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.

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

“…Naringin, the main component of BPF, is able to reverse SR stress, induced in diabetic cardiomyopathy. Since BPF has anti-inflammatory, antioxidant [ 94 ], hypoglycemic, and hypolipemic effects [ 46 , 53 , 58 , 59 , 150 , 152 , 153 ], in this review, we further examined the beneficial role of BPF on the pathophysiological mechanisms of diabetic cardiomyopathy. If the protective effects of BPF are further confirmed in clinical trials with a large number of enrolled patients, a greater contribution could be made in the management of diabetic cardiomyopathy through nutraceutical supplementation and the use of optimal micronutrients.…”

“…Analyzing the pathophysiological mechanisms of diabetic cardiomyopathy, especially the onset of oxidative stress, mitochondrial and SR dysfunctions were evidenced [ 151 , 152 ]. Under these conditions, protective mechanisms that include the overexpression of endogenous antioxidant enzymes, UPR, and autophagic responses are activated with the aim of antagonizing the apoptotic cell death of myocardial cells [ 153 ]. Since BPF counteracts oxidative stress in in vitro and in vivo cardiotoxicity models [ 49 , 50 , 53 ], in addition to reverting mitochondrial dysfunction [ 94 , 148 , 153 ], it is likely to assume its protective role even in the early stages of diabetic cardiomyopathy, in cardiac dysfunction, and in countering the development of heart failure.…”

Interaction between Cadmium and Zinc Levels in the Biological Samples of Type 1 Diabetic Mellitus Children, Reside in Different Areas of Sindh, Pakistan

“…The intake of toxic elements may promote DM, hypertensive and atherosclerosis disorders by increasing oxidative stress due to the deficiency of Zn [14]. The deficiency of essential nutrients, lack of homeostatic control or an excess intake of some toxic elements causes chronic physiological disorders [15]. The toxic metals can interfere with the normal functioning of essential trace elements in the enzymatic systems.…”

“…The toxic metals can be replacing the nutritional minerals in the enzymes and inactive to them. Whereas, a higher dietary level of essential minerals and vitamins helps to prevent toxic metal toxicity, as well as helps to eliminate them from the body [15]. Metal ions bonded to melanosomes according to atomic weight and volume.…”

“…Metal ions bonded to melanosomes according to atomic weight and volume. Heavy metals can effectively compete to same binding sites as foreign ions to replace previously bound metals [15]. However, these bonded heavy metals cannot easily manageable to displacement [16].…”