CoQ10 deficiency diseases in adults

Deficiency of Coenzyme Q₁₀ (CoQ₁₀) in muscle has been associated with a spectrum of diseases including infantile-onset multi-systemic diseases, encephalomyopathies with recurrent myobinuria, cerebellar ataxia, and pure myopathy. CoQ₁₀ deficiency predominantly affects children, but patients have presented with adult-onset cerebellar ataxia or myopathy. Mutations in the CoQ10 biosynthetic genes, COQ2 and PDSS2, have been identified in children with the infantile form of CoQ₁₀ deficiency; however, the molecular genetic bases of adult-onset CoQ₁₀ deficiency remains undefined.     

Infantile and pediatric quinone deficiency diseases

Coenzyme Q₁₀ (CoQ₁₀) plays a pivotal role in oxidative phosphorylation (OXPHOS) as it distributes electrons between the various dehydrogenases and the cytochrome segments of the respiratory chain. Primary coenzyme Q₁₀ deficiency is a rare, but possibly treatable, autosomal recessive condition with four major clinical presentations, an encephalomyopathic form, a generalized infantile variant with severe encephalopathy and renal disease, a myopathic form and an ataxic form. The diagnosis of ubiquinone deficiency is supported by respiratory chain analysis and eventually by the quantification of CoQ₁₀ in patient tissues. We review here the infantile and pediatric quinone deficiency diseases as well as the clinical improvement after oral CoQ₁₀ therapy. The clinical heterogeneity of ubiquinone deficiency is suggestive of a genetic heterogeneity that should be related to the large number of enzymes, and corresponding genes, involved in ubiquinone biosynthesis.     

Intracellular cholesterol accumulation and coenzyme Q10 deficiency in Familial Hypercholesterolemia

Familial Hypercholesterolemia (FH) is an autosomal co-dominant genetic disorder characterized by elevated low-density lipoprotein (LDL) cholesterol levels and increased risk for premature cardiovascular disease. Here, we examined FH pathophysiology in skin fibroblasts derived from FH patients harboring heterozygous mutations in the LDL-receptor.Fibroblasts from FH patients showed a reduced LDL-uptake associated with increased intracellular cholesterol levels and coenzyme Q₁₀ (CoQ₁₀) deficiency, suggesting dysregulation of the mevalonate pathway.Secondary CoQ₁₀ deficiency was associated with mitochondrial depolarization and mitophagy activation in FH fibroblasts. Persistent mitophagy altered autophagy flux and induced inflammasome activation accompanied by increased production of cytokines by mutant cells. All the pathological alterations in FH fibroblasts were also reproduced in a human endothelial cell line by LDL-receptor gene silencing.Both increased intracellular cholesterol and mitochondrial dysfunction in FH fibroblasts were partially restored by CoQ₁₀ supplementation. Dysregulated mevalonate pathway in FH, including increased expression of cholesterogenic enzymes and decreased expression of CoQ₁₀ biosynthetic enzymes, was also corrected by CoQ₁₀ treatment.Reduced CoQ₁₀ content and mitochondrial dysfunction may play an important role in the pathophysiology of early atherosclerosis in FH. The diagnosis of CoQ₁₀ deficiency and mitochondrial impairment in FH patients may also be important to establish early treatment with CoQ₁₀.     

Pediatric reference intervals for muscle coenzyme Q10

Coenzyme Q₁₀ (CoQ₁₀) is present in humans in both the reduced (ubiquinol, CoQ₁₀H₂) and oxidized (ubiquinone, CoQ₁₀) forms. CoQ₁₀ is an essential cofactor in mitochondrial oxidative phosphorylation, and is necessary for ATP production. Total, reduced and oxidized CoQ₁₀ levels in skeletal muscle of 148 children were determined by HPLC coupled with electrochemical detection, and we established three level thresholds for total CoQ₁₀ in muscle. We defined as “severe deficiency”, CoQ₁₀ levels falling in the range between 0.82 and 4.88 μmol/g tissue; as “intermediate deficiency”, those ranging between 5.40 and 9.80 μmol/g tissue, and as “mild deficiency”, the amount of CoQ₁₀ included between 10.21 and 19.10 μmol/g tissue. Early identification of CoQ₁₀ deficiency has important implications in children, not only for those with primary CoQ₁₀ defect, but also for patients with neurodegenerative disorders, in order to encourage earlier supplementation with this agent also in mild and intermediate deficiency.     

Coenzyme Q10 in phenylketonuria and mevalonic aciduria

Mevalonic aciduria (MVA) and phenylketonuria (PKU) are inborn errors of metabolism caused by deficiencies in the enzymes mevalonate kinase and phenylalanine 4-hydroxylase, respectively. Despite numerous studies the factors responsible for the pathogenicity of these disorders remain to be fully characterised. In common with MVA, a deficit in coenzyme Q₁₀ (CoQ₁₀) concentration has been implicated in the pathophysiology of PKU. In MVA the decrease in CoQ₁₀ concentration may be attributed to a deficiency in mevalonate kinase, an enzyme common to both CoQ₁₀ and cholesterol synthesis. However, although dietary sources of cholesterol cannot be excluded, the low/normal cholesterol levels in MVA patients suggests that some other factor may also be contributing to the decrease in CoQ₁₀.The main factor associated with the low CoQ₁₀ level of PKU patients is purported to be the elevated phenylalanine level. Phenylalanine has been shown to inhibit the activities of both 3-hydroxy-3-methylglutaryl-CoA reductase and mevalonate-5-pyrophosphate decarboxylase, enzymes common to both cholesterol and CoQ₁₀ biosynthesis.Although evidence of a lowered plasma/serum CoQ₁₀ level has been reported in MVA and PKU, few studies have assessed the intracellular CoQ₁₀ concentration of patients. Plasma/serum CoQ₁₀ is influenced by dietary intake as well as its lipoprotein content and therefore may be limited as a means of assessing intracellular CoQ₁₀ concentration. Whether the pathogenesis of MVA and PKU are related to a loss of CoQ₁₀ has yet to be established and further studies are required to assess the intracellular CoQ₁₀ concentration of patients before this relationship can be confirmed or refuted.     

Ubiquinol-10 ameliorates mitochondrial encephalopathy associated with CoQ deficiency

Coenzyme Q10 (CoQ₁₀) deficiency (MIM 607426) causes a mitochondrial syndrome with variability in the clinical presentations. Patients with CoQ₁₀ deficiency show inconsistent responses to oral ubiquinone-10 supplementation, with the highest percentage of unsuccessful results in patients with neurological symptoms (encephalopathy, cerebellar ataxia or multisystemic disease). Failure in the ubiquinone-10 treatment may be the result of its poor absorption and bioavailability, which may be improved by using different pharmacological formulations. In a mouse model (Coq9^X/X) of mitochondrial encephalopathy due to CoQ deficiency, we have evaluated oral supplementation with water-soluble formulations of reduced (ubiquinol-10) and oxidized (ubiquinone-10) forms of CoQ₁₀. Our results show that CoQ₁₀ was increased in all tissues after supplementation with ubiquinone-10 or ubiquinol-10, with the tissue levels of CoQ₁₀ with ubiquinol-10 being higher than with ubiquinone-10. Moreover, only ubiquinol-10 was able to increase the levels of CoQ₁₀ in mitochondria from cerebrum of Coq9^X/X mice. Consequently, ubiquinol-10 was more efficient than ubiquinone-10 in increasing the animal body weight and CoQ-dependent respiratory chain complex activities, and reducing the vacuolization, astrogliosis and oxidative damage in diencephalon, septum–striatum and, to a lesser extent, in brainstem. These results suggest that water-soluble formulations of ubiquinol-10 may improve the efficacy of CoQ₁₀ therapy in primary and secondary CoQ₁₀ deficiencies, other mitochondrial diseases and neurodegenerative diseases.     

The evidence basis for coenzyme Q therapy in oxidative phosphorylation disease

The evidence supporting a treatment benefit for coenzyme Q₁₀ (CoQ₁₀) in primary mitochondrial disease (mitochondrial disease) whilst positive is limited. Mitochondrial disease in this context is defined as genetic disease causing an impairment in mitochondrial oxidative phosphorylation (OXPHOS). There are no treatment trials achieving the highest Level I evidence designation. Reasons for this include the relative rarity of mitochondrial disease, the heterogeneity of mitochondrial disease, the natural cofactor status and easy ‘over the counter availability’ of CoQ₁₀ all of which make funding for the necessary large blinded clinical trials unlikely. At this time the best evidence for efficacy comes from controlled trials in common cardiovascular and neurodegenerative diseases with mitochondrial and OXPHOS dysfunction the etiology of which is most likely multifactorial with environmental factors playing on a background of genetic predisposition. There remain questions about dosing, bioavailability, tissue penetration and intracellular distribution of orally administered CoQ₁₀, a compound which is endogenously produced within the mitochondria of all cells. In some mitochondrial diseases and other commoner disorders such as cardiac disease and Parkinson’s disease low mitochondrial or tissue levels of CoQ₁₀ have been demonstrated providing an obvious rationale for supplementation. This paper discusses the current state of the evidence supporting the use of CoQ₁₀ in mitochondrial disease.     

CoQ10 deficiencies and MNGIE: Two treatable mitochondrial disorders

Background

Although causative mutations have been identified for numerous mitochondrial disorders, few disease-modifying treatments are available. Two examples of treatable mitochondrial disorders are coenzyme Q₁₀ (CoQ₁₀ or ubiquinone) deficiency and mitochondrial neurogastrointestinal encephalomyopathy (MNGIE).

Scope of review

Here, we describe clinical and molecular features of CoQ₁₀ deficiencies and MNGIE and explain how understanding their pathomechanisms have led to rationale therapies. Primary CoQ₁₀ deficiencies, due to mutations in genes required for ubiquinone biosynthesis, and secondary deficiencies, caused by genetic defects not directly related to CoQ₁₀ biosynthesis, often improve with CoQ₁₀ supplementation. In vitro and in vivo studies of CoQ₁₀ deficiencies have revealed biochemical alterations that may account for phenotypic differences among patients and variable responses to therapy. In contrast to the heterogeneous CoQ₁₀ deficiencies, MNGIE is a single autosomal recessive disease due to mutations in the TYMP gene encoding thymidine phosphorylase (TP). In MNGIE, loss of TP activity causes toxic accumulations of the nucleosides thymidine and deoxyuridine that are incorporated by the mitochondrial pyrimidine salvage pathway and cause deoxynucleoside triphosphate pool imbalances, which, in turn cause mtDNA instability. Allogeneic hematopoetic stem cell transplantation to restore TP activity and eliminate toxic metabolites is a promising therapy for MNGIE.

Major conclusions

CoQ₁₀ deficiencies and MNGIE demonstrate the feasibility of treating specific mitochondrial disorders through replacement of deficient metabolites or via elimination of excessive toxic molecules.

General significance

Studies of CoQ₁₀ deficiencies and MNGIE illustrate how understanding the pathogenic mechanisms of mitochondrial diseases can lead to meaningful therapies. This article is part of a Special Issue entitled: Biochemistry of Mitochondria, Life and Intervention 2010.     

Treatment of CoQ10 Deficient Fibroblasts with Ubiquinone,CoQ Analogs,and Vitamin C: Time- and Compound-Dependent Effects

Background

Coenzyme Q₁₀ (CoQ₁₀) and its analogs are used therapeutically by virtue of their functions as electron carriers, antioxidant compounds, or both. However, published studies suggest that different ubiquinone analogs may produce divergent effects on oxidative phosphorylation and oxidative stress.

Methodology/Principal Findings

To test these concepts, we have evaluated the effects of CoQ₁₀, coenzyme Q₂ (CoQ₂), idebenone, and vitamin C on bioenergetics and oxidative stress in human skin fibroblasts with primary CoQ₁₀ deficiency. A final concentration of 5 µM of each compound was chosen to approximate the plasma concentration of CoQ₁₀ of patients treated with oral ubiquinone. CoQ₁₀ supplementation for one week but not for 24 hours doubled ATP levels and ATP/ADP ratio in CoQ₁₀ deficient fibroblasts therein normalizing the bioenergetics status of the cells. Other compounds did not affect cellular bioenergetics. In COQ2 mutant fibroblasts, increased superoxide anion production and oxidative stress-induced cell death were normalized by all supplements.

Conclusions/Significance

These results indicate that: 1) pharmacokinetics of CoQ₁₀ in reaching the mitochondrial respiratory chain is delayed; 2) short-tail ubiquinone analogs cannot replace CoQ₁₀ in the mitochondrial respiratory chain under conditions of CoQ₁₀ deficiency; and 3) oxidative stress and cell death can be counteracted by administration of lipophilic or hydrophilic antioxidants. The results of our in vitro experiments suggest that primary CoQ₁₀ deficiencies should be treated with CoQ₁₀ supplementation but not with short-tail ubiquinone analogs, such as idebenone or CoQ₂. Complementary administration of antioxidants with high bioavailability should be considered if oxidative stress is present.     

COQ4 Mutations Cause a Broad Spectrum of Mitochondrial Disorders Associated with CoQ10 Deficiency

Primary coenzyme Q10 (CoQ₁₀) deficiencies are rare, clinically heterogeneous disorders caused by mutations in several genes encoding proteins involved in CoQ₁₀ biosynthesis. CoQ₁₀ is an essential component of the electron transport chain (ETC), where it shuttles electrons from complex I or II to complex III. By whole-exome sequencing, we identified five individuals carrying biallelic mutations in COQ4. The precise function of human COQ4 is not known, but it seems to play a structural role in stabilizing a multiheteromeric complex that contains most of the CoQ₁₀ biosynthetic enzymes. The clinical phenotypes of the five subjects varied widely, but four had a prenatal or perinatal onset with early fatal outcome. Two unrelated individuals presented with severe hypotonia, bradycardia, respiratory insufficiency, and heart failure; two sisters showed antenatal cerebellar hypoplasia, neonatal respiratory-distress syndrome, and epileptic encephalopathy. The fifth subject had an early-onset but slowly progressive clinical course dominated by neurological deterioration with hardly any involvement of other organs. All available specimens from affected subjects showed reduced amounts of CoQ₁₀ and often displayed a decrease in CoQ₁₀-dependent ETC complex activities. The pathogenic role of all identified mutations was experimentally validated in a recombinant yeast model; oxidative growth, strongly impaired in strains lacking COQ4, was corrected by expression of human wild-type COQ4 cDNA but failed to be corrected by expression of COQ4 cDNAs with any of the mutations identified in affected subjects. COQ4 mutations are responsible for early-onset mitochondrial diseases with heterogeneous clinical presentations and associated with CoQ10 deficiency.     

Bioenergetic and Antioxidant Properties of Coenzyme Q<Subscript>10</Subscript>: Recent Developments

For a number of years, coenzyme Q (CoQ₁₀ in humans) was known for its key role in mitochondrial bioenergetics; later studies demonstrated its presence in other subcellular fractions and in plasma, and extensively investigated its antioxidant role. These two functions constitute the basis on which research supporting the clinical use of CoQ₁₀ is founded. Also at the inner mitochondrial membrane level, coenzyme Q is recognized as an obligatory co-factor for the function of uncoupling proteins and a modulator of the transition pore. Furthermore, recent data reveal that CoQ₁₀ affects expression of genes involved in human cell signalling, metabolism, and transport and some of the effects of exogenously administered CoQ₁₀ may be due to this property. Coenzyme Q is the only lipid soluble antioxidant synthesized endogenously. In its reduced form, CoQH₂, ubiquinol, inhibits protein and DNA oxidation but it is the effect on lipid peroxidation that has been most deeply studied. Ubiquinol inhibits the peroxidation of cell membrane lipids and also that of lipoprotein lipids present in the circulation. Dietary supplementation with CoQ₁₀ results in increased levels of ubiquinol-10 within circulating lipoproteins and increased resistance of human low-density lipoproteins to the initiation of lipid peroxidation. Moreover, CoQ₁₀ has a direct anti-atherogenic effect, which has been demonstrated in apolipoprotein E-deficient mice fed with a high-fat diet. In this model, supplementation with CoQ₁₀ at pharmacological doses was capable of decreasing the absolute concentration of lipid hydroperoxides in atherosclerotic lesions and of minimizing the size of atherosclerotic lesions in the whole aorta. Whether these protective effects are only due to the antioxidant properties of coenzyme Q remains to be established; recent data point out that CoQ₁₀ could have a direct effect on endothelial function. In patients with stable moderate CHF, oral CoQ₁₀ supplementation was shown to ameliorate cardiac contractility and endothelial dysfunction. Recent data from our laboratory showed a strong correlation between endothelium bound extra cellular SOD (ecSOD) and flow-dependent endothelial-mediated dilation, a functional parameter commonly used as a biomarker of vascular function. The study also highlighted that supplementation with CoQ₁₀ that significantly affects endothelium-bound ecSOD activity. Furthermore, we showed a significant correlation between increase in endothelial bound ecSOD activity and improvement in FMD after CoQ₁₀ supplementation. The effect was more pronounced in patients with low basal values of ecSOD. Finally, we summarize the findings, also from our laboratory, on the implications of CoQ₁₀ in seminal fluid integrity and sperm cell motility.     

Current state of coenzyme Q10 production and its applications

Coenzyme Q₁₀ (CoQ₁₀), an obligatory cofactor in the aerobic respiratory electron transfer for energy generation, is formed from the conjugation of a benzoquinone ring with a hydrophobic isoprenoid chain. CoQ₁₀ is now used as a nutritional supplement because of its antioxidant properties and is beneficial in the treatment of several human diseases when administered orally. Bioprocesses have been developed for the commercial production of CoQ₁₀ because of its increased demand, and these bioprocesses depend on microbes that produce high levels of CoQ₁₀ naturally. However, as knowledge of the biosynthetic enzymes and the regulatory mechanisms modulating CoQ₁₀ production increases, approaches arise for the genetic engineering of CoQ₁₀ production in Escherichia coli and Agrobacterium tumefaciens. This review focused on approaches for CoQ₁₀ production, strategies used to engineer CoQ₁₀ production in microbes, and potential applications of CoQ₁₀.     

Disruption of the human COQ5-containing protein complex is associated with diminished coenzyme Q10 levels under two different conditions of mitochondrial energy deficiency

BackgroundThe Coq protein complex assembled from several Coq proteins is critical for coenzyme Q₆ (CoQ₆) biosynthesis in yeast. Secondary CoQ₁₀ deficiency is associated with mitochondrial DNA (mtDNA) mutations in patients. We previously demonstrated that carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP) suppressed CoQ₁₀ levels and COQ5 protein maturation in human 143B cells.MethodsThis study explored the putative COQ protein complex in human cells through two-dimensional blue native-polyacrylamide gel electrophoresis and Western blotting to investigate its status in 143B cells after FCCP treatment and in cybrids harboring the mtDNA mutation that caused myoclonic epilepsy with ragged-red fibers (MERRF) syndrome. Ubiquinol-10 and ubiquinone-10 levels were detected by high-performance liquid chromatography. Mitochondrial energy status, mRNA levels of various PDSS and COQ genes, and protein levels of COQ5 and COQ9 in cybrids were examined.ResultsA high-molecular-weight protein complex containing COQ5, but not COQ9, in the mitochondria was identified and its level was suppressed by FCCP and in cybrids with MERRF mutation. That was associated with decreased mitochondrial membrane potential and mitochondrial ATP production. Total CoQ₁₀ levels were decreased under both conditions, but the ubiquinol-10:ubiquinone-10 ratio was increased in mutant cybrids. The expression of COQ5 was increased but COQ5 protein maturation was suppressed in the mutant cybrids.ConclusionsA novel COQ5-containing protein complex was discovered in human cells. Its destabilization was associated with reduced CoQ₁₀ levels and mitochondrial energy deficiency in human cells treated with FCCP or exhibiting MERRF mutation.General significanceThe findings elucidate a possible mechanism for mitochondrial dysfunction-induced CoQ₁₀ deficiency in human cells.     

Coenzyme Q10 and statins: Biochemical and clinical implications

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 Q treatment of neurodegenerative diseases of aging

The etiology of several neurodegenerative disorders is thought to involve impaired mitochondrial function and oxidative stress. Coenzyme Q-10 (CoQ₁₀) acts both as an antioxidant and as an electron acceptor at the level of the mitochondria. In several animal models of neurodegenerative diseases including amyotrophic lateral sclerosis, Huntington’s disease, and Parkinson’s disease, CoQ₁₀ has shown beneficial effects. Based on its biochemical properties and the effects in animal models, several clinical trials evaluating CoQ₁₀ have been undertaken in many neurodegenerative diseases. CoQ₁₀ appears to be safe and well tolerated, and several efficacy trials are planned.     

Design and implementation of the first randomized controlled trial of coenzyme Q10 in children with primary mitochondrial diseases

We report the design and implementation of the first phase 3 trial of CoenzymeQ₁₀ (CoQ₁₀) in children with genetic mitochondrial diseases. A novel, rigorous set of eligibility criteria was established. The trial, which remains open to recruitment, continues to address multiple challenges to the recruitment of patients, including widely condoned empiric use of CoQ₁₀ by individuals with proven or suspected mitochondrial disease and skepticism among professional and lay mitochondrial disease communities about participating in placebo-controlled trials. These attitudes represent significant barriers to the ethical and scientific evaluation – and ultimate approval – of nutritional and pharmacological therapies for patients with life-threatening inborn errors of energy metabolism.     

Update on the application of magnetic fields to microalgal cultures

Coenzyme Q₁₀ (CoQ₁₀) is the main CoQ species in human and is used extensively in food, cosmetic and medicine industries because of its antioxidant properties and its benefit in prophylactic medicine and therapy for a variety of diseases. Among various approaches to increase the production of CoQ₁₀, microbial fermentation is the most effective. As knowledge of the biosynthetic enzymes and regulatory mechanisms modulating CoQ₁₀ production increases, opportunities arise for metabolic engineering of CoQ₁₀ in microbial hosts. In this review, we present various strategies used up to date to improve CoQ₁₀ production and focus on metabolic engineering of CoQ₁₀ overproduction in microbes. General strategies of metabolic engineering include providing sufficient precursors for CoQ₁₀, increasing metabolic fluxes, and expanding storage capacity for CoQ₁₀. Based on these strategies, CoQ₁₀ production has been significantly improved in natural CoQ₁₀ producers, as well as in heterologous hosts.

     

Plasma coenzyme Q10 concentrations are not decreased in male patients with coronary atherosclerosis

Coenzyme Q₁₀ (CoQ₁₀) is an important mitochondrial electron transfer component and has been postulated to function as a powerful antioxidant protecting LDL from oxidative damage. It could thus reduce the risk of cardiovascular disease. Thus far, beneficial effects of supplementation with CoQ₁₀ have been reported. To study the relation between unsupplemented concentrations of plasma CoQ₁₀ and coronary atherosclerosis, we performed a case-control study among 71 male cases with angiographically documented severe coronary atherosclerosis and 69 healthy male controls free from symptomatic cardiovascular disease and without atherosclerotic plaques in the carotid artery.

Plasma CoQ₁₀ concentrations (mean ± SE) were 0.86 ± 0.04 vs. 0.83 ± 0.04 μmol/l for cases and controls, respectively. The CoQ₁₀/LDL-cholesterol ratio (μmol/mmol) was slightly lower in cases than in controls (0.22 ± 0.01 vs. 0.26 ± 0.03). Differences in CoQ₁₀ concentrations and CoQ₁₀/LDL-cholesterol ratio did not reach significance. The odds ratios (95% confidence interval) for the risk of coronary atherosclerosis calculated per μmol/l increase of CoQ₁₀ was 1.12 (0.28–4.43) after adjustment for age, smoking habits, total cholesterol and diastolic blood pressure.

We conclude that an unsupplemented plasma CoQ₁₀ concentration is not related to risk of coronary atherosclerosis.