coenzyme-q10 and Hyperlipidemias

Topics: Animals; Atherosclerosis; Drug Interactions; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Hypolipidemic Agents; Muscular Diseases; Risk Factors; Ubiquinone

Elevated lipid level is supposed to be one of the main risk factors of atherosclerosis and related cardiovascular diseases and stroke (and is connected to mortality and morbidity). Therefore, lipid lowering is one of the major approaches in prevention of coronary heart diseases and stroke. Though drugs of various categories acting through different mechanisms are available in the antihyperlipidemic therapy, there are still a few problems associated with the currently available lipid lowering drugs. Therefore, medicinal chemists worldwide are designing, synthesizing and evaluating a variety of new molecules for antihyperlipidemic activity to address these problems. One of the important approaches to this is identifying new drug targets for antihyperlipidemic activity. This review summarizes nineteen recently identified and currently being exploited targets for the ongoing research by researchers world over to discover novel leads as potential drugs for antihyperlipidemic therapy.

Topics: ATP Citrate (pro-S)-Lyase; C-Reactive Protein; Carrier Proteins; Cholesterol Ester Transfer Proteins; Humans; Hyperlipidemias; Hypolipidemic Agents; Lipoproteins; Peroxisome Proliferator-Activated Receptors; Sterol O-Acyltransferase; Ubiquinone

Statins are drugs of known and undisputed efficacy in the treatment of hypercholesterolemia, usually well tolerated by most patients. In some cases treatment with statins produces skeletal muscle complaints, and/or mild serum CK elevation; the incidence of rhabdomyolysis is very low. As a result of the common biosynthetic pathway Coenzyme Q (ubiquinone) and dolichol levels are also affected, to a certain degree, by the treatment with these HMG-CoA reductase inhibitors. Plasma levels of CoQ10 are lowered in the course of statin treatment. This could be related to the fact that statins lower plasma LDL levels, and CoQ10 is mainly transported by LDL, but a decrease is also found in platelets and in lymphocytes of statin treated patients, therefore it could truly depend on inhibition of CoQ10 synthesis. There are also some indications that statin treatment affects muscle ubiquinone levels, although it is not yet clear to which extent this depends on some effect on mitochondrial biogenesis. Some papers indicate that CoQ10 depletion during statin therapy might be associated with subclinical cardiomyopathy and this situation is reversed upon CoQ10 treatment. We can reasonably hypothesize that in some conditions where other CoQ10 depleting situations exist treatment with statins may seriously impair plasma and possible tissue levels of coenzyme Q10. While waiting for a large scale clinical trial where patients treated with statins are also monitored for their CoQ10 status, with a group also being given CoQ10, physicians should be aware of this drug-nutrient interaction and be vigilant to the possibility that statin drugs may, in some cases, impair skeletal muscle and myocardial bioenergetics.

Topics: Animals; Biochemistry; Biosynthetic Pathways; Clinical Trials as Topic; Coenzymes; Cricetinae; Dogs; Heart Diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Models, Biological; Rats; Ubiquinone; Vitamins

To assess the effects of fenofibrate therapy on concentrations of plasma ubiquinol-10 and ubiquinone-10-the reduced and oxidized forms, respectively, of coenzyme Q(10).. Prospective, open-label, non-controlled study.. University clinic and laboratory.. Eighteen patients with hyperlipidemia and type 2 diabetes mellitus.. Patients received fenofibrate 150 mg/day for 12 weeks.. Metabolic parameters were assessed 4, 8, and 12 weeks after the start of fenofibrate treatment. Plasma ubiquinol-10 and ubiquinone-10 levels were measured by reverse-phase high-performance liquid chromatography. At 4, 8, and 12 weeks, significant reductions in fasting triglyceride levels and significant increases in high-density lipoprotein cholesterol levels were noted. Total cholesterol, low-density lipoprotein cholesterol, fasting plasma glucose, and adiponectin levels, however, did not change significantly. Plasma ubiquinol-10 concentrations significantly increased after 8 and 12 weeks (p<0.05 for both), whereas ubiquinone-10 concentrations tended to decrease, especially at 12 weeks.. Our findings suggest that fenofibrate may help produce energy or prevent oxidation by increasing plasma ubiquinol-10 concentration; this effect may protect against the development and progression of atherosclerosis. In addition, treatment with fenofibrate demonstrated a favorable effect on serum lipid parameters.

Topics: Coenzymes; Diabetes Mellitus, Type 2; Disease Progression; Female; Fenofibrate; Humans; Hyperlipidemias; Male; Middle Aged; Prospective Studies; Ubiquinone

Our objective was to assess effects of dietary supplementation with coenzyme Q10 (CoQ) on blood pressure and glycaemic control in subjects with type 2 diabetes, and to consider oxidative stress as a potential mechanism for any effects.. Seventy-four subjects with uncomplicated type 2 diabetes and dyslipidaemia were involved in a randomised double blind placebo-controlled 2x2 factorial intervention.. The study was performed at the University of Western Australia, Department of Medicine at Royal Perth Hospital, Australia.. Subjects were randomly assigned to receive an oral dose of 100 mg CoQ twice daily (200 mg/day), 200 mg fenofibrate each morning, both or neither for 12 weeks.. We report an analysis and discussion of the effects of CoQ on blood pressure, on long-term glycaemic control measured by glycated haemoglobin (HbA(1c)), and on oxidative stress assessed by measurement of plasma F2-isoprostanes.. Fenofibrate did not alter blood pressure, HbA(1c), or plasma F2-isoprostanes. There was a 3-fold increase in plasma CoQ concentration (3.4+/-0.3 micro mol/l, P<0.001) as a result of CoQ supplementation. The main effect of CoQ was to significantly decrease systolic (-6.1+/-2.6 mmHg, P=0.021) and diastolic (-2.9+/-1.4 mmHg, P=0.048) blood pressure and HbA(1c) (-0.37+/-0.17%, P=0.032). Plasma F2-isoprostane concentrations were not altered by CoQ (0.14+/-0.15 nmol/l, P=0.345).. These results show that CoQ supplementation may improve blood pressure and long-term glycaemic control in subjects with type 2 diabetes, but these improvements were not associated with reduced oxidative stress, as assessed by F2-isoprostanes.. This study was supported by a grant from the NH&MRC, Australia.

Topics: Antioxidants; Blood Glucose; Blood Pressure; Coenzymes; Diabetes Mellitus, Type 2; Dietary Supplements; Double-Blind Method; F2-Isoprostanes; Female; Fenofibrate; Glycated Hemoglobin; Humans; Hyperlipidemias; Hypolipidemic Agents; Male; Middle Aged; Oxidative Stress; Ubiquinone

Statins are the most widely used to lower elevated low-density lipoprotein levels and preventing cardiovascular diseases in humans. However, about 20% of patients treated with this medication suffer from statin-related myalgia. To this end, this study investigated the potential effect of nano-particulate formulation in alleviating the muscles and liver damage either alone or when co-administered with nano coenzyme Q10 and nano vitamin E.. Male Wistar rats were fed normal diet or high-fat diet for 12 weeks, following which rats were treated with either (i) atorvastatin (5 or 20 mg/kg/day, p.o.) or (ii) atorvastatin with CoQ10 (10 mg/kg/day, p.o.) (iii) and/or vitamin E (30 mg/kg/day, p.o.) in free particle or nanoparticle forms for another 4 weeks. In all rats, serum total cholesterol (CH), triglycerides (TGs), low (LDL) and high (HDL) density lipoproteins, alanine (ALT) and aspartate (AST) transaminases, alkaline phosphatase (ALP), creatine kinase (CK), albumin (ALB), as well as hepatic malondialdehyde (MDA) and antioxidants "reduced glutathione (GSH) and superoxide dismutase (SOD)" were measured. Additionally quadriceps muscles and liver tissues were used for histopathological examination.. The antihyperlipidemic effect of statins was not altered when formulated as nanoparticles; albeit the former showed a prominent reduction in the liver and muscle enzymes and histopathological alterations together with a marked decline in the oxidative stress as compared to the free particulate form. These results were augmented when atorvastatin was combined with CoQ10 and/or Vit.E.. Nanoparticulate formulation alleviated the statins induced liver and muscle damage especially when combined with CoQ10 and/or Vit.E.

Topics: Animals; Anticholesteremic Agents; Antioxidants; Atorvastatin; Drug Compounding; Hyperlipidemias; Liver; Male; Muscles; Nanoparticles; Oxidative Stress; Rats; Rats, Wistar; Ubiquinone; Vitamin E; Vitamins

Statins are the first line treatment for the management of hyperlipidemia. However, the primary adverse effect limiting their use is myopathy. This study examines the efficacy and safety of red yeast rice (RYR), a source of natural statins, as compared with atorvastatin, which is the most widely used synthetic statin. Statin interference with the endogenous synthesis of coenzyme Q10 (CoQ10) prompted the hypothesis that its deficiency may be implicated in the pathogenesis of statin-associated myopathy. Hence, the effects of combination of CoQ10 with either statin have been evaluated. Rats were rendered hyperlipidemic through feeding them a high-fat diet for 90 days, during the last 30 days of the diet they were treated daily with either atorvastatin, RYR, CoQ10, or combined regimens. Lipid profile, liver function tests, and creatine kinase were monitored after 15 and 30 days of drug treatments. Heart contents of CoQ9 and CoQ10 were assessed and histopathological examination of the liver and aortic wall was performed. RYR and CoQ10 had the advantage over atorvastatin in that they lower cholesterol without elevating creatine kinase, a hallmark of myopathy. RYR maintained normal levels of heart ubiquinones, which are essential components for energy production in muscles. In conclusion, RYR and CoQ10 may offer alternatives to overcome atorvastatin-associated myopathy.

Topics: Animals; Aorta; Atorvastatin; Biological Products; Combined Modality Therapy; Creatine Kinase; Diet, High-Fat; Heptanoic Acids; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Lipoproteins; Liver; Male; Muscular Diseases; Myocardium; Pyrroles; Rats; Ubiquinone

Topics: Atorvastatin; Clinical Trials as Topic; Drug Monitoring; Drug-Related Side Effects and Adverse Reactions; Evidence-Based Practice; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Outcome Assessment, Health Care; Practice Guidelines as Topic; Pyrroles; Rhabdomyolysis; Risk Adjustment; Ubiquinone; Vitamins

Obesity is the major cause of type 2 diabetes with hyperlipidemia as one of its complications and antioxidants were found to be beneficial in such disease conditions. The present investigation is geared towards reduction of the dose required/improve the bioavailability of the combination of antioxidants, ellagic acid and coenzyme Q10 by co-encapsulating them into nanoparticles and study the possible synergism in ameliorating hyperlipidemia in high fat diet fed rats. The co-encapsulated particles at 10% (w/w of polymer) loading of ellagic acid and coenzyme Q10 have particle size of 260 nm. Male Sprague-Dawley (SD) rats on feeding high fat diet for over 4 weeks developed hyperlipidemia. The hyperlipidemic rats on 2 weeks post treatment with antioxidant combination administered as oral suspension or nanoparticles found to ameliorate the hyperlipidemic conditions and nanoparticles were found to be equally/more effective at 3 times lower dose in sustaining cholesterol lowering effect for extended periods, lowering glucose and triglycerides and in improving endothelial functioning, indicating the ability of the nanoparticles in improving efficacy of the duo. The results promise the potential of nanoparticles in improving the efficacy of ellagic acid and coenzyme Q10 in treating high fat diet induced hyperlipidemia in rats.

Topics: Administration, Oral; Animals; Antioxidants; Dietary Fats; Drug Carriers; Drug Compounding; Ellagic Acid; Hyperlipidemias; Male; Nanoparticles; Rats; Rats, Sprague-Dawley; Treatment Outcome; Ubiquinone

Tamoxifen (TAM), a non-steroidal anti-estrogen that is widely used in adjuvant therapy for all stages of breast carcinomas and in chemoprevention of high-risk group. The hepatic estrogenic effect of TAM induces hypertriglyceridemia by reduced activity of lipolytic enzymes (LPL) on triglycerides. Coenzyme Q10 (Co Q10), riboflavin and niacin are proved to be potent antioxidant and protective agents against many diseases including cancer and cardiovascular diseases (CVD). In this context, the objective of the study is to find the effect of the combined modality of Co Q10 (100 mg), riboflavin (10 mg) and niacin (50 mg) with TAM (10 mg twice a day) on serum lipids and lipoprotein levels in postmenopausal women with breast cancer.. The vitamin supplementation with tamoxifen was given for a period of 90 days. Blood samples were collected at the base line, 45th and 90th day during the course of treatment. Plasma total cholesterol (TC), free cholesterol (FC), ester cholesterol (EC), phospholipids (PL), triglycerides (TGL), free fatty acids (FFA), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and very low density cholesterol (VLDL-C) were estimated in 78 untreated, only TAM-treated and combinatorialy treated group along with 46 age- and sex-matched controls.. Serum TGL and VLDL-C (p<0.001) were found to be significantly elevated and LDL-C (p<0.01), significantly reduced among TAM-treated patients as compared to the untreated breast cancer subjects. All the lipids and lipoprotein levels were found to be significantly altered in the untreated breast cancer patients when compared to their normal counterparts. All the lipid and lipoprotein abnormalities were reverted back to near normal levels on 90 days of treatment on combinatorial therapy.. The study figures the altered lipid and lipoprotein levels in the untreated and TAM-treated breast cancer patients. On combination therapy with Co Q10, riboflavin and niacin, it counteracts the tamoxifen-induced hyperlipidemia to normal levels.

Topics: Adult; Aged; Breast Neoplasms; Cholesterol, LDL; Cholesterol, VLDL; Coenzymes; Drug Therapy, Combination; Female; Humans; Hyperlipidemias; Lipid Metabolism; Lipoproteins; Middle Aged; Niacin; Postmenopause; Riboflavin; Tamoxifen; Triglycerides; Ubiquinone

It has been shown that treating hypercholesterolemic patients (HPC) with statins leads to a decrease, at least in plasma, not only in cholesterol, but also in important non-sterol compounds such as ubiquinone (CoQ10), and possibly dolichols, that derive from the same biosynthetic pathway. Plasma CoQ10 decrease might result in impaired antioxidant protection, therefore leading to oxidative stress. In the present paper we investigated the levels in plasma, lymphocytes and erythrocytes, of ubiquinol and ubiquinone, other enzymatic and non-enzymatic lipophilic and hydrophilic antioxidants, polyunsaturated fatty acids of phosfolipids and cholesterol ester fractions, as well as unsaturated lipid and protein oxidation in 42 hypercholesterolemic patients treated for 3 months. The patients were treated with different doses of 3 different statins, i.e. atorvastatin 10 mg (n = 10) and 20 mg (n = 7), simvastatin, 10 mg (n = 5) and 20 mg (n = 10), and pravastatin, 20 mg (n = 5) and 40 mg (n = 5). Simvastatin, atorvastatin and pravastatin produced a dose dependent plasma depletion of total cholesterol (t-CH), LDL-C, CoQ10H2, and CoQ10, without affecting the CoQ10H2/CoQ10 ratio. The other lipophilic antioxidants (d-RRR-alpha-tocopherol-vit E-, gamma-tocopherol, vit A, lycopene, and beta-carotene), hydrophilic antioxidants (vit C and uric acid), as well as, TBA-RS and protein carbonyls were also unaffected. Similarly the erythrocyte concentrations of GSH and PUFA, and the activities of enzymatic antioxidants (Cu,Zn-SOD, GPx, and CAT) were not significantly different from those of the patients before therapy. In lymphocytes the reduction concerned CoQ10H2, CoQ10, and vit E; other parameters were not investigated. The observed decline of the levels of CoQ10H2 and CoQ10 in plasma and of CoQ10H2, CoQ10 and vit E in lymphocytes following a 3 month statin therapy might lead to a reduced antioxidant capacity of LDL and lymphocytes, and probably of tissues such as liver, that have an elevated HMG-CoA reductase enzymatic activity. However, this reduction did not appear to induce a significant oxidative stress in blood, since the levels of the other antioxidants, the pattern of PUFA as well as the oxidative damage to PUFA and proteins resulted unchanged. The concomitant administration of ubiquinone with statins, leading to its increase in plasma, lymphocytes and liver may cooperate in counteracting the adverse effects of statins, as already pointed out by various authors on the ba

Topics: Antioxidants; Atorvastatin; Catalase; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Coenzymes; Erythrocytes; Fatty Acids, Unsaturated; Glutathione; Glutathione Peroxidase; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Lymphocytes; Male; Middle Aged; Pravastatin; Pyrroles; Simvastatin; Superoxide Dismutase; Ubiquinone; Vitamin E

Familial combined hyperlipidemia (FCH) is characterized by a familial occurrence of a multiple-type hyperlipidemia, associated with coronary risk. The latter may be related to increased levels of small, dense LDL particles that have been found to be more prone to oxidative modification. We isolated total LDL as fresh as possible from 12 normolipidemic relatives with a buoyant LDL subfraction profile (group 1), 7 normolipidemic subjects with a dense LDL subfraction profile (group 2), and 16 hyperlipidemic FCH subjects with a dense LDL subfraction profile (group 3). In these nonobese and normotensive men, we studied the resistance of total LDL against Cu(2+)-oxidation in vitro. In addition, we analyzed the alpha-tocopherol and the coenzyme Q10 contents of LDL and determined their relation to LDL oxidizability. LDL isolated from group 3 subjects was more susceptible to oxidative modification than LDL from group 1 subjects (lag time: 60.4 +/- 8.1 versus 70.4 +/- 11.4 minutes; P < .05). For the combined groups, the ratio of ubiquinol-10 to polyunsaturated fatty acids in LDL, together with the basal amount of dienes in LDL, were good predictors of the rate of LDL oxidation (R2 = .73, P = .0001). In groups 2 and 3, the redox status of coenzyme Q10 (ubiquinol-10/ubiquinone-10) and the ratio of ubiquinol-10 to alpha-tocopherol in LDL were reduced compared with group 1 (P < .05). The K-value a measure of the LDL density, correlated with the the redox status (r = .37, P < .05). We conclude that in subjects with FCH total LDL is more prone to oxidation, due to the predominance of dense LDL particles. In addition, the decreased redox status of coenzyme Q10 in LDL from subjects with a dense LDL subfraction profile suggests that the LDL in the circulation has already undergone some oxidation.

Topics: Adult; Biomarkers; Coenzymes; Family; Female; Humans; Hyperlipidemias; Lipoproteins, LDL; Male; Middle Aged; Oxidation-Reduction; Ubiquinone