ascorbic-acid and Carotid-Artery-Diseases

Natural products including botanicals for both therapy of clinical manifestations of atherosclerosis and reduction of atherosclerosis risk factors are topics of recent patents. Only a few recent patents are relevant to the direct antiatherosclerotic therapy leading to regression of atherosclerotic lesions. Earlier, using a cellular model we have developed and patented several anti-atherosclerotic drugs. The AMAR (Atherosclerosis Monitoring and Atherogenicity Reduction) study was designed to estimate the effect of two-year treatment with time-released garlic-based drug Allicor on the progression of carotid atherosclerosis in 196 asymptomatic men aged 40-74 in double-blinded placebo-controlled randomized clinical study. The primary outcome was the rate of atherosclerosis progression, measured by high-resolution B-mode ultrasonography as the increase in carotid intima-media thickness (IMT) of the far wall of common carotid arteries. The mean rate of IMT changes in Allicor-treated group (-0.022±0.007 mm per year) was significantly different (P = 0.002) from the placebo group in which there was a moderate progression of 0.015±0.008 mm at the overall mean baseline IMT of 0.931±0.009 mm. A significant correlation was found between the changes in blood serum atherogenicity (the ability of serum to induce cholesterol accumulation in cultured cells) during the study and the changes in intima-media thickness of common carotid arteries (r = 0.144, P = 0.045). Thus, the results of AMAR study demonstrate that long-term treatment with Allicor has a direct anti-atherosclerotic effect on carotid atherosclerosis and this effect is likely to be due to serum atherogenicity inhibition. The beneficial effects of other botanicals including Inflaminat (calendula, elder and violet), phytoestrogen- rich Karinat (garlic powder, extract of grape seeds, green tea leafs, hop cones, β-carotene, α-tocopherol and ascorbic acid) on atherosclerosis have also been revealed in clinical studies which enforces a view that botanicals might represent promising drugs for anti-atherosclerotic therapy.

Topics: Adult; Aged; alpha-Tocopherol; Ascorbic Acid; beta Carotene; Biomarkers; Cardiovascular Agents; Carotid Artery Diseases; Carotid Intima-Media Thickness; Cholesterol; Disease Progression; Double-Blind Method; Garlic; Humans; Male; Middle Aged; Phytotherapy; Plant Preparations; Plants, Medicinal; Time Factors; Treatment Outcome

Plant foods may lower the risk of cardiovascular disease.. We assessed changes in the intima media thickness (IMT) of the carotid artery and diet in elderly men. Men (n=563) aged 70+/-5 years were randomly assigned to 1 of 4 groups (dietary intervention, omega-3 supplementation, both or neither) using a 2 x 2 factorial design. B-mode ultrasound of the carotid arteries and calculation of dietary intake were performed at baseline and after 3 years. We previously showed that omega-3 supplementation did not influence the IMT, thus the dietary intervention (n=233) and no dietary intervention (n=231) groups were pooled. The dietary intervention group had less progression in the carotid IMT compared with the controls (0.044+/-0.091 mm versus 0.062+/-0.105 mm; P=0.047). This group increased their daily vitamin C intake (P=0.005) and intake of fruit, berries and vegetables (P

Topics: Aged; Ascorbic Acid; Carotid Arteries; Carotid Artery Diseases; Diet; Fruit; Humans; Linear Models; Male; Tunica Intima

Limited data exist from randomized trials evaluating, noninvasively, the impact of antioxidant supplementation on vascular structure and function.. This is a substudy of the SU.VI.MAX Study, which is a randomized, double-blind, placebo-controlled, cardiovascular and cancer primary prevention trial. Eligible participants (free of symptomatic chronic diseases and apparently healthy) were randomly allocated to daily receive either a combination of antioxidants (120 mg vitamin C, 30 mg vitamin E, 6 mg beta carotene, 100 microg selenium, and 20 mg zinc) or placebo and followed-up over an average of 7.2+/-0.3 years. At the end-trial examination, the carotid ultrasound examination and carotid-femoral pulse-wave velocity (PWV) measurement were performed blindly in 1162 subjects aged older than 50 years and living in the Paris area. The percentage of subjects with carotid plaques was higher in the intervention group compared with the placebo group (35.2% versus 29.5%, P=0.04). Common carotid intima-media thickness (mean+/-SD) was not different between the 2 groups (0.70+/-0.08 versus 0.70+/-0.08 mm, P=0.38). Mean PWV tended to be lower (indicating less stiff aortic arteries) in the intervention group but the difference did not reach statistical significance (P=0.13).. These results suggest no beneficial effects of long-term daily low-dose supplementation of antioxidant vitamins and minerals on carotid atherosclerosis and arterial stiffness.

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Carotid Arteries; Carotid Artery Diseases; Double-Blind Method; Female; Femoral Artery; Follow-Up Studies; Humans; Male; Middle Aged; Minerals; Paris; Selenium; Treatment Failure; Tunica Intima; Tunica Media; Ultrasonography; Vitamin E; Vitamins; Zinc

Self-selected supplementation of vitamin E has been associated with reduced coronary events and atherosclerotic progression, but the evidence from clinical trials is controversial. In the first 3 years of the ASAP trial, the supplementation with 136 IU of vitamin E plus 250 mg of slow-release vitamin C twice daily slowed down the progression of carotid atherosclerosis in men but not women. This article examines the 6-year effect of supplementation on common carotid artery (CCA) intima-media thickness (IMT).. The subjects were 520 smoking and nonsmoking men and postmenopausal women aged 45 to 69 years with serum cholesterol > or =5.0 mmol/L (193 mg/dL), 440 (84.6%) of whom completed the study. Atherosclerotic progression was assessed ultrasonographically. In covariance analysis in both sexes, supplementation reduced the main study outcome, the slope of mean CCA-IMT, by 26% (95% CI, 5 to 46, P=0.014), in men by 33% (95% CI, 4 to 62, P=0.024) and in women by 14% (not significant). In both sexes combined, the average annual increase of the mean CCA-IMT was 0.014 mm in the unsupplemented and 0.010 mm in the supplemented group (25% treatment effect, 95% CI, 2 to 49, P=0.034). In men, this treatment effect was 37% (95 CI, 4 to 69, P=0.028). The effect was larger in subjects with either low baseline plasma vitamin C levels or CCA plaques. Vitamin E had no effect on HDL cholesterol.. These data replicate our 3-year findings confirming that the supplementation with combination of vitamin E and slow-release vitamin C slows down atherosclerotic progression in hypercholesterolemic persons.

Topics: Aged; Antioxidants; Arteriosclerosis; Ascorbic Acid; Carotid Artery Diseases; Carotid Artery, Common; Cholesterol, HDL; Delayed-Action Preparations; Dietary Supplements; Disease Progression; Drug Therapy, Combination; F2-Isoprostanes; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Patient Compliance; Time Factors; Ultrasonography; Vitamin E

To study the efficacy of vitamin E and C supplementation on the progression of carotid atherosclerosis, hypothesizing an enhanced preventive effect in men and in smokers and synergism between vitamins.. Double-masked two-by-two factorial trial, randomization in four strata (by gender and smoking status) to receive twice daily either 91 mg (136 IU) of d-alpha-tocopherol, 250 mg of slow-release vitamin C, a combination of these or placebo for three years. A randomized sample of 520 smoking and nonsmoking men and postmenopausal women aged 45-69 years with serum cholesterol >/= 5.0 mmol L-1 were studied.. The population of the city of Kuopio in Eastern Finland.. Twice daily either a special formulation of 91 mg of d-alpha-tocopherol, 250 mg of slow-release vitamin C, a combination of these (CellaVie(R)) or placebo for three years.. Atherosclerotic progression, defined as the linear regression slope of ultrasonographically assessed common carotid artery mean intima-media thickness (IMT), was calculated over semi-annual assessments.. The average increase of the mean IMT was 0.020 mm year-1 amongst men randomized to placebo and 0.018 mm year-1 in vitamin E, 0.017 mm year-1 in vitamin C and 0.011 mm year-1 in the vitamin combination group (P = 0.008 for E + C vs. placebo). The respective means in women were 0.016, 0.015, 0.017 and 0.016 mm year-1. The proportion of men with progression was reduced by 74% (95% CI 36-89%, P = 0.003) by supplementation with the formulation containing both vitamins, as compared with placebo.. Our study shows that a combined supplementation with reasonable doses of both vitamin E and slow-release vitamin C can retard the progression of common carotid atherosclerosis in men. This may imply benefits with regard to other atherosclerosis-based events.

Topics: Aged; Antioxidants; Arteriosclerosis; Ascorbic Acid; Carotid Artery Diseases; Disease Progression; Double-Blind Method; Drug Synergism; Female; Follow-Up Studies; Humans; Male; Middle Aged; Patient Compliance; Smoking; Vitamin E

Homocysteine is increasingly recognized as a risk factor for atherothrombotic arterial diseases. We investigated the relation between plasma concentrations of total homocysteine (tHcy) and common carotid artery intima-media wall thickness, measured by B-mode ultrasonography, in 513 asymptomatic men and women from eastern Finland aged 45-69 years. The subjects were examined in 1994-95 at the baseline of the Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study, a randomized double-blind placebo-controlled two by two factorial trial on the effect of vitamin E and C supplementation in the prevention of atherosclerotic progression. The subjects were assigned into two categories according to the plasma tHcy concentration; concentration over 11.5 micromol/L (highest quartile) or concentration below 11.5 micromol/L. In this study population the mean plasma tHcy concentration was 10.0 micromol/L, and the prevalence of plasma tHcy concentration exceeding 11.5 micromol/L was 33% in men and 18% in women. The adjusted mean intima-media thickness of the right and left common carotid arteries was 1.12 mm in men with elevated plasma tHcy concentration and 1.02 mm in men with a plasma tHcy concentration below 11.5 micromol/L (P = 0.029). In women there was no significant difference. We conclude that elevated plasma tHcy concentrations are associated with early atherosclerosis, as manifested by increased common carotid artery intima-media wall thickness, in middle-aged eastern Finnish men.

Topics: Adult; Aged; Arteriosclerosis; Ascorbic Acid; Carotid Artery Diseases; Carotid Artery, Common; Double-Blind Method; Female; Homocysteine; Humans; Intracranial Arteriosclerosis; Male; Middle Aged; Risk Factors; Smoking; Ultrasonography; Vitamin E

Vitamin C has efficient antioxidant properties and is involved in important physiological processes such as collagen synthesis. As such, vitamin C deficiency leads to serious complications, including vascular diseases. The aim of this study was to investigate the effects of vitamin C treatment on collar-induced intimal thickening. Rabbits were fed a normocholesterolemic diet and a non-occlusive silicon collar was placed around the left carotid artery for 3, 7, and 14 days. The rabbits were treated with or without vitamin C (150 mg/kg/day). Collar-induced intimal thickening became apparent at day 7. The effect of the collar on intimal thickening was more prominent at day 14. Vitamin C treatment significantly inhibited collar-induced intimal thickening at day 14. The placement of the collar around the carotid artery decreased maximum contractile responses against contractile agents (KCl, phenylephrine, 5-hydroxytryptamine). The effect of the collar on contractile responses was enhanced as days elapsed. Decreased contractile responses of collared carotid arteries normalized at day 14 in the vitamin C treatment group. Vitamin C treatment also restored sensitivity to phenylephrine. The collar also significantly decreased acetylcholine-induced relaxations at day 3 and day 7. Acetylcholine-induced relaxations normalized in collared-arteries in the placebo group at day 14. Vitamin C treatment significantly increased acetylcholine-induced relaxations of both normal and collared carotid arteries at day 14. MMP-9 expression increased in collared arteries at day 3 and day 7 but did not change at day 14. MMP-2 expression increased in collared arteries at day 14. However, vitamin C treatment reduced collar-stimulated expression of MMP-2 at day 14. These findings indicate that vitamin C may have potentially beneficial effects on the early stages of atherosclerosis. Furthermore these results, for the first time, may indicate that vitamin C can also normalize decreased contractile response through perivascular collar placement.

Topics: Animals; Antioxidants; Ascorbic Acid; Carotid Arteries; Carotid Artery Diseases; Disease Models, Animal; Dose-Response Relationship, Drug; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Neointima; Plaque, Atherosclerotic; Rabbits; Time Factors; Vascular Remodeling; Vasoconstriction; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents

Topics: alpha-Tocopherol; Antioxidants; Arteriosclerosis; Ascorbic Acid; Cardiovascular Diseases; Carotid Artery Diseases; Clinical Trials as Topic; Drug Therapy, Combination; Endpoint Determination; Female; Humans; Male; Oxidative Stress; Vitamin E

The results of the few studies conducted on the relation between antioxidant vitamins and carotid atherosclerosis have been inconclusive.. We evaluated the association between preclinical carotid atherosclerosis, as determined by high-resolution B-mode ultrasound, and both the intake amounts and plasma concentrations of antioxidant vitamins.. Among 5062 participants in Progetto Atena, a population-based study on the etiology of cardiovascular disease and cancer in women, 310 women were examined by B-mode ultrasound to detect early signs of carotid atherosclerosis. The participants answered a food-frequency questionnaire, and their plasma concentrations of vitamin E, vitamin A, and carotenoids were measured. None of the women took vitamin supplements.. The occurrence of atherosclerotic plaques at the carotid bifurcation was inversely associated with tertiles of vitamin E intake; the test for a linear trend across tertiles was significant (P < 0.05). Similarly, the ratio of plasma vitamin E to plasma cholesterol was inversely related to the presence of plaques at the carotid bifurcation; the test for a linear trend across tertiles was significant (P < 0.02). No association was found between the intake of other antioxidant vitamins (vitamins A and C and carotenoids) or their plasma concentrations and the presence of carotid plaques.. An inverse association was found between both the intake amount and plasma concentration of vitamin E and preclinical carotid atherosclerosis in middle-aged women. This association was independent of other cardiovascular risk factors, was not related to vitamin supplements, and supports the hypothesis that low vitamin E intake is a risk factor for early atherosclerosis.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Carotid Arteries; Carotid Artery Diseases; Carotid Artery, Common; Cholesterol; Diet; Estrogen Replacement Therapy; Female; Humans; Logistic Models; Middle Aged; Postmenopause; Ultrasonography; Vitamin A; Vitamin E; Vitamins

The oxidative modification of LDL is thought to play a crucial role in the initiation of atherosclerosis. Antioxidant vitamins can protect LDL from oxidation, and high intakes or blood concentrations of these vitamins have been linked with a reduced risk of cardiovascular disease. Few data are available on the importance of antioxidant vitamins in earlier stages of atherogenesis.. We investigated the cross-sectional relation between antioxidant vitamin status and carotid atherosclerosis in a group of elderly persons.. The study sample comprised 468 men and women aged 66-75 y living in Sheffield, United Kingdom. Duplex ultrasonography was used to measure intima-media thickness and the degree of stenosis in the extracranial carotid arteries. Antioxidant vitamin status was assessed by measuring fasting plasma concentrations of vitamin C, vitamin E, and beta-carotene.. In the men, after adjustment for age and cardiovascular disease risk factors, a 20% higher plasma vitamin C concentration was associated with a 0.004-mm smaller intima-media thickness; a 20% higher beta-carotene concentration was associated with a 0.005-mm smaller intima-media thickness. Compared with men with high blood concentrations of beta-carotene or cholesterol-adjusted vitamin E, those with low blood concentrations of these vitamins were 2.5 times as likely to have carotid stenosis of >30%. We found no significant trends between plasma concentrations of antioxidant vitamins and either measure of carotid atherosclerosis in the women.. A high antioxidant vitamin status may help to prevent the initiation and progression of early atherosclerotic lesions in men.

Topics: Aged; Aging; Antioxidants; Ascorbic Acid; beta Carotene; Carotid Artery Diseases; Carotid Stenosis; Cross-Sectional Studies; Female; Humans; Male; Nutritional Status; Tunica Media; Vitamin E; Vitamins

This study examined whether dietary intake or plasma levels of antioxidant vitamins were independently associated with common carotid artery intima-media (wall) thickness (IMT) or focal plaque, or both, in a large, randomly selected community population.. Oxidation of low-density lipoprotein (LDL) cholesterol is thought to be important in early atherogenesis. Antioxidant micronutrients may therefore protect against lipid peroxidation and atherosclerotic vascular disease.. We studied 1,111 subjects (558 men and 553 women; age 52 +/- 13 years [mean +/- SD], range 27 to 77). We measured dietary vitamin intake and fasting plasma levels of vitamins A, C and E, lycopene and alpha- and beta-carotene and performed bilateral carotid artery B-mode ultrasound imaging. RESULTS; After adjustment for age and conventional risk factors, there was a progressive decrease in mean IMT, with increasing quartiles of dietary vitamin E intake in men (p = 0.02) and a nonsignificant trend in women (p = 0.10). Dietary vitamin E levels accounted for 1% of the variance in measured IMT in men. For plasma antioxidant vitamins, there was an inverse association between carotid artery mean IMT and plasma lycopene in women (p = 0.047), but not in men. None of the other dietary or plasma antioxidant vitamins, nor antioxidant vitamin supplements, were associated with carotid artery IMT or focal carotid artery plaque.. This study provides limited support for the hypothesis that increased dietary intake of vitamin E and increased plasma lycopene may decrease the risk of atherosclerosis. No benefit was demonstrated for supplemental antioxidant vitamin use.

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Carotid Artery Diseases; Health Surveys; Humans; Lycopene; Nutritional Requirements; Risk; Ultrasonography; Vitamin A; Vitamin E; Vitamins; Western Australia

Using microdialysis, levels of metabolites in the extracellular fluid of the cerebral cortex were monitored during neurovascular surgery (9 aneurysm and 5 extra-intracranial bypass operations). Our aim was to use microdialysis to detect any local ischemia which might be caused by brain retraction or temporary clipping. Parameters were therefore quantified whose levels in the dialysate are known to be influenced by ischemia (on-line pH, ascorbic acid, uric acid, glutathione, cysteine, glucose, lactate, glucose:lactate ratio). In the aneurysm series, on-line pH fell after introduction of the retractor, and in the majority of cases the other parameters also showed changes in accordance with ischemic conditions in the region of the probe. These changes disappeared at the end of retraction, or sometimes even before. During the bypass operations, there were no marked changes in on-line pH or in any of the measured parameters. However, in some of these patients values for the glucose:lactate ratio, ascorbic acid and uric acid lay outside the suggested basal levels for minimally disturbed cortex, indicating possible changes in metabolism caused by inadequate perfusion (carotid artery occlusion). We conclude that microdialysis is a sensitive method of detecting intraoperative changes in cerebral metabolism.

Topics: Ascorbic Acid; Biomarkers; Brain Ischemia; Carotid Artery Diseases; Carotid Artery, Internal; Cerebral Cortex; Cerebral Revascularization; Constriction; Cysteine; Energy Metabolism; Extracellular Space; Glucose; Glutathione; Humans; Hydrogen-Ion Concentration; Intracranial Aneurysm; Intraoperative Complications; Lactates; Microdialysis; Monitoring, Intraoperative; Sensitivity and Specificity; Subarachnoid Hemorrhage; Uric Acid