Pathophysiological Basis for Nutraceutical Supplementation in Heart Failure: A Comprehensive Review

Abstract

There is evidence demonstrating that heart failure (HF) occurs in 1-2% of the global population and is often accompanied by comorbidities which contribute to increasing the prevalence of the disease, the rate of hospitalization and the mortality. Although recent advances in both pharmacological and non-pharmacological approaches have led to a significant improvement in clinical outcomes in patients affected by HF, residual unmet needs remain, mostly related to the occurrence of poorly defined strategies in the early stages of myocardial dysfunction. Nutritional support in patients developing HF and nutraceutical supplementation have recently been shown to possibly contribute to protection of the failing myocardium, although their place in the treatment of HF requires further assessment, in order to find better therapeutic solutions. In this context, the Optimal Nutraceutical Supplementation in Heart Failure (ONUS-HF) working group aimed to assess the optimal nutraceutical approach to HF in the early phases of the disease, in order to counteract selected pathways that are imbalanced in the failing myocardium. In particular, we reviewed several of the most relevant pathophysiological and molecular changes occurring during the early stages of myocardial dysfunction. These include mitochondrial and sarcoplasmic reticulum stress, insufficient nitric oxide (NO) release, impaired cardiac stem cell mobilization and an imbalanced regulation of metalloproteinases. Moreover, we reviewed the potential of the nutraceutical supplementation of several natural products, such as coenzyme Q10 (CoQ10), a grape seed extract, Olea Europea L.-related antioxidants, a sodium-glucose cotransporter (SGLT2) inhibitor-rich apple extract and a bergamot polyphenolic fraction, in addition to their support in cardiomyocyte protection, in HF. Such an approach should contribute to optimising the use of nutraceuticals in HF, and the effect needs to be confirmed by means of more targeted clinical trials exploring the efficacy and safety of these compounds.

Keywords: dysfunctional cardiomyocytes; heart failure; nutraceuticals; oxidative stress; patho-physiological mechanisms.

Figure 1

Effects of nutraceuticals on the mitochondrial function in heart diseases. Coenzyme Q10 (CoQ10) plays a critical role in adenosine triphosphate (ATP) generation by accepting electrons from complexes I and II and transporting them to complex III of the mitochondrial electron transport chain. Moreover, CoQ10 is involved in the protons’ transfer in the inner mitochondrial membrane, called the proton motive Q-cycle, leading to the free movement of protons through the internal mitochondrial membrane; sodium–glucose cotransporter (SGLT2) inhibitors increase the amount of ketone bodies; proanthocyanidins significantly increase the activities of mitochondrial enzymes (isocitrate dehydrogenase, succinate dehydrogenase, malate dehydrogenase and α-ketoglutarate dehydrogenase) and respiratory chain enzymes (nicotinamide adenine dinucleotide (NADH) dehydrogenase and cytochrome c oxidase); hydroxytyrosol (HT) is able to improve the integrity of complex-III of the mitochondrial electron transport chain.

Figure 2

Effects of nutraceuticals on the stem cell compartment in heart diseases. (A) CoQ10 inhibits high glucose-induced endothelial progenitor cell (EPC) dysfunction and death via modulation of the 5′ adenosine monophosphate-activated protein kinase (AMPK) pathway, upregulating endothelial nitric oxide synthase (eNOS) activity and heme oxygenase-1 (HO-1) expression; (B) oleuropein attenuates AngII-mediated oxidative stress in vascular progenitor cells (VPCs) though direct scavenging activity and regulates the ERK1/2-Prdx and Akt/eNOS signalling pathway; (C) the bergamot polyphenolic fraction (BPF) protects endogenous CSCs against DOXO-induced cardiotoxicity though its direct antioxidant properties and stimulates CSC activation and differentiation in newly formed cardiomyocytes.