ubiquinone and Stroke

Coenzyme Q10, or ubiquinone, is a non-prescription nutritional supplement. It is a fat-soluble molecule that acts as an electron carrier in mitochondria, and as a coenzyme for mitochondrial enzymes. Coenzyme Q10 deficiency may be associated with a multitude of diseases, including heart failure. The severity of heart failure correlates with the severity of coenzyme Q10 deficiency. Emerging data suggest that the harmful effects of reactive oxygen species are increased in people with heart failure, and coenzyme Q10 may help to reduce these toxic effects because of its antioxidant activity. Coenzyme Q10 may also have a role in stabilising myocardial calcium-dependent ion channels, and in preventing the consumption of metabolites essential for adenosine-5'-triphosphate (ATP) synthesis. Coenzyme Q10, although not a primary recommended treatment, could be beneficial to people with heart failure. Several randomised controlled trials have compared coenzyme Q10 to other therapeutic modalities, but no systematic review of existing randomised trials was conducted prior to the original version of this Cochrane Review, in 2014.. To review the safety and efficacy of coenzyme Q10 in heart failure.. We searched CENTRAL, MEDLINE, Embase, Web of Science, CINAHL Plus, and AMED on 16 October 2020; ClinicalTrials.gov on 16 July 2020, and the ISRCTN Registry on 11 November 2019. We applied no language restrictions.. We included randomised controlled trials of either parallel or cross-over design that assessed the beneficial and harmful effects of coenzyme Q10 in people with heart failure. When we identified cross-over studies, we considered data only from the first phase.. We used standard Cochrane methods, assessed study risk of bias using the Cochrane 'Risk of bias' tool, and GRADE methods to assess the quality of the evidence. For dichotomous data, we calculated the risk ratio (RR); for continuous data, the mean difference (MD), both with 95% confidence intervals (CI). Where appropriate data were available, we conducted meta-analysis. When meta-analysis was not possible, we wrote a narrative synthesis. We provided a PRISMA flow chart to show the flow of study selection.. We included eleven studies, with 1573 participants, comparing coenzyme Q10 to placebo or conventional therapy (control). In the majority of the studies, sample size was relatively small. There were important differences among studies in daily coenzyme Q10 dose, follow-up period, and the measures of treatment effect. All studies had unclear, or high risk of bias, or both, in one or more bias domains. We were only able to conduct meta-analysis for some of the outcomes. None of the included trials considered quality of life, measured on a validated scale, exercise variables (exercise haemodynamics), or cost-effectiveness. Coenzyme Q10 probably reduces the risk of all-cause mortality more than control (RR 0.58, 95% CI 0.35 to 0.95; 1 study, 420 participants; number needed to treat for an additional beneficial outcome (NNTB) 13.3; moderate-quality evidence). There was low-quality evidence of inconclusive results between the coenzyme Q10 and control groups for the risk of myocardial infarction (RR 1.62, 95% CI 0.27 to 9.59; 1 study, 420 participants), and stroke (RR 0.18, 95% CI 0.02 to 1.48; 1 study, 420 participants). Coenzyme Q10 probably reduces hospitalisation related to heart failure (RR 0.62, 95% CI 0.49 to 0.78; 2 studies, 1061 participants; NNTB 9.7; moderate-quality evidence). Very low-quality evidence suggests that coenzyme Q10 may improve the left ventricular ejection fraction (MD 1.77, 95% CI 0.09 to 3.44; 7 studies, 650 participants), but the results are inconclusive for exercise capacity (MD 48.23, 95% CI -24.75 to 121.20; 3 studies, 91 participants); and the risk of developing adverse events (RR 0.70, 95% CI 0.45 to 1.10; 2 studies, 568 participants). We downgraded the quality of the evidence mainly due to high risk of bias and imprecision.. The included studies provide moderate-quality evidence that coenzyme Q10 probably reduces all-cause mortality and hospitalisation for heart failure. There is low-quality evidence of inconclusive results as to whether coenzyme Q10 has an effect on the risk of myocardial infarction, or stroke. Because of very low-quality evidence, it is very uncertain whether coenzyme Q10 has an effect on either left ventricular ejection fraction or exercise capacity. There is low-quality evidence that coenzyme Q10 may increase the risk of adverse effects, or have little to no difference. There is currently no convincing evidence to support or refute the use of coenzyme Q10 for heart failure. Future trials are needed to confirm our findings.

Topics: Ataxia; Heart Failure; Humans; Mitochondrial Diseases; Muscle Weakness; Myocardial Infarction; Quality of Life; Stroke; Stroke Volume; Ubiquinone; Ventricular Function, Left

Mitochondrial encephalomyopathy with lactic acidosis and stroke- like episodes (MELAS) syndrome is caused by mitochondrial respiratory chain dysfunction and oxidative phosphorylation disorder. It is a rare clinical metabolic disease involved with multiple systems.. A 22-year-old patient presented with limb convulsion accompanied by loss of consciousness, headache, partial blindness, blurred vision, and so on.. Brain magnetic resonance imaging showed a high-intensity area in bilateral occipital cortex, left parietal lobe and cerebellum on diffusion-weighted imaging. These focus did not distribute as vascular territory. The pathological examination of skeletal muscle revealed several succinate dehydrogenase reactive vessels with overreaction and increased content of lipid droplets in some muscle fibers. Genetic testing showed that the patient carried m.10158T>C mutation.. She was provided with traditional arginine hydrochloride therapy and orally medication of coenzyme Q (10 mg).. Mitochondrial DNA of blood and hair follicle of patient carried m.10158T>C mutation LESSONS:: For the suspected patients of MELAS syndrome, if the hot-spot mutation test is negative, more detection sites should be selected.

Topics: Acidosis, Lactic; Administration, Oral; Arginine; Awareness; Brain; DNA, Mitochondrial; Female; Humans; Magnetic Resonance Imaging; MELAS Syndrome; Micronutrients; Mitochondrial Encephalomyopathies; Muscle, Skeletal; Mutation; Stroke; Succinate Dehydrogenase; Ubiquinone; Young Adult

Topics: Animals; Atorvastatin; Dietary Supplements; Rats; Stroke; Ubiquinone

Idebenone is a well-appreciated mitochondrial protectant while the mechanisms underlying the neuroprotection in cerebral ischemia and reperfusion (I/R) remain elusive. It has been manifested NLRP3 inflammasom activation contributed to I/R induced damage. It raises questions how exactly NLRP3 inflammasom was activated in microglia and neuron and whether idebenone reverses the process in I/R.. I/R rat model was utilized and BV2, primary microglia and PC12 cells were subjected to oxygen-glucose deprivation (OGD). Then, western-blotting, q-PCR, immunofluorescence staining, ELISA, flow cytometry and immunoprecipitation analysis were performed.. We found ROS-NLRP3 singaling was activated in BV2 cells at OGD/R 24 h. Importantly, microglial NLRP3 activation was essential for NLRP3 activation in PC12 cells under microglial-neuronal co-culture circumstance, which has been confirmed to induced neuronal apoptosis. Further, we found mitochondrial dysfunction in OGD/R led to mt-DNA translocation as well as generation of mt-ROS, resulting cytosolic accumulation of oxidized mt-DNA. Ultimately, oxidized mt-DNA binding to NLRP3 contributed to further activation of NLRP3 and dramatically augmented inflammation in BV2 and PC12 cells. Furthermore, idebenone treatment inhibited the process, thus suppressing the NLRP3-mediated inflammatory injury after OGD/R. In vivo, NLRP3 was activated in microglia of I/R rats and inhibition of NLRP3 was observed in idebenone treatment group, which had less neurological deficit and less infarct volume.. Our data revealed the anti-inflammatory effects of idebenone via suppressing activation of NLRP3 and ameliorating NLRP3-mediating damage in I/R, which may provide new insight in therapeutic strategy for ischemic stroke.

Topics: Animals; Animals, Newborn; Brain Ischemia; Cells, Cultured; Encephalitis; Inflammasomes; Male; Mice; Mice, Inbred C57BL; Neuroprotection; NLR Family, Pyrin Domain-Containing 3 Protein; PC12 Cells; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Signal Transduction; Stroke; Ubiquinone

Neonatal ischemic stroke has a higher incidence than childhood stroke. Seizures are the first sign for the need for clinical assessment in neonates, but many questions remain regarding treatments and follow-up modalities. In the absence of a known pathophysiological mechanism, only supportive care is currently provided. Stroke-induced microglia activation and neuroinflammation are believed to play a central role in the pathological progression of neonatal ischemic stroke. We induced a photothrombotic infarction with Rose Bengal in neonatal rats to investigate the effects of pre- and post-treatment with Aspirin (ASA), Clopidogrel (Clop), and Coenzyme Q10 (CoQ10), which are known for their neuroprotective effects in adult stroke. Pre-stroke medication ameliorates cerebral ischemic injury and reduces infarct volume by reducing microglia activation, cellular reactive oxygen species (ROS) production, and cytokine release. Post-stroke administration of ASA, Clop, and CoQ10 increased motor function and reduced the volume of infarction, and the statistical evidence was stronger than that seen in the pre-stroke treatment. In this study, we demonstrated that ASA, Clop, and CoQ10 treatment before and after the stroke reduced the scope of stroke lesions and increased behavioral activity. It suggests that ASA, Clop, and CoQ10 medication could significantly have neuroprotective effects in the neonates who have suffered strokes.

Topics: Animals; Animals, Newborn; Aspirin; Brain Ischemia; Clopidogrel; Disease Models, Animal; Inflammation; Neuroprotective Agents; Rats; Rose Bengal; Stroke; Ubiquinone

Coenzyme Q10 (CoQ10, ubiquinone) stands among the safest supplements in the elderly to protect against cardiovascular disorders. Noteworthy, CoQ10 deficiency is common in many surviving stroke patients as they are mostly prescribed statins for the secondary prevention of stroke incidence lifelong. Accordingly, the current study aims to experimentally examine whether CoQ10 supplementation in animals receiving atorvastatin may affect acute stroke-induced injury.. Adult rats underwent transient middle cerebral artery occlusion after atorvastatin pretreatment (5 or 10 mg/ kg/day; po; 30 days) with or without CoQ10 (200 mg/kg/day). After 24 hours ischemic/reperfusion injury, animals were subjected to functional assessments followed by cerebral molecular and histological to detect inflammation, apoptosis and oxidative stress.. Animals dosed with 10 mg/kg presented the worst neurological function and brain damage in the acute phase of stroke injury. CoQ10 supplementation efficiently improved functional deficit and cerebral infarction in all stroke animals, particularly those exhibiting statin toxicity. Such benefits were associated with remarkable anti-inflammatory and anti-apoptotic effects, based on the analyzed tumor necrosis factor-α, interleukin-6, Bax/Bcl2 and cleaved caspase 3/9 immunoblots. Importantly, our fluoro-jade staining data indicated CoQ10 may revert the stroke-induced neurodegeneration. No parallel alteration was detected in stroke-induced oxidative stress as determined by malondialdehyde and 8-oxo-2'-deoxyguanosine levels.. These data suggest that all stroke animals may benefit from CoQ10 administration through modulating inflammatory and degenerative pathways. This study provides empirical evidence for potential advantages of CoQ10 supplementation in atorvastatin-receiving patients which may not shadow its antioxidant properties.

Topics: Animals; Apoptosis; Atorvastatin; Brain Ischemia; Encephalitis; Male; Neuroprotective Agents; Oxidative Stress; Rats, Wistar; Stroke; Treatment Outcome; Ubiquinone

Oxidative stress has been implicated in the pathophysiology of cerebral stroke. As NADPH oxidases (NOXs) play major roles in the regulation of oxidative stress, we hypothesized that reduction of NOX activity by depletion of p22phox, an essential subunit of NOX complexes, would prevent cerebral stroke. To investigate this, we used the stroke-prone spontaneously hypertensive rat (SHRSP) and the p22phox-deleted congenic SHRSP. Although p22phox depletion reduced blood pressure under salt loading, it did not ameliorate oxidative stress or reduce the incidence of salt-induced stroke in SHRSPs. Additional pharmacological reduction of oxidative stress using antioxidant reagents with different mechanisms of action was necessary to prevent stroke, indicating that NOX was not the major target in salt-induced stroke in SHRSPs. On the other hand, oxidative stress measured based on urinary isoprostane levels showed significant correlations with blood pressure, stroke latency and urinary protein excretion under salt loading, suggesting an important role of oxidative stress per se in hypertension and hypertensive organ damage. Overall, our results imply that oxidative stress from multiple sources influences stroke susceptibility and other hypertensive disorders in salt-loaded SHRSPs.

Topics: Animals; Antioxidants; Blood Pressure; Cyclic N-Oxides; Enzyme Inhibitors; Febuxostat; Male; NADPH Oxidases; Oxidative Stress; Rats; Rats, Inbred SHR; Rats, Transgenic; Reactive Oxygen Species; Sodium Chloride; Spin Labels; Stroke; Ubiquinone; Xanthine Oxidase

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.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Case-Control Studies; Female; Humans; Male; Malondialdehyde; Middle Aged; Stroke; Superoxide Dismutase; Ubiquinone

Ndufc2, a subunit of the NADH: ubiquinone oxidoreductase, plays a key role in the assembly and activity of complex I within the mitochondrial OXPHOS chain. Its deficiency has been shown to be involved in diabetes, cancer and stroke. To improve our knowledge on the mechanisms underlying the increased disease risk due to Ndufc2 reduction, we performed the present in vitro study aimed at the fine characterization of the derangements in mitochondrial structure and function consequent to Ndufc2 deficiency. We found that both fibroblasts obtained from skin of heterozygous Ndufc2 knock-out rat model showed marked mitochondrial dysfunction and PBMC obtained from subjects homozygous for the TT genotype of the rs11237379/NDUFC2 variant, previously shown to associate with reduced gene expression, demonstrated increased generation of reactive oxygen species and mitochondrial damage. The latter was associated with increased oxidative stress and significant ultrastructural impairment of mitochondrial morphology with a loss of internal cristae. In both models the exposure to stress stimuli, such as high-NaCl concentration or LPS, exacerbated the mitochondrial damage and dysfunction. Resveratrol significantly counteracted the ROS generation. These findings provide additional insights on the role of an altered pattern of mitochondrial structure-function as a cause of human diseases. In particular, they contribute to underscore a potential genetic risk factor for cardiovascular diseases, including stroke.

Topics: Animals; Electron Transport Complex I; Fibroblasts; Humans; Leukocytes, Mononuclear; Metabolism, Inborn Errors; Mitochondria; Mitochondrial Diseases; Mitochondrial Proteins; Oxidation-Reduction; Oxidative Phosphorylation; Oxidative Stress; Protein Subunits; Rats; Rats, Inbred SHR; Reactive Oxygen Species; Stroke; Ubiquinone

It is established that intravenous injection of solubilized coenzyme Q10 provides quick and lasting increase in its level in the brain as compared to control intact rats and those with cerebral ischemia. These new data provide a basis for studying the efficacy of coenzyme Q10 as a neuroprotective agent in ischemic stroke.

Topics: Animals; Brain; Brain Ischemia; Injections, Intravenous; Male; Neuroprotective Agents; Rats; Rats, Wistar; Stroke; Ubiquinone

An aim of the study was to assess the severity of asthenic syndrome, emotional disorders and quality of life indicators in post stroke patients treated with idebenone (noben). We studied 35 patients aged from 47 to 76 years, mean age 58,85±7,99 years, 21 men and 14 women. The time after stroke was 1-8 years (mean 2,63±1,51 years). The duration of follow-up was 6 months. Patients were examined at baseline and 3 and 6 months after treatment with noben in dose 90 mg daily (30 mg 3 times a day). Patients were examined clinically, the following scales were used as well: the Scandinavian stroke scale, the modified MFIS-21, the hospital anxiety and depression scale (HADS) and EQ5D including VAS. It has been shown that asthenic syndrome negatively influenced quality of life and emotional sphere thus impeding the recovery of daily activities. The follow-up study revealed that the treatment with idebenone in dose 90 mg daily decreased the severity of asthenia and emotional disorders and significantly improved quality of life.

Topics: Affective Symptoms; Aged; Aged, 80 and over; Antioxidants; Female; Humans; Male; Middle Aged; Quality of Life; Severity of Illness Index; Stroke; Ubiquinone

Mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) is a maternally-inherited multisystem disorder. Mitochondrial angiopathy mediated by nitric oxide, a metabolite of L-arginine, is among the proposed pathophysiologic mechanisms of stroke-like episodes (SLEs) in MELAS. There are very few reports on long-term prevention of SLEs with oral L-arginine and idebenone treatment in MELAS adult patients.. A 38-year-old patient with MELAS and SLEs was treated with oral L-arginine and idebenone for 27months. She remained free of attacks throughout the treatment period except when she stopped her treatment on two occasions during which she had recurrent cerebral metabolic attacks. The patient experienced no side effect of treatment with L-arginine and idebenone.. Our observation suggests long-term safety and potential benefit of oral L-arginine and idebenone in the prevention of recurrence of SLEs in adult MELAS patients.

Topics: Administration, Oral; Adult; Antioxidants; Arginine; Drug Combinations; Female; Humans; MELAS Syndrome; Stroke; Time Factors; Treatment Outcome; Ubiquinone

Predominant cerebellar involvement has not been previously reported as a common neuroradiologic feature in pediatric mitochondrial cytopathies. Here we report the neuroradiologic findings of predominant cerebellar volume loss in children with various mitochondrial disorders.. A retrospective analysis of the medical records of 400 consecutive patients referred for evaluation of mitochondrial encephalomyopathies was performed. In 113 cases, definite diagnosis of mitochondrial disease was based on the modified adult criteria that include clinical, histologic, biochemical, functional, molecular, and metabolic parameters.. Predominant cerebellar volume loss with progressive cerebellar atrophy and, less often, cerebellar hypoplasia were found in a heterogeneous group of patients with mitochondrial disease that consisted of four patients with complex I deficiency; four patients with multiple respiratory chain deficiencies; two patients with combined complex I + III and II + III deficiencies, including one patient with partial coenzyme Q10 deficiency; three patients with complex II deficiency; two patients with complex IV deficiency; one patient with mitochondrial neurogastrointestinal encephalomyopathy; and two patients with mitochondrial encephalomyopathy, lactic acidosis, and strokes.. Our retrospective study shows that isolated or predominant cerebellar involvement can be found in various respiratory chain defects or mitochondrial disorders expanding the classical neuroradiologic findings observed in mitochondrial encephalomyopathies. The diagnostic workup in patients with neuromuscular features whose brain MR imaging exhibits cerebellar volume loss should include the evaluation for mitochondrial encephalomyopathies.

Topics: Acidosis, Lactic; Adolescent; Adult; Cerebellum; Child; Child, Preschool; Female; Humans; Infant; Leigh Disease; Magnetic Resonance Imaging; Male; Metabolism, Inborn Errors; Mitochondrial Encephalomyopathies; Multienzyme Complexes; Retrospective Studies; Stroke; Ubiquinone

Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are widely used for the treatment of hypercholesterolemia and coronary heart disease and for the prevention of stroke. There have been various adverse effects, most commonly affecting muscle and ranging from myalgia to rhabdomyolysis. These adverse effects may be due to a coenzyme Q(10) (CoQ(10)) deficiency because inhibition of cholesterol biosynthesis also inhibits the synthesis of CoQ(10).. To measure CoQ(10) levels in blood from hypercholesterolemic subjects before and after exposure to atorvastatin calcium, 80 mg/d, for 14 and 30 days.. Prospective blinded study of the effects of short-term exposure to atorvastatin on blood levels of CoQ(10).. Stroke center at an academic tertiary care hospital. Patients We examined a cohort of 34 subjects eligible for statin treatment according to National Cholesterol Education Program: Adult Treatment Panel III criteria.. The mean +/- SD blood concentration of CoQ(10) was 1.26 +/- 0.47 micro g/mL at baseline, and decreased to 0.62 +/- 0.39 micro g/mL after 30 days of atorvastatin therapy (P<.001). A significant decrease was already detectable after 14 days of treatment (P<.001).. Even brief exposure to atorvastatin causes a marked decrease in blood CoQ(10) concentration. Widespread inhibition of CoQ(10) synthesis could explain the most commonly reported adverse effects of statins, especially exercise intolerance, myalgia, and myoglobinuria.

Topics: Aged; Analysis of Variance; Atorvastatin; Cardiovascular Diseases; Coenzymes; Female; Heptanoic Acids; Humans; Hypercholesterolemia; Longitudinal Studies; Male; Middle Aged; Prospective Studies; Pyrroles; Risk Factors; Stroke; Ubiquinone