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Background: Selenium-dependent deiodinases play a central role in thyroid hormone regulation and metabolism. In many European countries, insufficient selenium intake may consequently lead to adverse effects on thyroid function. In this randomised placebo-controlled double-blind study, we examined the effect of supplementation with selenium and coenzyme Q 10 on thyroid hormonal status, cardiovascular (CV) mortality and health-related quality of life (Hr-QoL)., Methods: Free T3, free T4, reverse T3, and TSH were determined in 414 individuals at baseline, and the effect of selenium yeast (200 µg/day) and coenzyme Q 10 (200 mg/day) supplementation on hormone concentrations, CV mortality and Hr-QoL was evaluated after 48 months using Short Form 36 (SF-36). Pre-intervention plasma selenium was low, mean 67 µg/L, corresponding to an estimated intake of 35 µg/day. Changes in concentrations of thyroid hormones following the intervention were assessed using T-tests, repeated measures of variance, and ANCOVA analyses., Results: In the total population, the group with the lowest selenium concentration at baseline presented with significantly higher levels of TSH and lower levels of fT3 as compared to subjects with the highest selenium concentration. Supplementation with selenium and coenzyme Q 10 for 4 years significantly increased fT3 and rT3, decreased fT4, and diminished the increase in TSH levels compared with placebo treatment (p = 0.03, all). In the placebo group, TSH and fT4 values above the median were associated with an increase in 10-year CV mortality, as compared with the mortality rate among those with TSH and fT4 below the median (p < 0.04, both), with no difference in mortality rate according to TSH and fT4 levels in the active intervention group. Similarly, TSH > median and fT3 < median were associated with a decline in mental Hr-QoL measures vs. TSH < and fT3 > median in the placebo group during 4 years of follow-up, but this was wiped out in the active group., Conclusions: Supplementation with selenium and coenzyme Q 10 had a beneficial effect on thyroid hormones with respect to CV mortality and Hr-QoL outcomes. The initial deficient selenium status was associated with an impaired thyroid function and the changes in thyroid hormone levels can be explained by increased activity of deiodinases. We conclude that a substantial part of the elderly study population might suffer from suboptimal thyroidal function with adverse clinical implications due to selenium deficiency., Trial Registration: This study was registered at ClinicalTrials.gov and has the identifier NCT01443780. Since it was not mandatory to register at the time the study began, the study has been registered retrospectively., (© 2024. The Author(s).)

Background: The protective effect of Coenzyme Q10 (CoQ10) on the cardiovascular system has been reported, however, whether it can promote early recovery of cardiac function and alleviate cardiac remodeling after myocardial infarction (MI) remains to be elucidated. Whether CoQ10 may regulate the macrophage-mediated pro-inflammatory response after MI and its potential mechanism are worth further exploration., Methods: To determine the baseline plasma levels of CoQ10 by LC-MS/MS, healthy controls and MI patients (n = 11 each) with age- and gender-matched were randomly enrolled. Additional MI patients were consecutively enrolled and randomized into the blank control (n = 59) or CoQ10 group (n = 61). Follow-ups were performed at 1- and 3-month to assess cardiac function after percutaneous coronary intervention (PCI). In the animal study, mice were orally administered CoQ10/vehicle daily and were subjected to left anterior descending coronary artery (LAD) ligation or sham operation. Echocardiography and serum BNP measured by ELISA were analyzed to evaluate cardiac function. Masson staining and WGA staining were performed to analyze the myocardial fibrosis and cardiomyocyte hypertrophy, respectively. Immunofluorescence staining was performed to assess the infiltration of IL1β/ROS-positive macrophages into the ischemic myocardium. Flow cytometry was employed to analyze the recruitment of myeloid immune cells to the ischemic myocardium post-MI. The expression of inflammatory indicators was assessed through RNA-seq, qPCR, and western blotting (WB)., Results: Compared to controls, MI patients showed a plasma deficiency of CoQ10 (0.76 ± 0.31 vs. 0.46 ± 0.10 µg/ml). CoQ10 supplementation significantly promoted the recovery of cardiac function in MI patients at 1 and 3 months after PCI. In mice study, compared to vehicle-treated MI mice, CoQ10-treated MI mice showed a favorable trend in survival rate (42.85% vs. 61.90%), as well as significantly alleviated cardiac dysfunction, myocardial fibrosis, and cardiac hypertrophy. Notably, CoQ10 administration significantly suppressed the recruitment of pro-inflammatory CCR2 + macrophages into infarct myocardium and their mediated inflammatory response, partially by attenuating the activation of the NLR family pyrin domain containing 3 (NLRP3)/Interleukin-1 beta (IL1β) signaling pathway., Conclusions: These findings suggest that CoQ10 can significantly promote early recovery of cardiac function after MI. CoQ10 may function by inhibiting the recruitment of CCR2 + macrophages and suppressing the activation of the NLRP3/IL1β pathway in macrophages., Trial Registration: Date of registration 09/04/2021 (number: ChiCTR2100045256)., (© 2024. The Author(s).)

Ubiquinol, the reduced form of Coenzyme Q 10 (CoQ 10 ), is a key factor in bioenergetics and antioxidant protection. During competition, professional soccer players suffer from considerable physical stress causing high risk of muscle damage. For athletes, supplementation with several antioxidants, including CoQ 10 , is widely recommended to avoid oxidative stress and muscle damage. We performed an observational study of plasma parameters associated with CoQ 10 levels in professional soccer players of the Spanish First League team Athletic Club de Bilbao over two consecutive seasons (n = 24-25) in order determine their relationship with damage, stress and performance during competition. We analyzed three different moments of the competition: preterm, initial phase and mid phase. Metabolites and factors related with stress (testosterone/cortisol) and muscle damage (creatine kinase) were determined. Physical activity during matches was analyzed over the 2015/16 season in those players participating in complete matches. In the mid phase of competition, CoQ 10 levels were higher in 2015/16 (906.8 ± 307.9 vs. 584.3 ± 196.3 pmol/mL, p = 0.0006) High levels of CoQ 10 in the hardest phase of competition were associated with a reduction in the levels of the muscle-damage marker creatine kinase (Pearsons' correlation coefficient (r) = - 0.460, p = 0.00168) and a trend for the stress marker cortisol (r = -0.252, p = 0.150). Plasma ubiquinol was also associated with better kidney function (r = -0.287, p = 0.0443 for uric acid). Furthermore, high CoQ 10 levels were associated with higher muscle performance during matches. Our results suggest that high levels of plasma CoQ 10 can prevent muscle damage, improve kidney function and are associated with higher performance in professional soccer players during competition.

Purpose: Familial hypercholesterolemia (FH) requires early treatment. However, statins, which are regarded the first-line therapy, have an influence on redox balance. Antioxidant vitamins are important for many metabolic processes in the developing body. There are few data available on the long-term safety of statin use in children. The aim of this study was to evaluate the influence of statin treatment in children with FH on plasma concentrations of antioxidant vitamins: retinol, alpha-tocopherol and coenzyme Q10., Methods: The first study group consisted of 13 children aged 10-18 years treated with simvastatin for at least 6 months, and the second group comprised 13 age- and sex-matched children with hypercholesterolemia, in whom pharmacological treatment had not been applied yet. Analyses were performed using a high-performance liquid chromatograph coupled with a MS detector., Results: The analysis did not reveal significant differences in the concentration of retinol, alpha-tocopherol or coenzyme Q10 between the studied groups. The adjustment of the concentrations of the vitamins to the cholesterol level also indicated no significant differences. We found no deficits in antioxidant vitamins in patients treated with statins, or any risk of adverse effects associated with an increase in their concentration., Conclusion: There is no rationale for additional supplementation using antioxidant vitamins or modification of low-fat and low-cholesterol diet in pediatric patients treated with statins., (© 2020. The Author(s).)

Improving the aqueous solubility of poorly soluble compounds have been a major issue in the pharmaceutical industry. In the present study, binary amorphous solid dispersions (SDs) of Coenzyme Q10 (CoQ 10 ), a biopharmaceutics classification system (BCS) II compound and Soluplus ® were prepared to enhance the solubility and pharmacokinetic properties compared to crystalline CoQ 10 . SDs were prepared with different ratios of CoQ 10 and Soluplus ® (1:3, 1:5, and 1:7) using spray drying technology, and the physicochemical properties of the SDs were evaluated. X-ray powder diffraction, differential scanning calorimetry, and scanning electron microscopy suggested the conversion of the crystalline form of CoQ 10 to a binary amorphous system in the SDs. Fourier transform infrared spectroscopy revealed no potential interactions between CoQ 10 and Soluplus ® . The solubility of the optimal SD formulation (SD 1:7) was approximately 9000-fold higher than that of crystalline CoQ 10, and the increment was Soluplus ® concentration dependent. As a result, optimized SD 1:7 also showed significantly enhanced dissolution rate where maximum drug release was observed within 30 min in two different dissolution media. Moreover, in contrast to crystalline CoQ 10, CoQ 10 SDs showed improved pharmacokinetic parameters. Thus, the SD 1:7 formulation is expected to improve biopharmaceutical properties and therapeutic efficacy of CoQ 10 ., (© 2022. The Pharmaceutical Society of Korea.)

Aim: Hereditary hemochromatosis (HH) is a group of inherited disorders that causes a slow and progressive iron deposition in diverse organs, particularly in the liver. Iron overload induces oxidative stress and tissue damage. Coenzyme Q10 (CoQ10) is a cofactor in the electron-transport chain of the mitochondria, but it is also a potent endogenous antioxidant. CoQ10 interest has recently grown since various studies show that CoQ10 supplementation may provide protective and safe benefits in mitochondrial diseases and oxidative stress disorders. In the present study we sought to determine CoQ10 plasma level in patients recently diagnosed with HH and to correlate it with biochemical, genetic, and histological features of the disease., Methods: Plasma levels of CoQ10, iron, ferritin, transferrin and vitamins (A, C and E), liver tests (transaminases, alkaline phosphatase and bilirubin), and histology, as well as three HFE gene mutations (H63D, S654C and C282Y), were assessed in thirty-eight patients (32 males, 6 females) newly diagnosed with HH without treatment and in twenty-five age-matched normolipidemic healthy subjects with no HFE gene mutations (22 males, 3 females) and without clinical or biochemical signs of iron overload or liver diseases., Results: Patients with HH showed a significant decrease in CoQ10 levels respect to control subjects (0.31 ± 0.03 µM vs 0.70 ± 0.06 µM, p < 0.001, respectively) independently of the genetic mutation, cirrhosis, transferrin saturation, ferritin level or markers of hepatic dysfunction. Although a decreasing trend in CoQ10 levels was observed in patients with elevated iron levels, no correlation was found between both parameters in patients with HH. Vitamins C and A levels showed no changes in HH patients. Vitamin E was significantly decreased in HH patients (21.1 ± 1.3 µM vs 29.9 ± 2.5 µM, p < 0.001, respectively), but no correlation was observed with CoQ10 levels., Conclusion: The decrease in CoQ10 levels found in HH patients suggests that CoQ10 supplementation could be a safe intervention strategy complementary to the traditional therapy to ameliorate oxidative stress and further tissue damage induced by iron overload., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Introduction and Objectives: Despite the growing interest and the potential benefits of idebenone as a repurposed drug for different orphan conditions, data regarding its monitoring are scarce. Our main goal was to report plasma idebenone values in a cohort of Friedreich's ataxia (FRDA) patients during a long-term follow-up. Taking advantage of this, we also assessed cardiological and neurological status together with idebenone values and genetic background., Methods: Long-term follow-up retrospective study in 27 FRDA patients with a disease onset at the paediatric age treated with idebenone by compassionate use. Plasma idebenone was measured by HPLC with electrochemical detection., Results: Median plasma idebenone values increased when doses were increased, but apparently linearity was lost in the highest dose group. Marked intraindividual and interindividual differences were observed among patients. We did not find a consistent positive effect after analysis of paired data at the beginning and the end of the study. We only found a correlation between some cardiological measures and the duration of idebenone therapy at high doses, but with uncertain significance., Conclusions: The large variations observed among the different individuals involved in this study should be considered for optimization of individual dosage regimens., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The aims of this study are to compare serum ubiquinone levels in children with attention deficit hyperactivity disorder (ADHD) with healthy controls and to investigate the correlation between ubiquinone levels of children with ADHD and their ADHD symptoms. Twenty-seven children who are 6-12 years old age with attention deficit hyperactivity disorder having clinically normal intelligence and 23 children with clinically normal intelligence and no psychiatric disorder of similar age and sex who referred to Ankara University School of Medicine Department of Child and Adolescent Psychiatry were included in this study. All children were diagnosed by same researcher using the Semi-Structured Clinical Interview for DSM-IV Scale for Affective Disorders and Schizophrenia Interview for School Children-Now and for the Life-Long Version (K-SADS-PL). Parents and teachers of the children completed the Conners Parent Rating Scale Revised Long Form (CPRS-LF) and Conners Teacher Rating Scale Revised Long Form (CTRS-LF). There were no statistically significant differences regarding the age, gender, and sociodemographic data of the groups. Serum ubiquinone levels of the ADHD group were significantly lower than the control group. We did not find any correlation between ubiquinone levels and clinical values. Since ubiquinone levels are lower in children with ADHD compared with controls, we suggest that decreased antioxidant levels may play a role in ADHD pathogenesis by disrupting oxidative balance., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Left ventricular remodelling that frequently occurs after acute myocardial infarction is associated with an increased risk of heart failure and cardiovascular death. Although several risk factors have been identified, there is still no marker in clinical use to predict left ventricular remodelling. Plasma concentration of coenzyme Q10, which plays a key role in mitochondrial energy production and as an antioxidant, seems to be negatively correlated with left ventricular function after acute myocardial infarction., Objective: The goal of our study was to determine whether the plasma coenzyme Q10 baseline concentrations at time of the ST-elevation myocardial infarction (STEMI) could predict left ventricular remodelling at six months' follow-up., Methods: Sixty-eight patients who were admitted to hospital for STEMI and successfully revascularized with primary percutaneous coronary intervention were recruited. All patients underwent a 3D-echocardiography examination within the first four days after percutaneous coronary intervention and six months later then divided into two groups based on the presence or not of left ventricular remodelling. Plasma coenzyme Q10 concentration at the time of percutaneous coronary intervention was determined using high-performance liquid chromatography-tandem mass spectrometry., Results: While we found similar plasma coenzyme Q10 concentrations compared with other studies, no association was evidenced between coenzyme Q10 concentrations and left ventricular remodelling ( P  = 0.89)., Conclusion: We found no evidence for using plasma coenzyme Q10 concentration as an early prediction marker of left ventricular remodelling after STEMI.

A low intake of selenium is associated with increased cardiovascular mortality. This could be reduced by supplementation with selenium and coenzyme Q 10 . D-dimer, a fragment of fibrin mirroring fibrinolysis, is a biomarker of thromboembolism, increased inflammation, endothelial dysfunction and is associated with cardiovascular mortality in ischemic heart disease. The objective was to examine the impact of selenium and coenzyme Q 10 on the level of D-dimer, and its relationship to cardiovascular mortality. D-dimer was measured in 213 individuals at the start and after 48 months of a randomised double-blind placebo-controlled trial with selenium yeast (200 µg/day) and coenzyme Q 10 (200 mg/day) ( n = 106) or placebo ( n = 107). The follow-up time was 4.9 years. All included individuals were low in selenium (mean 67 μg/L, SD 16.8). The differences in D-dimer concentration were evaluated by the use of T-tests, repeated measures of variance and ANCOVA analyses. At the end, a significantly lower D-dimer concentration was observed in the active treatment group in comparison with those on placebo ( p = 0.006). Although D-dimer values at baseline were weakly associated with high-sensitive CRP, while being more strongly associated with soluble tumour necrosis factor receptor 1 and sP-selectin, controlling for these in the analysis there was an independent effect on D-dimer. In participants with a D-dimer level above median at baseline, the supplementation resulted in significantly lower cardiovascular mortality compared to those on placebo ( p = 0.014). All results were validated with a persisting significant difference between the two groups. Therefore, supplementation with selenium and coenzyme Q 10 in a group of elderly low in selenium and coenzyme Q 10 prevented an increase in D-dimer and reduced the risk of cardiovascular mortality in comparison with the placebo group. The obtained results also illustrate important associations between inflammation, endothelial function and cardiovascular risk.

Background: The increased oxidative stress resulting from the inflammatory responses in sepsis initiates changes in mitochondrial function which may result in organ damage, the most common cause of death in the intensive care unit (ICU). Deficiency of coenzyme Q10 (CoQ10), a key cofactor in the mitochondrial respiratory chain, could potentially disturb mitochondrial bioenergetics and oxidative stress, and may serve as a biomarker of mitochondrial dysfunction. Hence, we aimed to investigate in initially non-septic patients whether CoQ10 levels are decreased in sepsis and septic shock compared to ICU admission, and to evaluate its associations with severity scores, inflammatory biomarkers, and ICU outcomes., Methods: Observational retrospective analysis on 86 mechanically-ventilated, initially non-septic, ICU patients. CoQ10 was sequentially measured on ICU admission, sepsis, septic shock or at ICU discharge. CoQ10 was additionally measured in 25 healthy controls. Inflammatory biomarkers were determined at baseline and sepsis., Results: On admission, ICU patients who developed sepsis had lower CoQ10 levels compared to healthy controls (0.89 vs. 1.04 µg/ml, p < 0.05), while at sepsis and septic shock CoQ10 levels decreased further (0.63 µg/ml; p < 0.001 and 0.42 µg/ml; p < 0.0001, respectively, from admission). In ICU patients who did not develop sepsis, admission CoQ10 levels were also lower than healthy subjects (0.81 µg/ml; p < 0.001) and were maintained at the same levels until discharge., Conclusion: CoQ10 levels in critically-ill patients are low on ICU admission compared to healthy controls and exhibit a further decrease in sepsis and septic shock. These results suggest that sepsis severity leads to CoQ10 depletion.

Coenzyme Q10 (CoQ10) plays a potential role in the prevention and treatment of cardiovascular disease through improved cellular bioenergetics. Critical illness in the intensive care unit has been reported to be associated with decreased circulating CoQ10 levels, and we previously demonstrated the association of low CoQ10 levels with in-hospital mortality. However, the association of CoQ10 with the acute phase of cardiovascular disease and long-term mortality remains unclear. We enrolled 242 consecutive patients with cardiovascular disease admitted to the coronary care unit of Juntendo University Hospital to investigate the association between long-term mortality and serum CoQ10 levels. During a mean follow-up of 3.2 years, 58 patients died. The mean serum CoQ10 levels were significantly lower in the non-survivors than in the survivors (0.48 ± 0.27 vs. 0.58 ± 0.38 mg/L; p = 0.035). Compared with the patients with above-median CoQ10 levels (0.46 mg/L), the cumulative incidence of all-cause mortality was significantly higher in those with lower CoQ10 levels (p = 0.025). Multivariate Cox regression analysis further demonstrated that lower CoQ10 levels were associated with poor prognosis. Low serum CoQ10 levels during the acute phase of cardiovascular diseases were associated with long-term mortality in patients, suggesting the utility of low serum CoQ10 levels as a predictor and potential therapeutic target.

Background: Coenzyme Q10 (CoQ10) is a ubiquitous molecule in living organisms serving as a cofactor in energy production. Epidemiological studies have reported low CoQ10 levels being associated with an increased risk of various cancers. We conducted the first study to evaluate the association of CoQ10 concentrations with lung cancer risk., Methods: A nested case-control study including 201 lung cancer cases and 395 matched controls from the Southern Community Cohort Study was conducted. Plasma CoQ10 levels were measured using high-performance liquid chromatography with photo-diode array detection. Conditional logistic regression models were applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between plasma CoQ10 levels and lung cancer risk., Results: Plasma CoQ10 concentration was inversely associated with the risk of lung cancer. After adjusting for age, sex, race, and socioeconomic status, the OR (95% CI) comparing the third to first tertile was 0.57 (0.36-0.91, P for trend = 0.02). Further adjustments for smoking, alcohol, chronic obstructive pulmonary disease, and body mass index attenuated the point estimate slightly (OR = 0.60, 95% CI = 0.34-1.08, P for trend = 0.11), comparing third to first tertiles. Stratified analyses identified a significant inverse association between plasma CoQ10 levels and lung cancer risk in current smokers, but not in former/never smokers. The association was more evident in cases who were diagnosed within 1 year of blood draw than in cases diagnosed after 1 year., Conclusions: Low plasma CoQ10 was significantly associated with increased lung cancer risk, particularly among current smokers. The stronger association seen shortly following the blood draw suggests that CoQ10 may be related to disease progression., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objectives: To evaluate the clinical symptoms and biochemical findings and establish the genetic etiology in a cohort of pediatric patients with combined deficiencies of the mitochondrial respiratory chain complexes., Study Design: Clinical and biochemical data were collected from 55 children. All patients were subjected to sequence analysis of the entire mitochondrial genome, except when the causative mutations had been identified based on the clinical picture. Whole exome sequencing/whole genome sequencing (WES/WGS) was performed in 32 patients., Results: Onset of disease was generally early in life (median age, 6 weeks). The most common symptoms were muscle weakness, hypotonia, and developmental delay/intellectual disability. Nonneurologic symptoms were frequent. Disease causing mutations were found in 20 different nuclear genes, and 7 patients had mutations in mitochondrial DNA. Causative variants were found in 18 of the 32 patients subjected to WES/WGS. Interestingly, many patients had low levels of coenzyme Q10 in muscle, irrespective of genetic cause., Conclusions: Children with combined enzyme defects display a diversity of clinical symptoms with varying age of presentation. We established the genetic diagnosis in 35 of the 55 patients (64%). The high diagnostic yield was achieved by the introduction of massive parallel sequencing, which also revealed novel genes and enabled elucidation of new disease mechanisms., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Cognitive impairments, negative symptoms, affective symptoms, and low energy are highly prevalent features of schizophrenia. Mitochondrial dysfunction has been hypothesized as one of the numerous factors to underlie the manifestation of these symptoms. The objective of this study was to evaluate whether Coenzyme Q10 (CoQ10) has a role in the treatment of schizophrenia and schizoaffective disorder., Methods: A double-blind, randomized, placebo-controlled trial was conducted to assess the effects of CoQ10 supplementation (300 mg/day) on the co-primary outcomes of attention and working memory performance after 3 and 6 months. Secondary outcomes included plasma CoQ10 levels, mitochondrial function, energy, depression, anxiety, negative symptoms, and quality oflife., Findings: In total, 72 patients were randomized to intervention groups. Overall, there was no effect of CoQ10 supplementation on the primary outcome measures at 3 or 6 months. Further, with the exception of plasma CoQ10 levels, CoQ10 supplementation also had no effect on the secondary outcomes. At 3 months, CoQ10 concentration was significantly higher in the CoQ10 group (3.85 μg/mL) compared with placebo (1.13 μg/mL); this difference was not present at 6 months., Conclusions: The results of the study suggest that CoQ10 supplementation at 300 mg/day for 6 months is unlikely to be beneficial for cognitive, psychological and health-related outcomes in schizophrenia and schizoaffective disorder. However, a number of limitations including low adherence, modest sample size, and attrition, likely reduce estimates of effects. As such, results should be considered preliminary., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Endothelial dysfunction is common in patients undergoing hemodialysis (HD). However, little is known about the relationship between endothelial dysfunction and coenzyme Q10 (CoQ10) levels in HD patients., Methods: Eligible HD patients were enrolled in this study according to prespecified inclusion and exclusion criteria. Endothelial function was assessed by brachial artery flow-mediated dilation (FMD). Plasma CoQ10, serum malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG) levels were measured. The potential confounders identified by univariate analyses (P < 0.15) were selected in a stepwise multiple regression model., Results: In total, 111 HD patients were enrolled in this study. The mean CoQ10 level was 633.53 ± 168.66 ng/mL, and endothelial dysfunction was prevalent (91.0%) using a cut-off value of 10% FMD. A significant correlation was observed between FMD and plasma CoQ10 level (r = 0.727, P < 0.001). After adjusting for potential parameters, a stepwise multivariate linear regression analysis revealed that CoQ10 level was an independent predictor of FMD (β = 0.018, P < 0.001). When CoQ10 was dichotomized using the median value (639.74 ng/mL), the conclusion remained unchanged (β = 0.584, P < 0.001). Pearson's correlation analyses revealed that plasma CoQ10 level was negatively correlated with MDA (r = -0.48, P < 0.001) and 8-OHdG (r = -0.43, P < 0.001) levels., Conclusion: Our data demonstrate that impaired brachial artery FMD was common in HD patients. CoQ10 level was independently associated with FMD, and oxidative stress may constitute a link between CoQ10 level and endothelial dysfunction in these patients., (© 2020 Asian Pacific Society of Nephrology.)

This case-control study aimed to assess oxidative stress alterations in autism spectrum disorder (ASD). We used the MULTIS method, an electron spin resonance-based technique measuring multiple free radical scavenging activities simultaneously, in combination with conventional oxidative stress markers to investigate the ability of this MULTIS approach as a non-behavioural diagnostic tool for children with ASD. Serum samples of 39 children with ASD and 58 age-matched children with typical development were analysed. The ASD group showed decreased hydroxyl radical ( · OH) and singlet oxygen scavenging activity with increased serum coenzyme Q10 oxidation rate, indicating a prooxidative tendency in ASD. By contrast, scavenging activities against superoxide (O 2 ·- ) and alkoxyl radical (RO · ) were increased in the ASD group suggesting antioxidative shifts. In the subgroup analysis of 6-year-olds or younger, the combination of · OH, O 2 ·- , and RO · scavenging activities predicted ASD with high odds ratio (50.4), positive likelihood (12.6), and percentage of correct classification (87.0%). Our results indicate that oxidative stress in children with ASD is not simply elevated but rather shows a compensatory shift. MULTIS measurements may serve as a very powerful non-behavioural tool for the diagnosis of ASD in children.

Objective: The reduction of Coenzyme Q10 (CoQ10) levels following statin use has been linked to cause peripheral neuropathy. Hence, this study was planned to explore the effect of statin on the serum HMGCR (3-hydroxy-3-methyl-glutaryl-coenzyme A reductase), serum CoQ10 levels and nerve conduction and their correlation., Patients and Methods: In an open labelled, cross-sectional, observational study, estimation of serum HMGCR and CoQ10 levels was performed in 50 atorvastatin/rosuvastatin users and 50 normal healthy volunteers (NHV). Statin users were also subjected to nerve conduction studies (NCS)., Results: Mean serum HMGCR level in NHV was higher (73.58 ± 7.64 ng/ml; p = 0.003) than that in statin users (49.11 ± 1.98 ng/ml). Similarly, mean serum CoQ10 levels was also lower (30.54 ± 2.03 ng/ml, p < 0.0001) in statin users than in NHV (49.43 ± 3.23 ng/ml). Amongst the 50 statin users, 29 had impaired NCS in sural, tibial and common peroneal nerve with lower mean serum CoQ10 levels (24.05 ± 1.96 ng/ml; p < 0.0001). Significant negative correlation was observed between onset time of action potential (AP) of the sural nerve and serum CoQ10 (r=-0.32) and HMGCR (r=-0.43) levels. There was significant positive correlation of conduction velocity of sural (r = 0.38) and tibial (r = 0.31) nerves with serum CoQ10 level. While conduction velocity in sural (r = 0.37) and common peroneal (r = 0.34) nerves positively correlated with serum HMGCR levels. The amplitude of the AP of the common peroneal nerve positively correlated with both serum CoQ10 (r = 0.52) and HMGCR (r = 0.46) levels., Conclusion: Statin users had lower serum CoQ10 and HMGCR levels associated with nerve conduction deficits suggesting a role of CoQ10 in the occurrence of the neurological adverse effects., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background/aim: Verruca vulgaris is a benign disease characterized with papillomas on the skin and mucosa. The aim of this study was to investigate the serum levels of coenzyme Q10, MDA, and zinc as well as the lipid profile of verruca vulgaris patients and examine the relationship between these parameters and clinical manifestations of the disease., Materials and Methods: The study included 49 verruca vulgaris patients (mean age: 32.01 ± 14.20 years; 22 males, 27 females) and 40 healthy volunteers (mean age: 31.63 ± 8.98 years; 21 males and 19 females). Coenzyme Q10 levels were assessed by using an enzyme- linked immunosorbent assay. Serum MDA levels were measured spectrophotometrically. Zinc levels were measured using a Perkin Elmer AAnalyst 800 atomic absorption spectrometer with a deuterium background correction and additional standard techniques., Results: The coenzyme Q10 levels were found to be higher in the verruca vulgaris group compared to the healthy volunteers. However, this increase was not statistically significant (P = 0.195). Zinc levels were significantly lower in the verruca vulgaris group compared to the healthy volunteers (P = 0.002). In the patient group, MDA levels and HDL levels were significantly higher compared to the healthy volunteers (P = 0.023 and P = 0.004, respectively). Additionally, there was no statistically significant difference between the groups in the CoQ10/Total cholesterol ratio (P = 0.433)., Conclusion: Reduced serum zinc levels and increase of oxidative stress in verruca vulgaris may be a factor responsible for development of verruca vulgaris., Competing Interests: The authors declare that they have no conflict of interest., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Ubiquinol is a fundamental component of cellular metabolism. Low ubiquinol levels have been associated with mortality. This was a substudy of a randomized trial in patients undergoing coronary artery bypass grafting. We drew blood before and after surgery. Ubiquinol or placebo was added to peripheral blood mononuclear cells for oxygen consumption (OCR) measurements. In vivo ubiquinol levels were lower postsurgery compared to presurgery (0.16 μmol/L [quartiles: 0.02-0.39], P = .01), although the difference disappeared when adjusting for hemoglobin levels ( P = .30). There was no difference in presurgical basal (1.0 mL/min/mg [95% confidence interval [CI]: -0.9 to 2.2], P = .08) and maximal (0.5 mL/min/mg [95% CI: -4.3 to 7.3], P = .56) OCR in cells receiving ubiquinol or placebo. There was a difference in postsurgical basal (1.1 mL/min/mg [95% CI: 0.9-1.6], P < .001) and maximal (4.2 mL/min/mg [95% CI: 0.3-7.0], P = .01) OCR between the groups. We found no association between ubiquinol and OCR levels (all P > .05).

Objectives Coenzyme Q10 (CoQ10) has many vital functions in human body and its endogenous level can be affected either by various diseases or by administrated drugs. This study reveals the effect of atorvastatin, amlodipine and ethoxidol on the endogenous CoQ10 plasma concentration. Methods It was determined the total plasma concentration of endogenous CoQ10 in the plasma of 54 healthy individuals and 62 patients with cardiovascular diseases during treatment with various drugs using high performance liquid chromatography with mass spectrometric detection (HPLC-MS/MS). Results It was found that CoQ10 plasma concentration in patients is statistically significantly lower (on average -49.0 Δ%) than in practically healthy individuals. The total CoQ10 plasma level in patients receiving atorvastatin in the complex therapy is statistically significantly lower (-15.2 Δ%), and in patients taking amlodipine or ethoxidol is statistically significantly higher (+18.2 and +20.2 Δ%, respectively) than in patients of control groups (a group of patients who receive the same drugs, except for the studied one). Conclusions The study showed that in patients with CVDs treated with various drugs the CoQ10 plasma level is statistically significantly lower than in practically healthy individuals. So, to avoid the adverse reactions connected with low CoQ10 plasma levels, it is recommended to adjust the therapy to maintain its constant level.

Our double-blind, placebo-controlled study evaluated effects of ubiquinol, the reduced form of coenzyme Q 10 , on mild fatigue in healthy individuals experiencing fatigue in daily life that had continued for more than 1 and less than 6 months. The participants received 100-mg/day (Ubq100; age 44.0 ± 9.8 years; 14 females and 6 males) or 150-mg/day ubiquinol (Ubq150; age 40.4 ± 11.8 years; 14 females and 8 males) or placebo (Plc; age 41.3 ± 13.4 years; 13 females and 7 males) daily for 12 weeks. Measurements of subjective and objective fatigue were conducted by using questionnaires-based fatigue scales/visual analogue scales and autonomic nerve function/biological oxidation index, respectively, prior to the first dosing and every 4 weeks thereafter. Serum ubiquinol level increased three- to four-fold after 4 weeks and remained significantly higher than that after Plc administration throughout the intake period. Although a higher blood level of ubiquinol was observed with Ubq150 than with Ubq100, the difference was not statistically significant. In both Ubq100 and Ubq150 groups, subjective levels of fatigue sensation and sleepiness after cognitive tasks, which consisted of the modified Advanced Trail Making Test, the modified Stroop Color-Word Test, and the Digit Symbol Substitution Test, improved significantly compared with those in the placebo group, suggesting an anti-fatigue effect. The Ubq150 group demonstrated significant improvement compared with the Plc group regarding subjective level of relaxation after task, sleepiness before and after task, motivation for task, and serum level of oxidative stress. Correlation analysis between blood level of ubiquinol and each evaluated effect suggested a positive relationship with relaxation after task, motivation for cognitive task, and parasympathetic activity. The results of the study suggest that ubiquinol intake relieves mild fatigue in healthy individuals.

Aim: Intrahepatic cholestasis of pregnancy (ICP) is considered a high-risk condition because it may have serious consequences for the fetus health. ICP is characterized by the accumulation of bile acids in maternal serum which contribute to an imbalance between the production of reactive oxygen species and the antioxidant defenses increasing the oxidative stress experienced by the fetus. Previously, it was reported a significant decrease in plasma coenzyme Q10 (CoQ10) in women with ICP. CoQ10 is a redox substance integrated in the mitochondrial respiratory chain and is recognized as a potent antioxidant playing an intrinsic role against oxidative damage. The objective of the present study was to investigate the levels of CoQ10 in umbilical cord blood during normal pregnancy and in those complicated with ICP, all of them compared to the maternal ones., Methods: CoQ10 levels and bile acid levels in maternal and umbilical cord blood levels during normal pregnancies (n=23) and in those complicated with ICP (n=13), were investigated., Results: A significant decrease in neonate CoQ10 levels corrected by cholesterol (0.105±0.010 vs. 0.069±0.011, P<0.05, normal pregnancy vs. ICP, respectively), together with an increase of total serum bile acids (2.10±0.02 vs. 7.60±2.30, P<0.05, normal pregnancy vs. ICP, respectively) was observed., Conclusions: A fetus from an ICP mother is exposed to a greater risk derived from oxidative damage. The recognition of CoQ10 deficiency is important since it could be the starting point for a new and safe intervention strategy which can establish CoQ10 as a promising candidate to prevent the risk of oxidative stress., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Low levels of coenzyme Q10 (CoQ10) have been reported in the circulation of patients with breast cancer, particularly in metastatic features. Our objective was to study the correlation between plasma levels of CoQ10 and the tumoral expression levels of AMPK, PFKFB3, VEGF, and VEGFR2. This study was a part of consecutive case series conducted on 100 women with newly diagnosed invasive ductal breast carcinoma, with an age range of 30-60 years. Plasma levels of CoQ10 were measured using HPLC coupled to an UV detector. The expression levels were quantified using quantitative real-time PCR. Structural equation modeling (SEM) was applied to generate pathways describing gene-to-gene inter-correlations. Using SEM identified AMPK expression to contribute positively to VEGF-A/VEGFR2 ratio (coefficient b = 0.64, P < 0.001). The VEGFR2 expression positively correlated with tumor size (coefficient b = 0.31, P < 0.001). A linear correlation between expression levels of AMPK and PFKFB3 was observed (r Adj  =  - 0.273, P = 0.02). Similarly, VEGF-A was correlated with VEGFR2 (r Adj  = 0.698, P < 0.001). There were inverse significant correlations between CoQ10 and the fold changes of AMPK (r Adj  =  - 0.276, P = 0.030), VEGF-A (r Adj  =  - 0.319, P = 0.011) and VEGFR2 (r Adj  =  - 0.262, P = 0.045). The correlation between CoQ10 and the fold changes of PFKFB3 was significantly progesterone receptor (PR) dependent (r Adj  =  - 0.284, P = 0.041). Plasma CoQ10 was correlated with VEGF-A in hormone receptor-dependent mode (ER + : r Adj  =  - 0.286, P = 0.032 and PR + : r Adj  =  - 0.313, P = 0.025). Our findings could provide new insights suggesting CoQ10 can inversely correlate to the expression levels of VEGF-A/VEGFR2 as angiogenic factors and AMPK/PFKFB3 as biomarkers for tumoral glycolysis, especially in a hormone receptor-dependent manner to possibly prevent the progression of breast carcinogenesis.

Background: Coenzyme Q10 (CoQ10) supplementation can improve cognition in patients with Alzheimer's disease (AD) and AD transgenic model mice. To ameliorate the discomfort that patients with AD suffer after several blood extractions, a non-invasive method for detecting urine CoQ10 levels needs to be established., Methods: Here, we developed a new technique of fluorescence spectrophotometry with ethyl cyanoacetate (FS-ECA), on the basis of the principle that the chemical derivative obtained from the interaction between CoQ10 and ECA was detected by a fluorescence detector at λ ex/em  = 450/515 nm. As a standard reference method, the same batches of the clinical samples were analyzed by high-performance liquid chromatography with an ultraviolet detector (HPLC-UV) at 275 nm., Results: The limits of detection (LOD) and limits of quantization (LOQ) (serum: 0.021 and 0.043 mg/L; urine: 0.012 and 0.025 mg/L) determined by the FS-ECA method were similar to that obtained through HPLC-UV (serum: 0.017 and 0.035 mg/L; urine: 0.012 and 0.025 mg/L). More importantly, this new FS-ECA technique as well as the conventional HPLC-UV method could detect a marked difference in urine CoQ10 levels between AD and controls., Conclusion: Our findings suggest that this non-invasive method for quantifying urine CoQ10 potentially replaces HPLC to detect blood CoQ10., (© 2019 The Authors. Journal of Clinical Laboratory Analysis Published by Wiley Periodicals, Inc.)

Background: The balance of the oxidative state in the body is fundamental for the maintenance of homeostasis. It has been implicated in the onset and progression of several diseases including breast cancer. The way in which the Reactive Oxygen Species (ROS) / antioxidants balance leads to or responds to disease is still controversial. In this study, TAC is used as a reference for the total antioxidant power of the body and Coenzyme Q10 (CoQ10) for its vital importance in cellular antioxidant action and being the only lipid soluble antioxidant synthesized endogenously. Copper and zinc were measured as trace elements reflecting the antioxidant micronutrient profile of the body., Methods: After approval of the ethical committee, 60 recently diagnosed non-intervened breast cancer patients were recruited from the Medical Research Institute hospital, Alexandria University along with 20 apparently healthy volunteers as control group. Full patient history was taken including breastfeeding history, parity, hormone replacement therapy use, body mass index, pathological examination, metastatic work up results, past medical history and drug use. CA 15-3 and laboratory investigations evaluating blood glucose, kidney and liver functions were performed. Q10 levels were measured by HPLC using a kit from Recipe®. TAC was assayed spectrophotometrically (Biodiagnostics®). Copper and Zinc levels were determined by inductively coupled plasma-optical emission spectrometry., Results: There was a statistically significant increase in the CoQ10, TAC and copper levels in the breast cancer group when compared to the control group. Zinc showed no statistically significant difference between the studied groups., Conclusion: Inspite of the fact that a high antioxidant level is usually considered as a favourable state, TAC, CoQ10 and copper levels showed significantly higher levels in the breast cancer group when compared to the control group. It is worth mentioning that the cancer group were all recently diagnosed, non-intervened and showed no signs of metastasis. It is still unclear whether the increased antioxidant levels offer a selective growth advantage to tumor cells over their surrounding normal cells or serve as a protective measure by the body in an attempt to correct the assault triggered by the ROS.

Background: Autism spectrum disorder (ASD) is a complex group of heterogeneous neurodevelopmental disorders the prevalence of which has been in the rise in the past decade. In an attempt to better target the basic causes of ASD for diagnosis and treatment, efforts to identify reliable biomarkers related to the body's metabolism are increasing. Despite an increase in identifying biomarkers in ASD, there are none so far with enough evidence to be used in routine clinical examination, unless medical illness is suspected. Promising biomarkers include those of mitochondrial dysfunction, oxidative stress, energy metabolism, and apoptosis., Methods and Participants: Sodium (Na+), Potassium (K+), glutathione (GSH), glutathione-s-transferase (GST), Creatine kinase (CK), lactate dehydrogenase (LDH), Coenzyme Q10, and melatonin (MLTN) were evaluated in 13 participants with ASD and 24 age-matched healthy controls. Additionally, five ratios, which include Na+/K+, GSH:GST, CK:Cas7, CoQ10: Cas 7, and Cas7:MLTN, were tested to measure their predictive values in discriminating between autistic individuals and controls. These markers, either in absolute values, as five ratios, or combined (9 markers + 5 ratios) were subjected to a principal component analysis and multidimensional scaling (MDS), and hierarchical clustering, which are helpful statistical tools in the field of biomarkers., Results: Our data demonstrated that both PCA and MDS analysis were effective in separating autistic from control subjects completely. This was also confirmed through the use of hierarchical clustering, which showed complete separation of the autistic and control groups based on nine biomarkers, five biomarker ratios, or a combined profile. Excellent predictive value of the measured profile was obtained using the receiver operating characteristics analysis, which showed an area under the curve of 1., Conclusion: The availability of an improved predictive profile, represented by nine biomarkers plus the five ratios, inter-related different etiological mechanisms in ASD and would be valuable in providing greater recognition of the altered biological pathways in ASD. Our predictive profile could be used for the diagnosis and intervention of ASD., Competing Interests: The authors have declared that no competing interests exist.

Background: Glycemia is related to energy production during exercise. Coenzyme Q10 is an antioxidant that participates in adenosine triphosphate synthesis in mitochondria. The aim of this study was to investigate the level of coenzyme Q10, glucose parameters, and antioxidant capacity in athletes., Methods: This study was designed as a cross-sectional study. Well-trained college athletes (n = 43) and age-gender matched healthy subjects (n = 25) were recruited from a college. The levels of glucose parameters, oxidative stress, antioxidant enzymes activity, Trolox equivalent antioxidant capacity (TAC), and coenzyme Q10 status were measured in the present study., Results: The athletes had a significantly lower level of white blood cells (WBC) coenzyme Q10 than the healthy subjects (0.34 ± 0.24 vs. 0.65 ± 0.43 nmol/g, p < 0.01); however, no significant difference was detected in plasma coenzyme Q10 between the two groups. Regarding the glucose parameters, the athletes had significantly higher values for HbA1c (5.5 ± 0.3 vs. 5.3 ± 0.3%, p < 0.05) and quantitative insulin sensitivity check index (QUICKI, 0.37 ± 0.03 vs. 0.34 ± 0.03, p < 0.05), and lower homeostatic model assessment-insulin resistance (HOMA-IR, 1.5 ± 0.8 vs. 2.9 ± 3.8, p < 0.05) than the healthy subjects. A higher level of TAC was found in the athletes (serum, 5.7 ± 0.3 vs. 5.4 ± 0.2 mM Trolox; erythrocyte, 10.5 ± 0.6 vs. 10.0 ± 0.5 mM Trolox, p < 0.05). In addition, WBC coenzyme Q10 status was significantly correlated with catalase activity (r = 0.56, p < 0.01), GPx activity (r = 0.56, p < 0.01), serum TAC (r = 0.54, p < 0.01), fasting glucose (β = - 1.10, p < 0.01), HbA1c (β = - 0.82, p < 0.01), HOMA-IR (β = - 1.81, p < 0.01), and QUICK (β = 0.08, p < 0.01)., Conclusions: Athletes may suffer from a marginal coenzyme Q10 deficiency, and the level was related to glycemic control and antioxidant capacity. Further interventional studies are needed to clarify an adequate dose of coenzyme Q10 supplementation in athletes to optimize their coenzyme Q10 status and athletic performance or recovery during exercise.

Background: Striae gravidarum (SG) can cause pregnant women severe psychological stress., Objective: This study aimed to compare primigravidas with and without SG concerning fasting blood coenzyme Q10 (CoQ10), age, skin type, family history, gestational weight gain, pre- and post-pregnancy BMI, daily water consumption during pregnancy, gender and weight of baby, and the educational level., Methods: The study included 79 primigravidas in the gestational week of 36 or above. The patients were divided into two groups based on the presence of SG. The fasting blood CoQ10 levels and other associated parameters were compared between the groups., Results: Of the 79 primigravidas, 35 (44.3%) had SG. There was no statistically significant relationship between striae and CoQ10 (P = 0.144 and P = 0.189, respectively). Predisposing factors for striae were young pregnancy, light skin color, family history, high pre- and post-pregnancy BMI, increased gestational weight gain, and increased newborn weight. There was no significant relationship between striae development and educational level or water consumption during pregnancy., Conclusion: This is the first study to show that CoQ10 did not significantly differ between women with and without SG. Further studies with a larger case series are needed to elucidate predisposing factors for striae and involvement of CoQ10 in this condition., (© 2019 Wiley Periodicals, Inc.)

Objective : Stabilizers, especially carbohydrate polymers, have been shown to be necessary for the stabilization of drug nanocrystals. However, the impacts of select stabilizers on the in vitro and in vivo efficacy of therapeutics have rarely been reported. The aim of this study was to evaluate the importance of stabilizers in the formulation of drug nanocrystals. Research design and methods : Idebenone nanocrystals (IDBNC) stabilized by various stabilizers were formulated using a milling method. The in vitro dissolution profiles in water and in situ absoprtion were compared. Finally, an in vivo pharmacokinetic study was performed. Results : The IDBNC profiles were found to have acceptable sizes and similar morphology and crystallinity. The dissolution profiles of IDBNC stabilized by different stabilizers were notably different, indicating the critical influence of stabilizers on the release rate of IDB. The Soluplus-stabilized IDBNC (IDBNC 400 nm /Soluplus) achieved better absorption than HPMC stabilized IDBNC (IDBNC 400 nm /HPMC). The pharmacokinetic study demonstrated that Soluplus-stabilized IDBNC had preferable kinetics, with an AUC 0-24h of IDBNC 400 nm /Soluplus (3.08-fold relative to IDB suspension), compared to IDBNC 400 nm /HPMC (1.88-fold). Conclusions : Choice of stabilizer plays an important role in the formulation of IDBNC. We anticipate that the role of stabilizers in the pharmacokinetic disposition of IDBNC has significant implications for a wide range of other drug crystal formulations.

Objectives: Coenzyme Q 10 , incorporated in DOPC lyposomes or naturally present in liver bovine mitochondria or in human blood plasma, was reacted with nitrogen dioxide • NO 2 or with a • NO/ • NO 2 mixture. Methods and Results: The reaction course was monitored by Electron Paramagnetic Resonance (EPR) spectroscopy and in all cases the formation of a di- tert -alkyl nitroxide was observed, deriving from the addition of • NO 2 to one of the double bonds, most likely the terminal one, of the isoprenic chain. The rate constant for nitroxide formation was also determined by EPR spectroscopy and an initial rate of ca. 7 × 10 -8  M s -1 was obtained.

During studies on related substances in coenzyme Q 10 (CoQ 10 ) active pharmaceutical ingredient (API) and capsules, two impurities (Impurity 1 and Impurity 2) with each content more than 0.1% attracted our attention. Accelerated testing (40 °C /75%RH) and forced degradation of CoQ 10 API and drug products in different stress conditions (base and heat) gave rise to the two unknown impurities. These unknown impurities were separated by reverse phase ultra-performance liquid chromatography (UPLC), where they were eluted at 0.77 (Impurity 1) and 1.10 (Impurity 2) relative retention times to CoQ 10 peak. Impurity 2 was separated into two peaks (Impurity 2-1 and Impurity 2-2) by normal phase high performance liquid chromatography (NP-HPLC). In this study, an ultra-performance liquid chromatography complied with quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF/MS) via atmospheric pressure chemical ionization (APCI) was used to identify the proposed structure of the three impurities (Impurity 1, Impurity 2-1 and Impurity 2-2). We got the three impurities through preparative high performance liquid chromatography and their structures were further confirmed by 1D and 2D nuclear magnetic resonance (NMR). Based on the significance of these results, Impurity 1 was the impurity E referred in British Pharmacopoeia (BP), Impurity 2-1 and Impurity 2-2 were a pair of isomers which had not been reported before., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Backgrounds and aims: Migraine and inflammation are correlated. Coenzyme Q10 (CoQ10) as an anti-inflammatory agent has shown useful effects in other diseases. The present study aimed to assess the effect of CoQ10 supplementation on inflammation and clinical features of migraine. Methods: This randomized double-blind placebo-controlled clinical trial was conducted among 45 non-menopausal women aged 18-50 years, diagnosed for episodic migraine according to the International Headache Society. After one month run-in period, subjects received CoQ10 (400 mg/day CoQ10, n = 23) or placebo (wheat starch, n = 22) for three months. All the patients got prophylactic medication too. Serum CoQ10 concentration, Calcitonin gene-related peptide (CGRP), interleukin (IL)-6, IL-10 and tumor necrosis factor-α (TNF-α) were measured at the beginning and end of the study. Results: CoQ10 supplementation reduced CGRP and TNF-α significantly ( p = 0.011 and p = 0.044, respectively), but there were no significant differences in serum IL-6 and IL-10 between the two groups. Significant increase in serum CoQ10 levels was evident with CoQ10 therapy ( P < 0.001). A significant improvement was found in frequency ( p = 0.018), severity ( p = 0.001) and duration ( p = 0.012) of migraine attacks in CoQ10 group compared to placebo. Conclusion: CoQ10 supplementation may decrease CGRP and TNF-α with no favorable effects on IL-6 and IL-10 in patients with migraine.

Background: Changing the resources of vitamin D and antioxidant nutrients may affect the course of allergic diseases. The aim of the study was to investigate the association between CoQ10, vitamin D, retinol, and α-tocopherol serum levels and severity of atopic dermatitis (AD) in children., Methods: Twenty-nine children with AD aged from 1 to 15 years were enrolled into the study. The severity of AD was categorized into mild or moderate (≤50 points in SCORAD - Scoring Atopic Dermatitis index) and severe (>50 SCORAD points). The control group was comprised of 22 children with negative history of allergy aged from 2 to 15. The serum measurements included vitamin D, retinol, α-tocopherol, CoQ10, C-reactive protein (CRP), complete blood count (CBC), and total immunoglobulin E (IgE)., Results: Low vitamin D concentration (<20 ng/ml) was observed mainly in patients with severe AD (77.8%), compared to children with mild or moderate AD (25%) or the control group (31.8%). Concentration of retinol was decreased significantly in patients with severe AD (median 1.32 μmol/l), compared to children with mild and moderate AD (median 1.66 μmol/l), but not to the control. Among inflammatory markers, only the group with severe AD demonstrated significantly elevated platelet count (PLT), red blood cell distribution width (RDW), and eosinophil count (EO). Retinol level correlated with PLT (R = -0.7; P = 0.003), white blood count (WBC) (R = -0.54; P = 0.01), total IgE (R = -0.51; P = 0.016), mean platelet volume (MPV) (R = 0.51; P = 0.02), and also with a disease severity index, SCORAD (R = -0.55; P = 0.007), whereas vitamin D level correlated only with MPV (R = 0.61; P = 0.003). No significant changes were found in tocopherol and CoQ10 levels between groups., Conclusions: Children with AD should be routinely tested for vitamin D deficiency, especially during disease exacerbation. Our results confirmed correlation of serum inflammatory markers with decreased concentration of vitamin A in children with AD. This finding, however, might be an effect of severe stage of disease and not only of inadequate intake of retinol in the diet., (© 2019 The International Society of Dermatology.)

Seasonal variations in temperature may influence the physiological and pathological metabolic pathways, concentrations of antioxidants, degree of oxidative stress and mitochondrial function. The aim of this study was to evaluate platelet mitochondrial function in human subjects during seasonal variations in temperature. Two groups of healthy young subjects were enroled in the study. Winter group, mean outside temperature was 4.77°C and Spring group, mean outside temperature was 24.32°C. High-resolution respirometry method was used for determination of mitochondrial respiration and oxidative phosphorylation in platelets. Concentrations of coenzyme Q10 (CoQ10) and tocopherols were determined in platelets, blood and plasma. Our data showed slightly (not significantly) reduced respiration in intact platelets, basal and ADP-stimulated mitochondrial respiration at Complex I, as well as CoQ10-TOTAL and α-tocopherol concentrations in winter. The concentration of γ-tocopherol was higher in winter. Platelet mitochondrial ATP production depended on platelet CoQ10-TOTAL concentration in winter, not in spring. We conclude that seasonal temperature participates in the mechanism of platelet mitochondrial respiratory chain function and oxidative phosphorylation that depends on their CoQ10-TOTAL concentration at lower winter outside temperature. CoQ10 supplementation may improve platelets mitochondrial ATP production at winter season. High-resolution respirometry offers sensitive method for detection of changes of platelets mitochondrial respiratory function.

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., (Copyright © 2019 Endocrine Society.)

Type 2 diabetic patients possess a two to four fold-increased risk for Cardiovascular Diseases (CVD). Hyperglycemia, oxidative stress associated with endothelial dysfunction and dyslipidemia are regarded as pro-atherogenic mechanisms of CVD. In this study, high-fat diet-induced diabetic and non-diabetic vervet monkeys were treated with 90 mg/kg of aspalathin-rich green rooibos extract (Afriplex GRT) for 28 days, followed by a 1-month wash-out period. Supplementation showed improvements in both the intravenous glucose tolerance test (IVGTT) glycemic area under curve (AUC) and total cholesterol (due to a decrease of the low-density lipoprotein [LDL]) values in diabetics, while non-diabetic monkeys benefited from an increase in high-density lipoprotein (HDL) levels. No variation of plasma coenzyme Q10 (CoQ 10 ) were found, suggesting that the LDL-lowering effect of Afriplex GRT could be related to its ability to modulate the mevalonate pathway differently from statins. Concerning the plasma oxidative status, a decrease in percentage of oxidized CoQ 10 and circulating oxidized LDL (ox-LDL) levels after supplementation was observed in diabetics. Finally, the direct correlation between the amount of oxidized LDL and total LDL concentration, and the inverse correlation between ox-LDL and plasma CoQ 10 levels, detected in the diabetic monkeys highlighted the potential cardiovascular protective role of green rooibos extract. Taken together, these findings suggest that Afriplex GRT could counteract hyperglycemia, oxidative stress and dyslipidemia, thereby lowering fundamental cardiovascular risk factors associated with diabetes., Competing Interests: The authors report no conflicts of interest. All authors are responsible for the content and writing of the paper.

Objective: The purpose of this study was to determine the oxidative states of head and neck squamous cell carcinoma (HNSCC) patients by measuring their plasma levels of malondialdehyde (MDA), an indicator of lipid peroxidation, 3-nitrotyrosine (3-NT), an indicator of protein oxidation, and the coenzyme Q10 (CoQ10), an important antioxidant, and compare them with healthy individuals., Materials and Methods: The plasma MDA, 3-NT and CoQ10 levels of 35 patients and 20 healthy individuals were measured with the high-performance liquid chromatography (HPLC) method. By comparing the patients' smoking habits, stage of the disease, size of the primary tumor and the presence of lymph nodes and the values of healthy individuals, the oxidative stress load of HNSCC patients was determined., Results: The mean plasma MDA levels of carcinoma patients were two times higher than those of healthy individuals (p < 0.001). When the mean plasma 3-NT levels of patients and healthy individuals were compared, no significant difference was found (p > 0.05). The mean plasma CoQ10 level of patients was low when compared with healthy individuals; however, no significant difference was detected (p > 0.05). In addition, as the stage and tumor size increased in HNSCC patients, their non-enzymatic antioxidant levels significantly decreased (p < 0.05)., Conclusions: In HNSCC patients, lipo-oxidative damage increased while nitrosative stress did not change; however, antioxidant activity decreased which in turn increased both lipid peroxidation and oxidative stress. These findings support the contention that oxidative stress strongly reflects the health status of HNSCC patients.

This study was carried out to determine vit. E, Se, vit. A, malondialdehyde (MDA), 8-hydroxy-2-deoxyguanosine (8-OHdG), and ubiquinone-10 (CoQ10) levels and histopathological changes in sheep with white muscle disease (WMD). A total of 30 sheep were used; 20 sheep with WMD were brought to our clinic for diagnosis and treatment at various times, and 10 healthy sheep were in the control group. The Se, vit. E, vit. A, MDA, 8-OHdG, and CoQ10 values of the healthy and WMD sheep were as follows: 0.917 ± 0.037, 0.790 ± 0.067; 1.190 ± 0.011, 1.090 ± 0.021; 5.400 ± 0.275, 5.200 ± 0.173; 1.602 ± 0.264, 2.636 ± 0.576; 0.656 ± 0.197, 1.485 ± 0.271; and 0.280 ± 0.044, 1.753 ± 0.551 respectively (p < 0.05). According to histopathological and immunohistochemical findings in the WMD group, hyaline degeneration, Zenker's necrosis, and dystrophic calcification were observed in the muscle fibers. Immunohistochemically, 8-OHdG staining of the heart tissue determined a severe 8-OHdG expression in the WMD group. The findings of this study suggest that MDA, 8-OHdG, and CoQ10 values could be used as diagnostic and prognostic biomarkers in sheep affected with WMD.

Objective: The purpose of this study was to evaluate the antioxidant status of plasma vitamin E and plasma and intracellular coenzyme Q10 in children with type 1 diabetes., Method: This case-control study was conducted on 72 children with type 1 diabetes and compared to 48 healthy children, who were age, sex, and ethnicity-matched. The diabetic children were divided according to their glycosylated hemoglobin (A1c %) into two groups: poor and good glycemic control groups. All children underwent full history taking, clinical examination, and laboratory measurement of complete blood count, A1c %, plasma cholesterol, triglycerides, and vitamin E levels and coenzyme Q10 levels in plasma, erythrocytes, and platelets., Results: Children with poor glycemic control showed significantly higher plasma vitamin E, coenzyme Q10, triglycerides, low-density lipoproteins, waist circumference/height ratio, cholesterol levels, and lower high-density lipoproteins and platelet coenzyme Q10 redox status in comparison to those with good glycemic control and the control group (p<0.05). Plasma coenzyme Q10 showed a positive correlation with the duration of type 1 diabetes, triglycerides, cholesterol, vitamin E, and A1c %, and negative correlation with the age of the diabetic group (p<0.05). The platelet redox status showed a negative correlation with the A1c % levels (r=-0.31; p=0.022) and the duration of type 1 diabetes (r=-0.35, p=0.012)., Conclusion: Patients with type 1 diabetes, especially poorly controlled, had elevation of plasma vitamin E and coenzyme Q10 levels and decreased platelet redox status of coenzyme Q10, which may be an indicator of increased oxidative stress., (Copyright © 2018 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

Identifying diseases displaying chronic low plasma Coenzyme Q 10 (CoQ) values may be important to prevent possible cardiovascular dysfunction. The aim of this study was to retrospectively evaluate plasma CoQ concentrations in a large cohort of pediatric and young adult patients. We evaluated plasma CoQ values in 597 individuals (age range 1 month to 43 years, average 11 years), studied during the period 2005-2016. Patients were classified into 6 different groups: control group of healthy participants, phenylketonuric patients (PKU), patients with mucopolysaccharidoses (MPS), patients with other inborn errors of metabolism (IEM), patients with neurogenetic diseases, and individuals with neurological diseases with no genetic diagnosis. Plasma total CoQ was measured by reverse-phase high-performance liquid chromatography with electrochemical detection and ultraviolet detection at 275 nm. ANOVA with Bonferroni correction showed that plasma CoQ values were significantly lower in the PKU and MPS groups than in controls and neurological patients. The IEM group showed intermediate values that were not significantly different from those of the controls. In PKU patients, the Chi-Square test showed a significant association between having low plasma CoQ values and being classic PKU patients. The percentage of neurogenetic and other neurological patients with low CoQ values was low (below 8%). In conclusión, plasma CoQ monitoring in selected groups of patients with different IEM (especially in PKU and MPS patients, but also in IEM under protein-restricted diets) seems advisable to prevent the possibility of a chronic blood CoQ suboptimal status in such groups of patients.

Objectives: The goal of this investigation was to determine if acute influenza infection is associated with depletion of CoQ10 compared to healthy controls and to determine any associations between CoQ10 levels and illness severity and inflammatory biomarkers., Patients and Methods: We analyzed serum CoQ10 concentrations of patients with acute influenza enrolled in a randomized clinical trial prior to study drug administration. Patients were enrolled at a single urban tertiary care center over 3 influenza seasons (December 27, 2013 to March 31, 2016). Wilcoxon rank sum test was used to compare CoQ10 levels between influenza patients and healthy controls. Correlations with inflammatory biomarkers and severity of illness were assessed using Spearman correlation coefficient., Results: We analyzed CoQ10 levels from 50 patients with influenza and 29 controls. Overall, patients with acute influenza had lower levels of CoQ10 (.53 μg/mL, IQR .37-.75 vs .72, IQR .58-.90, P = .004). Significantly more patients in the influenza group had low CoQ10 levels (<.5 μg/mL) compared to controls (48% vs 7%, P < .001). Among influenza patients, there were significant but weak correlations between CoQ10 levels and IL-2 (r = -.30, P = .04), TNF-alpha (r = -.35, P = .01) and VEGF (r = .38, P = .007), but no correlation with IL-6, IL-10, VCAM or influenza severity of illness score (all P > .05)., Conclusions: We found that CoQ10 levels were significantly lower in patients with acute influenza infection and that these levels had significant although weak correlations with several inflammatory biomarkers., (© 2018 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Context: Heart failure (HF) is rapidly increasing in incidence and is often present in patients receiving long-term statin therapy., Objective: To test whether or not patients with HF on long-term statin therapy respond to discontinuation of statin therapy and initiation of coenzyme Q 10 (CoQ 10 ) supplementation., Design: We prospectively identified patients receiving long-term statin therapy in whom HF developed in the absence of any identifiable cause. Treatment consisted of simultaneous statin therapy discontinuation and CoQ 10 supplementation (average dosage = 300 mg/d)., Main Outcome Measures: Baseline and follow-up physical examination findings, symptom scores, echocardiograms, and plasma CoQ 10 and cholesterol levels., Results: Of 142 identified patients with HF, 94% presented with preserved ejection fraction (EF) and 6% presented with reduced EF (< 50%). After a mean follow-up of 2.8 years, New York Heart Association class 1 increased from 8% to 79% (p < 0.0001). In patients with preserved EF, 34% had normalization of diastolic function and 25% showed improvement (p < 0.0001). In patients with reduced EF at baseline, the EF improved from a mean of 35% to 47% (p = 0.02). Statin-attributable symptoms including fatigue, muscle weakness, myalgias, memory loss, and peripheral neuropathy improved (p < 0.01). The 1-year mortality was 0%, and the 3-year mortality was 3%., Conclusion: In patients receiving long-term statin therapy, statin-associated cardiomyopathy may develop that responds safely to statin treatment discontinuation and CoQ 10 supplementation. Statin-associated cardiomyopathy may be a contributing factor to the current increasing prevalence of HF with preserved EF.

Introduction: Multiple system atrophy (MSA) is a progressive neurodegenerative disease. Recent studies revealed decreased coenzyme Q10 (COQ10) levels in the cerebellum and blood samples of MSA patients. But few studies focused on the associations of COQ10 with the clinical symptoms of MSA. In this study, we aimed to quantify plasma COQ10 and characterize its association with clinical features., Methods: We recruited 40 patients with MSA, 30 patients with Parkinson's disease (PD), and 30 healthy participants. Plasma COQ10 was quantified by UPLC-MS. The basic demographic data, motor symptoms, and non-motor symptoms were also assessed., Results: Plasma COQ10 levels were significantly different in MSA, PD, and controls (P = 0.001). Post-hoc analysis revealed plasma COQ10 levels in MSA patients were lower than that in controls after adjusting for age, gender, and total cholesterol (P = 0.001). COQ10 levels differentiated MSA patients from controls with modest accuracy (P = 0.001). A sensitivity of 40% and a specificity of 97.5% was calculated with the receiver operating characteristic curve. However, COQ 10 levels did not discriminate between the MSA and PD groups (P = 0.07). Plasma COQ10 levels were correlated with the severity of motor symptoms only in MSA-C patients (b = -0.025, P = 0.009)., Conclusion: The association between decreased COQ10 levels and the severity of motor symptoms in MSA-C patients promotes further research. Plasma COQ10 levels alone may not be a reliable MSA diagnostic biomarker, and cannot be considered a useful biomarker in the differential diagnosis of MSA vs PD., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Coenzyme Q10 (CoQ10) exerts its functions in the body through the ability of its benzoquinone head group to accept and donate electrons. The primary functions are to relay electrons for ATP production in the electron transport chain and to act as an important lipophilic antioxidant. Ubiquinone, the oxidized form of CoQ10, is commonly formulated in commercial supplements, and it must be reduced to ubiquinol to exert CoQ10's functions after consumption. Thus, we aimed to examine whether as compared to ubiquinone, ubiquinol would be more effective to enhance the CoQ10 status in older men. We conducted a double-blind, randomized, crossover trial with two 2-week intervention phases and a 2-week washout between crossovers. Ten eligible older men were randomized to consume either the ubiquinol or ubiquinone supplement at a dose of 200 mg d-1 with one of the main meals. A total of 4 blood samples were collected after an overnight fast for the determination of ubiquinone and ubiquinol in plasma and PBMC and the assessment of FRAP, total thiol, and malondialdehyde (MDA) in plasma and ATP in PBMC. After 2 weeks of the supplementation, the ubiquinol supplement significantly increased plasma ubiquinone 1.7 fold from 0.2 to 0.6 μmol L-1 and total CoQ10 (the sum of 2 forms) 1.5 fold from 1.3 to 3.4 μmol L-1 (p < 0.05) and tended to increase the plasma ubiquinol status 1.5 fold from 1.1 to 2.8 μmol L-1, but did not alter the ratio of ubiquinol to total CoQ10. The ubiquinone supplement insignificantly increases plasma ubiquinol, ubiquinone, and total CoQ10 and did not affect the ratio. Of 10 subjects, six were more responsive to the ubiquinol supplement and 2 were more so to the ubiquinone. The supplementation of both CoQ10 forms did not alter the CoQ10 status in PBMC. FRAP, total thiol, and MDA in plasma and ATP in PBMC were not changed during the intervention. The significant increase in plasma CoQ10 status observed after the 2-week supplementation suggested that ubiquinol appeared to be a better supplemental form to enhance the CoQ10 status than ubiquinone in older men. Neither ubiquinol nor ubiquinone supplement affected the measured biomarkers of oxidative stress.

Background: The effect of statin treatment on circulating coenzyme Q10 (CoQ10) has been studied in numerous randomized controlled trails (RCTs). However, whether statin treatment decreases circulating CoQ10 is still controversial., Methods: PubMed, EMBASE, and the Cochrane Library were searched to identify RCTs to investigate the effect of statin treatment on circulating CoQ10. We calculated the pooled standard mean difference (SMD) using a fixed effect model or random effect model to assess the effect of statin treatment on circulating CoQ10. The methodological quality of the studies was determined according to the Cochrane Handbook. Publication bias was evaluated by a funnel plot, the Egger regression test, and the Begg-Mazumdar correlation test., Results: Twelve RCTs with a total of 1776 participants were evaluated. Compared with placebo, statin treatment resulted in a reduction of circulating CoQ10 (SMD, - 2.12; 95% CI, - 3.40 to - 0.84; p = 0.001), which was not associated with the duration of statin treatment (Exp, 1.00; 95% CI, 0.97 to 1.03; p = 0.994). Subgroup analysis demonstrated that both lipophilic statins (SMD, - 1.91; 95% CI, - 3.62 to 0.2; p = 0.017) and hydrophilic statins (SMD, - 2.36; 95% CI, - 4.30 to - 0.42; p = 0.028) decreased circulating CoQ10, and no obvious difference was observed between the two groups (SMD, - 0.20; 95% CI, - 0.208 to 0.618; p = 0.320). In addition, both low-middle intensity statins (SMD, - 2.403; 95% CI, - 3.992 to - 0.813; p < 0.001) and high intensity statins (SMD, - 1.727; 95% CI, - 2.746 to - 0.709; p < 0.001) decreased circulating CoQ10. Meta-regression showed that the effect of statin on decreasing circulating CoQ10 was not closely associated with the duration of statin treatment (Exp, 1.00; 95% CI, 0.97 to 1.03; p = 0.994)., Conclusions: Statin treatment decreased circulating CoQ10 but was not associated with the statin solution, intensity, or treatment time. The findings of this study provide a potential mechanism for statin-associated muscle symptoms (SAMS) and suggest that CoQ10 supplementation may be a promising complementary approach for SAMS.

Background: Pediatric dilated cardiomyopathy (PDCM) is a life-threatening type of cardiac muscle dysfunction in children. Ubiquinone is a lipid-soluble nutrient that participates in energy synthesis. Recently, a novel hydrophilic ubiquinol supplement was developed. The purpose of this study was to assess the effect of liquid ubiquinol supplementation (10 mg/kg body weight/day) on cardiac function in children with PDCM., Methods: Ten children diagnosed with PDCM were recruited to this study and administered with liquid ubiquinol for 24 weeks. The cardiac function was measured by echocardiography. The New York Heart Association (NYHA) functional classification was used to assess symptoms of heart failure. Plasma coenzyme Q10 levels were measured during the study., Results: Ejection fraction (EF) and fractional shortening (FS) were significantly higher than the baseline values until week 16 of supplementation. Subjects who had higher plasma coenzyme Q10 concentration had significantly better EF and FS values. In addition, 30% of the subjects showed improvement in the NYHA classification after 24 weeks of supplementation., Conclusion: Liquid ubiquinol supplementation is associated with an increase the level of coenzyme Q10 to complementary improve cardiac function (particularly EF and FS) and ameliorate the symptoms of heart failure in children with PDCM.

Disruption of prooxidant-antioxidant balance may lead to oxidative stress which is known as a mechanism contributing to ischemic stroke. Coenzyme Q10 (CoQ10) is an endogenous antioxidant that could be effective in preventing oxidative stress. However, the contribution of serum levels of CoQ10 in clinical neurological outcomes following ischemic stroke has not been clearly established. This study aims at measuring serum concentration of CoQ10 along with major indicators of antioxidant and oxidant among patients within 24 h after onset of the stroke symptoms, and investigating their relation with the clinical status of patients. Serum levels of CoQ10, superoxide dismutase (SOD), and malondialdehyde (MDA) were measured in 76 patients and 34 healthy individuals. Severity of the neurological deficit, functional disability, and cognitive status in ischemic subjects were respectively studied with the National Institutes of Health stroke scale (NIHSS), modified Rankin Scale (MRS), and Mini-Mental State Examination (MMSE). Stroke patients had significantly lower serum level of CoQ10 and SOD as compared to controls (27.34 ± 35.40 ng/ml, 18.58 ± 0.76 μ/ml, respectively; p < 0.05), whereas the serum MDA level was significantly higher (38.02 ± 2.61 μm, p < 0.05). A significant negative correlation was detected between the serum CoQ10 level and scores of NIHSS and MRS. A similar association was discerned between the SOD level and the neurological deficit score. The serum MDA level was also found to be strongly correlated with all three neurological scales. These findings suggest that the serum level of CoQ10 like other antioxidant and oxidant markers can significantly change early after ischemic stroke and they are substantially associated with clinical neurological outcomes.

Antioxidants and oxidative stress can participate in pathobiochemical mechanisms of autism spectrum disorders (ASDs). The aim was to identify the effects of early CoQ 10 supplementation on oxidative stress in children with ASDs. Ninety children with ASDs were included in this study, based on DSM-IV criteria and using Childhood Autism Rating Scale (CARS) scores. Concentrations of CoQ 10 , MDA, total antioxidant status (TAS) assay, and antioxidant enzymes (superoxide dismutase or SOD and glutathione peroxidase or GPx) activity were determined in serum before and after 100 days of supportive therapy with CoQ 10 at daily doses of 30 and 60 mg. Data on children's behavior were collected from parents and babysitters. CoQ 10 supportive therapy was determined after three months with daily dose 2 ͯ 30 mg improved oxidative stress in the children with ASDs. A relation was seen between serum MDA (r 2  = 0.668) and TAS (r 2  = 0.007), and antioxidant enzymes (SOD [r 2  = 0.01] and GPx [r 2  = 0.001]) activity and CARS score. Based on the results, high doses of CoQ 10 can improve gastrointestinal problems (P = 0.004) and sleep disorders (P = 0.005) in children with ASDs with an increase in the CoQ 10 of the serum. We concluded that the serum concentration of CoQ 10 and oxidative stress could be used as relevant biomarkers in helping the improvement of ASDs., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Autism spectrum disorder (ASD) is a neuro-behavioral syndrome with a broad spectrum of different mechanisms and etiologies that are caused by abnormal brain development. To date, no highly reliable and effective diagnostic biomarker to assess ASD is available so far. The present study investigated the predictivity potential of some suggested markers in ASD diagnosis focusing onto the relative ratios of several plasma biomarkers of electron transport chain function, and mitochondrial metabolism in 41 patients with ASD evaluated for behavior deficits measured using Childhood Autism Rating Scales (CARS). The control matched for further 41 healthy subjects. The relation of these relative ratios to ASD severity was also examined, as well as their ability to distinguish ASD children from neurotypical children. All predictive ratios were found to be markedly altered and correlated in ASD patients. However, no ratio was connected with autism severity. Interestingly, MRCC-I/caspase-7, GSH/GST, and MRCC-I/COQ10 were the most distinctive relative ratios between neurotypical controls and ASD patients and may thereby be useful biomarkers for early diagnosis of ASD. Overall, this investigation proves that relative ratios of numerous mitochondrial biomarkers might be predictive and efficient to differentiate between neurotypical children and ASD.