coenzyme-q10 and Muscular-Diseases

Statins can trigger a series of muscle-related adverse events, commonly referred to collectively as statin-induced myopathy. Although coenzyme Q10 (CoQ10) is widely used as a supplement in statin therapy, there is little clinical evidence for this practice.. This study aims to assess the effect of adding CoQ10 on statin-induced myopathy.. Searching the PubMed, EMBASE, and the Cochrane Library databases to identify randomized controlled trials investigating the effect of adding CoQ10 on creatine kinase (CK) activity and degree of muscle pain as two indicators of statin-induced myopathy. Two reviewers will independently extract data from the included articles.. Study screening included a randomized controlled trial of oral CoQ10 versus placebo in patients with statin-induced myopathy. We had a total of 8 studies in which 472 patients were treated with statins: 6 studies with 281 participants assessed the impact of adding CoQ10 on CK activity, and 4 studies with 220 participants were included to evaluate the impacts of CoQ10 addition on muscle pain. Compared with the controls, CK activity increased after adding CoQ10, but the change was not significant (mean difference, 3.29 U/L; 95% CI, - 29.58 to 36.17 U/L; P = 0.84). Similarly, the meta-analysis did not benefit CoQ10 over placebo in improving muscle pain (standardized mean difference, - 0.59; 95% CI, - 1.54 to 0.36; P = 0.22).. The outcomes of this meta-analysis of existing randomized controlled trials showed that supplementation with CoQ10 did not have any significant benefit in improving statin-induced myopathy.

Topics: Dietary Supplements; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Muscular Diseases; Randomized Controlled Trials as Topic; Ubiquinone

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

This review examines recent randomized clinical trials evaluating the role of coenzyme Q10 (CoQ10) in the management of coronary heart disease.. CoQ10 is one of the most commonly used dietary supplements in the USA. Due to its antioxidant and anti-inflammatory effects, CoQ10 has been studied extensively for possible use in managing coronary heart disease. One of the most common applications of CoQ10 is to mitigate statin-associated muscle symptoms (SAMS) based on the theory that SAMS are caused by statin depletion of CoQ10 in the muscle. Although previous studies of CoQ10 for SAMS have produced mixed results, CoQ10 appears to be safe. Because CoQ10 is a cofactor in the generation of adenosine triphosphate, supplementation has also recently been studied in patients with heart failure, which is inherently an energy deprived state. The Q-SYMBIO trial found that CoQ10 supplementation in patients with heart failure not only improved functional capacity, but also significantly reduced cardiovascular events and mortality. Despite these positive findings, a larger prospective trial is warranted to support routine use of CoQ10. Less impressive are the effects of CoQ10 on specific cardiovascular risk factors such as blood pressure, dyslipidemia, and glycemic control. Current evidence does not support routine use of CoQ10 in patients with coronary heart disease. Additional studies are warranted to fully determine the benefit of CoQ10 in patients with heart failure before including it in guideline-directed medical therapy.

Topics: Antioxidants; Blood Glucose; Cardiovascular Diseases; Chronic Disease; Coronary Disease; Diabetes Mellitus; Dietary Supplements; Dyslipidemias; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Muscular Diseases; Randomized Controlled Trials as Topic; Risk Factors; Ubiquinone

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are extremely well tolerated but are associated with a range of mild-to-moderate statin-associated muscle symptoms (SAMS). Estimates of SAMS incidence vary from <1% in industry-funded clinical trials to 10-25% in nonindustry-funded clinical trials and ∼60% in some observational studies. SAMS are important because they result in dose reduction or discontinuation of these life-saving medications, accompanied by higher healthcare costs and cardiac events. The mechanisms that produce SAMS are not clearly defined. Statins block the production of farnesyl pyrophosphate, an intermediate in the mevalonate pathway, which is responsible for the production of coenzyme Q10 (CoQ10). This knowledge has prompted the hypothesis that reductions in plasma CoQ10 concentrations contribute to SAMS. Consequently, CoQ10 is popular as a form of adjuvant therapy for the treatment of SAMS. However, the data evaluating the efficacy of CoQ10 supplementation has been equivocal, with some, but not all, studies suggesting that CoQ10 supplementation mitigates muscular complaints. This review discusses the rationale for using CoQ10 in SAMS, the results of CoQ10 clinical trials, the suggested management of SAMS, and the lessons learned about CoQ10 treatment of this problem.

Topics: Dietary Supplements; Energy Metabolism; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Muscle, Skeletal; Muscular Diseases; Myalgia; Polyisoprenyl Phosphates; Polymorphism, Single Nucleotide; Sesquiterpenes; Ubiquinone

Background Previous studies have demonstrated a possible association between the induction of coenzyme Q10 (CoQ10) after statin treatment and statin-induced myopathy. However, whether CoQ10 supplementation ameliorates statin-induced myopathy remains unclear. Methods and Results PubMed, EMBASE , and Cochrane Library were searched to identify randomized controlled trials investigating the effect of CoQ10 on statin-induced myopathy. We calculated the pooled weighted mean difference ( WMD ) using a fixed-effect model and a random-effect model to assess the effects of CoQ10 supplementation on statin-associated muscle symptoms and plasma creatine kinase. The methodological quality of the studies was determined, according to the Cochrane Handbook. Publication bias was evaluated by a funnel plot, Egger regression test, and the Begg-Mazumdar correlation test. Twelve randomized controlled trials with a total of 575 patients were enrolled; of them, 294 patients were in the CoQ10 supplementation group and 281 were in the placebo group. Compared with placebo, CoQ10 supplementation ameliorated statin-associated muscle symptoms, such as muscle pain ( WMD , -1.60; 95% confidence interval [ CI ], -1.75 to -1.44; P<0.001), muscle weakness ( WMD , -2.28; 95% CI , -2.79 to -1.77; P=0.006), muscle cramp ( WMD , -1.78; 95% CI , -2.31 to -1.24; P<0.001), and muscle tiredness ( WMD , -1.75; 95% CI , -2.31 to -1.19; P<0.001), whereas no reduction in the plasma creatine kinase level was observed after CoQ10 supplementation ( WMD , 0.09; 95% CI , -0.06 to 0.24; P=0.23). Conclusions CoQ10 supplementation ameliorated statin-associated muscle symptoms, implying that CoQ10 supplementation may be a complementary approach to manage statin-induced myopathy.

Topics: Dietary Supplements; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Muscular Diseases; Randomized Controlled Trials as Topic; Ubiquinone; Vitamins

Coenzyme Q-10 (CoQ10) is a widely used alternative medication or dietary supplement and one of its roles is as an antioxidant. It naturally functions as a coenzyme and component of oxidative phosphorylation in mitochondria. Decreased levels have been demonstrated in diseased myocardium and in Parkinson disease. Farnesyl pyrophosphate is a critical intermediate for CoQ10 synthesis and blockage of this step may be important in statin myopathy. Deficiency of CoQ10 also has been associated with encephalomyopathy, severe infantile multisystemic disease, cerebellar ataxia, nephrotic syndrome, and isolated myopathy. Although supplementation with CoQ10 has been reported to be beneficial in treating hypertension, congestive heart failure, statin myopathy, and problems associated with chemotherapy for cancer treatement, this use of CoQ10 as a supplement has not been confirmed in randomized controlled clinical trials. Nevertheless, it appears to be a safe supplementary medication where usage in selected clinical situations may not be inappropriate. This review is an attempt to actualize the available information on CoQ10 and define its potential benefit and appropriate usage.

Topics: Animals; Cardiovascular Diseases; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Muscular Diseases; Neoplasms; Ubiquinone

Coenzyme Q (CoQ) is an essential lipid of cells present in all cellular compartments. The functions of CoQ in mitochondrial respiration and as an antioxidant are established, although the lipid likely has additional, presently unknown, roles. While the therapeutic utility of CoQ10 supplements is recognized in the rare cases of primary CoQ10 deficiencies, a potential role for CoQ10 supplements in cardiovascular disease, particularly heart failure, has also been studied for over 40 years. This review summarizes our current knowledge in these areas derived from animal studies and human trials. Current evidence for a benefit of CoQ10 supplements in diseases other than primary CoQ10 deficiencies is insufficient.

Topics: Age Factors; Animals; Antioxidants; Diet; Dietary Supplements; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Muscle, Skeletal; Muscular Diseases; Myocardial Ischemia; Tissue Distribution; Ubiquinone

Statins inhibit hydroxymethylglutaryl-coenzyme A reductase, decrease plasma low-density lipoprotein cholesterol and reduce cardiovascular morbidity and mortality. They can also exert adverse effects, mostly affecting skeletal muscle, ranging from mild myalgia to rhabdomyolysis.. Based on a PubMed search until December 2014, this review summarizes studies on statin effects on muscle mitochondrial morphology and function in the context of myopathy.. Possible mechanisms of statin-induced myopathy include lower cholesterol synthesis and production of prenylated proteins, reduced dolichols and increased atrogin-1 expression. Statin-treated patients frequently feature decreased muscle coenzyme Q10 (CoQ10) contents, suggesting that statins might impair mitochondrial function. In cell cultures, statins diminish muscle oxygen consumption, promote mitochondrial permeability transient pore opening and generate apoptotic proteins. Animal models confirm the statin-induced decrease in muscle CoQ10, but reveal no changes in mitochondrial enzyme activities. Human studies yield contradictory results, with decreased CoQ10, elevated lipids, decreased enzyme activities in muscle and impaired maximal oxygen uptake in several but not all studies. Some patients are susceptible to statin-induced myopathy due to variations in genes encoding proteins involved in statin uptake and biotransformation such as the solute carrier organic anion transporter family member 1B1 (SLCO1B1) or cytochrome P450 (CYP2D6, CYP3A4, CYP3A5). Carriers for carnitine palmitoyltransferase II deficiency and McArdle disease also present with higher prevalence of statin-induced myopathy.. Despite the widespread use of statins, the pathogenesis of statin-induced myopathy remains unclear, requiring prospective randomized controlled trials with intensive phenotyping also for identifying strategies for its risk assessment, prevention and treatment.

Topics: Animals; Cell Line; Disease Models, Animal; Energy Metabolism; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Mitochondria, Muscle; Muscle, Skeletal; Muscular Diseases; Rabbits; Rats; Risk Factors; Ubiquinone

Heart disease is the leading cause of death in the United States. HMG-CoA reductase inhibitors, or statins, are medications at the forefront of the battle against cardiovascular disease. Despite their effectiveness, patient compliance with statins has lagged because of medication cost and adverse effects, namely myopathy. Myopathy is the most common side effect of statin use. The purpose of this review is to report plasma levels of CoQ10 in patients taking statins and then to determine the benefit of Coenzyme Q10 (CoQ10) supplementation on statin-related myopathy as evidenced by symptomatic improvement and increase in serum levels of CoQ10.. CINAHL, Medline, Health Source: Nursing/Academic Edition, and Cochrane Library.. Evidence from this review suggests that studies showed a significant relationship between statin intake and decreased serum levels of CoQ10. A few studies showed a benefit in symptoms of myalgia or improvement of serum levels of CoQ10 with supplementation. One study showed no benefit of CoQ10 supplementation when taken with statins. There were no risks of supplementation reported in any of the studies.. CoQ10 supplementation might benefit those patients suffering from statin-induced myopathy as evidenced by the results of these studies. Supplementation of CoQ10 at a dose of between 30 and 200 mg daily has shown to have beneficial effects on statin myopathy with no noted side effects. Further research is necessary.

Topics: Dietary Supplements; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Muscular Diseases; Ubiquinone; Vitamins

Statins have demonstrated substantial benefits in supporting cardiovascular health. Older individuals are more likely to experience the well-known muscle-related side effects of statins compared with younger individuals. Elderly females may be especially vulnerable to statin-related muscle disorder. This review will collate and discuss statin-related muscular effects, examine their molecular and genetic basis, and how these apply specifically to elderly women. Developing strategies to reduce the incidence of statin-induced myopathy in older adult women could contribute to a significant reduction in the overall incidence of statin-induced muscle disorder in this vulnerable group of patients. Reducing statin-related muscle disorder would likely improve overall patient compliance, thereby leading to an increase in improved short- and long-term outcomes associated with appropriate use of statins.

Topics: Aged; Aging; Cell Death; Comorbidity; Drug Interactions; Female; Genetic Predisposition to Disease; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Incidence; Muscular Diseases; Myositis; Polyisoprenyl Phosphates; Quality of Life; Rhabdomyolysis; Sesquiterpenes; Sex Factors; Ubiquinone

Statin treatment can cause muscular side effects. It has been suggested that the mechanism is reduced synthesis of coenzyme Q10 (coQ10) and a subsequent dysfunction of the respiratory chain. A literature review resulted in insufficient evidence supporting this theory. It is uncertain whether intramuscular levels of coQ10 and mitochondrial function are affected by statin therapy and whether the symptoms of myopathy can be alleviated with coQ10 supplementation. Nevertheless, due to a favourable safety profile, coQ10 can be tested in patients whose muscular symptoms cannot be managed otherwise.

Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Mitochondria, Muscle; Muscles; Muscular Diseases; Risk Factors; Ubiquinone

Some small clinical trials seem to show that coenzyme Q10 supplements can be used to lower blood pressure and to treat or prevent myalgia caused by hydroxymethylglutaryl coenzyme A reductase inhibitors (statins). However, larger trials are needed to determine if they are truly effective for these purposes. The authors examine the evidence and also discuss issues such as bioavailability, elimination, safety, and cost.

Topics: Antihypertensive Agents; Dietary Supplements; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Muscular Diseases; Risk Assessment; Ubiquinone; Vitamins

Statin-associated muscle symptoms are a relatively common condition that may affect 10% to 15% of statin users. Statin myopathy includes a wide spectrum of clinical conditions, ranging from mild myalgia to rhabdomyolysis. The etiology of myopathy is multifactorial. Recent studies suggest that statins may cause myopathy by depleting isoprenoids and interfering with intracellular calcium signaling. Certain patient and drug characteristics increase risk for statin myopathy, including higher statin doses, statin cytochrome metabolism, and polypharmacy. Genetic risk factors have been identified, including a single nucleotide polymorphism of SLCO1B1. Coenzyme Q10 and vitamin D have been used to prevent and treat statin myopathy; however, clinical trial evidence demonstrating their efficacy is limited. Statin-intolerant patients may be successfully treated with either low-dose statins, alternate-day dosing, or using twice-weekly dosing with longer half-life statins. An algorithm is presented to assist the clinician in managing myopathy in patients with dyslipidemia.

Topics: Algorithms; Cardiovascular Diseases; Cholesterol; Evidence-Based Medicine; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Muscular Diseases; Prognosis; Risk Factors; Ubiquinone; Vitamin D; Vitamins

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are safe and effective in lowering low-density lipoprotein cholesterol. As a result, they confer an all-cause mortality benefit across a wide range of patient groups. The utility of statins is limited by their adverse effects, including myalgias and rhabdomyolysis. These clinical events, plus other symptoms, constitute what is termed statin myopathy. This review summarizes current concepts of statin myopathy and presents strategies to minimize statin-associated myopathic complaints.

Topics: Algorithms; Creatine Kinase; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Muscular Diseases; Risk Factors; Ubiquinone; Vitamins

The aim of this review is to provide an update on disorders of lipid metabolism affecting skeletal muscle exclusively or predominantly and to summarize recent clinical, genetic, and therapeutic studies in this field.. Over the past 5 years, new clinical phenotypes and genetic loci have been described, unusual pathogenic mechanisms have been elucidated, and novel pharmacological approaches have been developed. At least one genetic defect responsible for the myopathic form of CoQ10 deficiency has been identified, causing a disorder that is allelic with the late-onset riboflavine-responsive form of multiple acyl-coenzyme A dehydrogenation deficiency. Novel mechanisms involved in the lipolytic breakdown of cellular lipid depots have been described and have led to the identification of genes and mutations responsible for multisystemic neutral lipid storage disorders, characterized by accumulation of triglyceride in multiple tissues, including muscle.. Defects in lipid metabolism can affect either the mitochondrial transport and oxidation of exogenous fatty acid or the catabolism of endogenous triglycerides. These disorders impair energy production and almost invariably involve skeletal muscle, causing progressive myopathy with muscle weakness, or recurrent acute episodes of rhabdomyolysis triggered by exercise, fasting, or infections. Clinical and genetic characterization of these disorders has important implications both for accurate diagnostic approach and for development of therapeutic strategies.

Topics: Acyl-CoA Dehydrogenase; Carnitine; Carnitine O-Palmitoyltransferase; Electron Transport Complex I; Electron-Transferring Flavoproteins; Fatty Acids; Humans; Lipid Metabolism, Inborn Errors; Muscle, Skeletal; Muscular Diseases; Triglycerides; Ubiquinone

Genetic predisposition to statin myopathy is a rapidly expanding area of investigation. This review summarizes the latest information on genetic risk factors associated with statin-induced myopathy. Genetic determinants involved in both pharmacokinetics of statins and metabolic muscle diseases are discussed. Data are provided on the prevalence of statin use in the United States; incidence of associated myopathy; terminology relating to statin myopathy and genetic susceptibility; and common myths surrounding this disorder.. Technological advances now make it possible to identify genetic variation in the human genome that reveals disease-causing mutations and single nucleotide polymorphisms associated with disease. More than 30,000 individuals in the United States suffer from severe life-threatening symptoms of statin-induced myopathy that may, in some cases, persist long after the cessation of therapy. Genes of interest include those involved in the pharmacokinetics of the statin response, muscle atrophy, exercise intolerance, pain perception, and mitochondrial energy metabolism.. Genetic analysis for variants and disease-causing mutations relevant to statin myopathy will provide predisposition testing for this and other drug-induced disorders. This testing will become an integral part of personalized medicine that will contribute to the safe and informed use of selected drugs and improved compliance.

Topics: Carnitine O-Palmitoyltransferase; Creatine Kinase; Gene Expression; Genetic Predisposition to Disease; Glycogen Storage Disease Type V; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Muscular Diseases; Pharmacogenetics; Rhabdomyolysis; Risk Factors; Ubiquinone; United States

Statins are associated with muscle complaints, including myositis. The mechanism through which statin use causes muscle toxicity is unknown. One of the theories is that statin therapy reduces coenzyme Q10 levels in muscle mitochondria, which leads to muscle injury and myopathy. The aim of the present article is to review published data on the association between coenzyme Q10 and statin-associated myopathy.. Studies have consistently shown that statins reduce coenzyme Q10 levels in serum and that supplementation of coenzyme Q10 increases these levels. However, the effect of statin therapy on coenzyme Q10 levels in muscle has been conflicting. Recently, two pilot studies on coenzyme Q10 supplementation in statin-induced myopathy and one study on the effect of coenzyme Q10 supplementation on serum muscle enzyme levels were published. These three studies were the first randomized trials with coenzyme Q10 supplementation in hypercholesterolemic patients treated with statins. The results of these trials have been contradictory; whereas one seems to support supplementation with coenzyme Q10, the other two do not.. This review summarizes the current evidence on coenzyme Q10 supplementation in statin-induced myopathy. We conclude that the present evidence does not support coenzyme Q10 supplementation in statin-induced myopathy.

Topics: Administration, Oral; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Mitochondria; Muscular Diseases; Ubiquinone

Coenzyme Q10 (Q10) is available as an over-the-counter dietary supplement in the United States. While its use could be considered a form of alternative therapy, the medical profession has embraced the use of Q10 in specific disease states, including a series of neurologic and muscular diseases. Clinical laboratory monitoring is available for measurement of total Q10 in plasma and tissue and for measurement of redox status, ie, the ratio of reduced and oxidized forms of Q10. Many published studies have been anecdotal, in part owing to the rarity of some diseases involved. Unfortunately, many studies do not report Q10 levels, and, thus, the relationship of clinical response to Q10 concentration in plasma frequently is not discernible. Consistent laboratory monitoring of patients treated with this compound would help ease interpretation of the results of the treatment, especially because so many formulations of Q10 exist in the marketplace, each with its own bioavailability characteristics. Q10 has an enviable safety profile and, thus, is ideal to study as an adjunct to more conventional therapy. Defining patient subpopulations and characteristics that predict benefit from exogenous Q10 and defining therapeutic ranges for those particular applications are major challenges in this field.

Topics: Coenzymes; Epilepsies, Myoclonic; Friedreich Ataxia; Humans; Huntington Disease; Kearns-Sayre Syndrome; Mitochondrial Encephalomyopathies; Muscular Diseases; Nervous System Diseases; Parkinson Disease; Ubiquinone

The inherited disorders of muscle metabolism affect both substrate utilization and the final intramitochondrial oxidation through the Krebs cycle and the respiratory chain. Almost every step of these complex biochemical pathways can be affected by inborn errors, whose expression depends on peculiar tissue-specific or systemic gene expression. This review updates current knowledge in this broad field.. New inherited defects are still being discovered, such as the beta-enolase deficiency in glycogenosis type XIII and mutations in the gene encoding an esterase/lipase/thioesterase protein in Chanarin-Dorfman syndrome, a multisystem triglyceride storage disease.. Therapeutic approaches to the metabolic myopathies are still lagging behind, although remarkable observations have been made on the rare coenzyme Q10 deficiency syndrome. However, transgenic animal models may offer the opportunity both to investigate muscle pathogenesis and explore therapeutic targets. Finally, human myotoxicity may provide novel paradigms for naturally occurring muscle disorders.

Topics: Animals; Animals, Genetically Modified; Antioxidants; Coenzymes; Glycogen Storage Disease; Humans; Hypolipidemic Agents; Lipid Metabolism; Metabolism, Inborn Errors; Mitochondria, Muscle; Mitochondrial Diseases; Muscular Diseases; Mutation; Phosphopyruvate Hydratase; Ubiquinone

The objective of this study was to evaluate the possible benefits of coenzyme Q10 and selenium supplementation administered to patients with statin-associated myopathy (SAM). Sixty eligible patients entered the pilot study. Laboratory examination (CoQ10, selenium, creatin kinase) and intensity of SAM (visual scale) were performed at baseline, after 1 month, and at the end of study at month 3. Plasma levels of CoQ10 increased from 0.81 ± 0.39 to 3.31 ± 1.72 μmol/L in the active group of patients treated by CoQ10, compared with the placebo (p = 0.001). Also, the symptoms of SAM significantly improved in the active group (p < 0.001): the intensity of muscle pain decreased from 6.7 ± 1.72 to 3.2 ± 2.1 (p < 0.01, -53.4 ± 28.2%); muscle weakness decreased from 7.0 ± 1.63 to 2.8 ± 2.34 (p < 0.01, -60 ± 24.0%); muscle cramps decreased from 5.33 ± 2.06 to 1.86 ± 2.42, p < 0.01, -65 ± 28%); tiredness decreased from the initial 6.7 ± 1.34 to 1.2 ± 1.32 (p < 0.01, -82 ± 22%). We did not observe any significant changes in the placebo group. In conclusion, supplementation of statin-treated patients with CoQ10 resulted in a decrease in the symptoms of SAM, both in absolute numbers and intensity. Additional selenium supplementation was not associated with any statistically significant decrease of SAM. However, it is not possible to draw any definite conclusions, even though this study was carried out in double-blind fashion, because it involved a small number of patients.

Topics: Analysis of Variance; Dietary Supplements; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Muscular Diseases; Pilot Projects; Prospective Studies; Selenium; Treatment Outcome; Ubiquinone

The aim of the present study was to evaluate the possible effects of Q10 and selenium supplementation on statin-induced myopathy (SIM), both for subjective symptoms and muscle function.. Patients (N = 43) who had experienced previous or ongoing SIM on atorvastatin therapy were recruited. Following a 6-week washout period during which no statins were administered, the patients were re-challenged with 10 mg of atorvastatin. Patients (N = 41) who experienced SIM continued the atorvastatin treatment and were in addition randomized to receive 12 weeks supplement of 400 mg Q10 and 200 μg selenium per day or a matching double placebo. SIM was assessed using 3 validated symptom questionnaires, and a muscle function test was performed at the beginning and at the end of the study.. The patients receiving the active supplement experienced significant increases in their serum Q10 and selenium concentrations compared with the group receiving placebo. No statistically significant differences in symptom questionnaire scores or muscle function tests were revealed between the groups.. Despite substantial increases in the serum Q10 and selenium levels following the oral supplementation, this study revealed no significant effects on SIM compared with the placebo.

Topics: Adult; Aged; Antioxidants; Atorvastatin; Dietary Supplements; Double-Blind Method; Drug Therapy, Combination; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Muscular Diseases; Prospective Studies; Pyrroles; Selenium; Surveys and Questionnaires; Treatment Outcome; Ubiquinone; Vitamins

Coenzyme Q10 (CoQ10) deficiency has been proposed to be causal in 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitor (statin)-induced myopathies. However, the clinical benefit of supplementation is unproved. The purpose of the present study was to assess the effect of CoQ10 supplementation on myalgias presumed to be caused by statins. Patients currently receiving a statin who developed new-onset myalgias in ≥ 2 extremities within 60 days of initiation or a dosage increase were eligible. Patients continued statin therapy and were randomized using a matched design to either CoQ10 60 mg twice daily or matching placebo. Double-blind treatment continued for 3 months, and patients completed a 10-cm visual analog scale (VAS) and the Short-Form McGill Pain Questionnaire at baseline and at each monthly visit. The primary end point was the comparison of the VAS score at 1 month. A total of 76 patients were enrolled (40 in the CoQ10 arm and 36 in the placebo arm). The mean VAS score was 6 cm at baseline in both groups. At 1 month, no difference was seen in the mean VAS score between the 2 groups (3.9 cm in the CoQ10 group and 4 cm in the placebo group; p = 0.97). However, 5 patients in the CoQ10 group and 3 in the placebo group discontinued therapy during the first month because of myalgias. The baseline median score on the Sensory Pain Rating Index subscale was 10 in the CoQ10 group and 11.5 in the placebo group. At 1 month, these scores had decreased to 6.5 and 7.5, respectively, with no statistically significant difference (p = 0.34). In conclusion, CoQ10 did not produce a greater response than placebo in the treatment of presumed statin-induced myalgias.

Topics: Double-Blind Method; Female; Follow-Up Studies; Georgia; Hospitals, Military; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Muscular Diseases; Musculoskeletal Pain; Pain Measurement; Treatment Outcome; Ubiquinone; Vitamins

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

Myalgia is the most frequently reported adverse side effect associated with statin therapy and often necessitates reduction in dose, or the cessation of therapy, compromising cardiovascular risk management. One postulated mechanism for statin-related myalgia is mitochondrial dysfunction through the depletion of coenzyme Q(10), a key component of the mitochondrial electron transport chain. This pilot study evaluated the effect of coenzyme Q(10) supplementation on statin tolerance and myalgia in patients with previous statin-related myalgia. Forty-four patients were randomized to coenzyme Q(10) (200 mg/day) or placebo for 12 weeks in combination with upward dose titration of simvastatin from 10 mg/day, doubling every 4 weeks if tolerated to a maximum of 40 mg/day. Patients experiencing significant myalgia reduced their statin dose or discontinued treatment. Myalgia was assessed using a visual analogue scale. There was no difference between combined therapy and statin alone in the myalgia score change (median 6.0 [interquartile range 2.1 to 8.8] vs 2.3 [0 to 12.8], p = 0.63), in the number of patients tolerating simvastatin 40 mg/day (16 of 22 [73%] with coenzyme Q(10) vs 13 of 22 [59%] with placebo, p = 0.34), or in the number of patients remaining on therapy (16 of 22 [73%] with coenzyme Q(10) vs 18 of 22 [82%] with placebo, p = 0.47). In conclusion, coenzyme Q(10) supplementation did not improve statin tolerance or myalgia, although further studies are warranted.

Topics: Coenzymes; Double-Blind Method; Drug Tolerance; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Muscular Diseases; Pilot Projects; Simvastatin; Ubiquinone; Vitamins

Fourty four patients with mitochondrial myopathies were treated with Ubidecarenone (CoQ10) for six months in an open multicentric trial. No side effects due to the drug administration were observed. Sixteen patients showing at least 25% decrease of post exercise lactate levels were selected as responders. Responsiveness was apparently not related to CoQ10 level in serum and platelets or to the presence or absence of mtDNA deletions. The responders were further treated for 3 months with CoQ10 or placebo in the second blind part of the trial; no significant differences between the 2 groups were observed. It is not clear why CoQ10 had therapeutic effects in some patients and not in others with the same clinical presentation and biochemical defect, and we failed to identify candidate responders before treatment. At the dosage of CoQ10 used in the study (2 mg/kg/day) the therapy requires long administration time before a response is demonstrable.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Coenzymes; DNA, Mitochondrial; Female; Humans; Lactates; Lactic Acid; Male; Middle Aged; Mitochondria, Muscle; Muscular Diseases; Ubiquinone

Forty-four patients with mitochondrial myopathies were treated with Ubidecarenone (CoQ10) for 6 months in an open multi-center trial. No side effects of the drug were observed. Sixteen patients showing at least 25% decrease of post-exercise lactate levels were selected as responders. Responsiveness was apparently not related to CoQ10 level in serum and platelets or to the presence or absence of mtDNA deletions. The responders were treated for a further 3 months with CoQ10 or placebo in the second blind part of the trial; no significant differences were observed between the 2 groups. It is not clear why CoQ10 had therapeutic effects in some patients and not in others with the same clinical presentation and biochemical defect, and we failed to identify candidate responders before treatment. At the dose of CoQ10 used in this study (2 mg/kg/day) the therapy requires a long administration time before a response is seen.

Topics: Blood Platelets; Chromosome Deletion; Coenzymes; DNA, Mitochondrial; Double-Blind Method; Female; Humans; Lactates; Lactic Acid; Male; Mitochondria; Mitochondria, Muscle; Muscles; Muscular Diseases; Physical Exertion; Ubiquinone

Cardiac disease is commonly associated with virtually every form of muscular dystrophy and myopathy. A double-blind and open crossover trial on the oral administration of coenzyme Q10 (CoQ10) to 12 patients with progressive muscular dystrophies and neurogenic atrophies was conducted. These diseases included the Duchenne, Becker, and limb-girdle dystrophies, myotonic dystrophy, Charcot-Marie-Tooth disease, and Welander disease. The impaired cardiac function was noninvasively and extensively monitored by impedance cardiography. Solely by significant change or no change in stroke volume and cardiac output, all 8 patients on blind CoQ10 and all 4 on blind placebo were correctly assigned (P less than 0.003). After the limited 3-month trial, improved physical well-being was observed for 4/8 treated patients and for 0/4 placebo patients; of the latter, 3/4 improved on CoQ10; 2/8 patients resigned before crossover; 5/6 on CoQ10 in crossover maintained improved cardiac function; 1/6 crossed over from CoQ10 to placebo relapsed. The rationale of this trial was based on known mitochondrial myopathies, which involve respiratory enzymes, the known presence of CoQ10 in respiration, and prior clinical data on CoQ10 and dystrophy. These results indicate that the impaired myocardial function of such patients with muscular disease may have some association with impaired function of skeletal muscle, both of which may be improved by CoQ10 therapy. The cardiac improvement was definitely positive. The improvement in well-being was subjective, but probably real. Likely, CoQ10 does not alter genetic defects but can benefit the sequelae of mitochondrial impairment from such defects. CoQ10 is the only known substance that offers a safe and improved quality of life for such patients having muscle disease, and it is based on intrinsic bioenergetics.

Topics: Administration, Oral; Cardiac Output; Charcot-Marie-Tooth Disease; Coenzymes; Double-Blind Method; Electrocardiography; Heart; Humans; Muscular Diseases; Muscular Dystrophies; Stroke Volume; Ubiquinone

Fenofibrate (FEN) is an antilipidemic drug that increases the activity of the lipoprotein lipase enzyme, thus enhancing lipolysis; however, it may cause myopathy and rhabdomyolysis in humans. Coenzyme Q10 (CoQ10) is an endogenously synthesized compound that is found in most living cells and plays an important role in cellular metabolism. It acts as the electron carrier in the mitochondrial respiratory chain. This study aimed to elucidate FEN-induced skeletal muscle changes in rats and to evaluate CoQ10 efficacy in preventing or alleviating these changes. Forty adult male rats were divided equally into four groups: the negative control group that received saline, the positive control group that received CoQ10, the FEN-treated group that received FEN, and the FEN + CoQ10 group that received both FEN followed by CoQ10 daily for 4 weeks. Animals were sacrificed and blood samples were collected to assess creatine kinase (CK). Soleus muscle samples were taken and processed for light and electron microscopic studies. This study showed that FEN increased CK levels and induced inflammatory cellular infiltration and disorganization of muscular architecture with lost striations. FEN increased the percentage of degenerated collagen fibers and immune expression of caspase-3. Ultrastructurally, FEN caused degeneration of myofibrils with distorted cell organelles. Treatment with CoQ10 could markedly ameliorate these FEN-induced structural changes and mostly regain the normal architecture of muscle fibers due to its antifibrotic and antiapoptotic effects. In conclusion, treatment with CoQ10 improved muscular structure by suppressing oxidative stress, attenuating inflammation, and inhibiting apoptosis.

Topics: Adult; Animals; Fenofibrate; Humans; Male; Muscle Fibers, Skeletal; Muscle, Skeletal; Muscular Diseases; Rats

Statins are medications that help lower cholesterol and treat cardiovascular disease, but muscle pain is the most common side effect of statins. Statins decrease the body's levels of coenzyme Q10 (CoQ10), and thus taking CoQ10 supplements (which are widely available over the counter in pharmacies) may help treat the muscle side effects from statins. However, the results of previous studies are not clear whether CoQ10 is effective for treating statin-associated muscle symptoms. Therefore, the purpose of this study was to analyze whether the use of CoQ10 supplements improved statin-associated muscle side effects in a large group of individuals. When the authors compared the survey responses of 64 CoQ10 users versus those of 447 non-CoQ10 users with statin-associated muscle symptoms, CoQ10 supplements did not improve their muscle symptoms.

Topics: Dietary Supplements; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Muscles; Muscular Diseases; Retrospective Studies; Ubiquinone

Multiple acyl-CoA dehydrogenase deficiency (MADD) is a treatable lipid metabolism disorder that presents as myopathy and episodic metabolic crisis. The metabolic crisis is typically associated with prolonged fasting or physical stress; however, the mechanism of metabolic crisis is not yet fully understood.. A 28-year-old Taiwanese woman presented with dyspnoea, poor appetite, and muscle weakness after using antiobesity drugs, including metformin, triiodothyronine, and topiramate. MADD was diagnosed, and her symptoms rapidly improved after treatment with riboflavin, carnitine, and ubiquinone. To date, antiobesity drugs have not been reported to be a provoking factor in fatty acid oxidation disorder.. The increase of β-oxidation activity due to antiobesity drugs supports the hypothetical substrate competition model for MADD metabolic crisis. Because the drugs our patient used are commonly prescribed, we report this case to increase the vigilance and proactivity of clinicians in recognising this treatable adult-onset myopathy.

Topics: Adult; Anti-Obesity Agents; Asian People; Carnitine; Female; Humans; Metformin; Multiple Acyl Coenzyme A Dehydrogenase Deficiency; Muscle Weakness; Muscular Diseases; Riboflavin; Topiramate; Triiodothyronine; Ubiquinone

Exercise induced metabolic myopathy in German Hunting Terrier dogs is an autosomal-recessively inherited disorder, caused by a nonsense variant of the gene encoding for the very long-chain acyl-CoA-dehydrogenase (VLCAD) enzyme. Clinical signs include exercise- induced fatigue, muscle pain and weakness. In the present study, the long-term course of this disease was investigated over a period of 1 year in 9 affected German Hunting Terriers. The dogs were treated symptomatically with oral L-carnitine, coenzyme Q10 and a special diet characterized by a low content of long-chain fatty acids and a high proportion of carbohydrates.. In 9 affected dogs, the phenotype as well as clinical, laboratory parameters, and histopathological findings are described (time point 1) and compared to follow-up examinations 1 year later (time point 2). At both time points clinical and neurological examinations, complete blood cell count, clinical chemistry profile and the concentration of brain natriuretic peptide (NT-proBNP) were investigated.. In the follow-up examinations, the same post-exercise clinical signs were present as in the initial presentation of the homozygous dogs. Dark-brownish discoloration of the urine, weakness, myalgia as well as stiff and tetraparetic gait were apparant. All hematological values and the concentration of NT-proBNP were within the relevant reference ranges. Plasma CK and ALT activities were compared between the first presentation and the follow- up examination and no significant differences were detected (p. Oral supplementation with L-carnitine, coenzyme Q10 and the special dietary management did not result in any improvement of clinical signs or laboratory parameters. No progression of the disease was observed. The prognosis for affected dogs remains cautious as long-term observations of affected dogs over several years are lacking. Our findings provide further important information on inherited disorders of mitochondrial β-oxidation in dogs, especially focused on the exercise induced metabolic myopathy in the German Hunting Terrier. This may provide new insights for novel treatment modalities in conjuntion with the development of improved breeding guidelines.. Die belastungsabhängige metabolische Myopathie beim Deutschen Jagdterrier ist eine autosomal-rezessive Erbkrankheit, die aufgrund einer Punktmutation zu einem Enzymdefekt der sehr langkettigen Acyl-CoA-Dehydrogenase führt und klinisch durch belastungsabhängige Schwäche, schwere Myalgien und Myoglobinurie charakterisiert ist. In dieser Studie wurde der klinische Verlauf der Erkrankung bei 9 betroffenen Deutschen Jagdterriern über 1 Jahr untersucht. Die Behandlung der Hunde umfasste die orale Supplementierung von L-Carnitin und Koenzym Q10 sowie eine Diät mit hohem Kohlenhydratgehalt und einem niedrigen Anteil an langkettigen Fettsäuren.. Die 9 Hunde mit nachgewiesenem Gendefekt wurden bei Auftreten der ersten Symptome (Messzeitpunkt 1, MZP1) und 1 Jahr später (Messzeitpunkt 2, MZP2) klinisch-neurologisch untersucht und es erfolgte eine Blutuntersuchung mit Analyse hämatologischer und klinisch-chemischer Parameter sowie der Konzentration des natriuretischen Peptids Typ B (NT-proBNP).. Zum MZP2 zeigten die Hunde, wie bereits zum MZP1, nach Belastung ein steifes Gangbild, Muskelschwäche und -schmerz und hatten einen dunkelbraun verfärbten Urin. Bei den hämatologischen Parametern und der NT-proBNP-Konzentration ergaben sich, wie zum MZP1, keine Abweichungen vom Referenzbereich. Die Aktivitäten der Kreatinkinase und Alanin-Aminotransferase unterschieden sich statistisch nicht signifikant zwischen beiden MZP (p. Die orale Supplementierung von L-Carnitin und Koenzym Q10 sowie spezielle diätetische Maßnahmen über 1 Jahr führten zu keiner Verbesserung der klinischen Symptomatik oder der untersuchten Laborparameter. Die Tiere zeigten keine progressive Verschlechterung der Symptomatik im Vergleich zur Erstvorstellung. Die Prognose ist jedoch als vorsichtig zu bezeichnen, da Daten zum Langzeitverlauf über einige Jahre fehlen. Unsere Ergebnisse bilden eine Grundlage für weitere Forschungen zu Lipidspeichermyopathien, insbesondere mit Fokus auf die belastungsabhängige metabolische Myopathie des Deutschen Jagdterriers, deren Therapie und eine entsprechende Zuchthygiene.

Topics: Acyl-CoA Dehydrogenase, Long-Chain; Animals; Carnitine; Diet; Dog Diseases; Dogs; Follow-Up Studies; Muscular Diseases; Physical Conditioning, Animal; Ubiquinone

3-Hydroxy-3-methylglutaryl-CoA reductase (HMGCR) is the rate-limiting enzyme of the mevalonic acid pathway and is required for cholesterol biosynthesis and the synthesis of Coenzyme Q10 (CoQ10). Statins inhibit HMGCR, thus inhibiting the downstream products of this pathway including the biosynthesis of decaprenyl-pyrophosphate that is critical for the synthesis of Coenzyme Q10 (CoQ10). We show that zebrafish (Danio rerio) larvae treated in tank water with Atorvastatin (ATV; Lipitor) exhibited movement alterations and reduced whole body tissue metabolism. The ATV-inhibition of HMGCR function altered transcript abundance of muscle atrophy markers (atrogen-1, murf) and the mitochondrial biogenesis marker (pgc-1α). Furthermore, ATV-induced reduction in larval response to tactile stimuli was reversed with treatment of CoQ10. Together, the implication of our results contributes to the understanding of the mechanisms of action of the statin-induced damage in this model fish species.

Topics: Animals; Atorvastatin; F-Box Proteins; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Larva; Locomotion; Muscle Proteins; Muscular Diseases; Protective Agents; RNA, Messenger; Transcription Factors; Ubiquinone; Zebrafish; Zebrafish Proteins

Myopathy is among the well documented and the most disturbing adverse effects of statins. The underlying mechanism is still unknown. Mitochondrial dysfunction related to coenzyme Q10 decline is one of the proposed theories. The present study aimed to investigate the mechanism of atorvastatin-induced myopathy in rats. In addition, the mechanism of the coenzyme Q10 protection was investigated with special focus of mitochondrial alterations. Sprague-Dawely rats were treated orally either with atorvastatin (100mg/kg) or atorvastatin and coenzyme Q10 (100mg/kg). Myopathy was assessed by measuring serum creatine kinase (CK) and myoglobin levels together with examination of necrosis in type IIB fiber muscles. Mitochondrial dysfunction was evaluated by measuring muscle lactate/pyruvate ratio, ATP level, pAkt as well as mitochondrial ultrastructure examination. Atorvastatin treatment resulted in a rise in both CK (2X) and myoglobin (6X) level with graded degrees of muscle necrosis. Biochemical determinations showed prominent increase in lactate/pyruvate ratio and a decline in both ATP (>80%) and pAkt (>50%) levels. Ultrastructure examination showed mitochondrial swelling with disrupted organelle membrane. Co-treatment with coenzyme Q10 induced reduction in muscle necrosis as well as in CK and myoglobin levels. In addition, coenzyme Q10 improved all mitochondrial dysfunction parameters including mitochondrial swelling and disruption. These results presented a model for atorvastatin-induced myopathy in rats and proved that mitochondrial dysfunction is the main contributor in statin-myopathy pathophysiology.

Topics: Adenosine Triphosphate; Animals; Atorvastatin; Creatine Kinase; Disease Models, Animal; Hydroxymethylglutaryl-CoA Reductase Inhibitors; L-Lactate Dehydrogenase; Lactic Acid; Male; Microscopy, Electron, Transmission; Mitochondria, Muscle; Motor Activity; Muscle, Skeletal; Muscular Diseases; Myoglobin; Pyruvic Acid; Rats; Rats, Sprague-Dawley; 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

Statins inhibit the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which is involved in the production of mevalonic acid in the cholesterol biosynthesis pathway. This pathway also results in the production of other bioactive molecules including coenzyme Q10 (also known as ubiquinone or ubidecarenone). Coenzyme Q10 is a naturally-occurring coenzyme with antioxidant effects that is involved in electron transport in mitochondria and is thought to play a role in energy transfer in skeletal muscle. Muscle-related problems are a frequently reported adverse effect of statins, and it has been hypothesised that a reduced endogenous coenzyme Q10 concentration is a cause of statin-induced myopathy. Coenzyme Q10 supplementation has therefore been proposed to reduce the adverse muscular effects sometimes seen with statins. Here, we consider whether coenzyme Q10 has a place in the management of statin-induced myopathy.

Topics: Energy Transfer; Humans; Hydroxymethylglutaryl CoA Reductases; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Mevalonic Acid; Muscular Diseases; Ubiquinone

Statins are useful in the armamentarium of the clinician dealing with dyslipidemia, which increases cardiovascular morbi-mortality in hypertensive and diabetic patients among others. Dyslipidemia commonly exists as a comorbidity factor in the development of atherosclerotic cardiovascular disease. Use of statins is however associated with side effects which at times are so disabling as to interfere with activities of daily living. There are various ways of dealing with this, including use of more water-soluble varieties, intermittent dosing, or use of statin alternatives. Of late, use of co-enzyme Q10 has become acceptable for the muscle side effects. Only one report of any benefit on the rarely reported memory side effect was encountered by the author in the search of English medical literature. This is a report of a documented case of a Nigerian woman with history of statin intolerance in this case, memory dysfunction despite persisting dyslipidemia comorbidity. Her memory dysfunction side effect which interfered with activities of daily living and background muscle pain cleared when coenzyme Q10 was administered alongside low dose statin. Her lipid profile normalized and has remained normal. It is being recommended for use when statin side effects (muscle- and memory-related) impair quality of life and leave patient at dyslipidemia-induced cardiovascular morbi-mortality.

Topics: Dyslipidemias; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Memory; Memory Disorders; Muscular Diseases; Recovery of Function; Treatment Outcome; Ubiquinone

The aim of this study was to evaluate the effect of low-energy laser irradiation, coenzyme Q10 and vitamin E supplementation on the apoptosis of macrophages and muscle precursor cells during skeletal muscle regeneration after bupivacaine-induced injury. The experiment was conducted on 75 gilts, divided into 5 experimental groups: I--control, II--low-energy laser irradiation, III--coenzyme Q10, IV--coenzyme Q10 and vitamin E, V--vitamin E. Muscle necrosis was induced by injection of 0.5% bupivacaine hydrochloride. The animals were euthanized on subsequent days after injury. Samples were formalin fixed and processed routinely for histopathology. Apoptosis was detected using the TUNEL method. The obtained results indicate that low-energy laser irradiation has a beneficial effect on macrophages and muscle precursor cell activity during muscle post-injury regeneration and protects these cells against apoptosis. Vitamin E has a slightly lower protective effect, limited mainly to the macrophages. Coenzyme Q10 co-supplemented with vitamin E increases the activity of macrophages and muscle precursor cells, myotube and young muscle formation. Importantly, muscle precursor cells seem to be more sensitive to apoptosis than macrophages in the environment of regenerating damaged muscle.

Topics: Animals; Antioxidants; Apoptosis; Bupivacaine; Dose-Response Relationship, Radiation; Drug Therapy, Combination; Female; Lasers; Muscle, Skeletal; Muscular Diseases; Swine; Swine Diseases; Ubiquinone; Vitamin E

Topics: Adenosine Triphosphate; Animals; Diabetes Mellitus, Type 2; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Insulin; Muscular Diseases; Ubiquinone

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

We evaluated coenzyme Q₁₀ (CoQ) levels in patients studied under suspicion of mitochondrial DNA depletion syndromes (MDS) (n=39). CoQ levels were quantified by HPLC, and the percentage of mtDNA depletion by quantitative real-time PCR. A high percentage of MDS patients presented with CoQ deficiency as compared to other mitochondrial patients (Mann-Whitney-U test: p=0.001). Our findings suggest that MDS are frequently associated with CoQ deficiency, as a possible secondary consequence of disease pathophysiology. Assessment of muscle CoQ status seems advisable in MDS patients since the possibility of CoQ supplementation may then be considered as a candidate therapy.

Topics: Adolescent; Ataxia; Child; Child, Preschool; Chromatography, High Pressure Liquid; DNA, Mitochondrial; Female; Humans; Infant; Infant, Newborn; Male; Metabolism, Inborn Errors; Mitochondrial Diseases; Mitochondrial Myopathies; Muscle Weakness; Muscular Diseases; Real-Time Polymerase Chain Reaction; Ubiquinone; Young Adult

Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Muscular Diseases; Oxidative Stress; Ubiquinone; Vitamins

Topics: Child; Fluorobenzenes; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipoproteinemia Type II; Muscular Diseases; Polymorphism, Genetic; Pyrimidines; Rosuvastatin Calcium; Sulfonamides; Ubiquinone

Topics: Anticholesteremic Agents; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Mitochondria; Muscular Diseases; Ubiquinone; Vitamins

Topics: Anticholesteremic Agents; Health Knowledge, Attitudes, Practice; Humans; Male; Middle Aged; Mitochondria; Muscular Diseases; Simvastatin; Ubiquinone; Vitamins

Statins lower cholesterol by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in the biosynthesis of cholesterol. However, severe adverse events, including myalgias and rhabdomyolysis, have been reported with statin treatment. Different mechanisms have been proposed to explain statin-induced myopathy, including reduction of mevalonate pathway products, induction of apoptosis, mitochondrial dysfunction, and genetic predisposition. A decrease in coenzyme Q(10) (CoQ), a product of the mevalonate pathway, could contribute to statin induced myopathy. This article reviews the clinical and biochemical features of statin-induced myopathy, the inter-relationship between statins and the concentration of CoQ in plasma and tissues, and whether there is a role for supplementation with CoQ to attenuate statin-induced myopathy.

Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Muscular Diseases; Ubiquinone

Topics: Coenzymes; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Muscular Diseases; Treatment Outcome; Ubiquinone; Vitamins

The pathogenesis of myopathy due to HMG-CoA reductase inhibitors is not entirely clear but the existence of myopathy due to other lipid-lowering medications suggests it is mediated through effects on lipid metabolism. We describe a patient who developed a myopathy after 27 months of ingestion of orlistat that slowly improved after discontinuation of the drug. Orlistat may have caused this myopathy through depletion of a critical nutrient or through some as of yet undefined mechanism.

Topics: Adult; Anti-Obesity Agents; Creatine Kinase; Humans; Lactones; Male; Muscular Diseases; Orlistat; Treatment Outcome; Ubiquinone

Topics: Cholesterol; Coenzymes; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Muscular Diseases; Myocardial Infarction; Ubiquinone; Vitamins

Coenzyme Q10 (CoQ10) deficiency is an autosomal recessive disorder with heterogenous phenotypic manifestations and genetic background. We describe seven patients from five independent families with an isolated myopathic phenotype of CoQ10 deficiency. The clinical, histological and biochemical presentation of our patients was very homogenous. All patients presented with exercise intolerance, fatigue, proximal myopathy and high serum CK. Muscle histology showed lipid accumulation and subtle signs of mitochondrial myopathy. Biochemical measurement of muscle homogenates showed severely decreased activities of respiratory chain complexes I and II + III, while complex IV (COX) was moderately decreased. CoQ10 was significantly decreased in the skeletal muscle of all patients. Tandem mass spectrometry detected multiple acyl-CoA deficiency, leading to the analysis of the electron-transferring-flavoprotein dehydrogenase (ETFDH) gene, previously shown to result in another metabolic disorder, glutaric aciduria type II (GAII). All of our patients carried autosomal recessive mutations in ETFDH, suggesting that ETFDH deficiency leads to a secondary CoQ10 deficiency. Our results indicate that the late-onset form of GAII and the myopathic form of CoQ10 deficiency are allelic diseases. Since this condition is treatable, correct diagnosis is of the utmost importance and should be considered both in children and in adults. We suggest to give patients both CoQ10 and riboflavin supplementation, especially for long-term treatment.

Topics: Adolescent; Adult; Biopsy; Child; Coenzymes; Electron-Transferring Flavoproteins; Female; Follow-Up Studies; Humans; Iron-Sulfur Proteins; Male; Muscle, Skeletal; Muscular Diseases; Mutation; Oxidoreductases Acting on CH-NH Group Donors; Riboflavin; Ubiquinone

Topics: Cachexia; Coenzymes; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Muscular Diseases; Ubiquinone

Topics: Coenzymes; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Muscular Diseases; Pain; Ubiquinone

Three unrelated, sporadic patients with muscle coenzyme Q10 (CoQ10) deficiency presented at 32, 29, and 6 years of age with proximal muscle weakness and elevated serum creatine kinase (CK) and lactate levels, but without myoglobinuria, ataxia, or seizures. Muscle biopsy showed lipid storage myopathy, combined deficiency of respiratory chain complexes I and III, and CoQ10 levels below 50% of normal. Oral high-dose CoQ10 supplementation improved muscle strength dramatically and normalized serum CK.

Topics: Adult; Coenzymes; Creatine Kinase; Delivery, Obstetric; Disease Progression; Electron Transport Complex I; Electron Transport Complex III; Female; Humans; Lactic Acid; Lipid Metabolism; Male; Metabolism, Inborn Errors; Muscle Weakness; Muscle, Skeletal; Muscular Diseases; Pregnancy; Pregnancy Complications; Ubiquinone

Topics: Coenzymes; Drug Therapy, Combination; Heart Diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Muscular Diseases; Ubiquinone

Topics: Anticholesteremic Agents; Antioxidants; Coenzymes; Exercise; Humans; Muscular Diseases; Pain; Ubiquinone

Zidovudine (ZDV) has been associated with 'ragged-red' fibre myopathy, due to its effects on myocyte mitochondria. Usually this is reversible with cessation of ZDV. We report a 52-year-old man, who in 1985 developed ragged-red fibre myopathy 14 years after diagnosis of HIV infection while on effective ZDV-based combination antiretroviral therapy (ART). He was treated with the mitochondrial anti-oxidant coenzyme Q10 and made an excellent recovery, without change of ARTs. This suggests a novel therapy for further investigation targeted at ZDV induced myopathy, potentially allowing continuation of antiviral treatments including ZDV.

Topics: Acquired Immunodeficiency Syndrome; Coenzymes; Drug Therapy, Combination; Humans; Male; Middle Aged; Muscle, Skeletal; Muscular Diseases; Reverse Transcriptase Inhibitors; Treatment Outcome; Ubiquinone; Zidovudine

Fifty consecutive new cardiology clinic patients who were on statin drug therapy (for an average of 28 months) on their initial visit were evaluated for possible adverse statin effects (myalgia, fatigue, dyspnea, memory loss, and peripheral neuropathy). All patients discontinued statin therapy due to side effects and began supplemental CoQ(10) at an average of 240 mg/day upon initial visit. Patients have been followed for an average of 22 months with 84% of the patients followed now for more than 12 months. The prevalence of patient symptoms on initial visit and on most recent follow-up demonstrated a decrease in fatigue from 84% to 16%, myalgia from 64% to 6%, dyspnea from 58% to 12%, memory loss from 8% to 4% and peripheral neuropathy from 10% to 2%. There were two deaths from lung cancer and one death from aortic stenosis with no strokes or myocardial infarctions. Measurements of heart function either improved or remained stable in the majority of patients. We conclude that statin-related side effects, including statin cardiomyopathy, are far more common than previously published and are reversible with the combination of statin discontinuation and supplemental CoQ(10). We saw no adverse consequences from statin discontinuation.

Topics: Adult; Aged; Aged, 80 and over; Anticholesteremic Agents; Cardiomyopathies; Coenzymes; Dyspnea; Fatigue; Female; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Memory Disorders; Middle Aged; Muscular Diseases; Pain; Peripheral Nervous System Diseases; Prospective Studies; Ubiquinone

The aim of the study was to observe the effect of coenzyme Q10 and vitamin E supplementation on the course of the regeneration process of the longissimus lumborum muscle after bupivacaine-induced myonecrosis as well as to determine the correlation between the level of those substances in plasma and their levels in damaged and non-damaged muscular tissue in pigs. The obtained results indicate that the course of regeneration of a damaged muscle is affected to a higher extent by coenzyme Q10 than by vitamin E. The administration of coenzyme Q10 and vitamin E has a significant impact on the increase in the level of those substances in damaged muscles and plasma of animals.

Topics: Anesthetics, Local; Animal Feed; Animals; Antioxidants; Bupivacaine; Coenzymes; Female; Muscle, Skeletal; Muscular Diseases; Necrosis; Regeneration; Swine; Swine Diseases; Ubiquinone; Vitamin E

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

Two brothers with myopathic coenzyme Q10 (CoQ10) deficiency responded dramatically to CoQ10 supplementation. Muscle biopsies before therapy showed ragged-red fibers, lipid storage, and complex I + III and II + III deficiency. Approximately 30% of myofibers had multiple features of apoptosis. After 8 months of treatment, excessive lipid storage resolved, CoQ10 level normalized, mitochondrial enzymes increased, and proportion of fibers with TUNEL-positive nuclei decreased to 10%. The authors conclude that muscle CoQ10 deficiency can be corrected by supplementation of CoQ10, which appears to stimulate mitochondrial proliferation and to prevent apoptosis.

Topics: Adolescent; Child; Child, Preschool; Coenzymes; Humans; Immunohistochemistry; Male; Microscopy, Electron; Muscles; Muscular Diseases; Phenotype; Ubiquinone

We report the case of 71-year-old male who was once diagnosed as having diabetic amyotrophy, because of pronounced wasting in proximal muscles, massive weight loss, and development of paresthesia in his legs. Afterwards, ragged red fibers and mitochondrial tRNA mutation at position 3243 were documented in muscle biopsy. He had diabetes mellitus associated with 3243 mitochondrial DNA mutation, suggesting that clinically, diabetic amyotrophy may be overlapped with mitochondria-related disease entities in some parts. Coenzyme Q10 administration was effective in relieving the symptoms in his legs, fatigue, and residual urine in his bladder. These were confirmed with the improvement in neurological parameters. In conclusion, this case gives important help in understanding myopathy in diabetes. It would be important to check on the 3243 mitochondrial tRNA mutation in patients with diabetic amyotrophy and/or diabetic neuropathic symptoms.

Topics: Animals; Coenzymes; Diabetes Complications; Diabetes Mellitus; Humans; Male; Muscular Diseases; Mutation; RNA; RNA, Mitochondrial; RNA, Transfer, Leu; Ubiquinone

In skeletal muscles from rats treated with germanium for 23 weeks, there were numerous ragged-red fibers and cytochrome-c oxidase (COX)-deficient fibers. Biochemically, germanium reduced the enzyme activities in the mitochondrial respiratory chain. Rotenone-sensitive NADH-cytochrome-c reductase as well as COX activities were markedly reduced, while succinate-cytochrome-c reductase was less severely, but significantly, affected. The histopathological findings in these muscles were similar to those seen in patients with mitochondrial encephalomyopathy, suggesting that germanium-induced myopathy may be a useful experimental model. Coenzyme Q10 administration appeared to be ineffective in preventing this experimental myopathy.

Topics: Animals; Body Weight; Coenzymes; Female; Germanium; Microscopy, Electron; Mitochondria, Muscle; Muscles; Muscular Diseases; Organ Size; Rats; Rats, Wistar; Ubiquinone

Coenzyme Q10 (CoQ) content was measured in isolated muscle mitochondria from 25 patients with mitochondrial encephalomyopathies (MEM), most of whom had mitochondrial DNA mutations. The CoQ level was significantly lower in MEM patients than in controls. CoQ levels varied widely from patient to patient, especially in those with chronic progressive external ophthalmoplegia including Kearns-Sayre syndrome, which may explain, at least in part, the variable response of patients to CoQ administration.

Topics: Adolescent; Adult; Child; Coenzymes; DNA, Mitochondrial; Female; Humans; Male; Middle Aged; Mitochondria, Muscle; Muscular Diseases; Mutation; Neuromuscular Diseases; Ubiquinone

An 18-year-old male with mitochondrial myopathy, encephalopathy and lactic acidosis was studied by electromyography (EMG) along with histological and biochemical studies on his biopsied muscle. Mitochondrial cytochrome c oxidase deficiency with a decrease in the amounts of the subunits 2, 6, and 7 was discovered. Although no apparent symptoms of peripheral neuropathy were present, EMG revealed high-amplitude motor unit action potentials with a reduced interference pattern and the histochemical study revealed fiber type grouping without grouped atrophy. These findings indicated lower motor neuron damage, probably due to the mitochondrial disorder, followed by reinnervation. Coenzyme Q10 administration was effective in reducing both the lactate and pyruvate levels and for recovering the muscle atrophy.

Topics: Acidosis, Lactic; Adolescent; Biopsy; Brain Diseases; Coenzymes; Cytochrome-c Oxidase Deficiency; Electromyography; Humans; Male; Mitochondria, Muscle; Muscular Diseases; Ubiquinone

We tested the efficacy of coenzyme Q10 (ubidecarenone, CoQ10) therapy in patients with Kearns-Sayre syndrome and other mitochondrial myopathies with chronic progressive external ophthalmoplegia (CPEO). We treated seven patients for 1 year with daily oral administration of 120 mg of CoQ10. Throughout the treatment most of our patients showed a progressive reduction of serum lactate and pyruvate levels following standard muscle exercise and generally improved neurologic functions. The ECG and echocardiogram showed no significant changes in our patients. None of our patients showed any improvement in ptosis and CPEO.

Topics: Adolescent; Adult; Coenzymes; Female; Humans; Kearns-Sayre Syndrome; Male; Mitochondria, Muscle; Muscular Diseases; Ophthalmoplegia; Ubiquinone

A male with mitochondrial myopathy, encephalopathy, lactic acidemia, and strokelike episodes is reported. He had also recurrent episodes of ileus. Muscle biopsy revealed ragged-red fibres. The cytochemistry of cytochrome c oxidase (CCO) showed scattered nonstained fibres, while all muscle fibres were heavily stained by immunocytochemistry using CCO antibody. These findings suggest that partical CCO deficiency may be present in the skeletal muscles of the patient. NADH cytochrome c reductase in the patient's muscle mitochondria was low compared with normal controls (about 26%), although succinate cytochrome c reductase was normal. Coenzyme Q10 administration (90 mg/day) did not improve CSF lactate levels, but did decrease plasma lactate levels. His muscle weakness slightly improved.

Topics: Acidosis, Lactic; Adult; Brain Diseases; Cerebrovascular Disorders; Coenzymes; Electron Transport Complex IV; Humans; Intestinal Obstruction; Male; Mitochondria, Muscle; Muscular Diseases; Recurrence; Ubiquinone

Topics: Acidosis, Lactic; Adult; Brain Diseases, Metabolic; Coenzymes; Cytochromes; Electron Transport; Humans; Male; Mitochondria, Muscle; Muscular Diseases; Ubiquinone

In a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes [MELAS] who had normal mitochondrial enzyme activity, high doses of coenzyme Q10 (CoQ) were administered. Clinical improvement with decreased serum lactate and pyruvate levels was observed. Though the mechanism of action of CoQ is not known, a trial is worthwhile in patients with MELAS.

Topics: Acidosis, Lactic; Adolescent; Betamethasone; Brain Diseases; Coenzymes; Female; Humans; Mitochondria, Muscle; Muscular Diseases; Prednisolone; Syndrome; Ubiquinone