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•Coenzyme Q10 (CoQ10) preparations show high differences in bioavailability in humans.•Physiological unknown factors affect CoQ10 bioavailability in humans.•Composition of vehicle in CoQ10 preparations affects bioavailability in humans.•Addition of antioxidants to CoQ10 preparations can decrease bioavailability.•For each individual, best CoQ10 preparation must be empirically determined. Bioavailability of supplements with coenzyme Q10 (CoQ10) in humans seems to depend on the excipients of formulations and on physiological characteristics of the individuals. The aim of this study was to determine which factors presented in CoQ10 supplements affect the different response to CoQ10 in humans. We tested seven different supplement formulations containing 100 mg of CoQ10 in 14 young, healthy individuals. Bioavailability was measured as area under the curve of plasma CoQ10 levels over 48 h after ingestion of a single dose. Measurements were repeated in the same group of 14 volunteers in a double-blind crossover design with a minimum of 4 wk washout between intakes. Bioavailability of the formulations showed large differences that were statistically significant. The two best absorbable formulations were soft-gel capsules containing ubiquinone (oxidized CoQ10) or ubiquinol (reduced CoQ10). The matrix used to dissolve CoQ10 and the proportion and addition of preservatives such as vitamin C affected the bioavailability of CoQ10. Although control measurements documented that all formulations contained 100 mg of either CoQ10 or ubiquinol, some of the participants showed high and others lower capacity to reach high increase of CoQ10 in blood, indicating the participation of individual unknown physiological factors. This study highlights the importance of individually adapted selection of best formulations to reach the highest bioavailability of CoQ10 in humans.

The effect of diminished ovarian reserves after undergoing hysterectomies with bilateral salpingectomies is one of the health concerns among reproductive-age women with benign gynecological diseases. Coenzyme Q10 (CoQ10), an antioxidant, is crucial in mitochondrial energy production, improving oocyte quality and quantity. This study compares the benefit of a 14-d preoperative (CoQ10) v. placebo on ovarian reserve by measuring anti-Müllerian hormone (AMH) in women undergoing hysterectomy with bilateral salpingectomy. A double-blinded, randomised, placebo-controlled trial was conducted. Forty-four women with benign gynecological diseases were randomised to receive either oral CoQ10 300 mg per d or placebo for 14 d before undergoing hysterectomy with bilateral salpingectomy. Serum AMH levels were collected for analysis before taking CoQ10 and 6 weeks postoperatively in each group. The baseline demographic, clinical characteristics and baseline AMH levels were comparable between the groups (1·47 (0·45, 2·49) v. 1·29 (0·47, 2·11), P = 0·763). The serum AMH levels after the surgery were significantly decreased from preoperative levels (median 0·99 (0·37, 1·63) v. 1·34 (0·57, 2·30)), P = 0·001. However, there was no significant difference in the AMH change between the CoQ10 group and the placebo group (AMH per cent change −28·2 % (64·09, −4·81) v. −20·07 % (–61·51, −2·92)), P = 0·99, respectively. Age, gynecological disease, operative time and blood loss were not significantly associated with the AMH change. There were no significant side effects or adverse operative outcomes among CoQ10 users. In conclusion, hysterectomy with bilateral salpingectomy led to a significantly decreased AMH level. However, pretreatment with CoQ10 for 2 weeks was ineffective in protecting an ovarian reserve.

Abstract Background Myalgia is a common adverse effect of statin therapy, but the underlying mechanism is unknown. Statins may reduce levels of coenzyme Q10 (CoQ10), which is an essential electron carrier in the mitochondrial electron transport system, thereby impairing mitochondrial respiratory function, potentially leading to myalgia. Objectives To investigate whether statin-induced myalgia is coupled to reduced intramuscular CoQ10 concentration and impaired mitochondrial respiratory function. Methods Patients receiving simvastatin (i.e., statin) therapy (n = 64) were recruited, of whom 25 experienced myalgia (myalgic group) and 39 had no symptoms of myalgia (NS group). Another 20 had untreated high blood cholesterol levels (control group). Blood and muscle samples were obtained. Intramuscular CoQ10 concentration was measured, and mitochondrial respiratory function and reactive oxygen species (ROS) production were measured. Citrate synthase (CS) activity was used as a biomarker of mitochondrial content in skeletal muscle. Results Intramuscular CoQ10 concentration was comparable among groups. Mitochondrial complex II–linked respiration was reduced in the statin-myalgic and -NS groups compared with the control group. When mitochondrial respiration was normalized to CS activity, respiration rate was higher in the myalgic group compared with the NS and control groups. Maximal ROS production was similar among groups. Conclusion Statin therapy appeared to impair mitochondrial complex-II–linked respiration, but the mitochondrial capacity for complex I+II–linked respiration remained intact. Myalgia was not coupled to reduced intramuscular CoQ10 levels. Intrinsic mitochondrial respiratory capacity was increased with statin-induced myalgia but not accompanied by increased ROS production. Mitochondrial respiratory capacity was assessed in skeletal muscle from statin-treated patients and complex II–linked respiration was reduced compared with that in well-matched control subjects.

The mitochondrial electron transport chain (ETC) is necessary for tumour growth 1 – 6 and its inhibition has demonstrated anti-tumour efficacy in combination with targeted therapies 7 – 9 . Furthermore, human brain and lung tumours display robust glucose oxidation by mitochondria 10 , 11 . However, it is unclear why a functional ETC is necessary for tumour growth in vivo. ETC function is coupled to the generation of ATP—that is, oxidative phosphorylation and the production of metabolites by the tricarboxylic acid (TCA) cycle. Mitochondrial complexes I and II donate electrons to ubiquinone, resulting in the generation of ubiquinol and the regeneration of the NAD+ and FAD cofactors, and complex III oxidizes ubiquinol back to ubiquinone, which also serves as an electron acceptor for dihydroorotate dehydrogenase (DHODH)—an enzyme necessary for de novo pyrimidine synthesis. Here we show impaired tumour growth in cancer cells that lack mitochondrial complex III. This phenotype was rescued by ectopic expression of Ciona intestinalis alternative oxidase (AOX) 12 , which also oxidizes ubiquinol to ubiquinone. Loss of mitochondrial complex I, II or DHODH diminished the tumour growth of AOX-expressing cancer cells deficient in mitochondrial complex III, which highlights the necessity of ubiquinone as an electron acceptor for tumour growth. Cancer cells that lack mitochondrial complex III but can regenerate NAD+ by expression of the NADH oxidase from Lactobacillus brevis ( Lb NOX) 13 targeted to the mitochondria or cytosol were still unable to grow tumours. This suggests that regeneration of NAD+ is not sufficient to drive tumour growth in vivo. Collectively, our findings indicate that tumour growth requires the ETC to oxidize ubiquinol, which is essential to drive the oxidative TCA cycle and DHODH activity. Oxidation of ubiquinol by the mitochondrial electron transfer chain drives tumour growth by maintaining the function of the oxidative Krebs cycle and de novo pyrimidine synthesis.

The purpose of this study was to investigate the effects of coenzyme Q10 supplementation on inflammatory markers (high-sensitivity C-reactive protein [hs-CRP], interleukin-6 [IL-6], and homocysteine) in patients with coronary artery disease (CAD). Patients with CAD (n = 51) were randomly assigned to a placebo group (n = 14) or one of two coenzyme Q10-supplemented groups (60 mg/d, Q10-60 group, n = 19; 150 mg/d, Q10-150 group, n = 18). The intervention was administered for 12 wk. Plasma coenzyme Q10 concentration, inflammatory markers (hs-CRP, IL-6, and homocysteine), malondialdehyde, and superoxide dismutase activities were measured. Forty subjects with CAD completed the intervention study. The plasma coenzyme Q10 concentration increased significantly in the Q10-60 and Q10-150 groups (P < 0.01). After 12 wk of intervention, the inflammatory marker IL-6 (P = 0.03) was decreased significantly in the Q10-150 group. Subjects in the Q10-150 group had significantly lower malondialdehyde levels and those in the Q10-60 (P = 0.05) and Q10-150 (P = 0.06) groups had greater superoxide dismutase activities. Plasma coenzyme Q10 was inversely correlated with hs-CRP (r = −0.20, P = 0.07) and IL-6 (r = −0.25, P = 0.03) at baseline. After supplementation, plasma coenzyme Q10 was significantly correlated with malondialdehyde (r = −0.35, P < 0.01) and superoxide dismutase activities (r = 0.52, P < 0.01). However, there was no correlation between coenzyme Q10 and homocysteine. Coenzyme Q10 supplementation at a dosage of 150 mg appears to decrease the inflammatory marker IL-6 in patients with CAD.

Coenzyme Q10 (CoQ10) plays a central role in mitochondrial oxidative phosphorylation. Several studies have shown the beneficial effects of dietary CoQ10 supplementation, particularly in relation to cardiovascular health. CoQ10 biosynthesis decreases in the elderly, and consequently, the beneficial effects of dietary supplementation in this population are of greater significance. However, most pharmacokinetic studies have been conducted on younger populations. The aim of this study was to investigate the single-dose bioavailability of different formulations of CoQ10 in a healthy geriatric population. A randomized, three-period, crossover bioavailability study was conducted on 21 healthy older adults (aged 65–74). The treatment was a single dose with a one-week washout period. Three different formulations containing the equivalent of 100 mg of CoQ10 were used: Q10Vital® water-soluble CoQ10 syrup (the investigational product—IP); ubiquinol capsules (the comparative product—CP); and ubiquinone capsules (the standard product—SP). Ubiquinone/ubiquinol was followed in the plasma for 48 h. An analysis of the ratio of the area under the baseline-corrected concentration curve (ΔAUC48) for total CoQ10 and a comparison to SP yielded the following: The bioavailability of CoQ10 in the IP was 2.4-fold higher (95% CI: 1.3–4.5; p = 0.002), while the bioavailability of ubiquinol (CP) was not significantly increased (1.7-fold; 95% CI: 0.9–3.1, p = 0.129). No differences in the redox status of the absorbed coenzyme Q10 were observed between formulations, showing that CoQ10 appeared in the blood mostly as ubiquinol, even if consumed as ubiquinone.

•Biological functions of high-density lipoprotein (HDL) helped explain the cardioprotective effect of HDL beyond its quantitative plasma levels.•Coenzyme Q10 (CoQ10) improved HDL-mediated cholesterol efflux capacity and antiinflammatory properties of HDL in Chinese adults with dyslipidemia.•CoQ10 improved HDL-mediated cholesterol efflux capacity more significantly in older, female, or non-obese patients.•Improving the biological function of HDL is expected to open a new era for primary prevention of cardiovascular diseases. Coenzyme Q10 (CoQ10) had shown promising effects in improving the lipid and glycemic profile in dyslipidemic individuals in our previous work, but little is known about how it affects high-density lipoprotein (HDL) function in patients with dyslipidemia. The aim of this study was to explore the effects of CoQ10 supplementation on HDL function in people with dyslipidemia. A 24-wk, randomized, double-blind, placebo-controlled trial was conducted in 101 people with dyslipidemia. All patients were randomized into the CoQ10 group (120 mg/d, n = 51) or the placebo group (n = 50). High-density lipoprotein–mediated cholesterol efflux capacity (CEC), HDL inflammatory index (HII), and HDL intrinsic oxidation were measured at baseline, 12 wk, and 24 wk. CoQ10 supplementation for 24 wk significantly improved HDL-mediated CEC (mean change, 1.21±2.44 versus –0.12±2.94; P = 0.014) and reduced HII (mean change, –0.32±0.58 versus –0.05±0.49, P = 0.014) compared with placebo. However, there was no significant difference in the effect of CoQ10 on HDL intrinsic oxidation between the two groups after 24 wk (P = 0.290). A positive correlation was found between the changes in CEC and HDL cholesterol in the CoQ10 group (r, 0.30; P = 0.032). Furthermore, we also found that the improved HDL functions were more obvious in elderly, female, or non-obese individuals, which indicated a specific population that benefits most from CoQ10 intervention. This study suggested that supplementation of CoQ10 for 24 wk can significantly improve HDL-mediated CEC and antiinflammatory function of HDL in patients with dyslipidemia.

Complex I (NADH:ubiquinone oxidoreductase) uses the reducing potential of NADH to drive protons across the energy-transducing inner membrane and power oxidative phosphorylation in mammalian mitochondria. Recent cryo-EM analyses have produced near-complete models of all 45 subunits in the bovine, ovine and porcine complexes and have identified two states relevant to complex I in ischemia–reperfusion injury. Here, we describe the 3.3-Å structure of complex I from mouse heart mitochondria, a biomedically relevant model system, in the ‘active’ state. We reveal a nucleotide bound in subunit NDUFA10, a nucleoside kinase homolog, and define mechanistically critical elements in the mammalian enzyme. By comparisons with a 3.9-Å structure of the ‘deactive’ state and with known bacterial structures, we identify differences in helical geometry in the membrane domain that occur upon activation or that alter the positions of catalytically important charged residues. Our results demonstrate the capability of cryo-EM analyses to challenge and develop mechanistic models for mammalian complex I.

Respiratory complex I (NADH:ubiquinone oxidoreductase), one of the largest membrane-bound enzymes in mammalian cells, powers ATP synthesis by using the energy from electron transfer from NADH to ubiquinone-10 to drive protons across the energy-transducing mitochondrial inner membrane. Ubiquinone-10 is extremely hydrophobic, but in complex I the binding site for its redox-active quinone headgroup is ∼20 Å above the membrane surface. Structural data suggest it accesses the site by a narrow channel, long enough to accommodate almost all of its ∼50-Å isoprenoid chain. However, how ubiquinone/ubiquinol exchange occurs on catalytically relevant timescales, and whether binding/dissociation events are involved in coupling electron transfer to proton translocation, are unknown. Here, we use proteoliposomes containing complex I, together with a quinol oxidase, to determine the kinetics of complex I catalysis with ubiquinones of varying isoprenoid chain length, from 1 to 10 units. We interpret our results using structural data, which show the hydrophobic channel is interrupted by a highly charged region at isoprenoids 4–7. We demonstrate that ubiquinol-10 dissociation is not rate determining and deduce that ubiquinone-10 has both the highest binding affinity and the fastest binding rate. We propose that the charged region and chain directionality assist product dissociation, and that isoprenoid stepping ensures short transit times. These properties of the channel do not benefit the exhange of short-chain quinones, for which product dissociation may become rate limiting. Thus, we discuss how the long channel does not hinder catalysis under physiological conditions and the possible roles of ubiquinone/ubiquinol binding/dissociation in energy conversion.

Friedreich ataxia (FRDA) is commonly associated with hypertrophic cardiomyopathy, but little is known about its frequency, severity, or treatment. In this 6-month randomized, double-blind, controlled study, we sought to determine whether idebenone improves cardiac measures in FRDA. Seventy pediatric subjects were treated either with idebenone (450/900 mg/d or 1,350/2,250 mg/d) or with placebo. Electrocardiograms (ECGs) were assessed at each visit, and echocardiograms, at baseline and week 24. We found ECG abnormalities in 90% of the subjects. On echocardiogram, 81.4% of the total cohort had left ventricular (LV) hypertrophy, as measured by increased LV mass index–Dubois, and the mean ejection fraction (EF) was 56.9%. In linear regression models, longer PR intervals at baseline were marginally associated with longer GAA repeat length (P = .011). Similarly, GAA repeat length did not clearly predict baseline EF (P = .086) and LV mass by M-mode (P = .045). Left ventricular mass index, posterior wall thickness, EF, and ECG parameters were not significantly improved by treatment with idebenone. Some changes in echocardiographic parameters during the treatment phase correlated with baseline status but not with treatment group. Idebenone did not decrease LV hypertrophy or improve cardiac function in subjects with FRDA. The present study does not provide evidence of benefit in this cohort over a 6-month treatment period.