COENZYME Q10 FOR HEART DISEASE

(CARDIOMYOPATHY & CONGESTIVE HEART FAILURE)
PETITION FOR HEALTH CLAIM

Prepared by David Heber MD, PhD, FACP, FACN
April 23, 2003

Prepared by:
Hemmi N. Bhagavan, PhD, FACN
Lancaster , PA 17602
May 27, 2003

Conclusions

There is sound scientific rationale for an important role for coenzyme Q10 in the maintenance of cardiovascular health in general and in the management of heart disease and in particular heart failure. Review of published literature in peer-reviewed journals on the use of coenzyme Q10 as an adjunct to conventional therapy in patients with congestive heart failure and cardiomyopathy shows that there is strong evidence in favor of significant clinical improvement with coenzyme Q10 supplementation. As a naturally-occurring nutrient that is produced in the body, coenzyme Q10 has an excellent safety record and no side effects. Therefore, coenzyme Q10 supplementation as supportive therapy for patients with or at risk for congestive heart failure or cardiomyopathy is justified and appropriate, since it can afford significant clinical benefit to the patients. Furthermore, by improving heart function and the quality of life in these patients, and by reducing the number of hospitalizations, coenzyme Q10 supplementation also has the potential to reduce overall healthcare costs.

The weight of the evidence based upon an objective assessment of available scientific literature supports the following proposed health claims for coenzyme Q10:
Coenzyme Q10 supplementation may help reduce the risk for congestive heart failure and cardiomyopathy.
Coenzyme Q10 supplementation may help reduce the risk for heart failure.
Coenzyme Q10 supplementation may help reduce the risk for certain types of heart diseases.
Coenzyme Q10 supplementation may help reduce the risk for certain types of heart diseases such as congestive heart failure and cardiomyopathy.
Coenzyme Q10 supplementation, as an adjunct to standard medical therapy, may help reduce the risk for certain types of heart diseases such as congestive heart failure and cardiomyopathy.

Introduction

Coenzyme Q10 (CoQ10) belongs to the homologous series of compounds called coenzyme Q that share the same basic ring structure but differ in the length of the isoprenoid side chain. Because of their wide and ubiquitous distribution in nature, these compounds are also called ubiquinones . CoQ10 stands for CoQ with 10 isoprene units in the side chain and it is the form present in humans and several other species. CoQ compounds play an essential role in the production of cellular energy in most aerobic organisms, from humans to plants and bacteria (Bliznakov, 1987; Ernster and Dallner, 1995; Crane 2001).

CoQ10 was first discovered and isolated in pure form from bovine heart mitochondria in 1957 by Dr. Fred Crane at the University of Wisconsin (Crane et al, 1957). Identification of the chemical structure and synthesis of CoQ10 was accomplished by Dr. Karl Folkers and his group at Merck in 1958 (Wolf et al, 1958). CoQ10 is a quinone with a structure similar to that of vitamin K, and is present in high concentrations in the mitochondria. Mitochondria are the fuel cells in each and every cell in the body where biological energy is produced. Research conducted during 1960s and 1970s clearly established the role of CoQ10 as a key component of the mitochondrial electron transport system (also known as the respiratory chain) where biological energy in the form of ATP (adenosine triphosphate) is produced. CoQ10 serves as the critical cofactor for at least three mitochondrial enzymes (called complexes I, II and III) that play a vital role in the electron transport chain (in a process known as oxidative phosphorylation). CoQ10 functions as the only non-protein component of the electron transport chain enabling the transfer of electrons between the donor and recipient molecules. Thus, CoQ10 plays an essential role in the synthesis of ATP, the energy that drives all cellular activities and without which cells cease to function (Crane, 2001). In addition to this role, CoQ10 is also an essential fat-soluble redox agent and an antioxidant (in its reduced form as ubiquinol) and furthermore, it can regenerate and recycle other antioxidants. CoQ10 is also a membrane stabilizer. Among the other functions of CoQ10 are cell signaling and gene expression (Ernster and Dallner, 1995; Rauchova et al, 1995; Crane, 2000; Crane 2001).

Although CoQ10 is sometimes referred to as a vitamin, by strict definition it does not meet the necessary criteria on one count. CoQ10 is an endogenous compound that is synthesized in our body, unlike vitamins that must be derived from exogenous sources. However, CoQ10 qualifies as a “conditionally essential nutrient”, since its production in the body cannot meet the needs under certain conditions. For instance, data show that CoQ10 production in the body slows down as we age, staring from the 20s. There are other conditions under which CoQ10 status is known to be compromised. Those tissues and organs with high-energy requirements such as the heart, liver, skeletal muscle pancreas, and kidney are ones most readily affected when CoQ10 supply becomes limiting (Ernster and Dallner, 1995).

CoQ10 for heart failure (cardiomyopathy and congestive heart failure)

The rationale for the use of CoQ10 in heart disease in general and particularly in heart failure lies in the fact that CoQ10 plays a pivotal role in the bioenergetics of the heart muscle as a cofactor in mitochondrial ATP production. This bioenergetic effect of CoQ10 is of fundamental importance in its clinical application, particularly as it relates to cells with exceedingly high metabolic demands such as the cardiac myocytes. It is also a potent antioxidant, a feature that has important implications in heart function, and especially under conditions of ischemia-reperfusion injury to the myocardium. The role of free radicals and their destructive potential in cell injury and in cell death in settings of ischemia and reperfusion are now well recognized. The antioxidant properties of CoQ10 and its localization within the mitochondria, a major source of free radicals, make it an obvious candidate for a potential therapeutic agent in these situations. Protection of LDL from oxidation is another important antioxidant function of CoQ10 that has an important bearing in maintaining cardiovascular health (Mohr et al, 1992; Ernster and Dallner, 1995; Rauchova et al, 1995; Alleva et al, 1997; Crane 2000, 2001).

Congestive heart failure (CHF) and cardiomyopathy are still among the major causes of morbidity and mortality in the US . The primary biochemical basis for the use of CoQ10 in the treatment of heart failure is defective bioenergetics, specifically availability of ATP that plays a central role in regulating myocardial contractility (Bashore et al, 1987; Rengo et al, 1993). A significant correlation has been demonstrated in the diseased heart between ATP content and systolic and diastolic left ventricular indices. Myocardial deficiency of CoQ10 has also been documented in patients with cardiomyopathy which serves to explain the underlying energy deficit in the heart muscle leading to impaired function (Folkers et al, 1985), and there is clear-cut evidence to show that CoQ10 acts at the mitochondrial level to improve the efficiency of energy production in human heart tissue (Rosenfeldt et al, 2002). Another interesting mechanism by which CoQ10 may aid heart function in CHF patients is by way of its inotropic action (Greenberg and Frishman, 1990). Such action increases the contractile force of the heart to improve cardiac output.

Pioneering studies on the efficacy of CoQ10 supplementation in patients with heart failure were carried out in Japan in the 1960s (Yamamura, 1977). S ince these early investigations, there has been a slow but steady accumulation of clinical experience worldwide with the use of CoQ10 as adjunct therapy in patients with various types of heart disease for over three decades. I n addition to numerous open-label studies, there have been over 15 randomized controlled clinical trials with both primary and secondary forms of heart failure. Furthermore, data from a large number of laboratory and preclinical studies using various animal models are also available that document the efficacy and safety of coenzyme Q10 in patients with heart failure, and heart disease in general (Linnane et al, 1995; Rosenfeldt et al, 2002).

The very first controlled randomized trials on CHF and cardiomyopathy were also carried out in Japan in 1972, and significant clinical improvement according to New York Heart Association (NYHA) classification was documented in CHF patients treated with a daily dose of 30 mg CoQ10 (Hashiba et al, 1972; Iwabuchi et al, 1972; cited by Langsjoen and Langsjoen, 1999). In the USA, pioneering research on the use of CoQ10 in heart disease was led by the late Dr. Karl Folkers in the 1960s, and the first report documenting a deficiency of CoQ10 in heart disease appeared in 1970 (Folkers et al, 1970). Dr. Folkers made invaluable contributions in this area in collaboration with Langsjoen and numerous other scientists (Folkers et al, 1985; Langsjoen et al, 1985; Langsjoen and Langsjoen, 1999).

Controlled clinical trials

There have been at least 15 randomized controlled clinical trials with a total of about 1400 patients on the efficacy of oral CoQ10 supplementation as adjunct therapy in heart failure that have demonstrated significant clinical improvement (Table 1). Furthermore, a meta-analyses of the controlled clinical trials in heart failure conducted during the years 1986-1995 was made in 1997 (Soja and Mortensen, 1997). Eight of the 14 trials met the inclusion criteria for reliable meta-analyses, and seven out the eight studies documented significant improvement in various parameters of heart function in patients with CHF of varying etiologies (idiopathic dilated, ischemia, hypertension, valvular heart disease, and congenital heart disease). Significant functional improvement was evident specifically with respect to stroke volume, cardiac output, cardiac index, and end-diastolic volume in patients treated with CoQ10.

The very first double-blind placebo-controlled trial in the USA was reported in 1985 that involved 19 heart failure patients, NYHA class II and IV, receiving either 100 mg of CoQ10 per day or placebo for three month periods in a cross-over design (Langsjoen et al, 1985). CoQ10 was administered as an adjunct to standard medical therapy. Assessment of clinical improvement included ejection fraction by impedence cardiography that showed a highly significant increase, concomitant with significant functional improvement. This was followed by three additional trials in 1986 using the same dosage of CoQ10 that confirmed and extended the clinical efficacy of CoQ10 in heart failure patients (VanFraechem et al, 1986; Judy et al, 1986a, 1986b). In 1990, Oda documented normalization of load-induced cardiac dysfunction in 40 patients with mitral valve prolapse using a dose of 3.1-3.4 mg CoQ10 per kg per day in a double-blind placebo-controlled trial (Oda, 1990). This was followed by two other double-blind studies, one involving 20 patients with ischemic cardiomyopathy receiving 200 mg CoQ10 per day for three months (Rossi et al, 1991) and the other with 20 patients with ischemic cardiomyopathy or dilated cardiomyopathy (NYAS class II and III) on 100 mg CoQ10 per day (Poggesi, 1991). Significant clinical improvements were seen in both studies, particularly with respect to exercise tolerance and left ventricular function. Similarly, Rengo et al (1993) documented significant improvements in clinical and echocardiographic parameters of cardiac performance, quality of life and tolerance in 60 patients with heart failure treated with 100 mg of CoQ10 per day for seven months.

The largest controlled trial to date was reported in 1993 that involved a total of 641 CHF patients (Morisco et al, 1993). This was a double-blind placebo-controlled study with NYHA class III and IV patients using a dose of 2 mg CoQ10 per kg per day or placebo for one year that documented a highly significant reduction (33%) in the number of hospital admissions ( p < 0.001). In addition, there were significant improvements in arrhythmias and episodes of pulmonary edema, associated with a low mortality rate in the treated group. The improvement in the overall quality of life of patients along with the reduction in hospitalizations in the CoQ10 group ( p < 0.01) also translates into highly significant savings in health care costs. This study was followed by a small double-blind
Fatal error: Maximum execution time of 30 seconds exceeded in D:\Sites\ALGLOBAL\misc\CoQ10_000.php on line 117