Current Challenges and Issues in the Application of Astaxanthin

Abstract

Astaxanthin, a xanthophyll carotenoid, exhibits potent biological functions, including antioxidant, immune regulation, growth promotion, improved reproductive capacity, and enhancement of the body color of aquatic animals. In recent years, with the rapid development of the aquaculture industry, the application of astaxanthin in aquaculture has garnered increasing attention. Studies have demonstrated that astaxanthin significantly enhances the antioxidant capacity of aquatic animals, reduces oxidative damage, and regulates the expression of immune-related genes, thereby improving immunity and disease resistance. Moreover, astaxanthin promotes growth and reproductive performance, particularly in high-value aquaculture species, where it also serves as a natural pigment to increase market competitiveness. However, the low bioavailability and high production costs of astaxanthin remain major constraints to its widespread use in aquaculture. To address these limitations, various strategies—such as microencapsulation, liposomal delivery, and nanotechnology—have been explored to improve its stability and water solubility. Additionally, expanding astaxanthin sources and optimizing production processes are effective approaches to reducing costs. This review summarizes recent advances in astaxanthin research within aquaculture, highlights its multifunctional roles in promoting the health and production efficiency of aquatic animals, and discusses the current challenges and future research directions.

1. Introduction

Aquaculture plays a crucial role in meeting the growing global demand for seafood. As wild fishery resources continue to deplete, the rapid development of aquaculture has become increasingly essential. However, the rapid expansion of aquaculture also faces several challenges, including the risk of disease transmission, associated with high-density farming, deteriorating farming conditions, health issues in farmed organisms, and the need to improve production efficiency [1]. In recent years, the use of functional feed additives has shown significant potential in addressing these challenges. Astaxanthin (AST), a xanthophyll compound, has garnered considerable attention in aquaculture due to its unique antioxidant, immune-regulating, and pigment-depositing properties [2].

Astaxanthin is a natural xanthophyll widely found in marine and freshwater ecosystems, primarily in crustaceans (e.g., shrimp and crabs), fish (e.g., salmon and Rainbow trout), and algae (such as Haematococcus pluvialis) [3]. Its molecular structure, characterized by a conjugated double-bond system and terminal hydroxyl and keto groups, confers strong antioxidant potential and facilitates its roles in pigmentation, physiological regulation, and immune enhancement [4]. Belonging to the ketocarotenoid family, astaxanthin has the molecular formula C₄₀H₅₂O₄ (shown in Figure 1). Its highly unsaturated structure allows for efficient free radical scavenging [5]. Astaxanthin exerts its biological functions through two primary mechanisms: (1) as a potent antioxidant, it activates antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) via the Nrf2 signaling pathway, thereby reducing cellular damage caused by reactive oxygen species (ROS) [6]; (2) it modulates multiple cellular signaling pathways, such as PI3K/Akt, AMPK, and mTOR, affecting energy metabolism, inflammatory responses, and immune responses [7].

Due to its molecular features, astaxanthin efficiently mitigates oxidative stress in aquatic animals. It also enhances resistance to diseases by modulating the expression of immune-related genes, and provides protection under environmental stressors such as elevated temperatures, hypoxia, and transportation stress [8]. Additionally, astaxanthin plays a critical role in enhancing the pigmentation of aquatic species such as salmon, shrimp, and crabs, which is essential for consumer appeal and market value [9]. Beyond coloration, astaxanthin contributes to the regulation of lipid and glucose metabolism, thereby supporting improved growth and reproductive performance [10]. Despite its numerous benefits, the high cost and limited availability of natural sources, along with the poor bioavailability of synthetic forms, restrict the broader application of astaxanthin in aquaculture. Currently, astaxanthin is primarily obtained through natural extraction (e.g., from H. pluvialis), chemical synthesis, and microbial fermentation. While natural astaxanthin exhibits superior biological activity, it is costly and limited in supply. In contrast, synthetic astaxanthin is more affordable but has lower bioavailability and potential environmental concerns [11]. Recent advances in biotechnology have enabled the production of astaxanthin via genetically engineered microorganisms such as H. pluvialis and Paracoccus carotinifaciens, offering a promising path toward cost-effective and sustainable production [11]. In this context, the present review synthesizes recent progress in astaxanthin research, with an emphasis on its mechanisms of action in promoting health, growth, immunity, and environmental resilience in aquatic species. This work aims to provide a theoretical foundation for optimizing astaxanthin application and exploring its future prospects in sustainable aquaculture.

2. The Growth-Promoting Effects of Astaxanthin in Aquatic Animals

Astaxanthin has been shown to enhance nutrient absorption and utilization efficiency in aquafeeds, thereby improving feed conversion ratios (FCR) and reducing feed costs. Studies have reported that the inclusion of astaxanthin in shrimp diets significantly improves feed efficiency, lowers feed conversion rates, and ultimately increases economic returns. Moreover, astaxanthin stimulates protein synthesis and promotes muscle development, contributing to steady weight gain in aquatic animals.

Numerous studies have demonstrated the growth-promoting effects of astaxanthin across various fish and crustacean species. In largemouth bass (Micropterus salmoides), dietary astaxanthin supplementation significantly increased weight gain and specific growth rate (SGR), while also enhancing intestinal morphology [12]. In rainbow trout (Oncorhynchus mykiss), dietary astaxanthin significantly improved growth rates and feed efficiency [13]. Similar outcomes were observed in Pacific white shrimp (Litopenaeus vannamei), where natural astaxanthin supplementation led to marked improvements in feed utilization and growth rate [14]. Notably, astaxanthin was also effective in mitigating growth suppression induced by microcystin-LR (MC-LR) in L. vannamei, restoring growth performance to levels comparable to the non-stressed control group [15]. These findings suggest that astaxanthin’s growth-promoting effects are broadly applicable across diverse aquaculture species.

Mechanistically, astaxanthin improves growth by enhancing feed utilization efficiency and regulating protein and carbohydrate metabolism. In L. vannamei, supplementation with 100 mg/kg astaxanthin significantly activated pyruvate metabolism and the glycolysis/gluconeogenesis pathway, supporting energy production and metabolic balance, which are essential for growth [11]. The glycolysis/gluconeogenesis pathway plays a vital role in promoting growth by regulating energy production and maintaining glucose homeostasis, which are essential for cellular metabolism and biosynthesis in aquatic animals. In hybrid red tilapia (O. niloticus × O. mossambicus), feed supplemented with H. pluvialis powder significantly improved growth performance and optimized intestinal morphology, including villus width and absorptive epithelial thickness [1]. In Nile tilapia (O. niloticus), supplementation with astaxanthin-rich Paracoccus carotinifaciens enhanced growth under low-temperature conditions by increasing weight gain, SGR, and carotenoid deposition in muscle tissue [16]. Collectively, these studies indicate that astaxanthin promotes growth through multiple metabolic and physiological pathways, including energy metabolism, protein synthesis, and gut health optimization.

Astaxanthin also indirectly supports growth by enhancing the antioxidant defense system. Moderate dietary supplementation (40–80 mg/kg) in large yellow croaker (Larimichthys crocea) larvae improved digestive enzyme activity, enhanced antioxidant capacity, and promoted lipid utilization, leading to superior growth performance [17]. In loach (Paramisgurnus dabryanus), dietary astaxanthin (100–151.06 mg/kg) enhanced antioxidant enzyme activity through activation of the Keap1–Nrf2 signaling pathway, thereby supporting growth under stress conditions [18]. Similarly, in snakehead (Channa argus), 100 mg/kg astaxanthin significantly improved growth performance and mitigated lipopolysaccharide (LPS)-induced immune stress [19]. By reducing oxidative stress and improving cellular resilience, astaxanthin supports both health and growth efficiency in aquaculture species.

In shellfish aquaculture, astaxanthin has also proven beneficial. In abalone (Haliotis discus hannai), dietary supplementation with 2 mg/kg of crystalline yeast astaxanthin (CrYst) and/or 80 mg/kg of synthetic astaxanthin (ASTA) significantly enhanced serum and hepatopancreas antioxidant capacity, upregulated hsp70 and hsp90 gene expression, reduced mortality and shell shedding rates under heat stress, and improved both weight gain and shell growth rate [20]. These findings demonstrate that astaxanthin contributes to improved survival and growth in shellfish through multifaceted physiological regulation.

Overall, astaxanthin enhances feed efficiency, optimizes protein and carbohydrate metabolism, and promotes growth in a wide range of aquaculture species. Its growth-promoting mechanisms include improved intestinal structure, enhanced antioxidant defense, and the regulation of energy metabolism. Even at relatively low dietary inclusion levels, astaxanthin provides significant functional benefits, making it a valuable feed additive in modern aquaculture. Future research should focus on optimizing its application strategies—such as dosage, formulation, and delivery systems—to maximize utilization efficiency and economic benefits across different cultured species.

3. The Role of Astaxanthin in Enhancing Antioxidant Capacity in Aquatic Animals

In aquaculture environments, aquatic animals are frequently exposed to various stressors, including fluctuations in water quality and pathogen invasion. These stressors can trigger immune stress responses, leading to immune dysfunction, impaired growth performance, and increased susceptibility to disease and mortality. Astaxanthin, a powerful antioxidant, plays a key role in mitigating oxidative damage induced by such stress. Its molecular structure, characterized by both ketone and hydroxyl functional groups, confers strong free radical scavenging ability and resistance to lipid peroxidation. Notably, the antioxidant capacity of astaxanthin is reported to be approximately 100 times greater than that of vitamin E and 10 times greater than that of β-carotene [21]. These properties underscore its potential value in aquaculture, where it contributes to enhanced survival and production efficiency.

Astaxanthin improves the antioxidant capacity of aquatic animals through multiple physiological mechanisms. It activates major antioxidant enzymes, including superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and catalase (CAT), thereby reducing oxidative stress and preventing cellular damage [13]. In addition to directly scavenging reactive oxygen species (ROS), astaxanthin enhances total antioxidant capacity (T-AOC), reduces lipid peroxidation, and maintains cellular integrity by lowering malondialdehyde (MDA) levels—a key marker of oxidative damage [22,23]. These actions indicate that astaxanthin not only exerts direct antioxidative effects but also stimulates endogenous antioxidant defense systems. The antioxidant efficacy of astaxanthin has been widely validated in various aquatic species. For example, in ridgetail white prawn (Exopalaemon carinicauda), dietary astaxanthin significantly reduced MDA levels and increased SOD, CAT, and GSH-PX activities following immune stress stimulation [24]. In hybrid grouper (Epinephelus fuscoguttatus × Epinephelus lanceolatus), astaxanthin modulated the AMPK and PI3K-Akt signaling pathways, reduced ROS accumulation, and significantly prolonged survival under bacterial infection [25]. In rainbow trout (O. mykiss), dietary supplementation with 100 mg/kg of astaxanthin improved liver lipid and glucose metabolism while reducing cellular oxidative damage [10]. In L. vannamei, astaxanthin reduced cellular oxidative damage by scavenging free radicals and increasing the gene expression of SOD and GSH-PX [14]. These findings consistently support the beneficial effects of astaxanthin on oxidative stress regulation in aquaculture species.

The antioxidant effects of astaxanthin are dose-dependent. Dietary supplementation in the range of 50–200 mg/kg has been shown to significantly improve antioxidant markers [21]. However, excessive dosages may elevate production costs or pose potential toxicity risks. In addition to its direct antioxidant activity, astaxanthin enhances the antioxidant defense system by modulating intracellular signaling pathways. One key mechanism involves the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, which promotes the transcription of antioxidant genes and strengthens the organism’s defense against oxidative damage [13]. Astaxanthin also protects mitochondrial function, thereby reducing oxidative stress-induced apoptosis and maintaining cellular homeostasis [23]. Furthermore, by alleviating oxidative stress, astaxanthin contributes to improved immune function, reversing immune suppression and enhancing overall health status in aquatic animals [22].

In summary, astaxanthin plays a pivotal role in enhancing antioxidant defense, improving stress resilience, and promoting the growth and health of aquatic organisms. Its functional mechanisms include direct free radical scavenging, upregulation of antioxidant enzyme activity, and modulation of critical signaling pathways. As such, astaxanthin represents a valuable functional additive in aquaculture. Future studies should focus on optimizing its application strategies—including dosage, formulation, and species-specific responses—to maximize its efficacy and support sustainable and healthy aquaculture practices.

4. The Role of Astaxanthin in Immune Regulation in Aquatic Animals

Astaxanthin, a xanthophyll carotenoid, not only exhibits potent antioxidant properties but also plays a crucial role in modulating the immune response of aquatic animals. Increasing evidence suggests that astaxanthin enhances immune defense by stimulating innate immune responses, exerting anti-inflammatory effects, and regulating the expression of immune-related genes, thereby improving disease resistance and survival under environmental or pathogenic stress.

Activation of the non-specific immune system: Astaxanthin can enhance the non-specific immune response in aquatic animals by stimulating the activity of immune effectors such as lysozyme (Lyz) and complement components C3 and C4 [19]. These factors contribute synergistically to improved pathogen recognition and clearance, thereby strengthening innate immunity. Additionally, astaxanthin modulates the expression of pro-inflammatory cytokines, reducing tissue damage caused by infection and improving overall immune status [26]. In L. vannamei, dietary supplementation with 100–200 mg/kg astaxanthin significantly increased hemocyte count, total protein content, lysozyme activity, phagocytic rate, and phenoloxidase activity [27], indicating enhanced non-specific immune function.

Anti-inflammatory effects: Astaxanthin can significantly inhibit the expression of pro-inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), by regulating multiple signaling pathways such as NF-κB, MAPK, and PI3K/Akt, thereby reducing inflammatory responses [28]. Dietary astaxanthin supplementation can significantly inhibit the expression of proinflammatory factors (such as IL-1β, IL-8, and TNF-α), reduce the inflammatory response caused by environmental stress or pathogenic infection, and protect intestinal and liver health [29]. In carp [8], astaxanthin derived from microalgae reduced the levels of inflammatory factors such as TNF-α, IL-4, and IFN-γ by regulating the mtROS-NF-κB signaling axis, thereby alleviating spleen lymphocyte pyroptosis and effectively reducing immune toxicity [8]. Additionally, astaxanthin can activate the Nrf2 signaling pathway, improve the antioxidant capacity of cells, reduce the production of inflammatory reactive oxygen species, inhibit the activation of NF-κB, reduce the expression of downstream inflammatory genes, and thus reduce tissue damage [30,31]. In lipopolysaccharide (LPS)-induced acute inflammation models, astaxanthin significantly reduced the expression of inflammation-related proteins such as iNOS and COX-2, further demonstrating its anti-inflammatory effects.

Regulation of immune-related gene expression: Astaxanthin enhances the expression of immune- and antioxidant-related genes through various molecular pathways. Activation of the Nrf2 signaling pathway leads to upregulation of genes encoding SOD, CAT, and GPx, improving resistance to oxidative stress [32]. Astaxanthin modulates PI3K/Akt and MAPK signaling pathways to upregulate immune-related gene expression, thereby strengthening host immunity [33]. Astaxanthin enhances the expression of antioxidant enzymes, such as superoxide dismutase (SOD) and catalase (CAT), by activating the Nrf2-ARE signaling pathway. At the same time, it downregulates the expression of Keap1, thereby further improving the immune capacity of aquatic animals [34]. In L. vannamei, astaxanthin significantly increased lysozyme activity, phagocytic activity, and phenoloxidase activity, and up-regulated the expression of defensin, anti-lipopolysaccharide factor, and lysozyme genes [11]. It also significantly increased the expression of heat shock proteins HSP70 and HSP90, which stabilize protein structures under stress conditions and protect against cellular damage [35,36]. Furthermore, astaxanthin suppresses the expression of inflammatory genes such as IL-1β and TNF-α, alleviating inflammation-induced tissue damage [37]. It also enhances the expression of the glucocorticoid receptor (GR) gene and inhibits the NF-κB signaling pathway, thereby reducing pro-inflammatory cytokine release and improving immune homeostasis [38]. Additionally, astaxanthin upregulates immune-related genes, such as acid phosphatase (ACP) and cytochrome c (CYC), which are closely associated with the activation of the non-specific immune response [37]. By improving antioxidant capacity and reducing the expression of inflammatory factors, astaxanthin indirectly enhances the resistance of aquatic animals to pathogens and environmental stress. For example, in rainbow trout, astaxanthin significantly reduced the release of inflammatory cytokines and improved liver morphology [39]. In hybrid grouper (E. fuscoguttatus × E. lanceolatus), dietary astaxanthin regulated the AMPK and PI3K-Akt signaling pathways, promoted the colonization of dominant probiotics in the intestine, and significantly reduced ROS levels during bacterial infection, thereby improving immune stress capacity [25]. In Nile tilapia (O. niloticus), astaxanthin significantly increased myeloperoxidase activity and enhanced immune responses [16]. Additionally, dietary astaxanthin significantly enhanced the resistance of Pacific white shrimp to Vibrio infection, with the astaxanthin-treated group showing significantly lower cumulative mortality compared to the control group, especially in the group fed astaxanthin alone, which exhibited the lowest mortality [40]. In summary, astaxanthin significantly enhances immune function in aquatic animals through multiple mechanisms, including the activation of non-specific immunity, suppression of inflammation, and regulation of immune-related gene expression. By boosting antioxidant capacity and modulating key signaling pathways, astaxanthin reduces tissue damage from environmental and pathogenic stress, thereby enhancing disease resistance and overall immune competence. Future research should focus on optimizing astaxanthin application strategies—such as dosage, duration, and delivery methods—to maximize its immunomodulatory effects in diverse aquaculture species.

5. The Impact of Astaxanthin on the Reproductive Capacity of Aquatic Animals

Astaxanthin, as a potent antioxidant, can significantly improve the reproductive performance of aquatic animals. It primarily exerts its positive effects on reproduction by alleviating oxidative stress, promoting gonadal development, regulating redox signaling pathways, and improving gamete quality. Astaxanthin reduces oxidative damage to the reproductive organs by scavenging active oxygen species (ROS) and up-regulating the activity of antioxidant defense systems such as SOD and CAT, thereby protecting the structural integrity of reproductive cells (sperm and oocytes) [41]. Studies have shown that dietary astaxanthin can effectively reduce lipid peroxidation, protecting reproductive cell membranes from oxidative stress damage [42]. Additionally, under winter low-temperature stress conditions, astaxanthin significantly reduced oxidative stress markers (such as MDA) in the ovaries of Nile tilapia (O. niloticus), significantly improving egg fertilization rates and embryo hatching rates [16]. Astaxanthin enhances the reproductive capacity of aquatic animals by increasing the secretion of hormones related to gonadal development. Research has found that in largemouth bass (M. salmoides), supplementation with different doses of astaxanthin (such as 40 mg/kg and 100 mg/kg) significantly increased the levels of vitellogenin (VTG), follicle-stimulating hormone (FSH), and luteinizing hormone (LH), while reducing the hepatosomatic index (HSI), thereby promoting ovarian development [12]. In O. mykiss, astaxanthin supplementation increased the levels of estrogen (E2) and testosterone (T), further promoting gonadal maturation [43]. These results indicate that astaxanthin can promote gonadal development in aquatic animals by regulating hormone levels, thereby enhancing reproductive capacity. Astaxanthin significantly improves the quality of both eggs and sperm in aquatic animals. It promotes ovarian development, enhances the structural integrity of oocytes, and increases sperm motility and survival rates. This effect is primarily attributed to astaxanthin’s regulation of reproductive hormones and its antioxidant protective effects [44]. In Nile tilapia, astaxanthin-rich P. carotinifaciens significantly increased sperm concentration and motility while significantly increasing egg production in female individuals [16]. In M. salmoides, astaxanthin improved semen quality by activating the MAPK/Nrf2 pathway, increasing antioxidant enzyme activity, and reducing lipid peroxidation levels [45]. These studies indicate that astaxanthin not only improves oocyte quality but also enhances sperm quality and reproductive efficiency. Astaxanthin regulates signaling pathways such as Nrf2 and PI3K/Akt, promoting the expression of antioxidant and anti-inflammatory genes, reducing the production of inflammatory factors, and providing protection for the reproductive system [46]. Additionally, astaxanthin improves mitochondrial function, enhancing energy metabolism efficiency and providing energy support for reproductive processes [41]. In black tiger shrimp (Penaeus monodon), dietary supplementation with 280 mg/kg astaxanthin significantly reduced embryo mortality and improved hatching rates and larval survival rates [47]. Similarly, in rainbow trout and Atlantic salmon (Salmo salar), astaxanthin has been shown to significantly enhance gamete quality and improve reproductive success rates [42]. These findings suggest that astaxanthin promotes reproductive health in aquatic animals by modulating key signaling pathways.

Astaxanthin significantly improves the reproductive performance of aquatic animals through its potent antioxidant effects, promotion of gonadal development, improvement in gamete quality, and regulation of immune-related signaling pathways. These effects make astaxanthin an important application in aquaculture, promoting the reproductive efficiency and farming benefits of aquatic animals. Future research can further explore the potential mechanisms of astaxanthin in aquaculture and optimize its application strategies to maximize its role in improving the reproductive capacity of aquatic animals.

6. The Role of Astaxanthin in Intestinal Health and Metabolic Regulation in Aquatic Animals

Astaxanthin plays a vital role in maintaining intestinal health and regulating metabolism in aquatic animals. Numerous studies have demonstrated that astaxanthin supplementation promotes growth and improves health by enhancing intestinal morphology, modulating gut microbiota, increasing digestive enzyme activity, and regulating key metabolic signaling pathways.

Astaxanthin has shown significant efficacy in improving intestinal structure. Dietary supplementation with astaxanthin has been found to increase the length, width, and absorptive surface area of intestinal villi, thereby enhancing nutrient absorption efficiency [48]. In European seabass (Dicentrarchus labrax), supplementation with 60–100 mg/kg astaxanthin significantly upregulated the expression of intestinal immune-related genes, including immunoglobulin M (IgM), defensin, and lysozyme (Lyz), thereby enhancing intestinal immune defense [49]. Additionally, astaxanthin increased the expression of the polymeric immunoglobulin receptor (pIgR), a key factor in mucosal immunity, contributing to improved resistance against intestinal pathogens [50]. In golden pompano (Trachinotus ovatus), moderate Oedocladium carolinianum powder supplementation (1%) up-regulated the expression of anti-inflammatory genes (such as Nrf2 and HO-1) while inhibiting the expression of pro-inflammatory factors, such as IL-1β and TNF-α, and increased the length and width of intestinal villi. However, high doses of astaxanthin (0.1%) led to villus atrophy, suggesting that excessive astaxanthin may negatively impact intestinal health [51]. Moderate astaxanthin supplementation is beneficial in preserving intestinal mucosal integrity, reducing epithelial apoptosis, and minimizing the risk of pathogen invasion [52].

Astaxanthin can optimize the structure of the gut microbiota in aquatic animals. Studies have shown that dietary astaxanthin supplementation increases the abundance of beneficial bacteria, such as Lactobacillus and Bifidobacterium, while reducing the number of harmful bacteria, such as Vibrio [53]. In large yellow croaker (L. crocea), dietary astaxanthin improved gut microbial composition and promoted intestinal homeostasis by enhancing short-chain fatty acid (SCFA) production [17]. Similarly, in golden pompano, supplementation with 0.005–0.1% astaxanthin significantly enriched beneficial bacterial populations, such as Bacillus, Lactobacillus, and Psychrobacter, while suppressing potential pathogens [51]. In experiments, dietary astaxanthin significantly increased the abundance of beneficial bacteria (such as Lactobacillus and Bifidobacterium) while reducing the number of harmful bacteria (such as Clostridium perfringens), thereby maintaining gut microbial balance [52]. Through its antioxidant and anti-inflammatory properties, astaxanthin also inhibits the proliferation of pro-inflammatory bacteria, thereby supporting intestinal health and reducing local inflammation [54]. Astaxanthin enhances the digestive capacity of aquatic animals by stimulating digestive enzyme secretion. In O. mykiss and O. niloticus, dietary astaxanthin significantly increased the activities of key digestive enzymes, including amylase, protease, and lipase, thereby improving nutrient digestion and assimilation [55]. In Pacific white shrimp, astaxanthin significantly increased digestive enzyme activity and reduced the feed conversion ratio (FCR), thereby improving growth rates [56]. Additionally, astaxanthin can activate the Nrf2 signaling pathway, increasing the expression of antioxidant enzymes (such as SOD, CAT, and GPx), reducing the accumulation of ROS in the intestine, and alleviating oxidative stress damage [51]. It also decreases lipid peroxidation products such as MDA, preserving intestinal cell function and structural integrity [57]. Astaxanthin also contributes to metabolic homeostasis by regulating lipid and energy metabolism in aquatic species. It activates key metabolic pathways, including AMPK and PI3K/Akt, which are involved in cellular energy sensing and lipid utilization [25]. In salmon (Salmo salar), astaxanthin promoted mitochondrial function, increased ATP synthesis, and reduced the impact of oxidative stress on energy metabolism [58]. Moreover, astaxanthin regulates fatty acid synthesis and β-oxidation, facilitating muscle protein accumulation while reducing hepatic lipid deposition [59]. In golden pompano, dietary astaxanthin significantly increased the activity of key enzymes related to energy metabolism (such as hexokinase and lactate dehydrogenase) and promoted the activation of the AMPK and PI3K/Akt signaling pathways [51]. Astaxanthin can promote the energy metabolism of aquatic animals by regulating the PI3K/Akt and mTOR signaling pathways, improving the utilization efficiency of nutrients, and thereby enhancing growth performance or increasing disease resistance [60]. Furthermore, astaxanthin improves insulin sensitivity, optimizing glucose and lipid metabolism and further promoting healthy growth [61]. In L. vannamei, dietary astaxanthin increased the activities of glycolysis-related enzymes such as hexokinase and phosphofructokinase, enhancing energy production and growth performance [59].

In conclusion, astaxanthin contributes significantly to intestinal health and metabolic regulation in aquatic animals. It improves intestinal morphology, enhances mucosal immunity, modulates gut microbiota composition, stimulates digestive enzyme activity, and regulates key metabolic signaling pathways. These multifaceted actions collectively promote nutrient utilization, energy balance, and overall health, making astaxanthin a valuable functional additive in aquaculture. Future research should focus on elucidating species-specific mechanisms and optimizing astaxanthin application strategies—including dosage, source, and delivery systems—to fully leverage its benefits in sustainable aquaculture production.

7. The Impact of Astaxanthin on the Body and Muscle Color of Aquatic Animals

Astaxanthin, a xanthophyll carotenoid, is renowned not only for its strong antioxidant properties but also for its remarkable pigmentation capabilities, which are of significant importance in aquaculture. It is widely distributed in aquatic organisms and plays a key role in enhancing the coloration of the body and muscles, thereby improving the visual appeal, marketability, and commercial value of farmed species. Astaxanthin contributes to pigmentation primarily by increasing the deposition and distribution of carotenoids in tissues, especially in muscle. This effect is achieved through the binding of astaxanthin to muscle proteins, which stabilizes pigment molecules and enhances their retention in tissue [62]. For instance, in O. mykiss, dietary astaxanthin significantly increased the redness (a* value) of the body and fillet, with synthetic astaxanthin demonstrating a more pronounced effect compared to its natural counterpart [53]. Similarly, in L. vannamei, dietary supplementation with astaxanthin at dosages of 35 mg/kg and 70 mg/kg markedly enhanced body coloration, with the higher dose producing the most intense pigmentation effect [63]. Astaxanthin enhances its coloring ability by binding to proteins and stabilizing pigment molecules. In addition to increasing color vibrancy, astaxanthin can also improve color uniformity and stability. Studies have shown that the binding of astaxanthin to muscle proteins effectively prevents pigment oxidation and decomposition, maintaining color stability. In S. salar and common carp (Cyprinus carpio), dietary astaxanthin significantly improved color uniformity and stability [64]. In leopard coral grouper (Plectropomus leopardus), dietary supplementation with 0.02% natural astaxanthin significantly increased the redness and yellowness of the body while promoting the expression of carotenoid-related genes [65]. In black tiger shrimp (Penaeus monodon), synthetic astaxanthin resulted in significantly higher redness compared to natural astaxanthin and control treatments, further emphasizing its superior pigmentation performance [66]. In crustaceans, which are unable to synthesize astaxanthin endogenously, dietary astaxanthin is essential for coloration. Its accumulation results in vibrant red and orange shell coloration, which is critical for consumer preference and commercial value. Moderate dietary inclusion of astaxanthin is sufficient to meet pigment requirements in shrimp and crabs, improving body color and enhancing their market competitiveness. Astaxanthin is also widely used in ornamental aquaculture, where body coloration is a primary determinant of aesthetic and economic value. In koi carp, astaxanthin supplementation significantly enhanced the saturation of red and yellow hues on the body surface, and color intensity was positively correlated with astaxanthin content in the tissue [67]. In discus fish (Symphysodon sp.), 100 mg/kg dietary astaxanthin enhanced red pigment deposition and improved the brightness and uniformity of skin color [68]. These findings underscore the high market potential of astaxanthin in ornamental fish production. For edible fish, muscle color reflects meat quality to some extent and affects market value. In S. salar, the orange or red-orange color of the muscle is closely related to astaxanthin deposition, and this color is widely recognized by consumers as an important indicator of fish freshness and quality [58]. Similar effects were observed in arctic char (Salvelinus alpinus), where dietary supplementation with 40–80 ppm astaxanthin significantly increased carotenoid concentrations in the abdominal skin and muscles, with muscle redness (a* value) positively correlated with carotenoid levels [69]. In O. mykiss, dietary supplementation with 15–30 mg/kg Haematococcus pluvialis astaxanthin also significantly increased astaxanthin content in muscle, with muscle redness positively correlated with astaxanthin dosage [70]. Using fishery and aquaculture shrimp by-products as a source of astaxanthin is a viable alternative, not only as a substitute for fishmeal, but also for enhancing the reddish appearance of farmed fish [71]. These studies indicate that astaxanthin can significantly improve the muscle color of edible fish, thereby increasing their market appeal and economic value. Astaxanthin plays a significant role in the body and muscle coloring of aquatic animals, significantly enhancing the vibrancy and uniformity of their colors. Its coloring effects vary depending on dosage, source (natural or synthetic), and aquatic species. Combined use with other natural pigments can further enhance coloring effects, demonstrating the broad application potential of astaxanthin in aquaculture and the ornamental fish industry.

8. Current Challenges and Issues in the Application of Astaxanthin

8.1. Challenges and Solutions for Improving the Bioavailability of Astaxanthin in Aquaculture

Astaxanthin, a lipid-soluble compound with high nutritional and functional value, faces significant limitations in aquaculture due to its inherently low bioavailability. This reduced bioavailability is primarily attributed to its poor water solubility, chemical instability, and limited absorption efficiency in aquatic animals. As a lipophilic molecule, astaxanthin exhibits low solubility in aqueous environments, which is particularly problematic in aquatic systems where nutrients are typically delivered in water-based formulations. Consequently, its poor solubility significantly restricts its intestinal absorption and biological efficacy in aquatic species [72]. In addition, the molecular structure of astaxanthin contains a polyene backbone that is highly susceptible to degradation under various environmental conditions, including acidic pH, elevated temperatures, light exposure, and oxidative stress. This chemical instability not only diminishes astaxanthin’s antioxidant capacity but also compromises its biological activity during storage, feed processing, and gastrointestinal digestion [72]. The intestinal absorption of astaxanthin depends on its emulsification by dietary lipids and subsequent incorporation into bile salt micelles—a prerequisite for its uptake by intestinal epithelial cells. Disruption in lipid digestion or micelle formation further impairs its bioavailability [73]. This is particularly relevant in aquatic animals, whose digestive physiology may not be optimally suited to efficiently absorb fat-soluble compounds, thereby limiting the health-promoting benefits of astaxanthin. To overcome these challenges, several strategies have been proposed to enhance the stability and bioavailability of astaxanthin in aquaculture applications. One of the most promising approaches involves microencapsulation and liposome encapsulation technologies. These encapsulation systems create protective barriers around astaxanthin molecules, shielding them from adverse environmental conditions such as heat, light, oxidation, and acidic pH. As a result, the chemical stability and gastrointestinal absorption of astaxanthin are markedly improved [73,74]. Another effective approach is the formation of astaxanthin–protein or astaxanthin–lipid complexes. The combination of astaxanthin with carrier molecules such as proteins, phospholipids, or fatty acids has been shown to enhance its aqueous dispersibility and promote its intestinal uptake. These complexes increase the solubility and emulsification efficiency of astaxanthin, thereby facilitating its micellar incorporation and improving its bioavailability in aquatic animals [75]. In recent years, nanotechnology-based delivery systems have emerged as a powerful tool to address the solubility and stability issues of astaxanthin. The encapsulation of astaxanthin within nanoparticles, such as polymeric nanoparticles, nanoliposomes, or nanoemulsions, offers several advantages, including improved water dispersibility, enhanced bioavailability, controlled release, and targeted delivery [76,77]. Astaxanthin delivery systems can be broadly classified into two categories based on particle size: micron-scale and nano-scale systems. Depending on the encapsulating materials, preparation techniques, and final structural forms, astaxanthin carriers can be further categorized into various types, including nanoemulsions, microcapsules, nanoparticles, liposomes, and nanostructured lipid carriers (NLCs). Each type of delivery system offers distinct advantages and is suitable for enhancing the stability, bioavailability, and application efficiency of astaxanthin [78]. The advantages, limitations, and potential improvement strategies for different astaxanthin delivery systems are summarized in

Table 1. Advantages, limitations, and potential improvements of astaxanthin delivery systems.

Delivery System	Advantages	Limitations
Nanoemulsions	Simple preparation process	Low encapsulation efficiency; prone to phase separation and flocculation
Microcapsule	Effective protection of active compounds; sustained release	Residual organic solvents; high cost of freeze-drying
Nanoparticle	Small particle size; high drug-loading capacity; biodegradable	Stability easily affected by environmental conditions
Liposome	Small particle size; high encapsulation efficiency; good biocompatibility	Use of cholesterol and organic solvents; limited industrial scalability
Nanostructured lipid carrier	Non-toxic; high drug-loading capacity; controlled release	Strict requirements for processing conditions

.

To address the poor water solubility of astaxanthin, dissolving it in an oil phase to form an emulsion has proven to be an effective strategy. Further encapsulation of the emulsion using biopolymers such as polysaccharides or proteins to form microcapsules significantly enhances astaxanthin stability. Nanostructured lipid carriers, by combining solid and liquid lipids, improve drug-loading efficiency. In addition, liposomes have demonstrated promising potential as delivery vehicles due to their excellent biocompatibility and high encapsulation rates. While current research efforts on astaxanthin delivery systems mainly focus on improving encapsulation efficiency and physical stability, future studies should prioritize enhancing drug-loading capacity, targeted delivery capabilities, and comprehensive toxicological safety assessments to enable the efficient and precise utilization of astaxanthin. The comprehensive application of these solutions is expected to overcome the issues of poor solubility and stability of astaxanthin, thereby effectively improving its bioavailability and application efficacy in aquaculture.

8.2. Current Status of Astaxanthin Production and Strategies for Reducing Production Costs

In recent years, microalgae—particularly H. pluvialis—have been the primary source for industrial-scale astaxanthin production due to their high synthesis efficiency. As the most widely used production strain, H. pluvialis has demonstrated substantial potential in meeting industrial demand. However, the commercial production of astaxanthin still faces several critical challenges, including high production costs, reliance on specific raw materials, and limitations in scalability [77,78]. To address these issues, researchers have proposed a variety of strategies aimed at diversifying astaxanthin sources and optimizing production processes. A comparative overview of the production cost and relative bioavailability of different astaxanthin sources is provided in

Table 2. The current comparison of production costs and relative bioavailability of various astaxanthin sources.

Astaxanthin Source	Estimated Production Cost (USD/kg)	Relative Bioavailability	Notes
H. pluvialis	1500–7000	High	Natural source, high bioavailability due to esterified form; widely used.
P. rhodozyma	1000–3000	Medium	Natural source, used mainly in aquaculture feed.
Chemical synthesis	500–1000	Low	Racemic mixture; not approved for human use in some regions.
Crustacean by-products	100–500	Low–Medium	From shrimp/crab shells; low yield and stability.
Genetically engineered microorganisms	500–2000	Medium–High	Emerging technology; cost-effective and scalable.

[79,80,81,82].

In addition to the traditional H. pluvialis, many microalgae, yeast, and bacteria have been explored as new sources of astaxanthin. For example, Chlorella zofingiensis and Chlorococcum have also been shown to efficiently accumulate astaxanthin [83]. In addition, bacterial strains such as Paracoccus carotinifaciens and Agrobacterium aurantiacum have been explored as alternative microbial sources, thereby expanding the biological pathways available for astaxanthin biosynthesis [84]. Natural astaxanthin is primarily derived from microalgae and red algae, but the supply of these resources is limited and subject to seasonal variations [85], and water pollution can also negatively impact astaxanthin production in algae [86]. Furthermore, some studies have reported the determination of astaxanthin content in different tissues of shrimp [87]. Research on extracting astaxanthin from crustacean byproducts is still in its early stages, and its economic feasibility has not been fully verified [88]. By diversifying raw material sources and reducing reliance on a single microalgal species, production costs can be reduced to some extent. Optimizing production conditions is another important approach to improving astaxanthin yield. Studies have shown that adjusting environmental conditions such as light, temperature, and nitrogen sources can significantly improve synthesis efficiency [82,89]. For example, under high light and nitrogen-deficient conditions, the astaxanthin content in H. pluvialis can be significantly increased [90,91]. Nanotechnology has also emerged as a promising tool to enhance astaxanthin productivity. Modifying microalgal cell structures and reducing particle size through nanotechnology can increase both the extraction efficiency and bioavailability of astaxanthin [90]. The encapsulation of astaxanthin at the nanoscale level improves water solubility, facilitates cellular uptake, and enables controlled release, contributing to higher production efficiency and product functionality. Another issue in astaxanthin production is the complexity and high cost of the extraction and purification processes. Traditional solvent extraction methods, although simple, require large amounts of organic solvents and may pose environmental risks [85]. Additionally, the complexity and inefficiency of raw materials when extracting astaxanthin from seaweed and microorganisms contribute to high production costs [88]. In recent years, green and efficient methods such as supercritical fluid extraction and microalgal solvent extraction have been developed. Although these technologies have made some progress in improving efficiency, further optimization is needed to reduce costs [92]. Researchers have also attempted to use low-cost waste materials as culture media to reduce production costs. For example, using molasses wastewater or pig manure wastewater as culture media for microalgae can not only reduce raw material costs but also achieve waste resource utilization [93]. These innovative approaches not only offer practical and effective strategies for reducing the production cost of astaxanthin but also contribute to resource recycling and environmental sustainability.

In summary, by expanding the sources of astaxanthin, optimizing production processes, applying nanotechnology, and utilizing low-cost raw materials, the production costs of astaxanthin can be significantly reduced. This will provide more economically viable solutions for its widespread application in aquaculture and other industries [83,85,94].

9. Conclusions

Astaxanthin, a potent xanthophyll carotenoid, exhibits multiple biological functions and holds substantial application value, particularly in the field of aquaculture (shown in Figure 2). Its exceptional antioxidant properties allow it to effectively scavenge free radicals, mitigate oxidative damage at the cellular level, and protect aquatic organisms from oxidative stress. These effects contribute to delayed senescence and enhanced physiological resilience, ultimately improving the health status and growth performance of cultured species. Astaxanthin also plays a crucial role in immune regulation by activating the non-specific immune system and enhancing resistance to pathogens. It modulates the expression of immune-related genes, suppresses inflammatory responses, and reduces immune dysfunction induced by environmental stressors or pathogenic infections. In addition to its immunostimulatory functions, astaxanthin promotes somatic growth by improving feed utilization efficiency, increasing digestive enzyme activity, and optimizing protein metabolism. It contributes to the development and functional integrity of the intestinal tract, thereby facilitating nutrient absorption and further supporting growth. Astaxanthin also exerts a positive influence on reproductive performance in aquatic animals. By reducing oxidative stress, promoting gonadal development, regulating endocrine function, and improving gamete quality, astaxanthin enhances reproductive parameters such as egg fertilization rates, embryo hatching success, and overall reproductive output. These multifaceted roles make astaxanthin a valuable additive for both enhancing growth and improving reproductive efficiency in aquaculture systems.

Despite its many beneficial properties, the application of astaxanthin in aquaculture is hindered by several challenges, foremost among them being its low bioavailability. As a fat-soluble compound, astaxanthin exhibits poor water solubility and low intestinal absorption efficiency in aquatic species. Furthermore, it is highly susceptible to degradation when exposed to unfavorable conditions such as low pH, elevated temperatures, and ultraviolet radiation. These characteristics limit its biological efficacy and functional stability in aquaculture settings. Compounding these issues are the high production costs associated with astaxanthin, particularly those stemming from the complex and resource-intensive extraction processes required for natural sources. Consequently, these technical and economic limitations constrain its widespread commercial application. To overcome these barriers, various strategies have been developed. Microencapsulation and liposomal encapsulation technologies have been employed to protect astaxanthin from environmental degradation and to improve its stability and bioavailability in aquatic animals. Nanotechnology-based delivery systems have also demonstrated promise in enhancing water dispersibility and controlled release, thereby promoting effective absorption and utilization. In parallel, efforts to expand astaxanthin sources—such as the exploration of novel microalgae, yeast, and bacterial strains—are underway to reduce production costs and improve sustainability. The optimization of cultivation parameters and metabolic engineering approaches have further contributed to improving astaxanthin yield. Nevertheless, several key knowledge gaps remain. The biosynthetic efficiency of astaxanthin varies significantly across different host organisms, and the precise functions and regulatory interactions of rate-limiting enzymes and key transcriptional factors remain incompletely characterized. For example, the molecular mechanisms regulating astaxanthin accumulation in H. pluvialis are still not fully elucidated. Additionally, in heterologous expression systems, the regulatory mechanisms that control the activity and stability of astaxanthin biosynthetic enzymes require further investigation. A major challenge in high-density fermentation is the inverse relationship observed between cell biomass and astaxanthin accumulation. The underlying mechanisms governing metabolic flux distribution and energy allocation in these systems are still poorly understood. To address these limitations, future research should leverage multi-omics approaches—such as transcriptomics, metabolomics, and proteomics—to identify critical regulatory nodes and elucidate metabolic bottlenecks. Integrating gene editing technologies and pathway reconstruction strategies can enhance biosynthetic efficiency. The use of systems biology tools and machine learning models can further aid in the prediction of metabolic constraints and guide rational strain design. Moreover, high-throughput screening techniques and dynamic metabolic control strategies should be implemented to maximize astaxanthin yield. It is also crucial to develop energy-efficient, cost-effective cell disruption and purification technologies to support the industrial-scale production of astaxanthin in a sustainable and economically viable manner.

In conclusion, astaxanthin holds great promise as a multifunctional feed additive in aquaculture, offering benefits across growth, immunity, reproduction, and health management. However, its practical application remains constrained by challenges related to low bioavailability, high production costs, and poor physicochemical stability. Continued advancements in biotechnology, production optimization, and delivery systems will be essential to unlock the full potential of astaxanthin and enable its broad-scale application in sustainable aquaculture systems.