Molecular Mechanisms, Endurance Athlete, and Synergistic Therapeutic Effects of Marine-Derived Antioxidant Astaxanthin Supplementation and Exercise in Cancer, Metabolic Diseases, and Healthy Individuals

Abstract

Marine-derived antioxidant astaxanthin (AST), a potent antioxidant carotenoid, has gained significant attention for its potential therapeutic effects in various diseases, including cancer and metabolic disorders. When combined with exercise, which is a well-established intervention for improving health, these two modalities may offer synergistic benefits that extend beyond their individual effects. This review explores the molecular mechanisms underlying the synergistic therapeutic effects of AST and exercise in cancer, metabolic diseases, and healthy individuals. AST exerts its beneficial effects primarily through its ability to reduce oxidative stress, modulate inflammation, and enhance cellular signaling pathways, including those involved in apoptosis, autophagy, and mitochondrial function. It has been shown to suppress tumor growth, improve insulin sensitivity, and protect against the adverse effects of chronic diseases, such as cardiovascular complications and neurodegenerative conditions. Similarly, exercise induces a wide array of molecular adaptations, including the activation of key metabolic pathways, enhancement of mitochondrial biogenesis, and modulation of inflammatory responses. These effects improve metabolic health, reduce cancer risk, and promote overall well-being. The combination of AST supplementation and exercise may provide a more potent therapeutic strategy, targeting multiple molecular pathways simultaneously. This synergy may not only enhance the effectiveness of each intervention but also reduce the side effects commonly associated with pharmacological treatments. This review discussed the current evidence for the synergistic effects of AST and exercise, highlighted the molecular mechanisms involved, and suggested potential clinical applications for these interventions in cancer, metabolic diseases, and healthy populations.

Keywords: astaxanthin; cancer; cognitive function; exercercise; molecular signaling.

FIGURE 1

Mechanistic overview of astaxanthin (AST) supplementation effects on exercise performance, metabolic responses, oxidative stress, and recovery in human studies. Astaxanthin, a potent lipid‐soluble antioxidant, exerts diverse physiological effects relevant to exercise adaptation. It supports enhanced performance by protecting mitochondrial membranes from oxidative damage, promoting efficient oxygen transport, and potentially increasing mitochondrial biogenesis. AST may shift substrate utilization toward greater fat oxidation while lowering lactate accumulation during submaximal exercise, although results vary across studies. It consistently reduces oxidative stress by scavenging free radicals and upregulating endogenous antioxidant systems such as superoxide dismutase and glutathione. Anti‐inflammatory actions—possibly mediated via NF‐κB pathway inhibition—have been observed in longer‐duration interventions. Although AST may aid muscle recovery by reducing delayed‐onset muscle soreness (DOMS), its effect on classical muscle damage biomarkers (e.g., CK, LDH) remains inconclusive. The variability in human trial outcomes highlights the need for standardized protocols regarding AST dosing, duration, and subject training status.

FIGURE 2

Synergistic anticancer mechanisms of astaxanthin (AST) and exercise. This figure illustrates the complementary biological pathways through which AST, a potent natural antioxidant derived from microalgae, and exercise exert anticancer effects. AST reduces oxidative stress, inflammation, and DNA damage by enhancing antioxidant enzyme activity and modulating key signaling pathways such as NF‐κB. Meanwhile, exercise improves immune function, increases mitochondrial biogenesis, and regulates systemic factors like cytokines and myokines. When combined, AST and exercise may act synergistically to enhance cancer cell apoptosis, suppress tumor growth, and improve overall therapeutic outcomes and quality of life. This integrated approach highlights the potential of combining nutritional and lifestyle interventions in cancer prevention and management.

FIGURE 3

Mechanistic summary of astaxanthin's (AST) effects on exercise performance, metabolism, oxidative stress, and recovery in human trials. AST, a marine xanthophyll carotenoid, has demonstrated multifaceted benefits in exercise contexts. It enhances performance potentially through mitochondrial protection, improved oxygen transport, and vascular effects. Metabolic changes, such as increased fat oxidation and reduced lactate accumulation, are inconsistently observed but may relate to AMPK and CPT1 modulation. AST consistently reduces oxidative stress by scavenging reactive oxygen species and boosting endogenous antioxidants like glutathione and SOD. Anti‐inflammatory effects, likely mediated through NF‐κB inhibition, are evident in some long‐duration studies. Although AST may reduce subjective muscle soreness, evidence for its effect on biochemical markers of muscle damage remains mixed. Variability in findings across studies may stem from differences in dosage, duration, training status of participants, and exercise protocols. Overall, AST shows promise as a nutraceutical to support exercise performance and recovery, warranting further mechanistic and clinical exploration.