Effect of coenzyme Q10 on risk of atherosclerosis in patients with recent myocardial infarction.
In a randomized, double-blind, controlled trial, the effects of oral treatment with coenzyme Q10 (CoQ10, 120 mg/day), a bioenergetic and antioxidant cytoprotective agent, were compared for 1 year, on the risk factors of atherosclerosis, in 73 (CoQ, group A) and 71 (B vitamin group B) patients after acute myocardial infarction (AMI). After 1 year, total cardiac events (24.6 vs. 45.0%, p < 0.02) including non-fatal infarction (13.7 vs. 25.3%, p < 0.05) and cardiac deaths were significantly lower in the intervention group compared to control group. The extent of cardiac disease, elevation in cardiac enzymes, left ventricular enlargement, previous coronary artery disease and elapsed time from symptom onset to infarction at entry to study showed no significant differences between the two groups. Plasma level of vitamin E (32.4 +/- 4.3 vs. 22.1 +/- 3.6 umol/L) and high density lipoprotein cholesterol (1.26 +/- 0.43 vs. 1.12 +/- 0.32 mmol/L) showed significant (p < 0.05) increase whereas thiobarbituric acid reactive substances, malondialdehyde (1.9 + 0.31 vs. 3.1 + 0.32 pmol/L) and diene conjugates showed significant reduction respectively in the CoQ group compared to control group. Approximately half of the patients in each group (n = 36 vs. 31) were receiving lovastatin (10 mg/day) and both groups had a significant reduction in total and low density lipoprotein cholesterol compared to baseline levels. It is possible that treatment with CoQ10 in patients with recent MI may be beneficial in patients with high risk of atherothrombosis, despite optimal lipid lowering therapy during a follow-up of 1 year. Adverse effect of treatments showed that fatigue (40.8 vs. 6.8%, p < 0.01) was more common in the control group than CoQ group.
Mol Cell Biochem. 2003 Apr;246(1-2):75-82
Overview on coenzyme Q10 as adjunctive therapy in chronic heart failure. Rationale, design and end-points of "Q-symbio"--a multinational trial.
Energy starvation of the myocardium is probably a dominant feature of heart failure and attention has been directed towards agents which may stabilize myocardial metabolism and maintain adequate energy stores. A reduced myocardial tissue content of the essential redox-component and natural antioxidant Coenzyme Q10 (CoQ10) has been detected in patients with heart failure and the observed level of CoQ10 deficiency was correlated to the severity of heart failure. CoQ10 fulfills various criteria of an obvious adjunct in patients with symptomatic heart failure: it is devoid of significant side effects and it improves symptoms and quality of life. Till this date, several double-blind placebo-controlled trials with CoQ10 supplementation in more than 1000 patients have been positive and statistically significant with respect to various clinical parameters, e.g. improvement in NYHA Class, exercise capacity and reduced hospitalisation frequency. Also treatment with CoQ10 led to a significant improvement of relevant hemodynamic parameters. In only 3 out of 13 double-blind studies comprising 10% of the total number of patients treated the results were neutral. Thus, based on the available controlled data CoQ10 is a promising, effective and safe approach in chronic heart failure. This is why a double-blind multicenter trial with focus on morbidity and mortality has been planned to start in 2003: Q-SYMBIO. Patients in NYHA classes III to IV (N=550) receiving standard therapy are being randomized to treatment with CoQ10 100 mg t.i.d. or placebo in parallel groups. End-points in a short-term evaluation phase of 3 months include symptoms, functional capacity and biomarker status (BNP). The aim of a subsequent 2-year follow-up study is to test the hypothesis that CoQ10 may reduce cardiovascular morbidity (unplanned cardiovascular hospitalisation due to worsening heart failure) and mortality as a composite endpoint. This trial should help to establish the future role of CoQ10 as part of a maintenance therapy in patients with chronic heart failure.
Anti-oxidant effects of coenzyme Q10 on experimental viral myocarditis in mice.
We studied the effects of coenzyme Q10 (CoQ10) on mice with acute myocarditis inoculated with the encephalomyocarditis (EMC) virus with the analysis of indices of effects of oxidative injury and DNA damage in the myocardium. The mice were treated as follows: CoQ10 group (n = 118); CoQ10 1.0 mg (0.1 mL) x 2/d (0.1 mg/g/d), control group (n = 128); sham-liquid 0.1 mL x 2/d. The mice were injected intraperitoneally 1 day before and daily for 12 days after EMC virus inoculation. The expression of thioredoxin, a marker of oxidative stress overload, as well as 8-hydroxy-2'-deoxyguanosine, an established marker of DNA damage, in the myocardium was investigated. The survival rate was significantly higher (P < 0.01) in the CoQ10 group (46.8%, 29/62) than in the control group (14.3%, 10/70). There were significant increases of CoQ9 and CoQ10 in the heart, which are the biologically active forms of CoQ in mice, and significant decrease of serum creatine kinase (CK)-MB in the CoQ10 group as compared with the control group. Histologic examination showed that the severity of myocarditis was less severe (P < 0.01) in the CoQ10 group than in the control group. In addition, the up-regulation of myocardial thioredoxin with DNA damage, which was induced by the inflammatory stimuli by the virus, was suppressed by the CoQ10 treatment, which may reflect the anti-oxidant effects of CoQ10 treatment. Thus, pretreatment with CoQ10 may reduce the severity of viral myocarditis in mice associated with decreasing oxidative stress in the condition.
J Cardiovasc Pharmacol. 2003 Nov;42(5):588-92
Systematic review of effect of coenzyme Q10 in physical exercise, hypertension and heart failure.
COENZYME Q10 IN PHYSICAL EXERCISE. We identified eleven studies in which CoQ10 was tested for an effect on exercise capacity, six showed a modest improvement in exercise capacity with CoQ10 supplementation but five showed no effect. CoQ10 IN HYPERTENSION. We identified eight published trials of CoQ10 in hypertension. Altogether in the eight studies the mean decrease in systolic blood pressure was 16 mm Hg and in diastolic blood pressure, 10 mm Hg. Being devoid of significant side effects CoQ10 may have a role as an adjunct or alternative to conventional agents in the treatment of hypertension. CoQ10 IN HEART FAILURE. We performed a randomised double blind placebo-controlled pilot trial of CoQ10 therapy in 35 patients with heart failure. Over 3 months, in the CoQ10 patients but not in the placebo patients there were significant improvements in symptom class and a trend towards improvements in exercise time. META-ANALYSIS OF RANDOMIZED TRIALS OF COENZYME Q10 IN HEART FAILURE. In nine randomised trials of CoQ10 in heart failure published up to 2003 there were non-significant trends towards increased ejection fraction and reduced mortality. There were insufficient numbers of patients for meaningful results. To make more definitive conclusions regarding the effect of CoQ10 in cardiac failure we recommend a prospective, randomised trial with 200-300 patients per study group. Further trials of CoQ10 in physical exercise and in hypertension are recommended.
Statins lower plasma and lymphocyte ubiquinol/ubiquinone without affecting other antioxidants and PUFA.
It has been shown that treating hypercholesterolemic patients (HPC) with statins leads to a decrease, at least in plasma, not only in cholesterol, but also in important non-sterol compounds such as ubiquinone (CoQ10), and possibly dolichols, that derive from the same biosynthetic pathway. Plasma CoQ10 decrease might result in impaired antioxidant protection, therefore leading to oxidative stress. In the present paper we investigated the levels in plasma, lymphocytes and erythrocytes, of ubiquinol and ubiquinone, other enzymatic and non-enzymatic lipophilic and hydrophilic antioxidants, polyunsaturated fatty acids of phosfolipids and cholesterol ester fractions, as well as unsaturated lipid and protein oxidation in 42 hypercholesterolemic patients treated for 3 months. The patients were treated with different doses of 3 different statins, i.e. atorvastatin 10 mg (n = 10) and 20 mg (n = 7), simvastatin, 10 mg (n = 5) and 20 mg (n = 10), and pravastatin, 20 mg (n = 5) and 40 mg (n = 5). Simvastatin, atorvastatin and pravastatin produced a dose dependent plasma depletion of total cholesterol (t-CH), LDL-C, CoQ10H2, and CoQ10, without affecting the CoQ10H2/CoQ10 ratio. The other lipophilic antioxidants (d-RRR-alpha-tocopherol-vit E-, gamma-tocopherol, vit A, lycopene, and beta-carotene), hydrophilic antioxidants (vit C and uric acid), as well as, TBA-RS and protein carbonyls were also unaffected. Similarly the erythrocyte concentrations of GSH and PUFA, and the activities of enzymatic antioxidants (Cu,Zn-SOD, GPx, and CAT) were not significantly different from those of the patients before therapy. In lymphocytes the reduction concerned CoQ10H2, CoQ10, and vit E; other parameters were not investigated. The observed decline of the levels of CoQ10H2 and CoQ10 in plasma and of CoQ10H2, CoQ10 and vit E in lymphocytes following a 3 month statin therapy might lead to a reduced antioxidant capacity of LDL and lymphocytes, and probably of tissues such as liver, that have an elevated HMG-CoA reductase enzymatic activity. However, this reduction did not appear to induce a significant oxidative stress in blood, since the levels of the other antioxidants, the pattern of PUFA as well as the oxidative damage to PUFA and proteins resulted unchanged. The concomitant administration of ubiquinone with statins, leading to its increase in plasma, lymphocytes and liver may cooperate in counteracting the adverse effects of statins, as already pointed out by various authors on the basis of human and animal studies.