ubiquinone and Heart-Failure

Chronic heart failure is a debilitating condition that accounts for an annual NHS spend of £2.3B. Low levels of endogenous coenzyme Q10 may exacerbate chronic heart failure. Coenzyme Q10 supplements might improve symptoms and slow progression. As statins are thought to block the production of coenzyme Q10, supplementation might be particularly beneficial for patients taking statins.. To assess the clinical effectiveness and cost-effectiveness of coenzyme Q10 in managing chronic heart failure with a reduced ejection fraction.. A systematic review that included randomised trials comparing coenzyme Q10 plus standard care with standard care alone in chronic heart failure. Trials restricted to chronic heart failure with a preserved ejection fraction were excluded. Databases including MEDLINE, EMBASE and CENTRAL were searched up to March 2020. Risk of bias was assessed using the Cochrane Risk of Bias tool (version 5.2). A planned individual participant data meta-analysis was not possible and meta-analyses were mostly based on aggregate data from publications. Potential effect modification was examined using meta-regression. A Markov model used treatment effects from the meta-analysis and baseline mortality and hospitalisation from an observational UK cohort. Costs were evaluated from an NHS and Personal Social Services perspective and expressed in Great British pounds at a 2019/20 price base. Outcomes were expressed in quality-adjusted life-years. Both costs and outcomes were discounted at a 3.5% annual rate.. A total of 26 trials, comprising 2250 participants, were included in the systematic review. Many trials were reported poorly and were rated as having a high or unclear risk of bias in at least one domain. Meta-analysis suggested a possible benefit of coenzyme Q10 on all-cause mortality (seven trials, 1371 participants; relative risk 0.68, 95% confidence interval 0.45 to 1.03). The results for short-term functional outcomes were more modest or unclear. There was no indication of increased adverse events with coenzyme Q10. Meta-regression found no evidence of treatment interaction with statins. The base-case cost-effectiveness analysis produced incremental costs of £4878, incremental quality-adjusted life-years of 1.34 and an incremental cost-effectiveness ratio of £3650. Probabilistic sensitivity analyses showed that at thresholds of £20,000 and £30,000 per quality-adjusted life-year coenzyme Q10 had a high probability (95.2% and 95.8%, respectively) of being more cost-effective than standard care alone. Scenario analyses in which the population and other model assumptions were varied all found coenzyme Q10 to be cost-effective. The expected value of perfect information suggested that a new trial could be valuable.. For most outcomes, data were available from few trials and different trials contributed to different outcomes. There were concerns about risk of bias and whether or not the results from included trials were applicable to a typical UK population. A lack of individual participant data meant that planned detailed analyses of effect modifiers were not possible.. Available evidence suggested that, if prescribed, coenzyme Q10 has the potential to be clinically effective and cost-effective for heart failure with a reduced ejection fraction. However, given important concerns about risk of bias, plausibility of effect sizes and applicability of the evidence base, establishing whether or not coenzyme Q10 is genuinely effective in a typical UK population is important, particularly as coenzyme Q10 has not been subject to the scrutiny of drug-licensing processes. Stronger evidence is needed before considering its prescription in the NHS.. A new independent, well-designed clinical trial of coenzyme Q10 in a typical UK heart failure with a reduced ejection fraction population may be warranted.. This study is registered as PROSPERO CRD42018106189.. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in. People living with chronic heart failure suffer from shortness of breath, ankle swelling, tiredness, frequent stays in hospital and reduced quality of life and have shorter lives. The NHS spends over £2 billion each year managing chronic heart failure. Coenzyme Q10 is a vitamin-like substance made by the body that helps cells produce energy. Low levels of coenzyme Q10 in heart muscle may lead to, or exacerbate, chronic heart failure. Taking coenzyme Q10 supplements might improve symptoms or slow deterioration. To the best of our knowledge, we found all randomised clinical trials of coenzyme Q10 in patients with the type of chronic heart failure caused by muscle weakness (i.e. heart failure with reduced ejection fraction, where the heart's pumping function is weaker than normal). We asked the research groups responsible for these trials to provide the patient data that they had collected in their trials. Most research groups did not share their data and so we mainly used information from published trial reports. This limited our planned analyses. We found that taking coenzyme Q10 alongside usual treatment for heart failure with reduced ejection fraction potentially reduced deaths by approximately one-third and reduced readmission to hospital by around 40%. However, these results were uncertain. Side effects were not increased. We had some concerns about how reliable the data were, and it is not clear how well the results apply to UK patients. We also worked out what the benefits and costs to the NHS would be if coenzyme Q10 became available on prescription for patients with heart failure with reduced ejection fraction. Our model found that prescription could be worthwhile; however, a new trial is needed first to make sure that coenzyme Q10 improves outcomes for patients. A new trial would be particularly important because coenzyme Q10 has not been assessed in the same way as prescribed medicines. A new trial could make sure that there is better evidence about whether or not prescribing would be a good use of NHS resources.

Topics: Cost-Benefit Analysis; Heart Failure; Humans; Quality-Adjusted Life Years; Technology Assessment, Biomedical; Ubiquinone

Mitochondrial ATP production requires a small electron carrier, coenzyme Q10 (CoQ10), which has been used as adjunctive therapy in patients with cardiovascular disease (CVD) and hypertension (HTN) because of its bioenergetics and antioxidant properties. Randomized controlled trials (RCTs) beyond the last 2 decades evaluating CoQ10 added to conventional therapy resulted in mixed results and were underpowered to address major clinical endpoints.. The objective of this systematic review was to examine the impact of CoQ10 supplementation on older adults with CVD or HTN in the last 2 decades (2000-2020).. PubMed/Medline, Cochrane Database, CINAHL, and Google Scholar databases were searched systematically, and references from selected studies were manually reviewed, to identify RCTs or crossover studies evaluating the efficacy of CoQ10 supplementation. Data extracted from selected studies included trial design and duration, treatment, dose, participant characteristics, study variables, and important findings.. A total of 14 studies (1067 participants) met the inclusion criteria. The effect of CoQ10 supplementation was examined among predominantly older adult males with heart failure (HF) (n = 6), HTN (n = 4), and ischemic heart disease (n = 3), and preoperatively in patients scheduled for cardiac surgery (n = 1). CoQ10 supplementation in patients with HF improved functional capacity, increased serum CoQ10 concentrations, and led to fewer major adverse cardiovascular events. CoQ10 had positive quantifiable effects on inflammatory markers in patients with ischemic heart disease. Myocardial hemodynamics improved in patients who received CoQ10 supplementation before cardiac surgery. Effects on HTN were inconclusive.. In predominantly older adult males with CVD or HTN, CoQ10 supplementation added to conventional therapy is safe and offers benefits clinically and at the cellular level. However, results of the trials need to be viewed with caution, and further studies are indicated before widespread usage of CoQ10 is recommended in all older adults.

Topics: Aged; Antioxidants; Cardiovascular Diseases; Heart Failure; Humans; Hypertension; Male; Myocardial Ischemia; Ubiquinone

Aim    The aim of the study was evaluation of the effect of the coenzyme Q10 (Q10) treatment on all-cause and cardiovascular mortality of patients with chronic heart failure (CHF). Q-10 increases the electron transfer in the mitochondrial respiratory chain and exerts anti-inflammatory and antioxidant effects. These effects improve the endothelial function and reduce afterload, which facilitates the heart pumping function. Patients with reduced left ventricular (LV) ejection fraction (EF) (CHFrEF) have low Q10.Material and methods    Criteria of inclusion in the meta-analysis: 1) placebo-controlled studies; 2) enrollment of at least 100 patients; 3) publications after 2010, which implies an optimal basic therapy for CHF; 4) duration of at least 6 months; 5) reported cardiovascular and/or all-cause mortality; 6) using sufficient doses of Q10 (>100 mg/day). The search was performed in CENTRAL, MEDLINE, Embase, Web of Science, E-library, and ClinicalTrials.gov databases. All-cause mortality was the primary efficacy endpoint in this systematic review and the meta-analysis. The secondary endpoint was cardiovascular mortality. Meta-analysis was performed according to the Mantel-Haenszel methods. The Cochrane criterion (I2) was used for evaluation of statistical heterogeneity. The random effects model was used at I2≥50 %, whereas the fixed effects model was used at I2<50.Results    Analysis of studies published from 01.01.2011 to 01.12.2021 identified 357 publications, 23 of which corresponded to the study topic, but only 6 (providing results of four randomized clinical trials, RCT) completely met the predefined criteria. The final analysis included results of managing 1139 patients (586 received Q10 and 553 received placebo). Risk of all-cause death was analyzed by data of four RCTs (1139 patients). The decrease in the risk associated with the Q10 treatment was 36 % (OR=0.64, 95 % CI 0.48-0.87, р=0.004). The heterogeneity of studies was low (Chi2=0.84; p=0.84; I2=0 %). Risk of cardiovascular mortality was analyzed by data of two RCTs (863 patients). The decrease in the risk associated with the Q10 treatment was significant, 55% (OR=0.45, 95 % CI: 0.32-0.64, р=0.00001). In this case, the data heterogeneity was also low (Chi2=0.41; p=0.52; I2=0 %).Conclusion    The meta-analysis confirmed the beneficial effect of coenzyme Q10 on the prognosis of patients with CHFrEF receiving the recommended basic therapy.

Topics: Chronic Disease; Heart Failure; Humans; Stroke Volume; Ubiquinone; Ventricular Function, Left; Vitamins

Coenzyme Q10, or ubiquinone, is a non-prescription nutritional supplement. It is a fat-soluble molecule that acts as an electron carrier in mitochondria, and as a coenzyme for mitochondrial enzymes. Coenzyme Q10 deficiency may be associated with a multitude of diseases, including heart failure. The severity of heart failure correlates with the severity of coenzyme Q10 deficiency. Emerging data suggest that the harmful effects of reactive oxygen species are increased in people with heart failure, and coenzyme Q10 may help to reduce these toxic effects because of its antioxidant activity. Coenzyme Q10 may also have a role in stabilising myocardial calcium-dependent ion channels, and in preventing the consumption of metabolites essential for adenosine-5'-triphosphate (ATP) synthesis. Coenzyme Q10, although not a primary recommended treatment, could be beneficial to people with heart failure. Several randomised controlled trials have compared coenzyme Q10 to other therapeutic modalities, but no systematic review of existing randomised trials was conducted prior to the original version of this Cochrane Review, in 2014.. To review the safety and efficacy of coenzyme Q10 in heart failure.. We searched CENTRAL, MEDLINE, Embase, Web of Science, CINAHL Plus, and AMED on 16 October 2020; ClinicalTrials.gov on 16 July 2020, and the ISRCTN Registry on 11 November 2019. We applied no language restrictions.. We included randomised controlled trials of either parallel or cross-over design that assessed the beneficial and harmful effects of coenzyme Q10 in people with heart failure. When we identified cross-over studies, we considered data only from the first phase.. We used standard Cochrane methods, assessed study risk of bias using the Cochrane 'Risk of bias' tool, and GRADE methods to assess the quality of the evidence. For dichotomous data, we calculated the risk ratio (RR); for continuous data, the mean difference (MD), both with 95% confidence intervals (CI). Where appropriate data were available, we conducted meta-analysis. When meta-analysis was not possible, we wrote a narrative synthesis. We provided a PRISMA flow chart to show the flow of study selection.. We included eleven studies, with 1573 participants, comparing coenzyme Q10 to placebo or conventional therapy (control). In the majority of the studies, sample size was relatively small. There were important differences among studies in daily coenzyme Q10 dose, follow-up period, and the measures of treatment effect. All studies had unclear, or high risk of bias, or both, in one or more bias domains. We were only able to conduct meta-analysis for some of the outcomes. None of the included trials considered quality of life, measured on a validated scale, exercise variables (exercise haemodynamics), or cost-effectiveness. Coenzyme Q10 probably reduces the risk of all-cause mortality more than control (RR 0.58, 95% CI 0.35 to 0.95; 1 study, 420 participants; number needed to treat for an additional beneficial outcome (NNTB) 13.3; moderate-quality evidence). There was low-quality evidence of inconclusive results between the coenzyme Q10 and control groups for the risk of myocardial infarction (RR 1.62, 95% CI 0.27 to 9.59; 1 study, 420 participants), and stroke (RR 0.18, 95% CI 0.02 to 1.48; 1 study, 420 participants). Coenzyme Q10 probably reduces hospitalisation related to heart failure (RR 0.62, 95% CI 0.49 to 0.78; 2 studies, 1061 participants; NNTB 9.7; moderate-quality evidence). Very low-quality evidence suggests that coenzyme Q10 may improve the left ventricular ejection fraction (MD 1.77, 95% CI 0.09 to 3.44; 7 studies, 650 participants), but the results are inconclusive for exercise capacity (MD 48.23, 95% CI -24.75 to 121.20; 3 studies, 91 participants); and the risk of developing adverse events (RR 0.70, 95% CI 0.45 to 1.10; 2 studies, 568 participants). We downgraded the quality of the evidence mainly due to high risk of bias and imprecision.. The included studies provide moderate-quality evidence that coenzyme Q10 probably reduces all-cause mortality and hospitalisation for heart failure. There is low-quality evidence of inconclusive results as to whether coenzyme Q10 has an effect on the risk of myocardial infarction, or stroke. Because of very low-quality evidence, it is very uncertain whether coenzyme Q10 has an effect on either left ventricular ejection fraction or exercise capacity. There is low-quality evidence that coenzyme Q10 may increase the risk of adverse effects, or have little to no difference. There is currently no convincing evidence to support or refute the use of coenzyme Q10 for heart failure. Future trials are needed to confirm our findings.

Topics: Ataxia; Heart Failure; Humans; Mitochondrial Diseases; Muscle Weakness; Myocardial Infarction; Quality of Life; Stroke; Stroke Volume; Ubiquinone; Ventricular Function, Left

There is evidence demonstrating that heart failure (HF) occurs in 1-2% of the global population and is often accompanied by comorbidities which contribute to increasing the prevalence of the disease, the rate of hospitalization and the mortality. Although recent advances in both pharmacological and non-pharmacological approaches have led to a significant improvement in clinical outcomes in patients affected by HF, residual unmet needs remain, mostly related to the occurrence of poorly defined strategies in the early stages of myocardial dysfunction. Nutritional support in patients developing HF and nutraceutical supplementation have recently been shown to possibly contribute to protection of the failing myocardium, although their place in the treatment of HF requires further assessment, in order to find better therapeutic solutions. In this context, the Optimal Nutraceutical Supplementation in Heart Failure (ONUS-HF) working group aimed to assess the optimal nutraceutical approach to HF in the early phases of the disease, in order to counteract selected pathways that are imbalanced in the failing myocardium. In particular, we reviewed several of the most relevant pathophysiological and molecular changes occurring during the early stages of myocardial dysfunction. These include mitochondrial and sarcoplasmic reticulum stress, insufficient nitric oxide (NO) release, impaired cardiac stem cell mobilization and an imbalanced regulation of metalloproteinases. Moreover, we reviewed the potential of the nutraceutical supplementation of several natural products, such as coenzyme Q10 (CoQ10), a grape seed extract,

Topics: Animals; Antioxidants; Citrus; Dietary Supplements; Endoplasmic Reticulum Stress; Grape Seed Extract; Heart Failure; Humans; Malus; Mitochondria, Heart; Myocardium; Nitric Oxide; Nutritional Support; Olea; Plant Extracts; Stem Cells; Ubiquinone

Coenzyme Q (CoQ) is ubiquitously embedded in lipid bilayers of various cellular organelles. As a redox cycler, CoQ shuttles electrons between mitochondrial complexes and extramitochondrial reductases and oxidases. In this way, CoQ is crucial for maintaining the mitochondrial function, ATP synthesis, and redox homeostasis. Cardiomyocytes have a high metabolic rate and rely heavily on mitochondria to provide energy. CoQ levels, in both plasma and the heart, correlate with heart failure in patients, indicating that CoQ is critical for cardiac function. Moreover, CoQ supplementation in clinics showed promising results for treating heart failure. This review provides a comprehensive view of CoQ metabolism and its interaction with redox enzymes and reactive species. We summarize the clinical trials and applications of CoQ in heart failure and discuss the caveats and future directions to improve CoQ therapeutics.

Topics: Cell Cycle; Heart Failure; Humans; Mitochondria; Oxidation-Reduction; Oxidoreductases; Ubiquinone

Cardiovascular diseases are the most common cause of death in Poland and in the world. People with cardiovascular disease or high cardiovascular risk require early detection and pharmacotherapy. New methods of prevention and treatment are needed. Coenzyme Q10 (CoQ10) is an essential component of the human body. CoQ10 plays an important role in the biosynthesis of adenosine-5'-triphosphate (ATP) and has antioxidant activity. More and more evidence indicates that CoQ10 is closely related to cardiovascular disorders. Its supplementation may be beneficial in various chronic and acute disorders. Coenzyme Q10 used in heart failure reduces mortality and improves exercise capacity. CoQ10 can reduce the values of systolic blood pressure (SBP) and diastolic blood pressure (DBP) in hypertensive patients. CoQ10 supplementation prevents electrocardiographic (ECG) changes in patients taking doxorubicin and has a positive effect on heart function during anthracycline chemotherapy. The review article was based on available literature found in the Medline database and includes preclinical and clinical research. Further research related to CoQ10 can contribute to significant progress in the prevention and treatment of cardiovascular diseases but may also be the basis for increasing the range of indications for this drug.

Topics: Cardiotoxicity; Cardiovascular Diseases; Heart Failure; Humans; Poland; Ubiquinone

Multiple micronutrient supplementation has been suggested to have a role on health outcomes in patients with heart failure (HF), but the evidence is inconclusive.. To elucidate the role of multiple micronutrient supplementation in heart failure we performed a comprehensive review of the literature.. The search in databases included PUBMED (until June 2018) to detect randomized controlled trials (RCTs) and meta-analyzes that investigated the impact of micronutrient supplementation in HF.. With more than 2357 titles and abstracts reviewed, we included only the studies suitable for the final review. Whether alone or in combination, micronutrients have been found to improve the health outcomes of patients with HF by improving symptoms, work capacity and left ventricular ejection fraction (LVEF), thus increasing the quality of life in these patients.. Future studies are needed to document the effects of multiple micronutrient associations in order to include them in nutritional guidelines to increase survival and to improve quality of life in patients with heart failure.

Topics: Amino Acids; Carnitine; Databases, Factual; Dietary Supplements; Energy Metabolism; Fatty Acids, Omega-3; Folic Acid; Heart Failure; Homocysteine; Humans; Magnesium; Micronutrients; Myocardium; Nutrition Therapy; Oxidative Stress; Potassium; Quality of Life; Selenium; Taurine; Ubiquinone; Vitamins

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

Mitochondrial dysfunction characterized by impaired bioenergetics, oxidative stress and aldehydic load is a hallmark of heart failure. Recently, different research groups have provided evidence that selective activation of mitochondrial detoxifying systems that counteract excessive accumulation of ROS, RNS and reactive aldehydes is sufficient to stop cardiac degeneration upon chronic stress, such as heart failure. Therefore, pharmacological and non-pharmacological approaches targeting mitochondria detoxification may play a critical role in the prevention or treatment of heart failure. In this review we discuss the most recent findings on the central role of mitochondrial dysfunction, oxidative stress and aldehydic load in heart failure, highlighting the most recent preclinical and clinical studies using mitochondria-targeted molecules and exercise training as effective tools against heart failure.

Topics: Aldehydes; Animals; Antioxidants; Biomimetic Materials; Cardiotonic Agents; Clinical Trials as Topic; Disease Models, Animal; Drug Evaluation, Preclinical; Energy Metabolism; Exercise; Heart Failure; Humans; Malondialdehyde; Mitochondria, Heart; Oxidative Stress; Reactive Nitrogen Species; Reactive Oxygen Species; Superoxide Dismutase; Ubiquinone

The therapeutic efficacy of coenzyme Q10 on patients with cardiac failure remains controversial. We pooled previous clinical studies to re-evaluate the efficacy of coenzyme Q10 in patients with cardiac failure.. We searched PubMed, Cochrane Library, EMBASE, and Clinical Trials.gov databases for controlled trials. The endpoints were death, left heart ejection fraction, exercise capacity, and New York Heart Association (NYHA) cardiac function classification after treatment. The pooled risk ratios (RRs) and standardized mean difference (SMD) were used to assess the efficacy of coenzyme Q10.. Patients with heart failure who used coenzyme Q10 had lower mortality and a higher exercise capacity improvement than the placebo-treated patients with heart failure. No significant differences between the efficacy of the administration of coenzyme Q10 and placebo in the endpoints of left heart ejection fraction and NYHA classification were observed.

Topics: Adult; Aged; Cardiovascular Agents; Chi-Square Distribution; Exercise Tolerance; Female; Heart Failure; Humans; Male; Middle Aged; Odds Ratio; Randomized Controlled Trials as Topic; Recovery of Function; Risk Factors; Stroke Volume; Treatment Outcome; Ubiquinone; Ventricular Function, Left

The current therapy for patients with stable systolic heart failure is largely limited to treatments that interfere with neurohormonal activation. Critical pathophysiological hallmarks of heart failure are an energetic deficit and oxidative stress, and both may be the result of mitochondrial dysfunction. This dysfunction is not (only) the result of defect within mitochondria per se, but is in particular traced to defects in intermediary metabolism and of the regulatory interplay between excitation-contraction coupling and mitochondrial energetics, where defects of cytosolic calcium and sodium handling in failing hearts may play important roles. In the past years, several therapies targeting mitochondria have emerged with promising results in preclinical models. Here, we discuss the mechanisms and results of these mitochondria-targeted therapies, but also of interventions that were not primarily thought to target mitochondria but may have important impact on mitochondrial biology as well, such as iron and exercise. Future research should be directed at further delineating the details of mitochondrial dysfunction in patients with heart failure to further optimize these treatments.

Topics: Antioxidants; Dietary Supplements; Exercise Therapy; Heart Failure; Humans; Iron; Mitochondria, Heart; Oligopeptides; Organophosphorus Compounds; Trace Elements; 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

Heart failure (HF) with either preserved or reduced ejection fraction is associated with increased morbidity and mortality. Evidence-based therapies are often limited by tolerability, hypotension, electrolyte disturbances, and renal dysfunction. Coenzyme Q10 (CoQ10) may represent a safe therapeutic option for patients with HF. CoQ10 is a highly lipophilic molecule with a chemical structure similar to vitamin K. Although being a common component of cellular membranes, CoQ10's most prominent role is to facilitate the production of adenosine triphosphate in the mitochondria by participating in redox reactions within the electron transport chain. Numerous trials during the past 30 years examining CoQ10 in patients with HF have been limited by small numbers and lack of contemporary HF therapies. The recent publication of the Q-SYMBIO randomized controlled trial demonstrated a reduction in major adverse cardiovascular events with CoQ10 supplementation in a contemporary HF population. Although having limitations, this study has renewed interest in evaluating CoQ10 supplementation in patients with HF. Current literature suggests that CoQ10 is relatively safe with few drug interactions and side effects. Furthermore, it is already widely available as an over-the-counter supplement. These findings warrant future adequately powered randomized controlled trials of CoQ10 supplementation in patients with HF. This state-of-the-art review summarizes the literature about the mechanisms, clinical data, and safety profile of CoQ10 supplementation in patients with HF.

Topics: Animals; Cardiovascular Agents; Dietary Supplements; Drug Interactions; Energy Metabolism; Heart Failure; Humans; Mitochondria, Heart; Myocardium; Treatment Outcome; Ubiquinone

Heart failure affects 5.1 million people in the USA annually. It accounts for a frequent cause of hospitalizations and disability. Patients with congestive heart failure have lower plasma levels of CoQ10, which is an independent predictor of mortality in this patient population. It has been hypothesized that a deficiency of CoQ10 can play a role in the development and worsening of heart failure, and that oral supplementation can possibly improve symptoms and survival in these patients. Based on previous small studies and meta-analyses, the use of CoQ10 in heart failure suggested an improvement ejection fraction, stroke volume, cardiac output, and cardiac index with CoQ10 supplementation, however most of these small studies appeared to be underpowered to result in any significant data. The results of the recent Q-SYMBIO trial demonstrated an improvement in heart failure symptoms with a significant reduction in major adverse cardiovascular events and mortality.

Topics: Cardiac Output; Clinical Trials as Topic; Dietary Supplements; Heart Failure; Humans; Stroke Volume; Ubiquinone

Coenzyme Q10 is the only endogenously synthesized lipid with a redox function which exhibits broad tissue and intracellular distribution in mammals. Beneficial effects of Coenzyme Q10 supplementation were observed in several age-related diseases including heart failure. CoQ10 (coenzyme Q10) level is significantly decreased in patients with this disease, which correlates with severity of clinical symptoms. Supplementation with various pharmaceutical formulations of CoQ10 improves impaired cardiac function and clinical course of heart failure. Current data from clinical trials indicate that CoQ10 can significantly reduce morbidity and mortality of heart failure patients in addition to guideline recommended pharmacotherapy.

Topics: Animals; Clinical Trials as Topic; Dietary Supplements; Heart Failure; Humans; Ubiquinone

Topics: Evidence-Based Medicine; Heart Failure; Humans; Ubiquinone; Vitamins

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

Advancing age is a major risk factor for the development of cardiovascular diseases. The aetiology of several cardiovascular disorders is thought to involve impaired mitochondrial function and oxidative stress. Coenzyme Q10 (CoQ10) acts as both an antioxidant and as an electron acceptor at the level of the mitochondria. Furthermore, in cardiac patients, plasma CoQ10 has been found to be an independent predictor of mortality. Based on the fundamental role of CoQ10 in mitochondrial bioenergetics and its well-acknowledged antioxidant properties, several clinical trials evaluating CoQ10 have been undertaken in cardiovascular disorders of ageing including chronic heart failure, hypertension, and endothelial dysfunction. CoQ10 as a therapy appears to be safe and well tolerated.

Topics: Aging; Antioxidants; Endothelial Cells; Heart Failure; Humans; Hypertension; Ubiquinone

Coenzyme Q10, or ubiquinone, is a non-prescription nutritional supplement. It is a fat-soluble molecule that acts as an electron carrier in mitochondria and as a coenzyme for mitochondrial enzymes. Coenzyme Q10 deficiency may be associated with a multitude of diseases including heart failure. The severity of heart failure correlates with the severity of coenzyme Q10 deficiency. Emerging data suggest that the harmful effects of reactive oxygen species are increased in patients with heart failure and coenzyme Q10 may help to reduce these toxic effects because of its antioxidant activity. Coenzyme Q10 may also have a role in stabilising myocardial calcium-dependent ion channels and preventing the consumption of metabolites essential for adenosine-5'-triphosphate (ATP) synthesis. Coenzyme Q10, although not a primary recommended treatment, could be beneficial to patients with heart failure. Several randomised controlled trials have compared coenzyme Q10 to other therapeutic modalities, but no systematic review of existing randomised trials has been conducted.. To review the safety and efficacy of coenzyme Q10 in heart failure.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 12); MEDLINE OVID (1950 to January Week 3 2013) and EMBASE OVID (1980 to 2013 Week 03) on 24 January 2013; Web of Science with Conference Proceedings (1970 to January 2013) and CINAHL Plus (1981 to January 2013) on 25 January 2013; and AMED (Allied and Complementary Medicine) (1985 to January 2013) on 28 January 2013. We applied no language restrictions.. We included randomised controlled trials of either parallel or cross-over design that assessed the beneficial and harmful effects of coenzyme Q10 in patients with heart failure. When cross-over studies were identified, we considered data only from the first phase.. Two authors independently extracted data from the included studies onto a pre-designed data extraction form. We then entered the data into Review Manager 5.2 for analysis. We assessed study risk of bias using the Cochrane 'Risk of bias' tool. For dichotomous data, we calculated the risk ratio and for continuous data the mean difference (MD). Where appropriate data were available, we performed meta-analysis. For this review we prioritised data from pooled analyses only. Where meta-analysis was not possible, we wrote a narrative synthesis. We provided a QUOROM flow chart to show the flow of papers.. We included seven studies with 914 participants comparing conenzyme Q10 versus placebo. There were no data on clinical events from published randomised trials. The included studies had small sample sizes. Meta-analysis was only possible for a few physiological measures and there was substantial heterogeneity.Only one study reported on total mortality, major cardiovascular events and hospitalisation. Five trials reported on the New York Heart Association (NYHA) classification of clinical status, but it was impossible to pool data due to heterogeneity. None of the included trials considered quality of life, exercise variables, adverse events or cost-effectiveness as outcome measures. Pooled analysis suggests that the use of coenzyme Q10 has no clear effect on left ventricular ejection fraction (MD -2.26; 95% confidence interval (CI) -15.49 to 10.97, n = 60) or exercise capacity (MD 12.79; 95% CI -140.12 to 165.70, n = 85). Pooled data did indicate that supplementation increased blood levels of coenzyme Q10 (MD 1.46; 95% CI 1.19 to 1.72, n = 112). However, there are only a small number of small studies with a risk of bias, so these results should be interpreted with caution.. No conclusions can be drawn on the benefits or harms of coenzyme Q10 in heart failure at this time as trials published to date lack information on clinically relevant endpoints. Furthermore, the existing data are derived from small, heterogeneous trials that concentrate on physiological measures: their results are inconclusive. Until further evidence emerges to support the use of coenzyme Q10 in heart failure, there might be a need to re-evaluate whether further trials testing coenzyme Q10 in heart failure are desirable.

Topics: Ataxia; Heart Failure; Humans; Mitochondrial Diseases; Muscle Weakness; Randomized Controlled Trials as Topic; Stroke Volume; Ubiquinone; Vitamins

Statins are effective in the prevention of coronary events and the treatment of acute coronary syndromes. However, their efficacy and safety in patients with heart failure (HF) is still a matter of debate. On the basis of literature evidence from subgroup analysis, retrospective, prospective cohort studies, and randomized controlled trials, in this review we try to answer the following question: Is statin therapy in HF patients for good, for bad, or indifferent? Some studies showed a negative impact of low cholesterol levels in patients with severe HF (endotoxin-lipoprotein hypothesis and coenzyme Q10 hypothesis). On the other hand, a large amount of literature demonstrates that in patients with HF, statins have a positive impact on survival and other outcomes, regardless of whether the HF was of ischemic or nonischemic origin, which is related to a combination of mechanisms (pleiotropic effects and cholesterol reduction). Much of this evidence, however, comes from observational and retrospective studies and subgroup analyses of statin use in patients with HF. Randomized clinical trials examining the efficacy of statins in HF (GISSI-HF and CORONA) did not show a benefit in mortality for patients with HF randomized to receive statins. Nevertheless, a meta-analysis found that statin therapy does not decrease all-cause or cardiovascular mortality but significantly decreases the rate of hospitalization for worsening HF and increased left ventricular ejection fraction compared with placebo.

Topics: Animals; Clinical Trials as Topic; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Treatment Outcome; Ubiquinone

Many theories and clinical trials have attempted to address the effect of low-density lipoprotein (LDL) lowering in chronic congestive heart failure (CHF). The current evidence suggests that there is no convincing reason for administering statins to patients with nonischemic heart failure. Although they do not reduce the mortality rate, statins reduce LDL cholesterol and may provide some benefit to patients with ischemic heart failure. In contrast, some authors believe that statin therapy may actually worsen outcomes in patients with CHF, especially if there is excessive reduction in LDL cholesterol. This review discusses the theories attempting to link the adverse effects of statin-mediated LDL lowering in CHF to increased levels of endotoxin or reduced levels of coenzyme Q10. In addition, the 2 largest randomized, double-blind, placebo-controlled clinical trials (CORONA and GISSI-HF) were discussed. It is clear that more trials are needed to definitely ascertain the effect of statins on CHF.

Topics: Aged; Aged, 80 and over; Chronic Disease; Endotoxins; Female; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipoproteins, LDL; Male; Randomized Controlled Trials as Topic; Survival Rate; Treatment Outcome; Ubiquinone

Heart failure (HF)-associated mortality remains high, despite guideline-recommended medical therapies. Poor nutritional status and unintentional cachexia have been shown to have a strong association with worse survival in HF patients. Importantly, micronutrient deficiencies are potential contributing factors to the progression of HF. This review aims to summarize contemporary evidence on the role of micronutrients in the pathophysiology and outcome of HF patients. Emphasis will be given to the most well-studied micronutrients, specifically, vitamin D, vitamin B complex, coenzyme Q10 and L-carnitine.

Topics: Carnitine; Heart Failure; Humans; Micronutrients; Ubiquinone; Vitamin B Complex; Vitamin D

Coenzyme Q₁₀ (CoQ₁₀; also called ubiquinone) is an antioxidant that has been postulated to improve functional status in congestive heart failure (CHF). Several randomized controlled trials have examined the effects of CoQ₁₀ on CHF with inconclusive results.. The objective of this meta-analysis was to evaluate the impact of CoQ₁₀ supplementation on the ejection fraction (EF) and New York Heart Association (NYHA) functional classification in patients with CHF.. A systematic review of the literature was conducted by using databases including MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and manual examination of references from selected studies. Studies included were randomized controlled trials of CoQ₁₀ supplementation that reported the EF or NYHA functional class as a primary outcome. Information on participant characteristics, trial design and duration, treatment, dose, control, EF, and NYHA classification were extracted by using a standardized protocol.. Supplementation with CoQ₁₀ resulted in a pooled mean net change of 3.67% (95% CI: 1.60%, 5.74%) in the EF and -0.30 (95% CI: -0.66, 0.06) in the NYHA functional class. Subgroup analyses showed significant improvement in EF for crossover trials, trials with treatment duration ≤12 wk in length, studies published before 1994, and studies with a dose ≤100 mg CoQ₁₀/d and in patients with less severe CHF. These subgroup analyses should be interpreted cautiously because of the small number of studies and patients included in each subgroup.. Pooled analyses of available randomized controlled trials suggest that CoQ₁₀ may improve the EF in patients with CHF. Additional well-designed studies that include more diverse populations are needed.

Topics: Adult; Dietary Supplements; Heart Failure; Humans; Randomized Controlled Trials as Topic; Severity of Illness Index; Stroke Volume; Ubiquinone; Ventricular Dysfunction, Left

In this review we summarise the current state of knowledge of the therapeutic efficacy and mechanisms of action of CoQ(10) in cardiovascular disease. Our conclusions are: 1. There is promising evidence of a beneficial effect of CoQ(10) when given alone or in addition to standard therapies in hypertension and in heart failure, but less extensive evidence in ischemic heart disease. 2. Large scale multi-centre prospective randomised trials are indicated in all these areas but there are difficulties in funding such trials. 3. Presently, due to the notable absence of clinically significant side effects and likely therapeutic benefit, CoQ(10) can be considered a safe adjunct to standard therapies in cardiovascular disease.

Topics: Adenosine Triphosphate; Anthracyclines; Antioxidants; Cardiovascular Diseases; Clinical Trials as Topic; Coenzymes; Diet; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Ischemia; Mitochondria; Models, Biological; Ubiquinone

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the Western world. Oxidative stress appears to play a pivotal role in atherosclerosis. Coenzyme Q10 (CoQ10), one of the most important antioxidants, is synthesized de novo by every cell in the body. Its biosynthesis decreases with age and its deficit in tissues is associated with degenerative changes of aging, thus implicating a possible therapeutic role of CoQl0 in human diseases. There is evidence to support the therapeutic value of CoQ10 as an adjunct to standard medical therapy in congestive heart failure. However, much further research is required, especially in the use of state-of-the-art techniques to assess functional outcomes in patients with congestive heart failure.

Topics: Aging; Antioxidants; Cardiac Output, Low; Coenzymes; Drug Interactions; Heart Failure; Humans; Oxidative Stress; Ubiquinone; Vitamins

Metabolic therapy involves the administration of a substance normally found in the body to enhance a metabolic reaction within the cell. This may be achieved in two ways. Firstly, for some systems a substance can be given to achieve greater than normal levels in the body so as to drive an enzymic reaction in a preferred direction. Secondly, metabolic therapy may be used to correct an absolute or relative deficiency of a cellular component. Thus, metabolic therapy differs greatly from most standard cardiovascular pharmacologic therapies such as the use of ACE Inhibitors, beta-blockers, statins and calcium channel antagonists that are given to block rather than enhance cellular processes.

Topics: Adaptation, Physiological; Cardiovascular Diseases; Coenzymes; Exercise; Glucose; Heart Failure; Humans; Hypertension; Insulin; Meditation; Orotic Acid; Physical Therapy Modalities; Potassium; Thioctic Acid; Ubiquinone

Topics: Amyotrophic Lateral Sclerosis; Antioxidants; Clinical Trials as Topic; Coenzymes; Costs and Cost Analysis; Heart Failure; Humans; Hypertension; Migraine Disorders; Mitochondrial Encephalomyopathies; Parkinson Disease; Ubiquinone

Physicians' use of micronutrients to improve symptoms or outcomes in chronic illness has until recently been guided by limited data on the actions of individual agents in vitro or in animal studies. However several recently published clinical trials have provided information about which groups of patients are likely to benefit from which combination of micronutrients. Patients with chronic cardiac failure (CCF), particularly elderly individuals, have several reasons to be deficient in micronutrients including reduced intake, impaired gastrointestinal absorption and increased losses on the background of increased utilisation due for example to increased oxidative stress. Studies of nutritional supplementation in CCF patients have usually concentrated on specific agents. However given that many micronutrients have synergistic influences upon metabolic processes this strategy might merely lead to a shifting of a limiting step. Rather, a strategy of increasing the availability of multiple agents at once might be more logical. The aim of this article is to briefly review the experimental rationale for each of the micronutrients of potential benefit in chronic heart failure and examine the current clinical trial evidence supporting their use.

Topics: Animals; Antioxidants; Ascorbic Acid; Calcium; Carnitine; Copper; Dietary Supplements; Heart Failure; Humans; Magnesium; Magnesium Deficiency; Micronutrients; Niacin; Oxidative Stress; Phosphocreatine; Ubiquinone; Vitamin B Complex; Vitamin B Deficiency; Vitamin E; Zinc

Patients suffering from congestive heart failure exhibit impaired myocardial energy production, myocyte calcium overload and increased oxidative stress. Nutritional factors known to be important for myocardial energy production, calcium homeostasis and the reduction of oxidative stress, such as thiamine, riboflavin, pyridoxine, L-carnitine, coenzyme Q10, creatine and taurine are reduced in this patient population. Furthermore, deficiencies of taurine, carnitine, and thiamine are established primary causes of dilated cardiomyopathy. Studies in animals and limited trials in humans have shown that dietary replacement of some of these compounds in heart failure can significantly restore depleted levels and may result in improvement in myocardial structure and function as well as exercise capacity. Larger scale studies examining micronutrient depletion in heart failure patients, and the benefits of dietary replacement need to be performed. At the present time, it is our belief that these conditioned nutritional requirements, if unsatisfied, contribute to myocyte dysfunction and loss; thus, restoration of nutritional deficiencies should be part of the overall therapeutic strategy for patients with congestive heart failure.

Topics: Animals; Calcium; Carnitine; Creatine; Energy Metabolism; Heart Failure; Homeostasis; Humans; Muscle Cells; Nutrition Disorders; Nutritional Requirements; Nutritional Status; Oxidative Stress; Taurine; Thiamine; Thiamine Deficiency; Ubiquinone; Vitamin B Complex

Preclinical and clinical studies suggest that anthracycline-induced cardiotoxicity can be prevented by administering coenzyme Q10 during cancer chemotherapy that includes drugs such as doxorubicin and daunorubicin. Studies further suggest that coenzyme Q10 does not interfere with the antineoplastic action of anthracyclines and might even enhance their anticancer effects. Preventing cardiotoxicity might allow for escalation of the anthracycline dose, which would further enhance the anticancer effects. Based on clinical investigation, although limited, a cumulative dose of doxorubicin of up to 900 mg/m2, and possibly higher, can be administered safely during chemotherapy as long as coenzyme Q10 is administered concurrently. The etiology of the dose-limiting cardiomyopathy that is induced by anthracyclines can be explained by irreversible damage to heart cell mitochondria, which differ from mitochondria of other cells in that they possess a unique enzyme on the inner mitochondrial membrane. This enzyme reduces anthracyclines to their semiquinones, resulting in severe oxidative stress, disruption of mitochondrial energetics, and irreversible damage to mitochondrial DNA. Damage to mitochondrial DNA blocks the regenerative capability of the organelle and ultimately leads to apoptosis or necrosis of myocytes. Coenzyme Q10, an essential component of the electron transport system and a potent intracellular antioxidant, appears to prevent damage to the mitochondria of the heart, thus preventing the development of anthracycline-induced cardiomyopathy.

Topics: Animals; Anthracyclines; Antibiotics, Antineoplastic; Antioxidants; Cardiomyopathies; Coenzymes; Cytoprotection; Dose-Response Relationship, Drug; Drug Therapy, Combination; Heart; Heart Failure; Humans; Mitochondria, Heart; Neoplasms; Ubiquinone

To review the clinical data demonstrating the safety and efficacy of coenzyme Q10 (CoQ10) in heart failure (HF).. Pertinent literature was identified through MEDLINE (1966-January 2005) using the search terms coenzyme Q10, heart failure, antioxidants, and oxidative stress. Only articles written in the English language and evaluating human subjects were used.. HF impairs the ability of the heart to maintain its normal cardiac output. Following an initial insult, cardiac remodeling ensues, resulting in left ventricular dilation and hypertrophy. Oxidative stress is also increased, while CoQ10 levels are decreased in patients with HF. This has led to the hypothesis that CoQ10, an antioxidant, may decrease oxidative stress, impair remodeling, and improve cardiac function.. Large, well-designed studies on this topic are lacking. The limited data from well-designed trials indicate there may be some minor benefits with CoQ10 therapy in ejection fraction and end diastolic volume. CoQ10 therapy has been shown to be relatively safe with a low incidence of adverse effects.

Topics: Antioxidants; Coenzymes; Heart Failure; Humans; Oxidative Stress; Ubiquinone; Ventricular Remodeling

Topics: Aging; Antioxidants; Biomarkers; Chromatography, High Pressure Liquid; Drug Monitoring; Electron Transport; Exercise; Heart Failure; Humans; Kidney Diseases; Liver Cirrhosis; Myocardial Ischemia; Myocardial Reperfusion Injury; Oxidative Stress; Reference Values; Specimen Handling; Ubiquinone

There are a number of theoretical reasons as to why 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) should be prescribed to patients with chronic heart failure (CHF). These agents are proven to prevent coronary heart disease, the major etiological factor in the development of CHF. Potential additional effects of these agents include inhibition of proinflammatory cytokine activity and other potential beneficial effects on cardiac remodeling. However, there are also possible adverse effects of this strategy, supported by the overriding observation that low plasma lipid levels portend a poorer prognosis in patients with established CHF. Potential mechanisms by which statins may directly confer adverse effects include a reduction in levels of the antioxidant ubiquinone and an increase in blood endotoxin levels, both of which may contribute to CHF disease progression. Given these uncertainties, an answer to the question of whether or not therapy for CHF should include statins requires a definitive clinical trial. The importance of such a trial is further highlighted by the already commonplace usage of statins amongst patients with CHF.

Topics: Antioxidants; Coronary Disease; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipids; Ubiquinone

The depletion of the essential nutrient CoQ10 by the increasingly popular cholesterol lowering drugs, HMG CoA reductase inhibitors (statins), has grown from a level of concern to one of alarm. With ever higher statin potencies and dosages, and with a steadily shrinking target LDL cholesterol, the prevalence and severity of CoQ10 deficiency is increasing noticeably. An estimated 36 million Americans are now candidates for statin drug therapy. Statin-induced CoQ10 depletion is well documented in animal and human studies with detrimental cardiac consequences in both animal models and human trials. This drug-induced nutrient deficiency is dose related and more notable in settings of pre-existing CoQ10 deficiency such as in the elderly and in heart failure. Statin-induced CoQ10 deficiency is completely preventable with supplemental CoQ10 with no adverse impact on the cholesterol lowering or anti-inflammatory properties of the statin drugs. We are currently in the midst of a congestive heart failure epidemic in the United States, the cause or causes of which are unclear. As physicians, it is our duty to be absolutely certain that we are not inadvertently doing harm to our patients by creating a wide-spread deficiency of a nutrient critically important for normal heart function.

Topics: Animals; Cholesterol, LDL; Clinical Trials as Topic; Coenzymes; Dietary Supplements; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Ubiquinone; United States

Randomized controlled trials are generally regarded as the gold standard of study designs to determine causality. The inclusion of a placebo group in these trials, when appropriate, is critical to access the efficacy of a drug or supplement. The placebo response itself has received some attention in the medical literature over the past fifty years. The recent increasing utilization of dietary supplements and herbal medications by patients makes it imperative to reevaluate the placebo response in conventional and alternative medicine. This article will review some of the negative and positive results from randomized trials utilizing dietary supplements (androstenedione, beta-carotene, CoQ10, garlic, soy, vitamin C and E...) for a number of non-urologic and urologic conditions, including cancer.

Topics: Androstenedione; Antioxidants; beta Carotene; Coenzymes; Complementary Therapies; Dehydroepiandrosterone; Garlic; Heart Failure; Hot Flashes; Humans; Libido; Neoplasms; Placebo Effect; Randomized Controlled Trials as Topic; Ubiquinone; Vitamin E

Topics: Animals; Coenzymes; Cricetinae; Disease Models, Animal; Female; Follow-Up Studies; Heart Failure; Heart Function Tests; Hemodynamics; Humans; Male; Randomized Controlled Trials as Topic; Sensitivity and Specificity; Severity of Illness Index; Survival Analysis; Treatment Outcome; Ubiquinone

This article provides a comprehensive review of 30 years of research on the use of coenzyme Q10 in prevention and treatment of cardiovascular disease. This endogenous antioxidant has potential for use in prevention and treatment of cardiovascular disease, particularly hypertension, hyperlipidemia, coronary artery disease, and heart failure. It appears that levels of coenzyme Q10 are decreased during therapy with HMG-CoA reductase inhibitors, gemfibrozil, Adriamycin, and certain beta blockers. Further clinical trials are warranted, but because of its low toxicity it may be appropriate to recommend coenzyme Q10 to select patients as an adjunct to conventional treatment.

Topics: Animals; Cardiomyopathies; Cardiovascular Diseases; Complementary Therapies; Coronary Disease; Heart Failure; Humans; Hypertension; Myocardial Infarction; Ubiquinone

Coenzyme Q10 (CoQ10) has a pathophysiologic role in many disease states. The purpose of this review is to provide recommendations regarding the safety, efficacy, and dosing of CoQ10 in the management of chronic heart failure (CHF), angina, and hypertension.. Literature pertaining to the safety and efficacy of CoQ10 specifically in cardiovascular indications was reviewed. We used relevant clinical trials, articles, reviews, and letters that were selected from a literature search of the MEDLINE database (1974-2000), Micromedex Healthcare Series, and the Natural Medicines Comprehensive Database.. Coenzyme Q10 administered orally has favorable actions in the described cardiovascular conditions and appears to be safe and well tolerated in the adult population. Issues concerning optimum target dosages, potential interactions, monitoring parameters, and the role of CoQ10 as a monotherapeutic agent need to be investigated further. Favorable effects of CoQ10 on ejection fraction, exercise tolerance, cardiac output, and stroke volume are demonstrated in the literature; thus, the use of CoQ10 as adjuvant therapy in patients with CHF may be supported.. Coenzyme Q10 therapy in angina and hypertension cannot be substantiated until additional clinical trials demonstrate consistent beneficial effects. However, CoQ10 may be recommended as adjuvant therapy in selected patients with CHE At this time, CoQ10 should not be recommended as monotherapy or first-line therapy in any disease state.

Topics: Angina, Unstable; Animals; Antioxidants; Chronic Disease; Clinical Trials as Topic; Coenzymes; Heart Failure; Humans; Hypertension; Ubiquinone

The clinical experience in cardiology with CoQ10 includes studies on congestive heart failure, ischemic heart disease, hypertensive heart disease, diastolic dysfunction of the left ventricle, and reperfusion injury as it relates to coronary artery bypass graft surgery. The CoQ10-lowering effect of HMG-CoA reductase inhibitors and the potential adverse consequences are of growing concern. Supplemental CoQ10 alters the natural history of cardiovascular illnesses and has the potential for prevention of cardiovascular disease through the inhibition of LDL cholesterol oxidation and by the maintenance of optimal cellular and mitochondrial function throughout the ravages of time and internal and external stresses. The attainment of higher blood levels of CoQ10 (> 3.5 micrograms/ml) with the use of higher doses of CoQ10 appears to enhance both the magnitude and rate of clinical improvement. In this communication, 34 controlled trials and several open-label and long-term studies on the clinical effects of CoQ10 in cardiovascular diseases are reviewed.

Topics: Antioxidants; Cardiovascular Diseases; Clinical Trials as Topic; Coenzymes; Coronary Artery Bypass; Heart Failure; Humans; Hypertension; Myocardial Ischemia; Reperfusion Injury; Ubiquinone; Ventricular Dysfunction, Left

The coenzyme Q (CoQ) concentration in the inner membrane of beef heart mitochondria is not kinetically saturating for NADH oxidation inasmuch as the K(m) of NADH oxidation for endogenous CoQ10 is in the mM range in membrane lipids. Using CoQ1 as an electron acceptor from complex I, we have found additional evidence that the high Km of NADH oxidase for CoQ is not an artifact due to the use of organic solvents in reconstitution studies. We have also obtained experimental evidence that CoQ concentration may be rendered more rate-limiting for NADH oxidation either by a decrease of CoQ content (as in liver regeneration or under an acute oxidative stress), or by a possible increase of the Km for CoQ, as in some mitochondrial diseases and ageing. The possibility of enhancing the rate of NADH oxidation by CoQ therapy is hindered by the fact that the CoQ concentration in mitochondria appears to be regulated by its mixability with the membrane phospholipids. Nevertheless CoQ10 incorporated into heart submitochondrial particles by sonication enhances NADH oxidation (but not succinate oxidation) up to twofold. Nontoxic CoQ homologs and analogs having shorter side-chains with respect to CoQ10 can be incorporated in the mitochondrial membrane without sonication, supporting an enhancement of NADH oxidation rate above 'physiological' values. It is worth investigating whether this approach can have a therapeutical value in vivo in mitochondrial bioenergetic disorders.

Topics: Aging; Animals; Cattle; Coenzymes; Electron Transport Complex I; Electron Transport Complex II; Heart Failure; Intracellular Membranes; Kinetics; Lipid Bilayers; Liver Regeneration; Membrane Lipids; Mitochondria, Heart; Multienzyme Complexes; NADH, NADPH Oxidoreductases; Oxidation-Reduction; Oxidative Stress; Oxidoreductases; Succinate Dehydrogenase; Ubiquinone

The purpose of this was to investigate the effect of coenzyme Q10 (CoQ10) in patients with congestive heart failure (CHF) by measuring the possible improvement of certain relevant hemodynamic heart parameters. A statistic aggregation method know as a meta-analysis was used to measure the changes in the cardiac parameters. To begin with we collected the total number of randomized controlled trials and from a total of 14 studies published in the period of 1984-1994, eight studies met our inclusion criteria. The rest were excluded because of a lack of data which made a meta-analysis impossible. The relevant effect parameters investigated were stroke volume (SV), cardiac output (CO), ejection fraction (EF), cardiac index (CI), end diastolic volume index (EDVI), systolic time intervals (PEP/LVET) and total work capacity (Wmax). Seven meta-analyses were performed, one for each of the parameters, and the calculated effect sizes were all positive. Statistical significance could be demonstrated for all of the parameters except the PEP/LVET and Wmax thereby indicating an improvement of greater or lesser magnitude in the CoQ10 group as opposed to the placebo group. Accordingly, the average patient in the CoQ10 group had a better score with regard to SV and CO than 76 and 73% respectively of the patients in the placebo group. In conclusion, supplemental treatment of CHF with CoQ10 is consistent with an improvement of SV, EF, CO, CI and EDVI. Homogeneity could be established for SV and CO. Additional clinical trials of the effect of CoQ10 on CHF are necessary, but, on the basis of the evidence currently available, the possibility remains that CoQ10 will receive a well-documented role as an adjunctive treatment of CHF.

Topics: Cardiac Output; Clinical Trials as Topic; Coenzymes; Diastole; Heart Failure; Hemodynamics; Humans; Randomized Controlled Trials as Topic; Stroke Volume; Systole; Treatment Outcome; Ubiquinone

Meta-analysis applied to eight controlled clinical trials of coenzyme Q10 (CoQ10)-treatment of congestive heart failure revealed a significant improvement a several important cardiac parameters such as ejection fraction (EF), stroke volume (SV), cardiac output (CO), cardiac index (CI) and end diastolic volume index (EDVI). Concerning the improvement in SV and CO the average patient in the CoQ10 group had a higher score than respectively 76% and 73% of the patients in the placebo group. The improvement in CO and SV was also significant when considering of homogeneity. Additional controlled clinical trials seem justified which may strengthen the power of the meta-analyses. However, based on available results, it can not be excluded that CoQ10 may have a future role a adjunctive therapy in a dosage of 100-200 mg/day in the treatment of chronic congestive heart failure.

Topics: Antioxidants; Clinical Trials as Topic; Heart Failure; Hemodynamics; Humans; Meta-Analysis as Topic; Ubiquinone

Coenzyme Q10 is an endogenous substance which has a well established role as electron carrier in the mitochondrial synthesis of adenosine triphosphate (ATP). In addition, coenzyme Q10 also has antioxidant and membrane stabilizing properties. Based on biopsy samples from patients undergoing cardiac surgery and blood samples from patients with congestive heart failure, the existence of a relative Q10 deficiency in patients with cardiac failure has been suggested. A total number of eight double blind, placebo controlled studies in patients with heart failure have been published. Most of these studies include a small number of patients, and various methodological problems have been attributed to these. The results, judged as improvement in ejection fraction or work capacity, are inconsistent. In one large study, coenzyme Q10 was found to have a positive effect on morbidity, and in another on quality of life. However, although some of the results appear to be promising, more studies are needed, including studies designed with mortality as a primary end point, before the effect of the substance in patients with heart failure can be established.

Topics: Clinical Trials as Topic; Coenzymes; Heart Failure; Humans; Ubiquinone

Co-enzyme Q10 (ubiquinone) is a naturally occurring substance which has properties potentially beneficial for preventing cellular damage during myocardial ischemia and reperfusion. It plays a role in oxidative phosphorylation and has membrane stabilizing activity. The substance has been used in oral form to treat various cardiovascular disorders including angina pectoris, hypertension, and congestive heart failure. Its clinical importance is now being established in clinical trails worldwide.

Topics: Administration, Oral; Cardiovascular Diseases; Chemical Phenomena; Chemistry; Coenzymes; Doxorubicin; Free Radicals; Heart Arrest, Induced; Heart Failure; Humans; Hypertension; Ischemia; Reperfusion; Ubiquinone

There are obviously several causes of myocardial dysfunction but energy deficiency of the myocytes may play a significant role and probably is a common mechanism during the progression of myocardial failure. Theoretically, a poor utilization efficiency of oxygen may be due to exhaustion of the myocardial stores of bioenergetics. In this report the authors review their biochemical results from measurements of coenzyme Q10 (CoQ10) levels in blood and human endomyocardial biopsies using an HPLC method from patients with suspected myocardial disease (n = 45). The levels of CoQ10, which has a key role in the respiratory chain and the synthesis of ATP, was found to be significantly decreased in various groups of patients with myocardial failure (dilated and restrictive cardiomyopathy and alcoholic heart disease) as compared to "normal" myocardium (0.42 +/- 0.04 micrograms/mg dry weight). The deficiency of CoQ10 was more pronounced with increasing symptoms; e.g. patients with dilated cardiomyopathy in NYHA Classes III and IV had lower tissue CoQ10 content than those of Classes I and II (0.28 +/- 0.04 vs. 0.37 +/- 0.06 micrograms/mg, p less than 0.001). Nearly two thirds of a series of 40 patients in severe heart failure (Classes III and IV) treated with CoQ10, 100 mg daily, in an open, controlled design showed subjective and objective improvement. Clinical responders were 69% and 43% of patients with cardiomyopathy and ischaemic heart disease, respectively. The results suggest that CoQ10 is a novel and effective breakthrough in heart-failure therapy and it appears safe, as no adverse reactions were registered. The through in heart-failure therapy and it appears safe, as no adverse reactions were registered.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Chronic Disease; Coenzymes; Heart Failure; Humans; Ubiquinone

Topics: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; Administration, Oral; Aminopyridines; Amrinone; Cardiotonic Agents; Coenzymes; Enoximone; Heart; Heart Failure; Hemodynamics; Humans; Imidazoles; Injections, Intravenous; Milrinone; Nifedipine; Oxyfedrine; Phosphodiesterase Inhibitors; Pyridazines; Pyridones; Quinazolines; Ubiquinone

Topics: Adenosine Triphosphate; Capsules; Exercise Tolerance; Heart Failure; Humans; Lactates; Middle Aged; Powders; Ribose; Stroke Volume; Ubiquinone; Ventricular Function, Left

Endothelial dysfunction is reportedly associated with worse outcomes in patients with chronic heart failure. Ubiquinol is a reduced form of coenzyme Q10 (CoQ10) that may improve endothelial function.. We assessed the hypothesis that ubiquinol improves peripheral endothelial function in patients with heart failure with reduced ejection fraction (HFrEF).. In this randomized, double-blind, placebo-controlled, crossover pilot study, 14 patients with stable HFrEF were randomly and blindly allocated to ubiquinol 400 mg/day or placebo for 3 months. After a 1-month washout period, patients were crossed over to the alternative treatment. Before and after each treatment, we assessed peripheral endothelial function using the reactive hyperemia index (RHI) and analyzed it using the natural logarithm of RHI (LnRHI).. Peripheral endothelial function as assessed by LnRHI tended to improve with ubiquinol 400 mg/day for 3 months (p = 0.076). Original RHI values were also compared, and RHI significantly improved with ubiquinol treatment (pre-RHI 1.57 [interquartile range (IQR) 1.39-1.80], post-RHI 1.74 [IQR 1.63-2.02], p = 0.026), but not with placebo (pre-RHI 1.67 [IQR 1.53-1.85], post-RHI 1.51 [IQR 1.39-2.11], p = 0.198).. Ubiquinol 400 mg/day for 3 months led to significant improvement in peripheral endothelial function in patients with HFrEF. Ubiquinol may be a therapeutic option for individuals with HFrEF. Large-scale randomized controlled trials of CoQ10 supplementation in patients with HFrEF are needed.. Japanese University Hospital Medical Information Network (UMIN-ICDR). Clinical Trial identifier number UMIN000012604.

Topics: Aged; Cross-Over Studies; Double-Blind Method; Endothelium, Vascular; Female; Heart Failure; Humans; Male; Pilot Projects; Ubiquinone

Geographical differences in patient characteristics, management and outcomes in heart failure (HF) trials are well recognized. The aim of this study was to assess the consistency of the treat- ment effect of coenzyme Q10 (CoQ10) in the European sub-population of Q-SYMBIO, a randomized double-blind multinational trial of treatment with CoQ10, in addition to standard therapy in chronic HF.. Patients with moderate to severe HF were randomized to CoQ10 300 mg daily or placebo in addition to standard therapy. At 3 months the primary short-term endpoints were changes in New York Heart Association (NYHA) functional classification, 6-min walk test, and levels of N-terminal pro-B type natriuretic peptide. At 2 years the primary long-term endpoint was major adverse cardiovascular events (MACE).. There were no significant changes in short-term endpoints. The primary long-term endpoint of MACE was reached by significantly fewer patients in the CoQ10 group (n = 10, 9%) compared to the placebo group (n = 33, 27%, p = 0.001). The following secondary endpoints were significantly improved in the CoQ10 group compared with the placebo group: all-cause and cardiovascular mortality, NYHA classification and left ventricular ejection fraction (LVEF). In the European sub-population, when compared to the whole group, there was greater adherence to guideline directed therapy and similar results for short- and long-term endpoints. A new finding revealed a significant improvement in LVEF.. The therapeutic efficacy of CoQ10 demonstrated in the Q-SYMBIO study was confirmed in the European sub-population in terms of safely reducing MACE, all-cause mortality, cardiovascular mortality, hospitalization and improvement of symptoms.

Topics: Aged; Biomarkers; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Double-Blind Method; Europe; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Stroke Volume; Survival Rate; Treatment Outcome; Ubiquinone; Ventricular Function, Left; Vitamins

Heart failure with preserved ejection fraction (HFpEF) is a leading cause of morbidity and mortality without an established treatment. Diastolic dysfunction, the hallmark of HFpEF, is associated with altered myocardial bioenergetics. No previous study has examined the effects of coenzyme Q10 (CoQ10) on left ventricle (LV) diastolic function in patients with HFpEF. We investigated whether CoQ10 could improve LV diastolic function in patients with HFpEF. We performed a randomized controlled trial (RCT) using pretest and posttest control groups of 30 patients with HFpEF. The patients received either CoQ10 100 mg three times a day or no CoQ10 in addition to routine treatment for 30 days. Echocardiographic study was performed at baseline and follow-up. LV diastolic function was evaluated by two dimensional and Doppler echocardiography as follows; average E/e׳, septal and lateral e׳velocity, and left atrium volume index (LAVI). A total of 28 patients completed the study. A statistically significant improvement was observed in the CoQ10 treatment group in terms between groups (∆E/e׳ ‒ 3.6 vs. ‒ 2.4; p = 0.28) and (∆LAVI ‒ 5.4 vs. ‒ 4.4; p = 0.83). Short term CoQ10 supplementation provided no additional benefits in improving LV diastolic function in patients with HFpEF.

Topics: Aged; Diastole; Dietary Supplements; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Stroke Volume; Ubiquinone; Ventricular Function, Left

Heart failure (HF), the leading cause of morbidity and mortality in the US, affects 6.6 million adults with an estimated additional 3 million people by 2030. More than 50% of HF patients have heart failure with preserved left ventricular ejection fraction (HFpEF). These patients have impaired cardiac muscle relaxation and diastolic filling, which investigators have associated with cellular energetic impairment. Patients with HFpEF experience symptoms of: (1) fatigue; (2) shortness of breath; and (3) swelling (edema) of the lower extremities. However, current HF guidelines offer no effective treatment to address these underlying pathophysiologic mechanisms. Thus, we propose a biobehavioral symptom science study using ubiquinol and D-ribose (therapeutic interventions) to target mitochondrial bioenergetics to reduce the complex symptoms experienced by patients with HFpEF.. Using a randomized, double-blind, placebo-controlled design, the overall objective is to determine if administering ubiquinol and/or D-ribose to HFpEF patients for 12 weeks would decrease the severity of their complex symptoms and improve their cardiac function. The measures used to assess patients' perceptions of their health status and level of vigor (energy) will be the Kansas City Cardiomyopathy Questionnaire (KCCQ) and Vigor subscale of the Profile of Mood States. The 6-min walk test will be used to test exercise tolerance. Left ventricular diastolic function will be assessed using innovative advanced echocardiography software called speckle tracking. We will measure B-type natriuretic peptides (secreted from ventricles in HF) and lactate/ATP ratio (measure of cellular energetics).. Ubiquinol (active form of Coenzyme Q10) and D-ribose are two potential treatments that can positively affect cellular energetic impairment, the major underlying mechanism of HFpEF. Ubiquinol, the reduced form of CoQ10, is more effective in adults over the age of 50. In patients with HFpEF, mitochondrial deficiency of ubiquinol results in decreased adenosine triphosphate (ATP) synthesis and reduced scavenging of reactive oxygen species. D-ribose is a substrate required for ATP synthesis and when administered has been shown to improve impaired myocardial bioenergetics. Therefore, if the biological underpinning of deficient mitochondrial ATP in HFpEF is not addressed, patients will suffer major symptoms including lack of energy, fatigue, exertional dyspnea, and exercise intolerance.. ClinicalTrials.gov Identifier: NCT03133793 ; Data of Registration: April 28, 2017.

Topics: Double-Blind Method; Energy Metabolism; Exercise Tolerance; Female; Heart Failure; Humans; Male; Middle Aged; Mitochondria, Heart; Randomized Controlled Trials as Topic; Recovery of Function; Ribose; Stroke Volume; Time Factors; Treatment Outcome; Ubiquinone; Ventricular Function, Left

There is mounting evidence to support the influence of inflammation and oxidative stress in the pathogenesis of atrial fibrillation (AF) and heart failure (HF). The efficacy of coenzymeQ10 (CoQ10), an antioxidant used as an adjunct treatment in patients with AF and HF, remains less well established.. Consecutive patients with HF were randomized and divided into 2 groups: the CoQ10 group (combined administration of common drugs and CoQ10) and the control group (administration of common drugs). Ambulatory electrocardiogram Holter monitoring (24 hours), Doppler echocardiography, and evaluation of inflammatory cytokines were performed before treatment and 6 and 12 months after treatment.. One hundred two patients (72 male and 30 female patients), with ages ranging from 45 to 82 years (mean age, 62.3 years), were examined. There was significant reduction in the level of malondialdehyde (3.9 ± 0.7 vs 2.5 ± 0.6 ng/mL; 3.9 ± 0.7 vs 2.3 ± 0.5 ng/mL, P < 0.05) in the CoQ10 group, whereas there was no significant difference (3.3 ± 0.8 vs 2.9 ± 0.8 ng/mL; 3.3 ± 0.8 vs 2.9 ± 0.5 ng/mL) in the control group after 6 and 12 months. Three patients (6.3%) in the CoQ10 group and 12 patients (22.2%) in the control group had episodes of AF after 12 months' treatment (P = 0.02). Four patients with AF in the control group went through the third Holter recording.. CoenzymeQ10 as adjuvant treatment in patients with HF may attenuate the incidence of AF. The mechanisms of the effect perhaps have relation with the reduced levels of malondialdehyde.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Double-Blind Method; Female; Follow-Up Studies; Heart Failure; Humans; Incidence; Male; Middle Aged; Prospective Studies; Treatment Outcome; Ubiquinone

This randomized controlled multicenter trial evaluated coenzyme Q10 (CoQ10) as adjunctive treatment in chronic heart failure (HF).. CoQ10 is an essential cofactor for energy production and is also a powerful antioxidant. A low level of myocardial CoQ10 is related to the severity of HF. Previous randomized controlled trials of CoQ10 in HF were underpowered to address major clinical endpoints.. Patients with moderate to severe HF were randomly assigned in a 2-year prospective trial to either CoQ10 100 mg 3 times daily or placebo, in addition to standard therapy. The primary short-term endpoints at 16 weeks were changes in New York Heart Association (NYHA) functional classification, 6-min walk test, and levels of N-terminal pro-B type natriuretic peptide. The primary long-term endpoint at 2 years was composite major adverse cardiovascular events as determined by a time to first event analysis.. A total of 420 patients were enrolled. There were no significant changes in short-term endpoints. The primary long-term endpoint was reached by 15% of the patients in the CoQ10 group versus 26% in the placebo group (hazard ratio: 0.50; 95% confidence interval: 0.32 to 0.80; p = 0.003) by intention-to-treat analysis. The following secondary endpoints were significantly lower in the CoQ10 group compared with the placebo group: cardiovascular mortality (9% vs. 16%, p = 0.026), all-cause mortality (10% vs. 18%, p = 0.018), and incidence of hospital stays for HF (p = 0.033). In addition, a significant improvement of NYHA class was found in the CoQ10 group after 2 years (p = 0.028).. Long-term CoQ10 treatment of patients with chronic HF is safe, improves symptoms, and reduces major adverse cardiovascular events. (Coenzyme Q10 as adjunctive treatment of chronic heart failure: a randomised, double-blind, multicentre trial with focus on SYMptoms, BIomarker status [Brain-Natriuretic Peptide (BNP)], and long-term Outcome [hospitalisations/mortality]; ISRCTN94506234).

Topics: Biomarkers; Chronic Disease; Death, Sudden, Cardiac; Double-Blind Method; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Ubiquinone; Vitamins

Studies have suggested that micronutrient deficiency has some role in the progression of chronic heart failure (CHF).. Oral supplementation with coenzyme Q(10) (CoQ(10)) and creatine may reduce mitochondrial dysfunction that contributes to impaired physical performance in CHF.. We conducted a randomized, double-blind, placebo-controlled trial to determine the effect of a mixture of water-soluble CoQ(10) (CoQ(10) terclatrate; Q-ter) and creatine on exercise tolerance and health-related quality of life. Exercise tolerance was measured as total work capacity (kg·m) and peak oxygen consumption (VO(2), mL/min/kg), both from a cardiopulmonary exercise test. Health-related quality of life was measured by the Sickness Impact Profile (SIP) in CHF secondary to left ventricular systolic dysfunction (left ventricular ejection fraction ≤ 35%). After baseline assessment, 67 patients with stable CHF were randomized to receive Q-ter 320 mg + creatine 340 mg (n = 35) or placebo (n = 32) once daily for 8 weeks.. At multivariate analysis, 8-week peak VO(2) was significantly higher in the active treatment group than in the placebo group (+1.8 ± 0.9 mL/min/kg, 95% CI: 0.1-3.6, P < 0.05). No untoward effects occurred in either group.. This study suggests that oral Q-ter and creatine, added to conventional drug therapy, exert some beneficial effect on physical performance in stable systolic CHF. Results may support the design of larger studies aimed at assessing the long-term effects of this treatment on functional status and harder outcomes.

Topics: Administration, Oral; Aged; Chi-Square Distribution; Chronic Disease; Creatine; Deficiency Diseases; Dietary Supplements; Double-Blind Method; Drug Combinations; Exercise Test; Exercise Tolerance; Female; Heart Failure; Humans; Male; Medication Adherence; Oxygen Consumption; Placebo Effect; Quality of Life; Stroke Volume; Time Factors; Treatment Outcome; Ubiquinone; Ventricular Function, Left

In this study we investigated benefits of a Pycnogenol - coenzyme Q10 combination (PycnoQ10) taken as an adjunct to medical treatment in stable heart failure patients. The aim of this single-blinded, 12-week observational study was to provide functional parameters such as exercise capacity, ejection fraction and distal edema.. The essential element for inclusion was a stable level of heart failure within the past three months and stable NYHA class II or III (6 months). The heart failure management was in accordance with AHA guidelines for "best treatment." The treatment and control groups were comparable at baseline. The mean age of the PycnoQ10-treated patients was 61.3+/-7.1 years and 62.1+/-3.7 in the control group. All patients were taking medication and most patients (>75%) used three or more drugs for heart failure treatment. There were two dropouts in the PycnoQ10 treatment group and 6 in the control group (5 NYHA III patients).. Nine PycnoQ10 treated patients (out of 32) and 3 (out of 21) taking placebo improved NYHA class. Systolic and diastolic pressure as well as heart rate and respiratory rate were significantly lowered with PycnoQ10 as compared to the control group (P<0.05). No significant changes were observed in controls. Heart ejection fraction increased by 22.4% in the treatment group (P<0.05) versus 4.0% in controls. Walking distance on treadmill increased 3.3-fold in PycnoQ10 treated patients (P<0.05) but marginally improved in the control group. Distal edema decreased significantly in PycnoQ10 treated patients and only slightly in controls.. The association of Pycnogenol and CoQ10 may offer an important therapeutic option with a very good tolerability that improves heart failure management without side effects.

Topics: Aged; Blood Pressure; Edema; Female; Flavonoids; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Placebos; Plant Extracts; Prospective Studies; Single-Blind Method; Treatment Outcome; Ubiquinone; Ventricular Function, Left

The purpose of this study was to determine whether coenzyme Q₁₀ is an independent predictor of prognosis in heart failure.. Blood and tissue concentrations of the essential cofactor coenzyme Q₁₀ are decreased by statins, and this could be harmful in patients with heart failure.. We measured serum coenzyme Q₁₀ in 1,191 patients with ischemic systolic heart failure enrolled in CORONA (Controlled Rosuvastatin Multinational Study in Heart Failure) and related this to clinical outcomes.. Patients with lower coenzyme Q₁₀ concentrations were older and had more advanced heart failure. Mortality was significantly higher among patients in the lowest compared to the highest coenzyme Q₁₀ tertile in a univariate analysis (hazard ratio: 1.50, 95% confidence interval: 1.04 to 2.6, p = 0.03) but not in a multivariable analysis. Coenzyme Q₁₀ was not an independent predictor of any other clinical outcome. Rosuvastatin reduced coenzyme Q₁₀ but there was no interaction between coenzyme Q₁₀ and the effect of rosuvastatin.. Coenzyme Q₁₀ is not an independent prognostic variable in heart failure. Rosuvastatin reduced coenzyme Q₁₀, but even in patients with a low baseline coenzyme Q₁₀, rosuvastatin treatment was not associated with a significantly worse outcome. (Controlled Rosuvastatin Multinational Study in Heart Failure [CORONA]; NCT00206310).

Topics: Aged; Aged, 80 and over; Biomarkers; Female; Fluorobenzenes; Follow-Up Studies; Heart Failure; Hospitalization; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Internationality; Male; Middle Aged; Prospective Studies; Pyrimidines; Rosuvastatin Calcium; Sulfonamides; Treatment Outcome; Ubiquinone

We aimed to determine the effect of supplementation with coenzyme Q10 on conventional therapy of children with cardiac failure due to idiopathic dilated cardiomyopathy. In a prospective, randomized, double-blinded, placebo-controlled trial, we randomized 38 patients younger than 18 years with idiopathic dilated cardiomyopathy to receive either coenzyme Q10, chosen for 17 patients, or placebo, administered in the remaining 21. Echocardiographic systolic and diastolic function parameters were determined for every patient at baseline, and after 6 months of supplementation. The index score for cardiac failure in children as established in New York was used for assessing the functional class of the patients. After 6 months supplementation, 10 patients randomized to receive coenzyme Q10 showed improvements in the grading of diastolic function, this being significantly more than that achieved by those randomized to the placebo group (p value = 0.011). The mean score for the index of cardiac failure index for those receiving coenzyme Q10 was also lower than the control group (p value = 0.024).Our results, therefore, indicate that administration of coenzyme Q10 is useful in ameliorating cardiac failure in patients with idiopathic dilated cardiomyopathy through its significant effect on improving diastolic function.

Topics: Adolescent; Cardiomyopathy, Dilated; Child; Child, Preschool; Double-Blind Method; Heart Failure; Humans; Infant; Prospective Studies; Ubiquinone; Vitamins

Patients with CHF, NYHA class IV, often fail to achieve adequate plasma CoQ10 levels on supplemental ubiquinone at dosages up to 900 mg/day. These patients often have plasma total CoQ10 levels of less than 2.5 microg/ml and have limited clinical improvement. It is postulated that the intestinal edema in these critically ill patients may impair CoQ10 absorption. We identified seven patients with advanced CHF (mean EF 22%) with sub-therapeutic plasma CoQ10 levels with mean level of 1.6 microg/ml on an average dose of 450 mg of ubiquinone daily (150-600 mg/day). All seven of these patients were changed to an average of 580 mg/day of ubiquinol (450-900 mg/day) with follow-up plasma CoQ10 levels, clinical status, and EF measurements by echocardiography. Mean plasma CoQ10 levels increased from 1.6 microg/ml (0.9-2.0 microg/ml) up to 6.5 microg/ml (2.6-9.3 microg/ml). Mean EF improved from 22% (10-35%) up to 39% (10-60%) and clinical improvement has been remarkable with NYHA class improving from a mean of IV to a mean of II (I to III). Ubiquinol has dramatically improved absorption in patients with severe heart failure and the improvement in plasma CoQ10 levels is correlated with both clinical improvement and improvement in measurement of left ventricular function.

Topics: Aged; Female; Heart Failure; Humans; Intestinal Absorption; Male; Middle Aged; Ubiquinone

There is evidence that both carnitine and coenzyme Q 10 (Co Q), which are important for the functioning of myocardial mitochondria, are deficient in patients with congestive heart failure, in association with increased pro-inflammatory cytokines. It is possible that supplementation with ubiquinol and L-carnitine may protect these patients by decreasing inflammation.. In a randomized, double-blind, placebo-controlled trial, the effects of carni Q-gel (2250 mg/d L-carnitine and 270 mg/d hydrosoluble ubiquinol) were examined for 12 weeks. Thirty-one patients with heart failure received intervention (group A) and another 31 patients served as controls (group B). Serum levels of interleukin (IL)-6, tumour necrosis factor (TNF)-alpha and IL-10 could be studied among 29 patients in each group. Statistical analysis was conducted by analysis of variance and chi square test.. Echocardiographic ejection fractions were lower at baseline (38.8 + 7.6 vs. 39.3 + 6.7% in the intervention and control groups, respectively) among both group of patients, indicating class II-IV heart failure. Serum concentration of interleukin-6 (IL-6), a pro-inflammatory cytokine, was high (18.7 +/- 5.8 vs. 15.0 +/- 3.3 pg/ml, normal 0.0-3.9) and IL-10 (anti-inflammatory) was normal (3.4 +/- 1.5 vs. 2.9 +/- 1.0 pg/ml, the normal range is 1.5-3.1 pg/ml) in both groups at baseline. After 12 weeks, there was a marked reduction in IL-6 in the intervention group without such changes in the control group (7.6 +/- 1.5 vs. 11.4 +/- 2.5 pg/ml, P < 0.01. IL-10 showed only the non-significant decrease in both groups from the baseline levels (3.2 +/- 1.0 vs. 2.8 +/- 0.9 pg/ml). TNF-alpha, which was comparable at baseline (17.6 +/- 4.3 vs. 20.0 +/- 5.3 pg/ml), also showed a greater decline in the carni Q-gel group compared to the placebo group (12.5 +/- 3.3 vs. 17.2 +/- 3.2 pg/ml, P < 0.05). Baseline serum CoQ levels (0.21 +/- 0.11 vs. 0.19 +/- 0.10 microg/ml) were low; however, after 12 weeks, serum CoQ showed a significant increase in the carni Q-gel group as compared to the control group (2.7 +/- 1.2 and 0.76 +/- 0.14 microg/ml, respectively). After 12 weeks of treatment, the quality of life visual analogous scale revealed that dyspnoea, palpitation and fatigue, (NYHA class II-III-IV), which were present at rest in all patients at baseline, showed beneficial effects in the intervention group compared to the placebo group. The six-minute walk test showed that there was a significant greater benefit in walking, from the baseline distance in the intervention group (208 +/- 15.8 vs. 281 +/- 20.6 metres, P < 0.02) compared to the placebo group (218.4 +/- 17.6 vs. 260.7 +/- 19.3 metres, P < 0.05). The symptom scale indicated that the majority of patients showed improvement in the intervention group compared to the control group (28 vs. 16 patients, respectively, P < 0.05). Three patients in the intervention group had nausea and vomiting, which were controlled with symptomatic treatment.. These findings indicate that treatment with ubiquinol + L-carnitine can cause a significant reduction in the pro-inflammatory cytokines that are neurohumoural precursors related to sympathetic and parasympathetic activity, which is impaired in patients with heart failure. There was no adverse effect on IL-10. There was a significant improvement in quality of life as well as decrease in NYHA-defined heart failure.

Topics: Adult; Analysis of Variance; Biomarkers; Carnitine; Cytokines; Double-Blind Method; Exercise Test; Female; Follow-Up Studies; Heart Failure; Heart Rate; Humans; Interleukin-10; Interleukin-6; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Quality of Life; Stroke Volume; Tumor Necrosis Factor-alpha; Ubiquinone; Vitamin B Complex; Walking

There is evidence that plasma coenzyme Q(10) (CoQ(10)) levels decrease in patients with advanced chronic heart failure (CHF). However, it is not known whether oral CoQ(10) supplementation may improve cardiocirculatory efficiency and endothelial function in patients with CHF.. We studied 23 patients in NYHA class II and III (20 men, three women, mean age 59+/-9 years) with stable CHF secondary to ischaemic heart disease [ejection fraction 37+/-7%], using a double-blind, placebo-controlled cross-over design. Patients were assigned to each of the following treatments: oral CoQ(10) (100 mg tid), CoQ(10) plus supervised exercise training (ET) (60% of peak VO(2), five times a week), placebo, and placebo plus ET. Each phase lasted 4 weeks. Both peak VO(2) and endothelium-dependent dilation of the brachial artery (EDDBA) improved significantly after CoQ(10) and after ET as compared with placebo. CoQ(10) main effect was: peak VO(2)+9%, EDDBA +38%, systolic wall thickening score index (SWTI) -12%; ET produced comparable effects. CoQ(10) supplementation resulted in a four-fold increase in plasma CoQ(10) level, whereas the combination with ET further increased it. No side effects were reported with CoQ(10).. Oral CoQ(10) improves functional capacity, endothelial function, and LV contractility in CHF without any side effects. The combination of CoQ(10) and ET resulted in higher plasma CoQ(10) levels and more pronounced effects on all the abovementioned parameters. However, significant synergistic effect of CoQ(10) with ET was observed only for peak SWTI suggesting that ET amplifies the already described effect of CoQ(10) on contractility of dysfunctional myocardium.

Topics: Chronic Disease; Coenzymes; Double-Blind Method; Exercise; Exercise Therapy; Female; Heart Failure; Humans; Male; Middle Aged; Ubiquinone

Although not currently indicated for chronic heart failure (CHF), statins have been associated with improved outcome in retrospective analysis. However, statin therapy reduces plasma levels of coenzyme Q(10) (ubiquinone), which may have adverse effects on heart failure states. We hypothesized that atorvastatin treatment improves endothelial function in patients with chronic heart failure independent of LDL-cholesterol alterations. Furthermore, we assessed how reductions in coenzyme Q(10) levels impact on potentially improved endothelial function. Twenty-four patients with stable, symptomatic heart failure (New York Heart Association Class II or III) and a left ventricular ejection fraction <40% were randomised to 40 mg atorvastatin or placebo for 6 weeks and crossed over to the other treatment arm for a further 6 weeks, after a 2-week wash out. Forearm resistance vessel function was assessed by venous occlusion plethysmography during infusion of acetylcholine (ACh), sodium nitroprusside (SNP), and N(G)-monomethyl-L-arginine (L-NMMA) into the brachial artery. Atorvastatin treatment lowered triglycerides, LDL-cholesterol and coenzyme Q(10) levels (all p<0.001) and improved endothelium-dependent vasodilatation during acetylcholine infusion (p=0.015). Endothelium-dependent forearm blood flow improvements correlated with reductions in coenzyme Q(10) levels (p=0.011), but not with LDL-cholesterol levels (p=0.084). Coenzyme Q(10) remained the significant variable predicting improvement in NO dependent endothelial function after adjusting for LDL-cholesterol levels (p=0.041). In conclusion, short-term atorvastatin therapy improved endothelial function in chronic heart failure patients. Further studies are required to determine whether coenzyme Q(10) reductions are limiting the maximum favourable effects of statin therapy on the microcirculation.

Topics: Atorvastatin; Chronic Disease; Coenzymes; Cross-Over Studies; Endothelium, Vascular; Heart Failure; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pyrroles; Ubiquinone; Vascular Resistance; Vasodilation

The number of patients awaiting heart transplantation is increasing in proportion to the waiting period for a donor. Studies have shown that coenzyme Q10 (CoQ10) has a beneficial effect on patients with heart failure.. The purpose of the present double-blind, placebo-controlled, randomized study was to assess the effect of CoQ10 on patients with end-stage heart failure and to determine if CoQ10 can improve the pharmacological bridge to heart transplantation.. A prospective double-blind design was used. Thirty-two patients with end-stage heart failure awaiting heart transplantation were randomly allocated to receive either 60 mg U/day of Ultrasome--CoQ10 (special preparation to increase intestinal absorption) or placebo for 3 months. All patients continued their regular medication regimen. Assessments included anamnesis with an extended questionnaire based partially on the Minnesota Living with Heart Failure Questionnaire, 6-min walk test, blood tests for atrial natriuretic factor (ANF) and tumor necrosis factor (TNF), and echocardiography.. Twenty-seven patients completed the study. The study group showed significant improvement in the 6-min walk test and a decrease in dyspnea, New York Heart Association (NYHA) classification, nocturia, and fatigue. No significant changes were noted after 3 months of treatment in echocardiography parameters (dimensions and contractility of cardiac chambers) or ANF and TNF blood levels.. The administration of CoQ10 to heart transplant candidates led to a significant improvement in functional status, clinical symptoms, and quality of life. However, there were no objective changes in echo measurements or ANF and TNF blood levels. Coenzyme Q10 may serve as an optional addition to the pharmacologic armamentarium of patients with end-stage heart failure. The apparent discrepancy between significant clinical improvement and unchanged cardiac status requires further investigation.

Topics: Adult; Aged; Atrial Natriuretic Factor; Cardiotonic Agents; Coenzymes; Double-Blind Method; Exercise Tolerance; Female; Heart Failure; Heart Transplantation; Humans; Male; Middle Aged; Prospective Studies; Quality of Life; Recovery of Function; Severity of Illness Index; Tumor Necrosis Factor-alpha; Ubiquinone; Ultrasonography; Waiting Lists

Congestive heart failure depletes the myocardium of carnitine, coenzyme Q10 (CoQ10), and taurine--substances known to influence mitochondrial function and cell calcium. We hypothesized that feeding patients a nutritional supplement that contained carnitine, CoQ10, and taurine would result in higher myocardial levels of these nutrients and improve left ventricular function.. Forty-one patients who underwent aortocoronary artery bypass with an ejection fraction < or =40% at referral were randomly assigned to a double-blind trial of supplement or placebo. Radionuclide ventriculography was performed at randomization and before surgery. Surgical myocardial biopsies, adjusted for protein content, were analyzed for carnitine, CoQ10, and taurine levels.. The groups were well matched. Minor exceptions were supplement group versus placebo group for digoxin use (7 vs 0, respectively; P =.009) and age (62 +/- 11 years vs 69 +/- 5 years, respectively; P =.04). There were significantly higher levels in the treated group compared with the placebo group for myocardial levels of CoQ10 (138.17 +/- 39.87 nmol/g wet weight and 56.67 +/- 23.08 nmol/g wet weight; P =.0006), taurine (13.12 +/- 4.00 micromol/g wet weight and 7.91 +/- 2.81 micromol/g wet weight; P =.003), and carnitine (1735.4 +/- 798.5 nmol/g wet weight and 1237.6 +/- 343.1 nmol/g wet weight; P =.06). The left ventricular end-diastolic volume fell by -7.5 +/- 21.7 mL in the supplement group and increased by 10.0 +/- 19.8 mL in the placebo group (P =.037).. Supplementation results in higher myocardial CoQ10, taurine, and carnitine levels and is associated with a reduction in left ventricular end-diastolic volume in patients with left ventricular dysfunction before revascularization. Because the risk of death for surgical revascularization is related to preoperative left ventricular end-diastolic volume, supplementation could improve outcomes.

Topics: Aged; Carnitine; Coenzymes; Dietary Supplements; Double-Blind Method; Female; Heart Failure; Humans; Male; Middle Aged; Myocardium; Radionuclide Ventriculography; Taurine; Ubiquinone; Ventricular Dysfunction, Left

Coenzyme Q10 is commonly used to treat congestive heart failure on the basis of data from several unblinded, subjective studies. Few randomized, blinded, controlled studies have evaluated objective measures of cardiac performance.. To determine the effect of coenzyme Q10 on peak oxygen consumption, exercise duration, and ejection fraction.. Randomized, double-blind, controlled trial.. University and Veterans Affairs hospitals.. 55 patients who had congestive heart failure with New York Heart Association class III and IV symptoms, ejection fraction less than 40%, and peak oxygen consumption less than 17.0 mL/kg per minute (or <50% of predicted) during standard therapy were randomly assigned. Forty-six patients completed the study.. Coenzyme Q10, 200 mg/d, or placebo.. Left ventricular ejection fraction (measured by radionuclide ventriculography) and peak oxygen consumption and exercise duration (measured by a graded exercise evaluation using the Naughton protocol) with continuous metabolic monitoring.. Although the mean (+/-SD) serum concentration of coenzyme Q10 increased from 0.95+/-0.62 microg/mL to 2.2+/-1.2 microg/mL in patients who received active treatment, ejection fraction, peak oxygen consumption, and exercise duration remained unchanged in both the coenzyme Q10 and placebo groups.. Coenzyme Q10 does not affect ejection fraction, peak oxygen consumption, or exercise duration in patients with congestive heart failure receiving standard medical therapy.

Topics: Antioxidants; Coenzymes; Double-Blind Method; Exercise Tolerance; Female; Heart Failure; Humans; Male; Middle Aged; Oxygen Consumption; Placebos; Radionuclide Ventriculography; Stroke Volume; Ubiquinone

This study evaluated the effects of oral therapy with coenzyme Q on echocardiographic and hemodynamic indexes of left ventricular function and on quality of life in patients with chronic left ventricular dysfunction.. Coenzyme Q is a coenzyme for oxidative phosphorylation and an antioxidant and free radical scavenger. It has been claimed to improve symptoms, quality of life, left ventricular ejection fraction and prognosis in patients with cardiac failure.. Thirty patients with ischemic or idiopathic dilated cardiomyopathy and chronic left ventricular dysfunction (ejection fraction 26 +/- 6%) were randomized to a double-blind crossover trial of oral coenzyme Q versus placebo, each for 3 months. Right heart pressures, cardiac output and echocardiographic left ventricular volumes were measured at baseline and after each treatment phase, and quality of life was assessed using the Minnesota "Living With Heart Failure" questionnaire. It was calculated that to demonstrate an increase in left ventricular ejection fraction from 25% to 30% with a standard deviation of 5% using 95% confidence intervals with a power of 80% we would require 17 patients.. Twenty-seven completed both treatment phases. There was no significant difference in left ventricular ejection fraction, cardiac volumes or hemodynamic and quality of life indices after treatment with coenzyme Q or placebo, although plasma coenzyme Q levels increased from 903 +/- 345 nmol/l(-1) to 2,029 +/- 856 nmol/l(-1).. In patients with left ventricular dysfunction, treatment for three months with oral coenzyme Q failed to improve resting left ventricular systolic function or quality of life despite an increase in plasma levels of coenzyme Q to more than twice basal values.

Topics: Administration, Oral; Adult; Aged; Chronic Disease; Cross-Over Studies; Double-Blind Method; Echocardiography; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Quality of Life; Stroke Volume; Treatment Failure; Ubiquinone; Ventricular Dysfunction, Left; Ventricular Function, Left

Several noninvasive studies have shown the effect on heart failure of treatment with coenzyme Q10. In order to confirm this by invasive methods we studied 22 patients with mean left ventricular (LV) ejection fraction 26%, mean LV internal diameter 71 mm and in NYHA class 2-3. The patients received coenzyme Q10 100 mg twice daily or placebo for 12 weeks in a randomized double-blinded placebo controlled investigation. Before and after the treatment period, a right heart catheterisation was done including a 3 minute exercise test. The stroke index at rest and work improved significantly, the pulmonary artery pressure at rest and work decreased (significantly at rest), and the pulmonary capillary wedge pressure at rest and work decreased (significantly at 1 min work). These results suggest improvement in LV performance. Patients with congestive heart failure may thus benefit from adjunctive treatment with coenzyme Q10.

Topics: Adult; Aged; Antioxidants; Blood Pressure; Cardiac Catheterization; Cardiac Output; Cardiomyopathy, Dilated; Coenzymes; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Ubiquinone; Ventricular Function, Left

Seventy-nine patients with stable chronic congestive heart failure were randomized into a double-blind, crossover placebo controlled study with 3-month treatment periods, where either 100 mg coenzyme Q10 (CoQ10) or placebo was added to conventional therapy. Mean patient age was 61 +/- 10 years, ejection fraction at rest was 22% +/- 10%, and maximal exercise tolerance was 91 +/- 30 W. The follow-up examinations included ejection fraction (primary objective), exercise test, and quality of life questions. Ejection fraction at rest, during a slight volume load, and during a submaximal supine exercise increased slightly compared with placebo: 24% +/- 12% versus 23% +/- 12% (NS), 25% +/- 13% versus 23% +/- 12% (P < .05), and 23% +/- 11% versus 22% +/- 11% (NS). Maximal exercise capacity increased from 94 +/- 31 W during the placebo period to 100 +/- 34 W during the CoQ10 period (P < .05). Total score for the quality of life assessment increased significantly from 107 +/- 23 during the placebo period to 113 +/- 22 during the CoQ10 period (P < .05). The results indicate that oral long-term treatment with 100 mg CoQ10 in patients with congestive heart failure only slightly improves maximal exercise capacity and the quality of life and that the clinical importance of this needs to be further evaluated.

Topics: Aged; Chronic Disease; Coenzymes; Cross-Over Studies; Double-Blind Method; Exercise Tolerance; Female; Heart Failure; Humans; Male; Middle Aged; Quality of Life; Stroke Volume; Ubiquinone

In patients with chronic heart failure (CHF), the addition of coenzyme Q10 to conventional therapy reduces the hospitalization rate for worsening of heart failure and the incidence of serious cardiovascular complications. The present study was planned to assess the hemodynamic mechanisms underlying this phenomenon. Cardiac hemodynamics was evaluated continuously using an ambulatory radionuclide detector (VEST) which allows a noninvasive monitoring of left ventricular function. Six patients wit CHF (mean ejection fraction (EF): 29%) clinically documented were studied. This study was organized as a randomized double-blind, placebo controlled, cross-over trial. The enrolled patients, after a washout period, underwent the first hemodynamic evaluation with VEST. Subsequently they were randomized to receive placebo or coenzyme Q10 for 4 weeks. At the end of this period they underwent the second VEST study. The third VEST study was performed after a further 4-week period with inverted treatment. Cardiac hemodynamics were evaluated during bicycle exercise. The EF in control conditions (CC) changed from 27 +/- 11%, at rest, to 24 +/- 8%, at peak exercise. During coenzyme Q10 treatment EF showed a significant increase both at rest (33 +/- 13%, P < 0.05 vs CC) and at peak exercise (30 +/- 12%, P < 0.05 vs CC). The same trends were recorded for the stroke volume and the cardiac output. Our results demonstrate that coenzyme Q10 improves cardiac hemodynamic response to exercise in patients with CHF and suggest that noninvasive monitoring of left ventricular function allows a more reliable assessment of therapy efficacy.

Topics: Adult; Coenzymes; Cross-Over Studies; Double-Blind Method; Exercise Test; Heart Failure; Heart Rate; Hemodynamics; Humans; Middle Aged; Monitoring, Ambulatory; Stroke Volume; Ubiquinone; Ventricular Function, Left

Digitalis, diuretics and vasodilators are considered the standard therapy for patients with congestive heart failure, for which treatment is tailored according to the severity of the syndrome and the patient profile. Apart from the clinical seriousness, heart failure is always characterized by an energy depletion status, as indicated by low intramyocardial ATP and coenzyme Q10 levels. We investigated safety and clinical efficacy of Coenzyme Q10 (CoQ10) adjunctive treatment in congestive heart failure which had been diagnosed at least 6 months previously and treated with standard therapy. A total of 2664 patients in NYHA classes II and III were enrolled in this open noncomparative 3-month postmarketing study in 173 Italian centers. The daily dosage of CoQ10 was 50-150 mg orally, with the majority of patients (78%) receiving 100 mg/day. Clinical and laboratory parameters were evaluated at the entry into the study and on day 90; the assessment of clinical signs and symptoms was made using from two-to seven-point scales. The results show a low incidence of side effects: 38 adverse effects were reported in 36 patients (1.5%) of which 22 events were considered as correlated to the test treatment. After three months of test treatment the proportions of patients with improvement in clinical signs and symptoms were as follows: cyanosis 78.1%, oedema 78.6%, pulmonary rales 77.8%, enlargement of liver area 49.3%, jugular reflux 71.81%, dyspnoea 52.7%, palpitations 75.4%, sweating 79.8%, subjective arrhytmia 63.4%, insomnia 662.8%, vertigo 73.1% and nocturia 53.6%. Moreover we observed a contemporary improvement of at least three symptoms in 54% of patients; this could be interpreted as an index of improved quality of life.

Topics: Administration, Oral; Cardiovascular Agents; Chemotherapy, Adjuvant; Coenzymes; Drug Therapy, Combination; Female; Heart Failure; Hemodynamics; Humans; Italy; Male; Quality of Life; Safety; Severity of Illness Index; Treatment Outcome; Ubiquinone

The improved cardiac function in patients with congestive heart failure treated with coenzyme Q10 supports the hypothesis that this condition is characterized by mitochondrial dysfunction and energy starvation, so that it may be ameliorated by coenzyme Q10 supplementation. However, the main clinical problems in patients with congestive heart failure are the frequent need of hospitalization and the high incidence of life-threatening arrhythmias, pulmonary edema, and other serious complications. Thus, we studied the influence of coenzyme Q10 long-term treatment on these events in patients with chronic congestive heart failure (New York Heart Association functional class III and IV) receiving conventional treatment for heart failure. They were randomly assigned to receive either placebo (n = 322, mean age 67 years, range 30-88 years) or coenzyme Q10 (n = 319, mean age 67 years, range 26-89 years) at the dosage of 2 mg/kg per day in a 1-year double-blind trial. The number of patients who required hospitalization for worsening heart failure was smaller in the coenzyme Q10 treated group (n = 73) than in the control group (n = 118, P < 0.001). Similarly, the episodes of pulmonary edema or cardiac asthma were reduced in the control group (20 versus 51 and 97 versus 198, respectively; both P < 0.001) as compared to the placebo group. Our results demonstrate that the addition of coenzyme Q10 to conventional therapy significantly reduces hospitalization for worsening of heart failure and the incidence of serious complications in patients with chronic congestive heart failure.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Coenzymes; Double-Blind Method; Female; Heart Failure; Humans; Incidence; Length of Stay; Longitudinal Studies; Male; Middle Aged; Ubiquinone

We compared the effect of oral administration of taurine (3 g/day) and coenzyme Q10 (CoQ10) (30 mg/day) in 17 patients with congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy, whose ejection fraction assessed by echocardiography was less than 50%. The changes in echocardiographic parameters produced by 6 weeks of treatment were evaluated in a double-blind fashion. In the taurine-treated group significant treatment effect was observed on systolic left ventricular function after 6 weeks. Such an effect was not observed in the CoQ10-treated group.

Topics: Administration, Oral; Cardiomyopathy, Dilated; Chronic Disease; Coenzymes; Coronary Disease; Double-Blind Method; Drug Evaluation; Echocardiography; Female; Heart Failure; Humans; Male; Stroke Volume; Taurine; Ubiquinone; Ventricular Function, Left

Coenzyme Q10 (CoQ10) is indispensable in mitochondrial bioenergetics and for human life to exist. 88/115 patients completed a trial of therapy with CoQ10 for cardiomyopathy. Patients were selected on the basis of clinical criteria, X-rays, electrocardiograms, echocardiography, and coronary angiography. Responses were monitored by ejection fractions, cardiac output, and improvements in functional classifications (NYHA). Of the 88 patients 75%-85% showed statistically significant increases in two monitored cardiac parameters. Patients with the lowest ejection fractions (approx. 10%-30%) showed the highest increases (115 delta %-210 delta %) and those with higher ejection fractions (50%-80%) showed increases of approx. 10 delta %-25 delta % on therapy. By functional classification, 17/21 in class IV, 52/62 in class III, and 4/5 in class II improved to lower classes. Clinical responses appeared over variable times, and are presumably based on mechanisms of DNA-RNA-protein synthesis of apoenzymes which restore levels of CoQ10 enzymes in a deficiency state. 10/21 (48%) of patients in class IV, 26/62 (42%) in class III, and 2/5 (40%) in class II had exceptionally low control blood levels of CoQ10. Clinical responses on therapy with CoQ10 appear maximal with blood levels of approx. 2.5 micrograms CoQ10/ml and higher during therapy.

Topics: Adult; Aged; Aged, 80 and over; Cardiac Output; Cardiomyopathies; Cardiomyopathy, Dilated; Clinical Trials as Topic; Coenzymes; Coronary Disease; Female; Heart Failure; Humans; Male; Middle Aged; Stroke Volume; Ubiquinone

Topics: Adult; Aged; Clinical Trials as Topic; Coenzymes; Female; Heart Failure; Humans; Male; Middle Aged; Ubiquinone

Expecting activation of myocardial energy liberation, coenzyme Q was applied as a treatment to 55 patients suffering from congestive heart failure. Daily doses of 50 to 100 mg of coenzyme Q7 were injected intravenously in 21 cases for 3 to 35 days. Daily doses of 60 mg of coenzyme Q7 were administered perorally in 17 cases for 14 to 196 days. Daily doses of 30 mg of coenzyme Q10 were administered perorally in 17 cases for 7 to 182 days. Clinical effects were evaluated within 4 weeks by the criteria using a scoring method of severity of congestive heart failure which was devised by the authors. In summary a certain effect was found in 20 cases and a mild effect was observed in 29 cases. No significant changes were observed in heart rate and blood pressure. Exanthema appeared in 2 patients of the group of coenzyme Q7 intravenous injection. In conclusion the therapeutic effect of coenzyme Q was thought to be mild but stable in supplement to digitalis therapy in cases of congestive heart failure.

Topics: Administration, Oral; Adolescent; Adult; Aged; Clinical Trials as Topic; Drug Evaluation; Female; Heart Failure; Heart Rate; Humans; Injections, Intravenous; Male; Middle Aged; Ubiquinone

Cardiovascular disease is associated with high morbidity and mortality. Doxorubicin (DOX) is an effective adjunct to cancer chemotherapy but leads to cardiovascular-related side effects. Because coenzyme Q10 (CoQ10) has been shown to protect against cardiac damage, this study was conducted to investigate the protective effects of CoQ10 against cardiac damage in mice.. We randomly divided six-week-old male C57BL/6 mice into four groups: control (n = 7), CoQ10 (n = 7), heart failure (HF) (n = 7), and HF+CoQ10 (n = 6) groups. HF group was induced via intraperitoneal injections with DOX (5 mg/kg) once weekly for 4 weeks. CoQ10 was solube in corn oil. The mice of CoQ10 and HF+CoQ10 group were given CoQ10 (100 mg/kg) once a day for 8 weeks. All mice were subjected to different treatment regimens for eight weeks. Metabolic characteristics, cardiac damage, oxidative stress markers (SIRT1, SIRT3, eNOS, TE, P53, SIRT5, CAT, HO-1, and SOD), energy metabolism markers (PARP-1 and PPAR-γ), myocardial fibrosis markers (Smad3 and TGF-β), and apoptosis markers (BAK, BCL-XL, and caspase-8) were analyzed at eight weeks after the different treatments.. CoQ10 reduced the levels of molecules related to cardiac damage, oxidative stress, energy metabolism, and myocardial fibrosis in mice with doxorubicin-induced HF. CoQ10 also exerted anti-apoptotic effects in HF mice.. CoQ10 may be useful for preventing cardiac damage in DOX-induced HF.

Topics: Animals; Doxorubicin; Fibrosis; Heart Failure; Male; Mice; Mice, Inbred C57BL; Oxidative Stress; Ubiquinone

Hydrogen sulfide (H2S) is a potent signalling molecule that activates diverse cardioprotective pathways by post-translational modification (persulfidation) of cysteine residues in upstream protein targets. Heart failure patients with reduced ejection fraction (HFrEF) exhibit low levels of H2S. Sulfide:quinone oxidoreductase (SQOR) catalyses the first irreversible step in the metabolism of H2S and plays a key role in regulating H2S-mediated signalling. Here, the aim of this study was to discover a first-in-class inhibitor of human SQOR and evaluate its cardioprotective effect in an animal model of HFrEF.. We identified a potent inhibitor of human SQOR (STI1, IC50 = 29 nM) by high-throughput screening of a small-molecule library, followed by focused medicinal chemistry optimization and structure-based design. STI1 is a competitive inhibitor that binds with high selectivity to the coenzyme Q-binding pocket in SQOR. STI1 exhibited very low cytotoxicity and attenuated the hypertrophic response of neonatal rat ventricular cardiomyocytes and H9c2 cells induced by neurohormonal stressors. A mouse HFrEF model was produced by transverse aortic constriction (TAC). Treatment of TAC mice with STI1 mitigated the development of cardiomegaly, pulmonary congestion, dilatation of the left ventricle, and cardiac fibrosis and decreased the pressure gradient across the aortic constriction. Moreover, STI1 dramatically improved survival, preserved cardiac function, and prevented the progression to HFrEF by impeding the transition from compensated to decompensated left ventricle hypertrophy.. We demonstrate that the coenzyme Q-binding pocket in human SQOR is a druggable target and establish proof of concept for the potential of SQOR inhibitors to provide a novel therapeutic approach for the treatment of HFrEF.

Topics: Animals; Heart Failure; Humans; Mice; Rats; Stroke Volume; Sulfides; Ubiquinone; Ventricular Remodeling

Topics: Heart Failure; Humans; Ubiquinone

Depletion of coenzyme Q (CoQ) is associated with disease, ranging from myopathy to heart failure. To induce a CoQ deficit, C2C12 myotubes were incubated with high dose simvastatin. This resulted in a concentration-dependent inhibition of cell viability. Simvastatin-induced effects were prevented by co-incubation with mevalonic acid. When myotubes were incubated with 60 μM simvastatin, mitochondrial CoQ content decreased while co-incubation with CoQ nanodisks (ND) increased mitochondrial CoQ levels and improved cell viability. Incubation of myotubes with simvastatin also led to a reduction in oxygen consumption rate (OCR). When myotubes were co-incubated with simvastatin and CoQ ND, the decline in OCR was ameliorated. The data indicate that CoQ ND represent a water soluble vehicle capable of delivering CoQ to cultured myotubes. Thus, these biocompatible nanoparticles have the potential to bypass poor CoQ oral bioavailability as a treatment option for individuals with severe CoQ deficiency syndromes and/or aging-related CoQ depletion.

Topics: Animals; Ataxia; Cell Line; Cell Survival; Heart Failure; Humans; Mice; Mitochondria; Mitochondrial Diseases; Muscle Fibers, Skeletal; Muscle Weakness; Muscular Diseases; Nanocomposites; Oxygen Consumption; Simvastatin; Ubiquinone

Evidence suggests that mitochondrial network integrity is impaired in cardiomyocytes from failing hearts. While oxidative stress has been implicated in heart failure (HF)-associated mitochondrial remodeling, the effect of mitochondrial-targeted antioxidants, such as mitoquinone (MitoQ), on the mitochondrial network in a model of HF (e.g., pressure overload) has not been demonstrated. Furthermore, the mechanism of this regulation is not completely understood with an emerging role for posttranscriptional regulation via long noncoding RNAs (lncRNAs). We hypothesized that MitoQ preserves mitochondrial fusion proteins (i.e., mitofusin), likely through redox-sensitive lncRNAs, leading to improved mitochondrial network integrity in failing hearts. To test this hypothesis, 8-wk-old C57BL/6J mice were subjected to ascending aortic constriction (AAC), which caused substantial left ventricular (LV) chamber remodeling and remarkable contractile dysfunction in 1 wk. Transmission electron microscopy and immunostaining revealed defective intermitochondrial and mitochondrial-sarcoplasmic reticulum ultrastructure in AAC mice compared with sham-operated animals, which was accompanied by elevated oxidative stress and suppressed mitofusin (i.e., Mfn1 and Mfn2) expression. MitoQ (1.36 mg·day

Topics: Animals; Antioxidants; Disease Models, Animal; Heart Failure; Mice; Mitochondria; Mitochondrial Dynamics; Myocardium; Myocytes, Cardiac; Organophosphorus Compounds; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species; RNA, Untranslated; Ubiquinone

Heart failure (HF) is rapidly increasing in incidence and is often present in patients receiving long-term statin therapy.. To test whether or not patients with HF on long-term statin therapy respond to discontinuation of statin therapy and initiation of coenzyme Q. Baseline and follow-up physical examination findings, symptom scores, echocardiograms, and plasma CoQ. Of 142 identified patients with HF, 94% presented with preserved ejection fraction (EF) and 6% presented with reduced EF (< 50%). After a mean follow-up of 2.8 years, New York Heart Association class 1 increased from 8% to 79% (p < 0.0001). In patients with preserved EF, 34% had normalization of diastolic function and 25% showed improvement (p < 0.0001). In patients with reduced EF at baseline, the EF improved from a mean of 35% to 47% (p = 0.02). Statin-attributable symptoms including fatigue, muscle weakness, myalgias, memory loss, and peripheral neuropathy improved (p < 0.01). The 1-year mortality was 0%, and the 3-year mortality was 3%.. In patients receiving long-term statin therapy, statin-associated cardiomyopathy may develop that responds safely to statin treatment discontinuation and CoQ

Topics: Aged; Cardiomyopathies; Cholesterol; Female; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Stroke Volume; Ubiquinone; Vitamin E

Increasing evidence indicates that mitochondrial-associated redox signaling contributes to the pathophysiology of heart failure (HF). The mitochondrial-targeted antioxidant, mitoquinone (MitoQ), is capable of modifying mitochondrial signaling and has shown beneficial effects on HF-dependent mitochondrial dysfunction. However, the potential therapeutic impact of MitoQ-based mitochondrial therapies for HF in response to pressure overload is reliant upon demonstration of improved cardiac contractile function and suppression of deleterious cardiac remodeling. Using a new (patho)physiologically relevant model of pressure overload-induced HF we tested the hypothesis that MitoQ is capable of ameliorating cardiac contractile dysfunction and suppressing fibrosis. To test this C57BL/6J mice were subjected to left ventricular (LV) pressure overload by ascending aortic constriction (AAC) followed by MitoQ treatment (2 µmol) for 7 consecutive days. Doppler echocardiography showed that AAC caused severe LV dysfunction and hypertrophic remodeling. MitoQ attenuated pressure overload-induced apoptosis, hypertrophic remodeling, fibrosis and LV dysfunction. Profibrogenic transforming growth factor-β1 (TGF-β1) and NADPH oxidase 4 (NOX4, a major modulator of fibrosis related redox signaling) expression increased markedly after AAC. MitoQ blunted TGF-β1 and NOX4 upregulation and the downstream ACC-dependent fibrotic gene expressions. In addition, MitoQ prevented Nrf2 downregulation and activation of TGF-β1-mediated profibrogenic signaling in cardiac fibroblasts (CF). Finally, MitoQ ameliorated the dysregulation of cardiac remodeling-associated long noncoding RNAs (lncRNAs) in AAC myocardium, phenylephrine-treated cardiomyocytes, and TGF-β1-treated CF. The present study demonstrates for the first time that MitoQ improves cardiac hypertrophic remodeling, fibrosis, LV dysfunction and dysregulation of lncRNAs in pressure overload hearts, by inhibiting the interplay between TGF-β1 and mitochondrial associated redox signaling.

Topics: Animals; Apoptosis; Biomarkers; Cardiomegaly; Disease Models, Animal; Echocardiography; Fibroblasts; Fibrosis; Heart Failure; Immunohistochemistry; Male; Mice; Models, Biological; Myocardium; Organophosphorus Compounds; Signal Transduction; Stress, Mechanical; Transforming Growth Factor beta; Ubiquinone; Ventricular Dysfunction, Left; Ventricular Remodeling

Heart failure remains a major public-health problem with an increase in the number of patients worsening from this disease. Despite current medical therapy, the condition still has a poor prognosis. Heart failure is complex but mitochondrial dysfunction seems to be an important target to improve cardiac function directly. Our goal was to analyze the effects of MitoQ (100 µM in drinking water) on the development and progression of heart failure induced by pressure overload after 14 weeks. The main findings are that pressure overload-induced heart failure in rats decreased cardiac function in vivo that was not altered by MitoQ. However, we observed a reduction in right ventricular hypertrophy and lung congestion in heart failure animals treated with MitoQ. Heart failure also decreased total mitochondrial protein content, mitochondrial membrane potential in the intermyofibrillar mitochondria. MitoQ restored membrane potential in IFM but did not restore mitochondrial protein content. These alterations are associated with the impairment of basal and stimulated mitochondrial respiration in IFM and SSM induced by heart failure. Moreover, MitoQ restored mitochondrial respiration in heart failure induced by pressure overload. We also detected higher levels of hydrogen peroxide production in heart failure and MitoQ restored the increase in ROS production. MitoQ was also able to improve mitochondrial calcium retention capacity, mainly in the SSM whereas in the IFM we observed a small alteration. In summary, MitoQ improves mitochondrial dysfunction in heart failure induced by pressure overload, by decreasing hydrogen peroxide formation, improving mitochondrial respiration and improving mPTP opening.

Topics: Animals; Antioxidants; Disease Models, Animal; Heart Failure; Mitochondria; Mitochondria, Heart; Organophosphorus Compounds; Rats; Ubiquinone

OBJECTIVE To determine the plasma total antioxidant capacity, erythrocyte superoxide dismutase activity, whole blood glutathione peroxidase activity, and plasma coenzyme Q

Topics: Animals; Antioxidants; Cardiovascular Diseases; Dog Diseases; Dogs; Enzyme-Linked Immunosorbent Assay; Female; Heart Failure; Male; Natriuretic Peptide, Brain; Ubiquinone

The mechanisms for cognitive impairment in heart failure (HF) are unclear. We investigated the relative contributions of cerebral blood flow velocity (BFV), oxidative stress, and inflammation to HF-associated cognitive impairment.. Thirty-six HF patients (≥60 years) and 40 healthy controls (68 ± 7 vs 67 ± 5 years, P > .05; 69% vs 50% male, P > .05) completed the Cognitive Drug Research computerized assessment battery and Stroop tasks. Common carotid (CCA) and middle cerebral arterial BFV were obtained by transcranial Doppler. Blood samples were collected for oxidant (diacron-reactive oxygen metabolites; F2-isoprostanes), antioxidant (coenzyme Q10; CoQ10), and inflammatory markers (high-sensitivity C-reactive protein). Compared with controls, patients exhibited impaired attention (Cognitive Drug Research's Power of Attention domain, congruent Stroop) and executive function (incongruent Stroop). Multiple regression modeling showed that CCA-BFV and CoQ10 but not group predicted performance on attention and executive function. Additionally, in HF patients, CCA-BFV and CoQ10 (β = -0.34 vs β = -0.35) were significant predictors of attention, and CCA-BFV (β = -0.34) was a predictor of executive function.. Power of Attention and executive function is impaired in older HF patients, and reduced CCA-BFV and CoQ10 are associated with worse cognition. Interventions addressing these mechanisms may improve cognition in older HF patients.

Topics: Aged; Blood Flow Velocity; C-Reactive Protein; Cerebrovascular Circulation; Cognition; Cognition Disorders; Female; Heart Failure; Humans; Inflammation; Male; Middle Aged; Neuropsychological Tests; Oxidative Stress; Ubiquinone

Deficiency of energy supply is a major complication contributing to the syndrome of heart failure (HF). Because the concurrent activity profile of mitochondrial bioenergetic enzymes has not been studied collectively in human HF, our aim was to examine the mitochondrial enzyme defects in left ventricular myocardium obtained from explanted end-stage failing hearts. Compared with nonfailing donor hearts, activity rates of complexes I and IV and the Krebs cycle enzymes isocitrate dehydrogenase, malate dehydrogenase, and aconitase were lower in HF, as determined spectrophotometrically. However, activity rates of complexes II and III and citrate synthase did not differ significantly between the two groups. Protein expression, determined by Western blotting, did not differ between the groups, implying posttranslational perturbation. In the face of diminished total glutathione and coenzyme Q10 levels, oxidative modification was explored as an underlying cause of enzyme dysfunction. Of the three oxidative modifications measured, protein carbonylation was increased significantly by 31% in HF (P < 0.01; n = 18), whereas levels of 4-hydroxynonenal and protein nitration, although elevated, did not differ. Isolation of complexes I and IV and F1FoATP synthase by immunocapture revealed that proteins containing iron-sulphur or heme redox centers were targets of oxidative modification. Energy deficiency in end-stage failing human left ventricle involves impaired activity of key electron transport chain and Krebs cycle enzymes without altered expression of protein levels. Augmented oxidative modification of crucial enzyme subunit structures implicates dysfunction due to diminished capacity for management of mitochondrial reactive oxygen species, thus contributing further to reduced bioenergetics in human HF.

Topics: Aconitate Hydratase; Aldehydes; Blotting, Western; Citrate (si)-Synthase; Citric Acid Cycle; Electron Transport Chain Complex Proteins; Electron Transport Complex I; Electron Transport Complex IV; Female; Glutathione; Heart Failure; Heart Ventricles; Humans; Isocitrate Dehydrogenase; Ketoglutarate Dehydrogenase Complex; Malate Dehydrogenase; Male; Middle Aged; Mitochondria, Heart; Mitochondrial Proton-Translocating ATPases; Myocardium; Oxidative Phosphorylation; Protein Carbonylation; Protein Processing, Post-Translational; Reactive Oxygen Species; Ubiquinone

Topics: Chronic Disease; Heart Failure; Humans; Mitochondria, Heart; Oxidative Stress; Randomized Controlled Trials as Topic; Reactive Oxygen Species; Treatment Outcome; Ubiquinone

Left ventricular (LV) volume overload (VO) results in cardiomyocyte oxidative stress and mitochondrial dysfunction. Because mitochondria are both a source and target of ROS, we hypothesized that the mitochondrially targeted antioxidant mitoubiquinone (MitoQ) will improve cardiomyocyte damage and LV dysfunction in VO. Isolated cardiomyocytes from Sprague-Dawley rats were exposed to stretch in vitro and VO of aortocaval fistula (ACF) in vivo. ACF rats were treated with and without MitoQ. Isolated cardiomyocytes were analyzed after 3 h of cyclical stretch or 8 wk of ACF with MitoSox red or 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate to measure ROS and with tetramethylrhodamine to measure mitochondrial membrane potential. Transmission electron microscopy and immunohistochemistry were used for cardiomyocyte structural assessment. In vitro cyclical stretch and 8-wk ACF resulted in increased cardiomyocyte mitochondrial ROS production and decreased mitochondrial membrane potential, which were significantly improved by MitoQ. ACF had extensive loss of desmin and β₂-tubulin that was paralleled by mitochondrial disorganization, loss of cristae, swelling, and clustering identified by mitochondria complex IV staining and transmission electron microscopy. MitoQ improved mitochondrial structural damage and attenuated desmin loss/degradation evidenced by immunohistochemistry and protein expression. However, LV dilatation and fractional shortening were unaffected by MitoQ treatment in 8-wk ACF. In conclusion, although MitoQ did not affect LV dilatation or function in ACF, these experiments suggest a connection of cardiomyocyte mitochondria-derived ROS production with cytoskeletal disruption and mitochondrial damage in the VO of ACF.

Topics: Animals; Antioxidants; Cytoskeleton; Desmin; Disease Models, Animal; Heart Failure; Male; Membrane Potential, Mitochondrial; Mitochondria, Heart; Myocardial Contraction; Myocytes, Cardiac; Oxidative Stress; Rats, Sprague-Dawley; Reactive Oxygen Species; Time Factors; Tubulin; Ubiquinone; Ventricular Dysfunction, Left; Ventricular Function, Left

Topics: Female; Heart Failure; Humans; Male; Ubiquinone; Vitamins

Topics: Female; Heart Failure; Humans; Male; Ubiquinone; Vitamins

Myocardial infarction (MI) was induced by subcutaneous injection of isoproterenol (ISO) to investigate the effect of ISO on Coenzyme Q10 (CoQ10) content of myocardium and subsequent effects on lipid peroxidation, electrocardiogram pattern and hemodynamic parameters of the rat's heart.36 male Wistar rats were divided randomly into 6 groups. To induce heart failure (HF) and MI, 10 and 100 mg/kg of ISO was administered subcutaneously for 10 and 2 consecutive days, respectively. The effects of ISO on myocardium CoQ10 content, concentration of malondialdehyde, ECG pattern and hemodynamic parameters of heart were analyzed.ISO-treated rats showed significant alteration in heart hemodynamic parameters such as reduction of left-ventricular systolic pressure, maximum and minimum rate of developed left ventricular pressure, besides increase of left ventricular end-diastolic pressure. Significant depletion of heart CoQ10 content (from 4.57 and 4.55 µg/100 mg tissue in control groups to 2.85 and 2.89 µg/100 mg tissue in ISO-induced HF and MI groups respectively) and increase in tissue levels of malondialdehyde (47.1 and 53.8 nmol/100 mg tissue in ISO-induced HF and MI groups, respectively) were also observed in ISO-treated animals compared with the normal animals (17.4 and 18.8 nmol/100 mg tissue in control groups, respectively). Additionally CoQ10 improved ISO effects on hemodynamic parameters and ECG pattern in ISO-induced HF and myocardial injury.The present findings have demonstrated that the cardiotoxic effects of ISO such as oxidative damage and hemodynamic declination might be related to depletion of CoQ10 concentration.

Topics: Animals; Heart Failure; Hemodynamics; Isoproterenol; Lipid Peroxidation; Male; Myocardial Infarction; Myocardium; Rats; Rats, Wistar; Ubiquinone

The present study was aimed to study the effects of different doses of atorvastatin on Co Q10 content in the myocardium tissue in rats. A subcutaneous injection of isoproterenol (5 mg/kg/day) for 10 days was used for the induction of heart failure. Rats were randomly assigned to control, treatment with atorvastatin (5, 10, 20 mg/kg/day) and treatment with atorvastatin plus coenzyme Q10 (10 mg/kg/day). Coenzyme Q10 content of myocardium was measured using HPLC method with UV detector after hemodynamic parameters measurements. The malondialdehyde (MDA) content of the myocardium was evaluated in order to determine coenzyme Q10 antioxidative effect. A high dose of atorvastatin (20 mg/kg/day) was significantly reduced the myocardium content of coenzyme Q10 as compared with isoproterenol treated group (p<0.001). Compared with atorvastatin alone treated animals, co-administration of coenzyme Q10 with atorvastatin was improved the level of coenzyme Q10 in the myocardium (p<0.05, p<0.001). Increasing the dose of atorvastatin also led to increase in MDA content of the myocardium (p<0.01). Serum lipid profile showed no changes in atorvastatin treated groups. The results of this study demonstrate that high doses of atorvastatin reduce coenzyme Q10 content of the myocardium and increase lipid peroxidation in myocardium which is reversed by coenzyme Q10 co-administration.

Topics: Animals; Antioxidants; Atorvastatin; Heart Failure; Heptanoic Acids; Isoproterenol; Lipid Peroxidation; Lipids; Male; Malondialdehyde; Myocardium; Pyrroles; Rats; Rats, Wistar; Ubiquinone

Topics: Female; Heart Failure; Humans; Male; Ubiquinone; Vitamins

Topics: Dietary Supplements; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Mitochondria, Heart; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Ubiquinone

Topics: Dietary Supplements; Drug Costs; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Ubiquinone

Topics: Cardiotonic Agents; Double-Blind Method; Heart Failure; Humans; Randomized Controlled Trials as Topic; Treatment Outcome; Ubiquinone

Topics: Dietary Supplements; Heart Failure; Humans; Ubiquinone; Ventricular Dysfunction, Left

Topics: Angiotensin-Converting Enzyme Inhibitors; Bundle-Branch Block; Cardiac Resynchronization Therapy; Cardiomyopathy, Dilated; Defibrillators, Implantable; Echocardiography; Echocardiography, Doppler; Echocardiography, Three-Dimensional; Electrocardiography; Heart Failure; Humans; Male; Myotonic Dystrophy; Stroke Volume; Tachycardia, Ventricular; Ubiquinone; Vitamins; Young Adult

The role of a secondary respiratory chain deficiency as an additional mechanism to intoxication, leading to development of long-term energy-dependent complications, has been recently suggested in patients with propionic acidemia (PA). We show for the first time a coenzyme Q(10) (CoQ(10)) functional defect accompanied by a multiple organ oxidative phosphorylation (OXPHOS) deficiency in a child who succumbed to acute heart failure in the absence of metabolic stress. Quinone-dependent activities in the liver (complex I+III, complex II+III) were reduced, suggesting a decrease in electron transfer related to the quinone pool. The restoration of complex II+III activity after addition of exogenous ubiquinone to the assay system suggests CoQ(10) deficiency. Nevertheless, we disposed of insufficient material to perform direct measurement of CoQ(10) content in the patient's liver. Death occurred before biochemical diagnosis of OXPHOS deficiency could be made. However, this case highlights the usefulness of rapidly identifying CoQ(10) defects secondary to PA since this OXPHOS disorder has a good treatment response which could improve heart complications or prevent their appearance. Nevertheless, further studies will be necessary to determine whether CoQ(10) treatment can be useful in PA complications linked to CoQ(10) deficiency.

Topics: Child; Electron Transport Complex I; Electron Transport Complex II; Electron Transport Complex III; Heart Failure; Humans; Liver; Male; Mitochondrial Diseases; Propionic Acidemia; Ubiquinone

Topics: Fluorobenzenes; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pyrimidines; Rosuvastatin Calcium; Sulfonamides; Treatment Outcome; Ubiquinone

Topics: Administration, Oral; Chronic Disease; Creatine; Deficiency Diseases; Dietary Supplements; Drug Combinations; Exercise Tolerance; Heart Failure; Humans; Oxygen Consumption; Quality of Life; Stroke Volume; Treatment Outcome; Ubiquinone; Ventricular Function, Left

The effect of atorvastatin on cardiac remodeling, function, and homodynamic parameters in isoproterenol-induced heart failure was evaluated in the present study. A subcutaneous injection of isoproterenol (5mg/kg/day) for 10 days was used for the induction of heart failure. Isoproterenol administration produced intensive myocardial necrosis and fibrosis with a significant decrease in the arterial pressure indices, heart rate, contractility (LVdP/dt(max)) and relaxation (LVdP/dt(min)), but an increase in the left ventricular end-diastolic pressure. Rats were randomly assigned to control, treatment with only atorvastatin, and treatment with atorvastatin plus coenzyme Q10. Histopathological analysis showed a marked attenuation of myocyte necrosis and interstitial fibrosis in all atorvastatin treated groups (P<0.001). A low dose of atorvastatin (5mg/kg/day) significantly improved the left ventricular systolic pressure, contractility and relaxation (P<0.01). On the contrary, a high dose of atorvastatin (20mg/kg/day) worsened the isoproterenol-induced left ventricular dysfunction by a further reduction of LVdP/dt(max) from +2780 ± 94 to +1588 ± 248 (mmHg/s; P<0.01) and LVdP/dt(min) from -2007 ± 190 to -2939 ± 291 (mmHg/s; P<0.05). Co-administration of coenzyme Q10 with atorvastatin reversed the hemodynamic depression and the left ventricular dysfunction to a high level (P<0.001). There was a lower level of LVEDPs in the atorvastatin+coenzyme Q10 treated groups (3 ± 1 and 4 ± 1.4 versus 8 ± 3.5 and 14 ± 3.6 mmHg, respectively), thereby suggesting improvement in the myocardial stiffness by the combined coenzyme Q10 and atorvastatin treatment. The atorvastatin therapy attenuated myocardial necrosis and fibrosis in isoproterenol-induced heart failure. However, a high dose of the drug considerably worsened the left ventricular dysfunction and hemodynamic depression, which was reversed by coenzyme Q10 co-administration.

Topics: Animals; Atorvastatin; Body Weight; Drug Interactions; Heart Failure; Hemodynamics; Heptanoic Acids; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Isoproterenol; Male; Myocardium; Organ Size; Pyrroles; Rats; Rats, Wistar; Ubiquinone; Ventricular Dysfunction, Left

Cardiomyopathy is reflected in a deterioration of heart function, increased risk of developing arrhythmias, and the potential for sudden cardiac death. The use of enhanced external counterpulsation has been recommended for treating chronic stable angina in high-risk surgical patients. Furthermore, cells require adequate levels of adenosine triphosphate for the maintenance of integrity and function. Lower myocardial levels of adenosine triphosphate are commonly found with ischemia and heart failure. d-Ribose, a natural occurring carbohydrate, enhances the regeneration of adenosine triphosphate levels and improves diastolic function following ischemia.. We present a patient with cardiomyopathy and marked reduced cardiac function.. This patient underwent enhanced external counterpulsation and metabolic supplementation, including d-ribose, and achieved a significant functional improvement.

Topics: Aged; Cardiomyopathies; Combined Modality Therapy; Counterpulsation; Dietary Supplements; Echocardiography; Heart Failure; Humans; Male; Myocardial Contraction; Quality of Life; Ribose; Treatment Outcome; Ubiquinone; Vitamins

Topics: Animals; Biomarkers; Disease Models, Animal; Dogs; Fluorobenzenes; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pyrimidines; Rosuvastatin Calcium; Sulfonamides; Ubiquinone

Topics: Administration, Oral; Adult; Aged; Blood Pressure; Dose-Response Relationship, Drug; Dyslipidemias; Female; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Middle Aged; Obesity; Quality of Life; Retrospective Studies; Surveys and Questionnaires; Treatment Outcome; Ubiquinone; Vitamins

Topics: Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Predictive Value of Tests; Ubiquinone

Statins and coenzyme Q10 are both used as adjuncts in the treatment of chronic heart failure (CHF) due to their anti-inflammatory and antioxidant effects, respectively. And both have been variously shown to improve cardiac function in patients with CHF. The two agents interact in two ways; statins inhibit coenzyme Q10 synthesis through inhibition of HMG-CoA reductase, the rate limiting step in cholesterol synthesis, also shared by coenzyme Q10. Secondly, they both exhibit their antioxidant effects through activation of the enzyme superoxide dismutase, the rate limiting step in nitric oxide metabolism and main antioxidant mechanism of coenzyme Q10. We hypothesize that the interaction between statins and coenzyme Q10 is more than just a replacement, but a synergistic interaction on superoxide dismutase that could result in better cardiac function, improvement in patient symptoms, shortening of duration of hospital stay and improvement in patient quality of life.

Topics: Chemotherapy, Adjuvant; Chronic Disease; Drug Therapy, Combination; Heart Failure; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Models, Cardiovascular; Ubiquinone

Coenzyme Q10 (CoQ10) is essential for electron transport within the mitochondria and hence for ATP generation and cellular energy production. We recently demonstrated that plasma levels of CoQ10 are an independent predictor of survival in a cohort of 236 patients with chronic heart failure (CHF) followed for a median of 2.69 years. This is consistent with previous studies which have shown myocardial CoQ10 depletion in CHF, and correlated with the severity of the underlying disorder. Several intervention studies have been undertaken with CoQ10 in CHF, including randomized controlled trials with mostly positive outcomes in relation to improvement in plasma levels of CoQ10. A meta-analysis showed that CoQ10 resulted in an improvement in ejection fraction of 3.7% (95%CI 1.59-5.77) and the mean increase in cardiac output was 0.28 L/minute (95%CI 0.03-0.53). In a subgroup analysis, studies with patients not taking ACE inhibitors found a 6.7% increase in ejection fraction. The ongoing Q-SYMBIO trial will address whether CoQ10 supplementation improves survival in CHF patients. CoQ10 depletion may also be a contributory factor for why statin intervention has not improved outcomes in CHF. There is an emerging evidence base in support of CoQ10 as an adjunctive therapy in CHF.

Topics: Cardiac Output; Dietary Supplements; Heart Failure; Humans; Micronutrients; Stroke Volume; Ubiquinone

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a medical illness characterized by disorders in inflammatory and oxidative and nitrosative (IO&NS) pathways.. This paper examines the role of Coenzyme Q10 (CoQ10), a mitochondrial nutrient which acts as an essential cofactor for the production of ATP in mitochondria and which displays significant antioxidant activities. Plasma CoQ10 has been assayed in 58 patients with ME/CFS and in 22 normal controls; the relationships between CoQ10 and the severity of ME/CFS as measured by means of the FibroFatigue (FF) scale were measured.. Plasma CoQ10 was significantly (p=0.00001) lower in ME/CFS patients than in normal controls. Up to 44.8% of patients with ME/CFS had values beneath the lowest plasma CoQ10 value detected in the normal controls, i.e. 490 microg/L. In ME/CFS, there were significant and inverse relationships between CoQ10 and the total score on the FF scale, fatigue and autonomic symptoms. Patients with very low CoQ10 (<390 microg/L) suffered significantly more from concentration and memory disturbances.. The results show that lowered levels of CoQ10 play a role in the pathophysiology of ME/CFS and that symptoms, such as fatigue, and autonomic and neurocognitive symptoms may be caused by CoQ10 depletion. Our results suggest that patients with ME/CFS would benefit from CoQ10 supplementation in order to normalize the low CoQ10 syndrome and the IO&NS disorders. The findings that lower CoQ10 is an independent predictor of chronic heart failure (CHF) and mortality due to CHF may explain previous reports that the mean age of ME/CFS patients dying from CHF is 25 years younger than the age of those dying from CHF in the general population. Since statins significantly decrease plasma CoQ10, ME/CFS should be regarded as a relative contraindication for treatment with statins without CoQ10 supplementation.

Topics: Adult; Autonomic Nervous System; Cognition Disorders; Coronary Artery Disease; Fatigue Syndrome, Chronic; Female; Heart Failure; Humans; Male; Middle Aged; Oxidative Stress; Risk Factors; Ubiquinone; Vasculitis

The aim of this study was to investigate the relationship between plasma coenzyme Q(10) (CoQ(10)) and survival in patients with chronic heart failure (CHF).. Patients with CHF have low plasma concentrations of CoQ(10), an essential cofactor for mitochondrial electron transport and myocardial energy supply. Additionally, low plasma total cholesterol (TC) concentrations have been associated with higher mortality in heart failure. Plasma CoQ(10) is closely associated with low-density lipoprotein cholesterol (LDL-C), which might contribute to this association. Therefore we tested the hypothesis that plasma CoQ(10) is a predictor of total mortality in CHF and could explain this association.. Plasma samples from 236 patients admitted to the hospital with CHF, with a median (range) duration of follow-up of 2.69 (0.12 to 5.75) years, were assayed for LDL-C, TC, and total CoQ(10).. Median age at admission was 77 years. Median (range) CoQ(10) concentration was 0.68 (0.18 to 1.75) micromol/l. The optimal CoQ(10) concentration for prediction of mortality (established with receiver-operator characteristic [ROC] curves) was 0.73 micromol/l. Multivariable analysis allowing for effects of standard predictors of survival--including age at admission, gender, previous myocardial infarction, N-terminal peptide of B-type natriuretic peptide, and estimated glomerular filtration rate (modification of diet in renal disease)--indicated CoQ(10) was an independent predictor of survival, whether dichotomized at the ROC curve cut-point (hazard ratio [HR]: 2.0; 95% confidence interval [CI]: 1.2 to 3.3) or the median (HR: 1.6; 95% CI: 1.0 to 2.6).. Plasma CoQ(10) concentration was an independent predictor of mortality in this cohort. The CoQ(10) deficiency might be detrimental to the long-term prognosis of CHF, and there is a rationale for controlled intervention studies with CoQ(10).

Topics: Aged; Biomarkers; Cholesterol; Cholesterol, LDL; Chronic Disease; Female; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Multivariate Analysis; Predictive Value of Tests; Prognosis; Retrospective Studies; Risk Factors; ROC Curve; Ubiquinone

Topics: Coenzymes; Fluorobenzenes; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pyrimidines; Rosuvastatin Calcium; Sulfonamides; Treatment Failure; Ubiquinone; Vascular Diseases

We present a case of a patient with longstanding transfusion-dependent congenital dyserythropoietic anaemia (CDA) who developed cardiomyopathy despite iron chelation therapy. She presented with severe heart failure that responded poorly to conventional therapy, recovering only when therapy was augmented with metabolic agents including antioxidants and with increased iron chelation. The present case gives support to the concept of treating oxidatively induced heart failure with metabolic and antioxidant therapy. This therapy may have wider application in refractory heart failure and in the prevention of cardiomyopathy in patients receiving regular red cell transfusions who are at risk of transfusional haemosiderosis.

Topics: Anemia, Dyserythropoietic, Congenital; Antioxidants; Child; Coenzymes; Drug Therapy, Combination; Female; Ferritins; Heart Failure; Humans; Iron Chelating Agents; Lipid Peroxidation; Severity of Illness Index; Ubiquinone

Topics: Aged; Biopsy; Carbazoles; Cardiomyopathies; Carvedilol; Coenzymes; Coronary Angiography; Enalapril; Female; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Magnetic Resonance Imaging; Mitochondria, Heart; Mitochondrial Diseases; Propanolamines; Ubiquinone

Topics: Atrial Natriuretic Factor; Cardiotonic Agents; Coenzymes; Heart Failure; Heart Transplantation; Humans; Randomized Controlled Trials as Topic; Tumor Necrosis Factor-alpha; Ubiquinone; Waiting Lists

Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) are of proven clinical benefit in coronary heart disease, at least in those patients who do not have overt chronic heart failure (CHF). However, as there have been no prospective clinical trials of statins in CHF patients, the question arises as to whether the benefits observed in the absence of CHF can be necessarily inferred in those patients in whom CHF is established. In this review, the evidence base stating support of the use of statins in CHF is presented, as well as theoretical considerations as to why these agents may not necessarily be of benefit in this setting. The beneficial potential of statins clearly relates to their plaque stabilization properties and associated improvements in endothelial function, which together should reduce the risk of further infarction and, perhaps, the ischemic burden on the failing ventricle. Furthermore, these agents may have beneficial effects independent of lipid lowering. These include actions on neoangiogenesis, downregulation of AT(1) receptors, inhibition of proinflammatory cytokine activity and favorable modulation of the autonomic nervous system. The potential adverse effects of statins in CHF include reduction in levels of coenzyme Q10 (which may further exacerbate oxidative stress in CHF) and loss of the protection that lipoproteins may provide through binding and detoxifying endotoxins entering the circulation via the gut. In support of these possibilities are epidemiologic data linking a lower serum cholesterol with a poorer prognosis in CHF. These uncertainties indicate the need for a definitive outcome trial to assess the efficacy and safety of statins in CHF, despite their current widespread, non-evidence based use in this population.

Topics: Anticholesteremic Agents; Cholesterol; Chronic Disease; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Outcome Assessment, Health Care; Prospective Studies; Survival Rate; Ubiquinone

Topics: Administration, Oral; Heart Failure; Humans; Stroke Volume; Treatment Outcome; Ubiquinone; Ventricular Function, Left

Topics: Antioxidants; Aortic Valve; Coenzymes; Heart Failure; Heart Valve Diseases; Humans; Ubiquinone

Topics: Antioxidants; Chemotherapy, Adjuvant; Coenzymes; Cytoprotection; Heart Failure; Humans; Middle Aged; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Stroke Volume; Treatment Outcome; Ubiquinone

Coenzyme Q10 (CoQ10) is essential for ATP generation and has antioxidant properties. Decreased CoQ10 levels have been reported in human heart failure (CHF), but it remains unclear if this is a conserved feature of CHF. The objective of the study was to determine if tachycardia-induced CHF in the dog is associated with reduced CoQ10 levels. Furthermore, it was hypothesized that CoQ10 supplementation may improve CHF severity by preventing CoQ10 deficiency (if present) or via antioxidant effects.. Serum and myocardial levels of CoQ10 were examined in normal dogs (n = 6), dogs with CHF (control, n = 5), and dogs with CHF treated with CoQ10 (CoQ10; 10 mg/kg/day, n = 5). Serum CoQ10 levels did not change with CHF in control dogs, and myocardial levels were similar to those of normal dogs. CoQ10 therapy increased serum but not myocardial levels of CoQ10. In early CHF, CoQ10-treated dogs had lower filling pressures, and, in severe CHF, CoQ10-treated dogs had less hypertrophy as compared with untreated dogs. Other indices of CHF severity were similar in control and CoQ10-treated dogs.. These data indicate that CoQ10 deficiency is not present in this model of CHF. Although dramatic effects on hemodynamics were not observed, CoQ10 supplementation did appear to attenuate the hypertrophic response associated with CHF. Key words: enzymes, cardiomyopathy, hormones, antioxidant.

Topics: Animals; Antioxidants; Coenzymes; Disease Models, Animal; Dogs; Heart Failure; Hypertrophy; Male; Myocardium; Tachycardia; Ubiquinone

Topics: Coenzymes; Heart Failure; Humans; Research Design; Ubiquinone

Topics: Heart Failure; Humans; Ubiquinone

Topics: Antioxidants; Coenzymes; Heart Failure; Humans; Ubiquinone

Coenzyme Q10 (CoQ10) is a critical adjuvant therapy for patients with congestive heart failure (CHF), even when traditional medical therapy is successful. Adjunctive therapy with Q10 may allow for a reduction of other pharmacological therapies, improvement in quality of life, and a decrease in the incidence of cardiac complications in congestive heart failure. However, dosing, clinical application, bioavailability and dissolution of CoQ10 deserve careful scrutiny whenever employing the nutrient. The assessment of blood levels in 'therapeutic failures' appears warranted.

Topics: Aged; Biological Availability; Coenzymes; Drug Therapy, Combination; Echocardiography; Female; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Pulmonary Edema; Ubiquinone; Ventricular Function, Left

Vitamin coenzyme Q10 is a critical adjuvant complementary therapy for patients with congestive heart failure, especially when traditional medical therapy is unsuccessful. The following case studies, with systolic and/or diastolic dysfunction, demonstrate the effectiveness of coenzyme Q10 in improving quality of life, as well as survival.

Topics: Aged; Coenzymes; Female; Heart Failure; Humans; Male; Myocardium; Quality of Life; Survival Rate; Ubiquinone

Published clinical research, as well as various theoretical considerations, suggest that supplemental intakes of the 'metavitamins' taurine, coenzyme Q10, and L-carnitine, as well as of the minerals magnesium, potassium, and chromium, may be of therapeutic benefit in congestive heart failure. High intakes of fish oil may likewise be beneficial in this syndrome. Fish oil may decrease cardiac afterload by an antivasopressor action and by reducing blood viscosity, may reduce arrhythmic risk despite supporting the heart's beta-adrenergic responsiveness, may decrease fibrotic cardiac remodeling by impeding the action of angiotensin II and, in patients with coronary disease, may reduce the risk of atherothrombotic ischemic complications. Since the measures recommended here are nutritional and carry little if any toxic risk, there is no reason why their joint application should not be studied as a comprehensive nutritional therapy for congestive heart failure.

Topics: Carnitine; Chromium; Coenzymes; Dietary Fats; Fish Oils; Heart Failure; Humans; Magnesium; Minerals; Models, Biological; Potassium; Taurine; Ubiquinone; Vitamins

Topics: Coenzymes; Heart Failure; Humans; Ubiquinone

Topics: Coenzymes; Heart Failure; Humans; Lovastatin; Simvastatin; Ubiquinone

Topics: Anticholesteremic Agents; Coenzymes; Contraindications; Heart Failure; Humans; Lovastatin; Ubiquinone

Topics: Anticholesteremic Agents; Coenzymes; Heart Failure; Humans; Lovastatin; Pravastatin; Ubiquinone

Topics: Anticholesteremic Agents; Coenzymes; Heart Failure; Humans; Risk Factors; Ubiquinone

Although prevention of heart failure recently has become a realistic issue, management of heart failure once the syndrome has developed, is mainly supportive, based on the various cardiac and peripheral changes which occur in the course of heart failure. Of these, abnormal neurohormonal activation is of major pathophysiologic and prognostic significance. Consequently, modulation of neuroendocrine activation is now recognized a prime target in the treatment of heart failure, besides diuretic therapy. In this respect, the value of converting enzyme inhibition is well established. Future developments in this area include dopaminergic agents, vasopressin antagonists, angiotensin II receptor antagonists, renin inhibitors, spironolactone and, possibly, ANF peptidase inhibitors. Besides diuretics, necessary when signs of fluid retention are present, the approach to heart failure management involves other pharmacologic issues. In view of abnormal vascular control with vasoconstriction prevailing during progressive heart failure, it clearly makes sense to vasodilate. However, of available vasodilators, only the combination of relatively high dose nitrates and hydralazine has proven to be of clinical significance, in terms of hemodynamics, exercise capacity and survival. It is possible, though, that novel generation dihydropyridine derivatives may prove beneficial as well. Thus far, there has been much debate concerning the usefulness and particularly the safety of positive inotrope therapy and inodilator treatment. Taken together, this concern relates to presence and predominance of cAMP-dependent mechanisms to induce these effects. Thus, sympathomimetic agents and phosphodiesterase inhibitors, such as milrinone or enoximone, are without beneficial effects, but instead shorten survival during long-term therapy. This may be different where compounds which act through cAMP-independent mechanisms, i.e., calcium sensitization or sodium channel stimulation, are concerned, but needs to be confirmed yet.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Carnitine; Coenzymes; Deoxyepinephrine; Dopamine Agents; Heart Failure; Humans; Taurine; Ubiquinone; Vasodilator Agents

Ninety-four consecutive hospital patients aged over 50 years were included in a cross-sectional study. Serum samples were analyzed for coenzyme Q10, alpha-tocopherol, and free cholesterol levels. Patients who died within a follow-up period of 6 months or had congestive heart failure or severe myalgia, and/or received cytostatic or lipid-lowering drug therapy showed significantly lower free cholesterol-related coenzyme Q10 values. Prospective controlled clinical trials will determine whether coenzyme Q10 has a potential to protect patients from such complications and become a useful therapy.

Topics: Adult; Aged; Aged, 80 and over; Cholesterol; Coenzymes; Cross-Sectional Studies; Data Interpretation, Statistical; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Predictive Value of Tests; Survival Rate; Ubiquinone; Vitamin E

Digitalis, diuretics, and vasodilators are considered standard therapy for patients with congestive heart failure, for which treatment is tailored according to the severity of the syndrome and the patient profile. Apart from the clinical seriousness, heart failure is always characterized by an energy depletion status, as indicated by low intramyocardial ATP and coenzyme Q10 levels. We investigated safety and clinical efficacy of coenzyme Q10 (CoQ10) adjunctive treatment in congestive heart failure, which had been diagnosed at least 6 months previously and treated with standard therapy. A total of 2500 patients in NYHA classes II and III were enrolled in this open noncomparative 3-month postmarketing drug surveillance study in 173 Italian centers. The daily dose of CoQ10 was 50-150 mg orally, with the majority of patients (78%) receiving 100 mg/day. Clinical and laboratory parameters were evaluated at the entry into the study and on day 90; the assessment of clinical signs and symptoms was made using from two- to seven-point scales. Preliminary results on 1113 patients (mean age 69.5 years) show a low incidence of side effects: 10 adverse reactions were reported in 8 (0.8%) patients, of which only 5 reactions were considered as correlated to the test treatment. After 3 months of test treatment the proportions of patients with improvement in clinical signs and symptoms were as follows: cyanosis 81%, edema 76.9%, pulmonary rales 78.4%, enlargement of the liver area 49.3%, jugular reflux 81.5%, dyspnea 54.2%, palpitations 75.7%, sweating 82.4%, arrhythmia 62%, insomnia 60.2%, vertigo 73%, and nocturia 50.7%.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Chemotherapy, Adjuvant; Coenzymes; Female; Heart Failure; Humans; Italy; Male; Middle Aged; Product Surveillance, Postmarketing; Ubiquinone

Topics: Coenzymes; Heart Failure; Humans; Norway; Ubiquinone

The effects of coenzyme Q10 (CoQ) and captopril on functional capacity, hemodynamics and survival were studied in 154 rats that recovered after experimental myocardial infarction. Rats were randomized into four groups receiving either CoQ, captopril, a combination of the two drugs or 1 ml of tap water once daily for 12 weeks from the day of coronary artery ligation. CoQ as well as captopril and the combined treatment significantly improved exercise capacity as evaluated by lactate production during a standardized treadmill exercise test. No significant changes in heart rate or mean blood pressure were observed during the study in the captopril-treated group. CoQ treatment increased the maximum heart rate significantly, whereas no effect on mean blood pressure was observed. Both captopril and CoQ decreased pulmonary congestion. Furthermore, the data may suggest that captopril prevents right ventricular hypertrophy seen in placebo-treated rats with large infarcts. This was not observed after CoQ treatment. Captopril treatment improved 3-month probability of survival (93%) as compared with placebo (74%) (P less than .05). CoQ and the combined treatment tended to improve survival, but this was, however, not statistically significant.

Topics: Animals; Body Weight; Captopril; Coenzymes; Drug Synergism; Energy Metabolism; Female; Heart Failure; Hemodynamics; Myocardial Infarction; Organ Size; Rats; Survival Rate; Ubiquinone

In 11 patients suffering from medium to severe heart failure, we performed a clinical and instrumental study to evaluate the effectiveness of ubidecarenone (60 mg/die in a single oral dose), in addition to conventional treatment with digitalis and diuretics. After an 8-month follow-up in most patients we observed a significant improvement in clinical symptoms and in quality of life. Furthermore we were able to demonstrate a statistically significant decrease in left atrium dimensions (p less than 0.01), end-diastolic (p less than 0.01) and end-systolic (p less than 0.05) left ventricular diameters and a significative reduction in the distance of the septum from the e point of the mitral valve (p less than 0.05), expression of significant improvement of cardiac output.

Topics: Aged; Aged, 80 and over; Cardiac Output; Coenzymes; Drug Evaluation; Female; Heart Failure; Humans; Male; Middle Aged; Ubiquinone

Coenzyme Q10 (CoQ10) is a redox component in the respiratory chain. CoQ10 is necessary for human life to exist; and a deficiency can be contributory to ill health and disease. A deficiency of CoQ10 in myocardial disease has been found and controlled therapeutic trials have established CoQ10 as a major advance in the therapy of resistant myocardial failure. The cardiotoxicity of adriamycin, used in treatment modalities of cancer, is significantly reduced by CoQ10, apparently because the side-effects of adriamycin include inhibition of mitochondrial CoQ10 enzymes. Models of the immune system including phagocytic rate, circulating antibody level, neoplasia, viral and parasitic infections were used to demonstrate that CoQ10 is an immunomodulating agent. It was concluded that CoQ10, at the mitochondrial level, is essential for the optimal function of the immune system.

Topics: Aged; Aging; Cardiac Output; Coenzymes; Double-Blind Method; Doxorubicin; Female; Heart Diseases; Heart Failure; Humans; Immunity; Male; Middle Aged; Myocardial Infarction; Stroke Volume; Ubiquinone

Coenzyme Q10 (CoQ10) treatment, orally administered as 100 mg daily dose, was initiated in a series of patients with advanced heart failure in an open, controlled design. They were all showing an insufficient response to classical therapy with diuretics and digitalis. Twelve patients with various causes of heart failure, classified clinically by echocardiography (ECHO), (12/12), and heart catheterization with endomyocardial biopsy, (10/12), were followed prospectively for a mean period of seven months. Serial assessments: Clinical examination (with questionnaire), ECG, chest X-ray, ECHO, systolic time intervals (STI) and blood levels of CoQ10 were performed. With a mean latency period of 30 days, eight out of 12 patients (67%) showed definite clinical improvement. Subjectively, the patients felt less tired, their general activity tolerance increased and dyspnoea at rest disappeared. There were obvious signs of decreased right-sided stasis (hepatic congestion). The heart rate fell significantly, and the heart volume (chest X-ray) decreased in the eight responders (although n.s.). A significant reduction in the left atrial size (ECHO) was registered, suggesting a reduced preload of the left ventricle, Furthermore, a significant decline in the PEP/LVET ratio (STI) was indicative of an improved myocardial performance. Preliminary CoQ10 withdrawal results showed severe clinical relapse with subsequent improvement on CoQ10 reinstatement, supporting the interpretation that treatment of these patients corrected a myocardial deficiency of CoQ10 and increased contractility. Hence CoQ10 appears to be an effective therapeutic agent in advanced cases of heart failure. This is an attractive circumvention of the traditional principles of therapy: supporting the myocardium directly by ameliorating a supposed underlying mitochondrial dysfunction (exhausted bioenergetics).

Topics: Adolescent; Adult; Aged; Cardiac Volume; Coenzymes; Drug Administration Schedule; Echocardiography; Female; Heart Failure; Heart Rate; Hemodynamics; Humans; Male; Middle Aged; Myocardium; Prospective Studies; Recurrence; Systole; Ubiquinone

Topics: Aged; Coenzymes; Female; Heart Failure; Humans; Male; Middle Aged; Ubiquinone

Topics: Aged; Coenzymes; Coronary Disease; Female; Heart Failure; Humans; Male; Middle Aged; Ubiquinone