Keywords

Introduction

Diet is an important factor for our healthy body, in other words, our bodies need healthy food and a balanced diet to function efficiently. Fruits and vegetables are one of the main food groups containing vitamins. Vitamins are essential for several body functions such as growth and development and do help the body to function properly. An unbalanced ratio of oxidants to antioxidant defenses induces various pathological conditions in the human body. Among antioxidants, there are vitamins, minerals, and other compounds which exist in foods. They have functions to help prevent diseases by fighting against the high level of oxidants such as free radicals. If there are not adequate amounts of antioxidants, these free radicals damage tissues and cells and consequently induced organ dysfunction. Therefore, as a headnote, vitamins play a vital role in many biochemical functions in the human body to maintain optimal health [1].

Vitamins are micronutrients and have essential importance for our body and there are 13 different types of vitamins classified according to their biological and chemical activity [2]. Briefly, the main functions of vitamins can be summarized as helping the body maintain good health, via regulating the repairing processes in tissues and cells and the formation of new cells and fighting against aging. Overall, it can conclude that vitamins are vital for human good health through many daily bodily functions and cells to process energy. All vitamins were discovered (identified) between 1913 and 1948, and these micronutrients can be divided as water (Hydro) soluble vitamins (Vitamins B and C) and fat (Lipo) soluble vitamins (Vitamins A, D, E, and K) as well as their roles in the body (Fig. 10.1) [3,4,5].

Fig. 10.1
2 diagrams. On the left, liposoluble vitamins are classified into vitamins A, E, D, and K. On the right, hypo soluble vitamins are classified into vitamins C, B 1, B 2, B 3, B 6, and B 12.

General classification of vitamins. Water (Hydro) soluble vitamins (Vitamins B and C) and fat (Lipo) soluble vitamins (Vitamins A, D, E, and K)

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Vitamin E is the term for a group of tocopherols and tocotrienols although it most often refers to α-tocopherol and is a fat-soluble vitamin and the most abundant having the highest biological activity. Current and early studies with Vitamin E show that members of the Vitamin E family are beneficial concerning their biological functions [6,7,8,9,10,11,12,13].

Metabolism and Functions of Vitamin E

Vitamins are organic compounds and people need small quantities of vitamins in their daily life. Each organism has different vitamin requirements while most vitamins are coming from our foods including green leafy vegetables, legumes, nuts, papaya, seeds, and whole grains. Some natural foods also contain Vitamin E such as canola oil, olive oil, margarine, almonds, and peanuts, while others such as meats, dairy, leafy greens, and fortified cereals. Vitamin E was first discovered in 1922 and used as an essential nutrient for reproduction [14]. The first study on tocopherol requirements in health and disease was given by Goldbloom [15]. Later studies have demonstrated its biological significance and, also its relationship with the ability to regulate several body functions [16, 17].

The eight naturally occurring fat-soluble nutrients are named Vitamin E while among them, α-tocopherol predominates in many species with the highest biological activity. Vitamin E is absorbed via the lymphatic pathway and is carried in plasma by lipoproteins in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) [18,19,20].

Vitamins are essential for humans because they prevent various health disorders. If the body lacks any vitamin for a long time, it can develop a deficiency and a related disease. Therefore, Vitamin E has important functions for health via its beneficial effects on various functions of the human body (Fig. 10.2). For instance, it is a potent antioxidant, at most, its ability to scavenge not only reactive oxygen species (ROS) but also reactive nitrogen species (RNS) in cellular membranes [20,21,22,23]. It can prevent various chronic health diseases such as cardiovascular diseases, lung diseases, strokes, immunity deficiencies, skin disorders, aging, and cancer [3, 24,25,26,27]. Particularly, it has been demonstrated the anti-cancer properties of tocopherols and tocotrienols as adjuvant therapy for fibrocystic breast disease in patients [28].

Fig. 10.2
A wheel diagram of the vitamin E with several roles. They are reduction in risks for heart disease, antioxidant benefits, boost lung function, prevent skin aging, protect cognitively, improvement in immunity, reduces inflammation, and reduces hyper pigmentation.

Principle roles of vitamin E in mammalian health. Vitamin E has important functions for health via its beneficial effects on various functions of the human body

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Vitamin E family has both antioxidant and non-antioxidant properties and plays a vital role as a nutrient in the human diet [12, 29,30,31,32]. Since the Vitamin E molecules consist of a functional domain, a signaling domain, and a hydrophobic domain, these three different domains, therefore, mediate its antioxidative capacity and also non-antioxidative effects [33]. Vitamin E family can behave as cell communication facilitators, thereby cells constantly communicate between each other and their environments via different signaling pathways to maintain the healthy functioning of tissues, organs, and body systems. Consequently, the Vitamin E family can modulate signal transduction and gene expression leading to different cellular outcomes despite exerting essentially equal antioxidant potency [34,35,36].

Although deficiencies of Vitamin E are rare in humans, however, some reports state that inadequate Vitamin E consumption from the diet is widespread, and therefore some humans have low Vitamin E levels although it is unlikely to result in a complete Vitamin E deficiency in humans [37]. However, as documented widely by review articles, Vitamin E deficiency seems to be associated with some pathological conditions in mammalians such as muscle weakness, peripheral neuropathy, vision deterioration, and immune system problems [38,39,40,41].

Vitamin E: Action in the Cell Membrane and Interaction with Intracellular Binding Proteins

The mechanisms of tissue uptake of Vitamin E from the lipoproteins are not known very well yet although most studies pointed out its uptake during catabolism of triacylglycerol-rich lipoproteins by the activity of lipoprotein lipase, via the LDL receptor or by nonreceptor-mediated uptake [42, 43]. Generally, early and recent in vivo and in vitro experimental studies described molecular and cellular signaling pathways regulated by Vitamin E, particularly associated with its antioxidant properties in cardiovascular diseases [44, 45]. Vitamin E, as a form of D-a-tocopherol, is a lipid-soluble molecule and has both antioxidant and non-antioxidant actions in biological cells. As an antioxidant, it can inhibit the peroxidation of membrane lipids [45] and can itself insert into cell membranes and organelle membranes [46, 47]. Tocopherol molecule has a hydrophilic head group, and a hydrophobic tail and thereby allowing it to bind to the cell membrane with the head group in the aqueous part and the tail embedded in the fatty interior. Vitamin E briefly plays important role in the suppression of lipid peroxidation and conversion of free radicals to water and further prevention of high amounts of ROS in the membrane (Fig. 10.4). This important role by Vitamin E can prevent harmful damage in the membrane. For sure, the protection level against the peroxidation of membrane lipids by Vitamin E is dependent on the amount present in membranes [48]. In some certain conditions, Vitamin E action can be regenerated by reaction with other antioxidants, such as Vitamin C, selenium, omega-3, and also cholesterol acting in partnership with them [49]. Overall, besides its antioxidant role in biological membranes, Vitamin E also functions to stabilize membranes [50, 51].

There are various pathways are defined for the regulation of Vitamin E for its cellular uptake and efflux. As reviewed greatly by authors, these pathways include scavenger receptor B type I and LDL receptors, the ATP-binding cassette transporter A1 (ABCA1), alpha-CEHC (2,5,7,8-tetramethyl-2-(2′-carboxyethyl)-6-hydroxychroman), and gamma-CEHC (2,7,8-trimethyl-2-(2′-carboxyethyl)-6-hydroxychroman) [52]. The role of specific binding proteins in α-tocopherol intracellular trafficking is increasingly being understood, leading to new insights into the non-antioxidant functions of Vitamin E. The Vitamin E-binding protein was first purified from rat heart cytosol for the purification of fatty acid-binding protein which was different from the rat liver protein [53]. The α-Tocopherol transfer protein (α-TTP) is a cytosolic protein that binds α-tocopherol and enhances its transfer across membranes [54]. In vitro studies have shown that α-TTP transfers α-tocopherol between membranes through a direct interaction between protein and membrane [55, 56]. It is believed that α-TTP is responsible for the intracellular transport and distribution of α-tocopherol in the tissues.

Correspondingly, in a recent review article, the author also documented the regulatory role of Vitamin E on various signal transductions including redox-dependent and redox-independent molecular mechanisms [57]. In these mechanisms, Vitamin E affects the activity of enzymes and receptors involved in modulating specific signal transduction and gene expression pathways.

Vitamin E and Cardiovascular Function

The effects of Vitamin E on heart disease have been documented at most with studies encompassing basic science, and animal studies, however, there are some important epidemiological and observational studies, and few intervention trials [3, 58,59,60,61,62]. Cellular and animal studies have strongly emphasized that Vitamin E has an important impact on protection against a variety of types of oxidative stress. Taking into consideration the general aspects related to the low contents of antioxidants as compared to the other organs condition in the normal heart, the heart is a highly susceptible organ to oxidative stress [63]. So, oxidative stress is accepted as a common factor in many aspects of the pathogenesis of cardiovascular diseases. Indeed, abnormal production of ROS/RNS and the subsequent decrease in muscular insufficient antioxidant defenses have long been proposed to be the common pathogenetic mechanism of cardiovascular dysfunction, resulting from diverse cardiovascular risk factors for various diseases. Briefly, oxidative stress, in general, arises from an imbalance between the production of ROS/RNS and the lack of antioxidant capacity of the biological system. Supporting these statements, several studies have reported beneficial effects of therapy with antioxidant agents, including vitamins (particularly E and/or C), and other antioxidants, against cardiovascular system dysfunction [26, 64,65,66,67,68,69].

The cellular-level effect of Vitamin E, as an antioxidant, mainly includes maintaining membrane integrity within cells [32, 33, 70]. Vitamin E can protect the membranes from destruction through its ability to prevent the oxidation of unsaturated fatty acids in membrane phospholipids. In this process, Vitamin E destroys the singlet molecular oxygen and stops the reactions associated with the production of free radicals. Vitamin E has been shown to increase oxidative resistance in vitro and prevent atherosclerotic plaque formation in mouse models. From these regards, it has been mentioned that consumption of foods rich in vitamin E has been associated with a lower risk of coronary heart disease in middle-aged to older humans.

There are several representative findings on why, how, and/or which types of effects arose with Vitamin E supplementations in humans and model animal studies as well as in their cells. Through general aspects, it is known that antioxidants, acting either directly or indirectly, provide effects through different mechanisms to prevent oxidant-induced cell damage. Particularly, modulating mitochondrial activity is an important possibility to keep the oxidants under control, therefore protect the heart against oxidative stress-induced damage/dysfunction [71, 72]. On the other hand, low levels of some vitamins have been detected in both men and women during the development of different types of cardiovascular abnormalities such as hypertension, atherosclerosis, diabetes, ischemic heart disease, heart failure, and stroke (Fig. 10.3). However, the cause-effects of vitamin deficiency and cardiovascular disease are not exactly known yet.

Fig. 10.3
A cyclic diagram of the vitamin E with several roles. They are coronary heart disease, atherosclerosis, abnormal E C Gs, cardiomyocyte damage, cardiomyopathy, and metabolic changes.

The roles of vitamin E in mammalian heart health. The roles of Vitamin E status in the development of different types of cardiovascular abnormalities such as hypertension, atherosclerosis, diabetes, ischemic heart disease, heart failure, and stroke in mammalians

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Fig. 10.4
An illustration presents how vitamin E itself inserts into the cell membrane and the damaged cell membrane causes a reduction in R O S production with vitamin E.

The effect of vitamin E on a cell membrane. Vitamin E briefly plays important role in the suppression of lipid peroxidation and conversion of free radicals to water and further prevention of high amounts of ROS in the membrane of the mammalian cells

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Excellent early and recent reviews and original articles on the management of cardiovascular disease by Vitamin E are available in the literature [3, 73,74,75,76,77,78,79]. Several epidemiological and observational studies, as well as animal experimentations, support the use of different vitamins in diverse cardiovascular disorders, but there do not exist enough and promissive well-controlled clinical studies to observe their beneficial effects in any of the cardiovascular diseases (Fig. 10.3). Furthermore, the most important aspects of these studies can not be discovered how and how much Vitamin E supplementations are needed to prevent and/or treat humans with cardiovascular disorders. On the other hand, it should be taken into consideration that it is difficult to obtain the proper answers to all these unknown points related to Vitamin E requirement and/or supplementation to humans.

Furthermore, among several promissive results, supplementation of Vitamin E has been reported to reduce blood pressure in patients with essential hypertension [80], to delay the progression and attenuated the extent of atherosclerosis as well as endothelial dysfunction [81, 82]. In addition, some studies mentioned that Vitamin E application could prevent ischemia–reperfusion-induced cardiac dysfunction via the reduction in oxidative stress and inflammation [83, 84]. In these considerations, in an early study authors demonstrated that Vitamin E supplements could reduce the risk of coronary artery disease in humans [85] and produced beneficial effects in ischemic heart disease in mice [86]. The beneficial effect of Vitamin E in myocardial infarction was associated with the modulation of different cellular signaling pathways [59, 87]. Pretreatments of rats with Vitamin E have also been shown to prevent abnormal cardiac functions as well as ventricular arrhythmias, while it can also benefits cellular levels such as recoveries in the cardiomyocyte damage, lipid peroxidation and subcellular abnormalities [76, 79, 88, 89]. These observations suggest that Vitamin E is beneficial as a cardioprotective intervention against different pathological stimuli.

However, although the existence of many strong supports for the beneficial effects of Vitamin E in cardiac function, several clinical trials have yielded conclusive and conflicting results. In these regards, it has been to be emphasized that the beneficial effects of different doses of Vitamin E were dependent upon not only the appropriate dose but also the forms of tocopherols [75]. In another study, authors demonstrated an increase in the risk of coronary artery disease and myocardial infarction by high doses of Vitamin E [90]. Prolonged treatment of high-risk patients with Vitamin E did not show any effect on different cardiovascular events [91].

There are several factors why differential clinical outcomes in patients by Vitamin E supplementation are obtained. Among them, the sizes of cohorts, dose, duration, and form of Vitamin E for supplementation, and/or pathophysiological conditions that affect Vitamin E levels can be the underlying factors affecting differential results [92]. Additionally, the personalized properties of individuals such as polymorphisms in genes can modulate the uptake and transportation of Vitamin E while the polymorphisms can regulate vitamin E-mediated signaling pathways and gene expressions [58, 93,94,95].

Beneficial Effects of Combined Treatment with Vitamin E and Other Antioxidants in the Cardiovascular System

Vitamin E locates in biological cell membranes together with lipoproteins and plays an important role as a lipid antioxidant to protect the membrane lipids against free radicals and other oxidant molecules (Fig. 10.4). It has also another major role to act as a membrane stabilizer by forming complexes with the products of membrane lipid hydrolysis [57, 96]. As mentioned previously, Vitamin E is known as a lipid-soluble antioxidant and can scavenge oxidized products that result from damaged molecules by hydroxyl radicals and peroxynitrite (Fig. 10.4). The current literature suggests that the primary role of the Vitamin E family within the body is to function as an antioxidant, through its action on the chain breaking in membranes [35, 97].

The role of micronutrients and vitamins in health and disease has increased curiosity and gained high interest among researchers. Indeed, deficiency of some vitamins and trace elements including Vitamin E and selenium are associated with cardiovascular abnormalities whereas their supplementations have been claimed to reduce risks for various CVDs [78, 91, 98,99,100,101,102,103,104,105,106]. However, the data from several experimental and clinical studies for the pathogenesis of CVDs due to deficiencies of various vitamins as well as their therapeutic benefits are conflicting and there are even some inconsistent results.

Correlatively, selenium, being a co-factor of glutathione peroxidase enzyme, participates in the lipo-oxygenase pathway in the organic antioxidant systems together with catalase, superoxide dismutase, Vitamin E, Vitamin C, carotenoids, exerting synergistic action [107]. However, it is not yet clinically proved this synergistic effect in humans, there are several published early and recent data from different experimental conditions [108,109,110,111]. Supporting the above literature, we have demonstrated that selenium combined with Vitamin E and Vitamin C restored structural alterations of bones in heparin-induced osteoporosis more effectively than the sole combination of these two vitamins [112]. A supporting study by Mahmood et al. [113] was performed to investigate the antioxidative function of Vitamin E and selenium on pregnant/nonpregnant animals, and their findings demonstrated that this combined supplementation ameliorated salinity-induced oxidative stress, improved antioxidant status, and enhanced reproductive and growth performance of suckling kids. Another study performed on lambs during the suckling period also demonstrated high benefits of the combined effect of Vitamin E and selenium on some productive and physiological characteristics of ewes and their lambs [114]. Similarly, Dhari and Kassim [115] used selenium-containing supplements with or without Vitamin E and their combined supplementations provided more benefits on some physiological and productive properties of Awassi lambs such as improvements in thyroxin hormone and growth hormone.

In an early clinical study, authors investigated the relationships between the levels of some vitamins and elements in blood samples of 116 healthy men aged 30–50 years [116]. The multivariate analysis of their data showed that there was no correlation between blood selenium concentrations or glutathione peroxidase activities and the risk factors for cardiovascular disease, while there was a strong association between Vitamin E and serum lipid concentrations. However, in a later study, authors demonstrated the synergistic effects of Vitamin E and selenium in iron-overloaded mouse hearts, by providing important antioxidant defenses in iron-overload states [101]. In these regards, supportingly, Schwenke and Behr [117] fed rabbits with an atherogenic diet or an atherogenic diet supplemented with Vitamin E plus selenium and analyzed several blood parameters and areas of atherosclerotic lesions. Their data provided important beneficial effects of Vitamin E plus selenium supplementation on these abnormalities such as inhibition of atherosclerosis by a mechanism, in part, independent of effects on plasma and lipoprotein cholesterol concentrations. However, there are various unresolved events regarding whether and/or how selenium, Vitamin E, or their combination has roles in the etiology of heart dysfunction. Furthermore, Pincemail and Meziane [118] recently reviewed widely the role of antioxidant and vitamin couples such as Vitamin E and selenium in skin and hair health, particularly during the aging of individuals. They mentioned that among all the antioxidants, Vitamin E and selenium have a unique profile, through their particularity to act in synergy in eliminating lipid peroxides [119]. They proposed a mechanistic point of view related to the synergistic effects of these two molecules: Both Vitamin E and Se can exhibit common effects in a wide range, beyond their antioxidant actions to protect cells against oxidative stress such as glucooxidation, metalloproteinase expression, telomere attrition, and DNA methylation.

More experimental studies also demonstrated the therapeutic effects of Vitamin E and selenium complex against toxic agents exposure-induced not only cardiac damage but also liver and aorta in animals [120,121,122] by using histological, biochemical, and pharmacological investigations. In an early study, it has been demonstrated that dietary selenium and Vitamin E intakes could affect the beta-adrenergic receptor response of L-type Ca2+-channel currents and beta-adrenoceptor-adenylate cyclase coupling in male adult rat heart, while their deficiencies could depress these currents, significantly [123]. Indeed, in these regards, there are early data including the important interrelations between Vitamin E and selenium and their metabolic functions [124]. Supporting studies have shown that alone selenium deficiency did not affect the electrophysiological or mechanical functions of rat hearts [146, 159], whereas the combined deficiency of selenium and vitamin E leads to some abnormalities in cardiovascular functions of both humans and laboratory animals [125,126,127,128,129].

The current data associated with the reduction of cardiovascular diseases via supplementation of Vitamin E together with other antioxidants are raised from basic research studies, through their ability to trap and deactivate free radicals and thereby prevent tissue damage (Fig. 10.4) [130,131,132,133,134]. Furthermore, antioxidants together with vitamins or alone can prevent and/or therapy the atherosclerotic plaque formation in mammalian animals and humans by affecting platelet function, and modifying vascular function [135,136,137,138,139]. However, there are some but not all prospective cohort studies supporting the above finding while some of them have opposite findings [85, 140,141,142,143]. Interestingly, some animal studies also emphasized the benefits of Vitamin E with other antioxidants on early atherosclerosis in mice and cause cell death in guinea pig skeletal muscle [23, 144].

Interestingly, authors, considering the conflictions on the benefits of vitamin E and n-3 polyunsaturated fatty acids in patients with myocardial infarction (MI), supplied over 10,000 patients following MI with either n-3 polyunsaturated fatty acids (PUFA) or Vitamin E [145]. The results demonstrated that n-3 PUFA supplementation led to a clinically important and statistically significant benefit with no benefits with Vitamin E. However, it was investigated whether omega-3 and vitamin E supplementation has benefits on the dry mouth in patients with Sjögren's syndrome of 61 patients and demonstrated that wheat germ oil supplementation provided better recoveries than n-3 supplementation [147]. In a controlled trial of Vitamin E and β-Carotene supplementation on stroke incidence and mortality in male smokers, it has been documented that either supplementation was nonsignificant as overall interpretations, on the contrary, Vitamin E increased the risk of fatal hemorrhagic strokes while preventing cerebral infarction, whereas β-Carotene increased the risk of intracerebral hemorrhage [148]. Also, a trial taken by the Cambridge Heart Antioxidant Study and some others indicated Vitamin E supplementation as safe for adults to the reduction of cardiovascular diseases [66, 149]. On the contrary, results of a five-year randomized, double-blind, placebo-controlled international trial conducted in patients at least 55 years old with vascular disease or diabetes mellitus have announced that long-term Vitamin E supplementation did not prevent cancer or major cardiovascular events and may increase the risk for heart failure [150].

Using few data, the authors mentioned the pro-oxidant effects of Vitamin E in the absence of co-antioxidants, failing to augment antioxidant defenses [151]. In this regard, studies documented some limitations of the effects of Vitamin E, such as its non-effectiveness on certain ROS products [152].

Although there are much data associated with antioxidants and their beneficial effects on cardiac function, either prevention, therapeutic, or both [153], it has been also shown omega-3 fatty acids are important nutrient in maintaining human health, in part, via decreasing the inflammatory reactions and lessen the tissue damages. The combination of Vitamin E and omega-3 FA were also evaluated in several studies which indicated the beneficial effects of the supplementation of omega-3 FA in combination with vitamin E on coronary artery disease patients by decreasing oxidative stress and inflammation [154]. Another group of studies (both in vitro and in vivo) also found the benefits of these combinations on oxidative stress and inflammation in vascular endothelial cells [155, 156]. Jamilian and coworkers [157], in their a randomized controlled clinical trial, investigated the effects of omega-3 fatty acids, and Vitamin E co-supplementation (6 weeks) on biomarkers of oxidative stress, inflammation, and pregnancy outcomes in gestational diabetes and demonstrated the important benefits, particularly in women with the incidence of the newborns’ hyperbilirubinemia.

There are various experimental data to demonstrate the efficient antioxidant effects of omega-3 combined with Vitamin E (omega-3E: containing 70% pure omega-3 and 2% natural vitamin E) on cardiovascular function under pathological conditions. Treatment of diabetic rats with this complex caused significant attenuation in the diabetes-induced altered activities of antioxidant enzymes in the heart tissues without no benefits on diabetes-induced decreases in left ventricular developed and end-diastolic pressures [158]. In a later study, authors examined the role of omega-3E supplementation on diabetes-induced vascular dysfunction [160]. This treatment could significantly improve impaired vascular responses and alterations in matrix metalloproteinases via preventing oxidative stress-associated injury in vascular tissues including prevention of thiol oxidation, alterations in endothelin-1 and PKC activity, and normalization of tissue nitrite level.

Overall, most studies in this field show a significant relationship between the availability of Vitamin E plus antioxidant supplementations and prevention of not only oxidative stress but also other risk factors in the heart and thereby prevention of cardiac abnormalities including heart failure (Fig. 10.5). Although micronutrient deficiencies are frequently observed among patients with various pathologies including heart failure, the roles of most micronutrients in pathogenesis and treatment strategies have not been completely understood yet.

Fig. 10.5
A diagram presents the vitamin E combined with antioxidants intervention, which is divided into individual undesirable factors, cardiovascular risk factors, and comorbidities, with its corresponding factors, reducing the risk of heart failure.

Overview of the risk factors and protective actions of vitamin E combined with other antioxidants on the development of heart failure. Both intrinsic (i.e. diabetes, hypertension, aging, and rare genes mutations) and extrinsic (i.e. unhealthy diet and lifestyle) factors have deleterious effects and represent risks to development of cardiac dysfunction. On the other hand, having a balanced and properf daily diet togerher with a well-programmed lifestyle (i.e. vitamin E plus antioxidant supplementations) can exert protective actions on cardiac abnormalities, which are further leading to heart failure via not only prevention of oxidative stress but also other risk factors in the heart

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Conclusions

Attempts to use antioxidants as adjuvant drugs to treat cardiac arrhythmias are justified because routinely used antiarrhythmic medications have many potential interactions and side effects. Paradoxically, antiarrhythmic drugs may also be proarrhythmic, that is, they may increase existing arrhythmia or induce arrhythmia. The use of various antioxidants, including vitamins and polyphenols, is likely to improve standard treatment effects. Combination therapy could potentially reduce the doses of standard drugs. Natural antioxidants are safe and have limited side effects, and research suggests they are associated with a low risk for the patient. Scavenging ROS production or downregulating enzymes related to ROS could be investigated as novel therapeutic approaches. The studies conducted so far indicate that their application may play a significant role in preventing and treating cardiac arrhythmias. Antioxidants could potentially be used not only as direct ROS scavengers but also in protecting against cardiac fibrosis and contributing to maintaining the normal function of the heart’s conduction system. Most available research is based on animal and cellular models. There is a great need for clinical trials in humans. In a current opinion, antioxidants can be useful not only in patients with chronic arrhythmias but also in emergency and critically ill patients, where redox imbalances are very pronounced and constitute a pathomechanism of many diseases. More importantly, treatment of patients with cardiovascular diseases can not be available for most patients because of several reasons, and so the aim must be focused to prevent the development and progression of them. Future research should focus on the development of specific antioxidant drugsin a manner of combination with vitamins (vitamins C and E), and even now, certain natural compounds (resveratrol, polyphenols, etc.) can serve as supportive and safe therapies.