beta-carotene and Arteriosclerosis

Results from experimental and epidemiologic studies suggest an influence of oxidative stress on development and progression of atherosclerosis in man. Prospective endpoint studies failed to support this hypothesis. The current literature is summarized in this review.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Antioxidants; Arteriosclerosis; Ascorbic Acid; Aspirin; beta Carotene; Cardiovascular Diseases; Controlled Clinical Trials as Topic; Double-Blind Method; Female; Follow-Up Studies; Free Radicals; Humans; Male; Nutritional Physiological Phenomena; Oxidative Stress; Placebos; Platelet Aggregation Inhibitors; Primary Prevention; Prospective Studies; Ramipril; Randomized Controlled Trials as Topic; Risk Factors; Time Factors; Tocopherols; Vitamins

Topics: Arteriosclerosis; beta Carotene; Biomarkers; Blood Chemical Analysis; Cardiovascular Diseases; Cataract; Humans; Hyperthyroidism; Liver Diseases; Lung Neoplasms; Pancreatic Diseases; Smoking; Specimen Handling; Stress, Physiological

The carotenoid pigment astaxanthin has important applications in the nutraceutical, cosmetics, food and feed industries. Haematococcus pluvialis is the richest source of natural astaxanthin and is now cultivated at industrial scale. Astaxanthin is a strong coloring agent and a potent antioxidant - its strong antioxidant activity points to its potential to target several health conditions. This article covers the antioxidant, UV-light protection, anti-inflammatory and other properties of astaxanthin and its possible role in many human health problems. The research reviewed supports the assumption that protecting body tissues from oxidative damage with daily ingestion of natural astaxanthin might be a practical and beneficial strategy in health management.

Topics: Adjuvants, Immunologic; Administration, Oral; Antioxidants; Arteriosclerosis; beta Carotene; Biological Availability; Blindness; Chlorophyta; Diet Therapy; Humans; Inflammation; Macular Degeneration; Neoplasms; Neurodegenerative Diseases; Nutritional Physiological Phenomena; Photosensitivity Disorders; Radiation-Sensitizing Agents; Species Specificity; Xanthophylls

People who consume a diet rich in fruit and vegetables have lower risks of cancer, cardiovascular disease and all-cause mortality. Many prospective cohort studies have reported inverse associations between dietary intake or blood levels of beta-carotene and risks of cancer. Several large-scale trials were set up to assess whether beta-carotene supplementation might reduce the risk of cancer. Subsequently, evidence emerged from basic research which indicated that oxidative modification of low-density lipoprotein cholesterol increases its atherogenicity. The evidence from basic research, and epidemiological evidence for a possible protective effect of antioxidant vitamins for cardiovascular disease was strongest for vitamin E. More recently, further trials were set up to examine if supplementation with anti-oxidant vitamins might also reduce the risk of cardiovascular disease. This review summarises the available randomised evidence from published trials of beta-carotene supplementation involving 70,000 people from 3 large-scale trials in healthy populations and on vitamin E supplementation involving 29,000 patients at high-risk of cardiovascular disease from 5 large-scale trials. The results of these trials have been disappointing and failed to confirm any protective effect of these vitamins for either cancer or for cardiovascular disease.

Topics: Antioxidants; Arteriosclerosis; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Carotenoids; Cholesterol, LDL; Humans; Lycopene; Oxidative Stress; Randomized Controlled Trials as Topic; Risk Assessment; Vitamin E; Vitamins

Oxidation is a biochemical process of loss of electrons associated with another of reception called reduction. This process is capital for life, because it takes part in the production of cellular energy. Oxidative stress appears when oxidation is excessive. This reality is complex in all biological levels, and cannot be measured or defined by a single parameter. A great number of diseases have been related to oxidative stress and generation of free radicals. For this reason, antioxidant therapies and diets (such as mediterranean diet) rich or enriched with antioxidants seem to prevent or at least to attenuate the organic deterioration originated by an excessive oxidative stress.

Topics: Acute Kidney Injury; Aged; Aging; Antioxidants; Arteriosclerosis; Ascorbic Acid; beta Carotene; Cataract; Diabetes Mellitus; Diet; Humans; Hypertension; Liver Diseases; Neoplasms; Oxidation-Reduction; Oxidative Stress; Primary Prevention; Risk Factors; Selenium; Vitamin E

The faith that an oxidizing of LDL is necessary for he foam cell formation is basically for the so called oxidative hypothesis of atherosclerosis. The role of LDL-oxidation for the atherosclerotic plaque formation, as well as its association with inflammatory processes in the vascular wall, are well established. The important conclusion of this hypothesis is the possible role of the antioxidants attenuating atherosclerotic mechanisms. The advances in studying the principal antioxidant vitamins E, C and beta-carotene effects, revealed a great part of their molecular mechanisms, which are not necessarily antioxidative. The important aspects of the cooperative antioxidant action are revealed too, including the so called tocopherol-mediated peroxidation, suggesting the need for the co-antioxidants for effective antioxidant defense. In the recent years many vitamin antioxidant supplementations are used. The epidemiological results of such supplementation do not always reveal the same beneficial effects as expected theoretically or based on the observations made with a diet rich in fruits and vegetables. The present paper generalizes the thought concerning the impact of oxidized LDL in atherosclerosis, as well as mechanisms of action and pharmacokinetiks of the most widely used antioxidant vitamins--E, C and beta-carotene, and the perspectives of their usage in cardiovascular prophylaxy bazed upon the recent experience in antioxidant vitamin supplementation.

Topics: Antioxidants; Arteriosclerosis; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Dietary Supplements; Humans; Lipoproteins, LDL; Oxidative Stress; Vitamin E

Increased production of reactive oxygen species is a feature of most, if not all, human disease, including cardiovascular disease and cancer. Dietary antioxidants may be especially important in protecting against human diseases associated with free radical damage to cellular DNA, lipids, and proteins. Ascorbic acid is an effective water-soluble antioxidant, and epidemiologic studies suggest that increased ascorbate nutriture is associated with reduced risk of some degenerative diseases, especially cancer and eye cataracts. Population studies have also shown that high vitamin E intakes are associated with decreased risk of coronary heart disease, possibly as a result of inhibition of atherogenic forms of oxidized low-density lipoprotein. Recent data suggest that beta-carotene provides protection against lipid peroxidation in humans, as well as provitamin A activity. Yet, present data are not sufficient to quantitate micronutrient requirements needed to protect against oxidative damage. The antioxidant roles of many food constituents, such as polyphenols, have not been clarified. Most antioxidants can act as prooxidants under certain conditions, and more research is needed to determine the occurrence and importance of this in vivo. The few controlled intervention trials carried out so far have shown mixed results as to the potential of antioxidant supplements for reducing the incidence of chronic diseases. Definitive recommendations on antioxidant intakes for disease prevention must await evidence from controlled studies and intervention trials, some currently in progress. Overall, the present data suggest that protection against oxidative damage and related disease is best served by the variety of antioxidant substances found in fruit and vegetables.

Topics: Antioxidants; Arteriosclerosis; Ascorbic Acid; beta Carotene; Carotenoids; Exercise; Homocysteine; Humans; Lipid Peroxidation; Neoplasms; Oxidative Stress; Reactive Oxygen Species; Vitamin E

Four antioxidant treatment modalities against atherosclerosis and coronary heart disease are scrutinized: probucol, beta-carotene, alpha-tocopherol and anti-iron treatment. A pattern seems to have emerged in which some treatments look promising, but others are disappointing. Most published studies of antioxidation in atherosclerosis have been ad-hoc in that the primary endpoint of the study has not been a diagnosis related to atherosclerosis; this may be misleading. The most promising antioxidant seems to be alpha-tocopherol, supported by the results of the Cambridge Heart Antioxidant Study. Probucol has the drawback of decreasing high density lipoprotein concentration and is therefore unlikely to influence atheroma in people. beta-Carotene has been repeatedly shown to be ineffective against coronary heart disease. Anti-iron treatment has not yet been tested in animal models or in man. More has to be learned of the role of antioxidation in atherosclerosis before the effectiveness of this treatment modality can be established.

Topics: Anticholesteremic Agents; Antioxidants; Arteriosclerosis; beta Carotene; Humans; Iron Chelating Agents; Probucol; 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: Antioxidants; Arteriosclerosis; Autoantigens; beta Carotene; Cardiovascular Diseases; Carotenoids; Coronary Artery Disease; Humans; Lipid Peroxidation; Lipoproteins, LDL; Male; Middle Aged; Vitamin E

The very extensive research into atherogenesis carried out in recent years has yielded new knowledge of the importance of oxidation by free radicals of low-density lipoproteins and lipids, for instance in endothelial cell membrane. This has provided greater insight into the potential benefit of preventive measures using anti-oxidants to inhibit atherogenesis, and the results of clinical trials carried out so far would seem to confirm this. Prospective, controlled epidemiological trials are still lacking, but this will probably be remedied within the next 2-3 decades. The most clinically interesting antioxidants are vitamins C and E, beta-carotene, the ubiquinones, and the trace element selenium, substances that are naturally integrated components of the complex biochemistry of the human organism. The review is intended to clarify the scientific rationale for an increased intake of such anti-oxidants with a view to reducing the incidence of ischaemic vascular disorders.

Topics: Antioxidants; Arteriosclerosis; Ascorbic Acid; beta Carotene; Carotenoids; Clinical Trials as Topic; Free Radicals; Humans; Ubiquinone; Vitamin E

Topics: Antioxidants; Arteriosclerosis; beta Carotene; Cardiovascular Diseases; Carotenoids; Humans; In Vitro Techniques; Lipoproteins, LDL; Oxidation-Reduction; Risk Factors

Topics: Animals; Antioxidants; Arteriosclerosis; Ascorbic Acid; beta Carotene; Carotenoids; Cholesterol; Chromatography, High Pressure Liquid; Diet; Energy Intake; Epidemiologic Methods; Fatty Acids, Unsaturated; Free Radicals; Humans; Lipid Peroxides; Lipoproteins; Models, Biological; Risk; Selenium; Vitamin A; Vitamin E

This trial evaluated the effect of antioxidant supplementation on the urinary excretion of 11-dehydro TXB(2)/2,3 dinor 6 keto PGF(1alpha) ratio, a marker of the pathogenesis of thrombosis and arteriosclerosis.. This study was a randomised, double-blind, placebo-controlled trial involving 186 presumably healthy volunteers. One hundred received a multi-antioxidant supplementation and 86 a placebo for two years. Blood zinc, selenium, beta-carotene, vitamin C and E and urinary excretion of 11-dehydro TXB(2) and 2,3 dinor 6 keto PGF(1alpha) were measured.. Baseline subject characteristics did not differ between the two groups. Blood zinc, selenium, and beta-carotene concentrations significantly increased between baseline and two years in the multi-antioxidant supplementation group supporting subject compliance (p < 0.05). At two years, the median urinary 11-dehydro TXB(2)/2,3 dinor 6 keto PGF(1alpha) ratio was significantly lower in the multi-antioxidant supplementation group (3.4 versus 2.78, p = 0.015). Serum selenium concentration was the only antioxidant studied that was significantly related to the urinary 11-dehydro TXB(2)/2,3 dinor 6 keto PGF(1alpha) ratio.. These results support the hypothesis that a low-dose multi-antioxidant supplementation may contributes to a reduction in platelet activation which is beneficial for cardiovascular function.

Topics: 6-Ketoprostaglandin F1 alpha; Antioxidants; Arteriosclerosis; beta Carotene; Biomarkers; Dietary Supplements; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Patient Compliance; Platelet Activation; Prostaglandins I; Selenium; Thrombosis; Thromboxane B2; Thromboxanes; Trace Elements; Vitamins; Zinc

The oxidative modification of LDL is believed to be an initial step in atherosclerosis. Thus, antioxidative substances such as carotenoids may have a role in the prevention of coronary heart disease. We examined the susceptibility of LDL to Cu2+ oxidation in young adults before and after a single dose of beta-cryptoxanthin.. 1.3 mg of beta-cryptoxanthin was administered to 12 apparently healthy young volunteers. Six of the volunteers received esters, the other six free beta-cryptoxanthin. The plasma concentration of beta-cryptoxanthin and the susceptibility of LDL to copper-induced oxidation ex vivo in terms of the duration of lag time were measured before and 12 h after beta-cryptoxanthin ingestion.. A single dose of beta-cryptoxanthin significantly increased the mean plasma beta-cryptoxanthin concentration and the mean cholesterol adjusted beta-cryptoxanthin concentration by 117 and 133%, respectively. No effect on the length of lag time was assessed. However, in LDL isolated from plasma 12 h after beta-cryptoxanthin administration the lengths of lag time correlated significantly with the plasma beta-cryptoxanthin concentration and with the cholesterol adjusted beta-cryptoxanthin levels. The lag time did not differ significantly between volunteers who received esters and those who received the same dosage as free beta-cryptoxanthin. At both measuring points, smokers, male volunteers and women using oral contraceptives tended to exhibit lower beta-cryptoxanthin concentrations and lower cholesterol adjusted beta-cryptoxanthin concentrations as well as increased LDL oxidizability compared to nonsmokers and women not using oral contraceptives.. A single dose of beta-cryptoxanthin does not enhance the duration of LDL lag time ex vivo in healthy young subjects.

Topics: Adult; Arteriosclerosis; beta Carotene; Contraceptive Agents, Female; Copper; Cryptoxanthins; Esterification; Female; Humans; Lipoproteins, LDL; Male; Oxidation-Reduction; Smoking; Time Factors; Xanthophylls

Effects of tomato juice supplementation on the carotenoid concentration in lipoprotein fractions and the oxidative susceptibility of LDL were investigated in 31 healthy Japanese female students. These subjects were randomized to one of three treatment groups; Control, Low and High. The Control, Low and High groups consumed 480 g of a control drink, 160 g of tomato juice plus 320 g of the control drink, and 480 g of tomato juice, providing 0, 15 and 45 mg of lycopene, respectively, for one menstrual cycle. The ingestion of tomato juice, rich in lycopene but having little beta-carotene, increased both lycopene and beta-carotene. Sixty-nine percent of lycopene in plasma was distributed in the LDL fraction and 24% in the HDL fraction. In the Low group, the lycopene concentration increased 160% each in the VLDL+IDL, LDL and HDL fractions (p<0.01). In the High group, the lycopene concentration increased 270% each in the VLDL+IDL and LDL fractions, and 330% in the HDL fraction (p<0.01). Beta-carotene also increased 120% and 180% in LDL fractions of the Low and the High groups, respectively. Despite these carotenoid increases in LDL, the lag time before oxidation was not prolonged as compared with that of the Control group. The propagation rate decreased significantly after consumption in the High group. Multiple regression analysis showed a positive correlation between lag time changes and changes in the alpha-tocopherol concentration per triglyceride in LDL, and a negative correlation between propagation rate changes and changes in the lycopene concentration per phospholipid in LDL. These data suggest that alpha-tocopherol is a major determinant in protecting LDL from oxidation, while lycopene from tomato juice supplementaion may contribute to protect phospholipid in LDI, from oxidation. Thus, oral intake of lycopene might be beneficial for ameliorating atherosclerosis.

Topics: Adult; Antioxidants; Arteriosclerosis; beta Carotene; Beverages; Carotenoids; Female; Humans; Lipoproteins; Lipoproteins, LDL; Lycopene; Oxidation-Reduction; Solanum lycopersicum

Accelerated atherosclerosis is common in patients with diabetes mellitus which may be linked to increased lipid peroxidation. Therefore, we compared the oxidation of LDL derived from patients with diabetes to normoglycemic controls and followed-up the effect of dietary beta-carotene supplementation on LDL oxidation.. Twenty patients with long-standing non-insulin-dependent diabetes mellitus were studied in comparison with age- and sex-matched control subjects. Dunaliella bardawil-derived beta-carotene was supplemented to the patients for 3 weeks, 60 mg daily dose. LDL oxidation was analyzed by measuring malondialdehyde (MDA), lipid peroxides (PD), and conjugated dienes (CD) generation in response to CuSO(4)-induced oxidation. LDL lipid composition and the LDL associated vitamins A, E and carotenoids were also measured.. LDL susceptibility to oxidation by CuSO(4) was increased in the patients by 40% with a 35% shorter lag time required for the initiation of LDL oxidation, i.e. 56 +/- 6 min in patients vs. 85 +/- 9 min in controls (p <0.01). Patients showed increased cholesterol/phospholipid and polyunsaturated/saturated ratios, as well as reduced content of LDL associated vitamins. Upon beta-carotene supplementation, there was a significant elevation in plasma and in LDL all-trans beta-carotene [from 0.296 +/- 0.020 to 0. 968 +/- 0.133 microg/mg LDL protein (p < 0.01)] paralleled by a significant reduction in LDL susceptibility to oxidation, as exhibited by increased lag time up to 115 +/- 10 min (p < 0.01) and reduction in MDA and PD generation (by 25 and 40%), respectively (p < 0.01).. Increased susceptibility to oxidation of LDL derived from patients with diabetes mellitus is associated with abnormal LDL lipid composition and antioxidant content. Natural beta-carotene dietary supplementation normalizes the enhanced LDL oxidation and consequently may be of importance in delaying accelerated development of atherosclerosis in these patients.

Topics: Adult; Arteriosclerosis; beta Carotene; Cholesterol, LDL; Diabetes Mellitus, Type 2; Dietary Supplements; Female; Humans; Lipid Peroxidation; Male; Middle Aged; Oxidation-Reduction; Time Factors

The Carotene and Retinol Efficacy Lung Cancer Chemoprevention Trial (CARET) ended prematurely due to the unexpected findings that the active treatment group on the combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate had a 46% increased lung cancer mortality and a 26% increased cardiovascular mortality compared with placebo. This study was designed when the CARET intervention was halted to evaluate the effects of long-term supplementation with beta-carotene and retinol on serum triglyceride and cholesterol levels, in an attempt to explore possible explanations for the CARET result.. Serum triglyceride levels, and total, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol levels were determined in a subgroup of 52 CARET participants. Baseline and mid-trial levels were available on 23 participants on placebo and 29 on active treatment who were then serially followed for 10 months after trial termination.. Triglyceride, and total, HDL and LDL cholesterol levels were similar in the two groups at baseline. After a mean of 5 years on the intervention there was a small nonsignificant increase in serum triglyceride levels in the active group, but no difference in total, HDL, or LDL cholesterol levels. After stopping the intervention there was a decrease in triglyceride levels in the active intervention group, and no change in the other parameters.. Based on a small convenience sample, CARET participants in the active treatment arm had a small nonsignificant increase in serum triglyceride levels while on the intervention, and a decrease in serum triglyceride levels after the intervention was discontinued. No significant changes in total or HDL cholesterol were noted. These results argue against a major contribution of treatment-induced changes in serum lipid and lipoprotein levels to the increased cardiovascular mortality in the active treatment group.

Topics: Adult; Antioxidants; Arteriosclerosis; beta Carotene; Cholesterol; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Lipoproteins, HDL; Male; Middle Aged; Reference Values; Sampling Studies; Time Factors; Triglycerides; Vitamin A

An elevated plasma total homocysteine level (tHcy) is considered an independent risk factor for atherosclerosis. The mechanisms by which hyperhomocysteinemia induces atherosclerosis are only partially understood, but promotion of LDL oxidation and endothelial injury have been suggested. The purpose of this study was to test the hypothesis that a high plasma tHcy is associated in men with increased in vivo lipid peroxidation, as measured by plasma F2-isoprostane concentrations. We investigated this association in a subset of the participants in the Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study. Of 256 male participants, a subsample of 100 consecutive men was selected for F2-isoprostane assays. The mean tHcy was 11.0 micromol/L, and the mean F2-isoprostanes was 29.6 ng/L. The simple correlation coefficient for association between tHcy and F2-isoprostane was 0.40 (P<0.001). In a linear regression model, the variables with the strongest associations with F2-isoprostane were tHcy (standardized coefficient 0.33, P<0.001), serum triglycerides (0.21, P=0.042), carbohydrate-deficient transferrin (0.15, P=0.132), and plasma lipid-standardized alpha-tocopherol (-0.11, P=0.252) (R2=0.24, P<0. 001 for model). Plasma F2-isoprostane levels increased linearly across quintiles of tHcy (P<0.001). The unadjusted mean (95% confidence interval) F2-isoprostanes was 47.5% greater in the highest tHcy quintile (37.4, 31.1 to 43.6 ng/L) than in the lowest quintile (25.3, 21.3 to 29.3 ng/L). Adjustment for the strongest other determinants of F2-isoprostane reduced this difference to 28. 2% (P=0.010). Our present data suggest that elevated fasting plasma tHcy is associated with enhanced in vivo lipid peroxidation in men.

Topics: Arteriosclerosis; Ascorbic Acid; beta Carotene; Dinoprost; Double-Blind Method; Fasting; Humans; Hyperhomocysteinemia; Linear Models; Lipid Peroxidation; Male; Middle Aged; Risk Factors; Transferrin; Triglycerides; Vitamin E

The intercellular adhesion molecule ICAM-1 mediates adhesion and transmigration of leucocytes to the vascular endothelial wall, a step proposed to be critical in the initiation and progression of atherosclerosis. Whether concentrations of soluble ICAM-1 (sICAM-1) are raised in apparently healthy individuals who later suffer acute myocardial infarction is unknown.. We obtained baseline plasma samples from a prospective cohort of 14,916 healthy men enrolled in the Physicians' Health Study. With a nested case-control design, we measured sICAM-1 concentrations for 474 participants who developed a first myocardial infarction, and 474 controls (participants who remained healthy throughout the 9-year follow-up). Cases were matched to controls according to age and smoking status at the time of myocardial infarction.. We found a significant association between increasing concentration of sICAM-1 and risk of future myocardial infarction (p = 0.003), especially among participants with baseline sICAM-1 concentrations in the highest quartile (> 260 ng/mL; relative risk 1.6 [95% Cl 1.1-2.4], p = 0.02). This association was present overall as well as among non-smokers, and persisted after control for lipid and non-lipid risk factors. In multivariate analyses, the risk of future myocardial infarction was 80% higher for participants with baseline sICAM-1 concentrations in the highest quartile (relative risk 1.8 [1.1-2.8], p = 0.02). Similar risk estimates were seen among non-smokers. We found slight but significant correlations between sICAM-1 and fibrinogen, high-density-lipoprotein cholesterol, homocysteine, triglycerides, tissue-type plasminogen-activator antigen, and C-relative protein, but adjustment for these altered the risk little. The risk of myocardial infarction associated with raised concentrations of sICAM-1 seemed to increase with length of follow-up.. Our data support the hypothesis that cellular mediators of inflammation have a role in atherogenesis and provide a clinical basis to consider antiadhesion therapies as a novel means of cardiovascular disease prevention.

Topics: Antioxidants; Arteriosclerosis; Aspirin; beta Carotene; Case-Control Studies; Double-Blind Method; Humans; Intercellular Adhesion Molecule-1; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Platelet Aggregation Inhibitors; Prospective Studies; Risk Factors

Among apparently healthy men, elevated levels of C-reactive protein (CRP), a marker for systemic inflammation, predict risk of myocardial infarction and thromboembolic stroke. Whether increased levels of CRP are also associated with the development of symptomatic peripheral arterial disease (PAD) is unknown.. Using a prospective, nested, case-control design, we measured baseline levels of CRP in 144 apparently healthy men participating in the Physicians' Health Study who subsequently developed symptomatic PAD (intermittent claudication or need for revascularization) and in an equal number of control subjects matched on the basis of age and smoking habit who remained free of vascular disease during a follow-up period of 60 months. Median CRP levels at baseline were significantly higher among those who subsequently developed PAD (1.34 versus 0.99 mg/L; P=.04). Furthermore, the risks of developing PAD increased significantly with each increasing quartile of baseline CRP concentration such that relative risks of PAD from lowest (referent) to highest quartile of CRP were 1.0, 1.3, 2.0, and 2.1 (Ptrend=.02). Compared with those with no clinical evidence of disease, the subgroup of case patients who required revascularization had the highest baseline CRP levels (median= 1.75 mg/L; P= .04); relative risks from lowest to highest quartile of CRP for this end point were 1.0, 1.8, 3.8, and 4.1 (Ptrend=.02). Risk estimates were similar after additional control for body mass index, hypercholesterolemia, hypertension, diabetes, and a family history of premature atherosclerosis.. These prospective data indicate that among apparently healthy men, baseline levels of CRP predict future risk of developing symptomatic PAD and thus provide further support for the hypothesis that chronic inflammation is important in the pathogenesis of atherothrombosis.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Arteriosclerosis; Aspirin; beta Carotene; Body Mass Index; C-Reactive Protein; Cyclooxygenase Inhibitors; Diabetes Mellitus; Double-Blind Method; Heart Diseases; Humans; Hypercholesterolemia; Intermittent Claudication; Male; Middle Aged; Myocardial Revascularization; Peripheral Vascular Diseases; Prospective Studies; Reference Values; Risk Factors

To examine if long-term supplementation with alpha-tocopherol (AT) or beta-carotene (BC) was associated with the prevalence of vascular changes in retinal arterioles.. An end-of-trial subsample from a double-blind, placebo-controlled clinical trial designed to study the effects of alpha-tocopherol and beta-carotene on lung cancer incidence (ATBC Study).. Source population of Helsinki and the surrounding province.. 1072 men 50-69 years old and smoking at least 5 cigarettes per day at study entry.. Random allocation to one of four supplementation regimens: 50 mg per day alpha-tocopherol, 20 mg per day beta-carotene, both alpha-tocopherol and beta-carotene, or placebo. Median follow-up time was 6.6 years (range 5.2-8.0 years).. Presence of vascular changes in retinal arterioles as determined from end-of-trial retinal color photographs.. Retinal vascular changes were most prevalent in the AT (161 men, 62%), and in the BC (163 men, 62%) groups. The prevalence rate was lowest in the AT plus BC group (161 men, 55%), and slightly higher in the placebo group (145 men, 57%). There was no statistically significant association of either AT (OR 0.9, 95% CI 0.7-1.2) or BC (OR 1.0, 95% CI 0.8-1.3) supplementation with the prevalence of retinal vascular changes after adjusting for major risk factors.. Supplementation with alpha-tocopherol or beta-carotene for a median of 6.6 years does not protect against retinal vascular changes among smoking males.

Topics: Aged; Aged, 80 and over; Antioxidants; Arterioles; Arteriosclerosis; beta Carotene; Double-Blind Method; Finland; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged; Prevalence; Retinal Artery; Retinal Diseases; Smoking; Vitamin E

Patients infected with HIV are at increased risk of atherosclerosis, and have evidence of endothelium dysfunction. The hypothesis was tested that HIV-related endothelium dysfunction is related to loss of antioxidants. This was done by the supplementation of the antioxidants selenium and beta-carotene. We supplemented the diet of 10 HIV-seropositive subjects with 100 microg selenium daily, 11 subjects with 30 mg beta-carotene twice daily while 15 subjects were not supplemented. Plasma was obtained at outset and after a year, and tested by ELISA for endothelial cell, platelet and inflammatory markers. The non-supplemented patients experienced increases in von Willebrand factor and soluble thrombomodulin (both p <0.01). There were no changes in any of the indices in the patients taking selenium or beta-carotene. Increased von Willebrand factor and soluble thrombomodulin in the non-supplemented patients imply increased damage to the endothelium over the year of the study. Therefore we interpret the lack of increase in the patients taking antioxidants as evidence of the protection of the endothelium by these agents.

Topics: Antioxidants; Arteriosclerosis; beta Carotene; Biomarkers; Diet; Disease Susceptibility; E-Selectin; Endothelium, Vascular; Female; HIV Infections; Humans; Intercellular Adhesion Molecule-1; Male; Oxidative Stress; Pilot Projects; Platelet Function Tests; Risk Factors; Selenomethionine; Thrombomodulin; Vascular Cell Adhesion Molecule-1; von Willebrand Factor

Evidence from observational epidemiologic studies has indicated that antioxidants consumed through the diet or as dietary supplements lower the risk of developing atherosclerotic cardiovascular disease. Evidence suggesting that the major mechanism for the protective effect of antioxidants is mediated through decreased oxidation of lipids, particularly low-density lipoprotein (LDL) cholesterol is accumulating. Other evidence, however, suggests that antioxidants may influence traditional modifiable cardiovascular risk factors such as the blood pressure and serum lipids favorably. The purpose of this study was to determine the effect of antioxidant vitamin supplementation on modifiable risk factors for atherosclerotic cardiovascular disease.. A randomized, placebo-controlled, clinical trial of antioxidant vitamin supplementation, conducted at a single community-based clinical research center.. We assigned 297 retired teachers who were members of the Maryland Retired Teachers Association randomly to 2-4 months of dietary supplementation with placebo or combined antioxidant vitamin capsules providing 400 IU/day vitamin E, 500 mg/day vitamin C, and 6 mg/day beta-carotene. The outcome measures were the blood pressure, fasting serum total cholesterol, high-density lipoprotein cholesterol, LDL cholesterol, and fasting glucose.. After 2-4 months of supplementation the combined antioxidant supplement had had no significant effect on the systolic and diastolic blood pressures, fasting serum lipids (total cholesterol, high-density lipoprotein cholesterol, and LDL cholesterol) and fasting glucose, with unadjusted and adjusted analyses.. Data from this trial suggest that the protective effect from antioxidant vitamin supplementation, if there is one, likely results from mechanisms other than modification of traditionally modifiable cardiovascular risk factors.

Topics: Antioxidants; Arteriosclerosis; Ascorbic Acid; beta Carotene; Blood Glucose; Blood Pressure; Cardiovascular Diseases; Double-Blind Method; Female; Humans; Lipids; Male; Middle Aged; Pilot Projects; Risk Factors; Time Factors; Vitamin E

The oxidative modification of human low density lipoprotein (LDL) has been widely investigated. However, there are no data concerning the oxidation susceptibility of combined very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and low density lipoprotein fraction, although all of them are atherogenic and contain antioxidants such as alpha-tocopherol. We investigated the oxidation susceptibility and oxidation resistance of VLDL + LDL (including IDL) fraction by induction with CuCl2 and its relation to plasma alpha-tocopherol concentration and lipid standardised alpha-tocopherol concentration in 406 non-vitamin E-supplemented men from eastern Finland. Even thought we did not give oral vitamin E or any other antioxidant supplementation to our study participants, we observed a significant, consistent relationship between measurements of oxidation resistance and plasma content of vitamin E. In the multivariate regression model, a high plasma content of vitamin E or lipid standardised vitamin E concentration were the most important determinants of lag time to maximal oxidation rate (standardised regression coefficient = 0.244, P < 0.0001 for vitamin E and 0.211, P < 0.0001 for lipid standardised vitamin E). After statistical adjustment for age, use of cigarettes, hypolipidemic medication (yes vs. no), month of the measurements, plasma concentrations of total ascorbic acid (ascorbic acid + dehydroascorbic acid), beta-carotene and phospholipids, serum concentrations of LDL cholesterol and triglycerides and dietary intake of linoleic acid, the lag time to maximal oxidation rate was 10% (95% C.I. 6.0-13.5%) longer in men in the highest fifth than in the lowest fifth of plasma vitamin E content (P < 0.0001 for trend). When the fifths of lipid standardised vitamin E were compared, the lag time to maximal oxidation rate was 6% (95% C.I. 1.8-10.1%) longer in men in the highest than in the lowest fifth (P < 0.0001 for trend). Our data suggest that alpha-tocopherol is an important antioxidant preventing the in vitro oxidation of VLDL + LDL fraction even in non-supplemented subjects.

Topics: Adult; Anticholesteremic Agents; Antioxidants; Arteriosclerosis; Ascorbic Acid; beta Carotene; Cholesterol, LDL; Copper; Dietary Fats; Double-Blind Method; Humans; Hypercholesterolemia; Linoleic Acid; Linoleic Acids; Lipids; Lipoproteins, LDL; Lipoproteins, VLDL; Male; Middle Aged; Oxidation-Reduction; Pravastatin; Risk Factors; Smoking; Vitamin E

The oxidative modification of low density lipoprotein (LDL) may play a role in the pathogenesis of atherosclerosis. Furthermore, evidence of oxidized LDL (ox-LDL) has been found in vivo. Supplementation of some animal models with antioxidants has been shown to retard the formation of aortic atherosclerosis. Ascorbate (vitamin C) is a highly potent aqueous-phase antioxidant in plasma, which has been shown in vitro to retard LDL oxidation. Cigarette smokers have reduced concentrations of ascorbate in their plasma, and their LDL may be more prone to oxidation. Hence, the objective of the present study was to examine the effect of ascorbate depletion and supplementation on the propensity of LDL to oxidize in smokers in a 6-week study. Nineteen healthy smokers followed a low ascorbate diet (< or = 30 mg/day) for 2 weeks, then were randomly assigned to receive placebo or 1000 mg ascorbate per day for 4 weeks. Blood was taken at 0 and 4 weeks of supplementation for study of LDL oxidative susceptibility. LDL was oxidized with 5 mumol/l copper. The ascorbate-supplemented group had significant increases in plasma ascorbate. The placebo group showed no change in the time course of LDL oxidation between 0 and 4 weeks. However, the ascorbate-supplemented group has a significant reduction in LDL oxidative susceptibility as measured by thiobarbituric acid-reactive substances (TBARS) and the formation of conjugated dienes. The ascorbate-supplemented group demonstrated significantly increased lag phase and decreased oxidation rate at 4 weeks compared to 0 weeks. No changes were found in the placebo group. The ascorbate-supplemented group showed no biochemical signs consistent with increased body iron stores. Supplementation of otherwise healthy smokers for 4 weeks with 1000 mg ascorbate per day resulted in increased plasma ascorbate and reduced LDL oxidative susceptibility.

Topics: Adult; Antioxidants; Arteriosclerosis; Ascorbic Acid; beta Carotene; Cholesterol; Female; Free Radicals; Humans; Lipid Peroxidation; Lipoproteins, HDL; Lipoproteins, LDL; Male; Middle Aged; Oxidation-Reduction; Smoking; Thiobarbituric Acid Reactive Substances; Vitamin E

Data continue to accumulate supporting a proatherogenic role for oxidized low-density lipoprotein (Ox-LDL). Antioxidant micronutrients such as ascorbate, alpha-tocopherol, and beta carotene, levels of which can be favorably manipulated by dietary measures without side effects, could be a safe approach in inhibiting LDL oxidation. In fact, in vitro studies have shown that all three antioxidants can inhibit LDL oxidation. The present study was undertaken to ascertain both the safety and antioxidant effect of combined supplementation with alpha-tocopherol, ascorbate, and beta carotene on LDL oxidation.. The effect of combined supplementation with alpha-tocopherol (800 IU/d) plus ascorbate (1.0 g/d) and beta carotene (30 mg/d) on copper-catalyzed LDL oxidation was tested in a randomized, placebo-controlled study in two groups of 12 male subjects over a 3-month period. Blood samples for the lipoprotein profile, antioxidant levels, and LDL isolation were obtained at baseline and at 3 months. Neither placebo nor combined antioxidant therapy resulted in any side effects or exerted an adverse effect on the plasma lipoprotein profile. Compared with placebo, combined antioxidant therapy resulted in a significant increase in plasma ascorbate and lipid standardized alpha-tocopherol and beta carotene levels (2.6-, 4.1-, and 16.3-fold, respectively). At baseline, there were no significant differences in the time course curves and kinetics of LDL oxidation as evidenced by the thiobarbituric acid reacting substances (TBARS) assay and the formation of conjugated dienes. However, at 3 months, combined supplementation resulted in a twofold prolongation of the lag phase and a 40% decrease in the oxidation rate. The combined antioxidant group was also compared with a group that received 800 IU of alpha-tocopherol only. Although the combined antioxidant group had significantly higher ascorbate and beta carotene levels than the group supplemented with alpha-tocopherol alone, there were no significant differences between the two groups with respect to LDL oxidation kinetics.. Combined supplementation with ascorbate, beta carotene, and alpha-tocopherol is not superior to high-dose alpha-tocopherol alone in inhibiting LDL oxidation. Hence, alpha-tocopherol therapy should be favored in future coronary prevention trials involving antioxidants.

Topics: Adult; Arteriosclerosis; Ascorbic Acid; beta Carotene; Carotenoids; Diet; Drug Synergism; Humans; Kinetics; Lipid Peroxidation; Lipoproteins, LDL; Male; Middle Aged; Oxidation-Reduction; Thiobarbituric Acid Reactive Substances; Vitamin E

Findings of observational studies suggest cardioprotective effects of antioxidant vitamins and carotenoids. However, recent meta-analyses failed to show the beneficial effects of supplemental intake of antioxidants on cardiovascular disease (CVD). We aimed to assess the association between CVD risk and β-cryptoxanthin in Japan, where Satsuma mandarin, a major source of β-cryptoxanthin, is widely consumed.. This was part of the Mikkabi cohort study. Surveys were conducted at baseline, in 2003 and 2005, and on follow-up in 2006, 2009, and 2013. We examined brachial-ankle pulse wave velocity (baPWV) with a high cut-off value set at 18.3 m s(-1). Hazard ratios (HR) and 95% confidence intervals for high baPWV were estimated using a Cox proportional hazards model with adjustment for potential confounders. A total of 635 participants with baPWV of less than 18.3 m s(-1) at baseline were included in the analysis. During the follow-up period of 57,921 person-months, 99 subjects developed high baPWV. After multivariate adjustment, the HR for high baPWV in the highest tertile compared with the lowest tertile was significantly low for β-cryptoxanthin, β-carotene, and total carotenoids. Serum concentrations of β-cryptoxanthin and β-carotene were higher in people who ate Satsuma mandarin frequently. Compared with <1/d intake of Satsuma mandarin, 3-4/d was associated with a low risk of high PWV.. This study indicated that β-cryptoxanthin and β-carotene derived from Satsuma mandarin are candidate micronutrients for preventing arteriosclerosis development. Further longitudinal and interventional studies will be required to validate the effect on CVD.

Topics: Adult; Aged; Ankle Brachial Index; Arteriosclerosis; beta Carotene; Beta-Cryptoxanthin; Citrus; Diet, Healthy; Female; Fruit; Health Surveys; Humans; Japan; Male; Middle Aged; Multivariate Analysis; Predictive Value of Tests; Prognosis; Prospective Studies; Pulse Wave Analysis; Risk Factors; Risk Reduction Behavior; Time Factors

Antioxidants are potentially beneficial in preventing vascular complications in diabetes because oxidative stress would be enhanced in such a condition and play an important role in vascular disorders. This study aimed to investigate whether brachial-ankle pulse wave velocity (baPWV) would be lower in the presence of high serum carotenoid concentrations stratified according to the glycemic state. A total of 297 men and 579 women between 30 and 70 years of age were analyzed cross-sectionally. Multivariate adjusted mean of baPWV in the highest tertile for beta-carotene (1386 cm/s) was lower than that in the lowest tertile (1432 cm/s) and that in the highest tertile for beta-cryptoxanthin (1382 cm/s) was lower than that in the middle tertile (1424 cm/s) in the case of normal fasting glucose. Similar inverse associations were observed in a group that included subjects with both impaired fasting glucose and diabetes, however, without statistical significance. The highest tertile of carotenoids was associated with a low risk for high baPWV (> or =1680 cm/s). Age, sex and glycemic state adjusted odds ratio was 0.35 (95% CI 0.20-0.60) for beta-carotene and 0.45 (0.27-0.77) for beta-cryptoxanthin. Multivariate adjustment did not alter the results. In conclusion, an inverse association of baPWV with beta-carotene and beta-cryptoxanthin was observed independently of the glycemic state.

Topics: Adult; Aged; Arteriosclerosis; beta Carotene; Biomarkers; Blood Flow Velocity; Blood Glucose; Brachial Artery; Cross-Sectional Studies; Cryptoxanthins; Diabetes Mellitus; Disease Progression; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prognosis; Pulsatile Flow; Retrospective Studies; Tibial Arteries; Xanthophylls

The effects of policosanol (P), of extract of red yeast rice (rice fermented with Monascus purpureus) (RYE) and of astaxanthin (A) (constituents of Armolipid) were investigated in a model of experimental atherosclerosis provoked in the rabbit by atherogenic cholesterol-enriched feed (ACEF). P and RYE and their combination were able to lower the increase of serum total cholesterol and of LDL cholesterol elicited by 3-month feeding with ACEF. They also were able to reduce the increase of blood malondialdehyde (MDA), a tracer of lipid peroxidation by the free radicals released by ACEF. When combined, the substances developed either additive or potentiated effects, supporting the rationale of their combination. Remarkable was the protective effect on lipid infiltration in the aortic wall provoked by ACEF, which was reduced by P and by RYE and almost completely prevented by the addition of A to the P-RYE combination. The results support the rationale of a combination of P, RYE and A as a useful food supplement in hyperlipemic patients.

Topics: Animals; Anticholesteremic Agents; Aorta; Arteriosclerosis; beta Carotene; Body Weight; Cholesterol; Diet, Atherogenic; Drugs, Chinese Herbal; Fatty Alcohols; Female; Free Radicals; Malondialdehyde; Monascus; Rabbits; Triglycerides; Xanthophylls

Recent epidemiologic and animal model data suggest that oxygenated carotenoids are protective against early atherosclerosis. We assessed the association between atherosclerotic progression, measured by carotid intima-media thickness (IMT), and plasma levels of oxygenated and hydrocarbon carotenoids, tocopherols, retinol, and ascorbic acid.. Participants were from an occupational cohort of 573 middle-aged women and men who were free of symptomatic cardiovascular disease at baseline. Ultrasound examination of the common carotid arteries, lipid level determination, and risk factor assessment were performed at baseline and 18-month follow-up. Plasma levels of antioxidants were determined at baseline only. Change in IMT was related to baseline plasma antioxidant levels in regression models controlling for covariates. In models adjusted for age, sex, and smoking status, 18-month change in IMT was significantly inversely related to the 3 measured oxygenated carotenoids (lutein, beta-cryptoxanthin, zeaxanthin; P<0.02 for all) and one hydrocarbon carotenoid, alpha-carotene (P=0.003). After adjusting for additional cardiac risk factors and potential confounders, including high-sensitivity C-reactive protein, these associations remained significant (P<0.05).. These findings suggest that higher levels of plasma oxygenated carotenoids (lutein, zeaxanthin, beta-cryptoxanthin) and alpha-carotene may be protective against early atherosclerosis.

Topics: Adult; Age Factors; Antioxidants; Arteriosclerosis; beta Carotene; Carotenoids; Carotid Artery, Common; Fasting; Female; Follow-Up Studies; Humans; Lipoproteins; Los Angeles; Lycopene; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Regression Analysis; Sex Factors; Smoking; Surveys and Questionnaires; Tunica Intima; Tunica Media; Vitamin A; Xanthophylls; Zeaxanthins

The aim of this study was to evaluate the influence of -tocopherol and astaxanthin on low-density lipoprotein (LDL) oxidation lag time and atherosclerotic lesion formation in Watanabe heritable hyperlipidemic (WHHL) rabbits. Thirty-one, 3-month-old WHHL rabbits were divided into three experimental groups. One group (n=10) was fed standard rabbit feed alone and served as a control, a second group (n=11) was supplied with the same feed containing 500 mg alpha-tocopherol/kg and a third group (n=10) was given a feed containing 100 mg astaxanthin/kg. Plasma lipids, lipoproteins and LDL oxidation lag time were followed for 24 weeks. At the end of the treatment period, the animals were killed and the thoracic aorta was used for evaluation of the degree of atherosclerosis. Colour photographs of the intimal surface of the vessel were taken for determination of the atherosclerotic area. Cross-sections of the thoracic aorta were used for histological examination and for determination of intimal thickening. Specimens of the vessel were used for determination of the tissue cholesterol content. Plasma cholesterol remained at a high level during the time of the experiment and there were no differences between the experimental groups. After 24 weeks, the LDL oxidation lag time was 53.7+/-1.7 min, 109+/-4 min (P<0.001) and 56.4+/-3.4 min (P=0.47) in the control, alpha-tocopherol and astaxanthin groups, respectively. In the thoracic aorta, the atherosclerotic area was 80.7+/-5.1%, 67.1+/-6.7% (P=0.13) and 75.2+/-5.7% (P=0.49) in the control, alpha-tocopherol and astaxanthin groups, respectively. The intimal thickening was 45.6+/-3.2%, 44.0+/-4.1% (P=0.89) and 40.0+/-4.5% (P=0.33) in the control, alpha-tocopherol and astaxanthin groups, respectively. Finally, the cholesterol content was 107+/-9 mol/g, 95.7+/-11.5 mol/g (P=0.31) and 101+/-5 mol/g (P=0.33) in the control, alpha-tocopherol and astaxanthin groups, respectively. It can be concluded that alpha-tocopherol but not astaxanthin prolonged the LDL oxidation lag time. The two antioxidative substances did not prevent atherogenesis in WHHL rabbits in this setting.

Topics: alpha-Tocopherol; Animals; Arteriosclerosis; beta Carotene; Biopsy, Needle; Disease Models, Animal; Female; Hyperlipoproteinemia Type II; Immunohistochemistry; Lipid Peroxidation; Lipoproteins, LDL; Male; Probability; Rabbits; Reference Values; Sensitivity and Specificity; Xanthophylls

The composition of atherosclerotic plaques, not just macroscopical lesion size, has been implicated in their susceptibility to rupture and the risk of thrombus formation. By focusing on the quality of lipids, macrophages, apoptosis, collagen, metalloproteinase expression and plaque integrity, we evaluated the possible anti-atherosclerotic effect of the antioxidants alpha-tocopherol and astaxanthin in Watanabe heritable hyperlipidemic (WHHL) rabbits. Thirty-one WHHL rabbits were divided into three groups and were fed a standard diet, as controls (N =10), or a standard diet with the addition of 500 mg alpha-tocopherol per kg feed (N =11) or 100 mg astaxanthin per kg feed (N =10) for 24 weeks. We found that both antioxidants, particularly astaxanthin, significantly decreased macrophage infiltration in the plaques although they did not affect lipid accumulation. All lesions in the astaxanthin-treated rabbits were classified as early plaques according to the distribution of collagen and smooth muscle cells. Both antioxidants also improved plaque stability and significantly diminished apoptosis, which mainly occurred in macrophages, matrix metalloproteinase three expressions and plaque ruptures. Although neither antioxidant altered the positive correlations between the lesion size and lipid accumulation, the lesion size and apoptosis were only positively correlated in the control group. Astaxanthin and alpha-tocopherol may improve plaque stability by decreasing macrophage infiltration and apoptosis in this atherosclerotic setting. Apoptosis reduction by alpha-tocopherol and astaxanthin may be a new anti-atherogenic property of these antioxidants.

Topics: alpha-Tocopherol; Animals; Antioxidants; Aorta, Thoracic; Apoptosis; Arteriosclerosis; beta Carotene; Cell Movement; Collagen; Hyperlipidemias; Lipid Peroxidation; Lipids; Macrophages; Matrix Metalloproteinase 3; Rabbits; Xanthophylls

Topics: Antioxidants; Arteriosclerosis; beta Carotene; Cholesterol, LDL; Dietary Supplements; Drug Therapy, Combination; Female; Free Radicals; Heart Diseases; Humans; Macular Degeneration; Male; Randomized Controlled Trials as Topic

Topics: Antioxidants; Arteriosclerosis; beta Carotene; Carotid Artery, Common; Dose-Response Relationship, Drug; Humans; Lutein; Vitamins

Antioxidants may prevent atherosclerosis by interfering with endothelial activation, which involves the expression of endothelial adhesion molecules. The aim of this study was to explore the relationship between plasma levels of some lipid-soluble antioxidants (gamma-tocopherol, alpha-tocopherol, lycopene, beta-carotene, and ubiquinone), carotid maximum intima-media thickness (IMTmax), an index of atherosclerotic extension/severity, and soluble adhesion molecules (vascular cell adhesion molecule-1 [VCAM-1], intercellular adhesion molecule-1 [ICAM-1], and E-selectin), which are taken as a reflection of vascular cell expression of adhesion molecules.. We studied 11 healthy control subjects, 11 patients with uncomplicated hypertension (UH), and 11 patients with essential hypertension plus peripheral vascular disease (PVD) who were matched for age, sex, smoking habit, and body mass index.. Patients with PVD had elevated IMTmax (2.7 [1.1-3.1] mm, median [range]) compared with both patients with UH(1.2 [0.8-2.4] mm) and control subjects (1.0 [0.6-2] mm). In patients with PVD, soluble (s)VCAM-1 and sICAM-1 were also significantly higher than in the 2 other categories. Plasma levels of lycopene had a trend toward lower values in patients with PVD compared with other groups (P =.13). A statistically significant correlation was found between lycopene and IMTmax (r = 0.42, P =.014) at univariate analysis, which persisted at multivariate analysis (P <.05) and was independent of low-density lipoprotein cholesterol, creatinine clearance, and plasma insulin. Plasma lycopene did not significantly correlate with any of the soluble adhesion molecules tested.. We conclude that the inverse relationship of plasma lycopene with IMTmax is compatible with a protective role of this natural dietary antioxidant in atherosclerosis, although the mechanism of protection does not apparently involve a decrease in endothelial activation measured through soluble adhesion molecules.

Topics: alpha-Tocopherol; Analysis of Variance; Antioxidants; Arteriosclerosis; beta Carotene; Biomarkers; Carotenoids; Carotid Artery Diseases; E-Selectin; Female; gamma-Tocopherol; Humans; Hypertension; Intercellular Adhesion Molecule-1; Lycopene; Male; Middle Aged; Peripheral Vascular Diseases; Ubiquinone; Vascular Cell Adhesion Molecule-1

Carotenoids are hypothesized to explain some of the protective effects of fruit and vegetable intake on risk of cardiovascular disease. The present study assessed the protective effects of the oxygenated carotenoid lutein against early atherosclerosis.. Progression of intima-media thickness (IMT) of the common carotid arteries over 18 months was determined ultrasonographically and was related to plasma lutein among a randomly sampled cohort of utility employees age 40 to 60 years (n=480). Coculture: The impact of lutein on monocyte response to artery wall cell modification of LDL was assessed in vitro by quantification of monocyte migration in a coculture model of human intima. Mouse models: The impact of lutein supplementation on atherosclerotic lesion formation was assessed in vivo by assigning apoE-null mice to chow or chow plus lutein (0.2% by weight) and LDL receptor-null mice to Western diet or Western diet plus lutein. IMT progression declined with increasing quintile of plasma lutein (P for trend=0.007, age-adjusted; P=0.0007, multivariate). Covariate-adjusted IMT progression (mean+/-SEM) was 0.021+/-0.005 mm in the lowest quintile of plasma lutein, whereas progression was blocked in the highest quintile (0.004+/-0.005 mm; P=0.01). In the coculture, pretreatment of cells with lutein inhibited LDL-induced migration in a dose-dependent manner (P<0.05). Finally, in the mouse models, lutein supplementation reduced lesion size 44% in apoE-null mice (P=0.009) and 43% in LDL receptor-null mice (P=0.02).. These epidemiological, in vitro, and mouse model findings support the hypothesis that increased dietary intake of lutein is protective against the development of early atherosclerosis.

Topics: Adult; Animals; Apolipoproteins E; Arteriosclerosis; beta Carotene; Carotid Arteries; Cell Movement; Cells, Cultured; Coculture Techniques; Cohort Studies; Culture Media, Conditioned; Disease Models, Animal; Disease Progression; Dose-Response Relationship, Drug; Endothelium, Vascular; Female; Humans; Lipoproteins, HDL; Lipoproteins, LDL; Los Angeles; Lutein; Male; Mice; Mice, Knockout; Middle Aged; Monocytes; Muscle, Smooth, Vascular; Oxidation-Reduction; Risk Factors; Ultrasonography

Interaction of peroxynitrite, the product of the reaction between nitric oxide and superoxide, with carotenes (lycopene, alpha-carotene, and beta-carotene) and oxocarotenoids (beta-cryptoxanthin, zeaxanthin, and lutein) was studied both in homogeneous solution and in human low-density lipoproteins (LDL). All carotenoids prevented the formation of rhodamine 123 from dihydrorhodamine 123 caused by peroxynitrite, suggesting that the carotenoids react with peroxynitrite. Oxocarotenoids were as effective as biothiols, known scavengers of peroxynitrite, whereas lycopene, alpha-carotene, and beta-carotene exhibited a considerably more pronounced effect. Moreover, peroxynitrite caused a loss of carotenoids in LDL as was revealed by HPLC. The concentration of peroxynitrite causing half-maximal loss of carotenoids in LDL ranged from 13 +/- 3 to 68 +/- 3 microM for lycopene and lutein, respectively. Again, oxocarotenoids were less reactive in this system. A correlation between efficiency of carotenoids in the competitive assay with dihydrorhodamine 123 and the concentration of peroxynitrite causing half-maximal loss of carotenoids in LDL was observed (r(2) = 0.91). These findings suggest that carotenoids can efficiently react with peroxynitrite and perform the role of scavengers of peroxynitrite in vivo.

Topics: Arteriosclerosis; beta Carotene; Carotenoids; Cryptoxanthins; Fluorescent Dyes; Free Radical Scavengers; Humans; In Vitro Techniques; Lipoproteins, LDL; Lutein; Lycopene; Nitrates; Rhodamine 123; Spectrometry, Fluorescence; Xanthophylls; Zeaxanthins

During passive smoking the body is attacked by an excess of free radicals inducing oxidative stress. In nonsmoking subjects even a short period of passive smoking breaks down serum antioxidant defense (TRAP) and accelerates lipid peroxidation leading to accumulation of their low-density lipoprotein (LDL) cholesterol in cultured human macrophages. We now studied whether these acute proatherogenic effects of secondhand smoke could be prevented by an effective free radical scavenger, vitamin C. Blood samples were collected from nonsmoking subjects (n = 10) as they were consecutively exposed to normal air or cigarette smoke during four separate days. During the last 2 d, a single dose of vitamin C (3 g) was given, which doubled its plasma concentration. Vitamin C did not influence the plasma antioxidant defense or the resistance of LDL to oxidation in normal air, but prevented the smoke-induced decrease in plasma TRAP (p <.001), the decrease in the resistance of LDL to oxidation (p <.05), and the accelerated formation of serum thiobarbituric acid reactive substances (TBARS) (p <.05) otherwise observed 1.5 h after the beginning of passive smoking. Vitamin C protected nonsmoking subjects against the harmful effects of free radicals during exposure to secondhand smoke.

Topics: Adult; Arteriosclerosis; Ascorbic Acid; beta Carotene; Female; Free Radicals; Humans; Lipid Peroxidation; Male; Middle Aged; Peroxides; Time Factors; Tobacco Smoke Pollution; Uric Acid; Vitamin A

A large number of studies have contributed to the hypothesis that carotenoids, vitamins A and E are protective against atherosclerosis by acting as antioxidants. The aim of this study was to assess the relationship between plasma levels of carotenoids (alpha- and beta- carotene, lutein, lycopene, zeaxanthin, beta-cryptoxanthin), vitamins A and E, and atherosclerosis in the carotid and femoral arteries.. This prospective and cross sectional study involved a randomly selected population sample of 392 men and women aged 45-65 years. Carotid and femoral artery atherosclerosis was assessed by high-resolution duplex ultrasound.. alpha- and beta- carotene plasma levels were inversely associated with the prevalence of atherosclerosis in the carotid and femoral arteries (P=0.004) and with the 5-year incidence of atherosclerotic lesions in the carotid arteries (P=0.04). These findings were obtained after adjustment for other cardiovascular risk factors (sex, age, LDL (low density lipoproteins), ferritin, systolic blood pressure, smoking, categories of alcohol consumption, social status, C-reactive protein). Atherosclerosis risk gradually decreased with increasing plasma alpha- and beta-carotene concentrations (P=0.004). No associations were found between vitamin A and E plasma levels and atherosclerosis.. This study provides further epidemiological evidence of a protective role of high alpha- and beta- carotene in early atherogenesis.

Topics: Adult; Aged; Arteriosclerosis; beta Carotene; Carotenoids; Carotid Arteries; Cross-Sectional Studies; Female; Femoral Artery; Humans; Incidence; Italy; Male; Middle Aged; Osmolar Concentration; Prevalence; Prospective Studies; Risk Factors; Ultrasonography

Recent evidence suggests that HDL can directly inhibit LDL oxidation, a key early stage in atherogenesis. Patients with chronic renal failure are at increased cardiovascular risk, have reduced HDL levels and altered HDL composition. We have therefore investigated whether compositional changes in HDL lead to decreased HDL antioxidant capacity in these patients. In comparison to control subject HDL, patient HDL contained less total cholesterol, cholesterol esters, phospholipids and alpha-tocopherol. LDL, HDL and LDL + HDL were standardised for protein and oxidised in the presence of Cu2+. The rate of propagation during HDL oxidation was reduced in the patient group (3.28+/-0.65 x 10(-5) vs. 4.60+/-0.97 x 10(-5) abs. U/min, P < 0.01). Lipid peroxide generation in patient HDL was decreased: 6.56+4.4 versus 13.42+/-7.0 nmol malondialdehyde (MDA)/mg HDL protein after 90 min and 14.45+/-3.8 versus 20.11+/-7.8 nmol MDA/mg HDL protein after 180 min. This is attributable to reduced HDL polyunsaturated fatty acid content in patients (0.53+/-0.12 vs. 0.72+/-0.16 mmol/g HDL, P < 0.01). The inhibitory effect of HDL on LDL oxidation was similar: 71 and 33% for patient HDL compared to 68 and 31% for control HDL, after 90 and 180 min, respectively. Compositional changes of HDL in patients on haemodialysis did not affect the antioxidant capacity of HDL after standardisation for HDL protein. However, reduced HDL levels in vivo may result in reduced HDL antioxidant capacity in these patients.

Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Antioxidants; Arteriosclerosis; Aryldialkylphosphatase; beta Carotene; Carotenoids; Cholesterol; Cholesterol Esters; Cholesterol, HDL; Cholesterol, LDL; Esterases; Fatty Acids; Female; Humans; Kidney Failure, Chronic; Lipid Peroxidation; Lycopene; Male; Middle Aged; Oxidation-Reduction; Phospholipases A; Phospholipids; Platelet Activating Factor; Renal Dialysis; Risk Factors; Vitamin E

Although lipid oxidation plays a major role in atherogenesis, the role of antioxidants in the prevention and treatment of the process is not clear. Apolipoprotein (apo) E-deficient mice develop spontaneous atherosclerotic lesions in major arteries. The presence of oxidized lipoprotein epitopes in the lesion suggests that oxidation reactions are involved in atherogenesis in this mouse model, but the inhibitory effect of antioxidants on atherogenesis in the model is controversial. To test the effect of dietary antioxidants on atherogenesis, male apoE-deficient mice (n=15) were fed a standard chow diet supplemented with 0.05% alpha-tocopherol and 0.05% all-trans beta-carotene. A control group (n=15) received no antioxidant supplement. At the end of the trial, mice consuming vitamins had 5x more plasma vitamin E but undetectable beta-carotene levels. However, liver levels of the beta-carotene metabolite, retinyl palmitate, were higher in antioxidant-treated mice compared with control mice. The antioxidants had no effect on lipoprotein or on plasma anti-oxidatively modified low density lipoproteins (anti-oxLDL) antibody levels. The vitamins had a small but insignificant effect on lipoprotein resistance to ex vivo oxidation, determined by a longer lag period of conjugated diene formation. Atherosclerosis, determined by the lesion size at the aortic sinus, was insignificantly suppressed in antioxidant-treated mice (mean area+/-SE, 20 000+/-7129 versus 13 281+/-5861 micrometer(2); P=0.40). The aortic atherosclerotic lesion area was similar in both experimental groups (2.55+/-0.65% and 2.08+/-0.5% of total aortic area in the control and antioxidant group, respectively; P=0.58). The results of the current study suggest that moderate levels of synthetic antioxidant vitamins have no effect on atherogenesis in apoE-deficient mice.

Topics: Animals; Antioxidants; Apolipoproteins E; Arteriosclerosis; beta Carotene; Body Weight; Cholesterol; Lipoproteins; Male; Mice; Mice, Inbred C57BL; Oxidation-Reduction; Vitamin E

Carotenoids may protect low-density lipoprotein from oxidation, a process implicated in the development of atherosclerosis. Our previous studies showed that in vitro enrichment of low-density lipoprotein (LDL) with beta-carotene protected it from cell-mediated oxidation. However, in vitro enrichment with either lutein or lycopene actually enhanced oxidation of the LDL. In the present studies we have examined the impact of LDL carotenoid content on its oxidation by human aortic endothelial cells (EaHy-1) in culture, comparing the effects of in vivo supplementation with in vitro enrichments. The beta-carotene content in human LDL was increased three- to sixfold by daily supplementation with 15 mg beta-carotene for 4 weeks, and the lycopene content of LDL in other individuals was increased two- to threefold by ingestion of one glass (12 ounce) of tomato juice daily for 3 weeks. LDL isolated from these healthy, normolipidemic donors not taking supplemental carotenoid was incubated at 0.25 mg protein/ml with EaHy-1 cells in Ham's F-10 medium for up to 48 h. Following dietary beta-carotene supplementation, LDL oxidation (as assessed by formation of lipid hydroperoxides) was markedly inhibited, to an even greater extent than was observed for LDL enriched in vitro with beta-carotene (that resulted in an 11- to 12-fold increase in LDL beta-carotene). No effect on cell-mediated oxidation was observed, however, for LDL enriched in vivo with lycopene. Thus, beta-carotene appears to function as an antioxidant in protecting LDL from cell-mediated oxidation although lycopene does not. The fact that the three- to sixfold enrichments of LDL with beta-carotene achieved by dietary supplementation were more effective in inhibiting oxidation than the 11- to 12-fold enrichments achieved by an in vitro method suggests that dietary supplementation is a more appropriate procedure for studies involving the enrichment of lipoprotein with carotenoids.

Topics: Adult; Antioxidants; Arteriosclerosis; beta Carotene; Carotenoids; Cell Line; Diet; Endothelium, Vascular; Free Radicals; Humans; In Vitro Techniques; Lipid Peroxides; Lipoproteins, LDL; Lycopene; Middle Aged; Oxidation-Reduction

Total CoQ10 levels were evaluated in whole blood and in plasma obtained from a group of 83 healthy donors. Extraction with light petroleum ether/methanol was more efficient, for whole blood, than the extraction which is often used for plasma and serum, i.e., ethanol hexane. An excellent correlation was present between plasma CoQ10 and whole blood CoQ10. CoQ10 is mainly associated with plasma rather than with cellular components. Positive, significant correlations were found between the LDL-chol/CoQ10 ratio and the total-chol/HDL-chol ratio, which is usually considered a risk factor for atherosclerosis. The proportion of CoQ10 carried by LDL was 58 +/- 10%, while the amount carried by HDL was 26 +/- 8%. In VLDL + IDL CoQ10 was 16 +/- 8%. The content of CoQ10 in single classes of lipoproteins is strictly correlated with CoQ10 plasma concentration. In a parallel study conducted on a population of diabetic patients (one IDDM group and one NIDDM) CoQ10 plasma levels were generally higher compared to the control group, also when normalised to total cholesterol. In particular the LDL fraction showed a CoQ10/chol ratio higher in NIDDM but not in IDDM patients, compared to controls. The CoQ10/triglycerides ratio was lower in NIDDM respect to controls and even lower in IDDM patients.

Topics: Aged; Antioxidants; Arteriosclerosis; Ascorbic Acid; beta Carotene; Biomarkers; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Coenzymes; Female; Fructosamine; Humans; Lipoproteins; Male; Middle Aged; Reference Values; Risk Factors; Ubiquinone; Vitamin A; Vitamin E

Oxidized low density lipoprotein (LDL) promotes atherogenesis. Although pharmacological antioxidants such as probucol inhibit both LDL oxidation and atherosclerosis in hyperlipidemic animals, the effects of natural antioxidants such as vitamin E are inconclusive. To further determine the effects of supplemental dietary antioxidants in vivo, we evaluated whether combined dietary antioxidants (0.1% vitamin E, 0.5% beta-carotene, and 0.05% vitamin C) inhibit LDL oxidation and fatty streak lesion development in homozygous LDL receptor-null (LDLR-/-) mice fed a high-fat, high-cholesterol diet. An additional group of mice were fed black tea, which has been shown to inhibit LDL oxidation in vitro. After receiving a high-fat, high-cholesterol diet for 8 weeks, the combined antioxidant-supplemented (antioxidant) group (n=18), tea group (n=19), and control group (n=17) had equivalent plasma cholesterol levels. LDL oxidation, as measured by the lag phase of conjugated diene formation, was markedly inhibited in the antioxidant group compared with the tea or control groups [mean lag phases=143+/-7 (antioxidant), 100+/-5 (tea), and 84+/-4 (control) minutes; P<0.0001 antioxidant versus tea or control]. The cross-sectional surface area of fatty streak lesions in the aortic sinus was reduced by 60% in the antioxidant group compared with both the tea and control groups (P<0.0001 antioxidant versus tea or control). There was no difference in lesion area between tea and control groups. Although both LDL oxidation and atherosclerosis were significantly inhibited in the antioxidant group, no correlation between lag phase values and lesion size was observed among individual animals. Furthermore, black tea did not inhibit fatty streak development in LDLR-/- mice. These data suggest that combined natural dietary antioxidants inhibit both LDL oxidation and atherogenesis in animals with elevated LDL but that inhibition of LDL oxidation alone may not prevent the development of atherosclerosis.

Topics: Animals; Antioxidants; Arteriosclerosis; Ascorbic Acid; beta Carotene; Cholesterol; Cholesterol, Dietary; Diet; Dietary Fats; Dietary Supplements; Lipoproteins, LDL; Mice; Mice, Inbred C57BL; Muscle, Smooth, Vascular; Receptors, LDL; Tea; Triglycerides; Vitamin E

Topics: Antioxidants; Arteriosclerosis; Ascorbic Acid; beta Carotene; Coronary Disease; Humans; Neoplasms; Risk Factors; Treatment Outcome; 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 A and beta-carotene and the risk in adults of atherosclerosis, coronary heart disease, amd certain cancers. This interim final 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 interim final rule is effective immediately upon publication.

Topics: Adult; Arteriosclerosis; beta Carotene; Coronary Disease; Drug Approval; Food Labeling; Humans; Neoplasms; Risk Factors; United States; United States Food and Drug Administration; Vitamin A

Male New Zealand White rabbits were made hypercholesterolemic by feeding an atherogenic diet (0.5% cholesterol, 3% peanut oil, and 3% coconut oil) with or without (control) antioxidants for 8 weeks. The antioxidant treatments were intravenous injection of beta-carotene (25 mg/kg/BW, twice weekly), dietary supplementation of alpha-tocopherol (0.5%), and a combination of both. Antioxidant treatments significantly increased plasma and LDL antioxidant levels in the above three groups. Intravenous injection of beta-carotene significantly decreased total and LDL cholesterol concentrations, thoracic atherosclerotic lesion area, and intimal thickness, but had no effects on LDL oxidation ex vivo as compared to control. Added dietary alpha-tocopherol significantly decreased the susceptibility of LDL to oxidation ex vivo, aortic atherosclerotic lesion area and intimal thickness, but had no effects on plasma cholesterol levels as compared to control. Combination of both antioxidants significantly decreased total and LDL cholesterol concentrations, susceptibility of LDL to oxidation ex vivo, as well as atherosclerotic lesion area and intimal thickness at aortic arch and thoracic aorta as compared to control, but not beta-carotene or alpha-tocopherol groups. These data suggest that the antihypercholesterolemic effects of beta-carotene and antioxidant effects of alpha-tocopherol may benefit rabbits fed an atherogenic diet by inhibiting the development of atherosclerotic lesions.

Topics: Animals; Antioxidants; Aorta; Arteriosclerosis; beta Carotene; Cholesterol, LDL; Diet, Atherogenic; Drug Combinations; Hypercholesterolemia; Injections, Intravenous; Lipids; Lipoproteins; Male; Oxidation-Reduction; Rabbits; Random Allocation; Vitamin E

Oxidative modification of LDL by vascular cells has been proposed as a mechanism by which LDL becomes atherogenic. Antioxidants that can prevent LDL oxidation may therefore act as antiatherogens. We used endothelial cells (ECs) from human aortas (HAECs), human saphenous veins (HSECs), and bovine aortas (BAECs) to investigate the role of intracellular and extracellular vitamin C (ascorbate) in EC-mediated LDL modification. Incubation of LDL (0.1 mg protein per milliliter) with confluent HAECs in Ham's F-10 medium led to time-dependent modification of the lipoprotein. In contrast, incubation of LDL with HAECs in medium 199, which does not contain redox-active transition metal ions, did not lead to LDL modification. Both HAEC-mediated and cell-free LDL modifications in Ham's F-10 medium were strongly inhibited in a time- and dose-dependent manner by physiological concentrations of ascorbate. Confluent HAECs cultured under conventional conditions contained very little intracellular ascorbate (< 0.5 nmol/mg protein) but could be loaded with up to 20 nmol ascorbate per milligram protein in a time- and concentration-dependent manner. Ascorbate-loaded HAECs exhibited a lower capacity to modify LDL than did non-ascorbate-loaded control cells. When LDL was incubated with HSECs instead of HAECs, similar time- and concentration-dependent inhibitory effects on LDL modification of intracellular and extracellular ascorbate were observed. In contrast to human ECs, BAECs did not take up vitamin C and therefore only coincubation but not preincubation with ascorbate inhibited BAEC-mediated LDL modification. Our data show that enrichment of human vascular ECs with vitamin C lowers their capacity to modify LDL. In addition, extracellular vitamin C strongly inhibits EC-mediated, metal ion-dependent atherogenic modification of LDL.

Topics: Animals; Aorta; Arteriosclerosis; Ascorbic Acid; beta Carotene; Cattle; Cholesterol, LDL; Coculture Techniques; Dose-Response Relationship, Drug; Endothelium, Vascular; Extracellular Space; Humans; Intracellular Membranes; Muscle, Smooth, Vascular; Oxidation-Reduction; Time Factors; Vitamin E

The hypothesis that tea or dietary lipid-soluble antioxidants reduce atherogenesis by lowering the oxidizability of low-density lipoprotein (LDL) was investigated. Five groups of 20 female New Zealand white rabbits were fed a restricted amount of a high-fat (30 en%) semipurified diet supplemented with cholesterol (0.15%, w/w) for 21 weeks. The vitamin E content of the control diet was 40 mg/kg diet. The animals received either green tea or black tea in their drinking water or vitamin E (200 mg/kg diet) or beta-carotene (20 mg/kg). The serum cholesterol concentrations (in the order of 18-23 mmol/l) were not significantly different between the groups. Vitamin E was substantially increased as compared to controls in vitamin E supplemented animals (3-fold within 8 weeks in plasma and LDL; P < 0.01) and weakly (1.2-fold) by green and black tea (P < 0.05). Green tea consumption tended to reduce aortic lesion formation by 31% (24 +/- 3.2% versus 35 +/- 5.7% for control animals P = 0.11), while black tea, vitamin E and beta-carotene had no effect. This was in contrast to the resistance of isolated LDL to oxidation induced at high copper concentration. Green and black tea induced a 13% and 15% (P < 0.05) prolongation of the lag phase, respectively, with a correspondingly lower oxidation rate, while vitamin E increased the lag phase by 63% (P < 0.01) with a concomitant diminution of the oxidation rate and beta-carotene had no effect. Regression analysis showed that there was no relationship between the extent of atherosclerosis and LDL oxidizability or plasma malondialdehyde as marker of in vivo lipid peroxidation. The results of the present study raise the question whether LDL oxidizability (at least when tested at high induction rate ex vivo) is a primary causal mechanism in atherosclerosis in the cholesterol-fed rabbit. The suitability of the cholesterol-fed rabbit with extreme hypercholesterolaemia as a model to study antiatherosclerotic properties of dietary antioxidants, such as the tested polyphenols, is discussed.

Topics: Animal Feed; Animals; Antioxidants; Arteriosclerosis; beta Carotene; Cholesterol; Disease Models, Animal; Drinking Behavior; Eating; Female; Hypercholesterolemia; Lipids; Lipoproteins, LDL; Oxidation-Reduction; Rabbits; Tea; Vitamin E

In order to study the inhibitory effects of antioxidant vitamins on serum (low oxidative density lipoproteins, oxLDL) and experimental atherosclerosis in rabbits, 20 rabbits were fed on cholesterol rich diet and antioxidant vitamins (vitamin E, vitamin C and beta carotene) for 12 weeks. oxLDL were tested by ELISA at the beginning of experiment and after 4 weeks 8 weeks.. The results showed that supplement of antioxidant vitamins can decrease the oxLDL level significantly and inhibited development of atherosclerosis lesion around aorta in rabbits.

Topics: Animals; Antioxidants; Aorta; Arteriosclerosis; Ascorbic Acid; beta Carotene; Lipoproteins, LDL; Male; Rabbits; Vitamin E

Evidence that dietary antioxidants may prevent atherosclerotic disease is growing. The relationship between the intake of dietary and supplemental vitamin C, alpha-tocopherol, and provitamin A carotenoids and average carotid artery wall thickness was studied in 6318 female and 4989 male participants 45 to 64 years old int he Atherosclerosis Risk in Communities Study.. Intake was assessed by use of a 66-item semiquantitative food-frequency questionnaire. Carotid artery intima-media wall thickness was measured as an indicator of atherosclerosis at multiple sites with B-mode ultrasound. Among men and women > 55 years old who had not recently begun a special diet, there was a significant inverse relationship between vitamin C intake and average artery wall thickness adjusted for age, body mass index, fasting serum glucose, systolic and diastolic blood pressures, HDL and LDL cholesterol, total caloric intake, cigarette use, race, and education (test for linear trend across quintiles of intake, P = .019 for women and P = .035 for men). An inverse relationship was also seen between wall thickness and alpha-tocopherol intake but was significant only in women (test for linear trend, P = .033 for women and P = .13 for men). There was a significant inverse association between carotene intake and wall thickness in older men (test for linear trend, P = .015), but the association weakened after adjustment for potential confounders. No significant relationships were seen in participants < 55 years old.. These data provide limited support for the hypothesis that dietary vitamin C and alpha-tocopherol may protect against atherosclerotic disease, especially in individuals > 55 years old.

Topics: Antioxidants; Arteriosclerosis; Ascorbic Acid; beta Carotene; Carotenoids; Carotid Arteries; Diet; Energy Intake; Female; Humans; Intracranial Arteriosclerosis; Male; Middle Aged; Prospective Studies; Risk Factors; Ultrasonography; United States; Vitamin E

Oxidatively damaged LDL may be of central importance in atherogenesis. Epidemiological evidence suggests that high dietary intakes of beta-carotene and vitamin E decreases the risk for atherosclerotic vascular disease, raising the possibility that lipid-soluble antioxidants slow vascular disease by protecting LDL from oxidation. To test this hypothesis, we fed male New Zealand White rabbits a high-cholesterol diet or the same diet supplemented with either 1% probucol, 0.01% vitamin E, 0.01% all-trans beta-carotene, or 0.01% 9-cis beta-carotene; then we assessed both the susceptibility of LDL to oxidation ex vivo and the extent of aortic atherosclerosis. As in earlier studies, probucol protected LDL from oxidation and inhibited lesion formation. In contrast, vitamin E modestly inhibited LDL oxidation but did not prevent atherosclerosis. While beta-carotene had no effect on LDL oxidation ex vivo, the all-trans isomer inhibited lesion formation to the same degree as probucol. Moreover, all-trans beta-carotene was undetectable in LDL isolated from rabbits fed the compound, although tissue levels of retinyl palmitate were increased. The effect of all-trans beta-carotene on atherogenesis can thus be separated from the resistance of LDL to oxidation, indicating that other mechanisms may account for the ability of this compound to prevent vascular disease. Our results suggest that metabolites derived from all-trans beta-carotene inhibit atherosclerosis in hypercholesterolemic rabbits, possibly via stereospecific interactions with retinoic acid receptors in the artery wall.

Topics: Animals; Antioxidants; Arteriosclerosis; beta Carotene; Carotenoids; Cholesterol; Hypercholesterolemia; Lipoproteins; Lipoproteins, LDL; Male; Oxidation-Reduction; Rabbits; Vitamin E

The effects of administration of guava and papaya fruit (100 g/day), vegetables, and mustard oil (5 g/day) (group A); antioxidant vitamins C (50 mg/day) and E (30 mg/day), plus betacarotene (10 mg/day) (group B); a high-fat (5-10 g/day) (group C); or a low-fat (4-5 g/day) diet (group D) were compared over 24 diet weeks in a randomized fashion, while all groups of rabbits (five in each of four groups) received a hydrogenated fat diet (5-10 g/day) for a period of 36 weeks. After 12 weeks on the high-fat diet, each group of rabbits had an increase in blood lipoproteins. The fruit and vegetable-enriched prudent diet (group A) caused a significant decline in blood lipids at 24 and 36 weeks, whereas the lipid levels increased significantly in groups C and D. Group A also had a significant rise in vitamin E (2.1 Umol/l), C (10.5 Umol/l), A (0.66 Umol/l), and carotene (0.08 Umol/l) and a decrease in lipid peroxides (0.34 nmol/ml at 36 weeks, whereas the levels were unchanged in groups C and D. Group B rabbits had a significant and greater increase than group A in plasma vitamins E, C, A, and carotene; a rise in HDL cholesterol; and a greater decrease in lipid peroxides after 24 and 36 weeks of treatment. After stimulation of lipid peroxidation in all rabbits, 3 of 5 group C and 2 of 5 group D rabbits died due to coronary thrombosis, whereas in groups A and B there were no deaths, indicating that antioxidant therapy can provide protection against lipid peroxidation and free radical generation. Aortic lipids and sudanophilia, indicating atherosclerosis, were significantly higher in groups C and D than in groups A and B. Fatty streaks and atheromatous and fibrous plaques were noted in all the rabbits in groups C and D. Intimal fibrosis and medial degeneration were also present in the group C rabbits. While group A (36.4 +/- 4.4 microns) and group B (37.1 +/- 4.2 microns) rabbits had minimal coronary artery plaque sizes, group C (75.4 +/- 10.6 microns) and group D rabbits (69.5 +/- 6.2 microns) had significantly greater plaque sizes. Aortic plaque sizes were also greater in groups C and D than in groups A and B. It is possible that combined therapy with antioxidant vitamins C, E, and carotene, and a diet rich in antioxidants, could independently inhibit free radical generation and the development of atherosclerosis.

Topics: Animals; Antioxidants; Arteriosclerosis; Ascorbic Acid; beta Carotene; Dietary Fats; Hyperlipidemias; Lipid Peroxidation; Oxidative Stress; Rabbits; Vitamin E

Serum beta-carotene levels in patients with cardiovascular disease and control subjects were measured. The mean values for beta-carotene were found to be 82.2 +/- 3.5 micrograms/dl for the cases as a single group, 74.83 +/- 5.6 micrograms/dl in acute myocardial infarction (AMI) cases, 88.19 +/- 6.1 micrograms/dl in atherosclerotic cases, 85.11 +/- 6.1 micrograms/dl in others and 118.2 +/- 4.3 micrograms/dl in controls. beta-carotene levels in the cases were significantly lower than in the controls (P < 0.05). Serum beta-carotene levels in cases and controls were also compared to take account of age, sex and smoking status. Our data indicate that there are apparent associations between serum beta-carotene levels, sex and smoking status.

Topics: Adult; Age Factors; Aged; Arteriosclerosis; beta Carotene; Cardiovascular Diseases; Carotenoids; Female; Humans; Male; Middle Aged; Myocardial Infarction; Sex Characteristics; Smoking

The yellow color of atherosclerotic plaque is due to the presence of carotenoids, which absorb light between 430-530 nm and account for the preferential ablation of plaque by the pulsed dye laser operating at 480 nm. This study was designed to examine tissue uptake of beta-carotene and the effect of uptake on arterial plaque ablation. Forty-two atherosclerotic NZW rabbits were given intravenous beta-carotene at a dose of 40 mg/kg, twice weekly and killed between 1 hour and 28 days after the initial injection. beta-carotene was not detected in control specimens but was significantly greater in plaque than in normal wall at all time points following beta-carotene injection (P < 0.04 Mann Whitney U test). The ablation threshold was significantly lower in beta-carotene treated plaque than in untreated plaque or normal arterial wall (P < 0.01, Fisher's exact test). In this model beta-carotene is preferentially taken up into arterial plaque, resulting in increased absorption of laser radiation at 480 nm and enhanced tissue ablation.

Topics: Adipose Tissue; Angioplasty, Laser; Animals; Aorta; Aortic Diseases; Arteriosclerosis; beta Carotene; Bile; Carotenoids; Color; Injections, Intravenous; Muscles; Rabbits; Staining and Labeling; Time Factors; Tissue Distribution

Topics: Animals; Antioxidants; Arteriosclerosis; beta Carotene; Carotenoids; Coronary Artery Disease; Glutathione Peroxidase; Humans; Lipid Peroxidation; Lipoproteins, LDL; Male; Muscle, Smooth, Vascular; Reactive Oxygen Species; Risk Factors; Selenium; Tunica Intima; Vitamin E

Improved detection of plaque during cardiovascular procedures could enhance the outcome of diagnosis and therapy. We evaluated a new method to stain plaque using a special intravenous preparation of beta-carotene (beta-C) in an in vivo model. beta-C was used to enhance the absorption coefficient of plaque and decrease the laser-induced fluorescence emission. Using this approach the difference in fluorescence emission was accentuated between normal artery and atherosclerotic plaque. Twenty-nine NZW rabbits were divided into five groups, each receiving a different intervention. This included the administration of beta-C to rabbits on a normal or a high cholesterol diet, with or without endothelial debridement. Aortae were examined grossly, by histology, and relative total fluorescence was detected at 886 sites using 488 nm or 514 nm laser excitation. At 488 nm excitation, unstained plaque attenuated total fluorescence twice as much as normal controls (7.55 +/- 1.46 vs. 15.06 +/- 3.12; P < 0.0001); beta-C stained plaque attenuated total fluorescence 17 times more than normal controls (0.89 +/- 0.29 vs. 15.06 +/- 3.12; P < 0.0001). Total fluorescence from unstained plaque was eight times greater than plaque stained with beta-C (7.55 +/- 1.46 vs. 0.89 +/- 0.29; P < 0.0001). Results obtained using 514 nm excitation were similar. The attenuation effect persisted up to 8 weeks following beta-C administration. Thus, beta-C stained plaque displayed fluorescence attenuation, which suggests that pretreatment with beta-C may greatly enhance plaque detection. This may be useful as a guide during plaque removal procedures.

Topics: Animals; Aorta; Arteriosclerosis; beta Carotene; Carotenoids; Lasers; Rabbits; Spectrometry, Fluorescence

Oxidative modification of low density lipoproteins (LDL) has been implicated in the sequence of events leading to fatty streak formation in the arterial intima. Increased oxidative modifications of dense versus buoyant LDL particles could contribute to increased atherosclerosis associated with lipoprotein profiles enriched in small, dense LDL. In the present studies, we compared rates of copper-induced oxidative changes for six LDL subfractions ranging in density from 1.023 to 1.053 g/ml and mean particle diameter from 282 +/- 10 to 245 +/- 3. Rates of formation of thiobarbituric acid-reactive substances (TBARS), as indicated by the time required for half-maximal TBARS formation (T1/2max), decreased with increasing density and decreasing particle diameter to a minimum in fraction 5 (d = 1.046 g/ml, diameter = 250 +/- 5) (P = 0.007). In parallel studies using unfractionated LDL (d = 1.019-1.063 g/ml), T1/2max values were inversely correlated with the predominant LDL species diameter as determined by 2-16% gradient gel electrophoresis (P less than 0.05), consistent with the involvement of subclass composition in determining oxidative behavior. In separate experiments, subfraction differences in oxidation rates as assessed by TBARS formation were verified by the finding of similarly dispartate changes in fluorescence intensity and anionic electrophoretic mobility. T1/2max values were not related to LDL contents of alpha-tocopherol, beta-carotene, protein, triglycerides or phospholipids, but were significantly correlated with unesterified cholesterol content (r = 0.46; P less than 0.001) and were inversely associated with cholesteryl ester content (r = 0.28; P less than 0.05). The positive association of T1/2max with unesterified cholesterol suggests that this constituent may impart resistance to oxidative modification, possibly by altering properties of the surface monolayer where it resides.

Topics: Adult; Aged; Arteriosclerosis; beta Carotene; Carotenoids; Cholesterol; Cholesterol Esters; Densitometry; Humans; Lipoproteins, LDL; Male; Middle Aged; Oxidation-Reduction; Particle Size; Phospholipids; Proteins; Triglycerides; Vitamin E

Topics: Arteriosclerosis; beta Carotene; Canthaxanthin; Carotenoids; Combined Modality Therapy; Humans; Laser Therapy

Patients undergoing carotid endarterectomy were pretreated with low-dose, oral beta carotene to determine whether the carotenoid content of plaque could be increased in vivo. Beta carotene-treated patients had a 50-fold increase in their plaque beta carotene level from 0.066 to 3.3 micrograms beta carotene/g plaque. Microscopy and microspectrophotometry demonstrated that plaque from beta carotene-treated patients had higher carotenoid levels and higher absorption (450-500 nm) compared with control specimens, but normal media was unaffected. This demonstration of increased preferential absorption by plaque suggests that selective ablation of atherosclerotic plaque may be enhanced by pretreating patients with oral beta carotene.

Topics: Absorption; Administration, Oral; Arteriosclerosis; beta Carotene; Carotenoids; Carotid Artery Diseases; Chromatography, High Pressure Liquid; Endarterectomy; Humans; Laser Therapy; Muscle, Smooth, Vascular; Premedication; Reference Values; Spectrophotometry