparison; Cross-Sectional Studies; Finland; Humans; Italy; Linoleic Acids; Male; Middle Aged; Regression Analysis; Risk Factors; Scotland; Selenium; Vitamin E

The real-time kinetics of the release of ascorbyl free radicals in the coronary perfusate from isolated rat hearts submitted to an ischemia/reperfusion sequence has been achieved by continuous-flow ESR using high-speed acquisition techniques. Enhanced ESR detection of ascorbyl free radicals was obtained by addition of dimethyl sulfoxide (Me2SO), a strong cation chelator and oxidizing agent. A continuous-flow device allowed a direct monitoring of the ascorbyl free radical and/or ascorbate leakage in coronary perfusate by observation of the ascorbyl radical doublet (aH = 0.188 mT and g = 2.0054). 1. The results showed that ascorbyl free radical release occurred mainly during sequences of low-flow ischemia (90 min) coupled or not with 30 min of zero-flow ischemia followed by reperfusion (60 min). The kinetic profiles of ascorbyl-free-radical detection confirm in quantitative terms the expected correlation between the duration of the ischemic insult and the magnitude of ascorbate extracellular release upon reperfusion. There is indication that ascorbyl free radical depletion could be secondary to oxygen-derived-free-radical-induced cellular damage. 2. The amount of residual ascorbic acid was quantitated on myocardial tissue at the end of reperfusion using Me2SO as extracting solvent. Intense oxidation of ascorbate and chemical stabilization of the resulting free radical species provided by Me2SO allowed ESR measurement of a marked tissue ascorbate depletion related to the duration of ischemia. 3. Perfusion of superoxide dismutase during low-flow ischemia and the first 10 min of reperfusion greatly inhibited both extracellular release and endogenous ascorbate depletion. These results suggest that the ascorbate redox system constitutes a major protective mechanism against free-radical-induced myocardial injury. 4. The proposed direct ESR detection of ascorbyl free radicals in the coronary perfusates or in tissue extracts does not require extensive chemical preparation and conditioning of effluent or tissue samples. It provides an interesting straightforward alternative to the evaluation of detrimental free radical processes affecting the myocardium during ischemia and reperfusion.

Topics: Animals; Ascorbic Acid; Biomarkers; Coronary Disease; Electron Spin Resonance Spectroscopy; Free Radicals; Heart; In Vitro Techniques; Kinetics; Male; Myocardial Reperfusion; Myocardial Reperfusion Injury; Myocardium; Rats; Rats, Inbred Strains; Sulfuric Acid Esters; Time Factors

We investigated the vitamin C (ascorbic acid) status in 1077 eastern Finnish men aged 54 years of age examined in the "Kuopio Ischaemic Heart Disease Risk Factor Study" in 1984-86. Dietary intake of ascorbic acid had a strong linear correlation to plasma ascorbic acid, and we found a clear seasonal variation in the plasma ascorbic acid levels: the highest values were found in August-September and again in April, and the lowest levels in November-January and in June. A true vitamin C depletion was found in 8.8% of the 1077 men studied, and, in addition, 16.5% had a mild vitamin C deprivation. The decreased plasma levels of this antioxidant vitamin may be associated with elevated blood pressure.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Cohort Studies; Coronary Disease; Eating; Finland; Humans; Male; Middle Aged; Nutritional Status; Risk Factors; Seasons

Topics: Antioxidants; Ascorbic Acid; Coronary Disease; Diet; Dietary Fats; Fatty Acids; Humans; Male; Risk Factors; Scotland; Vitamin E

Topics: Adult; Antioxidants; Ascorbic Acid; Coronary Disease; Cross-Cultural Comparison; Europe; Humans; Male; Middle Aged; Vitamin E

Aim of this study was to confirm an increased free radical generation rate during ischemia-reoxygenation, by ultra-weak chemiluminescence detection at the surface of perfused rat heart. We observed that reoxygenation following 30 min global ischemia, induces an increase of ultraweak chemiluminescence emission in isolated perfused heart only if partial depletion of vitamin E is induced by dietary manipulation. Moreover, in normal diet fed rats, vitamin E is partially consumed during global ischemia, but not during reoxygenation. Since chemiluminescence increases during post-ischemic reperfusion, when vitamin E myocardial content is lowered, the most probable free radicals involved are the hydroperoxyl radical derivatives of lipids. These radicals, indeed, are known both to produce photoemission by disproportion and to react with vitamin E. On the other hand, the nature of the reaction that consumes vitamin E during ischemia is still obscure. Accordingly, the basal level of vitamin E myocardial content seems to be a key factor for protecting the heart against reoxygenation injury and its consumption during ischemia could be a determinant of myocardial sensitivity to oxidative stress during reperfusion.

Topics: Animals; Ascorbic Acid; Coronary Disease; Heart; Luminescent Measurements; Male; Myocardial Reperfusion; Myocardium; Rats; Rats, Inbred Strains; Reference Values; Vitamin E; Vitamin E Deficiency

The effects of CV-3611, a new free radical scavenger, on coronary circulation failure and infarct size after ischemia/reperfusion were studied in conscious beagle dogs. The dogs underwent occlusion of the left circumflex coronary artery for 60 min and then were reperfused for 14 days. The dogs were divided into three groups: a control group, a pre-treated group that received CV-3611 or alpha-tocopherol, and a post-treated group that received CV-3611. During occlusion, varying degrees of ventricular arrhythmia were noted; after reperfusion, the arrhythmia tended to become severe. CV-3611 at a daily dose of 10 mg/kg or 30 mg/kg and alpha-tocopherol at a daily dose of 60 mg/kg reduced the incidence of overall post-occlusion arrhythmia. Coronary blood flow in the control group was reduced to 20% of the preocclusion level at 7 days after reperfusion, whereas in the CV-3611 and alpha-tocopherol treated groups, the decreased coronary flow was remarkably suppressed. The infarct size for the CV-3611- and alpha-tocopherol-treated groups, measured at 14 days after reperfusion, was reduced by 70% when compared with the control group. Based on these observations, it is proposed that CV-3611 exerts its beneficial effects on ischemic tissue by protecting against oxygen free radical-mediated damage induced by ischemia/reperfusion.

Topics: Animals; Ascorbic Acid; Blood Pressure; Coronary Circulation; Coronary Disease; Dogs; Free Radicals; Heart Rate; Hemodynamics; Myocardial Infarction; Myocardial Reperfusion Injury; Vitamin E

We investigated the association of dietary fatty acids and antioxidants with blood pressure in 722 eastern Finnish men aged 54 y, examined in the Kuopio Ischaemic Heart Disease Risk Factor Study in 1984-86. Men with self-reported hypertension or cerebrovascular disease or under antihypertensive medication were excluded. Allowing for the major anthropometric, dietary, medical, and psychological determinants of blood pressure in multivariate regression analyses, both plasma ascorbic acid (p = 0.0008) and serum selenium (p = 0.0017) concentrations had a moderate, independent inverse association, estimated dietary intake of saturated fatty acids had a positive association (p = 0.013), and estimated dietary intake of linolenic acid had an inverse (p = 0.048) association with the mean resting blood pressure. The marked elevation of blood pressure at the lowest levels of plasma ascorbic acid and serum Se concentrations supports the hypothesis that antioxidants play a role in the etiology of hypertension.

Topics: Antioxidants; Ascorbic Acid; Blood Pressure; Cohort Studies; Coronary Disease; Dietary Fats; Fatty Acids; Fatty Acids, Unsaturated; Finland; Humans; Male; Middle Aged; Risk Factors

In a cross-sectional population study of 1132 unselected Eastern Finnish men aged 54 years, serum selenium concentration had a weak positive association with plasma HDL cholesterol (standardised partial regression coefficient, beta = 0.061, P = 0.019) and a fairly strong inverse relationship (beta = -0.223, P less than 0.001) with the extent of ADP-induced platelet aggregation. Neither plasma ascorbate concentration nor alpha-tocopherol to total cholesterol ratio had any association with plasma lipoproteins, platelet aggregability or prevalent ischaemic heart disease (IHD). When a covariance-correction was applied, men with ischaemic ECG findings at exercise had a lower mean serum selenium than others (81.5 micrograms/l vs. 85.9 micrograms/l, P less than 0.01 for difference). This difference was equally large for men with neither symptoms nor previous diagnosis of IHD.

Topics: Antioxidants; Ascorbic Acid; Cholesterol, HDL; Cholesterol, LDL; Coronary Disease; Cross-Sectional Studies; Finland; Glutathione Peroxidase; Humans; Lipoproteins; Male; Middle Aged; Platelet Aggregation; Risk Factors; Selenium; Vitamin E

We investigated the association of dietary fatty acids and plasma antioxidative vitamins with blood pressure in 722 eastern Finnish men aged 54 years, examined in the Kuopio Ischaemic Heart Disease Risk Factor Study in 1984-1986, who had no known hypertension nor any cerebrovascular disease. Allowing for the major anthropometric, dietary, medical and psychological determinants of blood pressure in a multivariate regression analysis, plasma ascorbic acid concentration had a moderate, independent inverse association (P less than 0.0001) and the estimated dietary intake of linolenic acid an inverse (P = 0.026) independent association with mean resting blood pressure. The marked elevation of blood pressure at the lowest levels of plasma vitamin C concentration supports the hypothesis of the role of antioxidants in the aetiology of hypertension.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Blood Pressure; Coronary Disease; Dietary Fats; Humans; Linolenic Acids; Male; Middle Aged; Prospective Studies; Regression Analysis; Risk Factors

Topics: Adult; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Coronary Disease; Cross-Cultural Comparison; Cross-Sectional Studies; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Vitamin A; Vitamin E; Vitamins

The present epidemiological data support and extend previous evidence in men and animals. Thus, a poor plasma status of vitamin C (less than 23 microM = 0.4 mg/dl) and/or of cholesterol-standardized vitamin E (less than 20-21.5 microM = 9 mg/l) occurs in westernized countries with an increased risk of IHD. A poor status in the major essential antioxidants may be a hitherto underrated, at least permissive, risk factor of IHD that could, at least in some European countries, substantially complement the previously established risk factors such as hypercholesterolemia.

Topics: Adult; Ascorbic Acid; Cholesterol; Coronary Disease; Cross-Sectional Studies; Finland; Humans; Ireland; Italy; Male; Middle Aged; Prospective Studies; Risk; Scotland; Switzerland; Vitamin E

The relationships between ascorbic acid (plasma and dietary) and plasma HDL cholesterol (HDL-C), total plasma cholesterol (T-C) and T-C:HDL-C ratio were examined in a population of 235 males and 445 females, age 60-98 years. Many known or suspected determinants of HDL-C and T-C, including age, sex, triceps skinfold thickness, fasting blood glucose, alcohol intake, and others, were considered as covariates due to their potential confounding or modifying effects on the relationships under study. The results show that plasma ascorbic acid is significantly (p less than 0.05) correlated with HDL-C (r = 0.09), T-C:HDL-C (r = 0.10), but not with T-C (r = 0.03). There is a strong age interaction with the largest effect of ascorbic acid in the youngest age group studied (60-69 years). The effects of dietary ascorbic acid are similar but slightly reduced in magnitude.

Topics: Aged; Aged, 80 and over; Ascorbic Acid; Cholesterol; Cholesterol, HDL; Coronary Disease; Female; Humans; Lipoproteins, HDL; Male; Middle Aged; Risk

The endothelo-protective activity of a series of low-molecular oxygen-derived free radical scavengers (OFRS) was tested in rats. A model of endothelaemia provoked by intravenous administration of hydrogen peroxide was used. With each OFRS the activity in the hydrogen peroxide model was compared with that in the less specific model using the provocation by citrate as a calcium chelating agent. Relatively unspecific but biologically important OFRS, ascorbic acid, tocopherol, troxerutin and glutathione were tested in the first phase of the study. A marked optimum of endothelo-protective activity was shown with all agents, the optimum against hydrogen peroxide having been observed at doses from 3 to 50 times lower than against citrate. Ascorbic acid, troxerutin and the combination of both were also tested in another model based on leg ischaemia produced by ligature of the common femoral artery. Without OFRS, a marked increase of endothelaemia was observed after 30-60 min ischaemia showing a second peak after the release of the ligature. This second peak was completely abolished by the preventive administration of OFRS in a dose which was also effective in the hydrogen peroxide model.

Topics: alpha-Tocopherol; Animals; Anticoagulants; Ascorbic Acid; Aspirin; Coronary Disease; Endothelium; Female; Femoral Artery; Free Radicals; Heparin; Hydrogen Peroxide; Hydroxyethylrutoside; Kinetics; Lactates; Lactic Acid; Perfusion; Pyruvates; Pyruvic Acid; Rats; Rats, Inbred Strains; Rutin; Tocopherols; Vitamin E

Indian and black patients admitted to King Edward VIII and R. K. Khan Hospitals with a diagnosis of cardiac infarction and diabetes mellitus were studied. The mean serum cholesterol levels were higher in the indian group. This preliminary study suggests a negative correlation between leucocyte ascorbic acid and serum cholesterol levels in Indians, especially in patients with infarction. This, however, does not preclude an effect of latent ascorbic acid deficiency on the vessel wall. The possible relevance of the findings to the development of atherosclerosis is discussed.

Topics: Adult; Age Factors; Ascorbic Acid; Black or African American; Black People; Cholesterol; Coronary Disease; Diabetes Complications; Diabetes Mellitus; Humans; India; Leukocytes; Middle Aged; Myocardial Infarction; South Africa

There is evidence that oxygen-derived free radicals may play a role in myocardial ischaemic and reperfusion injury. Major sources of O2 free radicals formation during ischaemia and reperfusion are: the enzyme xanthine oxidase, activated neutrophils and the myocardial mitochondria. However, in the heart there are defense mechanisms against the toxic oxygen metabolites. They include the enzyme superoxide dismutase, catalase and glutathione peroxidase plus endogenous antioxidants like vitamin E, ascorbic acid and cysteine. We have investigated in the isolated rabbit hearts the effects of ischaemia and reperfusion on these defence mechanisms. 90 min of ischaemia and/or hypoxia induced a significant reduction of mitochondrial superoxide dismutase, and of reduced glutathione/oxidized glutathione ratio which was further declined after reperfusion indicating that an oxidative stress has occurred. These alterations are associated with massive tissue and mitochondrial calcium accumulation, loss of mitochondrial function and severe membrane damage. The effects of vitamin E on these parameters have been investigated. Administration of 1.1 mg of dl-alpha-tocopherol acetate showed a protective effect on mitochondrial function but it failed to improve the recovery of mechanical function during reperfusion.

Topics: Animals; Ascorbic Acid; Catalase; Coronary Disease; Cysteine; Glutathione Peroxidase; Mitochondria, Heart; Oxygen; Rabbits; Superoxide Dismutase; Time Factors; Vitamin E

Topics: Adult; Aged; Angina, Unstable; Ascorbic Acid; Coronary Disease; Female; Humans; Male; Middle Aged; Platelet Aggregation

The content of lipid peroxidation products--hydroperoxides with conjugated double bonds and fluorescent compounds, which are formed on interaction of primary lipid peroxidation products and proteins, considerably increases in blood plasma of patients suffering from coronary heart disease. Treatment with combined vitamins E and C enables the blood plasma lipid peroxidation products to be decreased to a far greater extent as compared with conventional therapy.

Topics: Ascorbic Acid; Coronary Disease; Humans; Lipid Peroxides; Vitamin E

The effect of oral administration of vitamin C on platelet adhesive index (PAI), platelet aggregate ratio (PAg R) and serum ascorbic acid levels was studied. Feeding 75 g of butter to healthy males (group I, n = 10 cases), enhanced the tendency of platelet adhesiveness (PAd) and platelet aggregation (PAg) to a significant level at the end of 4 h. This was distinctly prevented when 1 g of vitamin C was added to the fatty meal. In coronary artery disease (CAD) patients (group II, n = 20 cases) 10 days of vitamin C administration at 1 g every 8 hours decreased the PAd (p less than 0.001) and PAg (p less than 0.05) significantly. There was also a significant (p less than 0.001) rise in the vitamin C levels. The study brings out a property of vitamin C which may be of considerable importance in prevention of chronic thromboatherosclerotic disease of the arteries.

Topics: Adult; Ascorbic Acid; Coronary Disease; Dietary Fats; Humans; Male; Platelet Adhesiveness; Platelet Aggregation

Topics: Aged; alpha-Tocopherol; Antioxidants; Ascorbic Acid; Blood Viscosity; Coronary Disease; Drug Combinations; Drug Therapy, Combination; Female; Humans; Lipid Peroxides; Male; Middle Aged; Rutin; Tocopherols; Vitamin E; Weather

Topics: Adult; Age Factors; Aged; Ascorbic Acid; Cholesterol, HDL; Chronic Disease; Coronary Disease; Female; Humans; Male; Middle Aged

Nutrient data from a short dietary questionnaire designed for self-administration in epidemiological studies of ischaemic heart disease were compared with those from 7-day weighed dietary records obtained 2 to 6 weeks later in a sample of 119 men from the general population. For the major nutrients correlation coefficients of between 0.27 (total carbohydrate) and 0.75 (alcohol) were obtained all of which were statistically significant. In the case of alcohol over 90 per cent of the weekly intake was consumed outside the home in standard measures. In the case of other nutrients improvement in the precision of the questionnaire estimates may be obtained by direct estimates of portion sizes.

Topics: Alcohol Drinking; Ascorbic Acid; Coronary Disease; Diet Surveys; Dietary Carbohydrates; Dietary Fats; Dietary Fiber; Dietary Proteins; Energy Intake; Food; Humans; Male; Nutrition Surveys; Surveys and Questionnaires; Weights and Measures

Free radicals and lipid peroxides have recently been identified by us [1, 2, 3] as metabolic intermediates during acute myocardial ischemia. The mechanisms by which evolving myocardial ischemia initiates free radical production are not clear. Based on studies in vitro, it is feasible to consider the following possibilities: (a) dissociation of intramitochondrial electron support system and altered phospholipid integrity with inactivation of cytochrome oxidase, which results in release of ubisemiquinone, flavoprotein and superoxide radicals; (b) accumulation and increased release of intra/extracellular metabolites like NADH, lactate flavoproteins and catecholamines which react either with themselves or with O2 and ascorbic acid; (c) interaction of the metabolic product hypoxanthine with O2 in the presence of xanthine oxidase and (d) activation of phospholipase by calcium influx with enhanced arachidonic acid metabolism and superoxide radical production. Detailed in vitro radiobiological studies [4] have demonstrated that free radical reactions occur even at very low O2 tensions (83% of maximum rate of PO2 approximately 6 mmHg and 50% at PO2 approximately 1 mmHg), and Smith [5] has demonstrated that free radical peroxidation takes place quite rapidly in rat brain homogenates incubated in gas mixtures containing only 5% O2. Thus, the low oxygen tensions in ischemic tissue are adequate to support free radical reactions. The free radicals thus produced may initiate and enhance lipid peroxidation by attacking polyunsaturated membrane lipids.

Topics: Animals; Ascorbic Acid; Catecholamines; Coronary Disease; Dogs; Electron Spin Resonance Spectroscopy; Free Radicals; Glutathione Peroxidase; Kinetics; Lipid Peroxides; Malondialdehyde; Oxidation-Reduction

Aged men and women with ischaemic heart disease had higher total triglyceride levels than controls, and also lower mean percentage cholesterol levels in the high-density lipoprotein fraction. Subnormal levels of leucocyte ascorbic acid were found in 15/25 patients. In men, but not in women, the initial leucocyte ascorbic acid levels were correlated positively with HDL-cholesterol concentrations. After six weeks treatment with ascorbic acid, the mean HDL-cholesterol concentration had increased not only in all men, but also in those women with IHD. Furthermore, total serum cholesterol and LDL-cholesterol concentrations were reduced in men with IHD, but triglyceride levels were not significantly changed; whereas in women with IHD both total serum and VLDL-triglycerides were reduced. Ascorbic acid deficiency appears to contribute to disorders of lipoprotein metabolism in the aged. Latent ascorbic acid deficiency may be one of several preventable 'risk' factors contributing to the present epidemic of IHD in the western world.

Topics: Aged; Aging; Ascorbic Acid; Ascorbic Acid Deficiency; Cholesterol; Coronary Disease; Female; Humans; Leukocytes; Lipids; Lipoproteins, HDL; Lipoproteins, LDL; Male; Sex Factors; Triglycerides

The ascorbic acid level of the leukocytes in patients with coronary artery disease was compared to the ascorbic acid level of the leukocytes in patients without coronary artery disease as demonstrated by coronary arteriography. The leukocyte ascorbic acid level was found significantly lower in patients with coronary arteriography. The leukocyte ascorbic acid level was found significantly lower in patients with coronary atherosclerosis (P < 0.001). There was also significant difference in the leukocyte ascorbic acid levels among patients with abnormal coronary arteriograms who smoked compared to those who did not. The anatomical changes secondary to atherosclerotic disease, and mainly those changes related to the ground substance, have been shown to be the changes that have been observed in patients with ascorbic acid deficiency. From the present study, with its limitations, it is suggested that ascorbic acid may play a role in the pathogenesis of atherosclerosis, and although not implicated as an etiological factor in coronary artery disease, it suggests that a closer look at its possible role in the pathogenesis and progression of coronary artery disease is warranted.

Topics: Adult; Aged; Aging; Arteriosclerosis; Ascorbic Acid; Ascorbic Acid Deficiency; Cardiac Catheterization; Coronary Disease; Female; Humans; Leukocytes; Male; Middle Aged; Sex Factors; Smoking

Plasma vitamin C, total and high density lipoprotein (HDL) cholesterol and cortisol levels were measured in a random sample of 337 elderly subjects living at home in S. Wales; measurements of relative body weight and information about fruit intake, smoking habits and symptoms of cardiovascular disease were also collected. There was a sex difference, over all age groups, in plasma vitamin C and in total HDL cholesterol levels. Plasma vitamin C was strongly correlated with fruit intake in both sexes. Both HDL cholesterol and low and very density lipoprotein (LDL + VLDL) cholesterol levels tended to increase with increasing plasma vitamin C but this reached significance only for the LDL + VLDL fraction. In addition, HDL cholesterol was negatively correlated with Quetelet's index in the women. Symptoms and medication for heart disease did not correlate significantly with plasma vitamin C or with HDL cholesterol levels, but reported angina showed a weak positive association with total cholesterol in the men, and there was some evidence of increased cortisol levels in subjects with heart disease.

Topics: Aged; Ascorbic Acid; Cholesterol; Coronary Disease; Diet; Female; Fruit; Humans; Hydrocortisone; Lipoproteins, HDL; Male; Sex Factors; Smoking

Topics: Ascorbic Acid; Coronary Disease; Humans; United States

The acute effect of 1 g oral ascorbic acid on serum fibrinolytic activity was studied in 40 adult males. In Group I (healthy adults) administration of ascorbic acid raised the serum level by about 71%, while the fibrinolytic activity increased to a peak of 137% at 6 h. In patients with CAD (Group II) an essentially similar increase in FA was observed. In Group III, simultaneous administration of ascorbic acid with 100 g fat effectively prevented a fall in fibrinolytic activity and actually raised it by 64% above the fasting level.

Topics: Adult; Ascorbic Acid; Circadian Rhythm; Coronary Disease; Fats; Fibrinolysis; Humans; Male; Middle Aged

Topics: Ascorbic Acid; Coronary Disease; Humans; Nitro Compounds; Nitrosamines

Topics: Ascorbic Acid; Cardiovascular Diseases; Cholesterol; Cholesterol, Dietary; Coronary Disease; Diet, Atherogenic; Dietary Carbohydrates; Dietary Fats; Finland; Humans; Male; Middle Aged; New York

Topics: Adult; Agriculture; Arteriosclerosis; Ascorbic Acid; Child; Cholesterol, Dietary; Coffee; Coronary Disease; Diet; Diet Therapy; Dietary Fats; Fats, Unsaturated; Humans; Lipid Metabolism; Lipoproteins; Male; Vitamin E; Water

Topics: Arteriosclerosis; Ascorbic Acid; Cholesterol, Dietary; Chromium; Coronary Disease; Diet, Atherogenic; Dietary Carbohydrates; Humans; Water Supply

Topics: Animals; Arteriosclerosis; Ascorbic Acid; Ascorbic Acid Deficiency; Cholesterol; Coronary Disease; Humans

Topics: Aged; Arteriosclerosis; Ascorbic Acid; Ascorbic Acid Deficiency; Cholesterol; Coronary Disease; Female; Humans; Male; Middle Aged; Thrombosis

Topics: Anticoagulants; Ascorbic Acid; Cholesterol; Coronary Disease; Drug Interactions; Female; Humans; Male; Middle Aged; Platelet Adhesiveness; Triglycerides

Topics: Adrenal Glands; Aged; Ascorbic Acid; Aspartate Aminotransferases; Autopsy; Coronary Disease; Female; Humans; Hydrocortisone; Leukocyte Count; Leukocytes; Male; Middle Aged; Myocardial Infarction; Myocardium; Stress, Physiological; Time Factors

Topics: Ascorbic Acid; Coronary Disease; Humans; Pyridoxine; Vitamin B 12; Vitamins

Topics: Adult; Aged; Ascorbic Acid; Coronary Disease; Cytoplasm; Humans; Leukocytes; Lipids; Male; Middle Aged; Neutrophils; Phagocytosis

Topics: Adult; Ascorbic Acid; Coronary Disease; Female; Humans; Male; Methionine; Middle Aged; Phenobarbital; Pyridoxine

Topics: Adult; Aged; Anticholesteremic Agents; Ascorbic Acid; Coronary Disease; Glycosaminoglycans; Humans; Lipid Metabolism; Male; Middle Aged; Propionates; Rutin

Topics: Ascorbic Acid; Aspirin; Asthma; Calcium; Citrates; Coronary Disease; Depression, Chemical; Diabetes Mellitus; Duodenal Ulcer; Dwarfism, Pituitary; Emphysema; Facial Paralysis; Gluconates; Histamine H1 Antagonists; Humans; Hypertension; Hyperthyroidism; Kidney Calculi; Liver Diseases, Parasitic; Magnesium; Oxalates; Phosphates; Pyridoxine; Schistosomiasis; Stimulation, Chemical; Terpenes; Tuberculosis, Pulmonary

Topics: Age Factors; Animals; Arteriosclerosis; Ascorbic Acid; Ascorbic Acid Deficiency; Cholesterol; Coronary Disease; Diet, Atherogenic; Electrocardiography; Fibroblasts; Guinea Pigs; Humans; Intracranial Arteriosclerosis; Time Factors

Topics: Adult; Aged; Arteriosclerosis; Ascorbic Acid; Calcium; Cholesterol; Coronary Disease; Electrocardiography; Female; Gluconates; Humans; Hypothyroidism; Male; Middle Aged; Niacinamide; Pantothenic Acid; Riboflavin; Thiamine; Thyroid Function Tests; Thyroid Gland; Thyroid Hormones; Thyroxine; Vitamin B 12

Topics: Adenosine Triphosphate; Ascorbic Acid; beta-Lipotropin; Coronary Disease; Drug Synergism; Electrocardiography; Female; Fibrinolytic Agents; Heparin; Humans; Male; Pituitary Hormones, Anterior

Topics: Arteriosclerosis; Ascorbic Acid; Blood Chemical Analysis; Cardiovascular Diseases; Coronary Disease; Geriatrics; Heart Failure; Humans; Hypertension

Topics: Ascorbic Acid; Blood Proteins; Chemical Industry; Cholinesterases; Coronary Disease; Environmental Health; Hematopoietic System; Hexachlorocyclohexane; Humans; Influenza, Human; Lead Poisoning; Liver Function Tests; Mercury Poisoning; Methionine; Mice; Nitrobenzenes; Pituitary Hormones; Pituitary Hormones, Posterior; Pituitary-Adrenal Function Tests; Rabbits; Rats; Research; Sulfur Isotopes; Toxicology

Topics: Ascorbic Acid; Capsules; Cholesterol; Coronary Artery Disease; Coronary Disease; Humans; Incidence; Vitamin A; Vitamin D; Vitamins

Topics: Ascorbic Acid; Cardiomyopathies; Child; Cholecalciferol; Coronary Disease; Heart; Humans; Infant; Vitamins

Topics: Arteriosclerosis; Ascorbic Acid; Coronary Disease; Coronary Vessels; Diuretics; Humans; Vitamins