LETTERS TO THE EDITOR
Lack of effect of coenzyme Q on left ventricular function in patients with congestive heart failure
Peter H. Langsjoen, MD, FACCa
a 1107 Doctors Drive, Tyler, Texas 75701, USA
The lack of benefit observed by Watson et al. (1) in patients with advanced congestive heart failure (CHF) treated with 100 mg of coenzyme Q10 (CoQ10) for three months was predictable. This is a case of too little for too short a time and, most importantly, as the authors postulate, too late in the course of CHF. The authors’ observations are in keeping with two previous trials similar in design and duration of therapy.
Permanetter et al. (2) studied 25 patients with advanced idiopathic dilated cardiomyopathy with documented normal coronary anatomy, using 100 mg of CoQ10 per day for four months, in a double-blind, crossover study design, and found a similar lack of significant effect on measurements of myocardial function. Hofman-Bang et al. (3) studied 79 patients, again using 100 mg of CoQ10 daily for three months, this time showing a very slight but significant improvement in ejection fraction, from 23 ± 12% to 25 ± 13% (p < 0.05).
In contrast, in a double-blind, crossover trial, Langsjoen et al. (4) evaluated 19 patients with idiopathic dilated cardiomyopathy who were much earlier in the course of their disease and showed an improvement in EF from 44 ± 3% to 56 ± 10% (p < 0.001) with three months of treatment with CoQ10, 100 mg per day. Although the methodology for myocardial function measurements in this early controlled trial (impedance cardiography and systolic time indexes) has been judged "outdated" by Watson et al., the measurements were nonetheless performed in a blinded fashion by an experienced laboratory. The largest double-blind, controlled trial to date by Morisco et al. (5) randomized 641 patients with CHF to receive either placebo or 2 mg/kg body weight per day of CoQ10 for one year. The number of patients requiring hospital admission for worsening heart failure was significantly lower in the CoQ10 group (73 vs. 118, p < 0.001), and episodes of pulmonary edema were significantly lower (20 vs. 51, p < 0.001). Thus, a higher dose of CoQ10 for a longer period showed a highly significant benefit. In a meta-analysis spanning the years of 1986 to 1995, Soja and Mortensen (6) reviewed 14 controlled trials of patients with CHF who were treated with CoQ10 in 60 to 200 mg/day doses as a supplement to conventional treatment. Eight of the 14 controlled trials met the authors’ inclusion criteria for reliable meta-analysis, with seven of the eight studies documenting significant improvement in different variables of heart function in patients with CHF of varying etiology (idiopathic dilated cardiomyopathy, ischemic heart disease, hypertension, valvular heart disease and congenital heart disease). Specifically, significant improvements in stroke volume, ejection fraction, cardiac output, cardiac index and end-diastolic volume were observed with CoQ10 treatment.
The findings by Watson et al. (1), Permanetter et al. (2) and Hofman-Bang et al. (3) are in keeping with the clinical observations of cardiologists who have had extensive practical experience with the use of this supplement in patients with advanced dilated cardiomyopathies. The most dramatic improvements in myocardial function have been observed in those patients fortunate enough to have been treated with supplemental CoQ10 shortly after the diagnosis of CHF, before the development of irreversible myocyte loss and fibrosis. Although the optimal dose of CoQ10 in the treatment of CHF has not been established, it has become clear, over the past 15 years, that 100 mg per day is suboptimal for the majority of patients. An increase in the CoQ10 plasma level, in the study by Watson et al., from 903 ± 345 to 2,029 ± 856 nmol/liter, converts roughly to a baseline level of 0.8 µg/ml up to a treatment value of 1.7 µg/ml. Optimal improvement in myocardial function in our own patients did not occur until we attained blood CoQ10 levels >2.0 µg/ml, with average blood level of 2.9 µg/ml, on an average dose of 240 mg of CoQ10 per day (7,8). Furthermore, it has also been our observation that maximal myocardial function improvement with CoQ10 supplementation is rarely observed at three months, but can be achieved at six to 12 months.
In summary, Watson et al. are to be commended for their efforts, for it is a difficult, poorly funded and often thankless task to evaluate any natural and nonpatentable substance. I am hopeful that these investigators and others will move forward to further our understanding of this remarkable nutrient, which, for many of us out here in the trenches of patient care, is rapidly showing itself to be a safe and effective addition to our therapeutic armamentarium.
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References
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1. Watson PS, Scalia GM, Galbraith A, Burstow DJ, Bett N, Aroney CN. Lack of effect of coenzyme Q on left ventricular function in patients with congestive heart failure. J Am Coll Cardiol. 1999;33:1549–1552[Abstract/Free Full Text]
2. Permanetter B, Rossy W, Klein G, Weingartner F, Seidl KF, Blomer H. Ubiquinone (coenzyme Q10) in the long-term treatment of idiopathic dilated cardiomyopathy. Eur Heart J. 1992;13:1528–1533[Abstract/Free Full Text]
3. Q10 Study GroupHofman-Bang C, Rehnqvist N, Swedberg K, Wiklund I, Astrom H. Coenzyme Q10 as an adjunctive in the treatment of chronic congestive heart failure. J Card Fail. 1995;1:101–107[CrossRef][Medline]
4. Langsjoen PH, Vadhanavikit S, Folkers K. Response of patients in classes III and IV of cardiomyopathy to therapy in a blind and crossover trial with coenzyme Q10. Proc Natl Acad Sci USA. 1985;82:4240–4244[Abstract/Free Full Text]
5. Morisco C, Trimarco B, Condorelli M. Effect of coenzyme Q10 therapy in patients with congestive heart failure: a long-term multicenter randomized study. In: Folkers K, Mortensen SA, Littarru GP, Yamagami T, Lenaz G, editors. Clin Invest 1993;71 Suppl:S134–6.
6. Soja AM, Mortensen SA. Treatment of congestive heart failure with coenzyme Q10 illuminated by meta-analyses of clinical trials. Mol Aspects Med. 1997;18(Suppl):S159–S168
7. Langsjoen H, Langsjoen P, Langsjoen P, Willis R, Folkers K. Usefulness of coenzyme Q10 in clinical cardiology: a long-term study. Mol Aspects Med. 1994;15(Suppl):165–175
8. Langsjoen PH, Langsjoen AM. Coenzyme Q10 in cardiovascular disease with emphasis on heart failure and myocardial ischaemia. Asia Pac Heart J. 1998;7:160–168[CrossRef]
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