Effects of Nutritional Supplements on Vascular Function: A Narrative Review

Figures

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  Figure 1. Schematic representation of the L-arginine–nitric oxide pathway and the role of L-citrulline supplementation in endothelial function. Under physiological conditions, L-arginine serves as the substrate for endothelial nitric oxide synthase (eNOS), which catalyzes the production of nitric oxide (NO) and L-citrulline. Nitric oxide is a key mediator of endothelium-dependent vasodilation and vascular homeostasis. In conditions such as aging, hypertension, and obesity, arginase activity is increased, competing with eNOS for available L-arginine by converting it into ornithine and urea, thereby reducing substrate availability for NO synthesis. This imbalance contributes to decreased NO bioavailability and endothelial dysfunction. Supplementation with L-citrulline, either directly or through natural sources such as watermelon, enhances circulating L-arginine levels via the citrulline–arginine recycling pathway, leading to increased NO production and improved endothelial function. The schematic illustration of the watermelon included in the figure was created with the assistance of ChatGPT-5 (OpenAI, https://chatgpt.com; accessed on 20 May 2025). Black arrows indicate the direction of the…

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  Figure 2. Schematic representation of the protective effects of flavan-3-ols on endothelial function under conditions of oxidative stress and inflammation. Reactive oxygen species (ROS) and inflammatory cytokines promote oxidative stress in endothelial cells, leading to reduced nitric oxide (NO) bioavailability and endothelial dysfunction. Flavan-3-ols exert vasoprotective effects by decreasing ROS levels, enhancing endothelial nitric oxide synthase (eNOS) activity, and upregulating endogenous antioxidant defense systems. In particular, flavan-3-ols increase the activity of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH), thereby contributing to the reduction in oxidative stress. These mechanisms collectively improve NO bioavailability and support endothelial function. The endothelial cell illustration included in the figure was created with the assistance of ChatGPT-5 (OpenAI, https://chatgpt.com; accessed on 20 May 2025). Black arrows indicate the direction of the biological pathway and interactions. Green boxes indicate protective or beneficial effects, whereas orange boxes indicate pathological stimuli or detrimental processes. Upward (↑)…

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  Figure 3. Schematic illustration of the vascular protective effects of coenzyme Q10 (CoQ10) on endothelial function. CoQ10 acts as a mitochondrial antioxidant, reducing mitochondrial reactive oxygen species (mtROS) production and attenuating oxidative stress. This leads to decreased oxidation of low-density lipoproteins (oxLDL) and increased nitric oxide (NO) bioavailability. Enhanced NO signaling improves vascular protection and flow-mediated dilation (FMD). Additionally, CoQ10 exerts anti-inflammatory effects through inhibiting nuclear factor-kappa B (NF-κB) signaling and reducing pro-inflammatory cytokine production, ultimately contributing to improved endothelial function. The schematic illustration of the CoQ10 compound included in the figure was created with the assistance of. ChatGPT-5 (OpenAI, https://chatgpt.com; accessed on 20 May 2025). Black arrows indicate the direction of the proposed biological effects. Upward (↑) and downward (↓) arrows indicate increased and decreased levels or activity, respectively. Green boxes represent beneficial vascular outcomes, whereas orange boxes highlight the intervention (CoQ10) and oxidative stress-related components.Abbreviations: CoQ10,…

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  Figure 4. Schematic representation of the role of mitochondrial oxidative stress in age-related vascular dysfunction and the proposed protective mechanisms of MitoQ. Aging is associated with increased mitochondrial reactive oxygen species (mtROS) production, which promotes oxidative stress, mitochondrial dysfunction, reduced nitric oxide (NO) bioavailability, and increased arterial stiffness, ultimately contributing to vascular dysfunction and cardiovascular disease. MitoQ, a mitochondria-targeted antioxidant composed of ubiquinol linked to a triphenylphosphonium (TPP+) cation, selectively accumulates within mitochondria and reduces mtROS production. By lowering mitochondrial oxidative stress, MitoQ is thought to improve NO bioavailability, enhance endothelium-dependent vasodilation, as reflected by increased flow-mediated dilation (FMD), and support vascular function. These effects have been associated with reduced arterial stiffness, lower levels of oxidized low-density lipoprotein (oxLDL), and decreased carotid–femoral pulse wave velocity (PWV). Black arrows indicate the direction of the proposed biological pathway. Upward (↑) and downward (↓) arrows indicate increased and decreased…

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  Figure 5. Schematic representation of the vascular protective effects of grape polyphenol extracts, as exemplified by the standardized formulation Taurisolo®, through modulation of gut microbiota-derived metabolites and reduction in oxidative stress. Polyphenolic compounds present in grape extracts, including resveratrol, catechins, and procyanidins, have been associated with reduced circulating levels of trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite linked to cardiovascular risk. This reduction may contribute to lower oxidative stress, as reflected by decreased levels of oxidized low-density lipoprotein (oxLDL) and derivatives of reactive oxygen metabolites (D-ROMs), as well as attenuation of vascular inflammation. Collectively, these mechanisms may improve endothelial function, enhance nitric oxide (NO) bioavailability, and promote endothelium-dependent vasodilation, reflected by improved flow-mediated dilation (FMD). Black arrows indicate the direction of the proposed biological pathway and interactions. Upward (↑) and downward (↓) arrows indicate increased and decreased levels or activity, respectively. Green boxes represent beneficial vascular effects, whereas…

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  Figure 6. Schematic illustration of the protective effects of the glycocalyx-targeted supplement Endocalyx-Pro on endothelial glycocalyx integrity and vascular function. The supplement contains bioactive components including fucoidan, hyaluronic acid, SOD-rich polyphenols, and glucosamine, which support glycocalyx protection by increasing glycocalyx thickness, inhibiting heparanase activity, and reducing oxidative stress. These mechanisms contribute to restoration of endothelial glycocalyx integrity, reflected by a reduction in the perfused boundary region (PBR). Improved glycocalyx structure is associated with reduced arterial stiffness, as indicated by decreased pulse wave velocity (PWV) and augmentation index (AIx), ultimately promoting improved vascular health. Black arrows indicate the direction of the proposed biological pathway and interactions. Upward (↑) and downward (↓) arrows indicate increased and decreased levels or activity, respectively. Green boxes represent beneficial vascular effects, whereas yellow boxes represent intermediate processes or favorable physiological changes. The schematic illustration of the Endocalyx-Pro supplement and endothelial glycocalyx included in…

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  Figure 7. Schematic representation of the cardiometabolic protective effects of olive-derived bioactive compounds. Bioactive molecules present in olives, including oleuropein (OL), hydroxytyrosol (HT), oleocanthal (OC), and oleanolic acid (OA), exert beneficial effects through antioxidant and anti-apoptotic mechanisms. These compounds activate antioxidant signaling pathways such as nuclear factor erythroid 2-related factor 2 (Nrf2), leading to upregulation of antioxidant enzymes including manganese superoxide dismutase (MnSOD) and catalase (CAT). This results in reduced oxidative stress and decreased levels of reactive oxygen species (ROS), oxidized low-density lipoprotein (oxLDL), and malondialdehyde (MDA). Additionally, olive-derived bioactive compounds exert anti-apoptotic effects by reducing the Bax/Bcl-xL ratio and limiting apoptosis. These mechanisms contribute to reduced NETosis, decreased atherosclerotic plaque formation, and overall cardiometabolic protection. Black arrows indicate the direction of the proposed biological pathway and interactions. Upward (↑) and downward (↓) arrows indicate increased and decreased levels or activity, respectively. Green boxes represent beneficial…

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  Figure 8. Schematic representation of the mechanisms by which black garlic extract and its major bioactive compound, S-allyl cysteine (SAC), promote vascular health. SAC acts as a hydrogen sulfide (H2S) donor, increasing intracellular H2S levels in endothelial cells. H2S signaling contributes to the reduction in reactive oxygen species (ROS) and enhances nitric oxide (NO) bioavailability through activation of endothelial nitric oxide synthase (eNOS). These effects lead to decreased oxidative stress, improved endothelial function, and enhanced vascular function, ultimately contributing to endothelial protection. Black arrows indicate the direction of the proposed biological pathway and interactions. Upward (↑) and downward (↓) arrows indicate increased and decreased levels or activity, respectively. Green boxes represent beneficial vascular effects, whereas orange boxes represent intermediate mechanisms or physiological processes, and blue boxes indicate increased bioavailability or signaling responses. The schematic illustrations of the black garlic extract, S-allyl cysteine structure, and endothelial cell included in the figure were created with the assistance of ChatGPT-5 (OpenAI,…

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  Figure 9. Schematic representation of the mechanisms through which curcumin improves vascular function. Curcumin exerts vascular protective effects through both antioxidant and anti-inflammatory pathways. It reduces reactive oxygen species (ROS) production by inhibiting NADPH oxidase and activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, leading to increased endogenous antioxidant defenses. Additionally, curcumin suppresses inflammatory signaling by reducing pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). These combined mechanisms decrease oxidative stress, improve endothelial function, and contribute to reduced arterial stiffness and improved vascular health. Black arrows indicate the direction of the proposed biological pathway and interactions. Upward (↑) and downward (↓) arrows indicate increased and decreased levels or activity, respectively. Green boxes represent antioxidant and beneficial vascular mechanisms, gray boxes represent anti-inflammatory mechanisms, and orange or pink boxes represent vascular outcomes and physiological effects. The schematic illustrations of curcumin, its chemical structure, and the…