The Effect of Coenzyme Q10 in Patients with Congestive Heart Failure

There are numerous reasons to believe that deficiency of coenzyme Q10 (ubiquinone) may exacerbate the poor contractility of myocardial cells in patients with heart failure. Not only does coenzyme Q10 play a central role in mitochondrial oxidative pho... show more

There are numerous reasons to believe that deficiency of coenzyme Q10 (ubiquinone) may exacerbate the poor contractility of myocardial cells in patients with heart failure. Not only does coenzyme Q10 play a central role in mitochondrial oxidative phosphorylation (1), but it may also act as an antioxidant scavenger (2). Because the myocardium of patients with congestive heart failure demonstrates oxidative stress (3) and coenzyme Q10 prevents lipid peroxidation (4), this substance conceivably could prevent myocardial destruction. Furthermore, the concentration of coenzyme Q10 is decreased in myocardial cells of patients with advanced heart failure (5), and the extent of myocardial coenzyme Q10 deficiency correlates with the clinical severity of heart failure (5, 6). It is thus not surprising that nutritional supplementation with coenzyme Q10 has been proposed as a treatment for congestive heart failure, that it is extensively advertised, and that it is commonly used by patients with this condition. Many small studies have been published, but most were uncontrolled and unblinded. Approximately 31 Japanese clinical reports describe favorable effects with intravenous or oral coenzyme Q10 (7). The studies involved only a small number of patients with heart failure and tended to include patients with cardiac disease of various causes. Nevertheless, in 1974 the Japanese government approved marketing of coenzyme Q10 for the treatment of heart failure. The few U.S. and European studies have had conflicting results. Some controlled studies showed no effect (8, 9), but their limitations make the results inconclusive. Other trials noted improvement (10-13), but concerns about end points, small numbers of patients, and the lack of blinding have limited the acceptance of these studies. With such conflicting data, randomized, controlled, and blinded studies are needed to test the hypothesis that patients with advanced heart failure are deficient in coenzyme Q10 and that oral supplementation with coenzyme Q10 results in clinical improvement. We therefore evaluated the effects of coenzyme Q10 supplementation on left ventricular ejection fraction and exercise tolerance in patients with symptomatic heart failure despite standard medical therapy. Methods We performed a randomized, double-blind, placebo-controlled trial to compare the effects of oral coenzyme Q10 (200 mg/d) and placebo. The two primary end points were change in ejection fraction, as assessed by nuclear ventriculography, and change in peak oxygen consumption. The study protocol was approved by the human volunteers committee of the University of Maryland School of Medicine. Inclusion and Exclusion Criteria Patients with New York Heart Association functional class III or IV disease were eligible for inclusion in this study. All patients had ejection fractions less than 40% (documented by radionuclide ventriculography) and maximal oxygen consumption less than 17.0 mL/kg of body weight per minute or less than 50% of the predicted value. These criteria were used to select symptomatic patients who would have the potential to improve. The mean peak oxygen consumption in our patients was 13.1 mL/kg per minute. In comparison, the peak oxygen consumption criterion for cardiac transplantation is generally considered to be less than 14.0 mL/kg per minute, and the mean peak oxygen consumption in nonexercising normal elderly persons (mean age, 67 years) has been reported to be 19.0 mL/kg per minute (14). Patients were required to have been receiving an unchanged medical regimen for at least 1 month. Patients who had previously taken coenzyme Q10 were excluded. Baseline Testing At baseline, three procedures were performed. First, a graded symptom-limited cardiopulmonary exercise test using the Naughton protocol was conducted to assess maximal oxygen consumption. The test was performed by the same operator and was repeated until the maximum oxygen consumption measures on two consecutive test results were within 15% of each other. The final test was considered to be the baseline test with which to assess change during therapy. Second, radionuclide ventriculography was performed by using standard techniques. Third, serum concentration of coenzyme Q10 was measured as described elsewhere (15). Three patients did not have concentrations obtained at baseline or follow-up. Intervention Patients were randomly assigned to receive 200 mg of coenzyme Q10 per day or placebo. Randomization was performed by using a random-number generator. All patients and study personnel were blinded to study group assignment until all data were final. The dosage was chosen to minimize the chance of inadequate treatment. Previous studies reporting benefit with coenzyme Q10 supplementation have generally used daily dosages of 100 or 150 mg (6, 7, 9-13, 16-18). Final Assessment After 6 months, all baseline procedures were repeated. At that time, patients were asked whether their symptoms were improved, worse, or the same. Statistical Analysis The change in values of primary and secondary end points were compared by using an unpaired Student t-test. All values are given as the mean SD. For significance, a P value less than 0.05 was required. The study was planned to have 80% power to detect a difference of 2.8 mL/kg per minute in the peak oxygen consumption, with a P value of 0.05. This assumed a mean oxygen consumption of 13.0 4.0 mL/kg per minute. We used StatMost, version 3.5 (Dataxiom Software, Inc., Los Angeles, California), for all statistical analyses. Results Fifty-five patients were randomly assigned. Nine patients did not finish the study: 5 in the coenzyme Q10 group and 4 in the placebo group. One patient (who was randomly assigned to receive coenzyme Q10) was withdrawn from the study before repeated assessments and unblinding because of error in enrollment criteria. Three patients died: One patient assigned to the placebo group died of progressive heart failure, and 2 patients a show less