Coenzyme Q10 for heart failure.

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 synthesis. We provided a PRISMA flow chart to show the flow of study selection. MAIN RESULTS: 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. AUTHORS' CONCLUSIONS: 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.

Effect of Coenzyme Q10 on statin-associated myalgia and adherence to statin therapy: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Statin associated muscle symptoms are common and affect adherence to statin treatment. The objective of this study was to assess whether patients with statin-associated myalgia can be successfully treated with Coenzyme Q10 (CoQ10) to improve symptoms and maintain them on statin therapy. METHODS: This systematic review was performed in line with the 2015 PRISMA statement. Relevant studies were identified via a search of MEDLINE, EMBASE and the Cochrane Library. Studies were screened to include randomised controlled trials of oral CoQ10 supplementation versus a placebo in adults with statin-associated myalgia. Continuation of statin therapy was a secondary outcome. Risk of bias was assessed using the Cochrane Risk of Bias tool. Pooled and sensitivity analyses were performed. RESULTS: 413 records were identified by the search strategy. Eight studies were selected for review, and 7 of them (with 321 patients) were included in the meta-analysis. Selected studies were published between 2007 and 2016 with the number of participants ranging from 37 to 76. Only two of these studies demonstrated a positive effect of CoQ10 therapy in relieving muscle pain. The meta-analysis did not demonstrate any benefit of CoQ10 supplementation in improving myalgia symptoms compared to placebo (weighted mean difference -0.42; 95% Confidence Interval [CI] -1.47 to 0.62). Similarly, CoQ10 did not improve the proportion of patients remaining on the statin treatment (RR 0.99; 95%CI, 0.81 to 1.20). CONCLUSIONS: This systematic review and meta-analysis did not demonstrate that CoQ10 supplementation was beneficial for patients with statin-associated muscle pain or improved adherence to statin therapy.

NT-Pro BNP Predicts Myocardial Injury Post-vascular Surgery and is Reduced with CoQ10: A Randomized Double-Blind Trial.

BACKGROUND: NT-Pro BNP levels provide incremental value in perioperative risk assessment prior to major noncardiac surgery. Whether they can be pharmacologically modified in patients prior to an elective vascular operation is uncertain. METHODS: A double-blind, randomized controlled trial was implemented at a single institution. Patients were screened during their preoperative vascular clinic appointment and randomly assigned to CoQ10 (400 mg per day) versus Placebo for 3 days prior to surgery. Biomarkers, including NT-Pro BNP, troponin I and C-reactive protein were obtained prior to and following surgery for up to 48 hours. The primary endpoint was postoperative NT-Pro BNP levels, and secondary endpoint measures included myocardial injury, defined by an elevated cardiac troponin level and length of stay. RESULTS: One hundred and twenty-three patients were randomized to receive either CoQ10 (N = 62) versus Placebo (N = 61) for 3 days before vascular surgery. Preoperative cardiac risks included ischemic heart disease (N = 52), CHF (N = 12), stroke (N = 23), and diabetes mellitus (N = 48) and the planned vascular procedures were infrainguinal (N = 78), carotid (N = 36), and intraabdominal (N = 9). There were no intergroup differences in these clinical variables. NT-Pro BNP levels (median; IQs) in the CoQ10 and Placebo groups were 179 (75-347) and 217 (109-585) pg/ml, respectively, (P = 0.08) preoperatively, and 397 (211-686) and 591 (288-1,433) pg/ml respectively, (P = 0.01) at 24 hours following surgery. Patients with an elevated NT-Pro BNP had a higher incidence of myocardial injury, (58% vs. 20%; P < 0.01) and a longer hospital stay (4.4 ± 3.8 vs. 2.8 ± 3.2 days; P < 0.02) compared with individuals without an elevated NT-Pro BNP level. CONCLUSIONS: NT-Pro BNP levels predict adverse events post-vascular surgery and are lowered in those patients assigned to preoperative administration of CoQ10. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03956017. Among patients undergoing elective vascular surgery, 123 patients were randomized to either CoQ10 (400 mg/day) versus placebo for three days preoperatively. NT-Pro BNP levels (median; IQs) in the CoQ10 and Placebo groups were 179 (75-347) and 217 (109-585) pg/ml, respectively, (P = 0.08) preoperatively, and 397 (211-686) and 591 (288-1,433) pg/ml, respectively, (P = 0.01) post-surgery. Patients with an elevated NT-Pro BNP had a higher incidence of myocardial injury (58% vs. 20%; P < 0.01) and a longer hospital stay (4.4 ± 3.8 vs. 2.8 ± 3.2 days; P < 0.02) compared with individuals without an NT-Pro BNP elevation. In conclusion, BNP predicts adverse outcomes and can be reduced with preoperative CoQ10.

Coenzyme Q10 nanostructured lipid carriers as an inducer of the skin fibroblast cell and its irritability test in a mice model.

Background Coenzyme Q10 is a fat-soluble antioxidant that can help to prevent collagen and elastin damage and avoid wrinkles. Coenzyme Q10 has several disadvantages to be formulated in topical dosage forms, such as low water solubility and large molecular weight. These make coenzyme Q10 retained in the stratum corneum and cause low skin penetration, so proper formulation is required to get products that can penetrate the skin layer. A nanostructured lipid carrier (NLC) consists of a matrix of solid lipids and liquid lipids in a certain amount with nanoparticle size; it may help increase the penetration of active ingredients. Methods For the antiaging activity test, mice were grouped into four treatment groups and killed on the 14th day; then the back of the skin was stained with Masson trichrome staining. For the irritation test, the mice were grouped into three groups and killed after 24 h; then the back of the mice was stained with hematoxylin-eosin staining. Results The number of fibroblasts in mice with NLC coenzyme Q10 is highest from all test groups. The irritation test results after 24 h of application preparation showed that NLC coenzyme Q10 did not irritate the skin of the back of male mice. Conclusions One percent coenzyme Q10 loaded in NLC induced the number of fibroblast cells in the mice model and showed no irritability effect in histopathology preparations.

Coenzyme Q10.

Coenzyme Q10 (CoQ10) is among the most widely used dietary and nutritional supplements on the market. CoQ10 has several fundamental properties that may be beneficial in several clinical situations. This article reviews the pertinent chemical, metabolic, and physiologic properties of CoQ10 and the scientific data and clinical trials that address its use in two common clinical settings: statin-associated myopathy syndrome (SAMS) and congestive heart failure (CHF). Although clinical trials of CoQ10 in SAMS have conflicting conclusions, the weight of the evidence, as seen in meta-analyses, supports the use of CoQ10 in SAMS overall. In CHF, there is a lack of large-scale randomized clinical trial data regarding the use of statins in patients receiving contemporary treatment. However, one relatively recent randomized clinical trial, Q-SYMBIO, suggests an adjunctive role for CoQ10 in CHF. Recommendations regarding the use of CoQ10 in these clinical situations are presented.

Supplementation with exogenous coenzyme Q10 to media for in vitro maturation and embryo culture fails to promote the developmental competence of porcine embryos.

The coenzyme Q10 (CoQ10) is a potent antioxidant with critical protection role against cell oxidative stress, caused by the mitochondrial dysfunction. This study evaluated the effects of CoQ10 supplementation to in vitro maturation (IVM) or embryo culture media on the maturation, fertilization and subsequent embryonic development of pig oocytes and embryos. Maturation (Experiment 1) or embryo culture (Experiment 2) media were supplemented with 0 (control), 10, 25, 50 and 100 µM CoQ10. The addition of 10-50 µM CoQ10 to the IVM medium did not affect the percentage of MII oocytes nor the fertilization or the parameters of subsequent embryonic development. Exogenous CoQ10 in the culture medium neither did affect the development to the 2-4-cell stage nor rates of blastocyst formation. Moreover, the highest concentration of CoQ10 (100 µM) in the maturation medium negatively affected blastocyst rates. In conclusion, exogenous CoQ10 supplementation of maturation or embryo culture media failed to improve the outcomes of our in vitro embryo production system and its use as an exogenous antioxidant should not be encouraged.

Interventions for preventing and treating cardiac complications in Duchenne and Becker muscular dystrophy and X-linked dilated cardiomyopathy.

BACKGROUND: The dystrophinopathies include Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and X-linked dilated cardiomyopathy (XLDCM). In recent years, co-ordinated multidisciplinary management for these diseases has improved the quality of care, with early corticosteroid use prolonging independent ambulation, and the routine use of non-invasive ventilation signficantly increasing survival. The next target to improve outcomes is optimising treatments to delay the onset or slow the progression of cardiac involvement and so prolong survival further. OBJECTIVES: To assess the effects of interventions for preventing or treating cardiac involvement in DMD, BMD, and XLDCM, using measures of change in cardiac function over six months. SEARCH METHODS: On 16 October 2017 we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE and Embase, and on 12 December 2017, we searched two clinical trials registries. We also searched conference proceedings and bibliographies. SELECTION CRITERIA: We considered only randomised controlled trials (RCTs), quasi-RCTs and randomised cross-over trials for inclusion. In the Discussion, we reviewed open studies, longitudinal observational studies and individual case reports but only discussed studies that adequately described the diagnosis, intervention, pretreatment, and post-treatment states and in which follow-up lasted for at least six months. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed the titles and abstracts identified from the search and performed data extraction. All three authors assessed risk of bias independently, compared results, and decided which trials met the inclusion criteria. They assessed the certainty of evidence using GRADE criteria. MAIN RESULTS: We included five studies (N = 205) in the review; four studies included participants with DMD only, and one study included participants with DMD or BMD. All studied different interventions, and meta-analysis was not possible. We found no studies for XLDCM. None of the trials reported cardiac function as improved or stable cardiac versus deteriorated.The randomised first part of a two-part study of perindopril (N = 28) versus placebo (N = 27) in boys with DMD with normal heart function at baseline showed no difference in the number of participants with a left ventricular ejection fraction (LVEF%) of less than 45% after three years of therapy (n = 1 in each group; risk ratio (RR) 1.04, 95% confidence interval (CI) 0.07 to 15.77). This result is uncertain because of study limitations, indirectness and imprecision. In a non-randomised follow-up study, after 10 years, more participants who had received placebo from the beginning had reduced LVEF% (less than 45%). Adverse event rates were similar between the placebo and treatment groups (low-certainty evidence).A study comparing treatment with lisinopril versus losartan in 23 boys newly diagnosed with Duchenne cardiomyopathy showed that after 12 months, both were equally effective in preserving or improving LVEF% (lisinopril 54.6% (standard deviation (SD) 5.19), losartan 55.2% (SD 7.19); mean difference (MD) -0.60% CI -6.67 to 5.47: N = 16). The certainty of evidence was very low because of very serious imprecision and study limitations (risk of bias). Two participants in the losartan group were withdrawn due to adverse events: one participant developed an allergic reaction, and a second exceeded the safety standard with a fall in ejection fraction greater than 10%. Authors reported no other adverse events related to the medication (N = 22; very low-certainty evidence).A study comparing idebenone versus placebo in 21 boys with DMD showed little or no difference in mean change in cardiac function between the two groups from baseline to 12 months; for fractional shortening the mean change was 1.4% (SD 4.1) in the idebenone group and 1.6% (SD 2.6) in the placebo group (MD -0.20%, 95% CI -3.07 to 2.67, N = 21), and for ejection fraction the mean change was -1.9% (SD 9.8) in the idebenone group and 0.4% (SD 5.5) in the placebo group (MD -2.30%, 95% CI -9.18 to 4.58, N = 21). The certainty of evidence was very low because of study limitations and very serious imprecision. Reported adverse events were similar between the treatment and placebo groups (low-certainty evidence).A multicentre controlled study added eplerenone or placebo to 42 patients with DMD with early cardiomyopathy but preserved left ventricular function already established on ACEI or ARB therapy. Results showed that eplerenone slowed the rate of decline of magnetic resonance (MR)-assessed left ventricular circumferential strain at 12 months (eplerenone group median 1.0%, interquartile range (IQR) 0.3 to -2.2; placebo group median 2.2%, IQR 1.3 to -3.1%; P = 0.020). The median decline in LVEF over the same period was also less in the eplerenone group (-1.8%, IQR -2.9 to 6.0) than in the placebo group (-3.7%, IQR -10.8 to 1.0; P = 0.032). We downgraded the certainty of evidence to very low for study limitations and serious imprecision. Serious adverse events were reported in two patients given placebo but none in the treatment group (very low-certainty evidence).A randomised placebo-controlled study of subcutaneous growth hormone in 16 participants with DMD or BMD showed an increase in left ventricular mass after three months' treatment but no significant improvement in cardiac function. The evidence was of very low certainty due to imprecision, indirectness, and study limitations. There were no clinically significant adverse events (very low-certainty evidence).Some studies were at risk of bias, and all were small. Therefore, although there is some evidence from non-randomised data to support the prophylactic use of perindopril for cardioprotection ahead of detectable cardiomyopathy, and for lisinopril or losartan plus eplerenone once cardiomyopathy is detectable, this must be considered of very low certainty. Findings from non-randomised studies, some of which have been long term, have led to the use of these drugs in daily clinical practice. AUTHORS' CONCLUSIONS: Based on the available evidence from RCTs, early treatment with ACE inhibitors or ARBs may be comparably beneficial for people with a dystrophinopathy; however, the certainty of evidence is very low. Very low-certainty evidence indicates that adding eplerenone might give additional benefit when early cardiomyopathy is detected. No clinically meaningful effect was seen for growth hormone or idebenone, although the certainty of the evidence is also very low.

Double-blind, randomized and controlled trial of EPI-743 in Friedreich's ataxia.

AIM: To evaluate the safety and clinical effects of EPI-743 in Friedreich's ataxia patients. EPI-743 is a compound that targets oxidoreductase enzymes essential for redox control of metabolism. METHODS: We conducted a multicenter trial that evaluated EPI-743 during a 6-month placebo-controlled phase, followed by an 18-month open-label phase. End points included low-contrast visual acuity and the Friedreich's Ataxia Rating Scale. RESULTS/CONCLUSION: EPI-743 was demonstrated to be safe and well tolerated. There were no significant improvements in key end points during the placebo phase. However, at 24 months, EPI-743 treatment was associated with a statistically significant improvement in neurological function and disease progression relative to a natural history cohort (p < 0.001).

Study protocol, randomized controlled trial: reducing symptom burden in patients with heart failure with preserved ejection fraction using ubiquinol and/or D-ribose.

BACKGROUND: Heart failure (HF), the leading cause of morbidity and mortality in the US, affects 6.6 million adults with an estimated additional 3 million people by 2030. More than 50% of HF patients have heart failure with preserved left ventricular ejection fraction (HFpEF). These patients have impaired cardiac muscle relaxation and diastolic filling, which investigators have associated with cellular energetic impairment. Patients with HFpEF experience symptoms of: (1) fatigue; (2) shortness of breath; and (3) swelling (edema) of the lower extremities. However, current HF guidelines offer no effective treatment to address these underlying pathophysiologic mechanisms. Thus, we propose a biobehavioral symptom science study using ubiquinol and D-ribose (therapeutic interventions) to target mitochondrial bioenergetics to reduce the complex symptoms experienced by patients with HFpEF. METHODS: Using a randomized, double-blind, placebo-controlled design, the overall objective is to determine if administering ubiquinol and/or D-ribose to HFpEF patients for 12 weeks would decrease the severity of their complex symptoms and improve their cardiac function. The measures used to assess patients' perceptions of their health status and level of vigor (energy) will be the Kansas City Cardiomyopathy Questionnaire (KCCQ) and Vigor subscale of the Profile of Mood States. The 6-min walk test will be used to test exercise tolerance. Left ventricular diastolic function will be assessed using innovative advanced echocardiography software called speckle tracking. We will measure B-type natriuretic peptides (secreted from ventricles in HF) and lactate/ATP ratio (measure of cellular energetics). DISCUSSIONS: Ubiquinol (active form of Coenzyme Q10) and D-ribose are two potential treatments that can positively affect cellular energetic impairment, the major underlying mechanism of HFpEF. Ubiquinol, the reduced form of CoQ10, is more effective in adults over the age of 50. In patients with HFpEF, mitochondrial deficiency of ubiquinol results in decreased adenosine triphosphate (ATP) synthesis and reduced scavenging of reactive oxygen species. D-ribose is a substrate required for ATP synthesis and when administered has been shown to improve impaired myocardial bioenergetics. Therefore, if the biological underpinning of deficient mitochondrial ATP in HFpEF is not addressed, patients will suffer major symptoms including lack of energy, fatigue, exertional dyspnea, and exercise intolerance. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03133793 ; Data of Registration: April 28, 2017.

Effects of Coenzyme Q10 Supplementation on Gene Expressions Related to Insulin, Lipid, and Inflammation Pathways in Patients With Diabetic Nephropathy.

INTRODUCTION: Data on the effects of coenzyme Q10 (CQ10) on gene expression related to insulin, lipid, and inflammation in patients with diabetic nephropathy (DN) are scarce. This study aimed to determine the effects of CQ10 supplementation on gene expression related to insulin, lipid, and inflammation pathways in patients with DN. MATERIALS AND METHODS: Forty patients with DN, aged 40 to 85 years old, were randomly assigned into 2 groups to receive either 100 mg/d of CQ10 supplements (n = 20) or placebo (n = 20), for 12 weeks. Gene expression related to signaling pathway of insulin, lipid, and inflammation were determined in blood samples using a reverse transcriptase polymerase chain reaction method. RESULTS: Quantitative results of reverse transcriptase polymerase chain reaction demonstrated that compared with the placebo, CQ10 administration upregulated gene expression of peroxisome proliferator-activated receptor-γ (P = .02) in peripheral blood mononuclear cells of the patients with DN. In addition, compared with the placebo, CQ10 supplementation downregulated gene expression of interleukin-1 (P = .003) and tumor necrosis factor-α (P = .02). No significant effects were observed on gene expression of oxidized low-density lipoprotein, lipoprotein(a), glucose transporter-1, transforming growth factor-ß in the CQ10 group. CONCLUSIONS: Overall, CQ10 supplementation for 12 weeks in DN patients significantly improved gene expression of peroxisome proliferator-activated receptor-γ, interleukin-1, and tumor necrosis factor-α.

The Effects of Coenzyme Q10 Supplementation on Blood Pressures Among Patients with Metabolic Diseases: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

INTRODUCTION: Although several trials have assessed the effect of coenzyme Q10 (CoQ10) supplementation on blood pressures among patients with metabolic diseases, findings are controversial. AIM: This review of randomized controlled trials (RCTs) was performed to summarize the evidence on the effects of CoQ10 supplementation on blood pressures among patients with metabolic diseases. METHODS: Randomized-controlled trials (RCTs) published in PubMed, EMBASE, Web of Science and Cochrane Library databases up to 10 August 2017 were searched. Two review authors independently assessed study eligibility, extracted data, and evaluated risk of bias of included studies. Heterogeneity was measured with a Q-test and with I2 statistics. Data were pooled by using the fix or random-effect model based on the heterogeneity test results and expressed as standardized mean difference (SMD) with 95% confidence interval (CI). RESULTS: A total of seventeen randomized controlled trials (684 participants) were included. Results showed that CoQ10 supplementation significantly decreased systolic blood pressure (SBP) (SMD - 0.30; 95% CI - 0.52, - 0.08). However, CoQ10 supplementation decreased diastolic blood pressure (DBP), but this was not statistically significant (SMD - 0.08; 95% CI - 0.46, 0.29). CONCLUSIONS: CoQ10 supplementation may result in reduction in SBP levels, but did not affect DBP levels among patients with metabolic diseases. Additional prospective studies regarding the effect of CoQ10 supplementation on blood pressure in patients with metabolic diseases are necessary.

Efficacy of coenzyme Q10 in patients with cardiac failure: a meta-analysis of clinical trials.

BACKGROUND: The therapeutic efficacy of coenzyme Q10 on patients with cardiac failure remains controversial. We pooled previous clinical studies to re-evaluate the efficacy of coenzyme Q10 in patients with cardiac failure. METHODS: We searched PubMed, Cochrane Library, EMBASE, and Clinical Trials.gov databases for controlled trials. The endpoints were death, left heart ejection fraction, exercise capacity, and New York Heart Association (NYHA) cardiac function classification after treatment. The pooled risk ratios (RRs) and standardized mean difference (SMD) were used to assess the efficacy of coenzyme Q10. RESULTS: A total of 14 RCTs with 2149 patients met the inclusion criteria and were included in the analysis. Coenzyme Q10 decreased the mortality compared with placebo (RR = 0.69; 95% CI = 0.50-0.95; P = 0.02; I 2  = 0%). A greater improvement in exercise capacity was established in patients who used coenzyme Q10 than in those who used placebo (SMD = 0.62; 95% CI = 0.02-0.30; P = 0.04; I 2  = 54%). No significant difference was observed in the endpoints of left heart ejection fraction between patients who received coenzyme Q10 and the patients in whom placebo was administered (SMD = 0.62; 95% CI = 0.02-1.12; P = 0.04; I 2  = 75%). The two types of treatment resulted in obtaining similar NYHA classification results (SMD = -0.70; 95% CI = -1.92-0.51; P = 0.26; I 2  = 89%). CONCLUSION: Patients with heart failure who used coenzyme Q10 had lower mortality and a higher exercise capacity improvement than the placebo-treated patients with heart failure. No significant differences between the efficacy of the administration of coenzyme Q10 and placebo in the endpoints of left heart ejection fraction and NYHA classification were observed.

The efficacy and safety of coenzyme Q10 in Parkinson's disease: a meta-analysis of randomized controlled trials.

The objective of this meta-analysis was to evaluate the effects of coenzyme Q10 (CoQ10) for the treatment of Parkinson's disease (PD) patients in order to arrive at qualitative and quantitative conclusions about the efficacy of CoQ10. Databases searched included PubMed, Google scholar, CNKI, Wan-Fang, and the Cochrane Library from inception to March 2016. We only included sham-controlled, randomized clinical trials of CoQ10 intervention for motor dysfunction in patients with PD. Relevant measures were extracted independently by two investigators. Weighted mean differences (WMD) were calculated with random-effects models. Eight studies with a total of 899 patients were included. Random-effects analysis revealed a pooled WMD of 1.02, indicating no significant difference when CoQ10 treatment compared with placebo in terms of UPDRS part 3 (p = 0.54). Meanwhile, the effect size of UPDRS part 1, UPDRS part 2, and total UPDRS scores were similar in CoQ10 group with in placebo group (p > 0.05). Moreover, we found CoQ10 was well tolerated compared with placebo group. Subgroup analysis showed that the effect size of CoQ10 in monocentric studies was larger than in multicenter studies. Using the GRADE criteria, we characterized the quality of evidence presented in this meta-analysis as moderate to high level. The current meta-analysis provided evidence that CoQ10 was safe and well tolerated in participants with PD and no superior to placebo in terms of motor symptoms. According to these results, we cannot recommend CoQ10 for the routine treatment of PD right now.

Pilot study of safety and efficacy of polyprenols in combination with coenzyme Q10 in patients with statin-induced myopathy.

BACKGROUND AND OBJECTIVE: Statin-induced myopathy (SIM) has been partially attributed to deficiency of dolichol and coenzyme Q10 (CoQ10). We aimed to test the safety and efficacy of plant polyprenols in combination with CoQ10 for alleviation of SIM. MATERIALS AND METHODS: In an open-label, one-center prospective pilot study patients with SIM received conifer-tree needle polyprenols (4mg/day) and CoQ10 (100mg/day) for 8 weeks. Symptoms and safety were evaluated according to symptom severity score (0-10), creatine kinase (CK) levels, exercise test, dynamometry, complete blood count, clinical biochemistry and electrocardiography. RESULTS: Of the 14 patients, 11 completed the study per protocol. Two patients withdrew consent due to travels abroad, and it was discontinued for one patient with stage 3 chronic kidney disease due to asymptomatic elevations of liver enzymes at week 4. No safety parameters changed significantly in per protocol group. Non-significant increase of CK levels was observed (P=0.231). Muscle pain (n=10) and weakness (n=7) scores improved significantly (P<0.001 and P=0.018, respectively). Muscle pain completely disappeared in 2 patients, weakness resolved in 3 patients and cramps disappeared in two patients. Four patients assessed improvement strong enough to consider increase of statin dose. No changes were observed in exercise test or dynamometry. CONCLUSIONS: Conifer-tree polyprenols in combination with CoQ10 may be generally safe in patients with SIM, but caution should be exercised in patients with glomerular filtration rate <60mL/min and routine monitoring of the liver enzymes and CK is advocated in all patients. The observed efficacy provides the rationale for a larger, double-blind controlled study with polyprenols.

Pharmacological treatments for Friedreich ataxia.

BACKGROUND: Friedreich ataxia is a rare inherited autosomal recessive neurological disorder, characterised initially by unsteadiness in standing and walking, slowly progressing to wheelchair dependency usually in the late teens or early twenties. It is associated with slurred speech, scoliosis, and pes cavus. Heart abnormalities cause premature death in 60% of people with the disorder. There is no easily defined clinical or biochemical marker and no known treatment. This is the second update of a review first published in 2009 and previously updated in 2012. OBJECTIVES: To assess the effects of pharmacological treatments for Friedreich ataxia. SEARCH METHODS: On 29 February 2016 we searched The Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, EMBASE and CINAHL Plus. On 7 March 2016 we searched ORPHANET and TRIP. We also checked clinical trials registers for ongoing studies. SELECTION CRITERIA: We considered randomised controlled trials (RCTs) or quasi-RCTs of pharmacological treatments (including vitamins) in people with genetically-confirmed Friedreich ataxia. The primary outcome was change in a validated Friedreich ataxia neurological score after 12 months. Secondary outcomes were changes in cardiac status as measured by magnetic resonance imaging or echocardiography, quality of life, mild and serious adverse events, and survival. We excluded trials of duration shorter than 12 months. DATA COLLECTION AND ANALYSIS: Three review authors selected trials and two review authors extracted data. We obtained missing data from the two RCTs that met our inclusion criteria. We collected adverse event data from included studies. We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We identified more than 12 studies that used antioxidants in the treatment of Friedreich ataxia, but only two small RCTs, with a combined total of 72 participants, both fulfilled the selection criteria for this review and published results. One of these trials compared idebenone with placebo, the other compared high-dose versus low-dose coenzyme Q10 and vitamin E (the trialists considered the low-dose medication to be the placebo). We identified two other completed RCTs, which remain unpublished; the interventions in these trials were pioglitazone (40 participants) and idebenone (232 participants). Other RCTs were of insufficient duration for inclusion.In the included studies, the primary outcome specified for the review, change in a validated Friedreich ataxia rating score, was measured using the International Co-operative Ataxia Rating Scale (ICARS). The results did not reveal any significant difference between the antioxidant-treated and the placebo groups (mean difference 0.79 points, 95% confidence interval -1.97 to 3.55 points; low-quality evidence).The published included studies did not assess the first secondary outcome, change in cardiac status as measured by magnetic resonance imaging. Both studies reported changes in cardiac measurements assessed by echocardiogram. The ejection fraction was not measured in the larger of the included studies (44 participants). In the smaller study (28 participants), it was normal at baseline and did not change with treatment. End-diastolic interventricular septal thickness showed a small decrease in the smaller of the two included studies. In the larger included study, there was no decrease, showing significant heterogeneity in the study results; our overall assessment of the quality of evidence for this outcome was very low. Left ventricular mass (LVM) was only available for the smaller RCT, which showed a significant decrease. The relevance of this change is unclear and the quality of evidence low.There were no deaths related to the treatment with antioxidants. We considered the published included studies at low risk of bias in six of seven domains assessed. One unpublished included RCT, a year-long study using idebenone (232 participants), published an interim report in May 2010 stating that the study reached neither its primary endpoint, which was change in the ICARS score, nor a key cardiological secondary endpoint, but data were not available for verification and analysis. AUTHORS' CONCLUSIONS: Low-quality evidence from two small, published, randomised controlled trials neither support nor refute an effect from antioxidants (idebenone, or a combination of coenzyme Q10 and vitamin E) on the neurological status of people with Friedreich ataxia, measured with a validated neurological rating scale. A large unpublished study of idebenone that reportedly failed to meet neurological or key cardiological endpoints, and a trial of pioglitazone remain unpublished, but on publication will very likely influence quality assessments and conclusions. A single study of idebenone provided low-quality evidence for a decrease in LVM, which is of uncertain clinical significance but of potential importance that needs to be clarified. According to low-quality evidence, serious and non-serious adverse events were rare in both antioxidant and placebo groups. No non-antioxidant agents have been investigated in RCTs of 12 months' duration.

Mitochondrial disease patients' perception of dietary supplements' use.

Surveys of mitochondrial disease physicians conducted through the Mitochondrial Medicine Society have shown that virtually all providers recommend a variety of dietary supplements as treatments to their patients in an effort to enhance energy production and reduce oxidative stress. In this survey, we asked patients and their parents about their experiences taking these dietary supplements for mitochondrial disease. The survey was disseminated through the North American Mitochondrial Disease Consortium (NAMDC) and the Rare Disease Clinical Research Network (RDCRN) registries and gathered 162 responses. The study ascertained each patient's mitochondrial disease diagnosis, dietary supplements used, adjunct therapy, and effects of the supplements on symptoms and health. Regardless of the specific underlying mitochondrial disease, the majority of the survey respondents stated they are or have been on dietary supplements. Most patients take more than four supplements primarily coenzyme Q10, l-carnitine, and riboflavin. The majority of patients taking supplements reported health benefits from the supplements. The onset of perceived benefits was between 2weeks to 3months of initiating intake. Supplements seem to be safe, with only 28% of patients experiencing mild side-effects and only 5.6% discontinuing their intake due to intolerance. Only 9% of patients had insurance coverage for their supplements and when paying out of pocket, 95% of them spend up to $500/month. Despite the use of concomitant therapies (prescribed medications, physical therapy, diet changes and other), 45.5% of patients think that dietary supplements are the only intervention improving their symptoms. Some limitations of this study include the retrospective collection of data probably associated with substantial recall bias, lack of longitudinal follow up to document pre- and post-supplement clinical status and second hand reports by parents for children which may reflect parents' subjective interpretation of symptoms severity and supplements effect rather than real patients' experience. More extensive prospective studies will help further elucidate this topic.

The randomized clinical trial of coenzyme Q10 for the prevention of periprocedural myocardial injury following elective percutaneous coronary intervention.

INTRODUCTION: Periprocedural myocardial injury (PMI) following elective percutaneous coronary intervention (PCI) is an important therapeutic concern with remaining some mortality and morbidity. To the best of our knowledge, there is no published study that investigates the potential benefit of CoQ10 in preventing PMI following elective PCI. METHODS: In a randomized, clinical trial, 100 patients who scheduled for elective PCI were allocated in to the intervention (n=50) and control group (n=50). The intervention received a 300 mg loading dose CoQ10 12 hours before procedure. The level of CK-MB and troponin-I was measured before procedure, and 8 and 24 hours after. Furthermore, hs-CRP was measured at baseline and 24 hours after. All patients were assessed for the incidence of major adverse cardiac effects (MACEs) after 1 month. RESULTS: The CK-MB elevation (above the upper limit normal) was occurred in 22% (n=11) of CoQ10 and 20% (n=10) of control (P=.806). The elevation of troponin-I was documented in 8% (n=4) of both groups. No significant change in the level of cardiac biomarkers was noted. However, the significant reduction in hs-CRP level was occurred in CoQ10 group (P=.032). CONCLUSION: The results showed that pretreatment with 300 mg CoQ10 12 hours before procedure could not reduce PMI following elective PCI, however, significantly decreased hs-CRP.

Combination Therapy With Coenzyme Q10 and Trimetazidine in Patients With Acute Viral Myocarditis.

BACKGROUND: Acute viral myocarditis is an inflammatory disease with global impact. Although it may resolve spontaneously, its course is not easily predicted, and there is a paucity of specific treatment options available with proven efficacy. Coenzyme Q10 (CQ10) and trimetazidine possess antioxidant and antiinflammatory effects. METHODS: We examined the therapeutic efficacy of these agents in acute viral myocarditis both individually and in combination. Patients were blinded and randomized to receive CQ10 (n = 42), trimetazidine (n = 39), or CQ10 + trimetazidine (n = 43) treatment. RESULTS: Serum inflammatory and oxidative stress marker and myocardial enzyme levels, and heart function were measured. Both CQ10 and trimetazidine decreased inflammatory and oxidative stress biomarker levels compared with baseline measurements. However, combination therapy with CQ10 and trimetazidine showed a significantly more powerful effect not only on markers of inflammation and oxidative stress, but also on left ventricular systolic function and troponin, compared with either treatment alone. CONCLUSION: This study confirmed the beneficial effect of CQ10 and trimetazidine individually, but demonstrated a superior effect of combining the therapies on cardiac left ventricular ejection fraction, and biochemical markers of myocardial damage in acute viral myocarditis.

n-3 Fatty Acid Supplementation and Leukocyte Telomere Length in Patients with Chronic Kidney Disease.

DNA telomere shortening associates with the age-related increase cardiovascular disease (CVD) risk. Reducing oxidative stress, could modify telomere erosion during cell replication, and CVD risk in patients with chronic kidney disease (CKD). The effect of n-3 fatty acids and coenzyme Q10 (CoQ) on telomere length was studied in a double-blind placebo-controlled trial in CKD. Eighty-five CKD patients were randomized to: n-3 fatty acids (4 g); CoQ (200 mg); both supplements; or control (4 g olive oil), daily for 8 weeks. Telomere length was measured in neutrophils and peripheral blood mononuclear cells (PBMC) at baseline and 8 weeks, with and without correction for cell counts. Main and interactive effects of n-3 fatty acids and CoQ on telomere length were assessed adjusting for baseline values. F2-isoprostanes were measured as markers of oxidative stress. There was no effect of n-3 fatty acids or CoQ on neutrophil or PBMC telomere length. However, telomere length corrected for neutrophil count was increased after n-3 fatty acids (p = 0.015). Post-intervention plasma F2-isoprostanes were negative predictors of post-intervention telomere length corrected for neutrophil count (p = 0.025).The effect of n-3 fatty acids to increased telomere length corrected for neutrophil count may relate to reduced oxidative stress and increased clearance of neutrophils with shorter telomeres from the circulation. This may be a novel mechanism of modifying CVD risk in CKD patients.