코큐텐 (심장)

BACKGROUND: Chronic heart failure is a debilitating condition that accounts for an annual NHS spend of £2.3B. Low levels of endogenous coenzyme Q10 may exacerbate chronic heart failure. Coenzyme Q10 supplements might improve symptoms and slow progression. As statins are thought to block the production of coenzyme Q10, supplementation might be particularly beneficial for patients taking statins. OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of coenzyme Q10 in managing chronic heart failure with a reduced ejection fraction. METHODS: A systematic review that included randomised trials comparing coenzyme Q10 plus standard care with standard care alone in chronic heart failure. Trials restricted to chronic heart failure with a preserved ejection fraction were excluded. Databases including MEDLINE, EMBASE and CENTRAL were searched up to March 2020. Risk of bias was assessed using the Cochrane Risk of Bias tool (version 5.2). A planned individual participant data meta-analysis was not possible and meta-analyses were mostly based on aggregate data from publications. Potential effect modification was examined using meta-regression. A Markov model used treatment effects from the meta-analysis and baseline mortality and hospitalisation from an observational UK cohort. Costs were evaluated from an NHS and Personal Social Services perspective and expressed in Great British pounds at a 2019/20 price base. Outcomes were expressed in quality-adjusted life-years. Both costs and outcomes were discounted at a 3.5% annual rate. RESULTS: A total of 26 trials, comprising 2250 participants, were included in the systematic review. Many trials were reported poorly and were rated as having a high or unclear risk of bias in at least one domain. Meta-analysis suggested a possible benefit of coenzyme Q10 on all-cause mortality (seven trials, 1371 participants; relative risk 0.68, 95% confidence interval 0.45 to 1.03). The results for short-term functional outcomes were more modest or unclear. There was no indication of increased adverse events with coenzyme Q10. Meta-regression found no evidence of treatment interaction with statins. The base-case cost-effectivenes

BACKGROUND: 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. OBJECTIVES: To review the safety and efficacy of coenzyme Q10 in heart failure. SEARCH METHODS: 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. SELECTION CRITERIA: 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. DATA COLLECTION AND ANALYSIS: 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 synth

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 Previous studies have demonstrated a possible association between the induction of coenzyme Q10 (CoQ10) after statin treatment and statin-induced myopathy. However, whether CoQ10 supplementation ameliorates statin-induced myopathy remains unclear. Methods and Results PubMed, EMBASE , and Cochrane Library were searched to identify randomized controlled trials investigating the effect of CoQ10 on statin-induced myopathy. We calculated the pooled weighted mean difference ( WMD ) using a fixed-effect model and a random-effect model to assess the effects of CoQ10 supplementation on statin-associated muscle symptoms and plasma creatine kinase. The methodological quality of the studies was determined, according to the Cochrane Handbook. Publication bias was evaluated by a funnel plot, Egger regression test, and the Begg-Mazumdar correlation test. Twelve randomized controlled trials with a total of 575 patients were enrolled; of them, 294 patients were in the CoQ10 supplementation group and 281 were in the placebo group. Compared with placebo, CoQ10 supplementation ameliorated statin-associated muscle symptoms, such as muscle pain ( WMD , -1.60; 95% confidence interval [ CI ], -1.75 to -1.44; P<0.001), muscle weakness ( WMD , -2.28; 95% CI , -2.79 to -1.77; P=0.006), muscle cramp ( WMD , -1.78; 95% CI , -2.31 to -1.24; P<0.001), and muscle tiredness ( WMD , -1.75; 95% CI , -2.31 to -1.19; P<0.001), whereas no reduction in the plasma creatine kinase level was observed after CoQ10 supplementation ( WMD , 0.09; 95% CI , -0.06 to 0.24; P=0.23). Conclusions CoQ10 supplementation ameliorated statin-associated muscle symptoms, implying that CoQ10 supplementation may be a complementary approach to manage statin-induced myopathy.

BACKGROUND: Blood pressure is a commonly measured risk factor for non-fatal and fatal cardiovascular adverse events such as heart attacks and strokes. Clinical trials have suggested that coenzyme Q10, a non-prescription nutritional supplement, can effectively lower blood pressure (BP). When this review was completed and published in October 2009, it concluded that "due to the possible unreliability of the 3 included studies, it is uncertain whether or not coenzyme Q10 reduces blood pressure in the long-term management of primary hypertension." OBJECTIVES: To determine the blood pressure lowering effect of coenzyme Q10 in primary hypertension. SEARCH METHODS: We searched the Hypertension Group Specialised Register (1946 to November 2015), The Cochrane Central Register of Controlled Trials (The Cochrane Library 2015, Issue 10), MEDLINE (1946 to November 2015), MEDLINE In-Process (accessed 10 November 2015), EMBASE (1974 to November 2015), Web of Science (1899 to November 2015), CINAHL (1970 to November 2015), and ClinicalTrials.gov (accessed 10 November 2015). We also searched reference lists of articles for relevant clinical trials in any language. SELECTION CRITERIA: Double blind, randomized, placebo-controlled parallel or cross-over trials evaluating the blood pressure (BP) lowering efficacy of coenzyme Q10 for a duration of at least three weeks, in patients with primary hypertension. DATA COLLECTION AND ANALYSIS: The primary author determined trial inclusion, extracted the data and assessed the risk of bias. The second author independently verified trial inclusion and data extraction. MAIN RESULTS: In this update of the review, one new randomized, controlled cross-over trial with a total of 30 participants was added, and one trial included in the initial review was excluded. Only two of the three included trials were pooled in the meta-analysis, as one trial was judged to have an unacceptably high risk of bias. In the meta-analysis of two RCTs (50 participants), coenzyme Q10 did not significantly change systolic BP: -3.68 mm Hg (95% confidence interval (CI) -8.86 to 1.49), or diastolic BP: -2.03 mm Hg (95% CI -4.86 to 0.81] ), based on clinic data. AUTHORS' CO

OBJECTIVE: To evaluate the efficacy of coenzyme Q10 (CoQ10) supplementation on statin-induced myopathy. PARTICIPANTS AND METHODS: We searched the MEDLINE, Cochrane Library, Scopus, and EMBASE databases (November 1, 1987, to May 1, 2014) to identify randomized controlled trials investigating the impact of CoQ10 on muscle pain and plasma creatine kinase (CK) activity as 2 measures of statin-induced myalgia. Two independent reviewers extracted data on study characteristics, methods, and outcomes. RESULTS: We included 6 studies with 302 patients receiving statin therapy: 5 studies with 226 participants evaluated the effect of CoQ10 supplementation on plasma CK activity, and 5 studies (4 used in the CK analysis and 1 other study) with 253 participants were included to assess the effect of CoQ10 supplementation on muscle pain. Compared with the control group, plasma CK activity was increased after CoQ10 supplementation, but this change was not significant (mean difference, 11.69 U/L [to convert to μkat/L, multiply by 0.0167]; 95% CI, -14.25 to 37.63 U/L; P=.38). Likewise, CoQ10 supplementation had no significant effect on muscle pain despite a trend toward a decrease (standardized mean difference, -0.53; 95% CI, -1.33 to 0.28; P=.20). No dose-effect association between changes in plasma CK activity (slope, -0.001; 95% CI, -0.004 to 0.001; P=.33) or in the indices of muscle pain (slope, 0.002; 95% CI, -0.005 to 0.010; P=.67) and administered doses of CoQ10 were observed. CONCLUSION: The results of this meta-analysis of available randomized controlled trials do not suggest any significant benefit of CoQ10 supplementation in improving statin-induced myopathy. Larger, well-designed trials are necessary to confirm the findings from this meta-analysis.

BACKGROUND: 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 patients 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 preventing the consumption of metabolites essential for adenosine-5'-triphosphate (ATP) synthesis. Coenzyme Q10, although not a primary recommended treatment, could be beneficial to patients with heart failure. Several randomised controlled trials have compared coenzyme Q10 to other therapeutic modalities, but no systematic review of existing randomised trials has been conducted. OBJECTIVES: To review the safety and efficacy of coenzyme Q10 in heart failure. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 12); MEDLINE OVID (1950 to January Week 3 2013) and EMBASE OVID (1980 to 2013 Week 03) on 24 January 2013; Web of Science with Conference Proceedings (1970 to January 2013) and CINAHL Plus (1981 to January 2013) on 25 January 2013; and AMED (Allied and Complementary Medicine) (1985 to January 2013) on 28 January 2013. We applied no language restrictions. SELECTION CRITERIA: We included randomised controlled trials of either parallel or cross-over design that assessed the beneficial and harmful effects of coenzyme Q10 in patients with heart failure. When cross-over studies were identified, we considered data only from the first phase. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data from the included studies onto a pre-designed data extraction form. We then entered the data into Review Manager 5.2 for analysis. We assessed study risk of bias using the Cochrane 'Risk of bias' tool. For dichotomous data

BACKGROUND: Coenzyme Q₁₀ (CoQ₁₀; also called ubiquinone) is an antioxidant that has been postulated to improve functional status in congestive heart failure (CHF). Several randomized controlled trials have examined the effects of CoQ₁₀ on CHF with inconclusive results. OBJECTIVE: The objective of this meta-analysis was to evaluate the impact of CoQ₁₀ supplementation on the ejection fraction (EF) and New York Heart Association (NYHA) functional classification in patients with CHF. DESIGN: A systematic review of the literature was conducted by using databases including MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and manual examination of references from selected studies. Studies included were randomized controlled trials of CoQ₁₀ supplementation that reported the EF or NYHA functional class as a primary outcome. Information on participant characteristics, trial design and duration, treatment, dose, control, EF, and NYHA classification were extracted by using a standardized protocol. RESULTS: Supplementation with CoQ₁₀ resulted in a pooled mean net change of 3.67% (95% CI: 1.60%, 5.74%) in the EF and -0.30 (95% CI: -0.66, 0.06) in the NYHA functional class. Subgroup analyses showed significant improvement in EF for crossover trials, trials with treatment duration ≤12 wk in length, studies published before 1994, and studies with a dose ≤100 mg CoQ₁₀/d and in patients with less severe CHF. These subgroup analyses should be interpreted cautiously because of the small number of studies and patients included in each subgroup. CONCLUSIONS: Pooled analyses of available randomized controlled trials suggest that CoQ₁₀ may improve the EF in patients with CHF. Additional well-designed studies that include more diverse populations are needed.

BACKGROUND: Mitochondrial respiratory chain disorders are the most prevalent group of inherited neurometabolic diseases. They present with central and peripheral neurological features usually in association with other organ involvement including the eye, the heart, the liver, and kidneys, diabetes mellitus and sensorineural deafness. Current treatment is largely supportive and the disorders progress relentlessly causing significant morbidity and premature death. Vitamin supplements, pharmacological agents and exercise therapy have been used in isolated cases and small clinical trials, but the efficacy of these interventions is unclear. The first review was carried out in 2003, and identified six clinical trials. This major update was carried out to identify new studies and grade the original studies for potential bias in accordance with revised Cochrane Collaboration guidelines. OBJECTIVES: To determine whether there is objective evidence to support the use of current treatments for mitochondrial disease. SEARCH METHODS: We searched the Cochrane Neuromuscular Disease Group Specialized Register (4 July 2011), CENTRAL (2011, Issue 2, MEDLINE (1966 to July 2011), and EMBASE (January 1980 to July 2011), and contacted experts in the field. SELECTION CRITERIA: We included randomised controlled trials (including cross-over studies). Two of the authors independently selected abstracts for further detailed review. Further review was performed independently by all five authors to decide which trials fit the inclusion criteria and graded risk of bias. Participants included males and females of any age with a confirmed diagnosis of mitochondrial disease based upon muscle histochemistry, respiratory chain complex analysis of tissues or cell lines or DNA studies. Interventions included any pharmacological agent, dietary modification, nutritional supplement, exercise therapy or other treatment. The review authors excluded studies at high risk of bias in any category. The primary outcome measures included an change in muscle strength and/or endurance, or neurological clinical features. Secondary outcome measures included quality of life assessments, biochemical markers of disea

BACKGROUND: Studies have shown that coenzyme Q10 deficiency is associated with cardiovascular disease. Hypertension is a commonly measured surrogate marker for non-fatal and fatal cardiovascular endpoints such as heart attacks and strokes. Clinical trials have suggested that coenzyme Q10 supplementation can effectively lower blood pressure (BP). OBJECTIVES: To determine the blood pressure lowering effect of coenzyme Q10 in primary hypertension. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (2009 Issue 2), MEDLINE (1966 -May 2008), EMBASE (1982 - May 2008), and CINAHL (1970 - May 2008) as well as the reference lists of articles were searched for relevant clinical trials in any language. SELECTION CRITERIA: Double-blind, randomized, placebo-controlled parallel or crossover trials evaluating the BP lowering efficacy of coenzyme Q10 for a duration of at least 3 weeks in patients with primary hypertension. DATA COLLECTION AND ANALYSIS: The primary author independently assessed the risk of bias and extracted the data. The second author verified data extraction. MAIN RESULTS: Three clinical trials with a total of 96 participants were evaluated for the effects of coenzyme Q10 on blood pressure compared to placebo. Treatment with coenzyme Q10 in subjects with systolic BP (SBP) > 140 mmHg or diastolic BP (DBP) > 90 mmHg resulted in mean decreases in SBP of 11 mmHg (95% CI 8, 14) and DBP of 7 mmHg (95% CI 5, 8). AUTHORS' CONCLUSIONS: Due to the possible unreliability of some of the included studies, it is uncertain whether or not coenzyme Q10 reduces blood pressure in the long-term management of primary hypertension.

Background. Research indicates that omega-3 fatty acids, resveratrol, astaxanthin, and coenzyme Q10 (CoQ10) possess anti-inflammatory properties, and their vascular benefits have been well-documented. This is a pilot study aimed at comprehensively evaluating the potential impact of the compound fish oil capsules on the microcirculation of multiple organs. Methods. In a triple-blind, randomized, placebo-controlled trial, 64 hypertensive patients were randomly assigned to either the compound fish oil (FO) group or the corn oil (CO) group (n = 32 per group) for a 3-week intervention. Participants were required to consume 2 capsules of the corresponding oil daily. The microcirculation functions of the heart, skin, and brain were examined by transthoracic Doppler echocardiography (TTDE), laser Doppler flowmetry (LDF), and magnetic resonance imaging (MRI), respectively. Data were primarily analyzed according to an intention-to-treat approach. Findings. In the left anterior descending artery (LAD), the end-diastolic velocity (EDV) and peak diastolic velocity (PDV) significantly increased in the FO group. The mean differences in change were 1.95 (0.13, 3.77; p = 0.036) and 2.95 (0.48, 5.41; p = 0.020), respectively. The resistance index (RI) showed a decreasing trend in the FO group, but the result was non-significant (p = 0.071). No significant differences were observed in blood pressure, brain and skin microcirculation parameters among the different groups. Interpretation. Compound fish oil capsules did not significantly improve RH. But compound fish oil capsules improved EDV and PDV levels in the LAD of hypertensive patients.

Ageing is associated with attenuated exercise responses in skeletal muscle, which may be related to a failure of muscle redox signalling. The attenuation of redox responses to exercise in aged muscle has been linked to perturbations in redox homeostasis induced by age-related increases in mitochondrial oxidative stress. Accordingly, we investigated the effects of supplementation with the mitochondria-targeted antioxidant MitoQ on mitochondrial bioenergetics and H2O2 emission as well as acute exercise-induced redox responses in skeletal muscle of older individuals. In a randomised, double-blind, placebo-controlled, parallel design, 10 males and 12 females aged 65-80 years were randomised to receive either MitoQ (20 mg/day) or a placebo for 12 weeks before completing a single bout of exercise. Vastus lateralis muscle biopsies were collected before supplementation and before, immediately post- and 4 h post-exercise. MitoQ supplementation reduced mitochondrial H2O2 emission capacity in skeletal muscle but did not impact mitochondrial respiration, H2O2 emission in the presence of ADP, or the sensitivity for ADP to stimulate respiration (apparent Km) and attenuate H2O2 emission (apparent IC50). Acute exercise-induced peroxiredoxin oxidation in skeletal muscle was not altered by MitoQ supplementation. Similarly, MitoQ had no effect on the phosphorylation of several redox-sensitive protein kinases (AMPK, p38 MAPK, and ERK1/2) or the upregulation of mitochondrial and antioxidant genes following exercise. Collectively, these findings indicate that MitoQ supplementation did not influence the basal myocellular redox state or redox responses to exercise in skeletal muscle of older individuals.

BACKGROUND: Selenoprotein P (SELENOP) transports selenium to extrahepatic tissues and is a biomarker of selenium status. Low soil selenium leads to low dietary selenium intake. A consequence is an increased risk of cardiovascular disease. OBJECTIVE: To investigate clinical aspects associated with SELENOP deficiency, including biomarkers of inflammation, quality of life, and mortality within 12 years, and the effect of dietary selenium and coenzyme Q10 supplementation on SELENOP. METHODS: SELENOP was determined at inclusion and after four years of supplementation in 403 elderly community-living participants low in selenium receiving selenium yeast (200 μg/day) and coenzyme Q10 (200 mg/day), or placebo. Pre-intervention, the average serum selenium level was 67 μg/L. T-tests, repeated measures of variance, Cox proportional regressions analyses, Kaplan-Meier graphs and ANCOVA analyses were applied. Associations with biomarkers of inflammation, telomere length, quality of life and mortality were investigated. Benchmark modelling was used to determine the serum selenium concentration at which the saturation levels of SELENOP and GPx3 was achieved. Comparison with GPx3 and serum selenium to identify increased mortality risk was performed, and the effect of supplementation on SELENOP levels were evaluated. RESULTS: Inverse associations were observed between the level of SELENOP at inclusion and biomarkers for inflammation. At follow-up, shorter telomere lengths were seen in those with low levels of SELENOP at inclusion, whereas high levels of SELENOP were associated with better quality of life and decreased mortality. SELENOP had increased prognostic power compared to GPx3 and selenium. Saturation of SELENOP was achieved at a serum selenium level of 146 μg/L, and for GPx3 at 99 μg/L. Supplementation induced higher levels of SELENOP. CONCLUSION: Significant associations between SELENOP and inflammation, length of telomeres, quality of life, and mortality were observed. Thus, selenium supplementation improved SELENOP expression, thereby facilitating systemic selenium bioavailability and resulting in the observed positive health effects.

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 Q10 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 Q10 (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 Q10 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 Q10 had a beneficial effect on thyroid hormones with respect to CV mortality and Hr-QoL outcomes. The initial deficient selenium status was associated

BACKGROUND: High-altitude exposure changes the electrical conduction of the heart. However, reports on electrocardiogram (ECG) characteristics and potent prophylactic agents during high-altitude acclimatization and de-acclimatization are inadequate. This study aimed to investigate the effects of ubiquinol on electrophysiology after high-altitude hypoxia and reoxygenation. METHODS: The study was a prospective, randomized, double-blind, placebo-controlled trial. Forty-one participants were randomly divided into two groups receiving ubiquinol 200 mg daily or placebo orally 14 days before flying to high altitude (3900 m) until the end of the study. Cardiopulmonary exercise testing was performed at baseline (300 m), on the third day after reaching high altitude, and on the seventh day after returning to baseline. RESULTS: Acute high-altitude exposure prolonged resting ventricular repolarization, represented by increased corrected QT interval (455.9 ± 23.4 vs. 427.1 ± 19.1 ms, P < 0.001) and corrected Tpeak-Tend interval (155.5 ± 27.4 vs. 125.3 ± 21.1 ms, P < 0.001), which recovered after returning to low altitude. Ubiquinol supplementation shortened the hypoxia-induced extended Tpeak-Tend interval (-7.7 ms, [95% confidence interval (CI), -13.8 to -1.6], P = 0.014), Tpeak-Tend /QT interval (-0.014 [95% CI, -0.027 to -0.002], P = 0.028), and reserved maximal heart rate (11.9 bpm [95% CI, 3.2 to 20.6], P = 0.013) during exercise at high altitude. Furthermore, the decreased resting amplitude of the ST-segment in the V3 lead was correlated with decreased peak oxygen pulse (R = 0.713, P < 0.001) and maximum oxygen consumption (R = 0.595, P < 0.001). CONCLUSIONS: Our results illustrated the electrophysiology changes during high-altitude acclimatization and de-acclimatization. Similarly, ubiquinol supplementation shortened the prolonged Tpeak-Tend interval and reserved maximal heart rate during exercise at high altitude. REGISTRATION: URL: www.chictr.org.cn; Unique identifier: ChiCTR2200059900.

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 inflam

Background: Ageing is associated with cardiovascular disease (CVD). As no single biomarker reflects the full ageing process, we aimed to investigate five CVD- and age-related markers and the effects of selenium and coenzyme Q10 intervention to elucidate the mechanisms that may influence the course of ageing. Methods: This is a sub-study of a previous prospective double-blind placebo-controlled randomized clinical trial that included 441 subjects low in selenium (mean age 77, 49% women). The active treatment group (n = 220) received 200 µg/day of selenium and 200 mg/day of coenzyme Q10, combined. Blood samples were collected at inclusion and after 48 months for measurements of the intercellular adhesion molecule (ICAM-1), adiponectin, leptin, stem cell factor (SCF) and osteoprotegerin (OPG), using ELISAs. Repeated measures of variance and ANCOVA evaluations were used to compare the two groups. In order to better understand and reduce the complexity of the relationship between the biomarkers and age, factor analyses and structural equation modelling (SEM) were performed, and a structural model is presented. Results: Correlation analyses of biomarker values at inclusion in relation to age, and relevant markers related to inflammation, endothelial dysfunction and fibrosis, demonstrated the biomarkers' association with these pathological processes; however, only ICAM1 and adiponectin were directly correlated with age. SEM analyses showed, however, that the biomarkers ICAM-1, adiponectin, SCF and OPG, but not leptin, all had significant associations with age and formed two independent structural factors, both significantly related to age. While no difference was observed at inclusion, the biomarkers were differently changed in the active treatment and placebo groups (decreasing and increasing levels, respectively) at 48 months (p ≤ 0.02 in all, adjusted), and in the SEM model, they showed an anti-ageing impact. Conclusions: Supplementation with selenium/Q10 influenced the analysed biomarkers in ways indicating an anti-ageing effect, and by applying SEM methodology, the interrelationships between two independent structural factors and age were validated.

Short telomeres have been associated with ageing and cardiovascular disease. The influence on leukocyte telomere length (LTL) of long-term intervention with combined selenium and coenzyme Q10 is unknown. Our aim was to determine whether 42 months of selenium and coenzyme Q10 supplementation prevented telomere attrition and further cardiovascular mortality. The investigation is an explorative sub-study of a double-blind, placebo-controlled, randomized trial. Swedish citizens low in selenium (n = 118), aged 70−80 years, were included. Intervention time was 4 years, with 10 years’ follow-up time. LTL was relatively quantified with PCR at baseline and after 42 months. At baseline, LTL (SD) was 0.954 (0.260) in the active treatment group and 1.018 (0.317) in the placebo group (p = 0.23). At 42 months, less shortening of LTL was observed after active treatment compared with placebo (+0.019 vs. −0.129, respectively, p = 0.02), with a significant difference in change basing the analysis on individual changes in LTL (p < 0.001). Subjects suffering future death presented with significantly shorter LTL at 42 months than survivors [0.791 (0.190) vs. 0.941 (0.279), p = 0.01], with a significant difference in change of LTL according to cardiovascular mortality and survival (p = 0.03). To conclude, preservation of LTL after selenium and coenzyme Q10 supplementation associated with reduced cardiovascular mortality.

Patients with heart failure with preserved ejection fraction (HFpEF) have few pharmacologic therapies, and it is not known if supplementing with ubiquinol and/or d-ribose could improve outcomes. The overall objective of this study was to determine if ubiquinol and/or d-ribose would reduce the symptoms and improve cardiac performance in patients with HFpEF. This was a phase 2 randomized, double-blind, placebo-controlled trial of 216 patients with HFpEF who were ≥ 50 years old with a left ventricular ejection fraction (EF) ≥ 50%. A total of 4 study groups received various supplements over 12 weeks: Group 1 received placebo ubiquinol capsules and d-ribose powder, Group 2 received ubiquinol capsules (600 mg/d) and placebo d-ribose powder, Group 3 received placebo ubiquinol capsules with d-ribose powder (15 g/d), and Group 4 received ubiquinol capsules and d-ribose powder. There were 7 outcome measures for this study: Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score, level of vigor using a subscale from the Profile of Mood States, EF, the ratio of mitral peak velocity of early filling to early diastolic mitral annular velocity (septal E/e' ratio), B-type natriuretic peptides, lactate/adenosine triphosphate ratio, and the 6-minute walk test. Treatment with ubiquinol and/or d-ribose significantly improved the KCCQ clinical summary score (17.30 to 25.82 points), vigor score (7.65 to 8.15 points), and EF (7.08% to 8.03%) and reduced B-type natriuretic peptides (-72.02 to -47.51) and lactate/adenosine triphosphate ratio (-4.32 to -3.35 × 10-4). There were no significant increases in the septal E/e' or the 6-minute walk test. In conclusion, ubiquinol and d-ribose reduced the symptoms of HFpEF and increased the EF. These findings support the use of these supplements in addition to standard therapeutic treatments for patients with HFpEF.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is common in elderly people and is increasing in prevalence. No specific treatment for this condition exists. Coenzyme Q10 (CoQ10) is an essential cofactor for energy production, with reduced levels being noted in HF. Previous studies have suggested a possible role for CoQ10 in the treatment of HF. This study examined the effect of CoQ10 supplementation on diastolic function in HFpEF patients. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled trial including patients aged > 55 years presenting with New York Heart Association class II-IV heart failure symptoms and left ventricular ejection fraction > 50%, with impaired diastolic function. Echocardiography and levels of serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) were performed at baseline and following 4 months of CoQ10 or placebo supplementation. RESULTS: A total of 39 patients were enrolled-19 in the CoQ10 group and 20 in the placebo group. Baseline clinical characteristics were similar between groups, while compliance was high and also similar between the CoQ10 and placebo groups. There was no significant effect of treatment on indices of diastolic function (difference in the lateral E/e' ratio: -0.86 ± 6.57 in the CoQ10 group, +0.18 ± 3.76 in the placebo group; p = 0.561) or on serum NT-proBNP levels (- 72 pg/mL vs. - 42 pg/mL; p = 0.195). CONCLUSIONS: In this pilot trial in elderly patients with HFpEF, treatment with CoQ10 did not significantly affect echocardiographic indices of diastolic function and serum NT-proBNP levels. TRIAL REGISTRATION: This trial was registered in the US National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier: NCT02779634). © 2021. The Author(s).

At the site of myocardial infarction (MI), various phenomena such as oxidative stress and myocardial apoptosis can be observed. Both epigallocatechin gallate (EGCG) and coenzyme Q10 (CoQ10) exhibit antioxidant and anti-inflammatory effects. Macrophages have demonstrated a higher internalization rate of cationic liposomes, thereby increasing their bioavailability. This study utilized EGCG in synergy with CoQ10 as an antioxidant agent and distearyl phosphatidylcholine (DSPC) as the carrier, to create liposome nanoparticles known as CE-LNPs. The CE-LNPs exhibited favorable biocompatibility and were effectively engulfed by macrophages in vitro. In addition, the CE-LNPs effectively eradicated reactive oxygen species (ROS) in hypoxic cardiomyocytes, mitigated myocardial cell apoptosis, and sustained the functionality and proliferation of myocardial cells. The anti-apoptotic effect of the CE-LNPs was further validated through TUNEL and Annexin V FITC/PI experiments. The therapeutic efficacy of CE-LNPs was evaluated in a murine model of MI. CE-LNPs demonstrated a significant reduction in scar area in vivo, facilitating cardiac repair and improving cardiac function. These findings provide evidence that EGCG synergistically combined with CoQ10 in DSPC liposome nanoparticles offers protection against MI.

BACKGROUND: Preconditioning of the heart ameliorates doxorubicin (Dox)-induced cardiotoxicity. We tested whether pretreating cardiomyocytes by mitochondrial-targeted antioxidants, mitoquinone (MitoQ) or SKQ1, would provide better protection against Dox than co-treatment. METHODS: We investigated the dose-response relationship of MitoQ, SKQ1, and vitamin C on Dox-induced damage on H9c2 cardiomyoblasts when drugs were given concurrently with Dox (e.g., co-treatment) or 24 h prior to Dox (e.g., pretreatment). Moreover, their effects on intracellular and mitochondrial oxidative stress were evaluated by 2,7-dichlorofluorescin diacetate and MitoSOX, respectively. RESULTS: Dox (0.5-50 μM, n = 6) dose-dependently reduced cell viability. By contrast, co-treatment of MitoQ (0.05-10 μM, n = 6) and SKQ1 (0.05-10 μM, n = 6), but not vitamin C (1-2000 μM, n = 3), significantly improved cell viability only at intermediate doses (0.5-1 μM). MitoQ (1 μM) and SKQ1 (1 μM) significantly increased cell viability to 1.79 ± 0.12 and 1.59 ± 0.08 relative to Dox alone, respectively (both p < 0.05). Interestingly, when given as pretreatment, only higher doses of MitoQ (2.5 μM, n = 9) and SKQ1 (5 μM, n = 7) showed maximal protection and improved cell viability to 2.19 ± 0.13 and 1.65 ± 0.07 relative to Dox alone, respectively (both p < 0.01), which was better than that of co-treatment. Moreover, the protective effects were attributed to the significant reduction in Dox-induced intracellular and mitochondrial oxidative stress. CONCLUSION: The data suggest that MitoQ and SKQ1, but not vitamin C, mitigated DOX-induced damage. Moreover, MitoQ pretreatment showed significantly higher cardioprotection than its co-treatment and SKQ1, which may be due to its better antioxidant effects. © 2021. The Author(s).

Heart failure (HF) with either preserved or reduced ejection fraction is associated with increased morbidity and mortality. Evidence-based therapies are often limited by tolerability, hypotension, electrolyte disturbances, and renal dysfunction. Coenzyme Q10 (CoQ10) may represent a safe therapeutic option for patients with HF. CoQ10 is a highly lipophilic molecule with a chemical structure similar to vitamin K. Although being a common component of cellular membranes, CoQ10's most prominent role is to facilitate the production of adenosine triphosphate in the mitochondria by participating in redox reactions within the electron transport chain. Numerous trials during the past 30 years examining CoQ10 in patients with HF have been limited by small numbers and lack of contemporary HF therapies. The recent publication of the Q-SYMBIO randomized controlled trial demonstrated a reduction in major adverse cardiovascular events with CoQ10 supplementation in a contemporary HF population. Although having limitations, this study has renewed interest in evaluating CoQ10 supplementation in patients with HF. Current literature suggests that CoQ10 is relatively safe with few drug interactions and side effects. Furthermore, it is already widely available as an over-the-counter supplement. These findings warrant future adequately powered randomized controlled trials of CoQ10 supplementation in patients with HF. This state-of-the-art review summarizes the literature about the mechanisms, clinical data, and safety profile of CoQ10 supplementation in patients with HF. © 2016 American Heart Association, Inc.

85. J Am Heart Assoc. 2016 Jan 27;5(1):e002497. doi: 10.1161/JAHA.115.002497. Overcoming Challenges With Statin Therapy. Spence JD(1), Dresser GK(2). Author information: (1)Stroke Prevention & Atherosclerosis Research Centre, Robarts Research Institute, Western University, London, Ontario, Canada (D.S.) Division of Clinical Pharmacology, Department of Medicine, Western University, London, Ontario, Canada (D.S., G.K.D.). (2)Division of Clinical Pharmacology, Department of Medicine, Western University, London, Ontario, Canada (D.S., G.K.D.). DOI: 10.1161/JAHA.115.002497 PMCID: PMC4859367 PMID: 26819251 [Indexed for MEDLINE]

Statins are the first-line pharmacotherapy for cholesterol reduction. Use of these drugs in large randomized clinical trials has consistently shown significant reductions in major vascular events, including death, myocardial infarction, stroke, and coronary revascularization. The updated guidelines for the treatment of high blood cholesterol from the American College of Cardiology/American Heart Association (ACC/AHA), will lead to an increase in the number of patients taking statins. Hence, the number of cases of statin intolerance may subsequently increase, emphasizing the need to understand and treat this important problem.

OBJECTIVE: Mitochondria-derived reactive oxygen species (ROS) play important roles in the development of cardiovascular disease highlighting the need for novel targeted therapies. This study assessed the potential therapeutic benefit of combining the mitochondria-specific antioxidant, MitoQ10, with the low-dose angiotensin receptor blocker (ARB), losartan, on attenuation of hypertension and left ventricular hypertrophy. In parallel, we investigated the impact of MitoQ10 on cardiac hypertrophy in a neonatal cardiomyocyte cell line. METHODS AND RESULTS: Eight-week-old male stroke-prone spontaneously hypertensive rats (SHRSPs, n=8-11) were treated with low-dose losartan (2.5 mg/kg per day); MitoQ10 (500 μmol/l); a combination of MitoQ10 and losartan (M+L); or vehicle for 8 weeks. Systolic pressure and pulse pressure were significantly lower in M+L rats (167.1 ± 2.9 mmHg; 50.2 ± 2.05 mmHg) than in untreated SHRSP (206.6 ± 9 mmHg, P<0.001; 63.7 ± 2.7 mmHg, P=0.001) and demonstrated greater improvement than MitoQ10 or low-dose losartan alone, as measured by radiotelemetry. Left ventricular mass index was significantly reduced from 22.8 ± 0.74 to 20.1 ± 0.61 mg/mm in the combination group (P<0.05). Picrosirius red staining showed significantly reduced cardiac fibrosis in M+L rats (0.82 ± 0.22 A.U.) compared with control (5.94 ± 1.35 A.U., P<0.01). In H9c2 neonatal rat cardiomyocytes, MitoQ10 significantly inhibited angiotensin II mediated hypertrophy in a dose-dependent manner (500 nmol/l MitoQ10 153.7 ± 3.1 microns vs. angiotensin II 200.1 ± 3.6 microns, P<0.001). CONCLUSION: Combining MitoQ10 and low-dose losartan provides additive therapeutic benefit, significantly attenuating development of hypertension and reducing left ventricular hypertrophy. In addition, MitoQ10 mediates a direct antihypertrophic effect on rat cardiomyocytes in vitro. MitoQ10 has potential as a novel therapeutic intervention in conjunction with current antihypertensive drugs.

Coenzyme Q10 (CoQ10) is critical to production of adenosine triphosphate and is an antioxidant that scavenges reactive oxygen species during oxidative stress. The use of CoQ10 in treating oxidative stress in cardiovascular diseases, diabetes, and cancer is reviewed.

BACKGROUND/HYPOTHESES: Doxorubicin is a standard adjuvant therapy for early-stage breast cancer, and it significantly improves disease-free and overall survival. However, 3% to 20% of breast cancer patients develop chronic cardiomyopathic changes and congestive heart failure because of doxorubicin therapy. Doxorubicin-induced cardiotoxicity is thought to be due to the increased generation of reactive oxygen species within cardiac myocyte mitochondria. Coenzyme Q10 (CoQ10) is a lipid-soluble antioxidant that may protect against mitochondrial reactive oxygen species and thus prevent doxorubicin-induced cardiotoxicity. Despite the potential benefits of CoQ10 in preventing cardiotoxicity, it is not known if CoQ10 diminishes the antineoplastic effects of doxorubicin therapy. STUDY DESIGN: In vitro cell culture experiments. METHODS: Breast cancer cell lines (MDA-MB-468 and BT549) were tested for their ability to uptake exogenous CoQ10 using high-performance liquid chromatography. Breast cancer cell lines were then treated with doxorubicin and a range of CoQ10 concentrations to determine the effect of CoQ10 on doxorubicin's cytotoxicity. RESULTS: This study demonstrated that intracellular and mitochondrial CoQ10 concentrations increased substantially as higher exogenous concentrations were administered to breast cancer cells. CoQ10 had no effect on the ability of doxorubicin to induce apoptosis or inhibit growth or colony formation in both the cell lines tested when applied over a wide dose range, which encompassed typical basal plasma levels and plasma levels above those typically achieved by supplemented patients. CONCLUSION: The clinical testing of CoQ10 as a supplement to prevent doxorubicin-induced cardiotoxicity requires confidence that it does not decrease the efficacy of chemotherapy. These results support the hypothesis that CoQ10 does not alter the antineoplastic properties of doxorubicin. Further in vivo studies, as well as combination chemotherapy studies, would be reassuring before a large-scale clinical testing of CoQ10 as a cardioprotective drug.

Cancer cells are long known to exhibit increased aerobic glycolysis, but glycolytic inhibition has not offered a viable chemotherapeutic strategy in part because of the systemic toxicity of antiglycolytic agents. However, recent studies suggest that a combined inhibition of glycolysis and mitochondrial function may help overcome this issue. In this study, we investigated the chemotherapeutic efficacies of mitochondria-targeted drugs (MTD) in combination with 2-deoxy-d-glucose (2-DG), a compound that inhibits glycolysis. Using the MTDs, termed Mito-CP and Mito-Q, we evaluated relative cytotoxic effects and mitochondrial bioenergetic changes in vitro. Interestingly, both Mito-CP and Mito-Q synergized with 2-DG to decrease ATP levels in two cell lines. However, with time, the cellular bioenergetic function and clonogenic survival were largely restored in some cells. In a xenograft model of human breast cancer, combined treatment of Mito-CP and 2-DG led to significant tumor regression in the absence of significant morphologic changes in kidney, liver, or heart. Collectively, our findings suggest that dual targeting of mitochondrial bioenergetic metabolism with MTDs and glycolytic inhibitors such as 2-DG may offer a promising chemotherapeutic strategy. ©2012 AACR.

The effect of atorvastatin on cardiac remodeling, function, and homodynamic parameters in isoproterenol-induced heart failure was evaluated in the present study. A subcutaneous injection of isoproterenol (5mg/kg/day) for 10 days was used for the induction of heart failure. Isoproterenol administration produced intensive myocardial necrosis and fibrosis with a significant decrease in the arterial pressure indices, heart rate, contractility (LVdP/dt(max)) and relaxation (LVdP/dt(min)), but an increase in the left ventricular end-diastolic pressure. Rats were randomly assigned to control, treatment with only atorvastatin, and treatment with atorvastatin plus coenzyme Q10. Histopathological analysis showed a marked attenuation of myocyte necrosis and interstitial fibrosis in all atorvastatin treated groups (P<0.001). A low dose of atorvastatin (5mg/kg/day) significantly improved the left ventricular systolic pressure, contractility and relaxation (P<0.01). On the contrary, a high dose of atorvastatin (20mg/kg/day) worsened the isoproterenol-induced left ventricular dysfunction by a further reduction of LVdP/dt(max) from +2780 ± 94 to +1588 ± 248 (mmHg/s; P<0.01) and LVdP/dt(min) from -2007 ± 190 to -2939 ± 291 (mmHg/s; P<0.05). Co-administration of coenzyme Q10 with atorvastatin reversed the hemodynamic depression and the left ventricular dysfunction to a high level (P<0.001). There was a lower level of LVEDPs in the atorvastatin+coenzyme Q10 treated groups (3 ± 1 and 4 ± 1.4 versus 8 ± 3.5 and 14 ± 3.6 mmHg, respectively), thereby suggesting improvement in the myocardial stiffness by the combined coenzyme Q10 and atorvastatin treatment. The atorvastatin therapy attenuated myocardial necrosis and fibrosis in isoproterenol-induced heart failure. However, a high dose of the drug considerably worsened the left ventricular dysfunction and hemodynamic depression, which was reversed by coenzyme Q10 co-administration.