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Nutraceutical Supplements in Heart Failure

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A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Clinical Nutrition".

Deadline for manuscript submissions: closed (30 June 2021) | Viewed by 27345

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Prof. Dr. Vincenzo Mollace

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Department of Health Sciences, Magna Graecia University, Campus Germaneto, 88100 Catanzaro, Italy
Interests: nutraceuticals; heart failure; endothelial dysfunction; metabolic syndrome
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Dear Colleagues,

Heart failure (HF) is a multifactorial disease with a prevalence of 1–2% in the global population. Co-morbidities such as diabetes, hypertension, obesity, or dyslipidemia are frequently associated with the occurrence of HF, thereby increasing the prevalence of the disease and the rate of hospitalization and mortality. In addition, ageing is affecting the number of patients undergoing HF, as the prevalence of the disease rises to 10% in people aged >70 years. Better management of risk factors and more substantial pharmacological and non-pharmacological treatment according to recent guidelines have significantly reduced the impact of HF and its consequences. In particular, recent data showed that all-cause mortality prevalence at 12 months for hospitalized and stable/ambulatory HF patients were 17% and 7%, respectively, and the 12-month hospitalization rates were 44% and 32%, respectively. Thus, several relevant outcomes of HF still remain unsatisfactory, and further improvements to the impact of the disease have to be taken into account while considering the overall approach to the management of the disease. Although preliminary evidence suggests that HF is associated with an increased deficiency of micronutrients and that nutraceuticals supply could be beneficial in treating patients undergoing failing myocardium, limited evidence supporting the benefits of nutraceuticals for patients with HF has been found in recent studies and meta-analyses.

The present Special Issue aims to collect contributions in this field in order to:

Identify a pathophysiological basis for nutraceutical supplementation at the early stages of cardiomyocyte dysfunction;
Optimize the nutraceutical supplementation process based on specific targets of myocardial dysfunction, in both animal models of HF and patients, with ejection fraction either preserved or compromised;
Promote and design clinical trials in order to verify, by means of an approach from “trees to bedside” , the efficacy and safety of nutraceutical supplementation in HF.

Prof. Dr. Vincenzo Mollace
Guest Editor

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Keywords

Heart failure
Pathophysiology
Cardiomyocyte dysfunction
Micronutrients
Nutraceutical supplementation

Published Papers (6 papers)

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Research

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22 pages, 4451 KiB

Open AccessArticle

Icariin Protects H9c2 Rat Cardiomyoblasts from Doxorubicin-Induced Cardiotoxicity: Role of Caveolin-1 Upregulation and Enhanced Autophagic Response

by Miriam Scicchitano, Cristina Carresi, Saverio Nucera, Stefano Ruga, Jessica Maiuolo, Roberta Macrì, Federica Scarano, Francesca Bosco, Rocco Mollace, Antonio Cardamone, Anna Rita Coppoletta, Lorenza Guarnieri, Maria Caterina Zito, Irene Bava, Luca Cariati, Marta Greco, Daniela Patrizia Foti, Ernesto Palma, Micaela Gliozzi, Vincenzo Musolino and Vincenzo Mollace Show full author list Hide full author list

Nutrients 2021, 13(11), 4070; https://doi.org/10.3390/nu13114070 - 14 Nov 2021

Cited by 13 | Viewed by 3280

Abstract

Doxorubicin (Doxo) is a widely used antineoplastic drug which often induces cardiomyopathy, leading to congestive heart failure through the intramyocardial production of reactive oxygen species (ROS). Icariin (Ica) is a flavonoid isolated from Epimedii Herba (Berberidaceae). Some reports on the pharmacological activity of Ica explained its antioxidant and cardioprotective effects. The aim of our study was to assess the protective activities of Ica against Doxo-detrimental effects on rat heart-tissue derived embryonic cardiac myoblasts (H9c2 cells) and to identify, at least in part, the molecular mechanisms involved. Our results showed that pretreatment of H9c2 cells with 1 μM and 5 μM of Ica, prior to Doxo exposure, resulted in an improvement in cell viability, a reduction in ROS generation, the prevention of mitochondrial dysfunction and mPTP opening. Furthermore, for the first time, we identified one feasible molecular mechanism through which Ica could exerts its cardioprotective effects. Indeed, our data showed a significant reduction in Caveolin-1(Cav-1) expression levels and a specific inhibitory effect on phosphodiesterase 5 (PDE5a) activity, improving mitochondrial function compared to Doxo-treated cells. Besides, Ica significantly prevented apoptotic cell death and downregulated the main pro-autophagic marker Beclin-1 and LC3 lipidation rate, restoring physiological levels of activation of the protective autophagic process. These results suggest that Ica might have beneficial cardioprotective effects in attenuating cardiotoxicity in patients requiring anthracycline chemotherapy through the inhibition of oxidative stress and, in particular, through the modulation of Cav-1 expression levels and the involvement of PDE5a activity, thereby leading to cardiac cell survival. Full article

(This article belongs to the Special Issue Nutraceutical Supplements in Heart Failure)

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18 pages, 3564 KiB

Open AccessArticle

The Effects of Bergamot Polyphenolic Fraction, Cynara cardunculus, and Olea europea L. Extract on Doxorubicin-Induced Cardiotoxicity

by Jessica Maiuolo, Irene Bava, Cristina Carresi, Micaela Gliozzi, Vincenzo Musolino, Federica Scarano, Saverio Nucera, Miriam Scicchitano, Francesca Bosco, Stefano Ruga, Maria Caterina Zito, Francesca Oppedisano, Roberta Macri, Annamaria Tavernese, Rocco Mollace and Vincenzo Mollace

Nutrients 2021, 13(7), 2158; https://doi.org/10.3390/nu13072158 - 23 Jun 2021

Cited by 13 | Viewed by 2715

Abstract

Doxorubicin is an anthracycline that is commonly used as a chemotherapy drug due to its cytotoxic effects. The clinical use of doxorubicin is limited due to its known cardiotoxic effects. Treatment with anthracyclines causes heart failure in 15–17% of patients, resulting in mitochondrial dysfunction, the accumulation of reactive oxygen species, intracellular calcium dysregulation, the deterioration of the cardiomyocyte structure, and apoptotic cell death. Polyphenols have a wide range of beneficial properties, and particular importance is given to Bergamot Polyphenolic Fraction; Oleuropein, one of the main polyphenolic compounds of olive oil; and Cynara cardunculus extract. These natural compounds have particular beneficial characteristics, owing to their high polyphenol contents. Among these, their antioxidant and antoproliferative properties are the most important. The aim of this paper was to investigate the effects of these three plant derivatives using an in vitro model of cardiotoxicity induced by the treatment of rat embryonic cardiomyoblasts (H9c2) with doxorubicin. The biological mechanisms involved and the crosstalk existing between the mitochondria and the endoplasmic reticulum were examined. Bergamot Polyphenolic Fraction, Oleuropein, and Cynara cardunculus extract were able to decrease the damage induced by exposure to doxorubicin. In particular, these natural compounds were found to reduce cell mortality and oxidative damage, increase the lipid content, and decrease the concentration of calcium ions that escaped from the endoplasmic reticulum. In addition, the direct involvement of this cellular organelle was demonstrated by silencing the ATF6 arm of the Unfolded Protein Response, which was activated after treatment with doxorubicin. Full article

(This article belongs to the Special Issue Nutraceutical Supplements in Heart Failure)

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Review

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16 pages, 1270 KiB

Open AccessReview

PUFA Supplementation and Heart Failure: Effects on Fibrosis and Cardiac Remodeling

by Francesca Oppedisano, Rocco Mollace, Annamaria Tavernese, Micaela Gliozzi, Vincenzo Musolino, Roberta Macrì, Cristina Carresi, Jessica Maiuolo, Maria Serra, Antonio Cardamone, Maurizio Volterrani and Vincenzo Mollace

Nutrients 2021, 13(9), 2965; https://doi.org/10.3390/nu13092965 - 26 Aug 2021

Cited by 21 | Viewed by 5853

Abstract

Heart failure (HF) characterized by cardiac remodeling is a condition in which inflammation and fibrosis play a key role. Dietary supplementation with n-3 polyunsaturated fatty acids (PUFAs) seems to produce good results. In fact, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have anti-inflammatory and antioxidant properties and different cardioprotective mechanisms. In particular, following their interaction with the nuclear factor erythropoietin 2 related factor 2 (NRF2), the free fatty acid receptor 4 (Ffar4) receptor, or the G-protein coupled receptor 120 (GPR120) fibroblast receptors, they inhibit cardiac fibrosis and protect the heart from HF onset. Furthermore, n-3 PUFAs increase the left ventricular ejection fraction (LVEF), reduce global longitudinal deformation, E/e ratio (early ventricular filling and early mitral annulus velocity), soluble interleukin-1 receptor-like 1 (sST2) and high-sensitive C Reactive protein (hsCRP) levels, and increase flow-mediated dilation. Moreover, lower levels of brain natriuretic peptide (BNP) and serum norepinephrine (sNE) are reported and have a positive effect on cardiac hemodynamics. In addition, they reduce cardiac remodeling and inflammation by protecting patients from HF onset after myocardial infarction (MI). The positive effects of PUFA supplementation are associated with treatment duration and a daily dosage of 1–2 g. Therefore, both the European Society of Cardiology (ESC) and the American College of Cardiology/American Heart Association (ACC/AHA) define dietary supplementation with n-3 PUFAs as an effective therapy for reducing the risk of hospitalization and death in HF patients. In this review, we seek to highlight the most recent studies related to the effect of PUFA supplementation in HF. For that purpose, a PubMed literature survey was conducted with a focus on various in vitro and in vivo studies and clinical trials from 2015 to 2021. Full article

(This article belongs to the Special Issue Nutraceutical Supplements in Heart Failure)

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20 pages, 1219 KiB

Open AccessReview

Effects of Bergamot Polyphenols on Mitochondrial Dysfunction and Sarcoplasmic Reticulum Stress in Diabetic Cardiomyopathy

by Jessica Maiuolo, Cristina Carresi, Micaela Gliozzi, Vincenzo Musolino, Federica Scarano, Anna Rita Coppoletta, Lorenza Guarnieri, Saverio Nucera, Miriam Scicchitano, Francesca Bosco, Stefano Ruga, Maria Caterina Zito, Roberta Macri, Antonio Cardamone, Maria Serra, Rocco Mollace, Annamaria Tavernese and Vincenzo Mollace

Nutrients 2021, 13(7), 2476; https://doi.org/10.3390/nu13072476 - 20 Jul 2021

Cited by 22 | Viewed by 4338

Abstract

Cardiovascular disease is the leading cause of death and disability in the Western world. In order to safeguard the structure and the functionality of the myocardium, it is extremely important to adequately support the cardiomyocytes. Two cellular organelles of cardiomyocytes are essential for cell survival and to ensure proper functioning of the myocardium: mitochondria and the sarcoplasmic reticulum. Mitochondria are responsible for the energy metabolism of the myocardium, and regulate the processes that can lead to cell death. The sarcoplasmic reticulum preserves the physiological concentration of the calcium ion, and triggers processes to protect the structural and functional integrity of the proteins. The alterations of these organelles can damage myocardial functioning. A proper nutritional balance regarding the intake of macronutrients and micronutrients leads to a significant improvement in the symptoms and consequences of heart disease. In particular, the Mediterranean diet, characterized by a high consumption of plant-based foods, small quantities of red meat, and high quantities of olive oil, reduces and improves the pathological condition of patients with heart failure. In addition, nutritional support and nutraceutical supplementation in patients who develop heart failure can contribute to the protection of the failing myocardium. Since polyphenols have numerous beneficial properties, including anti-inflammatory and antioxidant properties, this review gathers what is known about the beneficial effects of polyphenol-rich bergamot fruit on the cardiovascular system. In particular, the role of bergamot polyphenols in mitochondrial and sarcoplasmic dysfunctions in diabetic cardiomyopathy is reported. Full article

(This article belongs to the Special Issue Nutraceutical Supplements in Heart Failure)

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36 pages, 4024 KiB

Open AccessReview

The Potential Properties of Natural Compounds in Cardiac Stem Cell Activation: Their Role in Myocardial Regeneration

by Cristina Carresi, Miriam Scicchitano, Federica Scarano, Roberta Macrì, Francesca Bosco, Saverio Nucera, Stefano Ruga, Maria Caterina Zito, Rocco Mollace, Lorenza Guarnieri, Anna Rita Coppoletta, Micaela Gliozzi, Vincenzo Musolino, Jessica Maiuolo, Ernesto Palma and Vincenzo Mollace

Nutrients 2021, 13(1), 275; https://doi.org/10.3390/nu13010275 - 19 Jan 2021

Cited by 16 | Viewed by 5175

Abstract

Cardiovascular diseases (CVDs), which include congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, and many other cardiac disorders, cause about 30% of deaths globally; representing one of the main health problems worldwide. Among CVDs, ischemic heart diseases (IHDs) are one of the major causes of morbidity and mortality in the world. The onset of IHDs is essentially due to an unbalance between the metabolic demands of the myocardium and its supply of oxygen and nutrients, coupled with a low regenerative capacity of the heart, which leads to great cardiomyocyte (CM) loss; promoting heart failure (HF) and myocardial infarction (MI). To date, the first strategy recommended to avoid IHDs is prevention in order to reduce the underlying risk factors. In the management of IHDs, traditional therapeutic options are widely used to improve symptoms, attenuate adverse cardiac remodeling, and reduce early mortality rate. However, there are no available treatments that aim to improve cardiac performance by replacing the irreversible damaged cardiomyocytes (CMs). Currently, heart transplantation is the only treatment being carried out for irreversibly damaged CMs. Hence, the discovery of new therapeutic options seems to be necessary. Interestingly, recent experimental evidence suggests that regenerative stem cell medicine could be a useful therapeutic approach to counteract cardiac damage and promote tissue regeneration. To this end, researchers are tasked with answering one main question: how can myocardial regeneration be stimulated? In this regard, natural compounds from plant extracts seem to play a particularly promising role. The present review will summarize the recent advances in our knowledge of stem cell therapy in the management of CVDs; focusing on the main properties and potential mechanisms of natural compounds in stimulating and activating stem cells for myocardial regeneration. Full article

(This article belongs to the Special Issue Nutraceutical Supplements in Heart Failure)

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30 pages, 1170 KiB

Open AccessReview

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

by Vincenzo Mollace, Giuseppe M. C. Rosano, Stefan D. Anker, Andrew J. S. Coats, Petar Seferovic, Rocco Mollace, Annamaria Tavernese, Micaela Gliozzi, Vincenzo Musolino, Cristina Carresi, Jessica Maiuolo, Roberta Macrì, Francesca Bosco, Marcello Chiocchi, Francesco Romeo, Marco Metra and Maurizio Volterrani

Nutrients 2021, 13(1), 257; https://doi.org/10.3390/nu13010257 - 17 Jan 2021

Cited by 25 | Viewed by 4881

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. Full article

(This article belongs to the Special Issue Nutraceutical Supplements in Heart Failure)

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