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Coenzyme Q10 (coenzyme + q10)

Distribution by Scientific Domains

Life Sciences	53%
Medical Sciences	34%
Chemistry	12%

Selected Abstracts

Maternal transmission of diabetes

DIABETIC MEDICINE, Issue 2 2002
J. C. Alcolado
Abstract Type 2 diabetes mellitus represents a heterogeneous group of conditions characterized by impaired glucose homeostasis. The disorder runs in families but the mechanism underlying this is unknown. Many, but not all, studies have suggested that mothers are excessively implicated in the transmission of the disorder. A number of possible genetic phenomena could explain this observation, including the exclusively maternal transmission of mitochondrial DNA (mtDNA). It is now apparent that mutations in mtDNA can indeed result in maternally inherited diabetes. Although several mutations have been implicated, the strongest evidence relates to a point substitution at nucleotide position 3243 (A to G) in the mitochondrial tRNAleu(UUR) gene. Mitochondrial diabetes is commonly associated with nerve deafness and often presents with progressive non-autoimmune ,-cell failure. Specific treatment with Coenzyme Q10 or L-carnitine may be beneficial. Several rodent models of mitochondrial diabetes have been developed, including one in which mtDNA is specifically depleted in the pancreatic islets. Apart from severe, pathogenic mtDNA mutations, common polymorphisms in mtDNA may contribute to variations of insulin secretory capacity in normal individuals. Mitochondrial diabetes accounts for less than 1% of all diabetes and other mechanisms must underlie the maternal transmission of Type 2 diabetes. Possibilities include the role of maternally controlled environments, imprinted genes and epigenetic phenomena. [source]

Coenzyme Q10 and vitamin E deficiency in Friedreich's ataxia: predictor of efficacy of vitamin E and coenzyme Q10 therapy

EUROPEAN JOURNAL OF NEUROLOGY, Issue 12 2008
J. M. Cooper
Background and purpose:, A pilot study of high dose coenzyme Q10 (CoQ10)/vitamin E therapy in Friedreich's ataxia (FRDA) patients resulted in significant clinical improvements in most patients. This study investigated the potential for this treatment to modify clinical progression in FRDA in a randomized double blind trial. Methods:, Fifty FRDA patients were randomly divided into high or low dose CoQ10/ vitamin E groups. The change in International Co-operative Ataxia Ratings Scale (ICARS) was assessed over 2 years as the primary end-point. A post hoc analysis was made using cross-sectional data. Results:, At baseline serum CoQ10 and vitamin E levels were significantly decreased in the FRDA patients (P < 0.001). During the trial CoQ10 and vitamin E levels significantly increased in both groups (P < 0.01). The primary and secondary end-points were not significantly different between the therapy groups. When compared to cross-sectional data 49% of all patients demonstrated improved ICARS scores. This responder group had significantly lower baseline serum CoQ10 levels. Conclusions:, A high proportion of FRDA patients have a decreased serum CoQ10 level which was the best predictor of a positive clinical response to CoQ10/vitamin E therapy. Low and high dose CoQ10/vitamin E therapies were equally effective in improving ICARS scores. [source]

Functional connections and pathways of coenzyme Q10-inducible genes: An in-silico study

IUBMB LIFE, Issue 10 2007
Frank Döring
Abstract Coenzyme Q10 (CoQ10, ubiquinone) is an essential cofactor in the electron transport chain, serves as a potent antioxidant in mitochondria and lipid membranes, and is often used as a dietary supplement for a number of diseases including cardiovascular diseases. Recently, we obtained evidence that CoQ10 (Kaneka Q10Ô) affects the expression of hundreds of human genes. To decipher the functional and regulatory connections of these genes, a literature search combined with transcription factor binding site analysis was performed using Genomatix BiblioSphere and MatInspector. This in-silico analysis revealed 17 CoQ10-inducible genes which are functionally connected by signalling pathways of G-protein coupled receptors, JAK/STAT, integrin, and beta-arrestin. Promoter analysis of these CoQ10-inducible genes showed one group of NF, B-regulated genes, namely IL5, thrombin, vitronectin receptor and C-reactive protein (CRP). Furthermore, a common promoter framework containing binding sites of the transcription factor families EVI1, HOXF, HOXC, and CLOX was identified in the promoters of IL5, CRP, and vitronectin receptor. The identified CoQ10-inducible genes and pathways play an important role in inflammatory response. Since these effects are based on an in-vitro study, the effect of CoQ10 on vascular health in vivo needs to be addressed in further animal and/or human intervention studies. IUBMB Life, 59: 628-633, 2007 [source]

Safety and tolerability of high-dosage coenzyme Q10 in Huntington's disease and healthy subjects,

MOVEMENT DISORDERS, Issue 12 2010
Article first published online: 28 JUL 2010
Abstract Coenzyme Q10 (CoQ10), a potential neuroprotective compound, was previously investigated at a dosage of 600 mg/day in Huntington's disease (HD) patients and demonstrated a trend toward slowing disease progression. Higher CoQ10 dosages may prove beneficial. We investigated the tolerability and blood levels associated with 1,200, 2,400, and 3,600 mg/day of CoQ10 in HD and healthy subjects. Twenty-eight subjects (20 HD, 8 healthy) enrolled in a 20-week open-label trial. Subjects started on 1,200 mg/day of CoQ10, increasing every 4 weeks by 1,200 mg to a maximum dosage of 3,600 mg/day. Monthly evaluations included review of adverse events and CoQ10 blood levels. Twenty-three subjects (82%) achieved the target dosage of 3,600 mg/day. Six subjects (2 healthy, 4 HD) withdrew prematurely (gastrointestinal (GI) symptoms in 3, worsening HD in 2, and 1 because of a fall). All three serious adverse events occurred in a single subject, and were deemed unrelated to CoQ10. The most common adverse events seen were GI symptoms. Mean (± SD) CoQ10 blood levels achieved over the course of the trial were as follows: 1.26 ± 1.27 ,g/mL (baseline, n = 28), 5.59 ± 2.24 ,g/mL (1,200 mg/day, week 4, n = 26), 6.38 ± 3.25 ,g/mL (2,400 mg/day, week 8, n = 25), 7.49 ± 4.09 ,g/mL (3,600 mg/day, week 12, n = 23), and 6.78 ± 3.36,g/mL (3,600 mg/day, week 20, n = 20). CoQ10 was well tolerated with over 80% of subjects achieving the target dosage. Dosages of 2,400 mg/day may provide the best balance between tolerability and blood level achieved. Further studies examining the efficacy of 2,400 mg/day are planned. © 2010 Movement Disorder Society. [source]

Phase II trial of CoQ10 for ALS finds insufficient evidence to justify phase III,

ANNALS OF NEUROLOGY, Issue 2 2009
Petra Kaufmann MD
Objective Amyotrophic lateral sclerosis (ALS) is a devastating, and currently incurable, neuromuscular disease in which oxidative stress and mitochondrial impairment are contributing to neuronal loss. Coenzyme Q10 (CoQ10), an antioxidant and mitochondrial cofactor, has shown promise in ALS transgenic mice, and in clinical trials for neurodegenerative diseases other than ALS. Our aims were to choose between two high doses of CoQ10 for ALS, and to determine if it merits testing in a Phase III clinical trial. Methods We designed and implemented a multicenter trial with an adaptive, two-stage, bias-adjusted, randomized, placebo-controlled, double-blind, Phase II design (n = 185). The primary outcome in both stages was a decline in the ALS Functional Rating Scale-revised (ALSFRSr) score over 9 months. Stage 1 (dose selection, 35 participants per group) compared CoQ10 doses of 1,800 and 2,700mg/day. Stage 2 (futility test, 75 patients per group) compared the dose selected in Stage 1 against placebo. Results Stage 1 selected the 2,700mg dose. In Stage 2, the pre-specified primary null hypothesis that this dose is superior to placebo was not rejected. It was rejected, however, in an accompanying prespecified sensitivity test, and further supplementary analyses. Prespecified secondary analyses showed no significant differences between CoQ10 at 2,700mg/day and placebo. There were no safety concerns. Interpretation CoQ10 at 2,700mg daily for 9 months shows insufficient promise to warrant Phase III testing. Given this outcome, the adaptive Phase II design incorporating a dose selection and a futility test avoided the need for a much larger conventional Phase III trial. Ann Neurol 2009;66:235,244 [source]

Protective role of Coenzyme Q10 in two models of rat lung injury

ANZ JOURNAL OF SURGERY, Issue 4 2010
Hou-Kiat Lim
Abstract Background:, Ischaemia-reperfusion injury is a life-threatening complication of lung transplantation. Attempts to ameliorate this injury have included optimization of donor management and improving techniques of lung preservation. However, few investigators have sought to pretreat potential recipients. Coenzyme Q10 (CoQ10) is a potent antioxidant and cellular energizer that has been shown to protect the heart against injury. However, its protective effect in the lung is unknown. We therefore set out to study the impact of Coenzyme Q10 pretreatment in a model of mild and severe lung injury. Methods:, We evaluated the impact of CoQ10 in a two-stage laboratory study. In the first stage, in order to measure the magnitude of increase in tissue and plasma CoQ10 following oral therapy we administered high-dose oral CoQ10 to rats (n = 6). In the second stage we evaluated the impact of CoQ10 in the rat lung (n = 10) that was subjected to 230 min of normoxic lung injury or 90 min of warm ischaemia and 120 min of reperfusion in a model of lung transplantation. Results:, High-dose oral CoQ10 for 7 days produced a 15-fold increase in plasma and a 3-fold increase in lung CoQ10. In the normoxic lung, the injury-induced rise in peak airway pressure was reduced by CoQ10 treatment at 90 min (P = 0.037) and at 120 min (P = 0.005) without any change in arterial oxygen. In the lung subjected to severe ischaemia-reperfusion injury, CoQ10 did not reduce the injury-induced increase in peak airway pressure (P = 0.599) nor the decrease in arterial oxygen (P = 0.844). However, CoQ10 markedly reduced the increase in tumour necrosis factor-alpha in ischaemic compared with normoxic lung (P = 0.027). Conclusions:, The effect of CoQ10 pretreatment is insufficient to protect the lung against severe ischaemia-reperfusion as may occur in lung transplantation. However, in the setting of less severe pulmonary injury as in anaesthesia and non-transplant surgery, CoQ10 may have a protective role. [source]

Functional role of Coenzyme Q in the energy coupling of NADH-CoQ oxidoreductase (Complex I): Stabilization of the semiquinone state with the application of inside-positive membrane potential to proteoliposomes

BIOFACTORS, Issue 1-4 2008
Tomoko Ohnishi Ph.D.
Abstract Coenzyme Q10 (which is also designated as CoQ10, ubiquinone-10, UQ10, CoQ, UQ or simply as Q) plays an important role in energy metabolism. For NADH-Q oxidoreductase (complex I), Ohnishi and Salerno proposed a hypothesis that the proton pump is operated by the redox-driven conformational change of a Q-binding protein, and that the bound form of semiquinone (SQ) serves as its gate [FEBS Letters 579 (2005) 45,55]. This was based on the following experimental results: (i) EPR signals of the fast-relaxing SQ anion (designated as Q) are observable only in the presence of the proton electrochemical potential (,,); (ii) iron-sulfur cluster N2 and Q are directly spin-coupled; and (iii) their center-to-center distance was calculated as 12Å, but Q is only 5Å deeper than N2 perpendicularly to the membrane. After the priming reduction of Q to Nf, the proton pump operates only in the steps between the semiquinone anion (Q) and fully reduced quinone (QH2). Thus, by cycling twice for one NADH molecule, the pump transports 4H+ per 2e,. This hypothesis predicts the following phenomena: (a) Coupled with the piericidin A sensitive NADH-DBQ or Q1 reductase reaction, ,, would be established; (b) ,, would enhance the SQ EPR signals; and (c) the dissipation of ,, with the addition of an uncoupler would increase the rate of NADH oxidation and decrease the SQ signals. We reconstituted bovine heart complex I, which was prepared at Yoshikawa's laboratory, into proteoliposomes. Using this system, we succeeded in demonstrating that all of these phenomena actually took place. We believe that these results strongly support our hypothesis. [source]

Supplementation with CoQ10 lowers age-related (ar) NOX levels in healthy subjects

BIOFACTORS, Issue 1-4 2008
Dorothy M. Morré
Our work has identified an aging-related ECTO-NOX activity (arNOX), a hydroquinone oxidase which is cell surface located and generates superoxide. This activity increases with increasing age beginning > 30 y. Because of its cell surface location and ability to generate superoxide, the arNOX proteins may serve to propagate an aging cascade both to adjacent cells and to oxidize circulating lipoproteins as significant factors determining atherogenic risk. The generation of superoxide by arNOX proteins is inhibited by Coenzyme Q10 as one basis for an anti-aging benefit of CoQ10 supplementation in human subjects. In a preliminary pilot study, 25 female subjects between 45 and 55 y of age were recruited at Stanford University from the Palo Alto, CA area. Informed consent was obtained. Ten of the subjects received Coenzyme Q10 supplementation of 180 (3 × 60 mg) per day for 28 days. Serum, saliva and perspiration levels of arNOX were determined at 7, 14 and 28 days of CoQ10 supplementation and compared to the initial baseline value. Activity correlated with subject age up to a maximum between age 50 and 55 years of age for saliva and perspiration as well and then declined. With all three sources, the arNOX activity extrapolated to zero at about age 30. Response to Coenzyme Q10 also increased with age being least between ages 45 and 50 and greatest between ages 60 and 65. With all three biofluids, arNOX activity was reduced between 25 and 30% by a 3 × 60 mg daily dose Coenzyme Q10 supplementation. Inhibition was the result of Coenzyme Q10 presence. [source]

Coenzyme Q10 improves contractility of dysfunctional myocardium in chronic heart failure

BIOFACTORS, Issue 1-4 2005
Romualdo Belardinelli
Abstract Background: There is evidence that plasma CoQ10 levels decrease in patients with advanced chronic heart failure (CHF). Objective: To investigate whether oral CoQ10 supplementation could improve cardiocirculatory efficiency in patients with CHF. Methods: We studied 21 patients in NYHA class II and III (18M, 3W, mean age 59 ±9 years) with stable CHF secondary to ischemic heart disease (ejection fraction 37 ± 7%), using a double-blind, placebo-controlled cross-over design. Patients were assigned to oral CoQ10 (100 mg tid) and to placebo for 4 weeks, respectively. Results: CoQ10 supplementation resulted in a threefold increase in plasma CoQ10 level (P<0.0001 vs placebo). Systolic wall thickening score index (SWTI) was improved both at rest and peak dobutamine stress echo after CoQ10 supplementation (+12.1 and 15.6%, respectively, P<0.05 vs placebo). Left ventricular ejection fraction improved significantly also at peak dobutamine (15% from study entry P<0.0001) in relation to a decrease in LV end-systolic volume index (from 57 ± 7 mL/m2 to 45 mL/m2, P<0.001). Improvement in the contractile response was more evident among initially akinetic (+33%) and hypokinetic (+25%) segments than dyskinetic ones (+6%). Improvement in SWTI was correlated with changes in plasma CoQ10 levels (r=,0.52, P<0.005). Peak VO2 was also improved after CoQ10 as compared with placebo (+13%, <0.005). No side effects were reported with CoQ10. Conclusions: Oral CoQ10 improves LV contractility in CHF without any side effects. This improvement is associated with an enhanced functional capacity. [source]

Treatment of statin adverse effects with supplemental Coenzyme Q10 and statin drug discontinuation

BIOFACTORS, Issue 1-4 2005
Peter H. Langsjoen
Abstract Fifty consecutive new cardiology clinic patients who were on statin drug therapy (for an average of 28 months) on their initial visit were evaluated for possible adverse statin effects (myalgia, fatigue, dyspnea, memory loss, and peripheral neuropathy). All patients discontinued statin therapy due to side effects and began supplemental CoQ10 at an average of 240 mg/day upon initial visit. Patients have been followed for an average of 22 months with 84% of the patients followed now for more than 12 months. The prevalence of patient symptoms on initial visit and on most recent follow-up demonstrated a decrease in fatigue from 84% to 16%, myalgia from 64% to 6%, dyspnea from 58% to 12%, memory loss from 8% to 4% and peripheral neuropathy from 10% to 2%. There were two deaths from lung cancer and one death from aortic stenosis with no strokes or myocardial infarctions. Measurements of heart function either improved or remained stable in the majority of patients. We conclude that statin-related side effects, including statin cardiomyopathy, are far more common than previously published and are reversible with the combination of statin discontinuation and supplemental CoQ10. We saw no adverse consequences from statin discontinuation. [source]

Can coenzyme Q10 improve vascular function and blood pressure?

BIOFACTORS, Issue 1-4 2003
Potential for effective therapeutic reduction in vascular oxidative stress
Abstract Coenzyme Q10 (CoQ) is an endogenously synthesised compound that acts as an electron carrier in the mitochondrial electron transport chain. The presence of adequate tissue concentrations of CoQ may be important in limiting oxidative and nitrosative damage in vivo. Oxidative and nitrosative stress are likely to be elevated in conditions such as diabetes and hypertension. In these conditions elevated oxidative and nitrosative stress within the arterial wall may contribute to increased blood pressure and vascular dysfunction. The major focus of this review is the potential of CoQ to improve vascular function and lower blood pressure. Although there is substantial indirect support for the putative mechanism of effect of CoQ on the vascular system, to date there is little direct support for an effect of CoQ on in vivo markers of oxidative or nitrosative stress. The limited data available from studies in animal models and from human intervention studies are generally consistent with a benefit of CoQ on vascular function and blood pressure. The observed effects of CoQ on these endpoints are potentially important therapeutically. However, before any firm clinical recommendations can be made about CoQ supplementation, further intervention studies in humans are needed to investigate the effects of CoQ on vascular function, blood pressure and cardiovascular outcomes. The particularly relevant groups of patients for these studies are those with insulin resistance, type 2 diabetes, hypertension and the metabolic syndrome. [source]

Coenzyme Q10 prevents human lens epithelial cells from light-induced apoptotic cell death by reducing oxidative stress and stabilizing BAX,/,Bcl-2 ratio

ACTA OPHTHALMOLOGICA, Issue 3 2010
Marcus Kernt
Abstract. Background:, Cataract is one of the most prevalent eye disease and a major cause for legal blindness in the world. Beside others, cumulative light-exposure and apoptotic cell death are significantly associated with cataract development. In contrast, supplementation with antioxidants has been suggested to prevent premature cataractogenesis. This study investigates possible protective effects of Coenzyme Q10 (CoQ10) regarding light-induced stress and apoptotic cell death in human lens epithelial cells (LEC). Methods:, Human LEC were either pre-incubated with CoQ10 or not and then exposed to white light. After 10,40 min of irradiation viability, induction of intracellular reactive oxygen species (ROS), apoptosis and cell death was determined. Expression of apoptotic BAX and anti-apoptotic Bcl-2 protein and their mRNA were determined by RT-PCR and Western blot analysis. Results:, Light exposure decreased LEC viability and Bcl-2 expression and increased intracellular ROS, apoptotic cell death, and BAX expression in a time-of-irradiation-dependent manner. Phototoxic cell death and apoptosis, as well as decrease of Bcl-2 and increase in BAX expression was significantly reduced, when cells were pre-incubated with CoQ10. Conclusions:, In this study, CoQ10 significantly reduced light-induced LEC-damage and attenuated phototoxic effects on BAX and Bcl-2 expression. Therefore, CoQ10 supplementation might also be useful in preventing LEC death and consecutive cataract formation in vivo. [source]

Coenzyme Q10 and vitamin E deficiency in Friedreich's ataxia: predictor of efficacy of vitamin E and coenzyme Q10 therapy

Pituitary adenylate cyclase-activating polypeptide attenuates streptozotocin-induced apoptotic death of RIN-m5F cells through regulation of Bcl-2 family protein mRNA expression

FEBS JOURNAL, Issue 22 2008
Satomi Onoue
Oxidative stress, followed by the apoptotic death of pancreatic , cells, is considered to be one of causative agents in the evolution of the type 2 diabetic state; therefore, the protection of , cells can comprise an efficacious strategy for preventing type 2 diabetes. In the present study, RIN-m5F cells (i.e. the rat insulinoma , cell line) were stimulated with streptozotocin, resulting in a time- and concentration-dependent release of lactate dehydrogenase. There appeared to be significant apoptotic cell death after 2 h of treatment with streptozotocin at 10 mm, as demonstrated by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining and 2.6-fold activation of cellular caspase-3, an apoptotic enzyme. By contrast, some neuropeptides of the glucagon-secretin family and coenzyme Q10, an endogenous mitochondrial antioxidant, could attenuate streptozotocin cytotoxicity, and especially pituitary adenylate cyclase-activating polypeptide (PACAP), at a concentration of 10,7 m, exhibited 34% attenuation of lactate dehydrogenase release from streptozotocin-treated RIN-m5F cells. Quantitative RT-PCR experiments indicated the inhibitory effect of PACAP on streptozotocin-evoked up-regulation of pro-apoptotic factor (Noxa and Bax) and a 2.3-fold enhancement of Bcl-2 mRNA expression, a pro-survival protein, was also observed after addition of PACAP. The data obtained suggest the anti-apoptotic role of PACAP in streptozotocin-treated RIN-m5F cells through the regulation of pro-apoptotic and pro-survival factors. [source]

Effects of different dietary phytase activities on the concentration of antioxidants in the liver of growing broilers

JOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 4 2010
F. Karadas
Summary One-hundred and fifty male chickens were used to evaluate the effects of different activities (0, 250, 500, 12 500 FTU/kg) of phytase on their performance and antioxidant concentration in the liver. The chicks were housed in 30 cages and were allocated to six replicates of five dietary treatments. All diets were formulated to be adequate in energy and protein (12.90 MJ/kg metabolizable energy, 214 g/kg crude protein), however, the negative control (NC) was lower in available P compared with the positive control (PC) (2.5 vs. 4.5 g/kg diet). The other three diets were the NC supplemented with phytase at 250, 500 and 12 500 FTU/kg (NC + 250, NC + 500 and NC + 12 500 FTU respectively). The concentration of antioxidants in the liver of the birds was determined using HPLC at 21 days of age. Low P diets (NC) reduced weight gain, however, supplementation with phytase improved weight gain to the extent that it was better than the PC at the 12 500 FTU treatment (p < 0.05). Feed conversion ratio was also improved by the high level of phytase supplement more than other treatments (p < 0.05). Feed consumption was not affected either by dietary phosphorus concentration or by different phytase supplementation. The antioxidant data showed that the unsupplemented diet with low phosphorus (NC) decreased the concentration of coenzyme Q10 and retinol-linoleate in the liver compared with that of birds on the adequate phosphorus treatment (PC). Phytase supplementation, especially at the higher doses (500 and 12 500 FTU) increased the level of coenzyme Q10 to the same level as the PC treatment. In addition, the highest dose (12 500 FTU) of phytase increased retinol concentration in the liver of chickens compared with those on the NC treatment. The highest inclusion level of phytase increased the ,-tocopherol level in the liver compared with the lower levels of phytase (NC + 250 and NC + 500 FTU). [source]

Gene expression profiling of aging in multiple mouse strains: identification of aging biomarkers and impact of dietary antioxidants

AGING CELL, Issue 4 2009
Sang-Kyu Park
Summary We used DNA microarrays to identify panels of transcriptional markers of aging that are differentially expressed in young (5 month) and old (25 month) mice of multiple inbred strains (129sv, BALB/c, CBA, DBA, B6, C3H and B6C3F1). In the heart, age-related changes of five genes were studied throughout the mouse lifespan: complement component 4, chemokine ligand 14, component of Sp100-rs, phenylalanine hydroxylase and src family associated phosphoprotein 2. A similar analysis in the brain (cerebellum) involved complement component 1q (alpha polypeptide), complement component 4, P lysozyme structural, glial fibrillary acidic protein and cathepsin S. Caloric restriction (CR) inhibited age-related expression of these genes in both tissues. Parametric analysis of gene set enrichment identified several biological processes that are induced with aging in multiple mouse strains. We also tested the ability of dietary antioxidants to oppose these transcriptional markers of aging. Lycopene, resveratrol, acetyl- l -carnitine and tempol were as effective as CR in the heart, and ,-lipoic acid and coenzyme Q10 were as effective as CR in the cerebellum. These findings suggest that transcriptional biomarkers of aging in mice can be used to estimate the efficacy of aging interventions on a tissue-specific basis. [source]

Synthesis of [3,- 14C] coenzyme Q10

JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 10 2002
Kimio Hamamura
Abstract Radio-labelled coenzyme Q10, labelled at the 3,-position with 14C, was synthesized starting from natural solanesol and ethyl [3- 14C] acetoacetate. The radiochemical yield was 8.0% from ethyl [3- 14C] acetoacetate. The specific radioactivity of the product was 44.8 ,Ci, 1.66 MBq/mg. The specific radioactivity and radiochemical purity are sufficiently high to enable us to use this labelled form of coenzyme Q10 in metabolic studies. Copyright © 2002 John Wiley & Sons, Ltd. [source]

Safety and tolerability of high-dosage coenzyme Q10 in Huntington's disease and healthy subjects,

Oxidative stress, endothelial function and coenzyme Q10

BIOFACTORS, Issue 1-4 2008
Romualdo Belardinelli
Abstract Reactive oxygen species seem to play an important role in vascular homeostasis. In conditions of high oxidative stress, such as chronic heart failure and multiple coronary risk factors, the rate of inactivation of nitric oxide to peroxynitrite by superoxide anions may be reduced by CoQ10, which can also protect against nitrosative damage. CoQ10 may also influence vascular function indirectly via inhibition of oxidative damage to LDL. Patients with lower levels of extracellular superoxide dismutase (ecSOD) demonstrate greater improvements than patients with normal ec-SOD levels, suggesting that the higher the oxidative stress the greater the improvement in the endothelium-dependent relaxation after the administration of a compound with antioxidant properties like CoQ10. Future studies are needed to inquire whether these effects may translate into benefits in clinical practice. [source]

Positive inotropic effect of coenzyme Q10, omega-3 fatty acids and propionyl-L-carnitine on papillary muscle force-frequency responses of BIO TO-2 cardiomyopathic Syrian hamsters

BIOFACTORS, Issue 1-4 2008
Romina Vargiu
Abstract The inability of heart muscle to generate ventricular pressure to adequately propel blood through the cardiovascular system is a primary defect associated with congestive heart failure (CHF). Force-frequency relationship (FFR) is one of the main cardiac defects associated with congestive heart failure. Thus FFR is a convenient methodological tool for evaluating the severity of muscle contractile dysfunction and the effectiveness of therapeutic agents. Papillary muscle isolated from BIO TO-2 cardiomyopathic Syrian hamsters (CMSHs), show a depressed FFR and represents an animal model of human idiopathic dilated cardiomyopathy. In the present study we investigated the effect of CoQ10, omega-3 fatty acids, propionyl-L-carnitine (PLC) and a combination of these 3 agents (formulation HS12607) on FFR in 8 month old BIO TO-2 CMSHs. Papillary muscles isolated from the anesthetized animals were placed in an incubation bath and attached to an isometric force transducer. A digital computer with an analog/digital interface allowed control of both muscle developed force and electrical stimulus parameters. Force-frequency response was evaluated, at Lmax, with increasing frequencies: 0.06, 0.12, 0.25, 0.5, 1, 2 and 4 Hz. HS12607-treatment produced a positive inotropic effect resulting in a significant enhancement (p < 0.05) of the peak force at the highest frequencies (1,4 Hz). In the range of frequency of 1,4 Hz also CoQ10 and omega-3 significantly(p < 0.05) attenuated the fractional decline in developed force. The significant improvement (p < 0.05) of the timing parameter peak rate of tension rise (+T') and peak rate of tension fall (,T') indicating a faster rate of muscle contraction and relaxation respectively, found in CoQ10, omega-3 and PLC-treated CMSHs, may be due to the positive effects of these substances on sarcoplasmic reticulum functions. These findings suggest that naturally occurring CoQ10, omega-3 and PLC, particularly when administered together in a coformulation, might be a valid adjuvant to conventional therapy in dilated cardiomyopathy especially when considering that they are natural substances, devoid of side effects. [source]

arNOX activity of saliva as a non-invasive measure of coenzyme Q10 response in human trials

BIOFACTORS, Issue 1-4 2008
D. James Morré
arNOX is a coenzyme Q10 -inhibited, aging-related ECTO-NOX protein of the cell surface also present in sera. It is capable of Superoxide generation measured as Superoxide dismutase-inhibited reduction of ferricytochrome c and is a potential contributor to atherogenic risk. Here, we report an arNOX activity of saliva of older individuals also inhibited by coenzyme Q10. The activity first appears after age 30 to a near maximum at about age 55. Those surviving beyond age 55 usually have reduced arNOX activities. Our studies demonstrate significant (25 to 30%) reduction of arNOX levels with coenzyme Q10 supplementation of 60 mg (2 × 30 mg) per day for 28 days. Activity correlated with age. Response to coenzyme Q10 increased with age being greatest between ages 60 and 65. Saliva arNOX levels varied in a regular pattern throughout the day so it was important that samples be collected at approximately the same time each day for comparative purposes. The coenzyme Q10 response was reversible and within 12 h after the last intake of coenzyme Q10, the salivary arNOX levels returned to base line. The findings suggest that salivary arNOX provides a convenient and non-invasive method to monitor arNOX levels in clinical coenzyme Q10 intervention trials with the response levels paralleling those seen with serum and cellular arNOX. [source]

A metabolic approach to the treatment of dilated cardiomyopathy in BIO T0,2 cardiomyopathic Syrian hamsters

BIOFACTORS, Issue 1-4 2005
Rino Mancinelli
Abstract Mechanisms underlying dilated cardiomyopathy (DCM) are poorly understood and effective therapy is still unavailable. The aim of this study was to examine the heart ultrastructure and dynamic of BIO T0,2 cardiomyopathic hamsters, an animal model of DCM, and to study in these animals, the effects of a co-formulation (HS12607) of propionyl-L-carnitine, coenzyme Q10 and omega-3 fatty acids on cardiac mechanical parameters. Sarcomere length, Frank-Starling mechanism and force-frequency relations were studied on isolated ventricular papillary muscle from age-matched BIO F1B normal Syrian hamsters, BIO T0,2 control and BIO T0,2 HS12607-treated cardiomyopathic Syrian hamsters. At the optimum length to maximum active force, electron microscopy of left ventricular papillary muscle revealed that seven out of ten muscles studied showed shorter sarcomeres (1.20 ± 0.29,m), and the remaining three showed longer sarcomeres (2.80 ± 0.13,m), compared to those of normal hamsters (2.05± 0.06,m, n=10). Severe alterations of the Frank-Starling mechanism, force-frequency relations and derivative parameters of contractile waves were also observed in vitro in the BIO T0,2 control hamsters. Long-term (8 weeks) treatment with HS12607 prevented alterations in sarcomere length in the BIO T0,2 cardiomyopathic hamsters; the Frank-Starling mechanism and force-frequency relations were also significantly (P<0.05) improved in these hamsters. Therefore results of the present study strongly suggest the need for clinical studies on metabolic therapeutic intervention in the effort to stop the progression of dilated cardiomyopathy. [source]

Effect on absorption and oxidative stress of different oral Coenzyme Q10 dosages and intake strategy in healthy men

BIOFACTORS, Issue 1-4 2005
R. B. Singh
Abstract Introduction: The effect of various dosages and dose strategies of oral coenzyme Q10 (Q10) administration on serum Q10 concentration and bioequivalence of various formulations are not fully known. Subjects and Methods: In a randomized, double blind, placebo controlled trial 60 healthy men, aged 18,55 years, were supplemented with various dosages and dose strategies of coenzyme Q10 soft oil capsules (Myoqinon 100 mg, Pharma Nord, Denmark) or crystalline 100 mg Q10 powder capsules or placebo. After 20 days blood levels were compared and oxidative load parameters, malondialdehyde (MDA) and thiobarbituric acid reactive substances (TBARS) were monitored to evaluate bioequivalence. All the subjects were advised to take the capsules with meals. Blood samples were collected after 12 hours of overnight fasting at baseline and after 20 days of Q10 administration. Compliance was evaluated by counting the number of capsules returned by the subjects after the trial. Results: Compliance by capsule counting was >90%. Side effects were negligible. Serum concentrations of Q10 (average for groups) increased significantly 3,10 fold in the intervention groups compared with the placebo group. Serum response was improved with a divided dose strategy. TBARS and MDA were in the normal ranges at baseline. After 20 days intervention in the 200 mg group TBARS and MDA decreased, but the decrease was only significant for MDA (Fig. 2). Conclusions: All supplementations increased serum levels of Q10. Q10 dissolved in an oil matrix was more effective than the same amount of crystalline Q10 in raising Q10 serum levels. 200 mg of oil/soft gel formulation of Q10 caused a larger increase in Q10 serum levels than did 100 mg. Divided dosages (2 × 100 mg) of Q10 caused a larger increase in serum levels of Q10 than a single dose of 200 mg. Supplementation was associated with decreased oxidative stress as measured by MDA-levels. Indians appear to have low baseline serum coenzyme Q10 levels which may be due to vegetarian diets. Further studies in larger number of subjects would be necessary to confirm our findings. [source]

Effect of coenzyme Q10 as an antioxidant in ,-thalassemia/Hb E patients

BIOFACTORS, Issue 1-4 2005
Ruchaneekorn W. Kalpravidh
Abstract Thalassemia is a group of genetic disorders resulting from different mutations in the globin gene complex and leading to an imbalance in globin synthesis. Unmatched globin chains are less stable and susceptible to oxidation. Patients with ,-thalassemia/HbE are prone to increased oxidative stress as indicated by increased lipid peroxidation product, malondialdehyde (MDA), partly because of the presence of iron in the form of heme and hemichromes released from excess globin chains and excess iron deposition in various tissues. The level of antioxidant such as glutathione is markedly decreased while activities of antioxidant enzymes including superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px) are increased. We have recently found that the levels of coenzyme Q10 (CoQ10) are also very low in thalassemia. We therefore evaluated the oxidative stress and the antioxidants in these patients before and after supplementation with 100 mg CoQ10 daily for 6 months. The results showed that the plasma level of CoQ10 significantly increased and the oxidative stress decreased as the level of MDA declined. The administration of CoQ10 led to significant improvement of biochemical parameters of antioxidant enzymes. The antioxidant supplementation will be beneficial for thalassemia patients as adjunct therapy to increase their quality of life. [source]

Treatment of massive hypertriglyceridemia resistant to PUFA and fibrates: A possible role for the coenzyme Q10?

BIOFACTORS, Issue 1 2005
A.F.G. Cicero
Abstract Objective: to describe the effect of CoQ10 (added to either a fibrate, or PUFA or association of both) in patients affected by massive hypertriglyceridemia (MHTG) resistant to fibrates and PUFA. Design: Open, sequential, comparative intervention study. Setting: Specialised centres for dyslipidemia management. Subjects: 15 subjects (mean age: 45.1 ± 12.5 years) affected by MHTG and hyporesponsive to either fibrates, or PUFA, or fibrates-PUFA association, and 15 age-matched subjects regularly responders to PUFA and fenofibrate treatment. Interventions: Treatment for periods of 6 weeks each with the following consecutive treatments: CoQ10 150 mg/day, PUFA 3000 mg/day, fenofibrate 200 mg/day, PUFA 3000 mg/day + fenofibrate 200 mg/day, PUFA 3000 mg/day + CoQ10 150 mg/day, fenofibrate 200 mg/day + CoQ10 150 mg/day, and finally, fenofibrate 200 mg/day + PUFA 3000 mg/day + CoQ10 150 mg/day. Results: CoQ10 supplementation improved, in the control group, systolic and diastolic blood pressure, creatinine and Lp(a) plasma levels, both during fenofibrate and/or PUFA treatment. In MHTG group, CoQ10 supplementation significantly improved TG, TC, Lp(a), uric acid and blood pressure during fenofibrate treatment, but only Lp(a) and blood pressure during PUFA treatment. Fenofibrate appeared to have better effect on hsCRP and ,-GT plasma levels than PUFA. No significant change was observed in any group and under any treatment in regards to homocysteinemia, PAI-1, or t-PA. Conclusion: Even though the mechanism of action through which the effects were obtained is yet to be elucidated, adding CoQ10 to fenofibrate could improve the drug's efficacy in MHTG patients not responding to fenofibrate alone. [source]

Can coenzyme Q10 improve vascular function and blood pressure?

Trends in use of herbal and nutritional supplements in cardiovascular patients

CLINICAL CARDIOLOGY, Issue 2 2004
Tomasz Stys M.D.
Abstract Background: Use of herbs and nutritional supplements (known as naturoceuticals) is increasing in the USA, with about 50% of Americans taking naturoceuticals and spending over $10 billion per year for them. This raises concerns regarding their use instead of proven therapies, their side effects, and drug interaction potential. Hypothesis: The study sought to characterize cardiology patients who used supplements and to examine whether their use was diagnosis or doctor dependent, whether it affected patients' compliance, and what supplements were used. Methods: In all, 187 patients attending our cardiology clinic were interviewed, examined, and followed for up to 1 year. The users and nonusers of naturoceuticals were compared. Results: Supplements were used in 106 patients (an average of 3.1 naturoceutical per patient). There were no significant differences in their use by gender, age, primary care doctor specialty, or cardiovascular medications prescribed (except for statins). Patients with a history of myocardial infarction, coronary revascularization, hyperlipidemia, and a family history of coronary artery disease were more likely to use the supplements. Average low-density lipoprotein (106 vs. 108 mg/dl), average blood pressure (132/77 vs. 138/78 mmHg), and average hemoglobin (Hb)A1c (8.7 vs. 7.7%) showed no statistically significant differences between users and nonusers. Patients most commonly took multivitamins, vitamin E, vitamin C, vitamin B, folate, garlic, calcium, coenzyme Q10, and gingko. Conclusion: This study indicates that naturoceutical use is widespread among cardiovascular patients and it is difficult to predict clinically who the users are. Fortunately, according to our limited compliance measures, it appears that the naturoceutical use has not affected patients' compliance with traditional medications. Also, possibly a detrimental interaction potential between traditional medications and naturoceuticals has been demonstrated. [source]