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Leonardo Salviati - One of the best experts on this subject based on the ideXlab platform.

  • genetic bases and clinical manifestations of Coenzyme Q10 coQ10 deficiency
    Journal of Inherited Metabolic Disease, 2015
    Co-Authors: Maria Andrea Desbats, Mara Doimo, Eva Trevisso, Giada Lunardi, Leonardo Salviati
    Abstract:

    Coenzyme Q10 is a remarkable lipid involved in many cellular processes such as energy production through the mitochondrial respiratory chain (RC), beta-oxidation of fatty acids, and pyrimidine biosynthesis, but it is also one of the main cellular antioxidants. Its biosynthesis is still incompletely characterized and requires at least 15 genes. Mutations in eight of them (PDSS1, PDSS2, COQ2, COQ4, COQ6, ADCK3, ADCK4, and COQ9) cause primary CoQ10 deficiency, a heterogeneous group of disorders with variable age of onset (from birth to the seventh decade) and associated clinical phenotypes, ranging from a fatal multisystem disease to isolated steroid resistant nephrotic syndrome (SRNS) or isolated central nervous system disease. The pathogenesis is complex and related to the different functions of CoQ10. It involves defective ATP production and oxidative stress, but also an impairment of pyrimidine biosynthesis and increased apoptosis. CoQ10 deficiency can also be observed in patients with defects unrelated to CoQ10 biosynthesis, such as RC defects, multiple acyl-CoA dehydrogenase deficiency, and ataxia and oculomotor apraxia.

  • genetics of Coenzyme Q10 deficiency
    Molecular Syndromology, 2014
    Co-Authors: Mara Doimo, Maria Andrea Desbats, Cristina Cerqua, Matteo Cassina, Eva Trevisso, Leonardo Salviati
    Abstract:

    Coenzyme Q10 (CoQ10) is an essential component of eukaryotic cells and is involved in crucial biochemical reactions such as the production of ATP in the mitochondrial respiratory chain, the biosynthesis of pyrimidines, and the modulation of apoptosis. CoQ10 requires at least 13 genes for its biosynthesis. Mutations in these genes cause primary CoQ10 deficiency, a clinically and genetically heterogeneous disorder. To date mutations in 8 genes (PDSS1, PDSS2, COQ2, COQ4, COQ6, ADCK3, ADCK4, and COQ9) have been associated with CoQ10 deficiency presenting with a wide variety of clinical manifestations. Onset can be at virtually any age, although pediatric forms are more common. Symptoms include those typical of respiratory chain disorders (encephalomyopathy, ataxia, lactic acidosis, deafness, retinitis pigmentosa, hypertrophic cardiomyopathy), but some (such as steroid-resistant nephrotic syndrome) are peculiar to this condition. The molecular bases of the clinical diversity of this condition are still unknown. It is of critical importance that physicians promptly recognize these disorders because most patients respond to oral administration of CoQ10.

  • haploinsufficiency of coq4 causes Coenzyme Q10 deficiency
    Journal of Medical Genetics, 2012
    Co-Authors: Leonardo Salviati, Mara Doimo, Maria Andrea Desbats, Matteo Cassina, Eva Trevisso, Maria Angeles Rodriguez Hernandez, Alberto Casari, Vanessa Pertegato, Caterina Agosto, Geppo Sartori
    Abstract:

    Background COQ4 encodes a protein that organises the multienzyme complex for the synthesis of Coenzyme Q10 (CoQ10). A 3.9 Mb deletion of chromosome 9q34.13 was identified in a 3-year-old boy with mental retardation, encephalomyopathy and dysmorphic features. Because the deletion encompassed COQ4, the patient was screened for CoQ10 deficiency. Methods A complete molecular and biochemical characterisation of the patient's fibroblasts and of a yeast model were performed. Results The study found reduced COQ4 expression (48% of controls), CoQ10 content and biosynthetic rate (44% and 43% of controls), and activities of respiratory chain complex II+III. Cells displayed a growth defect that was corrected by the addition of CoQ10 to the culture medium. Knockdown of COQ4 in HeLa cells also resulted in a reduction of CoQ10. Diploid yeast haploinsufficient for COQ4 displayed similar CoQ deficiency. Haploinsufficency of other genes involved in CoQ10 biosynthesis does not cause CoQ deficiency, underscoring the critical role of COQ4 . Oral CoQ10 supplementation resulted in a significant improvement of neuromuscular symptoms, which reappeared after supplementation was temporarily discontinued. Conclusion Mutations of COQ4 should be searched for in patients with CoQ10 deficiency and encephalomyopathy; patients with genomic rearrangements involving COQ4 should be screened for CoQ10 deficiency, as they could benefit from supplementation.

  • early Coenzyme Q10 supplementation in primary Coenzyme Q10 deficiency
    The New England Journal of Medicine, 2008
    Co-Authors: Giovanni Montini, Cristina Malaventura, Leonardo Salviati
    Abstract:

    To the Editor: Primary Coenzyme Q10 deficiency is considered to be the only treatable mitochondrial disorder, since patients have a response to oral Coenzyme Q10 supplementation. The disease usually manifests with nephropathy and encephalomyopathy.1 It has been shown that oral Coenzyme Q10 may stop the progression of encephalopathy, but no benefit from this therapy has been noted with respect to the evolution of renal disease associated with this deficiency.1,2 We now describe the results of long-term Coenzyme Q10 supplementation in two patients with Coenzyme Q10 deficiency caused by a homozygous missense mutation in the COQ2 gene.3,4 The clinical . . .

  • a mutation in para hydroxybenzoate polyprenyl transferase coq2 causes primary Coenzyme Q10 deficiency
    American Journal of Human Genetics, 2006
    Co-Authors: Catarina M Quinzii, Eva Trevisson, Plácido Navas, Ali Naini, Salvatore Dimauro, Leonardo Salviati, Michio Hirano
    Abstract:

    Ubiquinone (Coenzyme Q10 or CoQ10) is a lipid-soluble component of virtually all cell membranes, where it functions as a mobile electron and proton carrier. CoQ10 deficiency is inherited as an autosomal recessive trait and has been associated with three main clinical phenotypes: a predominantly myopathic form with central nervous system involvement, an infantile encephalomyopathy with renal dysfunction, and an ataxic form with cerebellar atrophy. In two siblings of consanguineous parents with the infantile form of CoQ10 deficiency, we identified a homozygous missense mutation in the COQ2 gene, which encodes para-hydroxybenzoate-polyprenyl transferase. The A→G transition at nucleotide 890 changes a highly conserved tyrosine to cysteine at amino acid 297 within a predicted transmembrane domain. Radioisotope assays confirmed a severe defect of CoQ10 biosynthesis in the fibroblasts of one patient. This mutation in COQ2 is the first molecular cause of primary CoQ10 deficiency.

Michio Hirano - One of the best experts on this subject based on the ideXlab platform.

  • the coq2 genotype predicts the severity of Coenzyme Q10 deficiency
    Human Molecular Genetics, 2016
    Co-Authors: Maria Andrea Desbats, Michio Hirano, Mara Doimo, Matteo Cassina, Valeria Morbidoni, Micol Silicbenussi, Vincenzo Ciminale, Sabrina Sacconi, Giuseppe Asso, Fabie Pierrel
    Abstract:

    COQ2 (p-hydroxybenzoate polyprenyl transferase) encodes the enzyme required for the second step of the final reaction sequence of Coenzyme Q10 (CoQ) biosynthesis. Its mutations represent a frequent cause of primary CoQ deficiency and have been associated with the widest clinical spectrum, ranging from fatal neonatal multisystemic disease to late-onset encephalopathy. However, the reasons of this variability are still unknown.We have characterized the structure of human COQ2, defined its subcellular localization and developed a yeast model to validate all the mutant alleles reported so far.Our findings show that the main functional transcript of COQ2 is shorter than what was previously reported and that its protein product localizes to mitochondria with the C-terminus facing the intermembrane space. Complementation experiments in yeast showed that the residual activity of the mutant proteins correlates with the clinical phenotypes observed in patients.We defined the structure of COQ2 with relevant implications for mutation screening in patients and demonstrated that, contrary to other COQ gene defects such as ADCK3, there is a correlation between COQ2 genotype and patient's phenotype.

  • 176th enmc international workshop diagnosis and treatment of Coenzyme Q10 deficiency
    Neuromuscular Disorders, 2012
    Co-Authors: Shamima Rahma, Catherine F Clarke, Michio Hirano
    Abstract:

    An ENMC meeting was held in Naarden, the Netherlands (July 9–11th 2010) with 12 clinical and basic scientists and 3 industrial representatives from Europe (France, Belgium, Germany, Italy, Spain, Switzerland, the Netherlands and the UK) and the USA, to discuss their collective experience with the molecular underpinnings, diagnosis, and management of patients with deficiency of Coenzyme Q10 (CoQ10). CoQ10, also known as ubiquinone, is a unique electron carrier [1]. It is essential for aerobic organisms because of its role in mitochondrial energy production as a chaperone of electrons from complexes I and II (and also from the electron transfer flavoproteins, ETF) to complex III of the respiratory chain. In addition, this lipophilic molecule has numerous other vital functions in cells that include: serving as antioxidant in both lipoproteins and cell membranes; connecting energy production with important cellular pathways such as the cell cycle and DNA replication and repair through its role in pyrimidine biosynthesis; modulation of apoptosis through its regulation of the transition pore; and maintenance of body temperature via its action on uncoupling proteins. The aims of this workshop were: to define how to clinically recognise and diagnose patients with CoQ10 deficiency; to optimize strategies to identify the underlying molecular genetic defects; to review basic CoQ10 biology; and to delineate therapeutic options for this group of disorders, which represent the most readily treatable subset of mitochondrial diseases.

  • a nonsense mutation in coq9 causes autosomal recessive neonatal onset primary Coenzyme Q10 deficiency a potentially treatable form of mitochondrial disease
    American Journal of Human Genetics, 2009
    Co-Authors: Andrew J Duncan, Catarina M Quinzii, Michio Hirano, Maria Bitnerglindzicz, Brigitte Meunier, Harry Costello, Iain P Hargreaves, Luis C Lopez, Michael I Sadowski, John Hardy
    Abstract:

    Coenzyme Q10 is a mobile lipophilic electron carrier located in the inner mitochondrial membrane. Defects of Coenzyme Q10 biosynthesis represent one of the few treatable mitochondrial diseases. We genotyped a patient with primary Coenzyme Q10 deficiency who presented with neonatal lactic acidosis and later developed multisytem disease including intractable seizures, global developmental delay, hypertrophic cardiomyopathy, and renal tubular dysfunction. Cultured skin fibroblasts from the patient had a Coenzyme Q10 biosynthetic rate of 11% of normal controls and accumulated an abnormal metabolite that we believe to be a biosynthetic intermediate. In view of the rarity of Coenzyme Q10 deficiency, we hypothesized that the disease-causing gene might lie in a region of ancestral homozygosity by descent. Data from an Illumina HumanHap550 array were analyzed with BeadStudio software. Sixteen regions of homozygosity >1.5 Mb were identified in the affected infant. Two of these regions included the loci of two of 16 candidate genes implicated in human Coenzyme Q10 biosynthesis. Sequence analysis demonstrated a homozygous stop mutation affecting a highly conserved residue of COQ9, leading to the truncation of 75 amino acids. Site-directed mutagenesis targeting the equivalent residue in the yeast Saccharomyces cerevisiae abolished respiratory growth.

  • human Coenzyme Q10 deficiency
    Neurochemical Research, 2007
    Co-Authors: Catarina M Quinzii, Salvatore Dimauro, Michio Hirano
    Abstract:

    Ubiquinone (Coenzyme Q10 or CoQ10) is a lipid-soluble component of virtually all cell membranes and has multiple metabolic functions. Deficiency of CoQ10 (MIM 607426) has been associated with five different clinical presentations that suggest genetic heterogeneity, which may be related to the multiple steps in CoQ10 biosynthesis. Patients with all forms of CoQ10 deficiency have shown clinical improvements after initiating oral CoQ10 supplementation. Thus, early diagnosis is of critical importance in the management of these patients. This year, the first molecular defect causing the infantile form of primary human CoQ10 deficiency has been reported. The availability of genetic testing will allow for a better understanding of the pathogenesis of this disease and early initiation of therapy (even presymptomatically in siblings of patients) in this otherwise life-threatening infantile encephalomyopathy.

  • a mutation in para hydroxybenzoate polyprenyl transferase coq2 causes primary Coenzyme Q10 deficiency
    American Journal of Human Genetics, 2006
    Co-Authors: Catarina M Quinzii, Eva Trevisson, Plácido Navas, Ali Naini, Salvatore Dimauro, Leonardo Salviati, Michio Hirano
    Abstract:

    Ubiquinone (Coenzyme Q10 or CoQ10) is a lipid-soluble component of virtually all cell membranes, where it functions as a mobile electron and proton carrier. CoQ10 deficiency is inherited as an autosomal recessive trait and has been associated with three main clinical phenotypes: a predominantly myopathic form with central nervous system involvement, an infantile encephalomyopathy with renal dysfunction, and an ataxic form with cerebellar atrophy. In two siblings of consanguineous parents with the infantile form of CoQ10 deficiency, we identified a homozygous missense mutation in the COQ2 gene, which encodes para-hydroxybenzoate-polyprenyl transferase. The A→G transition at nucleotide 890 changes a highly conserved tyrosine to cysteine at amino acid 297 within a predicted transmembrane domain. Radioisotope assays confirmed a severe defect of CoQ10 biosynthesis in the fibroblasts of one patient. This mutation in COQ2 is the first molecular cause of primary CoQ10 deficiency.

Paul D Thompso - One of the best experts on this subject based on the ideXlab platform.

  • a randomized trial of Coenzyme Q10 in patients with confirmed statin myopathy
    Atherosclerosis, 2015
    Co-Authors: Eth A Taylo, Lindsay Lorso, Michael C White, Paul D Thompso
    Abstract:

    Abstract Background : Coenzyme Q10 (CoQ10) supplementation is the most popular therapy for statin myalgia among both physicians and patients despite limited and conflicting evidence of its efficacy. Objective : This study examined the effect of Coenzyme Q10 (CoQ10) supplementation on simvastatin-associated muscle pain, muscle strength and aerobic performance in patients with confirmed statin myalgia. Methods : Statin myalgia was confirmed in 120 patients with prior symptoms of statin myalgia using an 8-week randomized, double-blind crossover trial of simvastatin 20 mg/d and placebo. Forty-one subjects developed muscle pain with simvastatin but not with placebo and were randomized to simvastatin 20 mg/d combined with CoQ10 (600 mg/d ubiquinol) or placebo for 8 weeks. Muscle pain (Brief Pain Inventory [BPI]), time to pain onset, arm and leg muscle strength, and maximal oxygen uptake (VO2max) were measured before and after each treatment. Results : Serum CoQ10 increased from 1.3 ± 0.4 to 5.2 ± 2.3 mcg/mL with simvastatin and CoQ10, but did not increase with simvastatin and placebo (1.3 ± 0.3 to 0.8 ± 0.2) ( p p p  = 0.53 and 0.56). There were no changes in muscle strength or VO2max with simvastatin with or without CoQ10 (all p  > 0.10). Marginally more subjects reported pain with CoQ10 (14 of 20 vs 7 of 18; p  = 0.05). There was no difference in time to pain onset in the CoQ10 (3.0 ± 2.0 weeks) vs. placebo (2.4 ± 2.1 wks) groups ( p  = 0.55). A similar lack of CoQ10 effect was observed in 24 subjects who were then crossed over to the alternative treatment. Conclusions : Only 36% of patients complaining of statin myalgia develop symptoms during a randomized, double-blind crossover of statin vs placebo. CoQ10 supplementation does not reduce muscle pain in patients with statin myalgia. Trial Registration NCT01140308; www.clinicaltrials.gov.

  • the role of Coenzyme Q10 in statin associated myopathy a systematic review
    Journal of the American College of Cardiology, 2007
    Co-Authors: Leo Marcoff, Paul D Thompso
    Abstract:

    Statins (3-hydroxy-3-methylglutaryl Coenzyme A reductase inhibitors) are currently the most effective medications for reducing low-density lipoprotein cholesterol concentrations. Although generally safe, they have been associated with a variety of myopathic complaints. Statins block production of farnesyl pyrophosphate, an intermediate in the synthesis of ubiquinone or Coenzyme Q10 (CoQ10). This fact, plus the role of CoQ10 in mitochondrial energy production, has prompted the hypothesis that statin-induced CoQ10 deficiency is involved in the pathogenesis of statin myopathy. We identified English language articles relating statin treatment and CoQ10 levels via a PubMed search through August 2006. Abstracts were reviewed and articles addressing the relationship between statin treatment and CoQ10 levels were examined in detail. Statin treatment reduces circulating levels of CoQ10. The effect of statin therapy on intramuscular levels of CoQ10 is not clear, and data on intramuscular CoQ10 levels in symptomatic patients with statin-associated myopathy are scarce. Mitochondrial function may be impaired by statin therapy, and this effect may be exacerbated by exercise. Supplementation can raise the circulating levels of CoQ10, but data on the effect of CoQ10 supplementation on myopathic symptoms are scarce and contradictory. We conclude that there is insufficient evidence to prove the etiologic role of CoQ10 deficiency in statin-associated myopathy and that large, well-designed clinical trials are required to address this issue. The routine use of CoQ10 cannot be recommended in statin-treated patients. Nevertheless, there are no known risks to this supplement and there is some anecdotal and preliminary trial evidence of its effectiveness. Consequently, CoQ10 can be tested in patients requiring statin treatment, who develop statin myalgia, and who cannot be satisfactorily treated with other agents. Some patients may respond, if only via a placebo effect.

Salvatore Dimauro - One of the best experts on this subject based on the ideXlab platform.

  • human Coenzyme Q10 deficiency
    Neurochemical Research, 2007
    Co-Authors: Catarina M Quinzii, Salvatore Dimauro, Michio Hirano
    Abstract:

    Ubiquinone (Coenzyme Q10 or CoQ10) is a lipid-soluble component of virtually all cell membranes and has multiple metabolic functions. Deficiency of CoQ10 (MIM 607426) has been associated with five different clinical presentations that suggest genetic heterogeneity, which may be related to the multiple steps in CoQ10 biosynthesis. Patients with all forms of CoQ10 deficiency have shown clinical improvements after initiating oral CoQ10 supplementation. Thus, early diagnosis is of critical importance in the management of these patients. This year, the first molecular defect causing the infantile form of primary human CoQ10 deficiency has been reported. The availability of genetic testing will allow for a better understanding of the pathogenesis of this disease and early initiation of therapy (even presymptomatically in siblings of patients) in this otherwise life-threatening infantile encephalomyopathy.

  • a mutation in para hydroxybenzoate polyprenyl transferase coq2 causes primary Coenzyme Q10 deficiency
    American Journal of Human Genetics, 2006
    Co-Authors: Catarina M Quinzii, Eva Trevisson, Plácido Navas, Ali Naini, Salvatore Dimauro, Leonardo Salviati, Michio Hirano
    Abstract:

    Ubiquinone (Coenzyme Q10 or CoQ10) is a lipid-soluble component of virtually all cell membranes, where it functions as a mobile electron and proton carrier. CoQ10 deficiency is inherited as an autosomal recessive trait and has been associated with three main clinical phenotypes: a predominantly myopathic form with central nervous system involvement, an infantile encephalomyopathy with renal dysfunction, and an ataxic form with cerebellar atrophy. In two siblings of consanguineous parents with the infantile form of CoQ10 deficiency, we identified a homozygous missense mutation in the COQ2 gene, which encodes para-hydroxybenzoate-polyprenyl transferase. The A→G transition at nucleotide 890 changes a highly conserved tyrosine to cysteine at amino acid 297 within a predicted transmembrane domain. Radioisotope assays confirmed a severe defect of CoQ10 biosynthesis in the fibroblasts of one patient. This mutation in COQ2 is the first molecular cause of primary CoQ10 deficiency.

  • Coenzyme Q10 deficiency and isolated myopathy
    Neurology, 2006
    Co-Authors: Rita Horvath, Klaus Gempel, Ali Naini, Pete Schneidera, Enedik Schose, E Neuenjacob, H Ploge, J Mullerhocke, D Pongratz, Salvatore Dimauro
    Abstract:

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

  • muscle Coenzyme Q10 level in statin related myopathy
    JAMA Neurology, 2005
    Co-Authors: Costanza Lamperti, Ali Naini, Petra Kaufma, Valeria Lucchini, A Prelle, Nereo Esoli, Maurizio Moggio, M Sciacco, Salvatore Dimauro
    Abstract:

    Background Statin drugs (3-hydroxy-3-methylglutaryl Coenzyme A reductase inhibitors) reduce the level of cholesterol by inhibiting the synthesis of mevalonate, an intermediary in the cholesterol biosynthetic pathway. Use of statin drugs has been associated with a variety of skeletal muscle–related complaints. Coenzyme Q10(CoQ10), a component of the mitochondrial respiratory chain, is also synthesized from mevalonate, and decreased muscle CoQ10concentration may have a role in the pathogenesis of statin drug–related myopathy. Objectives To measure the CoQ10concentration and respiratory chain enzyme activities in muscle biopsy specimens from 18 patients with statin drug–related myopathy and to look for evidence of apoptosis using the TUNEL (terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling) assay. Design An open-labeled study of CoQ10concentration in muscle from patients with increased serum creatine kinase concentrations while receiving standard statin drug therapy. Setting Neuromuscular centers at 2 academic tertiary care hospitals. Results Muscle structure was essentially normal in 14 patients and showed evidence of mitochondrial dysfunction and nonspecific myopathic changes in 2 patients each. Muscle CoQ10concentration was not statistically different between patients and control subjects, but it was more than 2 SDs below the normal mean in 3 patients and more than 1 SD below normal in 7 patients. There was no TUNEL positivity in any patients. Conclusion These data suggest that statin drug–related myopathy is associated with a mild decrease in muscle CoQ10concentration, which does not cause histochemical or biochemical evidence of mitochondrial myopathy or morphologic evidence of apoptosis in most patients.

  • atorvastatin decreases the Coenzyme Q10 level in the blood of patients at risk for cardiovascular disease and stroke
    JAMA Neurology, 2004
    Co-Authors: Tatjana Rundek, Ali Naini, Ralph L Sacco, Kriste Coates, Salvatore Dimauro
    Abstract:

    Background: Statins (3-hydroxy-3-methylglutaryl Coenzyme A reductase inhibitors) are widely used for the treatment of hypercholesterolemia and coronary heart disease and for the prevention of stroke. There have been various adverse effects, most commonly affecting muscle and ranging from myalgia to rhabdomyolysis. These adverse effects may be due to a Coenzyme Q10 (CoQ10) deficiency because inhibition of cholesterol biosynthesis also inhibits the synthesis of CoQ10. Objective: To measure CoQ10 levels in blood from hypercholesterolemic subjects before and after exposure to atorvastatin calcium, 80 mg/d, for 14 and 30 days. Design: Prospective blinded study of the effects of shortterm exposure to atorvastatin on blood levels of CoQ10.

Gian Paolo Littarru - One of the best experts on this subject based on the ideXlab platform.

  • the effect of Coenzyme Q10 on morbidity and mortality in chronic heart failure results from q symbio a randomized double blind trial
    Jacc-Heart Failure, 2014
    Co-Authors: Svend Aage Mortense, Urba Alehage, Frankli L Rosenfeld, Adarsh Kuma, Pete Dolline, Krzysztof J Filipiak, Daniel Pella, Gunte Steure, Gian Paolo Littarru
    Abstract:

    Abstract Objectives This randomized controlled multicenter trial evaluated Coenzyme Q10 (CoQ10) as adjunctive treatment in chronic heart failure (HF). Background 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. Methods 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. Results 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). Conclusions 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 )

  • Coenzyme Q10 and statins biochemical and clinical implications
    Mitochondrion, 2007
    Co-Authors: Gian Paolo Littarru, Pete H Langsjoe
    Abstract:

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

  • Coenzyme Q10 and exercise training in chronic heart failure
    European Heart Journal, 2006
    Co-Authors: Romualdo Elardinelli, Andi Mucaj, Francesca Lacalaprice, Maridia Solenghi, Giovanna Seddaiu, Federica Principi, Luca Tiano, Gian Paolo Littarru
    Abstract:

    Aims There is evidence that plasma Coenzyme Q10 (CoQ10) levels decrease in patients with advanced chronic heart failure (CHF). However, it is not known whether oral CoQ10 supplementation may improve cardiocirculatory efficiency and endothelial function in patients with CHF. Methods and results 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 CoQ10 (100 mg tid), CoQ10 plus supervised exercise training (ET) (60% of peak VO2, five times a week), placebo, and placebo plus ET. Each phase lasted 4 weeks. Both peak VO2 and endothelium-dependent dilation of the brachial artery (EDDBA) improved significantly after CoQ10 and after ET as compared with placebo. CoQ10 main effect was: peak VO2+9%, EDDBA +38%, systolic wall thickening score index (SWTI) −12%; ET produced comparable effects. CoQ10 supplementation resulted in a four-fold increase in plasma CoQ10 level, whereas the combination with ET further increased it. No side effects were reported with CoQ10. Conclusions Oral CoQ10 improves functional capacity, endothelial function, and LV contractility in CHF without any side effects. The combination of CoQ10 and ET resulted in higher plasma CoQ10 levels and more pronounced effects on all the abovementioned parameters. However, significant synergistic effect of CoQ10 with ET was observed only for peak SWTI suggesting that ET amplifies the already described effect of CoQ10 on contractility of dysfunctional myocardium.

  • assay of Coenzyme Q10 in plasma by a single dilution step
    Analytical Biochemistry, 2002
    Co-Authors: Fabrizio Mosca, Daniele Fattorini, Stefano Ompadre, Gian Paolo Littarru
    Abstract:

    Abstract A new method is described for determining Coenzyme Q10 (CoQ10) in plasma. The method is based on oxidation of CoQ10 in the sample by treating it with para-benzoquinone followed by extraction with 1-propanol and direct injection into the HPLC apparatus. This method achieves a linear detector response for peak area measurements over the concentration range of 0.05–3.47 μM. Diode array analysis of the peak was consistent with CoQ10 spectrum. Supplementation of the samples with known amounts of CoQ10 yielded a quantitative recovery of 96–98.5%; the method showed a level of quantitation of 1.23 nmol per HPLC injection (200 μl of propanol extract containing 33.3 μl of plasma). A correlation of r = 0.99 (P