Effects of coenzyme Q10 on vascular endothelial function in humans: a meta-analysis of randomized controlled trials

ObjectiveThe purpose of this study was to quantify the effect of coenzyme Q10 on arterial endothelial function in patients with and without established cardiovascular disease.BackgroundEndothelial dysfunction has been implicated in the pathogenesis of atherosclerosis.Methods and resultsThe search included MEDLINE, Cochrane Library, Scopus, and EMBASE to identify studies up to 1 July 2011. Eligible studies were randomized controlled trials on the effects of coenzyme Q10 compared with placebo on endothelial function. Two reviewers extracted data on study characteristics, methods, and outcomes. Five eligible trials enrolled a total of 194 patients. Meta-analysis using random-effects model showed treatment with coenzyme Q10 significantly improvement in endothelial function assessed peripherally by flow-mediated dilatation (SMD 1.70, 95% CI: 1.00–2.4, p < 0.0001). However, the endothelial function assessed peripherally by nitrate-mediated arterial dilatation was not significantly improved by using fix-effects model (SMD ?0.19, 95% CI: ?1.75 to 1.38, p = 0.81).ConclusionCoenzyme Q10 supplementation is associated with significant improvement in endothelial function. The current study supports a role for CoQ10 supplementation in patients with endothelial dysfunction.     

Coenzyme Q10 attenuates the progression of cardiomyopathy in hamsters

Coenzyme Q10 (10 mg/kg/day) or digoxin (2 micrograms/kg/day) was given orally to cardiomyopathic hamsters (BIO 14.6) for 8 weeks from 12 weeks of age. The left ventricular weight per gram of body weight (mg/g) was lower (p less than 0.01) in the coenzyme Q10 group (3.09 +/- 0.13) than in the digoxin (3.32 +/- 0.20) and control (3.44 +/- 0.14) groups. Left ventricular function was evaluated in isovolumically beating hearts. Left ventricular developed pressure (63 +/- 5 vs. 54 +/- 10 mmHg, p less than 0.05), -dP/dt (1385 +/- 100 vs. 1211 +/- 136 mmHg/sec, p less than 0.05), and -dP/dt (1068 +/- 126 vs. 896 +/- 141 mmHg/sec, p less than 0.05) were greater in the coenzyme Q10 than in the control group. The time constant of left ventricular relaxation was shorter in the coenzyme Q10 group than in the control group (25 +/- 3 vs. 28 +/- 3 msec, p less than 0.05). By contrast, in the digoxin group, the indices of left ventricular function did not differ from the control group. These results suggest that coenzyme Q10, but not digoxin, attenuated disease progression and preserved left ventricular function in cardiomyopathic hamsters.     

Telmisartan versus angiotension-converting enzyme inhibitors in the treatment of hypertension: a meta-analysis of randomized controlled trials

Telmisartan and angiotensin-converting enzyme inhibitors (ACEIs) are both effective and widely used antihypertensive drugs targeting renin-angiotensin-aldosterone system. The study aimed to estimate the efficacy and tolerability of telmisartan in comparison with different ACEIs as monotherapy in the treatment of hypertension. Cochrane Central Register of Controlled Trials, PubMed and Embase were searched for relevant studies. A meta-analysis of all randomized controlled trials fulfilling the predefined criteria was performed. A random-effect model was used to account for heterogeneity among trials. Twenty-eight randomized controlled trials involving 5157 patients were ultimately identified out of 721 studies. Telmisartan had a greater diastolic blood pressure (DBP) reduction than enalapril (weighted mean difference (WMD) 1.82, 95% confidence interval (CI) 0.66-2.99), ramipril (WMD 3.09, 95% CI 1.94-4.25) and perindopril (WMD 1.48, 95% CI 0.33-2.62). Telmisartan also showed a greater DBP response rate than enalapril (relative risk (RR) 1.15, 95% CI 1.05-1.26), ramipril (RR 1.34, 95% CI 1.11-1.61) and perindopril (RR 1.22, 95% CI 1.05-1.41). There was no statistical difference in DBP reduction or therapeutic response rate between telmisartan and lisinopril (WMD -0.30, 95% CI -0.65 to 0.05; RR 0.99, 95% CI 0.80-1.23, respectively). Telmisartan had fewer drug-related adverse events than enalapril (RR 0.57, 95% CI 0.44-0.74), ramipril (RR 0.44, 95% CI 0.26-0.75), lisinopril (RR 0.70, 95% CI 0.56-0.89) and perindopril (RR 0.52, 95% CI 0.28-0.98). The meta-analysis indicates that telmisartan provides a superior BP control to ACEIs (enalapril, ramipril and perindopril) and has fewer drug-related adverse events and better tolerability in hypertensive patients.     

Blood pressure-lowering effects of biofeedback treatment in hypertension: a meta-analysis of randomized controlled trials.

To examine the blood pressure-lowering effects of biofeedback treatment in patients with essential hypertension, a meta-analysis was conducted on studies published between 1966 and 2001. A total of 22 randomized controlled studies with 905 essential hypertensive patients were selected for review. Compared with clinical visits or self-monitoring of blood pressure (non-intervention controls), biofeedback intervention resulted in systolic and diastolic blood pressure reductions that were greater by 7.3 mmHg (for systole; 95% confidence interval: 2.6 to 12.0) and 5.8 mmHg (for diastole; 95% confidence interval: 2.9 to 8.6). Compared with sham or non-specific behavioral intervention controls, the net reductions in systolic and diastolic blood pressures by biofeedback intervention were 3.9 (95% confidence interval: -0.3 to 8.2) and 3.5 (-0.1 to 7.0) mmHg, respectively. The results of multiple regression analysis also indicated that biofeedback intervention decreased systolic and diastolic blood pressures more than non-intervention controls (p < 0.001), but not more than sham or non-specific behavioral intervention controls (p > 0.05), when controlling for the effects of initial blood pressures. When biofeedback intervention types were classified into two types, simple biofeedback and relaxation-assisted biofeedback, only the relaxation-assisted biofeedback significantly decreased both systolic and diastolic blood pressures (p < 0.05) compared with those in sham or non-specific behavioral intervention controls. The results suggested that biofeedback was more effective in reducing blood pressure in patients with essential hypertension than no intervention. However, the treatment was only found to be superior to sham or non-specific behavioral intervention when combined with other relaxation techniques. Further studies will be needed to determine whether biofeedback itself has an antihypertensive effect beyond the general relaxation response.     

Coenzyme Q10 deficiency in patients with hereditary hemochromatosis

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

Recent Developments in the Role of Coenzyme Q10 for Coronary Heart Disease: a Systematic Review

Purpose of Review

This review examines recent randomized clinical trials evaluating the role of coenzyme Q10 (CoQ10) in the management of coronary heart disease.

Recent Findings

CoQ10 is one of the most commonly used dietary supplements in the USA. Due to its antioxidant and anti-inflammatory effects, CoQ10 has been studied extensively for possible use in managing coronary heart disease. One of the most common applications of CoQ10 is to mitigate statin-associated muscle symptoms (SAMS) based on the theory that SAMS are caused by statin depletion of CoQ10 in the muscle. Although previous studies of CoQ10 for SAMS have produced mixed results, CoQ10 appears to be safe. Because CoQ10 is a cofactor in the generation of adenosine triphosphate, supplementation has also recently been studied in patients with heart failure, which is inherently an energy deprived state. The Q-SYMBIO trial found that CoQ10 supplementation in patients with heart failure not only improved functional capacity, but also significantly reduced cardiovascular events and mortality. Despite these positive findings, a larger prospective trial is warranted to support routine use of CoQ10. Less impressive are the effects of CoQ10 on specific cardiovascular risk factors such as blood pressure, dyslipidemia, and glycemic control.

Summary

Current evidence does not support routine use of CoQ10 in patients with coronary heart disease. Additional studies are warranted to fully determine the benefit of CoQ10 in patients with heart failure before including it in guideline-directed medical therapy.

     

Myocardial dysfunction in mitochondrial diabetes treated with Coenzyme Q10

Maternally-inherited diabetes and deafness (MIDD) has been related to an A to G transition in the mitochondrial tRNA Leu (UUR) gene at the base pair 3243. Although some previous articles have reported that this mutation may be a cause of cardiomyopathy in diabetes, the degree of cardiac involvement and a specific treatment has not been established. Here, we reported a case of a patient with MIDD who developed congestive heart failure and the therapeutic usefulness of Coenzyme Q10 (CoQ10). In our patient, after the introduction of Coenzyme Q10 150 mg/day, there was a gradual improvement on left ventricular function evaluated by echocardiography. The fractional shortening (FS) and ejection fraction (EF) increased from 26 to 34% and from 49 to 64%, respectively. No side effects were noted. Three months after CoQ10 discontinuation, the parameters of systolic function evaluated by echocardiography decreased, suggesting that CoQ10 had a beneficial effect. Identification of diabetes and cardiomyopathy due to mitochondrial gene mutation may have therapeutic implications and Coenzyme Q10 is a possible adjunctive treatment in such patients.     

Effect of Q10 supplementation on body weight and body mass index: A systematic review and meta-analysis of randomized controlled clinical trials

AimsThis meta-analysis study was carried out to assess the effects of coenzyme Q10 supplementation on body weight and body mass index of patients in randomized controlled clinical trial studies.Materials and methodsA comprehensive systematic search of literature was performed through ISI web of sciences, PubMed, Scopus and Cochrane library databases up to February 2018 which was supplemented by manual search of the references list of included studies. From a total of 1579 identified articles, only 17 trials with 14 and 14 effect-sizes were included for pooling the effects of co-enzyme Q10 supplementation on body weight and body mass index, respectively.ResultsResults of random-effect size meta-analysis showed that supplementation with coenzyme Q10 had no significant decreasing effects on body weight (WMD: 0.28 kg; 95% CI = ?0.91, 1.47; P = 0.64) and BMI (WMD: ?0.03; 95% CI = ?0.4, 0.34; P = 0.86) of study participants. Subgroup analysis revealed that dosage of Q10 and trial duration could not differ the results of Q10 supplementation.ConclusionResults of this meta-analysis study failed to show any beneficial effect of coenzyme Q10 supplementation on body weight and BMI of patients in clinical trial studies.     

Clinical outcomes in statin treatment trials: a meta-analysis.

OBJECTIVE: To determine the risk of cardiovascular events and death in patients receiving statin treatment for cholesterol regulation. METHODS: Systematic review and meta-analysis of all randomized controlled trials that were published as of April 15, 1997. Primary or secondary prevention trials or regression trials were eligible. MAIN OUTCOME MEASURES: All-cause mortality, fatal myocardial infarction (MI) or stroke, nonfatal MI or stroke, angina, and withdrawal from the studies. Both random- and fixed-effects models were run for the outcomes of interests, and results are expressed as odds ratios (ORs). Sensitivity analyses tested the impact of the study type and duration, statin treatment type, and control arm event rates. Intent-to-treat denominators were used whenever they were available, and the number needed to treat was calculated when appropriate. RESULTS: Seventeen studies (21 303 patients) were included (2 secondary prevention studies, 5 mixed primary-secondary prevention population studies, and 10 regression trials). Treatment groups included lovastatin (t = 5), pravastatin (t = 10), and simvastatin (t = 3). For all-cause mortality, the OR was 0.76 (95% confidence interval [CI], 0.67-0.86) in favor of receiving statin treatment; for fatal MI, the OR was 0.61 (95% CI, 0.48-0.78); for nonfatal MI, the OR was 0.69 (0.54-0.88); for fatal stroke, the OR was 0.77 (95% CI, 0.57-1.04); for nonfatal stroke, the OR was 0.69 (95% CI, 0.54-0.88); and for angina, the OR was 0.70 (95% CI, 0.65-0.76). CONCLUSIONS: Patients who received statin treatment demonstrated a 20% to 30% reduction in death and major cardiovascular events compared with patients who received placebo. This advantage was generally present across study types and statin treatment types and for patients with less severe dyslipidemias. The benefit in clinical outcomes was noticeable as early as 1 year.     

非双盲随机临床试验中降压药物疗效组别偏倚中国高血压临床研究荟萃分析

目的了解非双盲临床试验中同一降压药物作为试验药物和对照药物时,被观察的疗效结果是否存在差别.方法按照一定的标准,通过《中国医院知识仓库》收集降压药物的随机对照试验,寻找同一药物作为试验组的研究与作为对照组的研究进行配组,在配组的用药剂量、疗程和疗效标准相同的情况下,比较两组疗效的差别.结果寻找到11个配组,涉及18项试验药物研究和19项对照药物研究.①同一降压药物作为试验药物的各项研究与作为对照药物的各项研究的总有效率的差异具有统计学意义;②试验药物与对照药物的各配组的总有效率的差异具有统计学意义;③试验药物与对照药物的各药物的总有效率的差异没有统计学意义.试验药物与对照药物的加权平均总有效率分别为85.38%和77.17%,试验药物比对照药物高约10%.结论在非双盲随机对照试验中,试验组降压药物的疗效可能被夸大,对照组被贬低.应重视这种偏倚在新药临床试验和Meta分析中的影响.     

Coenzyme Q10: contractile dysfunction of the myocardial cell and metabolic therapy]

Coenzyme Q10, a mitoquinone involved in mitochondrial energy synthesis and the removal of free radicals, may be lacking in a number of cardiac pathologies leading to reduced contractile activity. The administration of exogenous coenzyme Q10 may help to improve contractile activity. In order to assess this hypothesis 63 patients suffering from altered myocardial contractile function (29 dilated cardiopathies, 15 valvular cardiopathies, 19 ischemic cardiopathies) which presented a NYHA class above 2 were selected. The study was open and patients were subdivided into two groups, one of which received conventional therapy alone whereas the other also received exogenous coenzyme Q10. After 4 months of follow-up clinical (NYHA class, effort tolerance) and echocardiographical (ventricular diameter and contraction fraction %) parameters were evaluated. In those patients treated with coenzyme Q10 and suffering from dilated cardiomyopathy a significant reduction in the NYHA class and a marked improvement in echocardiographic parameters were observed at the end of this period. The variations observed in other groups of patients treated were less conspicuous and not always statistically significant. The results of this study confirm that the association of coenzyme Q10 and conventional therapy may lad to a marked improvement in contractile function and correlated clinical conditions.     

Coenzyme Q10 for Patients With Cardiovascular Disease: JACC Focus Seminar

Coenzyme Q₁₀ (CoQ₁₀) is a naturally occurring compound that is found in animals and all humans. It has a fundamental role in cellular energy production. Although it is produced in the body, tissue deficiency can occur due to medications such as statins, which inhibit the mevalonate pathway. The clinical syndromes of statin-associated muscle symptoms (SAMS) and some of the features observed in patients with heart failure (HF) may be related to blood and tissue deficiency of CoQ₁₀. Numerous clinical trials of CoQ₁₀ in SAMS have yielded conflicting results. Yet, the weight of evidence as reflected in meta-analyses supports the use of exogenous CoQ₁₀ in SAMS. In patients with HF, large-scale randomized clinical trials are lacking, although one relatively contemporary trial, Q-SYMBIO, suggests an adjunctive role for CoQ₁₀. The possibility that statin-related CoQ₁₀ deficiency may play a role in patients with diastolic HF is an intriguing hypothesis that warrants further exploration.     

CoQ10治疗慢性心功能不全: 一项随机、双盲、对照研究

目的探讨辅酶Q10（CoQ10）对慢性心功能不全的疗效。方法本研究为随机、双盲、对照研究。共完成Ⅱ～Ⅲ心功能不全（心功能纽约分级）病例100例,CoQ10组50例,口服CoQ10100mg,每日一次;对照组50例,口服安慰剂100mg,1次/d;疗程3个月。结果所有患者均完成试验。经过3个月治疗后,CoQ10组患者心功能纽约心脏病学会分级较对照组明显改善（P=0．01）;CoQ10组患者6min步行距离较治疗前明显增加（P=0．045）,而对照组患者6min试验步行距离无明显改善（P=0．63）;CoQ10组患者左室射血分数较治疗前有增高趋势,但无统计学差异（P=0．059）：CoQ10组患者血CoQ10水平较治疗前升高近3倍[（0．70±0．06）vs（2．15±0．26）mg／L],而对照组则无明显升高;CoQ10组患者血清脑钠肽水平较治疗前明显降低（P=0．002）,而对照组患者则无明显降低（P=0．31）。结论CoQ10可以改善Ⅱ～Ⅲ级心功能不全患者的心功能。