Sarcopenia is a condition characterized by a progressive reduction in skeletal muscle mass and strength, which affects balance, mobility, overall physical performance and quality of life (1). Risk factors for sarcopenia include increased age, being of the male sex, malnutrition and a sedentary lifestyle (2). Primary sarcopenia is often age-related without apparent underlying causes, whereas secondary sarcopenia is associated with one or more causes (1). Major co-morbidities associated with sarcopenia are obesity, osteoporosis and type 2 diabetes mellitus (3). A meta-analysis of 35 studies showed that the global prevalence of sarcopenia is 10% in men and women, and the prevalence is higher in non-Asian countries than in Asian countries (4). It is estimated that the cost of hospitalisation associated with sarcopenia was approximately $40.4 billion USD in the United States, with an average cost of $260 USD per individual (5). Sarcopenia has also become a topic of interest in recent years, as an increasing proportion of the global population being of advanced age is projected to triple between 2017 and 2050(6). The development of prophylactic and therapeutic strategies for sarcopenia may therefore become imperative to ensure healthy ageing. It is also noteworthy that there are no US Food and Drug Administration (FDA)-approved drugs for the treatment of sarcopenia (7). Understanding the pathogenesis of sarcopenia will be important in the design of prophylactic and therapeutic strategies for the disease. Oxidative stress, inflammation, impairment of mitochondrial function, increased protein turnover and capillary regression can result in the loss of skeletal muscle mass and ultimately sarcopenia (8-11). Previous studies have demonstrated that the administration of antioxidants reduced the level of oxidative stress during exercise (12) and the level of muscle atrophy (13). These findings suggest a potential role for antioxidants in reversing sarcopenia.

Astaxanthin is a fat-soluble, naturally occurring xanthophyll carotenoid identified in numerous organisms, such as microalgae, crustaceans and fish (such as salmon and trout) (14). Astaxanthin is a powerful antioxidant that effectively scavenges free radicals, quenches singlet oxygen, enhances antioxidant activities and reduces oxidative stress (15). The nutraceutical applications of astaxanthin previously reported include anti-inflammatory (16), anti-cancer (17) and anti-diabetic (18) and it has also been reported to have gastro- (19), hepato- (20), neuro- (21), cardio- (22), ocular- (23) and skin-protective (24) properties.

A recent review summarised the potential application of astaxanthin as a dietary supplement in exercising humans. The author concluded that there was an improvement of exercise metabolism, performance and recovery following astaxanthin supplementation (25). In addition, an in vitro study by Yu et al (26) demonstrated that incubation of the mouse myoblast C2C12 cell line with astaxanthin (5 µM) during heat stress (43˚C) prevented adverse changes to the tubular mitochondrial structure and mitochondrial membrane potential, as well as reactive oxygen species (ROS) production. Thus, astaxanthin may have a potential application in preventing muscle injury and degeneration. In the present review, the health-promoting effects of astaxanthin on the skeletal muscle in animal models and humans are presented. The molecular mechanisms underlying the health benefits of astaxanthin in reversing adverse muscle changes are also highlighted.

Evidence acquisition was conducted between February 1st and February 29th 2020 using PubMed and Medline electronic databases. The key words used to perform the search were ‘astaxanthin AND (sarcopenia OR muscle)’. All in vitro, in vivo and human studies detailing the effects of astaxanthin and its underlying mechanisms on muscle health were extracted. A total of 20 related studies are included in the present review.

The effects of astaxanthin on skeletal muscle have been explored in vivo (Table I). Recently, Aoi et al (27) compared the effects of three different forms of astaxanthin on endurance performance in 8-week-old ICR mice. Astaxanthin derived from Haematococcus pluvialis (esterified form), synthetic astaxanthin (non-esterified form) or astaxanthin derived from Phaffia rhodozyma (non-esterified form) was provided to the animals in their diet at a dose of 0.02% (w/w) for five weeks. The animals were subjected to treadmill exercise with a running speed of 25 m/min for the assessment of endurance and their running time to exhaustion was measured. The study indicated that animals fed with astaxanthin from H. pluvialis had the longest running time to exhaustion among the experimental groups (27). Long-term effects of astaxanthin supplementation were also evaluated using an exercised animal model. Adult male Wistar rats were administered mineral oil (vehicle) or astaxanthin (1 mg/kg) five days per week for 45 days. The animals treated with astaxanthin had a higher elapsed time until exhaustion in a forced-swimming activity when compared with exercised animals without treatment (28).

In another study, Kawamura et al (29) investigated the effects of astaxanthin alone, or in combination with other antioxidants (β-carotene and resveratrol), on muscle atrophy in 7-week-old male ICR mice. The knee and ankle joints of one hindlimb were fixed with a cast to induce muscle atrophy and removed after three weeks. After cast removal, the animals were fed a basal diet enriched with astaxanthin, β-carotene, resveratrol or a mixture of the three antioxidants for two weeks. The animals given a basal diet with astaxanthin alone or a mixture of the three antioxidants had significantly higher soleus muscle weight when compared to the normal animals (29).

An animal model of hindlimb unloading was also used to assess the effects of astaxanthin on atrophied soleus muscle. Kanazashi et al (30) performed hindlimb unloading on adult male Wistar rats for 7 days by suspending the tail, to prevent weight bearing of the hindlimb on the floor or contact with the sides of the cage. Astaxanthin was administered orally at 50 mg/kg twice per day for 7 days. Astaxanthin was demonstrated to prevent the changes caused by hindlimb unloading, indicated by the preserved capillary-to-fibre (C/F) ratio, capillary number per fibre (CAF), capillary volume and capillary diameter of the treated group. As astaxanthin supplementation alone was beneficial in preventing capillary regression, while exerting minimal impact on muscle mass, the same group of researchers hypothesized that a combination of astaxanthin and intermittent loading would work synergistically on the prevention of muscle atrophy and capillary regression during hindlimb unloading. In the subsequent study, the animals were subjected to hindlimb unloading followed by the release of the suspension device to allow for normal cage activity for one hour daily in darkness. The study duration was extended to two weeks. As expected, the results indicated that intermittent unloading combined with astaxanthin ameliorated both soleus muscle atrophy and capillary regression in the hindlimb unloaded animals (31). A recent study was conducted to evaluate the effects of a combined therapy of astaxanthin and electrical stimulation on muscle atrophy using hindlimb unloaded rats. For electrical stimulation, calf muscles of the rats were electrically stimulated using a surface electrode (diameter: 1 cm, frequency: 100 Hz) for 240 sec/day. Treatment with astaxanthin alone increased the C/F ratio. The combined therapy was more efficient than astaxanthin alone in reversing the adverse changes due to hindlimb unloading. The combination of astaxanthin and electrical stimulation increased absolute soleus muscle mass and fibre cross-sectional area (FCSA) (32). Another group of researchers reported that dietary astaxanthin supplementation prior to and during hindlimb unloading suppressed soleus muscle atrophy. Compared to the animals subjected to hindlimb unloading without treatment, astaxanthin supplementation caused higher muscle weight and FCSA in the soleus muscle (33). A comprehensive study done by Yoshihara et al (34) illustrated the effects of a combination of astaxanthin supplementation, heat stress and intermittent reloading on the hindlimb unweighted rats. Hindlimb unloading was conducted as aforementioned, whereby the tail was immobilized in a cast, allowing the animals to move only using their front feet. The animals were placed in a heat chamber at 41.0-41.5˚C for 30 min. Intermittent reloading was performed during the heating phase for one hour every other day to allow daily activities. Astaxanthin was mixed into their basal diet at 0.04% w/w. The combination of dietary astaxanthin, heat treatment and intermittent reloading resulted in higher soleus muscle weight and cross-sectional area in the hindlimb unloaded animals (34).

Hindlimb immobilization is another method to induce muscle atrophy. Immobilization refers to holding a joint or bone in place with a cast to prevent its movement, thus inducing muscle contracture and atrophy (35,36). In contrast, the rodents are in a head-down position to simulate weightlessness for hindlimb unloading (37). In an in vivo study, three groups of male Wistar rats were given either a placebo diet, or a 0.04 or 0.2% astaxanthin diet for 24 days. At day 14, hindlimb muscle immobilization was introduced to the rats in the maximum plantar flexion position with a plaster cast. It was demonstrated that the degree of muscle atrophy was lessened in the rats fed with a diet supplemented with astaxanthin (38). Similarly, Maezawa et al (39) introduced joint immobilization to 7-week-old male Wistar rats using the same approach. Astaxanthin (100 mg/kg) was administered orally each day for three weeks (one week before and two weeks during ankle joint immobilization). The treatment of astaxanthin reduced FCSA in the rats with joint immobilization (39).

In high-fat diet fed male C57BL/6J mice, astaxanthin was shown to increase exercise endurance. The astaxanthin-treated mice were able to run for a longer distance than the untreated mice when subjected to daily exercise using a treadmill and wheel. Astaxanthin also increased glucose tolerance after regular daily training, along with other metabolic syndrome parameters [fasting blood glucose, insulin, homeostatic model assessment of insulin resistance (HOMA-IR), glycated haemoglobin (HbA1c), systolic blood pressure, triglyceride and total cholesterol were reduced] (40).

The impact of astaxanthin supplementation on meat colouration in chickens has been evaluated. Using 15-day-old Broiler chicks as an animal model, Inoue et al (41) randomly assigned the chicks to one of the four groups using a 2x2 factorial design. The two main variables in this study were diet [basal diet or basal diet enriched with 0.15% Panaferd-P (containing 30 ppm astaxanthin)] and ambient temperature [thermo-neutral temperature (25±1˚C) or high temperature (35±1˚C)]. It was revealed that a diet containing Panaferd-P increased muscle carotenoid content, redness and yellowness of the skeletal muscle (meat) in the broiler chicks under the condition of thermo-neutral and high ambient temperature (41). Meat colour determines meat quality (42). A decrease in muscle redness might be a consequence of an alteration in muscle myoglobin concentration (the main protein responsible for meat colour), heat stress and feed restriction (42,43). Meanwhile, a reduction in muscle yellowness is an indicator for decreasing carotenoid (astaxanthin, adonixanthin, canthaxanthin, adonirubin, lutein and zeaxanthin) accumulations in muscle. Hence, the increases in muscle redness and yellowness indicated quality improvement of the meat (41).

Limited studies have been conducted in humans to test the effects of astaxanthin on muscle, particularly in the aspects of muscle injury/damage and muscle strength (Table II). The effects of astaxanthin on muscle injury were studied among resistance-trained men (n=20, aged 25.1±1.6 years). The subjects were equally divided into the placebo (administered 1,732 mg safflower oil) or astaxanthin (administered 4 mg astaxanthin and 480 mg lutein) groups. After three weeks of assigned treatments, the participants were subjected to eccentric exercise (10 sets of 10 repetitions at 85% of one repetition maximum) and followed through 96 h post-exercise. The parameters measured in this study include muscle soreness, creatine kinase (CK) activity and muscle performance. A similar response in these variables was noted for both groups, reiterating that astaxanthin supplementation exerted negligible effects on skeletal muscle injury following eccentric loading (44). Another human study demonstrated the effects of astaxanthin supplementation (4 mg) for 90 days on muscle damage, oxidative stress and antioxidant capacity during soccer training in elite young soccer players. Treatment with astaxanthin did not change the levels of thiobarbituric acid-reactive substances (TBARS) and advanced oxidation protein products (AOPP) throughout this study. The CK and aspartate aminotransferase (AST) activities in serum were significantly increased with soccer training without treatment but were lowered with astaxanthin administration (45). In a randomized, double-blind, placebo-controlled study, Liu et al (46) examined a test formulation consisting of astaxanthin (12 mg), tocotrienol (10 mg) and zinc (6 mg) on building strength, endurance and mobility in exercise training among the elderly. A total of 42 elderly subjects (aged 65-85 years) were recruited, fed with test formulation or placebo for 4 months and trained with increasing intervals of incline walking for three months (three times weekly for 40-60 min). In this study, muscle strength was presented as maximal voluntary contraction (MVC) in an ankle dorsiflexion exercise, and the tibialis anterior muscle size was measured as cross-sectional area (CSA) using magnetic resonance imaging. The authors identified a greater endurance in a 6-min walk upon exercise training in both experimental groups. The subjects administered astaxanthin formulation had higher MVC and CSA, indicating improved muscle strength and size as compared to the placebo-treated exercised subjects (46).

A recent study by Takami et al (47) assessed whether foods containing antioxidants (such as catechin, astaxanthin, quercetin, glutathione and anthocyanin) could boost aerobic metabolism during exercise training. All participants were divided into two groups subjected to supervised cycling training for 30 min (three days per week) for four weeks with or without taking antioxidant-rich foods. Several observations were made in this study. The values of oxygen consumption and carbohydrate oxidation after training during rest and exercise conditions were significantly increased in the antioxidant group. A positive correlation was observed between fat oxidation during exercise and maximum workload after training. The magnitude of decrease in serum insulin level after training was higher in the antioxidant group as compared to the control group (47).

Overall, the evidence derived from in vivo studies suggested a beneficial effect of astaxanthin in preventing muscle degeneration. In humans, the effects of astaxanthin alone or in combination with other antioxidants on muscle health were heterogenous, as both positive and negligible effects were reported.

Understanding of the biological mechanisms underlying the decline in muscle strength and mass is of substantial importance in the search for potential therapeutic agents to prevent sarcopenia. The widely accepted mechanisms involved in muscle atrophy leading to pathogenesis of sarcopenia include induction of oxidative stress, impaired mitochondrial dynamics and functions, negative protein turnover (defined as a disproportionate decrease in muscle protein synthesis and/or an increase in muscle protein breakdown) as well as regression of the capillary network in skeletal muscle (39).

Oxidative stress exerts dual actions on skeletal muscle, whereby a low level of oxidative stress is beneficial while excessive oxidative stress is detrimental (48). Oxidative stress is closely associated with sarcopenia, which is largely attributed to the excessive yield of reactive oxygen and nitrogen species (RONS) during ageing, high-intensity exercise and disuse atrophy (49). An increase in ROS level inflicts direct alteration or damage on important macromolecules, such as lipids, proteins and nucleic acids, contributing to the loss of muscle mass and strength (50). The anti-oxidative properties of astaxanthin have been widely demonstrated by researchers, evidenced by reduction in various lipid peroxidation by-products, oxidative stress biomarkers and markers of muscle damage (51). An earlier animal study demonstrated that astaxanthin attenuated exercise-induced skeletal and cardiac muscle damage in 7-week-old female C57BL/6 mice. The animals were randomly assigned to three groups: Rested controls, intense exercise and intense exercise supplemented with dietary astaxanthin (0.02% w/w). Exercise acclimation (running on a motor-driven treadmill with running intensity increased from 5 to 28 m/min) performed for 10 min/day three times per week for three weeks. At the end of the study, the exercise groups ran on a treadmill at 28 m/min until exhaustion. The data from this study showed that increases in 4-hydroxy-2-nonenal (4-HNE)-modified protein, 8-hydroxy-2'-deoxyguanosine (8-OHdG), plasma CK activity and myeloperoxidase (MPO) activity in the gastrocnemius and heart caused by exercise were attenuated by astaxanthin (52). Astaxanthin treatment was effective in lowering the concentrations of malondialdehyde (MDA) or TBARS, ROS and carbonylated protein in various animal models (28-32,38,39,41,53).

The complex endogenous antioxidant defence system, consisting of key antioxidant enzymes such as glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT), plays a crucial role in neutralizing damaging free radical species (54). High doses of astaxanthin (15 or 30 mg/kg) were shown to be effective in suppressing the levels of GPx, CAT and CK and raising SOD activity in plasma and muscle of mice after moderate-intensity swimming training (53). Another group of researchers pinpointed the reduction in SOD-1 expression in animals with muscle atrophy induced by hindlimb unloading treated with astaxanthin alone (30) or in combination with other interventions such as intermittent loading (31) or electrical stimulation (32). In line with these studies, a lowered SOD-1 level was also detected in two other studies using animals subjected to hindlimb immobilization-induced muscle atrophy (38,39). Astaxanthin supplementation also increased antioxidant capacity in the plasma, indicated by higher Trolox-equivalent antioxidant capacity (TEAC) levels and ferric-reducing activity of plasma (FRAP) capacity relative to the control animals (28).

At the molecular level, the signalling pathway involved in normalizing the disrupted balance between pro-oxidant and antioxidant levels is that of the nuclear factor erythroid 2-related factor 2 (Nrf2) (55). In the resting condition, Nrf2 assumes an inactive state by binding to Kelch-like ECH-associated protein 1 (Keap1) to cause its ubiquitination and degradation (56). Oxidative stress causes a conformational change in Keap1 by interfering in the interaction between Nrf2 and Keap1. Free Nrf2 is subsequently released, translocated into the nucleus and bound to antioxidant responsive elements (ARE) to allow transcription of genes that encode for detoxifying or antioxidant enzymes (56). The transcription of Nrf2 and Nrf2-dependent enzymes in the mouse heart during moderate-intensity swimming training were downregulated in astaxanthin-treated animals (53). In this context, it appears that either the lack of or excess of ROS and antioxidants elicited important pathological implications in skeletal muscle. An optimal amount of ROS and antioxidants may serve as an important factor in maximizing skeletal muscle performance.

The mitochondrial electron transport chain is the major site of ROS production in skeletal muscle, thus mitochondrial DNA is susceptible to oxidative damage by overwhelming ROS production, affecting mitochondrial homeostasis and function (57). Changes in mitochondrial membrane potential, reduction in mitochondrial energy production capacity, inhibition of mitochondrial oxygen consumption and reduction in mitochondrial biogenesis are common characteristics of mitochondrial dysfunction (58), which are (59). During physical activity, endothelial nitric associated with the development of sarcopenia oxide synthase (eNOS) is upregulated to increase nitric oxide production, which subsequently induces mitochondrial biogenesis and cell glucose uptake in skeletal muscle. Peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α) is a master regulator of mitochondrial biogenesis that regulates the genes involved in cellular energy metabolism (60,61). High levels of PGC-1α are an indicator of improved aerobic metabolism and function of mitochondria (62). Using an exercised mouse model, Liu et al (63) suggested that astaxanthin accelerated lipid utilization in skeletal muscle and reduced intermuscular pH during aerobic exercise through elevation of PGC-1α. Studies conducted by Kanazashi et al (31,32) identified a similar pattern to astaxanthin alone, astaxanthin with intermittent loading and astaxanthin with electrical stimulation retained mitochondrial biogenesis by raising PGC-1α and eNOS expression in the soleus muscle of hindlimb unloaded mice. The total 5'-adenosine monophosphate-activated protein kinase (AMPK) content in skeletal muscle was also significantly augmented in the exercised animals fed with astaxanthin from H. pluvialis than the control group. These findings suggested that astaxanthin enhanced energy production leading to a longer running time during treadmill exercise (27).

Under physiological conditions, the maintenance of skeletal muscle mass depends on the balance between muscle protein synthesis and muscle protein degradation (64). Muscle atrophy occurs when the rate of protein degradation outweighs the rate of protein synthesis (65). The suggested signal transduction involved in muscle protein synthesis and degradation includes the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of ripamycin (mTOR) signalling and Forkhead Box O (FoxO) transcription factor. The activation of PI3K/Akt/mTOR pathway is modulated by the interaction of insulin growth factor-1 (IGF-1) and insulin with their respective tyrosine kinase receptors. The activated PI3K/Akt eventually phosphorylates mTOR and its downstream factor, p70 ribosomal protein S6 kinase (P70S6K) to promote protein synthesis (66,67). The mixture of three antioxidants (astaxanthin, β-carotene and resveratrol) was shown to have greater efficacy than each antioxidant respectively in increasing relative soleus weight. This outcome was mediated through the increased phosphorylation of mTOR and its downstream factor (P70S6K) in male mice with muscle atrophy (29). FoxO transcription factors play a role in the catabolic pathway in skeletal muscle. FoxO is phosphorylated (inhibited) by Akt, thus the genes responsible for muscle atrophy cannot be transcribed (68). In the study performed by Kanazashi et al (32), it was noted that hindlimb unloading induced muscle atrophy in the rats by activating the ubiquitin-proteasome pathway through reduced phosphorylation (activation) of Forkhead box class O 3a (FoxO3a). It is also evident that protein degradation during muscle disuse is associated with activation of the ubiquitin-proteasome proteolytic pathway, resulting in increased ubiquitinated protein expression. Muscle atrophy induced by hindlimb unloading was reversed by the combined intervention of astaxanthin and electrical stimulation via increased phosphorylation (inhibition) of FoxO3a (32). In addition, it has been reported that the induction of oxidative stress stimulated protein degradation by upregulating calpain (a proteolytic enzyme act upstream of the ubiquitin-proteasome proteolytic pathway) (69). It was revealed that dietary astaxanthin intake protected against disuse muscle atrophy in rats, which was partly due to the reduction of oxidative stress, calpain and ubiquitin expression (38).

Another mechanism of action that explains the positive effects of astaxanthin in suppressing disuse skeletal muscle atrophy involves the inhibition of myonuclear apoptosis. Apoptosis of myonuclei contributes to the loss of muscle mass. Previous work by Yoshihara et al (33) indicated that dietary astaxanthin supplementation prevented the increase of apoptotic nuclei in soleus muscle [indicated by decreased number of terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL)-positive nuclei]. Satellite cells (also known as skeletal muscle stem cells) are the precursors of skeletal muscle cells required for muscle mass maintenance and muscle regeneration following muscle atrophy (70). Previous studies have demonstrated the alterations of satellite cell activity and density by muscle catabolic conditions, such as disuse and ageing (71). Indeed, Yoshihara and co-authors (34) also revealed that the protection against disuse muscle atrophy exerted by astaxanthin might be due to the increase in satellite cell numbers.

The capillary number in skeletal muscle is proportionate with muscle loading and activity levels. For instance, exercise and functional overload promote capillary growth (72) whereas unloading and immobilization result in capillary regression (73). The regression of the capillary network during low level muscle loading and activity is often attributed to an increase in oxidative injury (11). Kanazashi et al (30,31) performed two studies to assess the effects of astaxanthin on skeletal muscle capillaries. In these studies, they reported that hindlimb unloading induced an overproduction of ROS, resulting in capillary regression and muscle atrophy in the animals. Upon astaxanthin intervention, the decreases in angiogenic factors [such as vascular endothelial growth factor (VEGF), hypoxia inducible factor-1 alpha (HIF-1α), FMS-like tyrosine kinase 1 (Flt-1), kinase insert domain-containing receptor (KDR), angiopoietin 1 (ANG-1) and tyrosine kinase with Ig and EGF homology domains 2 (Tie-2)] caused by hindlimb unloading were counteracted (30). The subsequent study revealed that hindlimb unloading decreased PGC-1α, VEGF and succinate dehydrogenase (SDH) activity, which contributed to the detrimental effects on morphology and number of capillary networks in rat soleus muscle. Oral astaxanthin administration maintained the capillary network by increasing PGC-1α, VEGF and SDH activity near values of animals with sarcopenia (31).

In the present review, the role of astaxanthin on skeletal muscle was examined in two major conditions: Physical exercise and muscle atrophy. Though the direct beneficial effects of astaxanthin on skeletal muscle were marginal in certain studies, astaxanthin was shown to be a potentially effective agent to enhance skeletal muscle performance and counteract the detrimental effects of skeletal muscle disuse. The mechanisms of action of astaxanthin may be attributed to its potential to prevent oxidative stress, increase energy production in mitochondria, regulate the anabolic (regeneration) and catabolic (proteolysis) processes of skeletal muscle, suppress programmed cell death of the myonucleus and activate associated angiogenic pathways to maximize capillary network (Fig. 1). Among these molecular mechanisms, oxidative stress appears to be the common factor that ultimately causes stepwise escalation to the onset and progression of sarcopenia.

Several limitations of the currently available studies need to be addressed. Firstly, the evidence is largely preliminary and suggestive of the potential of astaxanthin in the management of sarcopenia. Much effort should be paid on further investigations to validate the clinical use of astaxanthin. Secondly, the induction of oxidative stress in skeletal muscle has a direct mechanistic link with chronic state of low-grade inflammation during disuse muscle atrophy (50). Despite exhibiting anti-oxidative properties, astaxanthin has been reported to be useful for improving chronic inflammation (24,74). Therefore, investigation of the anti-inflammatory properties of astaxanthin during exercise or skeletal muscle atrophy may be a beneficial area of research. Thirdly, the test formulation provided in certain studies was a mixture of astaxanthin with other antioxidants. The positive health outcomes of astaxanthin alone could not be concluded as the effects might be derived from other antioxidative agents. As a combination of astaxanthin with other interventions may show greater efficacy than astaxanthin alone in promoting skeletal muscle health and performance astaxanthin may be beneficial when used clinically in conjunction with other interventions, such as exercise, hormonal and nutritional intervention to improve muscle health.