Abstract
staxanthin, a potent antioxidant found in marine organisms such as microalgae and krill, may offer ergogenic benefits to endurance athletes. Originally used in fish feed, astaxanthin has shown a greater ability to mitigate various reactive oxygen species and maintain the structural integrity of mitochondria compared to other exogenous antioxidants. More recent work has shown that astaxanthin may improve: (1) cycling time trial performance, (2) cardiorespiratory measures such as submaximal heart rate during running or cycling, (3) recovery from delayed-onset muscle soreness, and (4) endogenous antioxidant capacity such as whole blood glutathione within trained populations. In this review, the history of astaxanthin and its chemical structure are first outlined before briefly describing the various adaptations (e.g., mitochondrial biogenesis, enhanced endogenous antioxidant capacity, etc.) which take place specifically at the mitochondrial level as a result of chronic endurance training. The review then concludes with the potential additive effects that astaxanthin may offer in conjunction with endurance training for the endurance athlete and offers some suggested practical recommendations for athletes and coaches interested in supplementing with astaxanthin. Keywords:astaxanthin; sports nutrition; endurance performance; antioxidants; oxidative stress 1. Introduction 1.1. Sports Nutrition—Past and Present Participation in non-professional endurance events continues to increase in popularity among adults in the United States. Regardless of the modality (e.g., cycling, running, or swimming), endurance training offers the participant a host of benefits for cardiometabolic health and cognition. Some of these benefits include a reduction in excess adipose tissue, reductions in
stress 1. Introduction 1.1. Sports Nutrition—Past and Present Participation in non-professional endurance events continues to increase in popularity among adults in the United States. Regardless of the modality (e.g., cycling, running, or swimming), endurance training offers the participant a host of benefits for cardiometabolic health and cognition. Some of these benefits include a reduction in excess adipose tissue, reductions in systemic and chronic low-grade inflammation, improved metabolic flexibility, and a decreased risk of dementia development [1,2]. Interestingly, endurance training and sports nutrition appear to have synergistic and additive effects, as various nutritional strategies also offer protection to cardiometabolic health and can improve performance as well as maximize training adaptations [3]. Although earlier sports nutrition research largely focused on meeting an athlete’s training needs by ensuring sufficient carbohydrates were being consumed during the peri-workout window and an effective hydration plan was in place, today’s research has expanded quite a bit to include nutritional approaches and physiological outcomes that were ignored in these earlier years. Today, sports nutrition now also focuses on optimal recovery strategies, enhancing the immune system and reducing muscle damage following exercise, and periodizing nutrition for the individual rather than a “one size fits all” approach [4]. While coaches and athletes alike place significant attention on meeting the energy demands of their respective sport via manipulation of macronutrients and overall caloric load, a growing body of evidence suggests that athletes of all backgrounds have reported supplementing with some form of dietary supplement that includes micronutrients, polyphenols, and antioxidants, as well as various ergogenic aids [5]. Nutrients2024,16, 1750.
Nutrients2024,16, 1750 2 of 18 1.2. Prevalence of Dietary Supplement Use among Athletes Dietary supplement use is prevalent among athletes, with studies indicating that elite athletes tend to use dietary supplements more frequently than non-elite athletes [6]. Overall, the prevalence of supplement consumption among athletes ranges from approx- imately40–60%, with proteins and multivitamins being the most commonly consumed supplements [5]. Despite the benefits sought by athletes, such as performance enhancement and recovery support, the prevalence of supplement use also raises concerns regarding the potential risks associated with adulterated or mislabeled products. To assist interested readers, the International Society of Sports Nutrition routinely publishes a thorough review aimed at maintaining an updated list of common dietary supplements used in athletics [7]. Still, no single article review can cover the wide range of dietary supplements that exist or provide an extensive discussion surrounding each supplement’s mechanisms of action. New dietary supplements are introduced to the sports nutrition market annually and there- fore, reviews of individual dietary supplements can serve as an educational tool for sports nutritionists, coaches, and athletes for determining the safety and efficacy of individual supplements. Among the various dietary supplements on the market today, exogenous antioxidants appear to be a common addition to an athlete’s ‘supplement stack’ and have garnered support for their potential protective effects against oxidative damage and inflammation following strenuous bouts of exercise [8]. One dietary supplement garnering attention specifically among endurance athletes is astaxanthin (AX), a powerful antioxidant that has demonstrated an ability to specifically target the mitochondria and serve there as a regula- tor of energy metabolism, potentially improving endurance performance [9,10]. However, an individual’s training and competition goals must be considered when deciding to sup- plement with antioxidants. While antioxidant supplements are used among athletes to protect against exercise-induced oxidative damage, several studies have documented that exogenous antioxidants may impair signaling to the stress-activated protein kinases and transcription factors that lead to gene transcription and muscle adaptation [11]. Currently, there are arguments for and against the use of dietary antioxidants among athletic pop- ulations, and consideration of the context is needed to make
among athletes to protect against exercise-induced oxidative damage, several studies have documented that exogenous antioxidants may impair signaling to the stress-activated protein kinases and transcription factors that lead to gene transcription and muscle adaptation [11]. Currently, there are arguments for and against the use of dietary antioxidants among athletic pop- ulations, and consideration of the context is needed to make informed supplementation suggestions/decisions. 1.3. Salmon—Nature’s Ultimate Endurance Athlete Endurance exercise is generally defined as anything lasting longer than 30 min. How- ever, interest has grown among the endurance community in ultra-endurance events (any event lasting longer than 4 h), such as ultramarathons. These events aim to challenge the limits of human physiology and metabolism during prolonged exercise. Ultramarathons, for example, may include athletes covering ~161 km in a 30 h duration [12]. It is also common for the cardiovascular system to experience insult across such demanding physi- cal tasks, including damage to the ventricular valves and elevations in cardiac troponin T [12,13], as well as chronic exposure to reactive oxygen species (ROS) and oxidative stress during the event [14]. While endurance exercise is often cited as a modality for improving metabolic health [15], ultra-endurance exercise may expose the athlete to excessive oxida- tive stress, resulting in an elevated risk of developing cardiovascular disease [14]. Although completing an ultra-endurance event is quite impressive, they pale in comparison to the distances covered by other migratory animals, such as salmon. Salmon are revered as unparalleled endurance athletes due to their extraordinary physiological adaptations and remarkable feats of strength and stamina which can be observed during the migratory “salmon run”. Upon returning to their birthplace to spawn, salmon can travel ~1400 km upstream and against strong downstream rapids and currents. These migrations require sustained physical exertion over prolonged periods, highlighting the salmon’s remarkable aerobic capacity and muscular endurance. Moreover, salmon stop feeding during this migration, suggesting that the majority of their metabolic fuel is coming from endogenous lipid stores. Like humans, animals can also experience oxidative
physical exertion over prolonged periods, highlighting the salmon’s remarkable aerobic capacity and muscular endurance. Moreover, salmon stop feeding during this migration, suggesting that the majority of their metabolic fuel is coming from endogenous lipid stores. Like humans, animals can also experience oxidative
Nutrients2024,16, 1750 3 of 18 stress, and exposure to excessive ROS is known to impair mitochondrial function and lipid metabolism and hamper muscle endurance performance [16]. From an endurance perspec- tive, salmon are an interesting species to study as they are able to complete the ultimate endurance event while still preserving an ability to utilize and oxidize lipids even in the presence of excessive exposure to ROS. This may be explained by the salmon’s high con- centration of AX found in their muscle [17]. The accumulation of AX within phospholipid bilayers is well documented [18], and AX effectively mitigates lipid peroxidation during endurance activity [19]. The powerful antioxidant properties of AX may be a primary determinant in mitigating ROS formation during the salmon run and these observations have led to implementing AX supplementation as one intervention for possibly mitigating oxidative damage following endurance exercise [19]. While the exact mechanisms exerted by AX are not still fully understood, research is currently examining AX as a potential dietary supplement for exercising humans. 1.4. What Is Astaxanthin? Astaxanthin is a red-orange and lipid-soluble keto-carotenoid that belongs to the terpenes class of chemical compounds. First discovered in 1938 [20], AX was originally used extensively as a natural ingredient in aquatic feed before researchers later discovered that AX possessed strong antioxidant properties due to its unique molecular structure [21]. At each end of itsβ-ionone rings, AX contains polar regions and a non-polar middle with 13 conjugated double polyunsaturated bonds (see Figure). Like other xanthophyll carotenoids (e.g., lutein, zeaxanthin), AX bears hydroxyl groups; however, itsβ-ionone rings have hydroxyl groups at the 3,3 ′ -positions and keto groups at the 4,4 ′ -positions. Moreover, its elongated structure allows it to permeate the membranes of a cell, allowing AX to neutralize free radicals and protect cells from oxidative stress within and outside of the cell [22]. Unlike other carotenoids which can exhibit pro-oxidative properties (lycopene and β-carotene), AX is deemed a “pure antioxidant” as it only exhibits antioxidant properties without the ability to convert to a pro-oxidant [23]. While AX can be found in certain fungi, as well
AX to neutralize free radicals and protect cells from oxidative stress within and outside of the cell [22]. Unlike other carotenoids which can exhibit pro-oxidative properties (lycopene and β-carotene), AX is deemed a “pure antioxidant” as it only exhibits antioxidant properties without the ability to convert to a pro-oxidant [23]. While AX can be found in certain fungi, as well as consumed from specific aquatic organisms such as krill, shrimp, and salmon, it is primarily supplemented through a microalgae (Haematococcus pluvialis), allowing a person to achieve the AX range of 4–12 mg/day often implemented in research to obtain potential health and performance benefits [24,25]. After its discovery and approval as a dietary supplement, a series of animal studies followed demonstrating the biological and antioxidative properties of AX [18]. While the mechanisms of action in AX were beginning to be better understood in the 1990s, it was not until the early 2000s that AX started being studied as a potential dietary supplement for enhancing exercise performance in animals [26,27] and humans [28]. However, it was almost a decade later (~2010) that AX demonstrated its potential for enhancing endurance performance when Earnest et al. (2011) showed a clear benefit in a 20 km cycling time trial in comparison to a placebo (PLA) [29]. In the present day, the last ~10 years of AX research have revealed several unique properties of AX that are not observed among other antioxidants. It is also clear now that a primary target following AX supplementation is the mitochondria [10]. This may then explain why null effects have been observed with AX in resistance training [28], but improvements have been found in events such as the 20 kmtime trial [29]. With regard to performance enhancement, it appears that individuals training for endurance events may benefit the most from AX supplementation. While a few well-written reviews on the benefits of AX supplementation and exercise performance exist [9,24], the purpose of this review is to briefly outline the training adaptations that follow from endurance exercise and then detail the role of AX in mitochondrial regulation, specifically as it relates to
individuals training for endurance events may benefit the most from AX supplementation. While a few well-written reviews on the benefits of AX supplementation and exercise performance exist [9,24], the purpose of this review is to briefly outline the training adaptations that follow from endurance exercise and then detail the role of AX in mitochondrial regulation, specifically as it relates to potentially improving endurance performance and enhancing mitochondrial training adaptations in the endurance athlete.
Nutrients2024,16, 1750 4 of 18Nutrients 2024, 16, x FOR PEER REVIEW 4 of 19 Figure 1. Astaxanthin’s structural formula. After its discovery and approval as a dietary supplement, a series of animal studies followed demonstrating the biological and antioxidative properties of AX [18]. While the mechanisms of action in AX were beginning to be better understood in the 1990s, it was not until the early 2000s that AX started being studied as a potential dietary supplement for enhancing exercise performance in animals [26,27] and humans [28]. However, it was almost a decade later (~2010) that AX demonstrated its potential for enhancing endurance performance when Earnest et al. (2011) showed a clear benefit in a 20 km cycling time trial in comparison to a placebo (PLA) [29]. In the present day, the last ~10 years of AX research have revealed several unique properties of AX that are not observed among other antiox- idants. It is also clear now that a primary target following AX supplementation is the mi- tochondria [10]. This may then explain why null effects have been observed with AX in resistance training [28], but improvements have been found in events such as the 20 km time trial [29]. With regard to performance enhancement, it appears that individuals train- ing for endurance events may benefit the most from AX supplementation. While a few well-written reviews on the benefits of AX supplementation and exercise performance ex- ist [9,24], the purpose of this review is to briefly outline the training adaptations that fol- low from endurance exercise and then detail the role of AX in mitochondrial regulation, specifically as it relates to potentially improving endurance performance and enhancing mitochondrial training adaptations in the endurance athlete. 2. Exercise-Induced Hormesis 2.1. Finding the Right Balance Exercise-induced hormesis refers to the phenomenon where low to moderate levels of stress from physical activity, such as endurance exercise, stimulate adaptive responses in the body, leading to improved physiological function and performance [30]. Endurance exercise, characterized by prolonged and repetitive movements, can induce the excessive production of ROS which can potentially overwhelm the mitochondria and cells, resulting
Right Balance Exercise-induced hormesis refers to the phenomenon where low to moderate levels of stress from physical activity, such as endurance exercise, stimulate adaptive responses in the body, leading to improved physiological function and performance [30]. Endurance exercise, characterized by prolonged and repetitive movements, can induce the excessive production of ROS which can potentially overwhelm the mitochondria and cells, resulting in oxidative stress [31]. Oxidative stress is the result of an imbalance in the redox Figure 1.Astaxanthin’s structural formula. 2. Exercise-Induced Hormesis 2.1. Finding the Right Balance Exercise-induced hormesis refers to the phenomenon where low to moderate levels of stress from physical activity, such as endurance exercise, stimulate adaptive responses in the body, leading to improved physiological function and performance [30]. Endurance exercise, characterized by prolonged and repetitive movements, can induce the excessive production of ROS which can potentially overwhelm the mitochondria and cells, resulting in oxidative stress [31]. Oxidative stress is the result of an imbalance in the redox envi- ronment such that the production of ROS overwhelms antioxidant defense mechanisms, resulting in oxidative damage to endogenous biomolecules. It is well accepted that the mitochondria are common sources of ROS and increased strain on the electron transport complex during mitochondrial respiration is likely to lead to oxygen/electron leakage from complexes I and III, leading to ROS formation, specifically the superoxide and hydroxyl radicals, and potentially oxidative stress [31]. Interestingly, stress in general has widely been associated with negative aspects and performance outcomes [32], even though over 100 years ago, work from Yerkes and Dodson demonstrated a U-shaped relationship (i.e., a positive effect) between moderate amounts of physiological arousal (i.e., stress) on physical performance [33]. It is therefore important to clarify that acute exposure to ROS is potentially beneficial, as moderate ROS exposure serves as a trigger to upregulate antioxidant defense mechanisms and initiate signaling cascades for mitochondrial biogenesis [31]. Thus, the same U-shaped relationship between stress and performance can also be applied to redox balance and the hormetic stress response from endurance exercise. In other words, excessive exposure to ROS leads to oxidative stress and chronic low-grade inflammation, while
moderate ROS exposure serves as a trigger to upregulate antioxidant defense mechanisms and initiate signaling cascades for mitochondrial biogenesis [31]. Thus, the same U-shaped relationship between stress and performance can also be applied to redox balance and the hormetic stress response from endurance exercise. In other words, excessive exposure to ROS leads to oxidative stress and chronic low-grade inflammation, while acute/moderate exposure to ROS is beneficial for facilitating favorable mitochondrial adaptations known as mitohormesis [34]. Too Much of a Good Thing: Sickness Prevalence among Endurance Athletes Although acute exposure to low/moderate amounts of ROS and oxidative stress is beneficial for stimulating favorable training adaptations such as mitochondrial biogenesis,
Nutrients2024,16, 1750 5 of 18 excessive ROS exposure observed during intense training periods leading up to competition can overwhelm the mitochondria’s endogenous antioxidant capacity, resulting in impaired immune system function and decreased resistance to infection [35,36]. ROS have been implicated in many aspects of the immune response to pathogens mainly related to innate immunity. Indeed, they have been proposed to be the common determinant of inflam- masome activation (e.g., lymphocyte activation and signaling of various immune-related enzymes such as B- and T-cell receptors), which is critical in the inflammatory process and thus necessary for an efficient immune response. However, repeated and chronic exposure to ROS may also mediate lymphocyte dysfunction and has been identified as a contributing component in various immune-related diseases, such as multiple sclerosis or inflammatory bowel disease [37]. Understanding this relationship between ROS and immune responses is of particular importance to endurance-trained athletes as 9 out of 10 runners report experiencing some type of running-related injury or illness leading into a half or full marathon [38]. These findings are supported by Peters and Bateman, who previ- ously reported a depressed immune system in 150 runners who were identified as having an increased prevalence of upper respiratory tract infection after a ~50 km run [39]. Along with the aforementioned findings, numerous dietary supplement interventions have been examined as potential methods for mitigating oxidative stress in endurance athletes, includ- ing supplementing with various exogenous antioxidants such as vitamins C and E, CoQ 10, and curcumin. While supplementing with exogenous antioxidants has demonstrated a capacity to help combat ROS generation during exercise, it is important to note that ROS do potentially serve a beneficial role depending on the magnitude of accumulation [31]. Moderate amounts of ROS generation, as produced from exercise, can trigger favorable skeletal muscle adaptations and signaling molecules to increase endogenous antioxidant status and drive mitochondrial biogenesis [31,40], while excessive production can be toxic to cellular function. Therefore, an interesting problem is presented to any serious athlete interested in supplementing with exogenous antioxidants. By supplementing with exoge- nous antioxidants, they may potentially enhance recovery and training time by
Description
This review discusses astaxanthin's role in enhancing mitochondrial adaptations in endurance athletes.