Clinical Briefs With Comments from Russell H. Greenfield, MD
October 1, 2006 4 minutes read
Clinical Briefs
With Comments from Russell H. Greenfield, MD, Dr. Greenfield is Medical Director, Carolinas Integrative Health, Carolinas HealthCare System, Charlotte, NC, and Clinical Assistant Professor, School of Medicine, University of North Carolina, Chapel Hill, NC.
A Q "Tip"—CoQ10 for Heart Failure
Source: Belardinelli R, et al. Coenzyme Q10 and exercise training in chronic heart failure. Eur Heart J 2006 Aug 1; Epub ahead of print.
Goal: To assess the effect of oral coenzyme Q10 (CoQ10) alone or in combination with exercise training (ET) in people with stable chronic heart failure.
Design: Double-blind, placebo-controlled crossover intervention trial.
Subjects: People with stable (no change in medications or need for hospitalization) NYHA Class II and III heart failure secondary to ischemic heart disease (n = 23, mean age 59 ± 9 years, including 20 men).
Methods: Following a one-week run-in period during which participants met with a cardiologist and underwent a "familiarization cardiopulmonary exercise test," subjects were assigned to one of four groups for four weeks: oral CoQ10 100 mg tid, CoQ10 plus supervised ET, placebo, and placebo plus ET. Subjects then experienced each group consecutively. At study entry and the end of each phase of the trial subjects underwent cardiopulmonary exercise testing, brachial artery vasomotor activity evaluation (EDDBA), dobutamine stress echocardiography, and blood chemistry testing.
Results: With supplementation, plasma CoQ10 increased four times over baseline levels and HDL levels increased very slightly, while no change was detected for levels of total cholesterol, triglycerides, or vitamin E. Peak VO2 (+9%), resting left ventricular ejection fraction (+10%), and regional contractility all improved with CoQ10 administration, the latter notably in segments initially akinetic or hypokinetic, an effect that was correlated with changes in plasma CoQ10 levels. EDDBA improved significantly with CoQ10 (+38%) and was likewise correlated with plasma CoQ10 levels, with levels higher than 2.4 mcg/mL associated with the most improvement. ET alone increased CoQ10 levels non-significantly and caused improvements in certain clinical parameters, but the combination of ET and CoQ10 administration significantly lessened peak systolic wall thickening. In addition, combination of CoQ10 with ET increased CoQ10 levels more than oral administration alone.
Conclusions: Oral CoQ10 supplementation in people with stable chronic heart failure (NYHA II-III) significantly improves left ventricular contractility, brachial artery endothelial-dependent relaxation, and peak VO2. Synergism between CoQ10 and ET was evident in improved myocardial contractility.
Study strengths: Methods of assessment of cardiovascular parameters; dose of CoQ10 employed.
Study weaknesses: Small sample size; subjects had reasonable ejection fraction considering their NYHA status (37 ± 7%), 18 of whom were NYHA Class II; short duration of study phases.
Of note: Statin drugs were discontinued one month prior to beginning the protocol in the nine people who had been using them; 61% were on ACE-inhibitors, 61% on beta-blockers; all patients had known coronary artery disease, having undergone coronary angiography within the prior six months; medications were not changed during the trial; some experts believe that very high serum levels of CoQ10 need to be reached to achieve clinical benefit for people with chronic heart failure, which may explain the lack of supportive evidence found in heart failure studies using only 100 mg CoQ10 per day; no side effects were noted with CoQ10 administration; a number of case reports exists raising concerns that CoQ10 might interfere with warfarin's anticoagulant effects.
We knew that: CoQ10 is a known antioxidant with an important role in the mitochondrial respiratory chain that produces ATP in cells, including in myocytes; prior evidence strongly suggests the presence of low levels of CoQ10 in people with advanced chronic heart failure, and that lower levels portend worsening disease; some studies of oral CoQ10 supplementation in the setting of chronic heart failure have suggested clinical benefit, but not all, with some of the more recent trials showing no benefit; normal plasma levels of CoQ10 are 0.6-1.0 mcg /mL; it is well known that ET improves endothelial-dependent vascular relaxation in both the coronary and systemic circulation; endothelial dysfunction plays a role in heart failure, and is likely tied to nitric oxide dysregulation; statin drugs affect the mevalonate pathway, impacting not only cholesterol synthesis but also CoQ10 production.
Clinical import: Despite tremendous technical and clinical advances, present treatment of chronic heart failure cannot adequately quell the seemingly inexorable worsening of cardiac function associated with this disorder. Unfortunately, the future is not yet hopeful in this regard, as these same extraordinary advances will save the lives of many people with ischemic heart disease, many of whom will later go on to develop chronic heart failure. Any treatment that might help stem the tide of progressive deterioration would be welcome indeed. Until a few years ago ET in the setting of chronic heart failure was relatively contraindicated. CoQ10 has been studied in this setting for decades, yet definitive data regarding clinical benefit remains elusive. In this light, the present study of small sample size is only a modest aid and cries out for replication with more participants. The notion of using higher doses to achieve clinical benefit is intriguing and likewise needs to be tested. Even now, however, provided the patient is not using coumadin, a trial of high-dose CoQ10 could be considered for select patients with NYHA Class II-III heart failure with confidence in its safety.
What to do with this article: Keep a copy of the abstract on your computer.
Greenfield RH. A Q "tip"-CoQ10 for heart failure. Altern Med Alert 2006;9(10):120.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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