ascorbic-acid and Hypercholesterolemia

Oxidative stress is involved in the pathogenesis of atherosclerosis, while a variety of antioxidants has been used in clinical studies, during the past few years, for the prevention and treatment of atherosclerosis. In small clinical studies it was found that both vitamins C and E may improve endothelial function in patients with risk factors for atherosclerosis such as diabetes mellitus, smoking, hypertension, or hypercholesterolemia. However, the initial, hopeful reports regarding the beneficial role of antioxidant vitamins against atherosclerosis, derived from purely observational studies, were followed by the negative results of almost all large randomized trials. Therefore, treatment with antioxidant vitamins C and E should not be recommended for the prevention or treatment of coronary atherosclerosis. New antioxidant strategies are needed to clarify the exact role of antioxidant treatment in coronary atherosclerosis.

Topics: Adult; Aged; Aged, 80 and over; Animals; Antioxidants; Arteriosclerosis; Ascorbic Acid; Cardiovascular Diseases; Case-Control Studies; Cohort Studies; Coronary Artery Disease; Diabetes Complications; Diet; Endothelium, Vascular; Female; Follow-Up Studies; Free Radicals; Humans; Hypercholesterolemia; Hypertension; Male; Middle Aged; Oxidative Stress; Prospective Studies; Randomized Controlled Trials as Topic; Risk; Risk Factors; Smoking; Time Factors; Vitamin E

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

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

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Disease Models, Animal; Guinea Pigs; Hypercholesterolemia

Topics: Animals; Anticholesteremic Agents; Arylsulfatases; Ascorbic Acid; Cattle; Cholesterol; Hypercholesterolemia; Intestinal Absorption; Liver; Rabbits; Triglycerides

Topics: Acute Disease; Animals; Arteriosclerosis; Ascorbic Acid; Ascorbic Acid Deficiency; Bile Acids and Salts; Cholesterol; Cholesterol, Dietary; Chronic Disease; Fatty Liver; Humans; Hypercholesterolemia; Lipid Metabolism; Liver Cirrhosis; Scurvy

As the second leading cause of death in the United States, cancer is a major public health problem today. Cancer incidence varies worldwide and tends to change with migration. These epidemiological observations have led to the concept that environmental factors may be important in carcinogenesis. Diet and nutrition are receiving increased attention and the National Cancer Institute, as mandated by the Nation Cancer Act Amendments of 1974, is playing a major leadership role in expanding research efforts in the areas of environmental carcinogenesis, and nutrition in relation to cancer. The subject of diet, nutrition, and cancer is complex. Different types of cancer are not necessarily affected by dietary components in the same manner. Although the development of certain neoplasms may be repressed by specific dietary deficiencies, other types, particularly those of the liver and upper gastrointestinal tract, are actually augmented or potentiated by such deficienceis. In extrapolating results from animal experiments to humans, caution must be exercised because of possible differences in species response to the same dietary stimulus and because spontaneous tumors may react differently from experimentally-induced tumors. Diet and nutrition are viewed more appropriately as modifiers, rather than initiators, of tumorigenesis. Caloric intake, type and amount of fat, protein, amino acids, vitamins, minerals, fiber, and other dietary constituents have been studied in regard to their influence on the development of neoplasms. Dietary components may have opposing effects on tumorigenesis, i.e., protective and predisposing, and the consequence to the host will depend on the balance between these opposing forces. Studies conducted to date indicate that the modifying effect of diet and nutrition may be exerted through specific effects on 1) intestinal bacteria and substrates for bacterial metabolism, 2) microsomal mixed-function oxidase system, 3) endocrine system, 4) immunological system, 5) availability of metabolites for cell proliferations, and 6) rate of carcinogen transfer and duration of exposure to the carcinogen. More research is needed to elucidate the interaction between diet and each of these factors and to test the validity of the mechanisms proposed to explain such interactions. These studies will lead not only to a better understanding of carcinogenesis itself but also to a new understanding of the influence of diet on human physiology and metabolism.

Topics: Animals; Ascorbic Acid; Bile Acids and Salts; Cholesterol; Diet; Dietary Fats; Digestive System; Energy Metabolism; Forecasting; Humans; Hypercholesterolemia; Intestines; Neoplasms; Nutrition Disorders; Nutritional Physiological Phenomena; Polysaccharides; Vitamin A; Vitamin A Deficiency; Vitamin B Complex; Vitamin B Deficiency

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cholesterol; Cholesterol, Dietary; Cholic Acids; Humans; Hypercholesterolemia; Scurvy

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

Topics: Adult; Aged; Animals; Arteriosclerosis; Ascorbic Acid; Catecholamines; Diet Therapy; Dietary Fats; Fats, Unsaturated; Female; Humans; Hypercholesterolemia; Hyperlipidemias; Hypertension; Injections, Intra-Arterial; Intermittent Claudication; Male; Mice; Middle Aged; Myocardial Infarction; Nicotine; Obesity; Procaine; Rabbits; Radiography; Smoking; Sympathectomy; Thiamine; Thromboangiitis Obliterans; Tolazoline; Vasodilator Agents

Topics: Antimetabolites; Arteriosclerosis; Ascorbic Acid; Cholesterol; Choline; Corrinoids; Ethyl Biscoumacetate; Heparin; Humans; Hypercholesterolemia; Iodoacetates; Lipotropic Agents; Magnesium Sulfate; Neomycin; Niacin; Nicotinic Acids; Progesterone; Pyridoxine; Thyroxine; Triparanol; Vitamin B 12

Vitamin C may enhance nitric oxide (NO) production through stepwise reduction of dietary nitrate (NO. We aimed to examine whether co-administration of vitamin C and nitrate for 4-weeks would improve endothelial function (primary outcome), plasma NO metabolites, oxidative stress, and blood lipids (secondary outcomes).. Subjects 50-70 years of age with low density lipoprotein (LDL) > 130 mg/dL and RHI ≤2 were enrolled in this randomized double-blind crossover study. Subjects were assigned to two 4-week supplementation treatments starting with 70 ml of concentrated beetroot juice (CBJ) with 1000 mg of vitamin C (NC) or CBJ with matched placebo (N), then switched to alternate treatment following 2-week washout. The change in reactive hyperemia index (RHI), sum of plasma NO metabolites (NO. Eighteen subjects (11M:7F) completed all study visits. No significant treatment differences were observed in RHI change (N: 0.21 ± 0.12; NC: 0.20 ± 0.17; p = 0.99). Secondary analysis revealed that a subgroup of NC subjects who started with a baseline RHI of <1.67 (threshold value for ED) had greater improvements in RHI compared to subjects with RHI >1.67 (1.23 ± 0.15 to 1.96 ± 0.19; n = 8 vs. 1.75 ± 0.11 to 1.43 ± 0.10; n = 8; p = 0.02). Compared to N, NC experienced a significant increase in plasma NOx (N: 94.2 ± 15.5 μmol/L; NC: 128.7 ± 29.1 μmol/L; p = 0.01). Although there was no significant difference in oxLDL change between treatments (N: -1.08 ± 9.8 U/L; NC: -6.07 ± 9.14 U/L; p = 0.19), NC elicited significant reductions in LDL (N: 2.2 ± 2; NC: -10.7 ± 23; p = 0.049), triglycerides (N: 14.6 ± 43; NC: -43.7 ± 45; p = 0.03), and no change in serum high density lipoprotein. Within treatment group comparisons showed that only NC reduced oxLDL significantly from baseline to 4 weeks (p = 0.01).. No between intervention differences were observed in RHI. RHI only improved in NC subjects with ED at intervention baseline. Four weeks of NC enriched the NO pool and promoted reduction of blood lipids and oxidative stress in subjects with hypercholesterolemia. These preliminary findings highlight a supplementation strategy that may reduce the progression of atherosclerotic disease and deserves further attention in studies using flow mediated dilation methods.. www.clinicaltrials.gov (NCT04283630).

Topics: Aged; Ascorbic Acid; Cross-Over Studies; Double-Blind Method; Endothelium; Female; Humans; Hypercholesterolemia; Lipids; Male; Middle Aged; Nitrates; Oxidative Stress; Vitamins

Hypercholesterolemia is a major risk factor for cardiovascular disorders and requires specific intervention through an adequate lifestyle (diet and physical exercise) and, if necessary, an appropriate drug treatment. Lipid-lowering drugs, although generally efficacious, may sometimes cause adverse events. A growing attention has been devoted to the correction of dyslipidemias through the use of dietary supplements. The aim of this study was to assess the lipid-lowering activity and safety of a dietary supplement containing monacolin K, L-arginine, coenzyme Q10 and ascorbic acid, named Argicolina (A), compared to a commercially available product containing monacolin K and coenzyme Q10, Normolip 5 (N).. This was a single center, controlled, randomized, open-label, cross-over clinical study enrolling 20 Caucasian outpatients aged 18-75 years with serum LDL-C between 130 and 180 mg/dL. Patients assumed two different dietary supplements (A and N) both containing monacolin K 10 mg for 8 weeks each, separated by a 4-week wash-out period. Evaluated parameters were: Total cholesterol (Tot-C), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides (TG), fasting blood glucose, aspartate aminotransferase, alanine aminotransferase, creatinekinase, gamma-glutamyl-transpeptidase, brachial arterial pressure and heart rate, measured at the start and at the end of each treatment period. Safety was monitored through the study.. LDL-C decreased by 23.3% during treatment with N (p < 0.0001) and by 25.6% during treatment with A (p < 0.0001); the LDL-C mean reduction was 36.4 (95% CI: 45,6-27,1) mg/dL during N treatment and 40.1 (95% CI: 49.2-30,9) mg/dL during A treatment. Tot-C decreased significantly (p < 0.0001) within each treatment period. HDL-C increase was negligible during A whereas it was significant during N. TG diminished markedly during A and not significantly during N. The difference between treatments was not statistically significant for all variables. No serious or severe adverse events occurred during the study.. Our results confirm the clinically meaningful LDL-C lowering properties of monacolin K. At variance with a supplement already in the market (N), the novel association (A) of monacolin K with L-arginine, coenzime Q10 and ascorbic acid also produces a significant reduction of triglycerides without significant effects on HDL.. ClinicalTrials.gov ID: NCT03425630 .

Topics: Adolescent; Adult; Aged; Analysis of Variance; Anticholesteremic Agents; Arginine; Ascorbic Acid; Cholesterol, HDL; Cholesterol, LDL; Cross-Over Studies; Dietary Supplements; Female; Humans; Hypercholesterolemia; Lovastatin; Male; Middle Aged; Severity of Illness Index; Triglycerides; Ubiquinone

Blond orange juice is the most consumed fruit juice in the world. It is a source of hesperidin, a bioavailable flavonoid reported to exhibit potential vascular protective actions. However, the specific impact on vascular function of Citrus phytomicronutrients, is unknown. For the first time, we investigated the effects of blond orange juice compared with a control beverage mimicking the composition of orange juice (including Vitamin C but no phytomicronutrients), on antioxidant markers, cardiovascular risk factors and endothelial function.. Twenty five male volunteers with two cardiovascular risk factors (age over 50 years and LDL-cholesterol between 130 and 190 mg/L) were enrolled in a randomized cross-over study. They received 3 times daily 200 mL of either blond orange juice or control beverage for 4 weeks, spaced by a 5-week wash-out. Endothelial function (flow mediated dilatation and plasma markers), oxidative status, lipid profile and inflammatory markers were assessed.. Daily intakes of orange juice significantly led to a marked antioxidant effect which was correlated to hesperetin plasma levels and related with a decrease in reactive oxygen species. A tendency towards reduction of endothelial dysfunction and modest increase in plasma apoA-I concentration were also observed. This allows further experiments demonstrating the specific effect of phytomicronutrients from orange juice.. These findings suggest that daily intake of nutritionally relevant dose of blond orange juice may contribute for a significant antioxidant effect through the phytochemicals contained in. Orange juice may be associated to other healthy foods to achieve a significant effect on the vascular function. This study is recorded in ClinicalTrials.com as NCT00539916.

Topics: Antioxidants; Apolipoprotein A-I; Ascorbic Acid; Biomarkers; Body Mass Index; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Citrus sinensis; Cross-Over Studies; Flavonoids; Fruit and Vegetable Juices; Hesperidin; Humans; Hypercholesterolemia; Male; Middle Aged; Oxidative Stress; Phytochemicals; Reactive Oxygen Species; Risk Factors; Single-Blind Method; Triglycerides

This study evaluated the effect of statins in Primary biliary cirrhosis (PBC) on endothelial function, anti-oxidant status and vascular compliance.. Primary biliary cirrhosis patients with hypercholesterolaemia were randomized to receive 20 mg simvastatin or placebo in a single blind, randomized controlled trial. Body mass index, blood pressure, glucose, liver function, lipid profile, immunoglobulin levels, serological markers of endothelial function and anti-oxidant status were measured as well as vascular compliance, calculated from pulse wave analysis and velocity, at recruitment and again at 3, 6, 9 and 12 months.. Twenty-one PBC patients (F = 20, mean age = 55) were randomized to simvastatin 20 mg (n = 11) or matched placebo (n = 10). At completion of the trial, serum cholesterol levels in the simvastatin group were significantly lower compared with the placebo group (4.91 mmol/L vs. 6.15 mmol/L, P = 0.01). Low-density lipoprotein (LDL) levels after 12 months were also significantly lower in the simvastatin group (2.33 mmol/L vs. 3.53 mmol/L, P = 0.01). After 12 months of treatment, lipid hydroperoxides were lower (0.49 μmol/L vs. 0.59 μmol/L, P = 0.10) while vitamin C levels were higher (80.54 μmol/L vs. 77.40 μmol/L, P = 0.95) in the simvastatin group. Pulse wave velocity remained similar between treatment groups at 12 months (8.45 m/s vs. 8.80 m/s, P = 0.66). Only one patient discontinued medication owing to side effects. No deterioration in liver transaminases was noted in the simvastatin group.. Statin therapy in patients with PBC appears safe and effective towards overall reductions in total cholesterol and LDL levels. Our initial study suggests that simvastatin may also confer advantageous effects on endothelial function and antioxidant status.

Topics: Ascorbic Acid; Biomarkers; Cholesterol; Endothelium, Vascular; Female; Hemodynamics; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Inflammation Mediators; Lipid Peroxides; Lipoproteins, LDL; Liver Cirrhosis, Biliary; Male; Middle Aged; Northern Ireland; Pulse Wave Analysis; Simvastatin; Single-Blind Method; Time Factors; Treatment Outcome; Vascular Stiffness

This study investigated the hypothesis that long-term orange juice consumption (≥ 12 months) was associated with low risk factors for cardiovascular disease in adult men and women with normal and moderately high cholesterol blood levels.. The sample consisted of 103 men (18-66 y) and 26 women (18-65 y); all were employees of an orange juice factory with daily access to free orange juice. The results showed that 41% of the individuals consumed 2 cups (480 mL) of orange juice per day for at least twelve months, while 59% of the volunteers are non-consumers of orange juice.. Orange juice consumers with normal serum lipid levels had significantly lower total cholesterol (-11%, p <0.001), LDL-cholesterol (-18%, p < 0.001), apolipoprotein B (apo B) (-12%, p < 0.01) and LDL/HDL ratio (-12%, p < 0.04) in comparison to non-consumers, as did the consumers with moderate hypercholesterolemia: lower total cholesterol (-5%, p <0.02), LDL-cholesterol (-12%, p <0.03), apolipoprotein B (-12%, p <0.01) and LDL/HDL ratio (-16%, p <0.05) in comparison the non-consumers counterparts. Serum levels of homocysteine, HDL- cholesterol and apolipoprotein A-1, body composition and the dietary intake of food energy and macronutrients did not differ among orange juice consumers and non-consumers, but vitamin C and folate intake was higher in orange juice consumers.. Long-term orange juice consumers had lower levels of total cholesterol, LDL-cholesterol, apo B and LDL/HDL ratio and an improvement of folate and vitamin C in their diet.

Topics: Adolescent; Adult; Aged; Apolipoprotein A-I; Apolipoproteins B; Ascorbic Acid; Beverages; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Citrus sinensis; Cross-Sectional Studies; Female; Folic Acid; Humans; Hypercholesterolemia; Male; Middle Aged; Treatment Outcome; Young Adult

Red yeast rice (RYR), sugar cane-derived policosanols (SCdP) and artichoke leaf extracts (ALEs) are currently incorporated alone or in combination into dietary supplements for their potential low-density-lipoprotein cholesterol (LDL-cholesterol)-lowering effects. Yet, there is no information supporting the efficacy of this association on the reduction in LDL-cholesterol. The main objective of this study was to investigate the effects of a new dietary supplement (DS) with RYR, SCdP and ALEs on LDL-cholesterol.. In a double-blind, randomized, parallel controlled study, 39 subjects from 21 to 55 years with moderate hypercholesterolemia without drug treatment were assigned to 2 groups and then consumed either a DS containing RYR, SCdP and ALEs or a placebo over a 16-week period. Plasma concentrations of lipids [LDL-cholesterol, total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-cholesterol), triacylglycerols (TG)] and plasma levels of vitamins C and E, total polyphenols and malondialdehyde were determined at baseline and after 4, 8, 12 and 16 weeks.. LDL-cholesterol and TC were reduced by, respectively, 21.4 % (95 % CI, -13.3 to -24.9 %, p < 0.001) and 14.1 % (95 % CI, -10.1 to -18.0 %, p < 0.001) at week 16 in the DS group compared with baseline. Similar results were obtained at weeks 4, 8 and 12. TG decreased by 12.2 % after 16 weeks in the DS group (95 % CI: -24.4 to -0.1 %, p < 0.05). For the vitamin E/TC ratio, a difference was observed between groups at week 16 (p < 0.05). Other parameters were not modified.. Daily consumption of this new DS decreased LDL-cholesterol and TC and is therefore an interesting, convenient aid in managing mild to moderate hypercholesterolemia.

Topics: Adult; Anticholesteremic Agents; Ascorbic Acid; Biological Products; Cholesterol, HDL; Cholesterol, LDL; Cynara scolymus; Dietary Supplements; Double-Blind Method; Fatty Alcohols; Female; Humans; Hypercholesterolemia; Male; Malondialdehyde; Middle Aged; Plant Extracts; Plant Leaves; Polyphenols; Triglycerides; Vitamin E; Young Adult

Oxidative stress is known to be an important component of cellular damage regarding hypercholesterolemia and its complications. In vitro study had demonstrated that extracts of Graptopetalum paraguayense E. Walther exhibited strong antioxidative activities. This study was aimed at investigating the effect of G. paraguayense consumption on antioxidative status and serum lipid profiles in hypercholesterolemic subjects.. Eighteen hypercholesterolemic subjects were instructed to consume 100 g G. paraguayense as a serving of vegetable daily for 8 consecutive weeks. After consumption, there were no changes in waist measurement, body mass index, body fat component, blood pressure, hepatic function (serum alanine aminotransferase activity), renal function (serum creatinine, uric acid) or fasting plasma glucose levels. Daily G. paraguayense consumption significantly increased ascorbic acid and α-tocopherol levels and decreased malondialdehyde level in plasma. Furthermore, daily G. paraguayense consumption significantly increased glutathione levels, glutathione peroxidase and catalase activities in erythrocyte. However, there were no significant changes in serum total cholesterol, triglyceride, low-density lipoprotein cholesterol or high-density lipoprotein cholesterol after G. paraguayense consumption.. The present study demonstrated that consumption of G. paraguayense may increase in vivo antioxidant activities and have some protective effects in decreasing oxidative stress in hypercholesterolemic subjects.

Topics: Adult; alpha-Tocopherol; Antioxidants; Ascorbic Acid; Catalase; Crassulaceae; Diet; Erythrocytes; Female; Glutathione; Glutathione Peroxidase; Humans; Hypercholesterolemia; Lipids; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Phytotherapy; Plant Leaves; Plant Preparations

Elevated low-density lipoproteins (LDL) are associated with cutaneous microvascular dysfunction partially mediated by increased arginase activity, which is decreased following a systemic atorvastatin therapy. We hypothesized that increased ascorbate-sensitive oxidant stress, partially mediated through uncoupled nitric oxide synthase (NOS) induced by upregulated arginase, contributes to cutaneous microvascular dysfunction in hypercholesterolemic (HC) humans. Four microdialysis fibers were placed in the skin of nine HC (LDL = 177 ± 6 mg/dl) men and women before and after 3 mo of a systemic atorvastatin intervention and at baseline in nine normocholesterolemic (NC) (LDL = 95 ± 4 mg/dl) subjects. Sites served as control, NOS inhibited, L-ascorbate, and arginase-inhibited+L-ascorbate. Skin blood flow was measured while local skin heating (42°C) induced NO-dependent vasodilation. After the established plateau in all sites, 20 mM ≪ngname≫ was infused to quantify NO-dependent vasodilation. Data were normalized to maximum cutaneous vascular conductance (CVC) (sodium nitroprusside + 43°C). The plateau in vasodilation during local heating (HC: 78 ± 4 vs. NC: 96 ± 2% CVC(max), P < 0.01) and NO-dependent vasodilation (HC: 40 ± 4 vs. NC: 54 ± 4% CVC(max), P < 0.01) was reduced in the HC group. Acute L-ascorbate alone (91 ± 5% CVC(max), P < 0.001) or combined with arginase inhibition (96 ± 3% CVC(max), P < 0.001) augmented the plateau in vasodilation in the HC group but not the NC group (ascorbate: 96 ± 2; combo: 93 ± 4% CVC(max), both P > 0.05). After the atorvastatin intervention NO-dependent vasodilation was augmented in the HC group (HC postatorvastatin: 64 ± 4% CVC(max), P < 0.01), and there was no further effect of ascorbate alone (58 ± 4% CVC(max,) P > 0.05) or combined with arginase inhibition (67 ± 4% CVC(max,) P > 0.05). Increased ascorbate-sensitive oxidants contribute to hypercholesteromic associated cutaneous microvascular dysfunction which is partially reversed with atorvastatin therapy.

Topics: Administration, Oral; Adult; Analysis of Variance; Antioxidants; Arginase; Ascorbic Acid; Atorvastatin; Enzyme Inhibitors; Female; Heating; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Microdialysis; Microvessels; Middle Aged; Nitric Oxide; Nitric Oxide Synthase; Oxidative Stress; Pennsylvania; Pyrroles; Skin; Time Factors; Treatment Outcome; Vasodilation; Vasodilator Agents

Aging and a variety of cardiovascular risk factors are associated with oxidative stress and impaired endothelial function. Whether such an association is already evident in the renal vascular bed in young patients at high cardiovascular risk has not yet been determined.. We compared renal haemodynamics in 23 young (age 30+/-5 years) male patients at high cardiovascular risk with impaired lipid metabolism and elevated blood pressure with 23 matched, healthy control subjects (age 28+/-3 years) without cardiovascular risk factors at baseline and following infusions of the nitric oxide (NO) synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA: 4.25mg/kg), the substrate of NO synthase L-arginine (100mg/kg) and the antioxidant Vitamin C (3g, co-infused with L-arginine 100mg/kg).. Baseline renal haemodynamics did not differ between the two groups. Infusion of L-NMMA decreased renal plasma flow (RPF) in both groups to a similar extent (-113+/-95 ml/min versus -128+/-133 ml/min, p=NS). The response of RPF to infusion of L-arginine was more pronounced in high risk patients than in control subjects (+123+/-64.4 ml/min versus +75.6+/-60.2 ml/min, p=0.012) and further exaggerated during co-infusion of L-arginine and Vitamin C (+299+/-164 ml/min versus +175+/-148 ml/min, p=0.003).. Basal NO activity of the renal vasculature appears to be unaltered in young patients at high cardiovascular risk. However, the greater response of RPF to L-arginine and to Vitamin C co-infused with L-arginine in these young patients suggests that decreased substrate availability for NO synthase and oxidative stress are key factors for alterations in endothelium-dependent vasodilation of the renal vasculature in this young high risk group of patients.

Topics: Adult; Antioxidants; Arginine; Ascorbic Acid; Humans; Hypercholesterolemia; Male; Nitric Oxide; Nitric Oxide Synthase; omega-N-Methylarginine; Oxidative Stress; Renal Plasma Flow; Substrate Specificity

Experimental evidence suggests a lipid-independent effect of statins on endothelial function and nitric oxide (NO) availability in humans. We investigated whether improvement in NO availability in hypercholesterolemia can be achieved rapidly with statins before lipid-lowering therapy is complete.. We studied 41 patients (52 +/- 11 years) with low-density lipoprotein (LDL) cholesterol > or = 130 mg/dL (179 +/- 45 mg/dL) randomly assigned to treatment either with atorvastatin (20 mg/day) or cerivastatin (0.4 mg/day). Endothelium-dependent vasodilation of the forearm vasculature was measured by plethysmography and intra-arterial infusion of acetylcholine (ACh) after 3 days (n = 18) and 14 days (n = 39) of treatment. NO availability and oxidative stress were assessed by coinfusion of l-NMMA and vitamin C.. After 3 days of treatment, LDL-cholesterol decreased by 11.9% with a further decrease to 29.6% after 14 days ( P < .001). Endothelium-dependent vasodilation improved by +46.7% after 3 days of statin therapy compared with before therapy (ACh 48 microg/min: +15.7 +/- 10.6 vs +10.7 +/- 10.8 mL/min per 100 mL, P < .05). No further improvement in endothelium-dependent vasodilation (+42.7% compared with before therapy) could be demonstrated after 14 days of treatment (ACh 48 microg/min: +17.7 +/- 10.3 vs +12.4 +/- 9.3 mL/min per 100 mL before therapy, P < .001). Coinfusion of ACh plus vitamin C was able to improve endothelium-dependent vasodilation before but not after 3 or 14 days of statin therapy either. The improvement in endothelium-dependent vasodilation after therapy was no longer observed when the NO-synthase inhibitor l-NMMA was coinfused together with ACh.. Short-term lipid-lowering therapy with statins is able to improve endothelial function and NO availability almost completely after 3 days in hypercholesterolemic patients probably by decreasing oxidative stress. This improvement seems to be more rapid than the accompanying decline in LDL-cholesterol and not related to these lipid changes. This finding can support the concept of lipid-independent effects of statins in humans.

Topics: Acetylcholine; Adult; Aged; Ascorbic Acid; Atorvastatin; Biological Availability; C-Reactive Protein; Dose-Response Relationship, Drug; Double-Blind Method; Endothelium, Vascular; Female; Forearm; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Lipid Metabolism; Male; Middle Aged; Nitric Oxide; Nitroprusside; omega-N-Methylarginine; Pyridines; Pyrroles; Regional Blood Flow; Vasodilation

This study was designed to research the effect of hypercholesterolaemia and ascorbic acid on forearm blood flow (FBF) reactive hyperaemia (RH). Reactive hyperaemia seems to be at least partly endothelium-dependent. Endothelial dysfunction has been described in patients with hypercholesterolaemia, and has been reversed with ascorbic acid administration.. Forearm blood flow was studied with venous occlusion plethsmography in 26 healthy volunteers and 46 hypercholesterolaemic patients. Hypercholesterolaemic patients were divided into two groups. Group A comprised 25 patients, who received ascorbic acid and group B comprised 21 patients, who received placebo. All subjects underwent measurement of FBF at baseline and during RH (phase A). Forearm blood flow during RH was measured every 15 seconds for three minutes. Subsequently patients in group A received 2 g of ascorbic acid orally in the form of effervescent tablets, and patients in group B received placebo orally in the same form. Forearm blood flow measurements at baseline and during RH were repeated two hours later (phase B).. Maximal percent increase of FBF was significantly higher in healthy subjects than in hypercholesterolaemic patients (139.1+/-12.1% versus 73.1+/-11.0% respectively, P<0.05). Duration of RH was smaller in hypercholesterolaemic patients compared to normal subjects (60.9+/-17.1 seconds versus 105.6+/-10.2 seconds, P<0.05). Administration of ascorbic acid but not of placebo increased the duration of RH (69.1+/-11.1 seconds versus 104.1+/-12.2 seconds, P<0.05) but not of peak RH FBF.. Hypercholesterolaemia seems to impair both the early and late phase of RH. Ascorbic acid improves only the duration of RH, possibly due to its antioxidant effect on endothelium.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Female; Forearm; Humans; Hypercholesterolemia; Hyperemia; Male; Middle Aged; Plethysmography; Regional Blood Flow; Vasodilation

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

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

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

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

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

We assessed whether third-generation oral contraceptive (OC) treatment (30 microg ethinylestradiol + 75 microg gestodene daily) could affect the endothelial function of healthy women.. In 20 young healthy women (HW) and 10 hypercholesterolemic women (CW) we assessed forearm blood flow (strain-gauge plethysmography) changes induced by the intrabrachial infusion of acetylcholine (ACH) (0.15-15 microg/100 ml forearm tissue/min) and sodium nitroprusside (SNP) (1-4 microg/100 ml forearm tissue/min). ACH was repeated during the nitric oxide synthase inhibitor intra-arterial NG-monomethyl-L-arginine (L-NMMA) (100 microg/100 ml forearm tissue/min) or the antioxidant vitamin C (8 mg/100 ml forearm tissue/min). HW repeated the protocol after 6-month OC (n = 10) or placebo (n = 10) treatment.. In HW the maximal vasodilation to ACH, similar between placebo and OC subgroups, was significantly reduced in CW (P < 0.01). Vasodilation to ACH was blunted (P < 0.01) by L-NMMA and unaffected by vitamin C, in both OC and placebo groups. In CW the vasodilation to ACH, not modified by L-NMMA, was improved by vitamin C (P < 0.01). OC treatment raised (P < 0.01) plasma total and low-density lipoprotein cholesterol, and values were similar to those shown by CW. Both OC and placebo intake did not change the response to ACH and the modulation induced by L-NMMA or vitamin C. Vasodilation to SNP was similar in all groups.. In HW 6-month treatment with third-generation OC, although associated with an abnormal lipid profile, does not adversely affect endothelium-dependent vasodilation. This neutral effect could be the balance between a deleterious effect of hypercholesterolemia and a protective effect of OC on endothelial function.

Topics: Acetylcholine; Adult; Antioxidants; Ascorbic Acid; Biomarkers; Cholesterol, LDL; Contraceptives, Oral; Dose-Response Relationship, Drug; Endothelium, Vascular; Enzyme Inhibitors; Female; Forearm; Humans; Hypercholesterolemia; Microcirculation; Nitroprusside; omega-N-Methylarginine; Reference Values; Regional Blood Flow; Triglycerides; Vasodilation; Vasodilator Agents; Women's Health

The purpose of this study was to observe the effects of dietary intervention, through the modification of dietary fatty acids composition and antioxidant vitamins, on plasma thromboxane B(2) (TXB(2)) levels in postmenopausal women with hypercholesterolemia. The subjects were treated for 12 weeks with one of three methods: hormone replacement therapy (HRT group, n=8), dietary intervention (DIET group, n=8), or HRT combined with dietary intervention (HRT +DIET group, n=8). Changes in serum phospholipid fatty acids composition, serum peroxides, and plasma TXB(2) levels were measured at weeks 0, 4 and 12. The P/S ratio increased and the n-6/ n-3 ratio decreased in the DIET and the HRT +DIET group at week 4 (p<0.05). The ratio of C20:5/C20:4 in serum phospholipid increased in the DIET (p<0.05) and the HRT +DIET groups (NS) at week 4. Plasma TXB(2) levels decreased in the DIET (-35%, p<0.05) and the HRT +DIET groups (-18.8%, NS) at week 4. Serum lipid peroxides levels significantly decreased by 10.5% and 15.2% in the DIET group at weeks 4 and 12, and by 10.8% in the HRT +DIET group only at week 12 (p<0.05). Dietary intervention may lower thrombotic risks in Korean postmenopausal women by changing the serum fatty acid composition, serum lipid peroxides levels and plasma thromboxane B(2) levels.

Topics: Antioxidants; Ascorbic Acid; Dietary Fats; Estrogen Replacement Therapy; Fatty Acids; Female; Humans; Hypercholesterolemia; Lipid Peroxidation; Middle Aged; Postmenopause; Thromboxane B2; Vitamin A; Vitamin E

Statins decrease the hepatic biosynthesis of cholesterol, and reduce the incidence of myocardial infarction in women who have already experienced a myocardial infarction. Statins also reduce the risk of atherosclerosis in diabetic patients, but it is unknown whether they influence the glucose tolerance. It has further been suggested that they may influence bone metabolism. Vitamin C is an antioxidant and it decreases serum cholesterol moderately. Antioxidants may also have other metabolic effects, but these are insufficiently studied. The aim of the present study was to investigate the metabolic effects of the cholesterol-lowering agent fluvastatin and the antioxidant vitamin C. Sixty-eight elderly, postmenopausal women with osteoporosis and mild hypercholesterolemia were randomly assigned to 12 weeks open treatment with either fluvastatin (40 mg daily) + 500 mg vitamin C (n = 45) or vitamin C only (n = 23). We measured biochemical markers of bone formation (serum osteocalcin and total alkaline phosphatase) and bone resorption (serum and urinary CTX), parameters related to diabetes and serum lipids and lipoproteins. Fluvastatin in combination with vitamin C had no effect on bone formation markers. We found a weak decrease in parameters of bone resorption, which was significant from baseline, but not different between the two groups. There were no significant effects on any of the other markers of either fluvastatin or vitamin C. The lipid-lowering effect of fluvastatin was confirmed with a decrease of 20% and 30% in serum total cholesterol and LDL-cholesterol, respectively. We conclude that fluvastatin given in clinically relevant doses has no influence on parameters of bone remodeling. Other statins remain to be investigated.

Topics: Aged; Anticholesteremic Agents; Antioxidants; Ascorbic Acid; Biomarkers; Bone Remodeling; Drug Therapy, Combination; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hypercholesterolemia; Indoles; Lipoproteins; Osteoporosis, Postmenopausal

The goal of this study was to determine the long-term effects of statins and antioxidant vitamins on flow-mediated vasodilation of the brachial artery in older adults with hypercholesterolemia.. Lipid-lowering therapy and antioxidant vitamins improve endothelium-dependent vasodilation in young and middle-aged adults with hypercholesterolemia, but their effects in older adults are not known.. Two double-blind, placebo-controlled studies were performed in individuals > or =70 years old with low-density lipoprotein cholesterol (LDL-C) > or =140 mg/dl. In the first study, 37 subjects were randomized to receive (group 1) pravastatin for six months then pravastatin and vitamin E for six additional months or (group 2) vitamin E for six months, then pravastatin and vitamin E for six additional months. In the second study, additional 17 subjects sequentially received simvastatin for six months, then simvastatin and vitamins C and E for six additional months. Flow-mediated vasodilation of the brachial artery was measured by high-resolution ultrasound.. At baseline, subjects in both studies were similar in age (mean +/- SD, 75.8 +/- 4.2 years), gender, systolic blood pressure, total cholesterol (261.6 +/- 37.4 mg/dl), LDL-C (180.3 +/- 28.1 mg/dl), high-density lipoprotein cholesterol and triglycerides levels. Flow-mediated vasodilation was severely impaired (2.2 +/- 3.9%). Both statins reduced total and LDL-C levels (p < 0.001); however, neither statin, antioxidant vitamin regimen nor the combination of statins and antioxidant vitamins improved flow-mediated vasodilation of the brachial artery. At baseline, nitroglycerin-mediated vasodilation also was impaired (10.7 +/- 5.6%) and did not change in either study.. Older adults with hypercholesterolemia have impaired flow-mediated vasodilation of the brachial artery that does not improve after one year of therapy with statins and antioxidant vitamins, despite significant lipid-lowering.

Topics: Aged; Aged, 80 and over; Ascorbic Acid; Brachial Artery; Cholesterol, LDL; Double-Blind Method; Drug Therapy, Combination; Endothelium, Vascular; Female; Humans; Hypercholesterolemia; Long-Term Care; Male; Pravastatin; Simvastatin; Vasodilation; Vitamin A

Although the use of vitamin E supplements has been associated with a reduction in coronary events, assumed to be due to lowered lipid peroxidation, there are no previous long-term clinical trials into the effects of vitamin C or E supplementation on lipid peroxidation in vivo. Here, we have studied the long-term effects of vitamins C and E on plasma F2-isoprostanes, a widely used marker of lipid peroxidation in vivo. As a study cohort, a subset of the "Antioxidant Supplementation in Atherosclerosis Prevention" (ASAP) study was used. ASAP is a double-masked placebo-controlled randomized clinical trial to study the long-term effect of vitamin C (500 mg of slow release ascorbate daily), vitamin E (200 mg of D-alpha-tocopheryl acetate daily), both vitamins (CellaVie), or placebo on lipid peroxidation, atherosclerotic progression, blood pressure and myocardial infarction (n = 520 at baseline). Lipid peroxidation measurements were carried out in 100 consecutive men at entry and repeated at 12 months. The plasma F2-isoprostane concentration was lowered by 17.3% (95% CI 3.9-30.8%) in the vitamin E group (p = 0.006 for the change, as compared with the placebo group). On the contrary, vitamin C had no significant effect on plasma F2-isoprostanes as compared with the placebo group. There was also no interaction in the effect between these vitamins. In conclusion, long-term oral supplementation of clinically healthy, but hypercholesterolemic men, who have normal vitamin C and E levels with a reasonable dose of vitamin E lowers lipid peroxidation in vivo, but a relatively high dose of vitamin C does not. This observation may provide a mechanism for the observed ability of vitamin E supplements to prevent atherosclerosis.

Topics: Aged; Analysis of Variance; Ascorbic Acid; Dietary Supplements; F2-Isoprostanes; Gas Chromatography-Mass Spectrometry; Humans; Hypercholesterolemia; Lipid Peroxidation; Male; Middle Aged; Smoking; Vitamin E

It has been claimed that coenzyme Q10 (Q10) would be an effective plasma antioxidant since it can regenerate plasma vitamin E. To test separate effects and interaction between Q10 and vitamin E in the change of plasma concentrations and in the antioxidative efficiency, we carried out a double-masked, double-blind clinical trial in 40 subjects with mild hypercholesterolemia undergoing statin treatment. Subjects were randomly allocated to parallel groups to receive either Q10 (200 mg daily), d-alpha-tocopherol (700 mg daily), both antioxidants or placebo for 3 months. In addition we investigated the pharmacokinetics of Q10 in a separate one-week substudy. In the group that received both antioxidants, the increase in plasma Q10 concentration was attenuated. Only vitamin E supplementation increased significantly the oxidation resistance of isolated LDL. Simultaneous Q10 supplementation did not increase this antioxidative effect of vitamin E. Q10 supplementation increased and vitamin E decreased significantly the proportion of ubiquinol of total Q10, an indication of plasma redox status in vivo. The supplementations used did not affect the redox status of plasma ascorbic acid. In conclusion, only vitamin E has antioxidative efficiency at high radical flux ex vivo. Attenuation of the proportion of plasma ubiquinol of total Q10 in the vitamin E group may represent in vivo evidence of the Q10-based regeneration of the tocopheryl radicals. In addition, Q10 might attenuate plasma lipid peroxidation in vivo, since there was an increased proportion of plasma ubiquinol of total Q10.

Topics: Aged; Antioxidants; Ascorbic Acid; Coenzymes; Dietary Supplements; Double-Blind Method; Drug Interactions; Female; Humans; Hypercholesterolemia; Lipid Peroxidation; Lipoproteins, LDL; Male; Middle Aged; Placebos; Ubiquinone; Uric Acid; Vitamin E

We tested the effects of vitamin C and atorvastatin treatment on endothelium-dependent and endothelium-independent vasodilation in 18 hypercholesterolemic patients (ten men and eight women, aged 20-46 years) in comparison with 12 normal volunteers (seven men and five women, aged 20-45 years). The responses of the forearm blood flow (FBF) to acetylcholine (ACh) (7.5, 15 and 30 microg/min), sodium nitroprusside (SNP) (0.8, 1.6, 3.2 microg/min) and L-NMMA (2, 4, 8 micromol/min) were evaluated at baseline and after 1 month of atorvastatin (10 mg/day) treatment. Drugs were infused into the brachial artery and FBF was measured by strain-gauge plethysmography. At baseline, the response to ACh was significantly attenuated in hypercholesterolemics versus controls: at the highest dose (30 microg/min), FBF was 27.0+/-3.4 versus 11.5+/-1.9 ml.100 ml tissue(-1).min(-1) respectively (P<0.0001). No significant differences were found between groups during SNP infusion. The atorvastatin treatment significantly improved ACh-stimulated FBF: at highest dose the FBF increased to 14.9+/-1.5 ml.100 ml tissue(-1). min(-1) (P<0.0001). Similarly, the L-NMMA endothelial effects were significantly enhanced by lipid-lowering treatment, supporting the improvement of basal nitric oxide. Vitamin C increased ACh-vasodilation in the same way before and after atorvastatin treatment. In conclusion, the endothelial dysfunction in hypercholesterolemics is due to an oxidative stress and atorvastatin rapidly improves both basal and stimulated endothelium-dependent vasodilation.

Topics: Acetylcholine; Adult; Anticholesteremic Agents; Antioxidants; Ascorbic Acid; Atorvastatin; Blood Flow Velocity; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Endothelium, Vascular; Female; Forearm; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Infusions, Intra-Arterial; Male; Middle Aged; Nitroprusside; omega-N-Methylarginine; Plethysmography; Pyrroles; Vasodilation; Vasodilator Agents

Orange juice-a rich source of vitamin C, folate, and flavonoids such as hesperidin-induces hypocholesterolemic responses in animals.. We determined whether orange juice beneficially altered blood lipids in subjects with moderate hypercholesterolemia.. The sample consisted of 16 healthy men and 9 healthy women with elevated plasma total and LDL-cholesterol and normal plasma triacylglycerol concentrations. Participants incorporated 1, 2, or 3 cups (250 mL each) of orange juice sequentially into their diets, each dose over a period of 4 wk. This was followed by a 5-wk washout period. Plasma lipid, folate, homocyst(e)ine, and vitamin C (a compliance marker) concentrations were measured at baseline, after each treatment, and after the washout period.. Consumption of 750 mL but not of 250 or 500 mL orange juice daily increased HDL-cholesterol concentrations by 21% (P: < 0.001), triacylglycerol concentrations by 30% (from 1.56 +/- 0.72 to 2.03 +/- 0.91 mmol/L; P: < 0.02), and folate concentrations by 18% (P: < 0.01); decreased the LDL-HDL cholesterol ratio by 16% (P: < 0.005); and did not affect homocyst(e)ine concentrations. Plasma vitamin C concentrations increased significantly during each dietary period (2.1, 3.1, and 3.8 times, respectively).. Orange juice (750 mL/d) improved blood lipid profiles in hypercholesterolemic subjects, confirming recommendations to consume >/=5-10 servings of fruit and vegetables daily.

Topics: Adult; Aged; Ascorbic Acid; Beverages; Body Mass Index; Cholesterol, HDL; Cholesterol, LDL; Citrus; Energy Intake; Female; Folic Acid; Homocysteine; Humans; Hypercholesterolemia; Male; Middle Aged; Nutritional Physiological Phenomena; Triglycerides

Endothelium-dependent vasodilation is impaired in humans with hypercholesterolemia. Oxidative degradation of endothelium-derived nitric oxide plays a major role in endothelial dysfunction in animal models of hypercholesterolemia. To assess whether this mechanism is relevant to humans, we studied the effect of vitamin C, an antioxidant, on vasodilator function in forearm resistance vessels of patients with hypercholesterolemia.. We studied 11 hypercholesterolemic and 12 healthy control subjects. Forearm blood flow was determined by venous occlusion plethysmography. Endothelium-dependent vasodilation was assessed by intra-arterial infusion of methacholine (0.3 to 10 micrograms/min). Endothelium-independent vasodilation was measured by intra-arterial infusion of nitroprusside (0.3 to 10 micrograms/min) and verapamil (10 to 300 micrograms/min). Forearm blood flow dose-response curves were determined for each drug before and during coadministration of vitamin C (24 mg/min). In hypercholesterolemic subjects, endothelium-dependent vasodilation to methacholine was augmented by coinfusion of vitamin C (P = .001); in contrast, endothelium-independent vasodilation to nitroprusside and verapamil were not affected by coinfusion of vitamin C (P = .8 and P = .3, respectively). In control subjects, vitamin C administration did not alter endothelium-dependent vasodilation (P = .2).. We conclude that vitamin C improves endothelium-dependent vasodilation in the forearm resistance vessels of patients with hypercholesterolemia. These findings suggest that nitric oxide degradation by oxygen-derived free radicals contributes to abnormal vascular reactivity in hypercholesterolemic humans.

Topics: Adult; Ascorbic Acid; Endothelium, Vascular; Female; Forearm; Humans; Hypercholesterolemia; Male; Middle Aged; Pharmaceutical Vehicles; Regional Blood Flow; Vascular Resistance; Vasodilation

Several recent studies have indicated the possible beneficial effects of antioxidants, specifically vitamin E, in primary and secondary coronary prevention. These studies suggest that a diet enriched in vitamin E is insufficient to have a significant protective effect, whereas supplements, in excess of 200 international units (IU) per day, are efficacious in preventing coronary disease in both men and women. The mechanisms by which vitamin E may exert its protection are uncertain, but, vitamin E is lipophilic and has been shown to inhibit the oxidative modification of low density lipoprotein (LDL), a process thought to be of crucial importance in atherogenesis. We have also previously shown that alpha-tocopherol (the biologically most potent isomer of vitamin E) has important direct effects on vascular endothelial and smooth muscle cells. In the present study we have investigated the effects of oral supplements of vitamin E (400 IU per day) on platelet and mononuclear cell function in patients with hypercholesterolaemia. We found that although vitamin E supplementation had no significant effect on mononuclear cell adhesion ex vivo, it had a significant effect on the thrombin-induced platelet aggregation (P < 0.01; ANOVA): 6 weeks after starting the vitamin E supplements, the mean EC50 for thrombin-induced aggregation increased 132% (P < 0.05; paired t-test) compared to treatment with placebo. The effects of vitamin E on platelet function may, in part, explain its anti-atherogenic properties.

Topics: Adult; Aged; Ascorbic Acid; Cell Adhesion; Cell Culture Techniques; Female; Humans; Hypercholesterolemia; Lipids; Male; Middle Aged; Monocytes; Platelet Aggregation; Single-Blind Method; Thrombin; Vitamin A; 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 aim of this investigation is to study the hypothesis that vitamin C has beneficial effects on some risk factors of cardiovascular diseases. Sixty-seven volunteers participated in this study. Thirty and thirty-seven subjects were assigned randomly to two groups. The first was given a placebo and the second was given a vitamin C, respectively. Both regimens were followed for six months. The dose of vitamin C was 500 mg/day. Double blind technique was used throughout the study. These data supported part of the beneficial effects of vitamin C on atherosclerosis process, i.e. reduce significantly body fat, systolic blood pressure, and pulse, and increase significantly high density lipoprotein. On the other hand, these data did not show favourable effects on other lipid parameters, i.e. cholesterol, triglyceride, low density lipoprotein, and very low density lipoprotein.

Topics: Ascorbic Acid; Blood Pressure; Body Composition; Body Weight; Double-Blind Method; Humans; Hypercholesterolemia; Risk Factors

A significantly lower vitamin C concentration has been found in the blood and particularly in the leukocytes of hypercholesterolemic diabetic patients than of healthy blood donors. Ascorbic acid administered in a dose of 500 mg per day for 12 months to metabolically stabilized hypercholesterolemic subjects with maturity-onset diabetes mellitus (diabetic diet without insulin or diabetic drugs) brought about a striking decline of cholesterolemia and a moderate decline of triglyceridemia. The serum lipid level in the control group given placebo remained unaltered. A daily administration of 500 mg of ascorbic acid for six months failed to affect the fasting level of serum immunoreactive insulin. It is assumed that the long-term administration of ascorbic acid to maturity-onset diabetics removed the tissue ascorbate deficiency and improved the liver ability to compensate the increased endogenous synthesis of cholesterol by its enhanced transformation to bile acids.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Cholesterol; Clinical Trials as Topic; Diabetes Complications; Diabetes Mellitus; Female; Humans; Hypercholesterolemia; Leukocytes; Male; Middle Aged; Placebos; Triglycerides

Topics: Adult; Ascorbic Acid; Bile Acids and Salts; Clinical Trials as Topic; Female; Humans; Hydroxylation; Hypercholesterolemia; Male; Placebos

The current study was carried out to estimate the protective effect of methanolic extract of Chaetomorpha gracilis (MECG) against High Cholesterol Diet (HCD) induced erythrocyte damage in mice. The results of the in vitro assay showed that MECG have higher antioxidant capacities in the DPPH, TAC, ABTS, NBT, NO

Topics: Advanced Oxidation Protein Products; Animals; Antioxidants; Ascorbic Acid; Body Weight; Chlorophyta; Cholesterol; Erythrocytes; Glutathione Peroxidase; Hypercholesterolemia; Male; Mice; Oxidative Stress; Plant Extracts; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances

We study the effect of an enriched cholesterol-methionine diet administered to females on the cardiac tissue remodelling of the offspring during two successive pregnancies. Two groups are constituted, standard diet (SD) group fed a standard diet and CD group fed a combined diet (standard + cholesterol 1%-methionine 0.25%). The diet is administered during 80 days. The results show changes in serum and cardiac parameters of CD newborn, with the involvement of phospholipids (PLs) (phosphatidylethanolamine (PE) and phosphatidylcholine (PC), variations in malondialdehyde (MDA), conjugated diene (CD), and vitamin C [VIT-C] rates). Under the CD effect, serum matrix metalloproteinase (MMP)-2, pro-MMP-9, and MMP-9 activities change. As to cardiac MMP-2 activity, a rise is noticed in the second pregnancy. Histological analysis reveals constricted blood capillaries, collagen fibre deposits, and lipid accumulation in the CD newborn heart. Our study shows the amplified effect of the maternal cholesterol-methionine diet in the second pregnancy on newborn cardiac disorders (matrix remodelling, oxidative stress, and lipid accumulation).

Topics: Animals; Animals, Newborn; Ascorbic Acid; Cholesterol; Diet, High-Fat; Female; Glutathione; Hypercholesterolemia; Lipid Peroxidation; Malondialdehyde; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Methionine; Myocardium; Oxidative Stress; Phosphatidylcholines; Phosphatidylethanolamines; Pregnancy; Rabbits

The antioxidant role of tender cluster beans (Cyamopsis tetragonoloba, CB), a rich source of soluble fibre, was investigated in a hypercholesterolemia-induced oxidative stress situation in rats. In the context of dietary garlic (Allium sativa) potentiating the hypocholesterolemic influence of CB, we also examined if dietary garlic enhances the antioxidant potential of CB. Groups of Wistar rats were rendered hypercholesterolemic by feeding them a 0.5% cholesterol diet for 8 weeks. Dietary interventions were made by inclusion of 15% tender CB powder or 1% garlic powder or their combination in a high-cholesterol diet. Concentrations of antioxidant molecules and activities of antioxidant enzymes in blood and liver were examined. Dietary CB displayed an antioxidant influence in terms of elevating ascorbic acid and glutathione concentrations and stimulating the activities of antioxidant enzymes both in blood and liver. The antioxidant effect of dietary CB was generally potentiated by co-administration of garlic. Thus, consumption of tender CB and garlic together could form a strategy for improving the body's antioxidant status.

Topics: Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Antioxidants; Ascorbic Acid; Catalase; Cholesterol, Dietary; Cyamopsis; Diet; Disease Models, Animal; Garlic; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Glutathione Transferase; Hypercholesterolemia; Liver; Male; Phytotherapy; Plants, Medicinal; Rats; Rats, Wistar; Superoxide Dismutase

An investigation was made to reveal the protective effects of veratric acid (VA), a phenolic acid against atherogenic diet-induced hyperlipidemic rats. Male albino Wistar rats were fed with atherogenic diet (4% cholesterol, 1% cholic acid, and 0.5% 2-thiouracil) daily for 30 days and treated with VA (40 mg/kg body weight) daily for a period of 30 days. Rats fed with atherogenic diet showed significant (P < 0.05) elevation in the level of plasma lipids, systolic and diastolic blood pressure, oxidative stress markers (thiobarbituric acid reactive substances, lipid peroxides) and significant (P < 0.05) reduction in the activities of enzymatic (superoxide dismutase, catalase, glutathione peroxidase) and non-enzymatic (vitamin C, vitamin E, and reduced glutathione) antioxidants in erythrocytes, plasma, and tissues (liver, kidney, and aorta). Oral administration of VA (40 mg/kg body weight) for 30 days to atherogenic diet fed rats markedly attenuates systolic, diastolic blood pressure and lipid peroxidation products. Further, VA treatment significantly improved enzymatic and non-enzymatic antioxidants levels and showed beneficial effects on lipid profile in atherogenic diet rats. All the above alterations were supported by histopathological observations. These results indicate that oral administration of VA ameliorates atherogenic diet-induced hyperlipidemia in rats by its free radical scavenging; improving the antioxidants and lipid lowering properties.

Topics: Animals; Anticholesteremic Agents; Aorta, Thoracic; Ascorbic Acid; Blood Pressure; Body Weight; Catalase; Cholesterol; Diet, Atherogenic; Energy Metabolism; Erythrocytes; Glutathione; Glutathione Peroxidase; Hypercholesterolemia; Kidney; Lipid Peroxidation; Lipids; Liver; Male; Oxidative Stress; Rats; Rats, Wistar; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Vanillic Acid; Vitamin E

The effect of Monascus purpureus red mould rice (RMR) on modulation of lipid metabolism and oxidative stress was studied in hypercholesterolemic rats. Cholesterol feeding for 14 weeks caused a significant increase in the lipid peroxides and total thiols and antioxidant enzymes, viz. glutathione peroxidase (GPx), glutathione reductase (GRd), superoxide dismutase (SOD) and catalase (CAT) in serum and liver in comparison to the control group. However, supplementation of RMR to hypercholesterolemic rats at 8, 12 and 16% significantly increased the GRd, GPx, SOD and CAT activities in serum and liver tissues. Furthermore, RMR feeding significantly decreased total thiols and lipid peroxides and also increased other antioxidant molecules such as glutathione and ascorbic acid in high-cholesterol fed rats. The efficiency of RMR (16%) in modulating the antioxidant molecules and antioxidant enzymes is comparable to standard drug-lovastatin. Thus, this study suggests that the long-term administration of RMR may play an important role in suppressing oxidative stress and, thus, may be useful for the prevention and/or early treatment of hypercholesterolemia.

Topics: Animals; Antioxidants; Ascorbic Acid; Catalase; Cholesterol; Fermentation; Glutathione Reductase; Hypercholesterolemia; Lipid Peroxidation; Liver; Lovastatin; Male; Monascus; Oryza; Oxidative Stress; Rats; Rats, Wistar; Superoxide Dismutase

The anti-lipidemic effects of orally administered antioxidant vitamins (vitamin A, vitamin C and vitamin E) individually and in combination were studied in cholesterol-fed rabbits and compared to the group of hypercholesterolemic animals that were treated with simvastatin. All treatment groups exhibited a decrease in serum total cholesterol, low density lipoprotein-cholesterol (LDL-C) and triglycerides concentrations, whilst vitamin C, vitamin E, the combination and simvastatin showed a more profound decrease in the lipid profile than vitamin A at different time intervals. The order of increase in high density lipoprotein-cholesterol (HDL-C) levels remained in favour of simvastatin, as none of the antioxidant vitamins treated group could exhibit a profound increase in the HDL-C.

Topics: Animals; Antioxidants; Ascorbic Acid; Cholesterol; Cholesterol, Dietary; Cholesterol, HDL; Cholesterol, LDL; Hypercholesterolemia; Male; Rabbits; Simvastatin; Triglycerides; Vitamin A; Vitamin E; Vitamins

Hypercholesterolaemia and oxidative stress are well-known risk factors in coronary artery diseases. Diphenyl diselenide is a synthetic organoselenium compound that has been shown to have in vitro and in vivo antioxidant properties. In this study, we investigated whether diphenyl diselenide could reduce the hypercholesterolaemia and diminish the tissue oxidative stress in cholesterol-fed rabbits. Twenty-four New Zealand white male rabbits were randomly divided into four groups. Each group was fed a different diet as follows: Control group--regular chow; Cholesterol group--1% cholesterol-enriched diet; diphenyl diselenide group--regular diet supplemented with 10 ppm diphenyl diselenide; and Chol/diphenyl diselenide group--the same cholesterol-rich supplemented with 10 ppm diphenyl diselenide. After 45 days of treatment, the rabbits were killed and the blood, liver, and brain were used for laboratory analysis. The results showed that the serum levels of total cholesterol were markedly increased in cholesterol-fed rabbits and the consumption of diphenyl diselenide decreased these levels approximately twofold in Chol/diphenyl diselenide rabbits (P < 0.05). The intake of diphenyl diselenide by hypercholesterolaemic rabbits diminished the serum and hepatic thiobarbituric acid reactive substances levels as well as the production of reactive oxygen species in the blood and brain (P < 0.05) when compared to the cholesterol group. In addition, diphenyl diselenide supplementation increased hepatic and cerebral delta-aminolevulinic dehydratase activity and hepatic non-protein thiol groups levels despite hypercholesterolaemia (P < 0.05). In summary, the results showed that diphenyl diselenide reduced the hypercholesterolaemia and the oxidative stress in cholesterol-fed rabbits.

Topics: Animal Feed; Animals; Antioxidants; Ascorbic Acid; Benzene Derivatives; Brain; Brain Chemistry; Cholesterol; Cholesterol, Dietary; Hypercholesterolemia; Liver; Male; Organoselenium Compounds; Oxidative Stress; Porphobilinogen Synthase; Rabbits; Random Allocation; Reactive Oxygen Species; Thiobarbituric Acid Reactive Substances; Triglycerides

Oxidative stress has been linked to such degenerative diseases as atherosclerosis, and it has been suggested that increased dietary intake of antioxidants may reduce its progression.. To determine the effect of mandarin juice consumption on biomarkers related to oxidative stress in hypercholesterolemic children.. The diet of 48 children with plasma cholesterol >200 mg/dL and low-density lipoprotein cholesterol >130 mg/dL was supplemented for 28 days with 500 mL/day of pure (100%) mandarin juice (Citrus clementina Hort. ex Tan.). The composition of the mandarin juice was analyzed, and its antioxidant antiradical activity was evaluated in vitro. Malondialdehyde, carbonyl groups, vitamins E and C, erythrocyte-reduced glutathione, and plasma lipids were measured at the onset and at the end of the supplementation period. The paired Student t test was used to compare values before and after supplementation.. Mandarin juice exerted a strong antioxidant effect mainly due to its high hydroxyl activity and, to a lesser extent, to its superoxide scavenger activity. At the end of the study, levels of the plasma biomarkers of oxidative stress were significantly decreased (malondialdehyde -7.4%, carbonyl groups -29.1%, P < 0.01), whereas the plasma antioxidants vitamin E and C (13.5%, P < 0.001 and 68.2%, P < 0.00001, respectively) and intraerythrocyte glutathione level (36.7%, P < 0.00001) were significantly increased. Plasma lipids and antibodies to oxidized low-density lipoproteins remained unchanged.. Regular ingestion of mandarin juice significantly reduces plasma biomarkers of lipid and protein oxidation and enhances the antioxidant status of consumers.

Topics: Antioxidants; Ascorbic Acid; Beverages; Biomarkers; Child; Cholesterol; Citrus; Dietary Supplements; Female; Free Radical Scavengers; Humans; Hypercholesterolemia; Lipid Peroxidation; Lipids; Male; Malondialdehyde; Nutritional Status; Oxidation-Reduction; Oxidative Stress; Vitamin E

Oxidative stress is believed to contribute to the pathogenesis of hypercholesterolaemic atherosclerosis; hence, various antioxidant compounds are being evaluated for potential anti-atherogenic effects. The present study assessed the efficacy of epigallocatechin gallate (EGCG), an antioxidant component of the plant Camellia sinensis, in improving serum lipid profile and antioxidant parameters in erythrocytes and cardiac tissue in rats fed an atherogenic diet. In male albino Wistar rats fed an atherogenic diet for 30 days, significantly increased serum levels of total cholesterol, triglycerides and lipoprotein cholesterol fractions and cardiac risk ratio were noted, compared with levels in rats fed a normal diet. Intraperitoneal administration of EGCG (100 mg/kg) for 7 or 15 days to the atherogenic diet-fed rats resulted in significantly lower serum levels of total cholesterol, triglycerides, low-density and very low density lipoprotein cholesterol fractions and a significantly higher serum level of high-density lipoprotein cholesterol compared with levels in atherogenic diet-fed, saline-treated rats. Significantly higher mean malondialdehyde levels and significantly lower mean activities of antioxidant enzymes and mean levels of non-enzymatic antioxidants occurred in atherogenic diet-fed rats compared with those fed a normal diet. When atherogenic diet-fed rats received EGCG treatment for 7 or 15 days, significantly lower mean levels of MDA, higher mean levels of non-enzymatic antioxidants and higher mean activities of enzymatic antioxidants occurred, compared with those in saline-treated rats. Thus, EGCG appears to ameliorate disruptions of serum lipid profile and of antioxidant parameters in erythrocyte and cardiac tissue of Wistar rats fed an atherogenic diet; these results may be relevant to treating human atherosclerosis.

Topics: Animals; Anticholesteremic Agents; Antioxidants; Aorta, Thoracic; Ascorbic Acid; Atherosclerosis; Camellia sinensis; Catalase; Catechin; Diet, Atherogenic; Erythrocytes; Glutathione Peroxidase; Hypercholesterolemia; Injections, Intraperitoneal; Lipid Peroxidation; Lipids; Male; Oxidative Stress; Plant Extracts; Rats; Rats, Wistar; Superoxide Dismutase; Vitamin E

1. The present study examined the efficacy of Chlorophytum borivilianum root (powder) in modulating the hyperlipaemic/hypercholesteraemic conditions in male albino rats. 2. Administration of C. borivilianum (0.75 and 1.5 g root powder/rat per day for 4 weeks) to hypercholesteraemic rats significantly increased high-density lipoprotein-cholesterol levels and decreased plasma and hepatic lipid profiles. 3. In addition, there were significant increases in faecal cholesterol, neutral sterol and bile acid excretion with elevated hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and bile acid production. 4. Furthermore, the hypercholesteraemic rats treated with both doses of C. borivilianum also exhibited increases in superoxide dismutase and ascorbic acid levels. 5. Normocholesteraemic animals treated with both doses of C. borivilianum root powder did not show any significant variation in either lipid or anti-oxidant profiles, except for an increase in the hepatic ascorbic acid concentration compared with their untreated counterparts. 6. The hypolipaemic/hypocholesteraemic effect of C. borivilianum root powder appears to be mediated by an increase in cholesterol turnover via increased faecal cholesterol excretion and, second, through an endogenous cholesterol conversion into bile acid. 7. Administration of C. borivilianum root powder also increased the activities of anti-oxidant enzymes and vitamin C levels, which may have enhanced the anti-oxidant capacity of the liver.

Topics: Animals; Antioxidants; Ascorbic Acid; Bile Acids and Salts; Catalase; Cholesterol; Diet; Feces; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hyperlipidemias; Liliaceae; Lipid Metabolism; Lipids; Liver; Male; Plant Extracts; Plant Roots; Rats; Sterols; Superoxide Dismutase; Triglycerides

High-fat diets and oxidative damage may contribute to the development of type 2 diabetes. Hypolipidaemic drugs and antioxidants were supposed to prevent the development of the disease. In this study, we investigated preventive effects of fenofibrate (200 mg kg(-1)), vitamin C (30 mg kg(-1)), combination of both in mice induced by streptozotocin (35 mg kg(-1)) and soluble lard (15 ml kg(-1)). The results showed the mice demonstrated hyperglycaemia and hypercholesterolaemia, visceral fat accumulation, and a slight increase in liver glycogen/triglyceride and oxidative stress within 60 days of treatment. Fenofibrate enhanced insulin sensitivity, improved glycaemic control, lowered serum triglycerides, reduced body and visceral fat weights, and decreased liver glycogen/lipid levels but showed hepatotoxicity in the mice. Vitamin C neither itself prevented nor enhanced preventive effects of fenofibrate on glucose and lipid metabolism but partly attenuated the hepatotoxicity of fenofibrate. These results suggest that fenofibrate inhibit development of type 2 diabetes induced by high-fat diets and oxidative stress. However, here, vitamin C just can serve as an adjunct to fenofibrate therapy against its hepatotoxicity. In the future study, we should investigate if higher dosage of vitamin C or other antioxidants would enhance preventive effects of fenofibrate in type 2 diabetes.

Topics: Animals; Antioxidants; Ascorbic Acid; Blood Glucose; Chemical and Drug Induced Liver Injury; Cholesterol; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Dietary Fats; Drug Therapy, Combination; Fenofibrate; Glycogen; Hypercholesterolemia; Hyperglycemia; Hypoglycemic Agents; Hypolipidemic Agents; Insulin Resistance; Intra-Abdominal Fat; Liver; Liver Diseases; Male; Matrix Metalloproteinase 9; Mice; Oxidative Stress; Streptozocin; Triglycerides

The study evaluates the effect of a high supplemental dose of ascorbic acid (AA) on plasma concentrations of total cholesterol (TC), triglycerides (TG), total lipids (TL), and lipoprotein fractions high-density, very-low-density-, and low-density lipoprotein (HDL, VLDL, LDL) in guinea pigs fed with atherogenic diet.. Group I consisted of 5 normally fed guinea pigs plus a low dose of AA (1 mg/100 g/day), group II consisted of 7 guinea pigs fed with food enriched with 2% cholesterol plus a low dose of AA (1 mg/100 g/day), and group III consisted of 7 guinea pigs fed with food enriched with 2% cholesterol plus a high dose of AA (30 mg/100 g/day). Cholesterolemic factors concentrations were determined after nine weeks.. Concentrations of TC, TG, TL, LDL, and VLDL were increased in group II compared to group I (p < 0.01 for all differences). Supplementation with a high dose of AA resulted in decreased concentrations of TC (p < 0.01), TG (p < 0.01), TL (p < 0.01), and LDL (p < 0.01) in group III compared to group II. Additionally, concentration of HDL was increased in group III compared to group II (p < 0.01).. High-dose AA supplementation to an atherogenic diet decreases concentrations of TC, TG, TL, and LDL and increases concentration of HDL compared to low-dose AA.

Topics: Animals; Ascorbic Acid; Cholesterol; Diet, Atherogenic; Dietary Supplements; Dose-Response Relationship, Drug; Guinea Pigs; Hypercholesterolemia; Lipids; Lipoproteins; Male; Risk Factors; Triglycerides

The notion that oxidation of lipids and propagation of free radicals may contribute to the pathogenesis of atherosclerosis is supported by a large body of evidence. To circumvent the damage caused by oxygen free radicals, antioxidants are needed which provide the much needed neutralization of free radical by allowing the pairing of electrons. In this study we have investigated the effect of ascorbic acid, a water soluble antioxidant on the development of hypercholesterolemia induced atherosclerosis in rabbits. Rabbits were made hypercholesterolemic and atherosclerotic by feeding 100 mg cholesterol/day. Different doses of ascorbic acid were administered to these rabbits. Low dose of ascorbic acid (0.5 mg/100 g body weight/day) did not have any significant effect on the percent of total area covered by atherosclerotic plaque. However, ascorbic acid when fed at a higher dose (15 mg/100 g body weight/day) was highly effective in reducing the atherogenecity. With this dose the percent of total surface area covered by atherosclerotic plaque was significantly less (p < 0.001). This suggests that use of ascorbic acid may have great promise in the prevention of hypercholesterolemia induced atherosclerosis.

Topics: Animals; Antioxidants; Aorta; Ascorbic Acid; Carotid Stenosis; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Coronary Artery Disease; Diet, Atherogenic; Hypercholesterolemia; Lipid Peroxidation; Malondialdehyde; Rabbits

Accumulation of advanced glycation end-products (AGEs) has been implicated in the pathogenesis of chronic transplant dysfunction and cardiovascular disease in renal transplant recipients. We aimed to investigate which factors are associated with tissue AGE accumulation in renal transplant recipients.. The AGE accumulation was assessed using a validated skin-autofluorescence reader (AFR) in 285 consecutive renal transplant recipients (57% male, aged 50+/-12 years) visiting the outpatient clinic at a median (interquartile range) time of 73 (32-143) months after transplantation. Furthermore, various transplant- and recipient-related factors of interest were collected.. Average skin-autofluorescence of lower arm and leg was 2.7+/-0.8 a.u. Skin-autofluorescence was positively determined by recipient age, systolic blood pressure, smoking, high-sensitivity C-reactive protein, duration of pre-transplant dialysis, and negatively by plasma vitamin C levels, creatinine clearance at baseline, and change in creatinine clearance since one year after transplantation in linear multivariate regression analysis. Together, these factors explained 41% of the variance of skin-autofluorescence.. Skin-autofluorescence was associated with several risk factors for cardiovascular disease and chronic renal transplant dysfunction. These results are in line with the hypothesis that AGEs play a role in the pathogenesis of these conditions in renal transplant recipients. Prospective studies are required to investigate whether the AFR can be used as a simple, non-invasive tool to identify and monitor patients at risk for chronic renal transplant dysfunction and cardiovascular disease.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Ascorbic Acid; C-Reactive Protein; Cardiovascular Diseases; Comorbidity; Creatinine; Delayed Graft Function; Diabetes Complications; Female; Fluorometry; Forearm; Glycated Hemoglobin; Glycation End Products, Advanced; Histocompatibility; Humans; Hypercholesterolemia; Hypertension; Immunosuppressive Agents; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Leg; Linear Models; Male; Middle Aged; Obesity; Risk Factors; Skin; Smoking; Vitamin E

The susceptibility of low-density lipoprotein (LDL) to oxidation is thought to be a crucial factor responsible for atherogenesis. There is substantial evidence for a role of dietary antioxidants in the prevention of atherogenesis and the protective effect of antioxidant nutrients may be mediated through inhibition of the oxidative modification of LDL.. We performed in vitro oxidation of LDL derived from normal and hypercholesterolemic individuals in absence and presence of different doses of ascorbic acid.. The serum lipid peroxidation level was significantly increased in hypercholesterolemic patients and their LDL has shown a greater propensity towards in vitro oxidation. Hypercholesterolemic LDL required a higher amount of ascorbic acid to reduce its oxidation level as compared to LDL isolated from normocholesterolemic individuals.. This observation may be of importance in designing future studies of antioxidant supplementation in patients with hypercholesterolemia which is one of the major risk factors for atherosclerosis.

Topics: Adult; Ascorbic Acid; Case-Control Studies; Dose-Response Relationship, Drug; Humans; Hypercholesterolemia; Lipid Peroxidation; Lipoproteins, LDL; Male; Middle Aged; Oxidation-Reduction

Intima-media remodeling, as frequently assessed by changes in the external elastic lamina-to-lumen area (EELLA), is well-described in coronary artery disease in contrast to adventitial remodeling, especially in the early disease stage.. Female domestic pigs were randomized to one of the following 12-week treatment groups: normal diet (N; n=6), high-cholesterol diet (HC; n=6), or renovascular hypertension (HT; n=4). Low-density lipoprotein (LDL) cholesterol serum concentration was higher in HC than in N and HT (395.5+/-106 versus 38.6+/-14 and 37.2+/-6.8 mg/dL; P<0.05 for both). Mean arterial pressure was higher in HT than in N and HC (141.3+/-21 versus 107.4+/-8.9 and 109.4+/-7.8 mm Hg; P<0.05 for both). EELLA ratio, as assessed by morphometry, was similar in N, HC, and HTN (1.03+/-0.32 versus 0.95+/-0.29 and 1.01+/-0.09; P<0.05 for both). Coronary vasa vasorum density, as assessed by 3-dimensional micro-computed tomography, was higher in HC than in N and HT (3.4+/-1.0 versus 1.9+/-0.3 and 2.0+/-1.2; P<0.05 for both). In contrast, immunostaining showed a higher collagen III content and the presence of adventitial myofibroblasts in HT compared with N and HC.. The current study suggests that adventitial remodeling precedes intima and media remodeling of coronary arteries early after exposure to hypercholesterolemia and hypertension, with distinct qualitative differences between them. Intima-media remodeling is well-described in coronary artery disease in contrast to adventitial remodeling. Results of the current study on coronary arteries of pigs, randomized to 12 weeks of normal diet (N), hypercholesterolemic diet (HC), or renovascular hypertensive (HT), indicate that adventitial remodeling precedes intima-media remodeling early after risk factor exposure with distinct qualitative differences.

Topics: Actins; Animals; Ascorbic Acid; Blood Pressure; Catalase; Cholesterol, Dietary; Collagen Type III; Coronary Vessels; Diet, Atherogenic; Female; Fibroblasts; Glutathione Peroxidase; Hypercholesterolemia; Hypertension, Renovascular; Myoblasts; Random Allocation; Superoxide Dismutase; Sus scrofa; Tunica Intima; Vasa Vasorum; Vitamin E

We tested the hypothesis that CD40 ligand (CD40L) induces a prothrombotic state by enhancing oxidative stress.. Patients with hypercholesterolemia show an ongoing prothrombotic state, but the underlying mechanism is still unclear.. Circulating levels of the soluble form of CD40L (sCD40L), prothrombin fragment (F1+2, a marker of thrombin generation), and 8-hydroxy-2'-deoxyguanosine (8-OHdG, a marker of oxidative stress) were measured in 40 patients with hypercholesterolemia and in 20 age- and gender-matched healthy subjects.. Patients with hypercholesterolemia showed significantly higher levels of sCD40L (p <0.005), 8-OHdG (p <0.005), and prothrombin F1+2 (p <0.005), as compared with control subjects. Soluble CD40L significantly correlated with 8-OHdG (r=0.85, p <0.0001) and prothrombin F1+2 (r=0.83, p <0.0001); a significant correlation between 8-OHdG and prothrombin F1+2 was also observed (r=0.64, p <0.0001). An in vitro study demonstrated that CD40L-stimulated monocytes from patients with hypercholesterolemia expressed more tissue factor (TF) and prothrombin F1+2 than monocytes from controls; co-incubation of monocytes with either an inhibitor of NADPH oxidase or an inhibitor of phosphatidylinositol-3-kinase significantly reduced CD40L-mediated clotting activation. A marked inhibition of CD40L-mediated clotting activation was also observed in two male patients with hereditary deficiency of gp91 phox, the central core of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Finally, we demonstrated that CD40L-mediated clotting activation was significantly inhibited by vitamin C, a known antioxidant.. This study indicates that in patients with hypercholesterolemia, CD40L over-expresses TF and increases the thrombin generation rate by an oxidative stress-mediated mechanism that requires the activation of NADPH oxidase.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Antioxidants; Ascorbic Acid; Blood Coagulation; CD40 Ligand; Cross-Sectional Studies; Deoxyguanosine; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Monocytes; Oxidative Stress; Peptide Fragments; Prothrombin; Thrombin

Vascular endothelial growth factor (VEGF) is believed to play a role in the development of atherosclerosis and has been found to be increased in hypercholesterolemia. We examined the hypothesis that endothelial VEGF and VEGF receptor-2 (VEGFR-2) expression is upregulated by hypercholesterolemic low-density lipoprotein (LDL) and, because it could be driven by oxidative stress, we tested whether vitamin C and E supplementation could modulate it.. Native LDL were characterized after isolation from adult normal (C-LDL), hypercholesterolemic (HC-LDL) and hypercholesterolemic mini-pigs receiving vitamins C and E (HCV-LDL). VEGF, VEGFR-2, HIF-1 alpha and superoxide anion (O(2)(-)) productions were measured in porcine coronary endothelial cells (ECs) incubated for 48 h with native LDL. The effect of exogenous ascorbic acid and alpha- or beta-tocopherol was also studied.. HC-LDL, with high cholesterol (P<0.05) and reduced tocopherol/cholesterol ratio (P<0.05), increased significantly VEGF and VEGFR-2 (p<0.001) in EC, associated with higher O(2)(-) and HIF-1 alpha expression, in comparison with C-LDL and HCV-LDL. The addition of vitamin C and alpha- or beta-tocopherol to the culture medium prevented the induction of VEGF and VEGFR-2 expression by HC-LDL, both at mRNA and protein levels.. Our data suggest HC-LDL induce endothelial VEGF and VEGFR-2 overexpression at least by increasing oxidative stress, and HIF-1 alpha is one of the signaling mechanisms involved. Prevention of VEGF and VEGFR-2 upregulation could help explain the beneficial effects of vitamins C and E in hypercholesterolemia-induced experimental atherosclerosis.

Topics: Animals; Antioxidants; Ascorbic Acid; Cells, Cultured; Cholesterol, LDL; Endothelium, Vascular; Hypercholesterolemia; Hypoxia-Inducible Factor 1, alpha Subunit; Male; Reactive Oxygen Species; Reverse Transcriptase Polymerase Chain Reaction; Swine; Swine, Miniature; Transcription Factors; Up-Regulation; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2; Vitamin E

Oxidative stress is thought to be involved in the pathogenesis of age-related diseases, such as atherosclerosis and retinal degeneration. The current study was conducted to examine vitreoretinal oxidative status in a model of porcine hypercholesterolemia to identify morphologic alterations and analyze the effect of dietary supplementation with vitamins C and E.. Adult miniature pigs were fed standard chow, cholesterol-rich chow, or a cholesterol-rich diet supplemented with vitamins C and E. Total cholesterol, triglycerides, high-density lipoproteins, lipid peroxidation, and tocopherol were measured in plasma. Lipid peroxidation and nitric oxide (NO) metabolites were measured in vitreous and retinal homogenates. Superoxide anion release in the retinal pigment epithelium (RPE) was analyzed by chemiluminescence. Retinal morphology was studied by transmission electron microscopy.. The high-cholesterol group, with increased retinal oxidative stress (P < 0.01) and NO metabolites in the retina (P < 0.05), had increased superoxide anion release (P < 0.05) and showed development of pyknosis, irregular nuclear membranes, and cytoplasmic accumulation of lipids and autophagocytic vacuoles in the RPE cells. Vitamins C and E prevented biochemical changes and most ultrastructural alterations in the RPE.. The results suggest an evolving role for hypercholesterolemia through increased retinal oxidative stress and NO synthesis that could be responsible for retinal ultrastructural alterations. The beneficial effects of vitamins C and E in the retinal tissue further support this hypothesis.

Topics: Animals; Antioxidants; Ascorbic Acid; Cholesterol; Cholesterol, Dietary; Dietary Supplements; Hypercholesterolemia; Lipid Peroxidation; Male; Nitric Oxide; Oxidative Stress; Retina; Retinal Diseases; Superoxides; Swine; Swine, Miniature; Tocopherols; Triglycerides; Vitamin E; Vitreous Body

The effects of amla on low-density lipoprotein (LDL) oxidation and cholesterol levels were investigated in vitro and in vivo using Cu(2+)-induced LDL oxidation and cholesterol-fed rats. SunAmla and ethyl acetate (EtOAc) extract of amla significantly inhibited thiobarbituric acid (TBA)-reactive substance level in the Cu(2+)-induced LDL oxidation and the effects were stronger than those of probucol. In addition, the administration of SunAmla (at a dose of 20 or 40 mg/kg body weight/d) or EtOAc extract of amla (at a dose of 10 or 20 mg/kg body weight/d) for 20 d to rats fed 1% cholesterol diet significantly reduced total, free and LDL-cholesterol levels in a dose-dependent manner, and EtOAc extract of amla exhibited more potent serum cholesterol-lowering effect than SunAmla in the same amount. Furthermore, the oxidized LDL level in serum was markedly elevated in cholesterol-fed control rats as compared with normal rats, while it was significantly decreased by the administration of SunAmla or EtOAc extract of amla. Moreover, the serum TBA-reactive substance level was also significantly decreased after oral administration of SunAmla or EtOAc extract of amla. These results suggest that amla may be effective for hypercholesterolemia and prevention of atherosclerosis.

Topics: Animals; Ascorbic Acid; Body Weight; Cholesterol; Cholesterol, Dietary; Flavonoids; Hypercholesterolemia; Lipid Peroxidation; Lipoproteins, LDL; Liver; Male; Organ Size; Phenols; Phyllanthus emblica; Plant Extracts; Polyphenols; Rats; Rats, Wistar

The levels of electronegative low-density lipoprotein (LDL-), LDL cholesterol oxidability, and plasma levels of molecular antioxidants and of beta(2)-glycoprotein I (beta(2) GPI) were studied in a group of 10 hypercholesterolemic (HC) and 10 normocholesterolemic (NC) elderly subjects. HC subjects showed significantly higher levels of cholesterol, LDL cholesterol, LDL-, and beta(2)GPI than NC, whereas high-density lipoprotein cholesterol and alpha-tocopherol levels were lower in HC as compared with NC subjects. Correlations among LDL- levels, LDL oxidation lag time, beta(2)GPI, and antioxidant plasma levels were studied in 100 HC elderly subjects. Lag time for in vitro LDL oxidation positively correlated with ubiquinol-10 levels (p = 0.008), but not with other antioxidants studied or beta(2)GPI. LDL- and alpha-tocopherol levels showed an inverse and significant correlation (p = 0.018). beta(2)GPI and LDL cholesterol levels were correlated (p = 0.001), whereas no significance was found between LDL- and beta(2)GPI levels (p = 0.057). The physiological significance of alpha-tocopherol and ubiquinol-10 levels on LDL- levels, and the presence of high levels of beta(2)-GPI, are discussed in terms of protective mechanisms operating during the overall atherosclerosis process.

Topics: Aged; Aged, 80 and over; alpha-Tocopherol; Anticoagulants; Antioxidants; Ascorbic Acid; beta 2-Glycoprotein I; Cholesterol, LDL; Female; Glycoproteins; Humans; Hypercholesterolemia; Oxidation-Reduction; Statistics as Topic; Ubiquinone

Hypercholesterolemia (HC) and atherosclerosis can elicit oxidative stress, coronary endothelial dysfunction, and myocardial ischemia, which may induce growth-factor expression and lead to myocardial neovascularization. We tested the hypothesis that chronic antioxidant intervention in HC would attenuate neovascularization and preserve the expression of hypoxia-inducible factor (HIF)-1alpha and vascular endothelial growth factor (VEGF).. Three groups of pigs (n=6 each) were studied after 12 weeks of normal or 2% HC diet or HC+antioxidant supplementation (100 IU/kg vitamin E and 1 g vitamin C daily). Myocardial samples were scanned ex vivo with a novel 3D micro-CT scanner, and the spatial density and tortuosity of myocardial microvessels were determined in situ. VEGF mRNA, protein levels of VEGF and VEGF receptor-1, HIF-1alpha, nitrotyrosine, and superoxide dismutase (SOD) were determined in myocardial tissue. The HC and HC+antioxidant groups had similar increases in serum cholesterol levels. HC animals showed an increase in subendocardial spatial density of microvessels compared with normal (160.5+/-11.8 versus 95.3+/-8.2 vessels/cm2, P<0.05), which was normalized in HC+antioxidant (92.5+/-20.5 vessels/cm2, P<0.05 versus HC), as was arteriolar tortuosity. In addition, HC induced upregulation of VEGF, HIF-1alpha, and nitrotyrosine expression and decreased SOD expression and activity, all of which were preserved by antioxidant intervention.. Changes in myocardial microvascular architecture invoked by HC are accompanied by increases in HIF-1alpha and VEGF expression and attenuated by antioxidant intervention. This underscores a role of increased oxidative stress in modulating myocardial microvascular architecture in early atherogenesis.

Topics: Animals; Antioxidants; Arteriosclerosis; Ascorbic Acid; Cardiotonic Agents; Coronary Circulation; Diet, Atherogenic; Dinoprost; Enzyme Induction; Female; Gene Expression Profiling; Gene Expression Regulation; Heart; Hypercholesterolemia; Hypoxia-Inducible Factor 1, alpha Subunit; Imaging, Three-Dimensional; Myocardial Ischemia; Neovascularization, Pathologic; Oxidative Stress; Superoxide Dismutase; Swine; Tomography, X-Ray Computed; Transcription Factors; Tyrosine; Vascular Endothelial Growth Factor A; Vitamin E

Experimental hypercholesterolemia (HC) may lead to microvascular neovascularization, but the underlying pathogenic mechanism remains unclear. We tested the hypothesis that HC-induced intra-renal neovascularization is associated with inflammation and increased oxidative stress, and would be prevented by chronic antioxidant intervention. Kidneys were excised from pigs after a 12-wk normal (n = 10) or HC diet (n = 8), or HC diet supplemented daily with antioxidant vitamins C (1 g) and E (100 IU/kg) (HC + vitamins, n = 7). Renal cortical samples were then scanned three dimensionally with micro-computed tomography, and microvessels were counted in situ. Blood and tissue samples were removed for measurements of superoxide dismutase (SOD) activity, protein expression of the NADP(H)-oxidase subunits gp91phox, p47phox, and p67phox, vascular endothelial growth factor (VEGF) levels and mRNA, VEGF receptors (Flt-1 and Flk-1), the proinflammatory transcription factor NFkappaB, and the oxidized LDL receptor LOX-1. Microvascular spatial density was significantly elevated in HC compared with normal kidneys but preserved in HC + vitamins. Expression of gp91phox and p67phox was decreased in HC pigs after antioxidant intervention, and SOD improved. The increased renal expression of VEGF and Flk-1 in HC was blunted in HC + vitamins, as were the significant increases in LOX-1, NFkappaB, and interstitial fibrosis. This study shows that renal cortical neovascularization elicited by diet-induced HC is associated with renal inflammation, fibrosis, and upregulation of VEGF and its receptor Flk-1, likely mediated by increased endogenous oxidative stress. Chronic antioxidant supplementation may preserve the kidney in HC.

Topics: Animals; Antioxidants; Ascorbic Acid; Blotting, Western; Body Weight; DNA, Complementary; Enzyme-Linked Immunosorbent Assay; Female; Fibrosis; Hypercholesterolemia; Image Processing, Computer-Assisted; Inflammation; Kidney; Membrane Glycoproteins; Microcirculation; NADPH Oxidase 2; NADPH Oxidases; Neovascularization, Pathologic; NF-kappa B; Oxidation-Reduction; Phosphoproteins; Receptors, Vascular Endothelial Growth Factor; Reverse Transcriptase Polymerase Chain Reaction; RNA; RNA, Messenger; Superoxide Dismutase; Swine; Tomography, X-Ray Computed; Vascular Endothelial Growth Factor A

Degradation of extracellular matrix, particularly interstitial collagen, promotes plaque instability and contributes to restenosis after vascular injury. We have explored the effects of vitamins C and E on the collagen content and metalloproteinase-1 (MMP-1) expression after angioplasty in hypercholesterolemic pigs. Iliac angioplasty was performed on 18 minipigs divided into three diet groups: a normal-cholesterol (NC), a high-cholesterol (HC) and a high-cholesterol plus vitamins C+E (HCV). Four weeks later, after sacrifice, the vascular collagen content and MMP-1 protein expression, along with the plasma caseinolytic activity and lipid peroxidation, were measured. MMP-1 was also determined in arterial rings stimulated with native low-density lipoproteins (LDL) isolated from experimental groups. Cholesterol-rich diet augmented plasma lipid peroxidation (P<0.05), reduced the collagen content and increased vascular MMP-1 expression after injury (P<0.05). Enhanced caseinolytic activity (identified as MMP-1) was also observed in HC plasma samples and in supernatants from arterial rings incubated with HC-LDL. Vitamins C and E markedly increased neointimal collagen content (P<0.01), reduced the hypercholesterolemia-induced changes in vascular MMP-1 (P<0.05) and diminished plasma and ex vivo caseinolytic activity. Vitamins C and E may help stabilize atherosclerotic plaque after angioplasty and favor vascular remodeling by increasing collagen content and reducing vascular MMP-1 expression in porcine hypercholesterolemia.

Topics: Analysis of Variance; Angioplasty; Animals; Antioxidants; Arteriosclerosis; Ascorbic Acid; Cholesterol; Cholesterol, Dietary; Diet, Atherogenic; Disease Models, Animal; Hypercholesterolemia; Iliac Artery; Lipid Peroxidation; Matrix Metalloproteinase 1; Probability; Sensitivity and Specificity; Swine, Miniature; Vitamin E

Coronary endothelial dysfunction is associated with an increase in cardiac events. Hypercholesterolemia (HC) and hypertension (HT) are both associated with endothelial dysfunction, and their coexistence is associated with an increased incidence of cardiac events in epidemiological studies. However, pathogenic mechanisms are poorly understood. Here we studied the effects of coexisting HC and HT on coronary endothelial function.. Four groups of pigs were studied after 12 weeks of a normal diet (n=9), a 2% HC diet (n=9), HT (achieved by unilateral renal artery stenosis, n=8), or HC+HT (n=6). Coronary endothelial function was tested, in epicardial arteries and arterioles, by using organ chamber techniques. Oxidative stress was measured in coronary artery tissue. Vasodilatory response to bradykinin and calcium ionophore was significantly impaired in animals with HC+HT compared with each risk factor alone (P<0.05 for both). In animals with coexistent HC and HT, the increase in oxidative stress was more pronounced compared with each risk factor alone (P<0.05). Furthermore, chronic antioxidant supplementation significantly improved coronary artery vasoreactivity.. These results suggest that HC and HT have a synergistic deleterious effect on coronary endothelial function, associated with increased oxidative stress. This interaction may contribute to the increased incidence of coronary heart disease and cardiac events seen when HC and HT coexist.

Topics: Animals; Antioxidants; Ascorbic Acid; Bradykinin; Calcimycin; Coronary Artery Disease; Coronary Vessels; Cyclic GMP; Diet, Atherogenic; Endothelin-1; Endothelium, Vascular; Female; Hemodynamics; Hypercholesterolemia; Hypertension, Renovascular; Lipids; Nitric Oxide; Nitroprusside; Oxidative Stress; Renal Artery Obstruction; Renin; Substance P; Swine; Vasodilator Agents; Vitamin E

Oxygen radical species can influence vascular tone, and antioxidants may have hemodynamic and vascular effects. To date, the vascular effects of chronic intervention with a combination of antioxidant vitamins E and C on renal blood flow (RBF) in hypercholesterolemia (which increases oxidative stress) have not been fully defined. The aim of this intervention study was to explore the involvement of increased oxidative stress in pig RBF disturbance by using chronic dietary antioxidant vitamin intervention. Responses of RBF to the acetylcholine (Ach) were measured in vivo using electron beam computed tomography (EBCT). Acetylcholine significantly increased RBF in normal and hypercholesterolemic + vitamins (P < 0.05 for both), but not in hypercholesterolemic pigs (P=0.1). In normocholesterolemic + vitamins pigs, Ach infusion did not induce any further increase in RBF, but RBF was similar to that observed in normal and hypercholesterolemic + vitamins under the same conditions, and tended to be higher than in hypercholesterolemic pigs (P=0.06). Thus, antioxidants improve RBF in hypercholesterolemic pigs and this effect may help to prevent renal diseases and hypertension in animals.

Topics: Acetylcholine; Animals; Antioxidants; Ascorbic Acid; Cholesterol; Cholesterol, LDL; Dietary Supplements; Hypercholesterolemia; Radiography; Renal Circulation; Swine; Swine Diseases; Vitamin E

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

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

Impaired endothelium-dependent vasodilation has been associated with decreased NO bioavailability in hypercholesterolemia. This study aimed to determine whether antioxidant vitamins C and E could improve hypercholesterolemia-derived endothelial dysfunction in the porcine model, and whether observed in vivo results could be reproduced in vitro by incubation of coronary endothelial cells (EC) in the presence of native low-density lipoproteins (LDL). Adult mini-pigs were fed standard (C), cholesterol rich (HC) or cholesterol rich diet supplemented with vitamins C and E (HCV). Endothelium-dependent blood flow increase in response to acetylcholine was determined. Endothelial nitric oxide synthase (eNOS) expression was measured in arterial samples and in EC incubated with LDL isolated from porcine plasma. Vasomotor response to acetylcholine in HC was significantly lower (P<0.05) than control and HCV. There was a significant (P<0.05) decrease in eNOS immunoreactivity in HC, compared with HCV and control. Native LDL from HC, but not from HCV, induced a significant decrease in eNOS expression. Vitamins C and E treatment improved the endothelium-dependent vasomotor capacity and prevented decreased expression of eNOS in hypercholesterolemic pigs. A similar effect could be demonstrated in vitro, by incubation of EC with native LDL, suggesting that the effect of physiologically-modified LDL on eNOS could have a role in recovering vascular function.

Topics: Analysis of Variance; Animals; Ascorbic Acid; Blotting, Western; Cells, Cultured; Coronary Vessels; Dietary Supplements; Disease Models, Animal; Down-Regulation; Endothelium, Vascular; Hypercholesterolemia; Immunohistochemistry; Male; Nitric Oxide Synthase; Probability; Reference Values; Sensitivity and Specificity; Statistics, Nonparametric; Swine; Vitamin E

Hypercholesterolemia (HC), a pro-oxidant condition, activates nuclear factor-kappa beta (NF-kappa B) and is associated with coronary endothelial dysfunction. The physiological significance of in vivo chronic antioxidant intervention on HC-induced NF-kappa B activation and coronary endothelial function remains unclear.. Four groups of pigs were studied after 12 weeks of normal diet, normal diet with concomitant antioxidant intervention (100 IU/kg of vitamin E and 1 g of vitamin C daily), 2% HC diet, or HC diet+antioxidant supplementation. NF-kappa B activation and the nitric oxide (NO) pathway were investigated by Western blotting and immunohistochemistry, while oxidative stress was evaluated by coronary artery tissue radical scavenger activity and levels of vitamin E and C. Endothelial function was studied in vitro by coronary vasoreactivity to bradykinin and substance P.. HC animals had increased activation of NF-kappa B, decreased endothelial NO synthase expression, and decreased radical scavenger system activity, associated with impaired coronary endothelial function. Antioxidant supplementation in HC normalized NF-kappa B activation and NO bioactivity, and preserves coronary endothelial function.. This study demonstrates for the first time that in vivo chronic interruption of the endogenous oxidative stress cascade reduces HC-induced NF-kappa B activation and normalizes NO bioactivity in association with preservation of coronary endothelial function. This study suggests a role for increased oxidative stress and NF-kappa B activation in early atherosclerosis.

Topics: Animals; Antioxidants; Ascorbic Acid; Cholesterol; Cyclic GMP; Dietary Supplements; Endothelium, Vascular; Female; Hypercholesterolemia; Muscle, Smooth, Vascular; NF-kappa B; Nitric Oxide Synthase; Oxidative Stress; Swine; Vitamin E

It is well known that eating fruits and vegetables lowers the risk of chronic diseases such as heart disease and cancer. The question of what is/are the active ingredient(s) is still unresolved. The initial hypothesis was that the antioxidant vitamins were responsible. However, recently the polyphenols have been investigated since they have been found to have beneficial properties such as being strong antioxidants. We measured the polyphenol content of citrus juices by an oxidation-reduction colorimetric method (Folin) using catechin as the standard. The order was tangerine juice > grapefruit juice > orange juice. The antioxidant contribution of ascorbic acid was measured by the difference in Folin reactive content following removal by ascorbate oxidase. Ascorbate contributed 56 to 77% of the antioxidant content of orange juice, 46% of the single tangerine juice measured, and 66 to 77% of grapefruit juices. Polyphenol quality in the juices was analyzed by using the inhibition of lower density lipoprotein oxidation promoted by cupric ion, an in vitro model of heart disease. Quality decreased in the following order: orange juice > grapefruit juice > tangerinejuice. In orange juice polyphenols accounted for 84-85% of antioxidant quality. The pure polyphenol hesperidin, which is common in juices, ascorbic acid, and the citrus juices, were not able to bind with LDL+VLDL and protect it from oxidation. In a hamster model of atherosclerosis, the juices were able to significantly inhibit atherosclerosis and lowered cholesterol and triglycerides. Ascorbic acid alone in the dose provided by the juices was found to have the same effect on atherosclerosis. However, the polyphenols in the citrus

Topics: Adult; Animals; Antioxidants; Arteriosclerosis; Ascorbic Acid; Beverages; Citrus; Cricetinae; Diet, Atherogenic; Disease Models, Animal; Drug Evaluation; Drug Evaluation, Preclinical; Female; Flavonoids; Heart Diseases; Hesperidin; Humans; Hypercholesterolemia; Hypertriglyceridemia; Lipids; Male; Mesocricetus; Middle Aged; Oxidation-Reduction; Phenols; Plant Extracts; Polymers; Species Specificity

The plasminogen activator inhibitor-1 (PAI-1), which modulates fibrinolysis and cell migration, may influence proteolysis and neointimal formation in the arterial wall contributing to restenosis after vascular injury. Antioxidants have been proposed as inhibiting multiple proatherogenic events. We explore the effect of vitamins C and E on PAI-1 expression in an experimental model of angioplasty in hypercholesterolemic pigs.. A total of 44 Yucatan minipigs were divided into three diet groups: a normal-cholesterol (NC), a high-cholesterol (HC), and a high-cholesterol plus vitamins C+E (HCV) group. Balloon injury was induced in the right internal iliac artery 4 weeks after initiation of either dietary regimen, and plasma and tissue samples were taken at different time periods to measure PAI-1 activity and vascular inhibitor expression. The cholesterol-rich diet induced an increased in vascular PAI-1 expression in the intima, media and adventitia which was markedly reduced in the HCV group. After injury, severe structural changes were observed in NC and HC animals associated with increased systemic PAI-1 activity (P<0.001) and local PAI-1 expression being more intense in HC group. Vitamins C and E significantly reduced plasma PAI-1 activity (P=0.018) and attenuated the inhibitor expression as compared with HC.. This experimental study in a porcine model of hypercholesterolemia demonstrates that vitamins C and E reduce local and systemic PAI-1 induced after angioplasty as well as the hypercholesterolemia-induced vascular PAI-1.

Topics: Analysis of Variance; Angioplasty, Balloon; Animals; Ascorbic Acid; Cholesterol; Dietary Supplements; Hypercholesterolemia; Iliac Artery; Immunohistochemistry; In Situ Hybridization; Plasminogen Activator Inhibitor 1; Recurrence; Statistics, Nonparametric; Swine, Miniature; Vitamin E

Nitric oxide (NO) reacts with thiol-containing biomolecules to form S-nitrosothiols (RSNOs). RSNOs are considered as NO reservoirs as they generate NO by homolytic cleavage. Ceruloplasmin has recently been suggested to have a potent catalytic activity towards RSNO production. Considering that NO activity is impaired in hypercholesterolemia and that RSNOs may act as important NO donors, we investigated the relation between concentrations of ceruloplasmin and RSNOs in plasma of hypercholesterolemic (HC) patients compared to normolipidemic (N) controls. Concentrations of ceruloplasmin (0.36 +/- 0.07 x 0.49 +/- 0.11 mg/dl, N x HC), nitrate (19.10 +/- 12.03 x 40.19 +/- 18.70 microM, N x HC), RSNOs (0.25 +/- 0.20 x 0.54 +/- 0.26 microM, N x HC), nitrated LDL (19.51 +/- 6.98 x 35.29 +/- 17.57 nM nitro-BSA equivalents, N x HC), and cholesteryl ester-derived hydroxy/hydroperoxides (CEOOH, 0.19 +/- 0.06 x 1.46 +/- 0.97 microM) were increased in plasma of HC as compared to N. No difference was found for nitrite levels between the two groups (1.01 +/- 0.53 x 1.02 +/- 0.33 microM, N x HC). The concentrations of RSNOs, nitrate, and nitrated LDL were positively correlated to those of total cholesterol, LDL cholesterol, and apoB. Ceruloplasmin levels were directly correlated to apoB and apoE concentrations. Data suggest that: (i) ceruloplasmin may have a role in the enhancement of RSNOs found in hypercholesterolemia; (ii) the lower NO bioactivity associated with hypercholesterolemia is not related to a RSNOs paucity or a defective NO release from RSNOs; and (iii) the increased nitrotyrosine levels found in hypercholesterolemia indicate that superoxide radicals contribute to inactivation of NO, directly generated by NO synthase or originated by RSNO decomposition.

Topics: Apolipoproteins B; Ascorbic Acid; Catalysis; Ceruloplasmin; Cholesterol; Cholesterol Esters; Cholesterol, LDL; Humans; Hydrogen Peroxide; Hypercholesterolemia; Lipoproteins, LDL; Mercaptoethanol; Nitrates; Nitrites; Nitroso Compounds; S-Nitrosothiols; Tyrosine; Uric Acid; Vitamin E

Hypercholesterolemia and hypertension are both risk factors for end-stage renal disease. This study was designed to examine whether their coexistence augmented impairment in renal function and redox status. Regional renal hemodynamics and function in response to vasoactive challenges with acetylcholine or sodium nitroprusside were quantified by using electron-beam computed tomography in pigs after 12 weeks of either a normal (n=10) or hypercholesterolemic (n=10) diet, renovascular hypertension (n=7), or combined hypercholesterolemia+hypertension (n=6). The hypercholesterolemic and hypercholesterolemic+hypertensive groups had significantly increased serum cholesterol levels, whereas in the hypertensive and hypercholesterolemic+hypertensive groups, mean arterial pressure was significantly elevated compared with the group fed a normal diet. Basal regional renal perfusion and glomerular filtration rates were similar among the groups. In response to acetylcholine, cortical perfusion increased in normal animals (15.6+/-4.7%, P=0.002) but not in hypercholesterolemic or hypertensive animals (8.0+/-7.4% and 8.2+/-5.9%, respectively; P>0.05). Moreover, in the hypercholesterolemic+hypertensive group, cortical perfusion response was further attenuated (2.5+/-4.8%, P=0.02) and significantly different from the group fed a normal diet (P<0.05). The response to sodium nitroprusside followed a similar pattern, and the impairment was augmented in the hypercholesterolemic+hypertensive group. The functional abnormalities in hypercholesterolemia or hypertension were associated with a decrease in systemic and/or renal tissue levels of oxygen radical scavengers that was again accentuated in hypercholesterolemia+hypertension. These results demonstrate that concurrent hypercholesterolemia and hypertension have a greater detrimental effect on renal perfusion responses compared with hypercholesterolemia or hypertension alone, associated with a marked pro-oxidant shift in redox status. These effects may potentially augment renal functional impairment and play a role in the initiation and progression of renal injury in hypertension and atherosclerosis.

Topics: Acetylcholine; Animals; Ascorbic Acid; Cholesterol; Cholesterol, LDL; Free Radical Scavengers; Hemodynamics; Hypercholesterolemia; Hypertension, Renovascular; Kidney; Nitroprusside; Oxidation-Reduction; Perfusion; Swine; Tomography, X-Ray Computed; Vascular Resistance; Vasodilator Agents; Vitamin E

This study tested the hypothesis that c-Myc activation, an oxidation-sensitive transcription factor, and its binding partner Max occurs in coronary arteries of hypercholesterolemic (HC) pigs, and can be attenuated by chronic antioxidant intervention. Coronary arteries were isolated from normal, HC pigs, or HC supplemented with antioxidant vitamins (HC + vitamins). The expression of the c-Myc/Max complex, and its target genes GADD45 and p53, was studied in nonatherosclerotic, early lesions (LL), positively staining for oil-red-O, in adjacent lesion-prone regions (PL), and in healthy segments (HV). The expression of c-Myc and Max in HC was 2- to 3-fold greater in PL, and 4-fold in LL, compared to normal vessels (P < 0.01). The expression of GADD45 was down-regulated, and of p53 increased, in the same regions. These alterations were attenuated in the HC + vitamins. Thus, c-Myc activation is an early atherosclerosis, in both PL and LL coronary arterial regions, and can be blunted by chronic dietary antioxidant intervention.

Topics: Animals; Antioxidants; Ascorbic Acid; Basic-Leucine Zipper Transcription Factors; Blotting, Western; Cholesterol; Cholesterol, Dietary; Coronary Vessels; Dinoprost; DNA-Binding Proteins; Drug Therapy, Combination; GADD45 Proteins; Hypercholesterolemia; Immunohistochemistry; Intracellular Signaling Peptides and Proteins; Lipoproteins, LDL; Proteins; Proto-Oncogene Proteins c-myc; Swine; Transcription Factors; Tumor Suppressor Protein p53; Vitamin E

Hypercholesterolemia impairs systemic vascular reactivity in response to endothelium-dependent vasodilators, which may be mediated partly through increased formation of lipid peroxides. However, it is unclear whether these pathophysiological mechanisms play a role in renal vascular impairment in experimental hypercholesterolemia. Hence, pigs were studied after a 3-mo normal (n = 7) or high cholesterol (HC) (n = 7) diet, HC diet supplemented daily with antioxidant vitamins E (100 IU/kg) and C (1000 mg; HC+vitamins, n = 5), or normal diet supplemented with vitamins (N+vitamins, n = 5). Renal blood flow was measured with electron-beam computed tomography before and during infusion of acetylcholine (Ach). Endothelial function, endothelial and inducible nitric oxide synthase (NOS), and nitrotyrosine immunoreactivity were studied in renal arteries ex vivo. Despite similar cholesterol levels, LDL oxidizability (lag time, malondialdehyde, and relative electrophoretic mobility) was increased in pigs that were fed the HC diet but was significantly decreased in pigs that were fed the HC+vitamins diet. Renal blood flow response to Ach was blunted in pigs that were fed the HC diet but was preserved in pigs that were fed the HC+vitamins diet. Maximal relaxation to Ach was attenuated in pigs that were fed the HC diet compared with those that were fed the normal diet (51.5 +/- 6.4% versus 97.0 +/- 2.9%; P < 0.01) but was preserved in pigs that were fed the HC+vitamins diet (103.1 +/- 3.0%; P = 0.39) and N+vitamins diet (87.7 +/- 3.0%; P = 0.1), as were relaxation responses to calcium ionophore A23187. Vascular smooth-muscle relaxation to diethylamine was enhanced in endothelium-denuded HC vessel but was restored in pigs that were on the HC+vitamins regimen. In HC, immuno-reactivity of endothelial NOS was decreased, that of inducible NOS was increased, and both were preserved in pigs that were fed the HC+vitamins and N+vitamins diets, whereas nitrotyrosine was not detected. The present study demonstrates that antioxidant intervention in experimental HC reduces LDL oxidizability and preserves renal vascular responses to endothelium-dependent vasodilators. Therefore, this beneficial effect potentially can protect the kidney from hypercholesterolemia-induced damage.

Topics: Animals; Antioxidants; Ascorbic Acid; Cholesterol; Cholesterol, Dietary; Cyclic GMP; Endothelium, Vascular; Hemodynamics; Hypercholesterolemia; Immunohistochemistry; In Vitro Techniques; Lipoproteins, LDL; Muscle, Smooth, Vascular; Reference Values; Renal Circulation; Swine; Time Factors; Tomography, X-Ray Computed; Vitamin E

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

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

Increased low-density lipoprotein (LDL) cholesterol is a recognized risk factor for atherosclerosis. There is also strong evidence that oxidatively modified LDL initiates the development of this pathological process and the administration of antioxidants might have a protective effect. However, the appropriate trials did not provide completely consistent results. We found in this study that the oxidation kinetics and also the antioxidant effectiveness are different depending on the cholesterol content in LDL. Higher cholesterol in LDL causes an acceleration of its oxidation as well as an increase of resistance to the antioxidative effect of ascorbic acid. In searching for a theoretical background of this dual impact of cholesterol in LDL, computer simulation of LDL oxidation was used. It was found that the pre-existing level of lipid hydroperoxides together with the total amount of oxidizable lipid substrate associated with the cholesterol level in LDL were satisfactory prerequisites for a best fit to the experimental data. In conclusion, this study provides at least a partial explanation for some failures to arrest, by administration of antioxidants, the progression of atherosclerosis in animal and human hypercholesterolemia.

Topics: Antioxidants; Arteriosclerosis; Ascorbic Acid; Cholesterol; Cholesterol, LDL; Computer Simulation; Humans; Hypercholesterolemia; Lipid Peroxides; Oxidation-Reduction

Topics: Ascorbic Acid; Coronary Circulation; Endothelium, Vascular; Humans; Hypercholesterolemia; Hypertension; Infusions, Intravenous; Vascular Resistance

There is evidence that formation of free radicals increases in patients with hypertension or hypercholesterolaemia, which may contribute to endothelial dysfunction of epicardial coronary arteries due to inactivation of the vasodilator NO. The present study was designed to test whether the abnormal constriction of epicardial coronary arteries due to sympathetic stimulation by the cold pressor test in patients with essential hypertension or hypercholesterolaemia could be reversed by administration of the antioxidant vitamin C.. In 28 patients without relevant coronary artery stenosis the cold pressor test was performed before and after a 3 g infusion of vitamin C. In five normal controls the cold pressor test led to a similar increase in luminal area before and after vitamin C (3.7+/-1.3% and 1.9+/-0.8%, ns vs before vitamin C). In nine hypercholesterolaemic patients the cold pressor test led to a -14.1+/-2.8% reduction in cross-sectional area before vitamin C. This constriction was significantly improved after vitamin C to -7.6%+/-2.0, P=0.027 vs before vitamin C. In nine hypertensive patients, the cold pressor test led to a -17.1+/-3.2% decrease in cross-sectional area before vitamin C, which was improved to -7.1+/-3.1 after vitamin C, P=0.004 vs before vitamin C. This increase in luminal area was significant in each group in comparison with normal controls (each P<0.05). Administration of saline (placebo group, five patients) had no significant effect on cold pressor test-induced constriction (-6.9+/-3.9% before and -6. 8+/-3.7% after saline).. The antioxidant vitamin C reverses cold pressor test-induced vasoconstriction of epicardial coronary arteries in patients with hypertension or hypercholesterolaemia. Our data suggest that enhanced oxidative stress contributes to impaired endothelial function in this patient population.

Topics: Aged; Ascorbic Acid; Cold Temperature; Coronary Vessels; Endothelium, Vascular; Female; Humans; Hypercholesterolemia; Hypertension; Infusions, Intravenous; Male; Middle Aged; Oxidative Stress; Vascular Resistance

Endogenous malondialdehyde and diene conjugate levels were increased in hypercholesterolemic subjects with serum cholesterol levels above 240 mg/dl as compared to normocholesterolemic subjects (below 20 mg/dl). A decrease in vitamin E/cholesterol and vitamin C/cholesterol ratios was observed in serum of hypercholesterolemic individuals. However, the susceptibility of serum to copper-induced lipid peroxidation and antioxidant activity were found unchanged. The present study indicates that hypercholesterolemic subjects have a high level of circulating lipid peroxides and that a higher tendency towards atherosclerosis in these subjects may be related to increased baseline levels of serum lipid peroxides.

Topics: Adult; Antioxidants; Ascorbic Acid; Cholesterol; Copper; Fatty Acids, Unsaturated; Female; Humans; Hypercholesterolemia; Lipid Peroxidation; Male; Malondialdehyde; Middle Aged; Vitamin E

Oxysterols as oxidation products of cholesterol are considered an atherogenic factor in the development of atherosclerosis in the arteries of cholesterol-fed rabbits. We compared the atherogenic effects of diets enriched either with 0.5% oxidized cholesterol (OC; characterized by high amounts of oxysterols) or with pure cholesterol (PC). The effects of antioxidant vitamins E and C added to the PC diet were also evaluated in view of their antioxidative properties for lipoproteins and cholesterol and how this could affect the severity of atherosclerosis. Four groups of rabbits were fed the following for 11 wk: 1) a nonpurified stock diet, 2) this stock diet plus 0.5% OC, 3) the stock diet plus 0.5% PC, and 4) the stock diet plus 0.5% PC and 1000 mg vitamin E and 500 mg vitamin C/kg diet (PC + antioxidants). The OC and PC diets were equally hyperlipidemic and hypercholesterolemic. The severity of atherosclerotic lesions was highest with the OC diet and lowest with the PC + antioxidants diet. The plasma oxysterol concentration was proportional to the severity of atherosclerosis in all three groups of cholesterol-fed rabbits. beta-Very-low-density-lipoprotein modification was minimized by vitamins E and C as indicated by its polyacrylamide gel electrophoretic pattern and its increased binding to the rabbit liver membrane in vitro. This study indicated that OC and PC were equally atherogenic but that the addition of antioxidants to the PC diet significantly reduced its severity, even when hypercholesterolemia persisted. This indicated that atherogenesis can result from an excessive accumulation of oxidation products of cholesterol in the plasma.

Topics: Animals; Arteriosclerosis; Ascorbic Acid; Cholesterol, Dietary; Diet, Atherogenic; Hypercholesterolemia; Lipid Peroxidation; Lipoproteins, VLDL; Liver; Male; Rabbits; Severity of Illness Index; Vitamin E

It has been suggested that iron plays an important role in the pathogenesis of atherosclerosis, primarily by acting as a catalyst for the atherogenic modification of LDL. Although some epidemiological data suggest that high stored iron levels are an independent risk factor for coronary artery disease and that iron has been detected in both early and advanced atherosclerotic lesions, the evidence is often contradictory and inconclusive. We used the New Zealand White rabbit to investigate the effects of iron overload (FeO) and iron deficiency (FeD) on atherosclerosis. Groups of 7 rabbits were either iron loaded by injections of iron dextran (FeO group), iron depleted by phlebotomy (FeD group), or given injections of saline (control group) for a total of 9 weeks. All rabbits were fed a chow diet containing 1% (wt/wt) cholesterol for the last 6 weeks of the study. Iron and antioxidant status and cholesterol levels were assayed in plasma before cholesterol feeding (week 3) and at the time that the rabbits were killed (week 9). In addition, the susceptibility of LDL to oxidation was measured and pathological examination of the aortic arch and thoracic aorta performed at the end of the study. FeD significantly decreased the levels of blood hemoglobin, serum iron, and transferrin saturation compared with controls. Conversely, FeO significantly increased transferrin Fe saturation. FeO but not FeD decreased plasma cholesterol levels compared with control animals both before (P < .05) and after (P = .055) cholesterol feeding. Neither FeO nor FeD had a significant effect on the levels of antioxidants and lipid peroxidation products in plasma and aortic tissue or on the susceptibility of LDL to ex-vivo oxidation. FeO significantly decreased aortic arch lesion formation by 56% compared with controls (P < .05), whereas FeD had no significant effect. These results indicate that in this animal model, FeO decreases rather than increases atherosclerosis, likely because iron dextran exerts a hypocholesterolemic effect. Our data do not support the hypotheses that elevation of Fe stores increases or that a reduction of Fe stores by phlebotomy decreases the risk of coronary artery disease.

Topics: Animals; Antioxidants; Aorta; Aortic Diseases; Arteriosclerosis; Ascorbic Acid; Diet, Atherogenic; Hypercholesterolemia; Iron; Iron Deficiencies; Iron Overload; Lipid Peroxidation; Lipids; Lipoproteins, LDL; Male; Phlebotomy; Prostaglandins F; Rabbits; Risk Factors; Vitamin E

We have recently shown that ascorbate has a hypocholesterolemic and hypotriglyceridemic effect on rats fed a diet enriched with 1.5% cholesterol and 25% hydrogenated coconut oil (Nath diet). In this study we evaluated the effect of intraperitoneal ascorbate administration on susceptibility to lipoperoxidation either in rats fed standard or Nath diet. In normal rats ascorbate treatment decreased (p<0.05) the susceptibility to lipoperoxidation induced by incubation of serum for 24 hours with 2.2 mM Cu++, without altering the normal serum fatty acid profile. In rats fed Nath diet we observed a reduced susceptibility of serum to CU++-induced lipoperoxidation (36%), according with their low levels of serum unsaturated fatty acids (40% less than rats fed standard diet). In these animals ascorbate administration affects serum fatty acid profile leading to a decrease of S/U ratio from 1.6 to 1.2 without significantly modifying the susceptibility of serum to lipoperoxidation. Moreover, the production of spontaneous lipid peroxides in liver homogenates, measured as TBARS levels, was strongly inhibited by ascorbate (p<0.01) in rats fed either standard or Nath diet. These data indicate that ascorbate administration exerts an antioxidant effect and that in hypercholesterolemic rats, in addition to a lipid lowering effect, ascorbate exerts a protective role against the peroxidative damage of lipids.

Topics: Animals; Ascorbic Acid; Body Weight; Cholesterol, Dietary; Copper; Copper Sulfate; Fatty Acids; Hypercholesterolemia; Lipid Peroxidation; Lipid Peroxides; Liver; Male; Rats; Rats, Wistar; Thiobarbituric Acid Reactive Substances

Individuals with low serum cholesterol experience greater than expected age-adjusted mortality from non-atherosclerotic diseases, including cancer, respiratory and digestive illnesses, but the basis for these associations remains unclear. The current investigation considered the hypothesis that hypocholesterolemia is associated with reduced antioxidant reserve. Serum total antioxidant activity as well as concentrations of vitamin E, vitamin C, and thiols were compared in two groups of 24 subjects distinct in both mean low density lipoprotein (LDL) cholesterol (2.3 v. 4.9 mM) and mean total cholesterol (4.3 v. 7.0 mM). The low and high cholesterol groups were equivalent in gender mix, age, weight, and serum total protein. Results reveal that compared with the high group, the low cholesterol group had decreased total serum antioxidant activity (p < .05). Thiol concentrations were also lower in the low cholesterol group (p < .05). Group differences in serum total antioxidant activity and thiol concentration were larger among men than women. The two groups did not differ in vitamin C. Low cholesterol was associated with reduced absolute vitamin E levels, although the tocopherol: cholesterol ratio was the same in low and high cholesterol individuals. These data indicate that hypocholesterolemia may be associated with low serum antioxidant reserve, possibly increasing susceptibility to oxidative stress.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Cholesterol; Cholesterol, LDL; Chromatography, High Pressure Liquid; Disease Susceptibility; Electron Spin Resonance Spectroscopy; Female; Humans; Hypercholesterolemia; Luminescent Measurements; Male; Middle Aged; Oxidative Stress; Risk Factors; Sex Factors; Smoking; Sulfhydryl Compounds; Triglycerides; Vitamin E

It is known that ascorbate has a lipid lowering effect, accompanied by a drop of apo B, in rats fed a diet enriched with 1.5% of cholesterol (Nath diet). In order to better clarify the role exerted by ascorbate in lipid metabolism, the effect of ascorbate administration on apolipoprotein pattern in rats fed the Nath diet was investigated. Wistar male rats fed for two months the Nath diet were treated i.p. with 60 mg/kg of body weight of ascorbate for 10 days. Blood collection before and after the treatment was performed by intracardiac puncture. Lipoproteins were prepared by preparative ultracentrifugation and their apoprotein content was obtained by densitometric scanning of the apoprotein electhrophoretic pattern. The decrease of total plasma cholesterol and triglycerides and of cholesterol, triglycerides and protein content of all plasma lipoproteins observed in ascorbate treated rats, is accompanied by a marked modification of the apolipoprotein pattern of all lipoprotein classes studied, with an increase of apo E content in VLDL-IDL and LDL fractions (135 and 44% respectively), and a decrease of C (37%), AI (70%) and B (37.5%) apoproteins in VLDL-IDL and of apo C (36%) in LDL. On the contrary, in HDL fraction ascorbate induces an increase of C apoproteins (26%) and a decrease of E and B apoproteins (47% and 71% respectively). The data reported clearly show that in hypercholesterolemic rats the lipid lowering effect of ascorbate administration, is accompanied by a marked modification of the apoprotein pattern of all lipoprotein classes studied.

Topics: Animals; Apolipoproteins; Ascorbic Acid; Cholesterol; Cholesterol, Dietary; Hypercholesterolemia; Lipoproteins; Lipoproteins, HDL; Lipoproteins, LDL; Lipoproteins, VLDL; Male; Rats; Rats, Wistar; Triglycerides

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

We examined the cross-sectional relation of dietary vitamin C intake to serum lipids in 1,825 preadolescent black and white girls. Dietary vitamin C intake exclusive of supplement use, determined by 3-day diet record, appeared unrelated to total serum cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and triglyceride levels. Because other investigators have demonstrated an inverse association between vitamin C and total serum cholesterol in individuals with elevated total serum cholesterol levels, we analyzed the subgroup of 285 girls (142 blacks and 143 whites) with total serum cholesterol levels > or = 200 mg per dl. Multivariate analyses of this subgroup, which adjusted for saturated fat, polyunsaturated fat, monounsaturated fat, cholesterol, fiber, and energy intake and for body mass index, demonstrated negative association between vitamin C intake and total serum cholesterol. In girls with total serum cholesterol levels > or = 200 mg per dl, each 100 mg per day increase in dietary vitamin C intake (ranges 13-373 and 14-242 mg per day for blacks and whites, respectively) was associated with a total serum cholesterol decrease of 4 mg per dl (95% confidence limits = -10.34, 2.77) in blacks and 13 mg per dl (95% confidence limits = -22.99, -2.68) in whites. If the observed association is causal and generalizable, our results suggest that increased vitamin C intake could play an important role in the cholesterol homeostasis of females with elevated total cholesterol levels.

Topics: Ascorbic Acid; Black People; California; Child; Cholesterol; Cross-Sectional Studies; Diet; District of Columbia; Female; Humans; Hypercholesterolemia; Lipids; Lipoproteins; Multivariate Analysis; Nutritional Physiological Phenomena; Ohio; Triglycerides; White People

Oxidative modification of LDL may represent an initiating event in the formation of monocyte-macrophage foam cells, a major cell present in fatty streaks and atherosclerotic fibrous plaques. Therefore, we studied the effect of such antioxidants as probucol (500 mg/kg) and vitamins E and C (500 mg/kg each) on the regression of induced iliac-femoral lesions and progression of naturally occurring thoracic aortic fatty streak lesions in hypercholesterolemic New Zealand White rabbits. Following an initial 9-week lesion induction phase, both therapies were evaluated for 8 weeks. Probucol lowered plasma cholesterol 47% while vitamins E and C had no effect on plasma cholesterol. Probucol decreased the cholesteryl ester (CE) content of the thoracic aorta by 31% without changing the thoracic aortic lesion coverage. Vitamins E and C decreased thoracic aortic CE content by 40% and lesion coverage by 46%. Neither probucol nor vitamins E and C altered the CE content, lesion size, or macrophage/lesion ratio of the iliac-femoral artery. Thus, we conclude that the effects of antioxidants are specific to the stage of atherosclerotic lesion development. Antioxidant therapy alters the progression and cholesteryl ester enrichment of diet-induced thoracic aortic fatty streaks but has no effect on the progression and/or regression of more complicated injury-induced iliac-femoral lesions.

Topics: Animals; Antioxidants; Aorta; Arteriosclerosis; Ascorbic Acid; Blood Vessels; Cholesterol; Cholesterol Esters; Femoral Artery; Hypercholesterolemia; Lipids; Lipoproteins; Male; Probucol; Rabbits; Vitamin E

Nutritional adequacy of diets with 18-30% of calories from fat was investigated in men with elevated serum cholesterol (n = 396) at the end of diet classes and 1 and 2 y later. On 4-d food records, intakes of vitamin A, beta-carotene, folate, vitamin C, magnesium, vitamin B-6, iron, thiamin, and riboflavin increased from baseline whereas niacin, selenium, vitamin E, and zinc decreased. Median zinc intake, 80% of the recommended dietary allowance (RDA) at baseline, decreased to approximately 75% of the RDA, most markedly when intakes of meat, fish, and poultry were limited to 85 g/d. Nutrient densities generally increased. Of the serum nutrients measured, median beta-carotene and vitamin C increased, whereas vitamin B-6, iron, and zinc were unchanged. Below-normal values were fewer for vitamin C and magnesium. Diets similar to the National Cholesterol Education Program Step-Two Diet [less than 7% saturated fatty acids, less than 200 mg cholesterol/d] appeared to provide increased levels of most micronutrients both short and long term to men receiving comprehensive dietary counseling.

Topics: Ascorbic Acid; beta Carotene; Carotenoids; Diet; Dietary Fats; Energy Intake; Folic Acid; Humans; Hypercholesterolemia; Magnesium; Male; Minerals; Niacin; Selenium; Vitamin A; Vitamin E; Vitamins; Zinc

Certain dietary practices are valid methods of lowering the risk of disease. Others, while popular, have unproven benefits or may even be associated with risks of their own. Careful evaluation of hypercholesterolemia is necessary. Persons with a high level of low-density lipoprotein (LDL) cholesterol and a low level of high-density lipoprotein (HDL) cholesterol need diet therapy, because they are at increased risk of cardiovascular disease. Weight reduction and fat restriction can lower blood pressure, help control hyperglycemia, and improve the LDL cholesterol-HDL cholesterol ratio. Some evidence indicates a protective role of beta carotene against cancer in animals. However, hypervitaminosis A is dangerous and relatively easy to accomplish, so supplementation beyond a multivitamin tablet is discouraged. Data about inhibition of cancer in humans through use of high doses of vitamin E or C or selenium are inconclusive, and studies of effects of long-term ingestion are not available. In general, megadoses of even healthy substances are thought to be dangerous. Decreased consumption of fat, increased consumption of foods high in fiber, and elimination of alcohol and tobacco are sensible recommendations. Consumption of cruciferous vegetables has not been proven to reduce the incidence of cancer, but a moderate amount of them in the diet would seem reasonable.

Topics: Adult; Aged; Ascorbic Acid; Diet; Dietary Fats; Dietary Fiber; Humans; Hypercholesterolemia; Middle Aged; Neoplasms; Selenium; Vegetables; Vitamin A; Vitamin E

Long-term feeding of purified diets containing (per kg diet) 100 mg of polychlorinated biphenyl (PCB) and 1000 mg of vitamin E (RRR-alpha-tocopheryl acetate) to male Wistar rats was carried out. Rats fed a diet containing PCB rapidly became hypercholesterolemic and maintained high cholesterol levels throughout the 240 d of the experiment. Rats fed a high dietary level of vitamin E plus PCB had higher serum cholesterol and lower liver cholesterol than rats fed a lower level of vitamin E plus PCB. In rats fed PCB, urinary excretion of ascorbic acid was higher than in rats not fed PCB. Urinary ascorbic acid was lower in rats fed high levels of vitamin E plus PCB than in those fed the normal levels of vitamin E plus PCB. Rats fed PCB had lower liver vitamin A storage and higher vitamin A in kidney than rats not fed PCB. This implies that a redistribution of vitamin A occurred in rats fed PCB. Histological observations revealed that central halves of the hepatic lobules of rats fed PCB showed distinct changes consisting of hypertrophy of hepatocytes in the perivenous region and accumulation of vacuoles (lipid droplets) in the cells in the remaining affected portion. Administration of a high dose of vitamin E could not ameliorate this lesion while the treatment depressed effectively the lipid peroxidation. This suggests that the lipid peroxidation was not responsible for the hepatic damage induced by PCB.

Topics: Animals; Ascorbic Acid; Body Weight; Diet; Hypercholesterolemia; Lipid Metabolism; Lipid Peroxides; Liver; Male; Polychlorinated Biphenyls; Rats; Rats, Inbred Strains; Time Factors; Vitamin A; Vitamin E

This report describes measurements of 50 variables in adult, female, reproductively inactive Vervet monkeys during prolonged nutrition realistic for westernized people. Dietary treatments consisted of an atherogenic Western diet (WD) and a prudent Western diet (PD). Ingredients were normal foods for man and no extra cholesterol was added. Fortification of both diets with vitamin C after cooking was necessary to prevent deficiency. Randomised groups of Vervet monkeys received either the PD or WD for 47 months, while a third group was fed WD for 20 months and then PD for 27 months (WD-PD). Before the dietary treatments nourishment was by a high carbohydrate diet (HCD) and baseline and reference values (RV) apply to this nutritional status. Plasma total cholesterol (mg/dl) was increased from 147 (HCD) to 174 (PD) and 376 (WD). Individual cholesterolaemio response ranged from mild to severe and was stable (PD and WD). Dietary reversal (WD-PD) reduced cholesterolaemia promptly. Statistically significant increases in calcium, zinc and vitamin E and decreased vitamin B6 were associated with the WD relative to the PD (in serum and plasma). Two cholesterol metabolising microsomal enzymes in liver were notably increased and one unchanged (WD). There were no dietary effects on triglycerides, vitamin A and glucose in plasma; insulin, glucagon, electrolytes, copper, magnesium or enzymes reflecting liver, muscle or brain cell damage in serum. Red blood cells, platelets and directly associated parameters increased (WD), haemoglobin was the same and haemoglobin per red cell decreased. Bleeding time was not affected. Bivariate correlations across the diets confirmed that Western nutrition promoted inherent individual susceptibility to cholesterolaemia. There were notable differences from RVs in total cholesterol, calcium, packed cell volume and haemoglobin, which emphasise excesses and deficiencies of the WD and PD.

Topics: Animal Nutritional Physiological Phenomena; Animals; Ascorbic Acid; Calcium; Cercopithecus; Chlorocebus aethiops; Cholesterol; Diet, Atherogenic; Female; Hemoglobins; Hypercholesterolemia; Pyridoxine; Time Factors; Vitamin E; Zinc

Possible mechanisms responsible for hepatic lysosomal fragility in hypercholesterolemic rats have been investigated. It was found that certain factor(s) present in the intracellular environment of liver were required for the release of lysosomal enzymes. Elevated hepatic dehydroascorbic acid content in hypercholesterolemic rats is thought to render the lysosomes fragile in this pathological state, since this compound was found to labilise the lysosomes in vitro. Quercetin and hesperidin were found to be responsible for lysosomal stability, probably by reducing the content of dehydroascorbic acid to a normal level in the hypercholesterolemic condition.

Topics: Animals; Ascorbic Acid; Dehydroascorbic Acid; Flavonoids; Hesperidin; Hypercholesterolemia; Liver; Lysosomes; Male; Quercetin; Rats

Topics: Animals; Arteriosclerosis; Ascorbic Acid; Female; Hypercholesterolemia; Male; Plants, Medicinal; Rabbits

Effects of 0.03% polychlorinated biphenyls (PCB) in the diet and various dietary fibers [konjac mannan (KM), pectin, sodium carboxymethyl cellulose (CMC) and cellulose] at a 5% level in the diet on serum and liver lipid metabolism and urinary ascorbic acid were studied. A comparison between dietary PCB and 1% cholesterol in the diet was also made. Serum albumin, protein, total and high density lipoprotein (HDL)-cholesterol, triglyceride, urinary and liver ascorbic acid, liver cholesterol and total lipids were increased in rats fed PCB. Pectin or KM depressed the elevation in serum protein, total and HDL-cholesterol, triglyceride and liver lipids due to PCB intake. Cellulose or CMC had no significant effect on these indices. Urinary ascorbic acid was not decreased by these dietary changes. Serum total cholesterol and low density lipoprotein (LDL) plus very low density lipoprotein (VLDL)-cholesterol, and liver total lipids, and cholesterol were significantly higher, and serum HDL-cholesterol and triglyceride were significantly lower in the cholesterol-fed group as compared to PCB-fed rats. Addition of KM to a cholesterol diet significantly depressed serum total cholesterol and LDL plus VLDL-cholesterol, liver cholesterol and total lipids. It seems likely that cholesterol metabolism is quite different during dietary PCB and cholesterol feeding.

Topics: Animals; Ascorbic Acid; Cholesterol, Dietary; Dietary Fiber; Female; Hypercholesterolemia; Lipoproteins; Liver; Male; Organ Size; Polychlorinated Biphenyls; Rats; Rats, Inbred Strains; Species Specificity

Topics: Adult; Aged; Ascorbic Acid; Fatty Acids; Humans; Hypercholesterolemia; Lipids; Male; Middle Aged; Phospholipids; Triglycerides

The activity of the cholesterol 7 alpha-hydroxylating system containing cyto-chrome P-450 is depressed in the liver of guinea-pigs with chronic marginal vitamin C deficiency. Slowing-down of this rate-limiting reaction of cholesterol transformation to bile acids causes cholesterol accumulation in the liver, blood plasma and arteries, increase in the index total: HDL cholesterol, prolongation of plasma cholesterol half-life, increase in the index cholesterol: bile acids in the gall-bladder bile, cholesterol gallstone formation and atheromatous changes on coronary arteries in guinea-pigs with long-lasting marginal vitamin C deficiency. The most effective means for preventing these changes are vitamin C doses ensuring maximal steady-state levels of ascorbate in the tissues. In most of hypercholesterolemic persons with a low vitamin C status, the administration of ascorbic acid in doses 500-1000 mg per day lowers total cholesterol concentration in blood plasma. This effect may be reinforced through a simultaneous administration of bile acids sequestrants, such as cholestyramine or pectin. In every form of hypercholesterolemia therapy (dietary and/or pharmacological), an adequate vitamin C supply should be ensured in doses capable of creating maximal steady-state levels of ascorbate in human tissues.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Cholesterol; Drug Synergism; Humans; Hypercholesterolemia; Pectins; Spleen; Time Factors

Following daily administration of cholesterol-enriched scorbutogenic diet to male guinea-pigs for 24 days, elevation of tissue cholesterol level occurred with concurrent pronounced depletion of tissue ascorbic acid. When these hypercholesterolemic guinea-pigs received clofibrate or diosgenin with or without daily supplementary vitamin C for 10 days, alterations in the bodyweight, plasma and hepatic ascorbic acid and clofibrate and diosgenin separately caused reduction in bodyweight and also in tissue ascorbic acid and cholesterol levels. In contrast, bodyweight and tissue ascorbic acid concentrations were increased by vitamin C alone or in combination with clofibrate or diosgenin. The cholesterol lowering actions of clofibrate and diosgenin were enhanced by daily supplementary vitamin C in hypercholesterolemic guinea-pigs. It is concluded that vitamin C plays an important role in the control of cholesterol metabolism in hypercholesterolemic guinea-pigs receiving clofibrate or diosgenin.

Topics: Animals; Ascorbic Acid; Cholesterol; Clofibrate; Diet; Diosgenin; Growth; Guinea Pigs; Hypercholesterolemia; Liver; Male; Sapogenins

Topics: Animals; Arteriosclerosis; Ascorbic Acid; Clofibrate; Diet; Drug Interactions; Humans; Hypercholesterolemia; Lipid Metabolism; Nicotinic Acids; Phospholipids

Topics: Adult; Ascorbic Acid; Cholesterol; Humans; Hypercholesterolemia; Hyperlipidemias; Leukocytes; Middle Aged; Triglycerides

Topics: Aged; Ascorbic Acid; Cholesterol; Dose-Response Relationship, Drug; Humans; Hypercholesterolemia; Reference Values

An addition of 5% citrus pectin and 0.5% ascorbic acid to high-fat diet of guinea pigs prevented total cholesterol accumulation in blood serum and the liver. Two groups of persons were given a preparation containing a daily dose of 15 g pectin and 450 mg ascorbic acid for 6 weeks. In 21 healthy persons with mild hypercholesterolemia total serum cholesterol dropped significantly by 24 mg/100 ml (8.6%), while the concentration of high density lipoprotein cholesterol remained unchanged. In 11 hyperlipemic outpatients (type IIa, IIb and IV) total serum cholesterol dropped by 68 mg/100 ml (18.7%). The changes in triglyceridemia proved inconsistent.

Topics: Animals; Anticholesteremic Agents; Ascorbic Acid; Cholesterol; Fasting; Guinea Pigs; Humans; Hypercholesterolemia; Hyperlipidemias; Lipoproteins, HDL; Liver; Male; Pectins; Reference Values; Triglycerides

The effects of L-ascorbic acid on 35S-incorporation into thoracic aorta glycosaminoglycans and upon aorta cholesterol levels were determined in hypercholesterolemic rabbits. No significant difference was observed in serum free or esterified cholesterol levels between animals receiving L-ascorbic acid supplementation or saline while maintained on a cholesterol diet (0.5%). A 15-fold higher serum cholesterol was observed in animals on the cholesterol diet to those animals which received a normal rabbit (Purina) diet. L-Ascorbic acid increased sulfated glycosaminoglycans concentrations in hypercholesterolemic rabbits which paralleled lower tissue free and esterified cholesterol levels. The 35S-specific activity of glycosaminoglycans in hypercholesterolemic animals receiving saline was much greater than in those animals receiving L-ascorbic acid. This suggests that L-ascorbic acid plays a role in the maintenance of adequate levels of aortic sulfated glycosaminoglycans. This then is a suggested biochemical mechanism of L-ascorbic acids interaction in the atherogenic process.

Topics: Animals; Aorta; Arteriosclerosis; Ascorbic Acid; Cholesterol; Glycosaminoglycans; Hypercholesterolemia; Male; Rabbits; Sulfur Radioisotopes

Topics: Animals; Aorta; Ascorbic Acid; Cattle; Cholesterol; Glycosaminoglycans; Hypercholesterolemia; Male; Rats; Vitamin A; Zinc

Topics: Adolescent; Adult; Aged; Arteriosclerosis; Ascorbic Acid; Cholesterol; Humans; Hypercholesterolemia; Lipids; Middle Aged; Nutritional Physiological Phenomena; Poland

The effects of L-ascorbate 2-sulfate (AAS) on the lipid metabolism were examined in Triton-induced hyperlipemic mice, hypercholesterolemic and normal rats, the following results being obtained. 1) In Triton-induced hyperlipemic mice, AAS (300 mg/kg) significantly decreased the serum cholesterol level, while L-ascorbate (AA, 175 mg/kg) was found ineffective. 2)In hypercholesterolemic rats fed 0.5% cholesterol diet, the consecutive administration of AAS decreased the level of serum cholesterol and liver triacylglycerols. AA only slightly affected these levels. However, both AAS and AA prevented the unordinal increase in the liver weight caused by cholesterol feeding. 3)In normal rats, the administration of AAS over a 4-week period decreased the levels of serum cholesterol and liver triacylglycerols.

Topics: Animals; Anticholesteremic Agents; Ascorbic Acid; Cholesterol; Clofibrate; Dose-Response Relationship, Drug; Female; Hypercholesterolemia; Hyperlipidemias; Lipid Metabolism; Liver; Male; Mice; Polyethylene Glycols; Rats; Sex Factors; Triglycerides

Rabbits on a high cholesterol diet were divided into three groups: one group received subcutaneous injections of physiological saline 3 times/day, 5 days/wk for 10 wk; another group received subcutaneous injections of L-ascorbic acid (0.37 mmole) according to the same timetable; and the third group was administered an equivalent amount of L-ascorbate 2-sulfate as outlined above. Each week the serum levels of total and free cholesterol and triglycerides were measured. At the end of 10 wk the animals were killed and the cholesterol content of the livers, spleens, and adrenal glands was measured. The aortas were examined for plaque deposition; the deposits were excised and pooled according to groups; and the total mass and cholesterol contents of the pooled plaques were determined. Administration of ascorbic acid or ascorbate 2-sulfate did not prevent hypercholesterolemia or elevated levels of serum triglycerides. No significant differences among the groups were found either in tissue cholesterol levels or in the extent or type of lesions found. Although plaque deposition appeared to be similar in the aortas of these animals, a marked difference was found in total mass and cholesterol content of the plaques: The plaques of the saline-treated group had a total mass and cholesterol content approximately 2.5 times that found in the group injected with ascorbic acid and about 1.5 times that found in the animals treated with ascorbate 2-sulfate. These results indicate that ascorbic acid, in particular, minimizes the total quantity of plaque deposition even though it is ineffective in preventing hypercholesterolemia, elevated serum triglycerides, and accumulation of cholesterol by several tissues.

Topics: Adrenal Glands; Animals; Aorta; Arteriosclerosis; Ascorbic Acid; Cholesterol; Cholesterol, Dietary; Hypercholesterolemia; Hyperlipidemias; Liver; Male; Rabbits; Spleen; Sulfates; Triglycerides

Rats fed a purified diet containing ascorbic acid developed hypercholesterolemia. Because rats do not require exogenous ascorbic acid, they may be comparable to humans who supplement their diets with ascorbic acid in capsular form. The amount of ascorbic acid in this experiment was equivalent to 82 to 630 mg of capsular ascorbic acid ingested by an average man and was well below the amount ingested by those in search of respiratory benefit. The data are consonant with those on humans consuming controlled diets.

Topics: Animals; Ascorbic Acid; Hypercholesterolemia; Male

In order to assess the possible effects of ascorbic acid on plasma cholesterol and triglyceride levels and plasma lipoprotein composition, nine hypercholesterolemic subjects were treated with oral ascorbic acid (4 g/day) for 2 months. The data demonstrate: 1) no significant change in plasma cholesterol or triglyceride levels; 2) no significant change in the cholesterol or triglyceride concentrations of the major lipoprotein classes; and 3) the unexpected appearance of extra pre-beta bands on lipoprotein electrophoresis by the end of the ascorbic acid treatment period.

Topics: Adult; Ascorbic Acid; Cholesterol; Female; Humans; Hypercholesterolemia; Lipoproteins, HDL; Lipoproteins, LDL; Lipoproteins, VLDL; Male; Middle Aged; Time Factors; Triglycerides

Latent chronic ascorbic acid deficiency provokes in guinea pigs a metabolic disorder in the liver, causing an impaired cholesterol transformation to its principal catabolic product, bile acids. This metabolic disorder induces hypercholesterolemia and accumulation of cholesterol in the liver and slows the release of cholesterol from the circulation. Ascorbic acid probably intervenes into the biosynthesis of bile acids at the stage of 7 alpha-hydroxylation of the cholesterol nucleus. High doses of ascorbic acid significantly stimulate cholesterol transformation to bile acids in guinea pigs and decrease plasma cholesterol concentration in humans.

Topics: Aged; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Bile Acids and Salts; Cholesterol; Cholesterol, Dietary; Female; Guinea Pigs; Humans; Hypercholesterolemia; Kinetics; Liver; Male; Middle Aged; Spleen

Hypercholesterolemia was induced in rats by experimental cholestasis and aminonucleoside nephrosis. After ascorbic acid administration the hypercholesterolemia was significantly decreased in both cases. In the case of cholestasis serum choelsterol was normal and in the case of nephrosis serum cholesterol remained above normal.

Topics: Animals; Ascorbic Acid; Cholestasis; Cholesterol; Hypercholesterolemia; Male; Nephrosis; Nucleosides; Rats

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Aspirin; Barbiturates; Common Cold; Humans; Hypercholesterolemia; Phenylbutazone; Pressure Ulcer; Tetracycline

Topics: Adolescent; Adult; Aged; Animals; Ascorbic Acid; Child; Child, Preschool; Cholesterol; Dietary Fats; Fatty Acids, Essential; Female; Government Agencies; Humans; Hypercholesterolemia; Infant; Infant, Newborn; Male; Metabolism; Middle Aged; Nutritional Requirements; Pregnancy; Triglycerides; United States

Topics: Animals; Anticholesteremic Agents; Ascorbic Acid; Hypercholesterolemia; Hypothyroidism; Iodine Radioisotopes; Rats; Thyroid Gland

Topics: Adult; Animals; Arteriosclerosis; Ascorbic Acid; Cholesterol; Diet, Atherogenic; Female; Guinea Pigs; Humans; Hypercholesterolemia; Male; Middle Aged; Rabbits; Time Factors

Topics: Arteriosclerosis; Ascorbic Acid; Cholesterol; Hypercholesterolemia; Time Factors

Topics: Animals; Ascorbic Acid; Cholesterol; Dermatologic Agents; Edible Grain; Fasting; Hypercholesterolemia; Lipoproteins; Phenols; Rabbits; Tannins

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cholesterol; Cholesterol, Dietary; Diet, Atherogenic; Disease Models, Animal; Hypercholesterolemia; Rabbits

Topics: Adrenal Glands; Animals; Arteriosclerosis; Ascorbic Acid; Body Weight; Cholesterol; Disease Models, Animal; Histocytochemistry; Hypercholesterolemia; Lipids; Male; Methods; Organ Size; Rabbits; Time Factors

Topics: Adrenal Glands; Animals; Arteriosclerosis; Ascorbic Acid; Body Weight; Cholesterol; Cold Temperature; Diet, Atherogenic; Environmental Exposure; Hypercholesterolemia; Lipid Metabolism; Liver; Male; Organ Size; Rabbits

Topics: Adrenal Glands; Animals; Aorta; Arteriosclerosis; Ascorbic Acid; Ascorbic Acid Deficiency; Bile; Carbon Isotopes; Erythrocytes; Hypercholesterolemia; Intestine, Small; Kidney; Liver; Lung; Male; Methods; Myocardium; Pancreas; Rabbits; Spleen; Testis

Topics: Adrenal Glands; Animals; Aorta; Arteriosclerosis; Ascorbic Acid; Carbon Isotopes; Cholesterol; Hypercholesterolemia; Intestine, Small; Kidney; Lipoproteins; Liver; Lung; Male; Methods; Models, Biological; Myocardium; Pancreas; Rabbits; Spleen; Testis

Topics: Animals; Ascorbic Acid; Blood Coagulation; Fibrinolysis; Hypercholesterolemia; Male; Rats; Riboflavin; Rutin; Thiamine

Topics: Arteriosclerosis; Ascorbic Acid; Cholesterol; Coronary Vessels; Humans; Hypercholesterolemia; Hypertension; Hypertension, Renal; Kidney; Vitamins

Topics: Animals; Aorta; Arteriosclerosis; Ascorbic Acid; Atherosclerosis; Blood Proteins; Cholesterol; Chromium Isotopes; Dietary Fats; Hypercholesterolemia; Lipid Metabolism; Liver; Rabbits; Research

Topics: Ammonium Compounds; Anti-Infective Agents, Local; Ascorbic Acid; Asthma; Bronchitis; Germany; Germany, West; Humans; Hydrocortisone; Hypercholesterolemia; Isoproterenol; Pentylenetetrazole; Pulmonary Emphysema; Quaternary Ammonium Compounds; Reserpine; Synephrine; Thyroxine

Topics: Ascorbic Acid; Humans; Hypercholesterolemia; Pathology; Rutin; Vasodilator Agents; Xanthomatosis

Topics: Ascorbic Acid; Atherosclerosis; Cholesterol; Humans; Hypercholesterolemia

Topics: Arteriosclerosis; Ascorbic Acid; Calcium; Cholesterol; Humans; Hypercholesterolemia; Vitamins

Topics: Adrenal Cortex; Ascorbic Acid; Carbohydrate Metabolism; Cholesterol; Glutathione; Hypercholesterolemia

Topics: Animals; Ascorbic Acid; Cholesterol; Diet; Hypercholesterolemia; Prednisolone; Rabbits; Vitamin A; Vitamin E; Vitamin K; Vitamins