coenzyme-q10 and Hypercholesterolemia

Coenzyme Q10 (CoQ10) is the only lipid-soluble antioxidant that animal cells synthesize de novo. It is found in cell membranes and is particularly well known for its role in the electron transport chain in mitochondrial membranes during aerobic cellular respiration. A deficiency in either its bioavailability or its biosynthesis can lead to one of several disease states. Primary deficiency has been well described and results from mutations in genes involved in CoQ10 biosynthesis. Secondary deficiency may be linked to hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), which are used for the treatment of hypercholesterolemia. Dietary contributions of CoQ10 are very small, but supplementation is effective in increasing plasma CoQ10 levels. It has been clearly demonstrated that treatment with CoQ10 is effective in numerous disorders and deficiency states and that supplementation has a favorable outcome. However, CoQ10 is not routinely prescribed in clinical practice. This review explores primary as well as statin-induced secondary deficiency and provides an overview of the benefits of CoQ10 supplementation.

Topics: Dietary Supplements; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Mutation; Ubiquinone

Topics: Anticholesteremic Agents; Cholesterol, LDL; Dietary Supplements; Dyslipidemias; Humans; Hypercholesterolemia; Lovastatin; Olea; Vitis

The use of nutritional supplements to treat hypercholesterolemia is gradually increasing, however further studies on their efficacy and safety are required.. The present clinical trial included patients with moderate hypercholesterolemia and cardiovascular risk who were treated either with a nutraceutical preparation containing 3.75mg of monacolin K, 515mg of berberine and 50mg of coenzyme Q10 per tablet (Lipok®) or with a placebo. The clinical and laboratory variables were analyzed at baseline and at three and six months. None of the patients was diabetic, and none was being treated with lipid-lowering drugs or with any other nutritional supplements affecting lipid metabolism.. In patients of the intervention group and of the placebo group, baseline LDL-C was 134.7mg/dL (14.4) and 138.7mg/dL (15.2), respectively. At three months after treatment start, LDL-C had decreased by 26.1mg/dL (-32.4 to 19.7) and increased by 4.5mg/dL (-1.5 to 10.5) in the respective groups. In the intervention group, a similar decrease in non-HDL-C and total cholesterol was observed, while no significant changes were observed in either group for HDL-C, triglycerides and lipoprotein(a). A good tolerance and safety profile was observed.. In conclusion, this study demonstrates that the combination of monacolin K, berberine and coenzyme Q10 is effective and safe for treating hypercholesterolemia in patients with a moderate degree of excess LDL-C and cardiovascular risk.

Topics: Berberine; Cardiovascular Diseases; Cholesterol, LDL; Dietary Supplements; Heart Disease Risk Factors; Humans; Hypercholesterolemia; Lipid Metabolism; Lovastatin; Risk Factors; Treatment Outcome; Ubiquinone

Probiotics incorporated into dairy products have been shown to reduce total (TC) and LDL cholesterolemia (LDL-C) in subjects with moderate hypercholesterolemia. More specifically, probiotics with high biliary salt hydrolase activity, e.g. Bifidobacterium longum BB536, may decrease TC and LDL-C by lowering intestinal cholesterol reabsorption and, combined with other nutraceuticals, may be useful to manage hypercholesterolemia in subjects with low cardiovascular (CV) risk. This study was conducted to evaluate the efficacy and safety of a nutraceutical combination containing Bifidobacterium longum BB536, red yeast rice (RYR) extract (10 mg/day monacolin K), niacin, coenzyme Q10 (Lactoflorene Colesterolo®). The end-points were changes of lipid CV risk markers (LDL-C, TC, non-HDL-cholesterol (HDL-C), triglycerides (TG), apolipoprotein B (ApoB), HDL-C, apolipoprotein AI (ApoAI), lipoprotein(a) (Lp(a), proprotein convertase subtilisin/kexin type 9 (PCSK9)), and of markers of cholesterol synthesis/absorption.. A 12-week randomized, parallel, double-blind, placebo-controlled study. Thirty-three subjects (18-70 years) in primary CV prevention and low CV risk (SCORE: 0-1% in 24 and 2-4% in 9 subjects; LDL-C: 130-200 mg/dL) were randomly allocated to either nutraceutical (N = 16) or placebo (N = 17).. Twelve-week treatment with the nutraceutical combination, compared to placebo, significantly reduced TC (- 16.7%), LDL-C (- 25.7%), non-HDL-C (- 24%) (all p < 0.0001), apoB (- 17%, p = 0.003). TG, HDL-C, apoAI, Lp(a), PCSK9 were unchanged. Lathosterol:TC ratio was significantly reduced by the nutraceutical combination, while campesterol:TC ratio and sitosterol:TC ratio did not change, suggesting reduction of synthesis without increased absorption of cholesterol. No adverse effects and a 97% compliance were observed.. A 12-week treatment with a nutraceutical combination containing the probiotic Bifidobacterium longum BB536 and RYR extract significantly improved the atherogenic lipid profile and was well tolerated by low CV risk subjects.. NCT02689934 .

Topics: Adult; Bifidobacterium longum; Biological Products; Cardiovascular Diseases; Dietary Supplements; Double-Blind Method; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Niacin; Placebos; Probiotics; Risk Factors; Ubiquinone

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

Metabolic syndrome (MetS) is a world-wide epidemic disease with an increased risk of morbidity and mortality. Treatment strategies of MetS include pharmacologic and non-pharmacologic interventions and in this respect a relevant role has been shown for nutraceutical compounds (NCs). The aim of this study was to investigate the efficacy and safety of NCs incorporated with diet and lifestyle management versus diet alone, in lowering blood pressure (BP) values and improving lipid and glucose profile, in a group of hypertensives and hyper-cholesterolemic patients with MetS.. 104 subjects with MetS (mean age 57.4 ± 8.8 years, 51% males) without history of cardio-vascular (CV) diseases were enrolled in the study. 52 subjects were treated with a once-daily oral formulation of a NCs containing red yeast rice and coenzyme Q10 added to their diet for 2 months and were compared with the 52 patients following a diet program. Differences in BP, serum total cholesterol (TC), low- and high-density-lipoprotein cholesterol (LDLC and HDLC), triglycerides (TG) and glucose values were compared by analysis of variance.. A significant reduction of BP, TC, TG, LDLC and glucose levels was observed in both treatment groups. However, a greater reduction of systolic BP (-5.2 vs. -3.0 mmHg), diastolic BP (-4.9 vs. 2.9 mmHg), total cholesterol (-17.2%), LDLC (-21.8%), TG (-16.0%) and serum glucose (-3.4%) was observed in the treatment group relative to the control (p < 0.001 for all); HDLC remained unchanged (p = N.S.). Gender difference was not found in either group (p = N.S.).. In patients with MetS, NC supplementation was safe, well tolerated and effective in improving clinic BP, lipid and glucose profile.

Topics: Aged; Anticholesteremic Agents; Blood Glucose; Cholesterol, HDL; Cholesterol, LDL; Diet, Mediterranean; Dietary Supplements; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hypertension; Lovastatin; Male; Metabolic Syndrome; Middle Aged; Treatment Outcome; Triglycerides; Ubiquinone

The aim of our study was to investigate whether treatment with red yeast rice added with Coenzyme Q10 is associated with changes in endothelial function and arterial stiffness.. This double blind, placebo-controlled, randomized clinical trial was carried out on 40 non-smoker moderately hypercholesterolemic subjects (ClinicalTrial.gov ID NCT02492464). After 4 weeks of diet and physical activity, patients were allocated to treatment with placebo or with an active product containing 10 mg monacolins and 30 mg Coenzyme Q10, to be assumed for 6 months. Endothelial reactivity and arterial stiffness have been measured through the validated Vicorder® device.. During monacolin treatment, patients experienced a more favorable percentage change in low density lipoprotein (LDL)-cholesterol (after monacolin treatment: -26.3%; after placebo treatment: +3.4%, p < 0.05). Endothelial reactivity (pulse volume displacement after monacolin treatment: +6.0%; after placebo treatment: -0.3%, p < 0.05), and arterial stiffness (pulse wave velocity (PWV) after monacolin treatment: -4.7%; after placebo: +1.1%, p < 0.05) also significantly improved only after monacolin treatment.. The long-term assumption of the tested dietary supplement is associated with an improvement in LDL-cholesterolemia, endothelial reactivity and PWV in moderately hypercholesterolemic subjects.

Topics: Anticholesteremic Agents; Biological Products; Cholesterol, LDL; Combined Modality Therapy; Diet, Mediterranean; Dietary Supplements; Double-Blind Method; Endothelium, Vascular; Exercise; Female; Humans; Hypercholesterolemia; Italy; Male; Middle Aged; Monascus; Naphthalenes; Severity of Illness Index; Ubiquinone; Vascular Diseases; Vascular Resistance; Vascular Stiffness

Primary cardiovascular (CV) prevention may be achieved by lifestyle/nutrition changes, although a relevant role is now emerging for specific, functional foods and nutraceutical compounds (NCs). The aim of this study was to investigate the efficacy and safety of NCs in lowering blood pressure (BP) and improving lipid profile, when added to diet and lifestyle management versus diet alone in a group of patients with hypertension (HT) and hypercholesterolemia (HCh) with low CV risk.. Sixty-six patients with HT and HCh with grade 1 essential HT (mean age 56.0 ± 4.6 years) without history of CV diseases or organ damage were analyzed. These subjects were started on one tablet of an NC-containing red yeast rice, policosanol, berberine, folic acid and coenzyme Q10 once daily for 6 months and were age and gender matched with subjects following a diet program. Differences in clinic BP, 24-h ambulatory BP (24 h-ABPM), serum total cholesterol, low-density and high-density lipoprotein cholesterol (LDL-C and HDL-C) and triglyceride values were compared by analysis of variance.. In the treatment group, a significant reduction of systolic 24 h-ABPM (141.6 ± 6.4 vs. 136.2 ± 4.8 mmHg; p < 0.05) and pulse pressure 24 h-ABPM (52.6 ± 7.2 vs. 47.3 ± 5.4 mmHg; p < 0.05) was found at the end of follow-up. A reduction of total cholesterol (-19.2%), LDL-C (-17.4%) and triglycerides (-16.3%) was observed (p < 0.001 for all); HDL-C remained unchanged. No difference was found in the control group.. The tested NCs was found to be safe, well tolerated and effective in reducing mean 24-h systolic and 24-h pulse pressure and in improving lipid pattern.

Topics: Berberine; Biological Products; Blood Pressure; Cardiovascular Diseases; Diet; Dietary Supplements; Fatty Alcohols; Female; Folic Acid; Health Behavior; Humans; Hypercholesterolemia; Hypertension; Life Style; Lipids; Male; Middle Aged; Risk Factors; Ubiquinone

Fibromyalgia (FM) is characterized by generalized pain and chronic fatigue of unknown etiology. To evaluate the role of oxidative stress in this disorder, we measured plasma levels of ubiquinone-10, ubiquinol-10, free cholesterol (FC), cholesterol esters (CE), and free fatty acids (FFA) in patients with juvenile FM (n=10) and in healthy control subjects (n=67). Levels of FC and CE were significantly increased in juvenile FM as compared with controls, suggesting the presence of hypercholesterolemia in this disease. However, plasma level of ubiquinol-10 was significantly decreased and the ratio of ubiquinone-10 to total coenzyme Q10 (%CoQ10) was significantly increased in juvenile FM relative to healthy controls, suggesting that FM is associated with coenzyme Q10 deficiency and increased oxidative stress. Moreover, plasma level of FFA was significantly higher and the content of polyunsaturated fatty acids (PUFA) in total FFA was significantly lower in FM than in controls, suggesting increased tissue oxidative damage in juvenile FM. Interestingly, the content of monoenoic acids, such as oleic and palmitoleic acids, was significantly increased in FM relative to controls, probably to compensate for the loss of PUFA. Next, we examined the effect of ubiquinol-10 supplementation (100 mg/day for 12 weeks) in FM patients. This resulted in an increase in coenzyme Q10 levels and a decrease in %CoQ10. No changes were observed in FFA levels or their composition. However, plasma levels of FC and CE significantly decreased and the ratio of FC to CE also significantly decreased, suggesting that ubiquinol-10 supplementation improved cholesterol metabolism. Ubiquinol-10 supplementation also improved chronic fatigue scores as measured by the Chalder Fatigue Scale.

Topics: Adolescent; Antioxidants; Ataxia; Case-Control Studies; Child; Cholesterol; Dietary Supplements; Double-Blind Method; Fatigue; Fatty Acids, Monounsaturated; Fatty Acids, Nonesterified; Female; Fibromyalgia; Humans; Hypercholesterolemia; Male; Mitochondrial Diseases; Muscle Weakness; Oleic Acid; Oxidative Stress; Pain Measurement; Ubiquinone

Statins are at the forefront of strategies to manage dyslipidemia, although they are not always well tolerated. At 6-7 months after the drug was supplied, discontinuation rates averaged 30%. Alternate agents to statins have been studied. Some nutraceuticals demonstrated an efficacy in reducing cholesterol concentrations. However, there are no data regarding the use of nutraceuticals in elderly dyslipidemic patients. The purpose of this study was to examine the efficacy, safety, and tolerability of a nutraceutical-based protocol in elderly hypercholesterolemic patients previously intolerant to statins.. This study was performed as a randomized, prospective, parallel group, single-blind study. Patients were included in the study if they had high total cholesterolemia, high low-density lipoprotein cholesterol (LDL-C), >75 years of age, statin-intolerant, and were refusing other pharmaceutical treatments for hypercholesterolemia. At the baseline visit, eligible patients were randomized to either nutraceutical-combined pill (containing berberine 500 mg, policosanol 10 mg, red yeast rice 200 mg, folic acid 0.2 mg, coenzyme Q10 2.0 mg, and astaxanthin 0.5 mg) or placebo, and the first dose was dispensed. The efficacy, safety, and tolerability of the proposed treatment were fully assessed after 3, 6, and 12 months of treatment.. Out of 106 consecutive patients screened, 80 eligible patients were randomized to receive either nutraceutical-combined pill (40 patients) or placebo (40 patients). No patients were lost and no deaths occurred during the follow-up. There was a statistically significant reduction in total cholesterolemia (-20%), LDL-C (-31%), and insulin resistance (-10%) with nutraceutical treatment. No significant changes were detected for plasma high-density lipoprotein cholesterol (HDL-C). Furthermore, no statistical differences were found between baseline and end-study safety parameters. Medication compliance and tolerability were high.. In this study the authors have demonstrated that combined nutraceuticals significantly reduce cholesterolemia and achieved acceptable plasma LDL-C levels in elderly hypercholesterolemic patients who were previously statin-intolerant. Combined nutraceuticals is also safe and well tolerated in these patients.

Topics: Aged; Aged, 80 and over; Anticholesteremic Agents; Berberine; Biological Products; Blood Glucose; Cholesterol; Dietary Supplements; Fatty Alcohols; Female; Folic Acid; Humans; Hypercholesterolemia; Lipoproteins, LDL; Male; Medication Adherence; Prospective Studies; Single-Blind Method; Ubiquinone; Xanthophylls

Statins are among the most widely used drugs in the management of hypercholesterolemia. In addition to inhibiting endogenous cholesterol synthesis, however, statins decrease coenzyme Q10 (CoQ10) synthesis. CoQ10 has been reported to have antioxidant properties, and administration of drugs that decrease CoQ10 synthesis might lead to increased oxidative stress in vivo. Our present study examined the hypothesis that atorvastatin increased oxidative stress in hypercholesterolemic patients due to its inhibition of CoQ10 synthesis. We investigated the effects of atorvastatin (10 mg/d) administration for 5 months on lowering hypercholesterolemia and blood antioxidant status. The study population included 19 hypercholesterolemic outpatients. Blood levels of lipid and antioxidant markers, consisting of vitamin C, vitamin E, CoQ10, and glutathione (GSH), and urinary levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) were examined pre- and postadministration of atorvastatin. Atorvastatin administration resulted in a significant decrease in blood levels of total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol, vitamin E, and CoQ10 (P < .05); however, a significant increase in the ratios of vitamin E/LDL cholesterol and CoQ10/LDL cholesterol was noted (P < .05). Atorvastatin had no significant effect on red blood cell (RBC) level of GSH and urinary 8-OHdG. The present study provides evidence that atorvastatin exerts a hypocholesterolemic effect, but on the basis of the urinary level of 8-OHdG and the blood ratios of vitamin E/LDL cholesterol and CoQ10/LDL cholesterol, has no oxidative stress-inducing effect.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Anticholesteremic Agents; Atorvastatin; Cholesterol, LDL; Deoxyguanosine; Erythrocytes; Female; Glutathione; Heptanoic Acids; Humans; Hypercholesterolemia; Lipids; Male; Middle Aged; Oxidative Stress; Pyrroles; Ubiquinone; Vitamin E

Treatment of hypercholesterolemia with statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) is effective in the primary and secondary prevention of cardiovascular disease. However, statin use is often associated with a variety of muscle-related symptoms or myopathies. Myopathy may be related in part to statin inhibition of the endogenous synthesis of coenzyme Q10, an essential cofactor for mitochondrial energy production. The aim of this study is to determine whether coenzyme Q10 supplementation would reduce the degree of muscle pain associated with statin treatment. Patients with myopathic symptoms were randomly assigned in a double-blinded protocol to treatment with coenzyme Q10 (100 mg/day, n = 18) or vitamin E (400 IU/day, n = 14) for 30 days. Muscle pain and pain interference with daily activities were assessed before and after treatment. After a 30-day intervention, pain severity decreased by 40% (p <0.001) and pain interference with daily activities decreased by 38% (p <0.02) in the group treated with coenzyme Q10. In contrast, no changes in pain severity (+9%, p = NS) or pain interference with daily activities (-11%, p = NS) was observed in the group treated with vitamin E. In conclusion, results suggest that coenzyme Q10 supplementation may decrease muscle pain associated with statin treatment. Thus, coenzyme Q10 supplementation may offer an alternative to stopping treatment with these vital drugs.

Topics: Activities of Daily Living; Aged; Biomarkers; Cholesterol, LDL; Coenzymes; Creatine Kinase; Double-Blind Method; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Middle Aged; Muscular Diseases; Pain; Pain Measurement; Patient Compliance; Severity of Illness Index; Surveys and Questionnaires; Treatment Outcome; Triglycerides; Ubiquinone; Vitamin E; Vitamins

The long-term efficacy and safety of HMG-CoA reductase inhibitors (statins) have been established in large multicenter trials. Inhibition of this enzyme, however, results in decreased synthesis of cholesterol and other products downstream of mevalonate, such as CoQ10 or dolichol. This was a randomized double-blind, placebo-controlled study that examined the effects of CoQ10 and placebo in hypercholesterolemic patients treated by atorvastatin. Eligible patients were given 10mg/day of atorvastatin for 16 weeks. Half of the patients (n=24) were supplemented with 100mg/day of CoQ10, while the other half (n=25) were given the placebo. Serum LDL-C levels in the CoQ10 group decreased by 43%, while in the placebo group by 49%. The HDL-C increment was more striking in the CoQ10 group than in the placebo group. All patients showed definite reductions of plasma CoQ10 levels in the placebo group, by 42%. All patients supplemented with CoQ10 showed striking increases in plasma CoQ10 by 127%. In conclusion atorvastatin definitely decreased plasma CoQ10 levels and supplementation with CoQ10 increased their levels. These changes in plasma CoQ10 levels showed no relation to the changes in serum AST, ALT and CK levels. Further studies are needed, however, for the evaluation of CoQ10 supplementation in statin therapy.

Topics: Aged; Atorvastatin; Cholesterol, HDL; Cholesterol, LDL; Coenzymes; Double-Blind Method; Drug Therapy, Combination; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Liver Function Tests; Male; Middle Aged; Muscles; Myoglobin; Pyrroles; Ubiquinone; Vitamins

Reduction of serum cholesterol levels with statin therapy decreases the risk of coronary heart disease. Inhibition of HMG-CoA reductase by statin results in decreased synthesis of cholesterol and other products downstream of mevalonate, which may produce adverse effects in statin therapy. We studied the reductions of serum ubiquinol-10 and ubiquinone-10 levels in hypercholesterolemic patients treated with atorvastatin. Fourteen patients were treated with 10 mg/day of atorvastatin, and serum lipid, ubiquinol-10 and ubiquinone-10 levels were measured before and after 8 weeks of treatment. Serum total cholesterol and LDL-cholesterol levels decreased significantly. All patients showed definite reductions of serum ubiquinol-10 and ubiquinone-10 levels, and mean levels of serum ubiquinol-10 and ubiquinone-10 levels decreased significantly from 0.81 +/- 0.21 to 0.46 +/- 0.10 microg/ml (p < 0.0001), and from 0.10 +/- 0.06 to 0.06 +/- 0.02 microg/ml (p = 0.0008), respectively. Percent reductions of ubiquinol-10 and those of total cholesterol showed a positive correlation (r = 0.627, p = 0.0165). As atorvastatin reduces serum ubiquinol-10 as well as serum cholesterol levels in all patients, it is imperative that physicians are forewarned about the risks associated with ubiquinol-10 depletion.

Topics: Aged; Atorvastatin; Biomarkers; Cholesterol; Coenzymes; Female; Follow-Up Studies; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Pyrroles; Risk Factors; Treatment Outcome; Ubiquinone

Statin drugs (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) reduce the level of cholesterol by inhibiting the synthesis of mevalonate, an intermediary in the cholesterol biosynthetic pathway. Use of statin drugs has been associated with a variety of skeletal muscle-related complaints. Coenzyme Q10 (CoQ10), a component of the mitochondrial respiratory chain, is also synthesized from mevalonate, and decreased muscle CoQ10 concentration may have a role in the pathogenesis of statin drug-related myopathy.. To measure the CoQ10 concentration and respiratory chain enzyme activities in muscle biopsy specimens from 18 patients with statin drug-related myopathy and to look for evidence of apoptosis using the TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling) assay.. An open-labeled study of CoQ10 concentration in muscle from patients with increased serum creatine kinase concentrations while receiving standard statin drug therapy.. Neuromuscular centers at 2 academic tertiary care hospitals.. Muscle structure was essentially normal in 14 patients and showed evidence of mitochondrial dysfunction and nonspecific myopathic changes in 2 patients each. Muscle CoQ10 concentration was not statistically different between patients and control subjects, but it was more than 2 SDs below the normal mean in 3 patients and more than 1 SD below normal in 7 patients. There was no TUNEL positivity in any patients.. These data suggest that statin drug-related myopathy is associated with a mild decrease in muscle CoQ10 concentration, which does not cause histochemical or biochemical evidence of mitochondrial myopathy or morphologic evidence of apoptosis in most patients.

Topics: Adult; Aged; Coenzymes; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Middle Aged; Muscle, Skeletal; Ubiquinone

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

Serum coenzyme Q10 (CoQ10: 2-(3,7,11,15,19,23,27,31,35,39-decamethyl-2,6,10,14,18,22,26,30,34 ,38 -tetracontadecaenyl)-5,6-dimethoxy-3-methyl-1,4-benzoquinone, CAS 303-98-0) and cholesterol levels were measured to assess the effect of cholesterol-lowering therapy in patients with non-insulin-dependent diabetes mellitus (NIDDM). Twenty healthy volunteers, 97 NIDDM patients and 2 patients with familial hypercholesterolemia were studied. None had overt heart failure or any other heart disease. Mean serum CoQ10 concentrations were significantly (p < 0.01) lower in diabetic patients with normal serum cholesterol concentrations, either with or without administration of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (HMG-CoA RIs) including simvastatin (normal: 0.91 +/- 0.26 (mean +/- SD) mumol 1(-1); diabetic with HMG-CoA RI: 0.63 +/- 0.19; diabetic without HMG-CoA RI: 0.66 +/- 0.21). CoQ10 concentrations were higher (1.37 +/- 0.48, p < 0.001) in diabetic patients with hypercholesterolemia. Simvastatin or low density lipoprotein apheresis decreased serum CoQ10 concentrations along with decreasing serum cholesterol. Oral CoQ10 supplementation in diabetic patients receiving HMG-CoA RI significantly (p < 0.001) increased serum CoQ10 from 0.81 +/- 0.24 to 1.47 +/- 0.44 mumol 1(-1), without affecting cholesterol levels. It significantly (p < 0.03) decreased cardiothoracic ratios from 51.4 +/- 5.1 to 49.2 +/- 4.7%. In conclusion, serum CoQ10 levels in NIDDM patients are decreased and may be associated with subclinical diabetic cardiomyopathy reversible by CoQ10 supplementation.

Topics: Adult; Anticholesteremic Agents; Antioxidants; Cholesterol; Chromatography, High Pressure Liquid; Coenzymes; Diabetes Mellitus, Type 2; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Middle Aged; Pravastatin; Simvastatin; Ubiquinone

The purpose of the present study was to evaluate the effects of MUFA vs PUFA enriched diets on the plasma and LDL lipid profile and antioxidant contents in mild hypercholesterolemic and triglyceridemic subjects. The study was divided in two consecutive diet periods. Two groups of 11 dyslipidemic patients each (type IIb and type IV) were recruited and during the first period (lasting four weeks) received a linoleic rich diet while during the following four weeks took an oleate rich diet. Both groups showed no significant changes in cholesterol and TG concentration either in plasma or in LDL. Coenzyme Q10 and vitamin E were also unaffected by the dietary treatments. LDL proneness to be oxidatively modified increased after dietary PUFA administration and markedly decreased following the virgin olive oil enriched diet. In fact, LDL from hypertrigliceridemic subjects on a oleate-enriched diet displayed a 26% (p < 0.05) longer lag-phase in conjugated dienes generation than during linoleate-enriched diet and at recruitment. In hypercholesterolemic subjects similar results were obtained: the lag-phase was 28% longer after MUFA diet that after PUFA diet. No differences were found in the maximum propagation rate and maximum concentration of conjugated dienes among dietary periods and at recruitment. Since we found that the vit. E and CoQ10 levels in plasma and in LDL particles remained unchanged during the course of the study, we may conclude that LDL proneness to undergo oxidative modifications is mainly the result of compositional change due to the enrichment from the different diets of the relative fats.

Topics: Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Coenzymes; Dietary Fats, Unsaturated; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Humans; Hypercholesterolemia; Hypertriglyceridemia; Olive Oil; Plant Oils; Soybean Oil; Triglycerides; Ubiquinone; Vitamin E

Coenzyme Q10 (ubiquinone) the essential mitochondrial redox-component and endogenous antioxidant, packaged into the LDL + VLDL fractions of cholesterol, has been suggested as an important anti-risk factor for the development of atherosclerosis as explained by the oxidative theory. Forty-five hypercholesterolemic patients were randomized in a double-blind trial in order to be treated with increasing dosages of either lovastatin (20-80 mg/day) or pravastatin (10-40 mg/day) over a period of 18 weeks. Serum levels of coenzyme Q10 were measured parallel to the levels of cholesterol at baseline on placebo and diet and during active treatment. A dose-related significant decline of the total serum level of coenzyme Q10 was found in the pravastatin group from 1.27 +/- 0.34 at baseline to 1.02 +/- 0.31 mmol/l at the end of the study period (mean +/- S.D.), P < 0.01. After lovastatin therapy the decrease was significant as well and more pronounced, from 1.18 +/- 0.36 to 0.84 +/- 0.17 mmol/l, P < 0.001. Although HMG-CoA reductase inhibitors are safe and effective within a limited time horizon, continued vigilance of a possible adverse consequence from coenzyme Q10 lowering seems important during long-term therapy.

Topics: Adult; Aged; Antioxidants; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cholesterol, VLDL; Coenzymes; Coronary Disease; Double-Blind Method; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Lovastatin; Male; Middle Aged; Oxidation-Reduction; Pravastatin; Risk Factors; Ubiquinone

This study was undertaken to clarify the mechanism of the antihypertensive effect of coenzyme Q10 (CoQ10). Twenty-six patients with essential arterial hypertension were treated with oral CoQ10, 50 mg twice daily for 10 weeks. Plasma CoQ10, serum total and high-density lipoprotein (HDL) cholesterol, and blood pressure were determined in all patients before and at the end of the 10-week period. At the end of the treatment, systolic blood pressure (SBP) decreased from 164.5 +/- 3.1 to 146.7 +/- 4.1 mmHg and diastolic blood pressure (DBP) decreased from 98.1 +/- 1.7 to 86.1 +/- 1.3 mmHg (P < 0.001). Plasma CoQ10 values increased from 0.64 +/- 0.1 microgram/ml to 1.61 +/- 0.3 micrograms/ml (P < 0.02). Serum total cholesterol decreased from 222.9 +/- 13 mg/dl to 213.3 +/- 12 mg/dl (P < 0.005) and serum HDL cholesterol increased from 41.1 +/- 1.5 mg/dl to 43.1 +/- 1.5 mg/dl (P < 0.01). In a first group of 10 patients serum sodium and potassium, plasma clinostatic and orthostatic renin activity, urinary aldosterone, 24-hour sodium and potassium were determined before and at the end of the 10-week period. In five of these patients peripheral resistances were evaluated with radionuclide angiocardiography. Total peripheral resistances were 2,283 +/- 88 dyne.s.cm-5 before treatment and 1,627 +/- 158 dyn.s.cm-5 after treatment (P < 0.02). Plasma renin activity, serum and urinary sodium and potassium, and urinary aldosterone did not change. In a second group of 11 patients, plasma endothelin, electrocardiogram, two-dimensional echocardiogram and 24-hour automatic blood pressure monitoring were determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aldosterone; Antihypertensive Agents; Blood Pressure; Cholesterol; Cholesterol, HDL; Coenzymes; Echocardiography; Electrocardiography; Endothelins; Female; Humans; Hypercholesterolemia; Hypertension; Male; Middle Aged; Potassium; Renin; Sodium; Treatment Outcome; Ubiquinone; Vascular Resistance

Topics: Berberine; Cardiovascular Diseases; Dietary Supplements; Heart Disease Risk Factors; Humans; Hypercholesterolemia; Lovastatin; Risk Factors

Alzheimer's disease (AD) is the most common form of dementia that progressively disrupts neurocognitive function, which has neither cure nor effective treatment. Hypercholesterolemia might be involved in brain alterations that could evolve into AD. The present study aims to evaluate the potential of omega-3, Co-enzyme Q10 (Co-Q10), as well as their combination in ameliorating hypercholesterolemia-initiated AD-like disease. We adapted a hypercholesterolemic (HC) rat model, a model of oxidative stress-mediated neurodegeneration, to study AD-like pathology. Hypercholesterolemia resulted in increased lipid peroxidation coupled with declined nitric oxide production, reduced glutathione levels, and decreased antioxidant activities of glutathione-s-transferase (GST) and glutathione peroxidase (GSH-Px) in the brain. Moreover, hypercholesterolemia resulted in decreased acetylcholine (ACh) levels and increased acetylcholine-esterase (AChE) activity, along with an increment of tumor necrosis factor and amyloid-β 42. Behaviorally, HC-rats demonstrated depressive-like behavior and declined memory. Treatment of HC-rats with omega-3 and Co-Q10 (alone or in combination) alleviated the brain oxidative stress and inflammation, regulated cholinergic functioning, and enhanced the functional outcome. These findings were verified by the histopathological investigation of brain tissues. This neuroprotective potential of omega-3 and Co-Q10 was achieved through anti-oxidative, anti-inflammatory, anti-amyloidogenic, pro-cholinergic, and memory-enhancing activities against HC-induced AD-like disease; suggesting that they may be useful as prophylactic and therapeutic agents against the neurotoxic effects of hypercholesterolemia.

Topics: Alzheimer Disease; Animals; Brain; Drug Therapy, Combination; Fatty Acids, Omega-3; Hypercholesterolemia; Male; Maze Learning; Neuroprotective Agents; Random Allocation; Rats; Rats, Wistar; Ubiquinone

Myalgia and muscle weakness may appreciably contribute to the poor adherence to statin therapy. Although the pathomechanism of statin-induced myopathy is not completely understood, changes in calcium homeostasis and reduced coenzyme Q10 levels are hypothesized to play important roles. In our experiments, fluvastatin and/or coenzyme Q10 was administered chronically to normocholesterolaemic or hypercholaestherolaemic rats, and the modifications of the calcium homeostasis and the strength of their muscles were investigated. While hypercholesterolaemia did not change the frequency of sparks, fluvastatin increased it on muscles both from normocholesterolaemic and from hypercholesterolaemic rats. This effect, however, was not mediated by a chronic modification of the ryanodine receptor as shown by the unchanged ryanodine binding in the latter group. While coenzyme Q10 supplementation significantly reduced the frequency of the spontaneous calcium release events, it did not affect their amplitude and spatial spread in muscles from fluvastatin-treated rats. This indicates that coenzyme Q10 supplementation prevented the spark frequency increasing effect of fluvastatin without having a major effect on the amount of calcium released during individual sparks. In conclusion, we have found that fluvastatin, independently of the cholesterol level in the blood, consistently and specifically increased the frequency of calcium sparks in skeletal muscle cells, an effect which could be prevented by the addition of coenzyme Q10 to the diet. These results support theories favouring the role of calcium handling in the pathophysiology of statin-induced myopathy and provide a possible pathway for the protective effect of coenzyme Q10 in statin treated patients symptomatic of this condition.

Topics: Animals; Calcium; Cholesterol; Fatty Acids, Monounsaturated; Female; Fluvastatin; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Indoles; Muscle, Skeletal; Muscular Diseases; Rats; Rats, Inbred F344; Ubiquinone

It is estimated that one-third of infertility cases are due to male factors. Hyper-cholesterolemia is a social problem in many developed countries and contributed with a heterogeneous group of disorders characterized by an excess of cholesterol and its derivatives in the blood stream.. The objective of the present study was to investigate the protective effects of coenzyme Q10 and L-Carnitine supplementation on semen parameters, sperm function and reproductive hormone profiles in male Wistar rats with high LDL and Oxidized LDL (OxLDL) blood levels.. Animals were fed with cholesterol and oxidized cholesterol-rich diets for 14 weeks to elevate the LDL and OxLDL blood level, respectively. Pretreatment with coenzyme Q10 (10 mg/kg/day, oral) and L-Carnitine (350 mg/kg/day, oral) were conducted for 5 consecutive weeks. Sex hormones levels, malondialdehyde and total antioxidant concentrations, as well as testis, epididymis and seminal vesicle weight were also analyzed.. Following high LDL and OxLDL blood levels, decrease in the sperms count and viability, weights of testis, epididymis and seminal vesicle as well as concentration of testosterone and LH hormone were observed. On the other hand, in contrast to reduction of total antioxidant level, malondialdehyde concentration, both in serum and testis, was increased. However, pretreatment with L-carnitine and coenzyme Q10 increased serum sex hormones level and improved semen parameters significantly.. Overall, pretreatment with coenzyme Q10 and L-Carnitine attenuated the destructive effects of high LDL and oxidized LDL levels on spermatogenesis parameters in male rats.

Topics: Animals; Antioxidants; Carnitine; Cell Survival; Cholesterol, Dietary; Cytoprotection; Disease Models, Animal; Epididymis; Hypercholesterolemia; Infertility, Male; Lipoproteins, LDL; Luteinizing Hormone; Male; Malondialdehyde; Rats, Wistar; Sperm Count; Sperm Motility; Spermatogenesis; Spermatozoa; Testis; Testosterone; Ubiquinone

The aim of this study was to evaluate the actions of coenzyme Q10 (CoQ10) on rats with a cholesterol-rich diet (HD) and high doses of atorvastatin (ATV, 0.2, 0.56 or 1.42 mg/day).. Two experiments were done, the first one without coenzyme Q10 supplementation. On the second experiment all groups received coenzyme Q10 0.57 mg/day as supplement. After a 6-week treatment animals were sacrificed, blood and liver were analyzed and liver mitochondria were isolated and its oxygen consumption was evaluated in state 3 (phosphorylating state) and state 4 (resting state) in order to calculate the respiratory control (RC).. HD increased serum and hepatic cholesterol levels in rats with or without CoQ10. ATV reduced these values but CoQ10 improved even more serum and liver cholesterol. Triacylglycerols (TAG) were also lower in blood and liver of rats with ATV + CoQ10. HDL-C decreased in HD rats. Treatment with ATV maintained HDL-C levels. However, these values were lower in HD + CoQ10 compared to control diet (CD) + CoQ10. RC was lessened in liver mitochondria of HD. The administration of ATV increased RC. All groups supplemented with CoQ10 showed an increment in RC. In conclusion, the combined administration of ATV and CoQ10 improved biochemical parameters, liver function and mitochondrial respiration in hypercholesterolemic rats.. Our results suggest a potential beneficial effect of CoQ10 supplementation in hypercholesterolemic rats that also receive atorvastatin. This beneficial effect of CoQ10 must be combined with statin treatment in patient with high levels of cholesterol.

Topics: Animals; Atorvastatin; Cell Respiration; Cholesterol, Dietary; Cholesterol, HDL; Diet, High-Fat; Dietary Supplements; Drug Evaluation, Preclinical; Heptanoic Acids; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Liver; Male; Mitochondria, Liver; Pyrroles; Rats; Rats, Wistar; Triglycerides; Ubiquinone

To explore the interventional effects of atorvastatin and CoQ(10) on myocardial energy metabolism in rabbits with hypercholesterolemia.. Forty male New Zealand white rabbits were randomly divided into 5 groups: i.e. normal control, high cholesterol, statin, coenzyme Q(10) 1 and coenzyme Q(10) 2. After feeding for 6 weeks, the fasting blood samples were collected through ear marginal vein and the serum level of total cholesterol was determined. Myocardium was sampled for ultrastructures by electron microscopy; high-performance liquid chromatography (HPLC) was used to measure myocardial mitochondria adenosine triphosphate (ATP) and coenzyme CoQ(10). Ultraviolet spectrophotometry was used to measure the activities of mitochondrial complexes II and IV.. In high cholesterol group, myocardial fibers were arrayed disorderly with partial rupture and dissolution. There was mitochondrial swelling with disorderly and fuzzy cristae. As compared with the controls, the activities of mitochondrial respiratory chain complexes II and IV declined (5.39 ± 0.53 vs 12.95 ± 0.99, 1.89 ± 0.26 vs 6.65 ± 0.95, P < 0.01), the contents of mitochondrial ATP and CoQ(10) decreased (0.17 ± 0.05 vs 0.44 ± 0.06, 0.09 ± 0.02 vs 0.25 ± 0.04, P < 0.01); for statin group versus high cholesterol group, the activities of mitochondrial respiratory chain complexes II and IV increased (9.12 ± 1.19 vs 5.39 ± 0.53, 4.61 ± 0.52 vs 1.89 ± 0.26, P < 0.01); the content differences of mitochondrial ATP and CoQ(10) were statistically insignificant. For CoQ(10) 1 group versus statin group, the differences of respiratory chain complexes II and IV were statistically insignificant; the contents of mitochondria ATP and CoQ(10) increased (0.35 ± 0.03 vs 0.16 ± 0.04, 0.17 ± 0.02 vs 0.07 ± 0.02, P < 0.01). For coenzyme Q(10) 2 group versus coenzyme Q(10) 1 group, none of the indices was statistically significant.. High cholesterol can cause myocardial ultrastructural changes and impaired mitochondrial energy metabolism. Atorvastatin reduces the myocardial structural damage and the combination of atorvastatin and CoQ(10) may further improve the myocardial mitochondrial energy metabolism.

Topics: Animals; Atorvastatin; Energy Metabolism; Heptanoic Acids; Hypercholesterolemia; Male; Mitochondria, Heart; Myocardium; Pyrroles; Rabbits; Ubiquinone

Inhibition of squalene synthesis could transform unstable, macrophage/lipid-rich coronary plaques into stable, fibromuscular plaques. We have here treated WHHLMI rabbits, a model for coronary atherosclerosis and myocardial infarction, with a novel squalene synthase inhibitor, lapaquistat acetate (TAK-475).. Young male WHHLMI rabbits were fed a diet supplemented with lapaquistat acetate (100 or 200 mg per kg body weight per day) for 32 weeks. Serum lipid levels were monitored every 4 weeks. After the treatment, lipoprotein lipid and coenzyme Q10 levels were assayed, and coronary atherosclerosis and xanthomas were examined histopathologically or immunohistochemically. From histopathological and immunohistochemical sections, the composition of the plaque was analysed quantitatively with computer-assisted image analysis. Xanthoma was evaluated grossly.. Lapaquistat acetate decreased plasma cholesterol and triglyceride levels, by lowering lipoproteins containing apoB100. Development of atherosclerosis and xanthomatosis was suppressed. Accumulation of oxidized lipoproteins, macrophages and extracellular lipid was decreased in coronary plaques of treated animals. Treatment with lapaquistat acetate increased collagen concentration and transformed coronary plaques into fibromuscular plaques. Lapaquistat acetate also suppressed the expression of matrix metalloproteinase-1 and plasminogen activator inhibitor-1 in the plaque and increased peripheral coenzyme Q10 levels. Increased coenzyme Q10 levels and decreased very low-density lipoprotein cholesterol levels were correlated with improvement of coronary plaque composition.. Inhibition of squalene synthase by lapaquistat acetate delayed progression of coronary atherosclerosis and changed coronary atheromatous plaques from unstable, macrophage/lipid accumulation-rich, lesions to stable fibromuscular lesions.

Topics: Animals; Apolipoprotein B-100; Cholesterol; Collagen; Coronary Artery Disease; Disease Models, Animal; Disease Progression; Dose-Response Relationship, Drug; Enzyme Inhibitors; Farnesyl-Diphosphate Farnesyltransferase; Hypercholesterolemia; Hypolipidemic Agents; Image Interpretation, Computer-Assisted; Immunohistochemistry; Lipid Metabolism; Lipoproteins, LDL; Macrophages; Male; Matrix Metalloproteinase 1; Oxazepines; Piperidines; Plasminogen Activator Inhibitor 1; Rabbits; Triglycerides; Ubiquinone; Xanthomatosis

Topics: Anticholesteremic Agents; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Sleep-Wake Transition Disorders; Ubiquinone

Statin therapy can reduce the biosynthesis of both cholesterol and coenzyme Q10 by blocking the common upstream mevalonate pathway. Coenzyme Q10 depletion has been speculated to play a potential role in statin-related adverse events, and withdrawal of statin is the choice in patients developing myotoxicity or liver toxicity. However, the effect of statin withdrawal on circulating levels of coenzyme Q10 remains unknown. Twenty-six patients with hypercholesterolemia received atorvastatin at 10 mg/day for 3 months. Serum lipid profiles and coenzyme Q10 were assessed before and immediately after 3 months and were also measured 2 and 3 days after the last day on the statin. After 3 months' atorvastatin therapy, serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and coenzyme Q10 (0.43 +/- 0.23 to 0.16 +/- 0.10 microg/mL) were all significantly reduced (all p<0.001). On day 2 after the last atorvastatin, the coenzyme Q10 level was significantly elevated (0.37 +/- 0.16 microg/mL) and maintained the same levels on day 3 (0.39 +/- 0.18 microg/mL) compared with those on month 3 (both p< 0.001), while TC and LDL-C did not significantly change within the same 3 days. These results suggest that statin inhibition of coenzyme Q10 synthesis is less strict than inhibition of cholesterol biosynthesis.

Topics: Atorvastatin; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Coenzymes; Female; Heptanoic Acids; Humans; Hypercholesterolemia; Male; Middle Aged; Pyrroles; Substance Withdrawal Syndrome; Triglycerides; Ubiquinone

As statin therapy has been reported to reduce antioxidants such as vitamin E and coenzyme Q10 and there are indications that this reduction may cause impairment of left ventricular function (LVF), we studied the influence of simvastatin on LVF and serum vitamin E and coenzyme Q10 levels in humans.. We assessed the effect of simvastatin on left ventricular function and coenzyme Q10 levels in 21 (11 male, 10 female) hypercholesterolaemic subjects (mean age = 56 years) with normal LVF, over a period of 6 months. Subjects were re-tested after a 1-month wash-out period (7 months). Echocardiography was performed on all subjects before commencement of simvastatin (20 mg day(-1)), and at 1, 3, 6 and 7 months after initiation of treatment. Fasting blood samples were also collected at these intervals to assess lipids, apoproteins, vitamin E and coenzyme Q10.. Serum lipids showed the expected reductions. Plasma vitamin E and coenzyme Q10 levels were reduced by 17 +/- 4% (P < 0.01) and 12 +/- 4% (P < 0.03) at 6 months. However, the coenzyme Q10/LDL-cholesterol ratio and vitamin E/LDL-cholesterol ratio increased significantly. Left ventricular ejection fraction (EF) decreased transiently after 1 month, while no significant change was observed at 3 and 6 months. Other markers of left ventricular function did not change significantly at any time point.. Despite reduced plasma vitamin E and coenzyme Q10, 20 mg of simvastatin therapy is associated with a significantly increased coenzyme Q10/LDL-cholesterol ratio and vitamin E/LDL-cholesterol ratio. Simvastatin treatment is not associated with impairment in left ventricular systolic or diastolic function in hypercholesterolaemic subjects after 6 months of treatment.

Topics: Adult; Aged; Aged, 80 and over; Anticholesteremic Agents; Antioxidants; Apolipoproteins; Cholesterol, LDL; Coenzymes; Echocardiography; Female; Humans; Hypercholesterolemia; Lipids; Male; Middle Aged; Simvastatin; Ubiquinone; Ventricular Function, Left; Vitamin E

Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are widely used for the treatment of hypercholesterolemia and coronary heart disease and for the prevention of stroke. There have been various adverse effects, most commonly affecting muscle and ranging from myalgia to rhabdomyolysis. These adverse effects may be due to a coenzyme Q(10) (CoQ(10)) deficiency because inhibition of cholesterol biosynthesis also inhibits the synthesis of CoQ(10).. To measure CoQ(10) levels in blood from hypercholesterolemic subjects before and after exposure to atorvastatin calcium, 80 mg/d, for 14 and 30 days.. Prospective blinded study of the effects of short-term exposure to atorvastatin on blood levels of CoQ(10).. Stroke center at an academic tertiary care hospital. Patients We examined a cohort of 34 subjects eligible for statin treatment according to National Cholesterol Education Program: Adult Treatment Panel III criteria.. The mean +/- SD blood concentration of CoQ(10) was 1.26 +/- 0.47 micro g/mL at baseline, and decreased to 0.62 +/- 0.39 micro g/mL after 30 days of atorvastatin therapy (P<.001). A significant decrease was already detectable after 14 days of treatment (P<.001).. Even brief exposure to atorvastatin causes a marked decrease in blood CoQ(10) concentration. Widespread inhibition of CoQ(10) synthesis could explain the most commonly reported adverse effects of statins, especially exercise intolerance, myalgia, and myoglobinuria.

Topics: Aged; Analysis of Variance; Atorvastatin; Cardiovascular Diseases; Coenzymes; Female; Heptanoic Acids; Humans; Hypercholesterolemia; Longitudinal Studies; Male; Middle Aged; Prospective Studies; Pyrroles; Risk Factors; Stroke; Ubiquinone

Cerivastatine was administered as a reversible HMG-CoA reductase inhibitor (statine) to treat hypercholesterolemia until its withdrawal from the market following 52 reports of death due to drug-related rhabdomyolysis and acute renal failure. In most cases, cerivastatine was applied in combination with drugs which influenced the liver metabolism of cerivastatine via cytochromeoxidase P 450 isoenzymes. We report a well-documented case of acute rhabdomyolysis following cerivastatine monotherapy. The diagnosis was confirmed additionally by muscle biopsy.Finally,we give an overview of the current knowledge concerning therapy with HMG-CoA reductase inhibitors,1 year after the withdrawal of cerivastatine from the market.

Topics: Acute Disease; Anticholesteremic Agents; Aryl Hydrocarbon Hydroxylases; Biopsy; Coenzymes; Comorbidity; Creatine Kinase; Cytochrome P-450 CYP2C8; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Diagnosis, Differential; Drug Interactions; Electromyography; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Liver Cirrhosis, Alcoholic; Liver Function Tests; Middle Aged; Muscle, Skeletal; Neurologic Examination; Pancreatic Diseases; Pyridines; Rhabdomyolysis; Stomach Neoplasms; Ubiquinone

Topics: Animals; Anticholesteremic Agents; Cause of Death; Coenzymes; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Muscular Diseases; Product Surveillance, Postmarketing; Randomized Controlled Trials as Topic; Treatment Outcome; Ubiquinone

Inhibitors of the key enzyme of cholesterol biosynthesis beta-hydroxy-beta-methylglutaryl-coenzyme A reductase (statins) decrease cholesterol content in atherogenic low-density lipoproteins in patients with coronary heart disease and hypercholesterolemia, but inhibited biosynthesis of ubiquinone Q10 protecting low-density lipoproteins from free radical oxidation. Cerivastatin in a daily dose of 0.4 mg markedly increased the content of lipid peroxides in low-density lipoproteins. However, complex therapy with cerivastatin and antioxidant probucol (250 mg/day) was accompanied by a sharp decrease in the content of lipid peroxides in low-density lipoproteins in patients with coronary heart disease in vivo. These data indicate that antioxidant agents should be used in combination with inhibitors of beta-hydroxy-beta-methylglutaryl-coenzyme A reductase (hypolipidemic preparations) for the therapy of patients with coronary heart disease.

Topics: Antioxidants; Cholesterol; Cholesterol, LDL; Coenzymes; Double-Blind Method; Enzyme Inhibitors; Free Radicals; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Lipid Metabolism; Lipoproteins, LDL; Male; Middle Aged; Myocardial Ischemia; Oxygen; Peroxides; Placebos; Probucol; Pyridines; Random Allocation; Time Factors; Ubiquinone

Topics: Anticholesteremic Agents; Attitude to Health; Cardiovascular Diseases; Coenzymes; Fatty Alcohols; Health Promotion; Humans; Hypercholesterolemia; Hypertension; Platelet Aggregation Inhibitors; Quality of Life; Self Medication; Ubiquinone; United States

Topics: Aging; Biomarkers, Tumor; Breast Neoplasms; Coenzymes; Cytoprotection; Female; Humans; Hydroxymethylglutaryl CoA Reductases; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Incidence; Lovastatin; Postmenopause; Ubiquinone

The aim of this study was to monitor the antioxidant status of patients with hypercholesterolaemia during treatment with Simvastatin. Forty-seven patients, of whom 25 had confirmed familial hypercholesterolaemia (FH), were treated with 10 or 20 mg of Simvastatin per day for 14 weeks. As expected, total cholesterol and LDL cholesterol concentrations decreased considerably, while HDL cholesterol concentrations increased during drug treatment. In neither FH nor non-FH patients were any significant changes observed for retinol status, while plasma vitamin C concentrations were also not adversely affected by the drug therapy. In both patient groups Simvastatin therapy led to a significant decrease in plasma alpha-tocopherol (P < 0.05) concentrations, however, the alpha-tocopherol/total cholesterol ratio increased by 9.1 (P < 0.01) and 12.1% (P < 0.01) in FH and non-FH patients, respectively, during the 14-week treatment period. The coenzyme Q10/total cholesterol ratio did not change significantly in non-FH patients, but was significantly lower (P < 0.05) than the baseline ratio after 4 and 14 weeks of Simvastatin treatment in FH patients. The alpha-tocopherol/total cholesterol ratio of FH patients remained consistently and significantly lower (P < 0.01) compared with non-FH patients, indicating that LDL from the former group may be more vulnerable to free radical-mediated damage and lipid peroxidation. Our results suggest that the significant decline in circulating alpha-tocopherol and coenzyme Q10 concentrations was mainly a function of the decrease in serum total cholesterol concentrations.

Topics: Adult; Anticholesteremic Agents; Antioxidants; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Coenzymes; Enzyme Inhibitors; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hyperlipoproteinemia Type II; Lipid Peroxidation; Lovastatin; Male; Middle Aged; Simvastatin; Ubiquinone; Vitamin E

Topics: Anticholesteremic Agents; Coenzymes; Drug Therapy, Combination; Humans; Hypercholesterolemia; Ubiquinone