Cardiovascular diseases (CVDs) constitute a major group of disorders, including conditions such as ischemic heart disease and stroke, and represent a leading cause of death worldwide, placing a considerable burden on public health [1]. Recent estimates from the World Health Organization indicate that nearly 19.8 million people died due to CVD in 2022, accounting for approximately one-third of all global deaths [2]. A comparable trend is also evident in Turkey. According to the 2024 mortality and cause-of-death data published by the Turkish Statistical Institute (TURKSTAT), circulatory system diseases rank as the leading cause of mortality, comprising 36.0% of all deaths [3].

Lifestyle-related factors characteristic of modern living—including chronic stress, sedentary behavior, poor dietary patterns, and environmental exposures—are closely associated with the rising prevalence of CVDs [4]. Many of these factors influence cardiovascular health by enhancing oxidative processes and stimulating inflammatory pathways. In this framework, oxidative stress is widely recognized as a key contributor to CVD development. It reflects a disruption in the balance between reactive oxygen species (ROS) generation and the body’s antioxidant defense capacity. Excessive oxidative load leads to endothelial injury, which in turn initiates inflammatory cascades and promotes the formation of atherosclerotic lesions [5]. Furthermore, oxidative stress is implicated not only in atherosclerotic progression but also in the emergence of cardiovascular conditions, including hypertension, myocardial infarction, and heart failure [6].

Accordingly, approaches targeting the reduction of oxidative stress have become increasingly important in both the prevention and clinical management of CVDs. Antioxidant compounds encompass a broad range of nutrients and bioactive substances, including vitamins (A, C, and E), trace elements such as selenium and zinc, polyphenolic compounds like flavonoids and resveratrol, as well as coenzyme Q10 and omega-3 fatty acids. These agents help mitigate oxidative damage primarily through free radical scavenging mechanisms. In addition, recent research has increasingly focused on their potential roles in preserving endothelial integrity, modulating inflammation, and reducing overall cardiovascular risk [7].

The antioxidant compounds addressed in this review were selected from among those that have been frequently investigated in the literature in the context of oxidative stress and inflammatory mechanisms associated with CVD and whose biological effects have been well characterized. Although numerous compounds exhibiting antioxidant activity are present in the diet, this review focuses on antioxidants that are supported by stronger clinical and epidemiological evidence and whose relationship with cardiovascular health has been more clearly established. However, beyond the traditional view of oxidative stress and antioxidants, it has become evident that this process involves more complex mechanisms at the cellular level. In recent years, the understanding of oxidative stress has moved beyond the simple balance model between oxidants and antioxidants toward a more integrative perspective that emphasizes the critical role of redox signaling in cellular communication [8, 9]. ROS are recognized not only as byproducts that cause cellular damage but also as key molecules involved in intracellular signaling, regulating fundamental physiological processes such as proliferation, differentiation, and apoptosis [10]. Mitochondria, which are an important source of ROS, are considered to play a central role not only in energy production but also in redox-based cellular signaling [8, 9].

This paper explores the contribution of oxidative stress to the development of CVDs and examines how antioxidant compounds influence endothelial integrity, inflammatory pathways, and atherosclerotic progression based on current evidence. Furthermore, it highlights the potential of nutrition-oriented antioxidant approaches in supporting both the prevention and clinical management of CVDs from a comprehensive perspective.

This study is based on a narrative review design and relies on a comprehensive evaluation of the existing scientific evidence regarding the role of antioxidants in CVD. Relevant studies were identified through searches conducted in the PubMed and Google Scholar databases. Only studies published up to March 2026 and written in English were included.

In the search strategy, the keywords “antioxidants in cardiovascular disease”, “oxidative stress and cardiovascular disease”, “dietary antioxidants”, “polyphenols”, “vitamins and cardiovascular disease”, and “antioxidants in CVD” were searched either individually or in combination using Boolean operators (AND, OR). In addition, the reference lists of the selected studies were manually examined to identify additional sources.

As this review is narrative in nature, a systematic selection protocol was not applied, and it is not intended to represent the entirety of the available literature. The selected studies were critically evaluated and synthesized in light of current scientific evidence.

Studies were initially screened based on their titles and abstracts, followed by a detailed full-text evaluation of those considered eligible.

Inclusion criteria:

(i) studies examining the relationship between CVD and antioxidants,

(ii) studies addressing the association between oxidative stress and cardiovascular pathophysiology,

(iii) human-based studies (clinical studies, randomized controlled trials, meta-analyses, and recent reviews),

(iv) studies published in peer-reviewed journals with sufficient scientific rigor.

Exclusion criteria:

(i) studies not directly related to CVD,

(ii) studies with methodological limitations,

(iii) studies with limited scientific contribution or not supported by current evidence,

(iv) studies conducted solely at the animal or in vitro level without clinical relevance.

Although a systematic selection protocol was not applied, care was taken to include studies reporting both positive and negative findings in order to minimize potential bias.

The findings are presented under the following thematic headings:

1.

The role of oxidative stress in CVDs.

Oxidative stress refers to a pathological state resulting from an imbalance between the production of ROS and the organism’s antioxidant defense capacity [11]. This disequilibrium causes damage at both cellular and tissue levels and contributes significantly to the onset and progression of CVDs, particularly atherosclerosis [12]. A key mechanism underlying cardiovascular injury involves the overproduction and accumulation of free radicals, especially ROS. These reactive species originate from multiple sources, including mitochondrial respiratory activity and enzymatic systems such as NADPH oxidase (NOX), xanthine oxidase, and uncoupled endothelial nitric oxide synthase (eNOS). In addition, processes like immune cell activation and various environmental influences further enhance ROS generation [13, 14].

At physiological and tightly regulated levels, ROS act as key signaling molecules that participate in the regulation of cellular defense systems, primarily through activation of the Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway [15]. Under basal conditions, Nrf2 exists in association with Keap1; however, increased ROS levels trigger its dissociation, followed by translocation into the nucleus, where it interacts with antioxidant response element (ARE) regions [16]. This mechanism supports cellular homeostasis by upregulating the expression of genes responsible for antioxidant enzyme production, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) [17].

The biological effects of ROS depend not only on their levels but also on their intracellular localization. This phenomenon is explained by the concept of “compartmentalized redox signaling” [18, 19]. In particular, mitochondria-derived ROS have been reported to act as regulatory molecules involved in intracellular signaling and to play a role in the regulation of vascular functions [20].

When ROS levels rise beyond physiological thresholds and antioxidant defenses fail to adequately compensate, these molecules begin to exert detrimental effects. Under these circumstances, the oxidative load increases, resulting in both structural and functional impairment of critical cellular components, including lipids, proteins, and nucleic acids [21]. Concurrently, redox-sensitive signaling pathways such as nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) become activated, accompanied by an upregulation of adhesion molecule expression. Consequently, the production of proinflammatory cytokines, adhesion molecules, and chemokines is intensified, facilitating the recruitment of monocytes and T lymphocytes into the vascular wall and thereby promoting the progression of inflammation [13, 22].

Moreover, the upregulation of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in endothelial cells promotes monocyte attachment to the endothelial surface and facilitates their migration into the vascular wall, thereby sustaining the inflammatory milieu and contributing to atherosclerotic lesion formation [23].

Beyond these mechanisms, oxidative stress plays a prominent role in atherogenesis through lipid peroxidation processes. Elevated ROS levels induce the oxidative modification of low-density lipoproteins, resulting in the generation of oxidized low-density lipoproteins (ox-LDL). The subsequent uptake of these modified lipoproteins by macrophages leads to foam cell formation, while the amplified inflammatory response further drives plaque progression and destabilization [24].

Throughout these processes, antioxidants reduce oxidative stress and the associated cellular damage by neutralizing free radicals [23]. The protective role of antioxidants and the dual mechanism of ROS are illustrated in Figure 1.

ROS originate from multiple sources, such as mitochondrial respiratory activity, NOX function, and the presence of inflammatory cells. Under physiological conditions, tightly regulated ROS levels act as signaling mediators and support vascular homeostasis via redox-dependent pathways, including Nrf2 signaling. During this process, Nrf2 separates from Keap1, subsequently translocates into the nucleus, and interacts with AREs, leading to enhanced expression of antioxidant and cytoprotective genes. Conversely, excessive ROS generation promotes oxidative stress, which induces lipid peroxidation, protein modification, and DNA damage. These alterations are closely linked to endothelial dysfunction, decreased nitric oxide (NO) availability, and heightened inflammatory activity, thereby contributing to the onset and progression of cardiovascular disorders, including atherosclerosis and myocardial infarction.

Oxidative stress impairs the functional integrity of vascular endothelial cells and contributes to the development of endothelial dysfunction. The endothelium is a highly metabolically active cellular layer lining the inner surface of blood vessels, acts as a selective interface between circulating blood and the vascular wall, and is essential for the regulation of vascular homeostasis [25]. By modulating vascular tone, regulating platelet activity, influencing inflammatory responses, and inhibiting vascular smooth muscle cell proliferation, the endothelium serves as a key regulator in maintaining the physiological balance of the cardiovascular system [26].

Under physiological conditions, vascular tone is regulated by vasodilatory mediators such as NO, prostacyclin, and endothelium-derived hyperpolarizing factors, while vasoconstrictive responses are mediated by factors including endothelin-1 (ET-1), angiotensin II, and thromboxane A₂ [25]. However, increased ROS production leads to the reaction of NO with superoxide, resulting in the formation of peroxynitrite and thereby reducing NO bioavailability [27].

This decrease in NO levels triggers processes such as enhanced vasoconstriction, increased expression of endothelial adhesion molecules, elevated inflammatory cell infiltration, and stimulation of vascular smooth muscle cell proliferation, thereby contributing to the early stages of atherosclerosis. Therefore, endothelial dysfunction is considered an early and potentially reversible stage of atherosclerosis and is regarded as a critical step in the pathogenesis of CVD [28].

Antioxidants are defined as compounds that slow down or inhibit oxidative reactions in order to limit the damage caused by oxidative stress in cells [29].

According to their mechanisms of action, antioxidants are classified as primary (chain-breaking) and secondary (preventive) antioxidants. Primary antioxidants directly neutralize free radicals and terminate oxidative chain reactions, whereas secondary antioxidants exert their effects through indirect mechanisms such as chelating metal ions, reducing ROS formation, and converting hydroperoxides into less reactive compounds [30].

According to their sources, antioxidants are examined in two main groups: endogenous and exogenous antioxidants [31]. Endogenous antioxidants refer to the defense system synthesized by the organism, consisting of enzymatic and non-enzymatic components, whereas exogenous antioxidants include compounds obtained through diet or supplementation [32, 33]. Both groups of antioxidants function in a complementary and synergistic manner in maintaining cellular homeostasis and protecting against oxidative stress [31]. The classification of endogenous antioxidants is presented in Table 1, while the classification of exogenous antioxidants is presented in Table 2.

However, the biological effects of antioxidants depend not only on their chemical structures but are also shaped by pharmacokinetic processes such as bioavailability and metabolism [34]. The bioavailability of antioxidant compounds is particularly influenced by intestinal absorption and metabolic processes [35]. In addition, metabolic transformations carried out by the gut microbiota play an important role in determining the biological effects of dietary antioxidants, especially polyphenols [36].

Furthermore, many antioxidant compounds are metabolized by the gut microbiota into biologically active metabolites, and these metabolites have been reported to exert various biological effects in circulation [37]. Accordingly, it is suggested that classification of antioxidants based solely on chemical properties or source-based approaches is not sufficient; for a more comprehensive evaluation, mechanistic, pharmacokinetic, and systems biology-based approaches should also be taken into consideration.

Recent literature has increasingly focused on the effects of dietary antioxidants on cardiovascular health. Experimental and clinical findings have reported that antioxidant intake may exert reducing effects on markers associated with vascular calcification and inflammation [125, 126]. In addition, dietary patterns with anti-inflammatory properties have been shown to be associated with reductions in systolic and diastolic blood pressure, LDL and total cholesterol levels, as well as decreases in inflammatory markers [127].

Epidemiological evidence generally supports the relationship between dietary antioxidants and cardiovascular risk. Higher Composite Dietary Antioxidant Index (CDAI) values have been reported to be associated with a lower prevalence of CVD; however, this association did not retain statistical significance in multivariable analyses. In subgroup analyses by sex, a protective trend was observed in men, whereas no similar association was identified in women [128]. These findings suggest that the cardiovascular effects of antioxidants may vary depending on population characteristics.

The effects of antioxidants on cardiovascular health are also addressed in the context of lipid metabolism. It has been reported that the combined use of natural antioxidants may be associated with improvements in lipid profiles [129], and these findings are supported by meta-analyses demonstrating that lipid supplementation is associated with favorable changes, particularly in blood lipid levels and blood pressure. However, it is emphasized that the effects of different lipid fractions on cardiometabolic markers are not uniform and may vary [130].

When evaluated in terms of cardiovascular mortality, higher dietary intake and circulating levels of vitamin C have been reported to be associated with a lower risk of cardiovascular death. For vitamin E and β-carotene, only circulating levels were found to be inversely associated with mortality, whereas dietary intake did not demonstrate a similar protective effect, and these findings were supported by low levels of evidence [131]. These results suggest that the cardiovascular effects of antioxidants may vary depending on the type of compound and the level of intake.

However, there are also studies indicating that antioxidants do not exert protective effects under all conditions. Findings from Mendelian randomization analyses suggest that high intake levels of certain antioxidants, particularly α-tocopherol and retinol, may be associated with an increased risk of specific CVDs [132]. In addition, prospective cohort studies have shown that some dietary antioxidants are associated with CVD risk; in particular, vitamin E intake has been linked to a lower risk, whereas no significant association has been identified for compounds such as vitamins A and C and zinc [133]. These findings suggest that discrepancies may arise between observational studies and approaches aimed at assessing causality.

When the available evidence is considered as a whole, the effects of antioxidants on cardiovascular health appear to be multidimensional and cannot be explained by a single mechanism. The beneficial effects of fruits and vegetables on the cardiovascular system are thought to arise not from a single antioxidant compound but from the synergistic interactions of various bioactive components present in these foods. Accordingly, it is emphasized that obtaining antioxidants through whole foods rather than isolated supplements may represent a more effective approach [134].

Within this framework, current evidence suggests that dietary antioxidant compounds may exert beneficial effects on cardiovascular health; however, these effects are not always consistent and may vary depending on the type of compound, level of intake, and individual characteristics.

The overall effects of dietary antioxidants on cardiovascular pathways are presented in Figure 5. The major dietary antioxidants associated with cardiovascular health, including their food sources, mechanisms of action, and recommended intake levels, are summarized in Table 3.

Dietary antioxidant components (vitamins, minerals, polyphenols, and carotenoids) may contribute to the maintenance of cardiovascular health by exerting regulatory effects on key cardiovascular pathways such as endothelial function, inflammatory processes, lipid metabolism, and mitochondrial activity. Through these interactions, potential benefits may include improved endothelial function, attenuation of inflammatory responses, improvements in lipid profiles, and enhanced mitochondrial function.

Although the potential protective effects of antioxidants on CVD have been extensively addressed in the literature, their translation into clinical outcomes does not present a consistent pattern. Findings obtained at the experimental and mechanistic levels suggest that antioxidants may contribute to the reduction of oxidative burden. However, analyses evaluating randomized controlled trials indicate that antioxidant use does not always provide clinically significant benefits [66, 138]. This phenomenon is referred to in the literature as the “antioxidant paradox” and describes the discrepancy between strong findings at the experimental level and inconsistent clinical outcomes [139].

In addition, there are notable differences between obtaining antioxidants naturally through food and consuming them in supplement form. Epidemiological evidence indicates that dietary patterns rich in antioxidants are associated with favorable health outcomes. In contrast, findings derived from isolated antioxidant supplementation tend to be more variable and often limited [134]. Moreover, a large-scale cohort study demonstrated that the intake of vitamins and minerals from foods is inversely associated with mortality, whereas supplement use does not confer a similar benefit [140].

These findings are also supported by large-scale meta-analyses. Notably, a Cochrane Collaboration review including more than 290,000 individuals reported that antioxidant supplementation does not provide a significant benefit in terms of mortality and, in some cases, may be associated with an increased risk of mortality [141].

Within this framework, promoting dietary patterns rich in antioxidants is of particular importance in clinical practice. Diet models that include fruits, vegetables, and plant-based foods may contribute to reducing oxidative burden by increasing antioxidant intake and have been associated with lower all-cause mortality [142]. In this regard, current literature indicates that the beneficial effects on health cannot be attributed solely to individual nutrients; rather, they are determined by the synergistic interactions of nutrients and bioactive compounds within their natural food matrix [134].

CVDs are among the leading determinants of global mortality and disease burden. Disruption of redox balance constitutes a key biological basis in the onset and progression of these diseases. An increase in ROS levels, together with insufficient antioxidant defense mechanisms, promotes cardiovascular pathologies by triggering processes such as endothelial dysfunction, activation of inflammatory responses, and acceleration of atherosclerotic progression. In this context, strategies aimed at controlling oxidative burden have gained increasing importance in the prevention and management of CVD.

Current literature indicates that both endogenous defense mechanisms and exogenous antioxidant components play a role in regulating oxidative burden. While enzymatic systems such as SOD, CAT, and GPx perform essential functions in maintaining cellular redox balance, dietary antioxidants—including vitamins, minerals, and polyphenolic compounds—may influence the cardiovascular system through various biochemical processes, such as neutralizing free radicals, inhibiting inflammatory signaling pathways, and supporting endothelial function. However, it should also be considered that these mechanistic effects are not always consistently reflected in clinical outcomes.

Dietary patterns characterized by high consumption of fruits, vegetables, whole grains, nuts, and other plant-based foods rich in antioxidants are considered to potentially contribute to the prevention of CVD by reducing oxidative burden and attenuating inflammatory processes. However, findings from clinical studies investigating the effects of antioxidant supplementation on cardiovascular outcomes do not consistently present a uniform pattern. These discrepancies may be attributed to multiple factors, including bioavailability, administered dose, interindividual genetic and metabolic variability, overall dietary composition, and interactions among antioxidants. Within this framework, obtaining antioxidants through the regular consumption of antioxidant-rich foods, rather than isolated supplements, appears to be a more appropriate approach for maintaining cardiovascular health.

In order to more comprehensively elucidate the effects of antioxidants on cardiovascular health, future studies should focus on large-scale and long-term clinical investigations that take into account bioavailability, metabolic processes, and interindividual variability in response. In addition, the use of advanced molecular analysis techniques may contribute to a more detailed and mechanistic understanding of the effects of dietary bioactive compounds on the cardiovascular system. Within this framework, current evidence indicates that the clinical effectiveness of antioxidant-based approaches may vary due to interindividual differences and the complex nature of biological systems. Accordingly, in order to enhance the effectiveness of antioxidant strategies, it is important to develop precision nutrition approaches that take individual characteristics into account and to place greater emphasis on interventions targeting redox balance.

Overall, available data indicate that antioxidants may play a supportive role in the prevention and management of CVDs. However, findings from the literature do not uniformly endorse antioxidant supplementation as a reliable strategy for reducing cardiovascular risk. Instead of functioning as an independent intervention, antioxidants appear to exert greater benefits when derived from whole foods within balanced and varied dietary patterns. From a public health perspective, approaches that encourage regular intake of antioxidant-rich foods constitute a key element of integrated strategies targeting CVD prevention. Further well-designed randomized controlled trials remain essential to better define optimal intake levels and long-term outcomes.