Astaxanthin: A promising nutraceutical for cardiovascular health

2.1. Chemical structure of ASX

ASX is a powerful xanthophyll carotenoid known for its complex molecular structure, which is essential to its biological functions. Its core consists of a conjugated polyene chain with an alternating pattern of double and single bonds. This specific configuration allows ASX to absorb light effectively across various wavelengths, playing a vital role in photosynthesis in some algae and offering protective mechanisms in multiple organisms (Budriesi et al., 2022).

Furthermore, ASX contains key functional groups, specifically hydroxyl (-OH) and keto (=O) groups, positioned strategically along its molecular backbone. These groups significantly boost their antioxidant properties. Acting as strong electron donors, ASX can effectively neutralize free radicals, which are unstable molecules that can cause significant oxidative damage within cells. Its antioxidant strength surpasses that of well-known carotenoids like β-carotene and vitamin E (α-tocopherol) due to the unique arrangement and synergy of its functional groups (Nishida et al., 2023). Additionally, ASX can undergo esterification to enhance its solubility in cells and stability against oxidation (Udayan et al., 2017). The hydroxyl groups on its rings can bond with fatty acids such as palmitic, oleic, stearic, or linoleic acid, forming monoesters or diesters. It can also remain free, where the hydroxyl groups are unbound and capable of interacting with proteins or lipoproteins (Higuera-Ciapara et al., 2006).

There are three configurational isomers of ASX: two enantiomers (3R,3′R and 3S,3′S) and one meso form (3R,3′S). The alga Haematococcus primarily produces the 3S,3′S isomer found in wild Atlantic salmon, while Antarctic krill mainly produces the 3R,3′R isomer (Fig. 1) (Brotosudarmo et al., 2020).

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Fig. 1.

Structures of the optical isomers all-E-(3S,3′ S) (1), all-E-(3R,3′ S; meso) (2), and all-E-(3R,3′ R) (3) ASX (Brotosudarmo et al., 2020)

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ASX’s ability to reduce oxidative stress is critical for various biological systems. In humans, it may help protect the skin from UV damage, support immune function, and improve eye health by safeguarding retinal cells from oxidative injury. Similarly, this carotenoid can shield aquatic organisms from environmental stressors, highlighting its importance in ecological and health-related contexts. Consequently, ASX’s intricate molecular structure not only determines its chemical properties but also underscores its significance in maintaining cellular health and fighting oxidative stress across different species (Park et al., 2010).

2.2. Safety and regulatory status

ASX has undergone rigorous safety evaluations by leading regulatory agencies such as the U.S. Food and Drug Administration (FDA) and the European Food Safety Authority (EFSA). These assessments confirm that dietary supplements containing ASX are safe for consumers. It is important to note that while synthetic ASX is approved for use in aquaculture to enhance the color of fish and seafood, only natural ASX, which is extracted from the microalga Haematococcus pluvialis, is considered safe for human consumption. This distinction is crucial because natural sources are generally viewed as safer and more beneficial due to their higher bioavailability and additional health-promoting compounds (Pereira et al., 2024).

Over the past decade, several reviews have examined the effects of natural ASX on humans, focusing on areas such as antioxidation, liver protection, eye function, skin health, immune response, inflammation, and cardiovascular health (Ekpe et al., 2018; Fakhri et al., 2018; Fassett et al., 2008). A comprehensive review analyzed 87 clinical trials involving over 2,000 participants. While all studies were included to evaluate adverse events and safety concerns, the quality of reporting varied, making comparisons difficult. More recent randomized clinical trials have demonstrated greater scientific rigor than earlier observational studies.

Eight studies investigated the safety of high doses of ASX (ranging from 8 to 45 mg per day for 4 to 12 weeks) (Spiller & Dewell, 2003; Kajita et al., 2010; Mashhadi et al., 2018). Additionally, 28 studies used doses of at least 12 mg for a minimum of 4 weeks. No serious adverse events were observed at doses up to 45 mg (Kajita et al., 2010). However, some studies reported red stool coloration at doses of 20 mg and 30 mg (Kajita et al., 2009; Choi et al., 2011) and increased bowel movement frequency. Kupcinskas et al. (2008) noted 36 adverse events among 131 patients, with fewer adverse events recorded in the higher dose group compared to the placebo group.

Overall, extensive research supports the safety of ASX as a dietary supplement, indicating minimal adverse effects when taken at recommended dosages. Regulatory bodies have established intake limits, suggesting that most individuals can safely incorporate ASX into their diets without experiencing adverse side effects. As a result, ASX is becoming increasingly popular as a powerful antioxidant and wellness supplement, celebrated for its potential health benefits.

3.1. Radical scavenging

One of ASX’s key functions is its remarkable ability to neutralize free radicals, highly reactive molecules that can initiate damaging chain reactions within cells. These free radicals can damage various cellular components, including lipids, proteins, and nucleic acids (DNA and RNA), resulting in oxidative stress and cellular harm. ASX does this by donating electrons to free radicals, turning them into non-reactive products. Furthermore, the conjugated bonds in the non-polar region of ASX enable it to transport high-energy electrons (free radicals) from inside the cell along its carbon chain. This process acts like a “lightning rod,” helping to neutralize these electrons with the help of other antioxidants outside the cell membrane, such as vitamin C (Dose et al., 2016). ASX stabilizes free radicals by donating electrons, converting them into non-reactive molecules, thus protecting cellular integrity. This radical scavenging capacity is vital for maintaining cellular health, preventing oxidative damage, and supporting the proper function of essential biological processes (Kidd, 2011; Pereira et al., 2020).

3.2. Cell membrane interaction

Cell membrane systems are particularly vulnerable to reactive oxygen and nitrogen species (RONS) damage because they contain a high concentration of polyunsaturated fatty acids (PUFAs). Additionally, cell metabolic processes can produce more oxidizing metabolites, further increasing this vulnerability (Pereira et al., 2020). ASX plays a key role in protecting cell membranes from RONS and oxidative damage. Its unique chemical structure allows the polar groups to align with the polar regions of the cell membrane, while the central non-polar portion fits into the inner non-polar region. This arrangement enables ASX to adopt a transmembrane orientation within biological membranes, helping maintain membrane integrity, reducing fluidity, and functioning effectively as an antioxidant (Park et al., 2010). Moreover, ASX safeguards cellular membranes, especially PUFAs. These fatty acids are essential for membrane stability and function but are particularly prone to oxidative degradation, which can cause cellular dysfunction. When incorporated into the lipid bilayer, ASX is strategically positioned to enhance PUFA stability and shield them from oxidative damage. This placement reduces the membrane’s susceptibility to oxidative insults and helps preserve cellular integrity (Barros et al., 2001). Additionally, ASX supports vital cellular functions such as nutrient transport and cell signaling by maintaining proper membrane structure. This structural integrity is crucial for forming functional cellular compartments and transmitting signals across the membrane. ASX also bolsters cellular resilience against environmental stressors like toxins and ultraviolet radiation. By reinforcing the cell membrane against these challenges, ASX significantly promotes long-term health and function across various biological systems (Barros et al., 2001; McNulty et al., 2007).

3.3. Nuclear factor erythroid 2-related factor 2 activation

ASX functions by activating the Nuclear Factor Erythroid 2-related factor 2 (Nrf2) signaling pathway, which is essential for cellular defense against oxidative stress. Normally, Nrf2 resides in the cytoplasm bound to an inhibitor that prevents its activity (Cui et al., 2020). However, when cells experience oxidative stress or encounter electrophilic compounds, Nrf2 is released from its inhibitor and moves to the nucleus. In the nucleus, Nrf2 binds to antioxidant response elements (AREs) in the DNA, initiating the transcription of various antioxidant genes (Ngo & Duennwald, 2022). This process increases the production of vital protective enzymes, such as glutathione peroxidase and superoxide dismutase (SOD), which are crucial for neutralizing harmful free radicals and reducing inflammation. Therefore, this mechanism demonstrates ASX’s potential to support long-term cellular health and decrease the risk of chronic diseases linked to oxidative damage, including cardiovascular and neurodegenerative disorders (Sariharyanti et al., 2024). Several preclinical studies have shown that ASX exerts an indirect antioxidant effect by activating the transcription factor Nrf2 (Pereira et al., 2020). This activation boosts the expression of its target antioxidant genes, including phase II biotransformation enzymes. In a study with a rat model of coronary microembolization, ASX supplementation significantly lowered the development of cardiac dysfunction, myocardial infarction, and cardiomyocyte apoptosis. This protective effect was associated with reduced oxidative stress through the activation of the Nrf2/heme oxygenase-1 signaling pathway (Tripathi & Jena, 2010; Kavitha et al., 2013; Saw et al., 2013; Xue et al., 2017).

3.4. Synergistic effects

The overall efficacy of ASX can be significantly increased when it is combined with other antioxidants, most notably omega-3 fatty acids. This synergistic interaction creates a more comprehensive antioxidant defense system, improving cellular protection against a wider range of oxidative stressors (Medoro et al., 2023). By working together with other compounds, ASX enhances the body’s ability to neutralize a broader spectrum of free radicals and reactive oxygen species (ROS). This collaboration strengthens the body’s defenses and contributes to better overall health, potentially lowering the risk of chronic conditions related to oxidative stress, such as inflammation-related diseases, metabolic syndrome (MetS), and certain types of cancer (Chae et al., 2022). Research shows that combining ASX with a tocotrienol-rich fraction (TRF) boosts anti-inflammatory and antioxidant activities in stimulated macrophages. This synergy may reduce inflammation and offer various health benefits (Radzun et al., 2022). A recent study has introduced an effective strategy for improving ASX and lipid yields in Haematococcus pluvialis by combining arginine (Arg) and calcium ions (Ca²⁺) under light conditions of 120 μmol m⁻² s⁻². The addition of Arg led to a 25% increase in ASX accumulation and a 24.5% rise in lipid content. Furthermore, co-supplementing with Ca²⁺ (0.25 mM Arg and 50 μM CaCl₂) further enhanced productivity, resulting in a 40.7% increase in ASX and a 32.6% increase in lipids compared to the control group. Arg and Ca²⁺ work together to activate the arginine metabolic pathway, boosting the expression of key genes involved in growth and stress responses. They also help regulate calcium channel signaling, promoting ASX and lipid production through carotenogenesis and lipogenesis (Acheampong et al., 2025).

4.1. Oxidative stress markers

Oxidative stress is a pathological condition marked by an imbalance between ROS and antioxidants in the body. ROS are highly reactive molecules capable of damaging cellular structures such as lipids, proteins, and DNA. This cellular damage poses a significant threat to endothelial cells, which line blood vessels and are vital for maintaining vascular health (Pizzino et al., 2017). Several factors can worsen oxidative stress and its harmful effects. Chronic high blood pressure (hypertension) creates shear stress on blood vessel walls, leading to endothelial dysfunction. Similarly, elevated blood glucose levels, common in diabetes, increase ROS production via various metabolic pathways. Additionally, a diet high in saturated fats and sugars promotes inflammation and contributes to oxidative damage by disrupting the body’s normal antioxidant defenses (Caturano et al., 2025). The combined impact of these factors is substantial, as they not only contribute to the development of atherosclerosis, a condition characterized by hardened and narrowed arteries, but also increase the risk of various CVDs. Atherosclerosis can cause serious complications such as heart attacks and strokes, underscoring the importance of managing oxidative stress for heart health (Rafieian-Kopaei et al., 2014). A study involving 61 adults with moderate hyperlipidemia examined the effects of ASX, a potent antioxidant, on lipid profiles. Participants took daily doses of 12 mg and 18 mg of ASX over 12 weeks. Results showed that both dosages significantly lowered serum triglyceride levels, a known risk factor for CVD. The supplementation also led to a notable increase in high-density lipoprotein (HDL) cholesterol levels, often called “good” cholesterol because of its role in removing excess cholesterol from cells and returning it to the liver for excretion. These findings suggest that ASX can positively influence lipid profiles and support cardiovascular health, making it a promising dietary supplement for those at risk of heart disease. Improving our understanding of oxidative stress and antioxidants like ASX is crucial for developing strategies to boost heart health and prevent disease (Yoshida et al., 2010). In summary, oxidative stress plays a major role in the development of CVDs, driven by an imbalance between ROS and the body’s antioxidants. Conditions such as hypertension, high blood glucose, and poor diets worsen this stress, causing vascular damage and increasing the risk of atherosclerosis. ASX shows promise as an antioxidant supplement by lowering triglycerides (TG) and raising HDL cholesterol. Understanding oxidative stress and antioxidants can help us design interventions that improve heart health and reduce cardiovascular risks.

4.2. Inflammation reduction

The research on overweight and obese individuals has examined the effects of ASX supplementation at daily doses of 5 mg and 20 mg over 3 weeks. The study produced significant findings, showing a notable reduction in plasma levels of malondialdehyde (MDA) and isoprostanes, both recognized as biomarkers of oxidative stress and inflammation in the body. Additionally, ASX supplementation was associated with an increase in the activity of SOD, an essential antioxidant enzyme that helps protect cells from oxidative damage. This evidence supports the idea that ASX can play a critical role in lowering inflammation and oxidative stress (Choi et al., 2011). Chronic inflammation has become a key factor in the development of CVDs. A vital event in this inflammatory process is the oxidation of low-density lipoprotein (LDL) cholesterol. When LDL cholesterol oxidizes, it triggers a biological response that activates the immune system, leading to the recruitment of monocytes, a specific type of white blood cell, to the damaged arterial wall. Once there, these monocytes differentiate into macrophages, specialized cells that can engulf and digest cellular debris and pathogens, including oxidized LDL particles (Poznyak et al., 2021). As macrophages consume the oxidized LDL, they become engorged foam cells. The accumulation of foam cells is crucial in forming fatty streaks, eventually leading to plaque buildup in the arteries. This plaque narrows the arteries, restricting blood flow and promoting the release of pro-inflammatory cytokines. These cytokines act as signaling molecules that further amplify the inflammatory response, creating a harmful cycle that contributes to endothelial dysfunction, the impairment of the inner lining of blood vessels (Ganesan et al., 2018). This ongoing cycle of inflammation and endothelial dysfunction poses a significant threat to vascular health and greatly increases the risk of serious cardiovascular events, such as heart attacks and strokes. As the cycle continues, the long-term presence of inflammation, coupled with oxidative stress, establishes a damaging feedback loop that significantly raises the likelihood of adverse cardiovascular outcomes. Therefore, understanding these interconnected biological processes is crucial for developing effective prevention and treatment strategies to combat CVDs. This knowledge can guide innovations in therapeutic interventions, dietary recommendations, and lifestyle modifications aimed at reducing inflammation and improving cardiovascular health (Angjelova et al., 2024). The anti-inflammatory and antioxidant effects of ASX were further confirmed in a clinical trial involving 42 healthy young women who received either a placebo or ASX at 2 or 8 mg daily doses. After 8 weeks, the 2 mg dose significantly reduced plasma levels of C-reactive protein (P<0.05) and enhanced immune responses. Specifically, the 8 mg dose increased natural killer cell cytotoxicity (67.9% vs. 57.8%; P<0.05), raised T and B lymphocyte levels (P<0.05), and boosted the production of IFN-γ and IL-6 (P<0.05). Both doses lowered the oxidative DNA damage biomarker 8-OHdG after 4 weeks (P<0.01) (Pereira et al., 2020). T lymphocytes and macrophages have a major role in the progression of CVDs, including atherosclerosis and heart failure. ASX has been shown to reduce oxidative stress and modulate T lymphocyte activity. The clinical study improved lymphoproliferation induced by mitogens without changing T-cell populations and enhanced responses to tuberculin. In a mouse model of non-alcoholic steatohepatitis (NASH), ASX decreased T-cell recruitment to the liver, improving inflammation and insulin resistance (Pereira et al., 2020). Overall, ASX enhances T lymphocyte immune responses and reduces harmful activation, which may benefit cardiovascular health. Its mechanisms include inhibiting NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways, helping to suppress inflammation and decrease foam cell formation. More research is needed to clarify ASX’s specific role in the risk and progression of CVDs (Chang & Xiong, 2020). In summary, ASX appears beneficial for heart health, although further studies are required.

4.3. Effects on lipid metabolism

Research indicates that ASX, a carotenoid pigment found in certain algae and seafood, can improve lipid metabolism. This benefit is especially important for individuals with dyslipidemia, a condition marked by abnormal lipid levels that can increase the risk of CVDs (Vargas et al., 2025). Animal studies have shown that ASX facilitates cholesterol efflux from macrophage immune cells prone to accumulating excess cholesterol in arterial walls. Such cholesterol buildup can lead to atherosclerotic plaque formation, a major contributor to heart disease (Ciaraldi, et al., 2023). In studies involving mice, ASX has been demonstrated to enhance reverse cholesterol transport, increasing cholesterol efflux and reducing plaque size (Yang et al., 2014). A clinical trial with adults experiencing moderate hyperlipidemia found that ASX improved lipid profiles by lowering TG, increasing HDL, and raising serum adiponectin, which benefits cardiovascular health (Yanai & Yoshida, 2023). Additionally, a recent study analyzed ASX as a common nutraceutical in people with prediabetes. Results showed reductions in total and LDL cholesterol and increases in HDL cholesterol. The study also noted improvements in several CVD risk markers, including fetuin-A, fibrinogen, and L-selectin, and suggested potential improvements in insulin sensitivity based on homeostatic model assessment 2-insulin resistance (HOMA2-IR) scores. The treatment was well tolerated, with no significant side effects (Ciaraldi et al., 2023). Overall, these findings suggest that ASX could be an effective supplement for improving metabolic profiles and reducing CVD risk in people with prediabetes and dyslipidemia. As a nutraceutical, ASX offers benefits such as lowering TG, raising HDL cholesterol, and enhancing insulin sensitivity, supporting overall cardiovascular and metabolic health

4.4. Blood pressure regulation

ASX, a potent antioxidant found in various marine organisms, has gained attention for its potential role in regulating blood pressure and improving vascular function. Research on spontaneously hypertensive rats has shown that ASX can significantly lower systolic blood pressure (SBP). In addition to this reduction, the studies revealed notable improvements in endothelial function, which is crucial for maintaining healthy blood vessel activity. These findings suggest that ASX may offer therapeutic benefits for individuals with hypertension by enhancing overall vascular health. The mechanism behind these effects may involve reducing oxidative stress and inflammation, both of which contribute to elevated blood pressure (Ambati et al., 2014). Clinical trials involving human participants have also indicated that ASX supplementation could lead to positive changes in blood pressure regulation. Some studies report decreases in SBP and DBP among those taking ASX compared to control groups. While the results are promising, further research is necessary to confirm these benefits and to explore the specific biological mechanisms involved. Understanding how ASX interacts with different pathways in the body will be essential for establishing clear guidelines for cardiovascular health (Gao et al., 2025). Overall, while the initial evidence suggests the potential of ASX as a natural agent for blood pressure management, more comprehensive studies are needed to validate these findings and determine the ideal dosages and forms for maximum benefit.

5.1. Cognitive function

Cognitive Enhancement: Emerging research suggests that ASX could significantly boost cognitive function, especially in people with diabetes. Due to its strong antioxidant properties, ASX helps protect neuronal cells from oxidative stress, which is often higher in diabetic conditions. This protective effect could reduce cognitive decline and memory problems commonly linked to diabetes, indicating that ASX might be a useful supplement for preserving mental clarity and cognitive health in at-risk groups (Queen et al., 2024). In summary, ASX could improve memory and thinking skills in people with diabetes by safeguarding brain cells. More research is needed to fully understand its benefits for cognitive health.

5.2. MetS

MetS, also known as syndrome X, is a group of conditions that markedly increase the risk of heart disease, stroke, and type 2 diabetes. The concept of MetS was first introduced in the 1920s by a Swedish doctor and has undergone several revisions over the years. The World Health Organization (WHO) provided a unified definition until 1998, after which multiple professional groups offered refined definitions (Grundy et al., 2005; Cornier et al., 2008). To be diagnosed with MetS, an individual must meet at least three of the following criteria: hypertension, dyslipidemia, obesity, and hyperglycemia (Alberti et al., 2009).

The global prevalence of MetS varies widely, ranging from 10% to 84%, with the highest rates occurring in developed countries (Regufe et al., 2020). For example, in Japan, nearly half of males and one-fifth of females aged 40 to 74 are affected by MetS or pre-MetS (Shirouchi & Matsuoka, 2019). This condition significantly raises the risk of sudden cardiac death by 70%, doubles the chances of cardiovascular events, and increases the risk of developing type 2 diabetes mellitus (T2DM) fivefold, adding to rising healthcare costs (Alberti et al., 2009; Hess et al., 2017).

Managing MetS typically involves medications, lifestyle changes, and regular exercise. However, many individuals face challenges such as side effects from medications, high treatment costs, difficulty sticking to exercise routines, and maintaining a healthy diet. As a result, there is growing interest in cost-effective strategies, including the use of bioactive compounds, nutraceuticals, and supplements to prevent and treat chronic diseases like T2DM (Leung et al., 2022).

Research has highlighted the potential benefits of ASX supplementation in improving key metabolic markers linked to MetS. Clinical studies show that ASX can significantly lower HbA1c levels, indicating improved long-term blood glucose control, and reduce TNF-α, a cytokine associated with inflammation. These effects suggest that ASX may enhance insulin sensitivity, making it a promising option for individuals seeking to improve their metabolic health (Hussein et al., 2007).

A comprehensive database search and validated appraisal tools were used to evaluate the effectiveness of ASX in reducing MetS risk factors. The results demonstrated that ASX effectively lowered SBP, total cholesterol (TC), and LDL cholesterol. The reductions in SBP and TC approached statistical significance (p = 0.05), while the decrease in LDL-C was statistically significant (p < 0.05). Notably, participants experienced reduced SBP after eight weeks of ASX treatment. The decrease in TC was significant when ASX was taken at doses of ≤6 mg/day for <8 weeks. Additionally, doses of ≤6 mg/day had a substantial impact on LDL-C over 8 weeks, while ASX effectively lowered TG at doses between 7 and 12 mg/day over >8 weeks (Leung et al., 2022).

Supporting these findings, Yanai et al. (2008) reported that ASX enhances superoxide scavenging and promotes vaso-relaxation. Choi et al. (2011) showed that ASX improves lipid profiles by promoting LDL breakdown and regulating its production. However, some studies present conflicting evidence. For instance, Xia et al. (2020) found that while ASX improved HDL levels, it did not significantly impact other lipid profiles, blood pressure, or serum glucose. A systematic review by Ursoniu et al. (2015) concluded that ASX had no notable effect on lipid profiles or serum glucose. These reviews mainly focused on physical biomarkers, while the other study centered on MetS. Notably, a 12-week study reported an adherence rate of over 92% in both groups, although it did not specify the strategies used to sustain this level of adherence (Leung et al., 2022). In summary, while ASX may help manage MetS, further research is needed to confirm its effectiveness and develop clear treatment guidelines in conjunction with lifestyle changes and standard care.

5.3. The therapeutic role of ASX in aging, neuroprotection, and CVD

The reviewed studies highlight the many benefits of ASX across various health areas, especially in aging, oxidative stress, and metabolic health. Preclinical research by Ni et al. (2018) shows that ASX can improve mitochondrial function and lower oxidative stress in aging models, pointing to its potential as a protector against age-related decline. This idea is backed by clinical findings from Sekikawa et al. (2020) and Petyaev et al. (2018), which suggest that ASX supplementation can boost cognitive function in older adults while improving oxidative status, highlighting its role in supporting brain health. The liver-protective effects noted by Ni et al. (2018), along with findings from Cao et al. (2021), stress ASX’s potential in managing MetS, especially in people with type 2 diabetes. These results imply that ASX might be key in improving antioxidant levels and glucose processing, which are crucial for handling diabetes complications.

Additionally, the antibacterial effects shown by Rather et al. (2021) suggest that ASX could serve as a natural antimicrobial against pathogens like E. coli and Salmonella typhi. The protective effects on eye health reported by Baccouche et al. (2018) imply that ASX might help prevent age-related macular degeneration, further supporting its importance in eye health. Moreover, studies by Ahmadi and Ayazi-Nasrabadi (2021) and Gasmi et al. (2021) show ASX’s potential to reduce inflammation and oxidative stress in COVID-19, emphasizing its relevance during current health crises. Overall, the evidence positions ASX as a promising dietary supplement with multiple health benefits, especially in aging, metabolic health, and inflammation. More research focusing on long-term effects and how it works in humans is needed to fully understand ASX’s therapeutic potential. The summarized studies provide strong evidence of ASX’s varied biological actions, particularly in protecting nerve cells and reducing inflammation, and its potential to address neurodegenerative diseases. Preclinical studies show that ASX can lower lipid peroxidation and oxidative DNA damage in models of excitotoxicity (Nakajima et al., 2008; Ye et al., 2013). Its antioxidant ability is vital in protecting neurons from oxidative stress, a major factor in neurodegenerative diseases.

Furthermore, ASX has been shown to improve cognitive function and lower oxidative stress markers in Alzheimer’s disease models (Ito et al., 2019; Craft & Watson, 2004), reinforcing its promise as a treatment for cognitive decline. ASX’s blockage of NF-κB signaling (RangaRao et al., 2010; Yang et al., 2019) indicates a strong anti-inflammatory effect, which is key to managing chronic neuroinflammation linked to diseases like Alzheimer’s and Parkinson’s. The regulation of cell death proteins, leading to less activation of caspase-3 and higher levels of Bcl-2 (Zhang & Wang, 2015; Dong et al., 2013), shows ASX’s potential to prevent neuron loss. Positive results in models of Parkinson’s disease (Ye et al., 2013; Ye et al., 2012) and ALS (Isonaka et al., 2011; Fitzgerald et al., 2013) suggest that ASX might improve neuron health and breathing function in these conditions, which is especially important given the few treatment options for such disabling diseases. Clinical studies have reported improvements in cognitive function in elderly groups (Ito et al., 2019; Sekikawa et al., 2020) and linked carotenoid intake with respiratory health in ALS patients (Fitzgerald et al., 2013; Nieves et al., 2016), showing that ASX has the potential to move from preclinical research to real-world use. Overall, the research emphasizes ASX as a hopeful candidate for therapies aimed at protecting nerves and fighting neurodegenerative diseases. More clinical trials are needed to find the best doses, understand how it works, and examine long-term effects to fully unlock its health benefits. The summarized studies highlight the promising role of ASX in heart health, especially because of its antioxidant, anti-inflammatory, and possible metabolic benefits. In lab studies, ASX shows superior antioxidant power compared to well-known antioxidants like vitamins C and E, especially in stopping lipid peroxidation (Stahl & Sies, 2003; Capelli et al., 2013). This implies that ASX could greatly help protect heart health by reducing oxidative stress, a main factor in the development of atherosclerosis. The findings regarding ASX’s effects on human umbilical vein endothelial cells (HUVECs) suggest its ability to reduce ROS and maintain antioxidant enzyme activity (Régnier et al., 2015; Nishigaki et al., 2010). This protective effect on endothelial cells is crucial for preserving vascular function and preventing CVDs. In preclinical studies, ASX treatment reduced LDL oxidation by approximately 30% in diabetic rats (Zhao et al., 2011). However, the lack of effect observed in hyperlipidemic rabbits indicates that ASX’s impact may vary depending on the model used, highlighting the need for further research to clarify its mechanisms and effectiveness across different populations.

Multiple studies support ASX’s anti-inflammatory properties, showing reductions in inflammation markers in models of NASH and MetS (Santos et al., 2012; Ni et al., 2015). These findings highlight ASX’s potential as a therapeutic agent due to the strong link between chronic inflammation and CVDs. Clinical studies suggest that ASX supplementation can lower plasma biomarkers of lipid peroxidation in overweight individuals (Choi et al., 2011), reinforcing its antioxidant benefits for humans. However, the lack of significant effects on blood pressure in normotensive subjects (Coombes et al., 2016) indicates that further investigation is necessary, especially in hypertensive populations where ASX might have a more pronounced effect. Additional preclinical evidence indicates that ASX improves insulin sensitivity and glucose metabolism in diabetic models (Bhuvaneswari et al., 2010; Bhuvaneswari et al., 2012), offering another potential benefit since metabolic disorders are closely linked to cardiovascular health. Furthermore, ASX has demonstrated renal protective effects and the ability to reduce oxidative stress in kidney injury models (Qiu et al., 2015; Sila et al., 2015), which could be particularly important for patients with diabetes at higher risk for kidney disease. The mixed results regarding lipid-lowering effects highlight the need for more targeted research. While some studies have reported beneficial effects on triglyceride and cholesterol levels (Yang et al., 2011; Yang et al., 2014), inconsistencies suggest that dosage, duration, and specific populations may influence outcomes. Overall, the body of research supports the potential of ASX as a versatile agent for cardiovascular health, mainly through its antioxidant and anti-inflammatory effects (Table 1). However, further clinical trials are essential to determine optimal dosages, clarify mechanisms of action, and evaluate long-term effects across diverse populations. This research could lead to ASX becoming a valuable dietary supplement for preventing and managing CVDs.