Coenzyme Q10 and Heart Failure

A State-of-the-Art Review
March 2016
Abhinav Sharma, Gregg C. Fonarow, Javed Butler, Justin A. Ezekowitz and G. Michael Felker

Abstract

Heart failure (HF) with either preserved or reduced ejection fraction is associated with increased morbidity and mortality. Evidence-based therapies are often limited by tolerability, hypotension, electrolyte disturbances, and renal dysfunction. Coenzyme Q10 (CoQ10) may represent a safe therapeutic option for patients with HF. CoQ10 is a highly lipophilic molecule with a chemical structure similar to vitamin K.

Although being a common component of cellular membranes, CoQ10’s most prominent role is to facilitate the production of adenosine triphosphate in the mitochondria by participating in redox reactions within the electron transport chain. Numerous trials during the past 30 years examining CoQ10 in patients with HF have been limited by small numbers and lack of contemporary HF therapies.

The recent publication of the Q-SYMBIO randomized controlled trial demonstrated a reduction in major adverse cardiovascular events with CoQ10 supplementation in a contemporary HF population. Although having limitations, this study has renewed interest in evaluating CoQ10 supplementation in patients with HF. Current literature suggests that CoQ10 is relatively safe with few drug interactions and side effects. Furthermore, it is already widely available as an over-the-counter supplement.

These findings warrant future adequately powered randomized controlled trials of CoQ10 supplementation in patients with HF. This state-of-the-art review summarizes the literature about the mechanisms, clinical data, and safety profile of CoQ10 supplementation in patients with HF.

Introduction

Despite numerous evidence-based medical and device therapies for patient with heart failure (HF) and reduced ejection fraction (HFrEF), the outcomes of these patients remain poor. HF is an energy-depleted state associated with low myocardial adenosine triphosphate (ATP) production, mitochondria dysfunction, abnormal calcium handling, increased reactive oxygen species generation, and endothelial dysfunction.

Many of the disease modifying therapies in chronic HF act by modulation of maladaptive neurohormonal pathways, such as the renin–angiotensin–aldosterone axis. Such therapies are limited by side effects, including hypotension leading to calls for new drugs with hemodynamically neutral profiles.1 Coenyzme Q10 (CoQ10) may represent a therapeutic option to treat individuals with HF.

Preclinical data suggest that CoQ10 has a critical role in ATP production, a potent anti-inflammatory agent, and may improve endothelial function. Lower CoQ10 levels are seen in patients with advanced HF symptoms and with lower ejection fractions. A recent randomized controlled trial has suggested that there may be a mortality benefit in patients with HFrEF with CoQ10 supplementation. Furthermore, there does not seem to be an adverse hemodynamic profile or safety concern about CoQ10 use.2 This review summarizes the literature about the mechanisms, clinical data, and safety profile of CoQ10 supplementation in HF.

Mitochondria, Energy, and HF

Patients with chronic HF typically have a relapsing and remitting disease course, with periods of decompensation causing worsening symptoms, such as dyspnea and peripheral edema, resulting in increases in therapy or hospitalization.3 Furthermore, despite drug therapies that can reduce morbidity and mortality, the management of chronic symptoms such as fatigue and exercise intolerance remains challenging.

One novel therapeutic avenue is to modulate cardiac energetics. Regardless of cause, it has been hypothesized that the failing heart is energy starved.4,5 HF is associated with abnormal calcium handling,6 ATP depletion,4 and mitochondria dysfunction7 within cardiomyocytes leading to a perturbation of the cardiac metabolic pathways.6 These alterations result in energy depletion and negatively affects on cardiac contractile function.6 Therapies that can prevent cardiac energy depletion may play a role in the treatment and management of HF.

Physiological Role of Coenzyme Q10:

Coenzyme Q10 (CoQ10) or ubiquinone can potentially enhance cardiac function through a variety of mechanisms (Figure 1). CoQ10 is highly lipophilic molecule composed of a 1,4-benzoquinone. The Q refers to the quinone chemical groups and the 10 refers to the number of isoprenyl chemical subunits in its tail. CoQ10 belongs to a group of compounds that are characterized by their quinone moieties in addition to the length and composition of their hydrophobic tails.

Although being a common component of most cellular membranes, CoQ10’s most prominent role is to facilitate the production of ATP by participating in redox reactions within the electron transport chain in the mitochondria.8 Within the electron transport chain, CoQ10 accepts electrons from complexes I and II and transports them to complex III. At this point, it is ready to be reduced by complexes I and II again (Figure 2).