Abstract
Astaxanthin (AST) is a potent carotenoid renowned for its exceptional antioxidant properties, which has attracted considerable scientific interest due to its broad spectrum of health benefits. This review comprehensively evaluates the therapeutic potential of AST in counteracting age-related decline, oxidative stress, and immune dysfunction, while also examining its beneficial effects on gut and skin health. Current evidence demonstrates that AST effectively mitigates oxidative stress and supports cellular health and longevity by neutralizing free radicals and upregulating endogenous antioxidant systems. In addition, AST modulates immune responses under conditions of immune dysfunction, thereby enhancing resilience against inflammatory disorders and infections. Emerging studies further indicate that AST promotes gut health by improving intestinal barrier integrity and maintaining a balanced gut microbiota, both of which are essential for systemic well-being. Moreover, its capacity to enhance skin elasticity and protect against ultraviolet-induced damage underscores its promising applications in cosmetic and dermatological products. This review highlights the urgent need for additional well-designed clinical trials to fully elucidate the underlying mechanisms, optimal bioavailability, dosage regimens, and long-term safety of AST. By integrating findings across multiple research domains, the present work provides a concise yet comprehensive overview of AST as a promising nutraceutical for promoting health, healthy aging, and the management of chronic diseases.
Introduction
Astaxanthin (AST) is a lipid-soluble, red-orange oxycarotenoid pigment [1]. It serves as a key colorant in aquaculture feeds for salmonids and crustaceans. As a xanthophyll carotenoid, AST belongs to the broader carotenoid family, which also comprises lutein, canthaxanthin, β-cryptoxanthin, and zeaxanthin [2]. Its natural sources are diverse and include yeasts, algae, and various marine animals (Table 1) [3]. Commercially, AST is primarily obtained through extraction from the microorganisms Blakeslea trispora, Phaffia rhodozyma, and Haematococcus pluvialis, or via chemical synthesis [4]. The green microalga H. pluvialis accumulates AST as a protective response to environmental stressors, including high irradiation, nutrient starvation, elevated salinity, intense light, and extreme temperatures [5]. Consequently, AST is present in krill, shrimp, salmon, crayfish, and trout, which acquire the pigment by consuming AST-rich algae or other marine organisms [6]. Although humans cannot synthesize AST endogenously, it is readily obtained through the diet, particularly from seafood [7]. Naturally occurring AST exists in multiple forms, including stereoisomers, geometric isomers, and both free and esterified configurations. Chemically, AST (3,3′-dihydroxy-4,4′-diketo-β,β′-carotene; molecular formula C40H52O4; molar mass 596.84 g/mol) consists of 40 carbon atoms arranged as two oxygenated β-ionone rings connected by a central polyene chain [8,9,10]. Because of its high susceptibility to oxidation and inherent chemical instability, AST in nature is predominantly found esterified with one or two fatty acids (forming mono- or di-esters) or bound to proteins, as observed in lobster exoskeletons and salmon muscle [11]. Synthetic AST, in contrast, may occur in chiral ((3S,3′S) or (3R,3′R)) or meso (3R,3′S) forms (Figure 1), with the chiral stereoisomers being the most common. Additionally, the polyene chain can adopt trans or cis configurations; however, owing to the thermodynamic instability of the cis isomers, the trans configuration predominates in both natural and synthetic AST [12].
Figure 1. Chemical structures of AST: (A) 3S,3′S-AST; (B) 3R,3′S-AST; (C) 3R,3′R-AST.
1.1. Astaxanthin Regulatory Landscape
The regulatory landscape for AST differs internationally and is largely contingent upon its origin (natural vs. synthetic) and purpose of use. In the United States, the regulation of supplements and food additives is managed by frameworks such as the Dietary Supplement Health and Education Act (DSHEA) and the Federal Food, Drug, and Cosmetic Act. Natural AST sourced from Haematococcus pluvialis has been granted Generally Recognized As Safe (GRAS) status by the U.S. Food and Drug Administration (FDA) for designated uses in foods and dietary supplements. The permissible levels of AST in food supplements were up to 8 mg per day, and the acceptable daily consumption for adults varied from 0.034 to 0.2 mg AST/kg body weight [13]. This classification indicates that certified professionals consider it safe for its intended usage conditions. Microalgae-derived AST serves as a pigment in aquaculture feeds and functions as a nutraceutical [14]. Synthetic AST, although extensively utilized in the aquaculture sector for its economic advantages, encounters heightened regulatory oversight about human intake [15,16]. It is widely recognized as a feed supplement for animals, especially for enhancing pigmentation in aquaculture species such as salmon, trout, and crustaceans [17]. Nonetheless, its endorsement for direct human supplementation necessitates individual assessment and lacks the universal acknowledgment afforded to natural AST.
1.2. Safety of Astaxanthin
The long-term safety profile and regulatory status of AST significantly differ between its natural and synthetic variants. Natural AST, especially derived from Haematococcus pluvialis, has a longstanding record of safe human consumption exceeding two decades, and is classified as GRAS in the United States, along with receiving approval from the European Food Safety Authority (EFSA) [18]. Synthetic AST, in contrast, lacks equivalent long-term safety data for humans and is typically not authorized for dietary supplements in significant jurisdictions. Its principal application is confined to animal feed, specifically in aquaculture, where it is utilized to augment the pigmentation of cultivated aquatic species such as salmon, shrimp, and rainbow trout [15,19]. The rigorous regulatory oversight for compounds purporting to treat diseases or those substantially modified from their natural form highlights the significance of a “do not harm” approach. The process of introducing a medicine or supplement to the market necessitates comprehensive testing for identification, purity, potency, and safety, hence ensuring product consistency and reliability. Synthetic technologies provide economical production; nevertheless, apprehensions about possible impurities or hazardous by-products restrict their applicability in human applications [20].
A number of studies and experiments have demonstrated that AST has a good safety record. Safety testing of an AST-enriched extract at 6 or 20 mg daily for 8 weeks and 4 weeks, respectively, in healthy adults revealed no changes in blood chemical, haematological, or blood pressure markers that were clinically important [21]. Likewise, taking 8 mg of AST daily for three months did not result in any gastrointestinal distress or any other adverse effects [22,23]. Patients with age-related macular degeneration who received a daily oral supplement containing 4 mg of AST for a period of 12 months did not notice any adverse reactions or toxicity [24], nor in those with practical dyspepsia who received H. pluvialis AST at 40 mg daily for 4 weeks [25], neither at a dose of 20 mg/day during three weeks in obese adults and overweight [26]. Similarly, in healthy men, there were no detrimental side effects after a single administration of 100 mg AST orally equivalents from its fatty acyl diesters [27] or free AST [28]. For example, rats given large doses (up to 1240 mg/kg/day) orally over a lengthy period of time (90 days) showed no harmful effects [29]. Moreover, the 13-week repeated oral administration of a natural AST-rich extract (ARE) from P. carotinifaciens to rats at dosage levels of 250, 500, and 1000 mg/kg/day did not result in any significant toxicological alterations [30]. Even when compared to the placebo in randomized trials, AST exhibits excellent clinical safety at low (up to 12 mg) or high (up to 100 mg) daily dosages [31]. No significant toxicities have been identified for this organism; consequently, the dry cell biomass has received approval from the US FDA and the European Food Safety Authority (EFSA) for use as a natural colouring agent in salmon and trout aquaculture [32]. For the past decade, this whole cell, AST-rich substance, commercially known as Panaferd®, has been widely utilised in the production of organic salmon and trout for human consumption. The findings suggest that AST supplementation at the specified dosage level is generally safe and well tolerated.
1.3. Astaxanthin Bioavailability
The bioavailability of AST is a crucial determinant of its effectiveness. Natural AST, especially the esterified forms present in Haematococcus pluvialis, typically has superior bioavailability relative to synthetically produced AST [33,34]. The enhanced bioavailability is due to better micellarization and lymphatic absorption of the esterified natural form. Research has demonstrated that natural sources can result in plasma Area Under the Curve (AUC) values in people that are two to three times greater than those of synthetic forms. The limited oral bioavailability of AST, a highly lipophilic molecule, poses a considerable impediment, restricting its extensive use in food and nutritional sectors [33,35,36]. To address this issue, multiple ways are being investigated to improve the bioavailability of AST, such as encapsulating techniques and emulsion systems [36,37]. Stable oil-in-water emulsions stabilized by casein–caffeic acid–glucose ternary conjugates exhibit enhanced resilience to unfavorable gastrointestinal conditions, potentially augmenting AST administration [36]. The chemical structure, transport proteins, food matrix effects, and gut flora all influence the oral bioavailability of AST, demanding further research to enhance its absorption. The debate between natural and synthetic AST is multifaceted, encompassing efficacy, safety, and market preference (Table S1).
AST prevents oxidative damage at the cellular and molecular levels by scavenging radicals, preventing lipid peroxidation, controlling OS-related gene expression, and quenching singlet oxygen [38]. AST enhances immune response and inflammation management and is a biomarker for oxidative damage to deoxyribonucleic acid (DNA) in young, healthy females. However, in circumstances of extreme oxidative stress and in immune compromised patients, antioxidants typically exhibit more significant physiologic regulation [39]. Although it is not meant to be comprehensive, the goal of this chapter is to summarize the well-researched activities and their likely modes of action.
Table 1. Sources of AST from natural and genetically modified organisms.
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Basher, A.A.; Ibrahim, N.A.; Liu, H.-Y.; Basher, N.S.; Essa, M.O.A.; Husien, H.M.; Adam, S.Y.; Cai, D. Exploring the Multifunctional Benefits of Astaxanthin in Aging, Oxidative Stress, Immune Dysfunction, Gut and Skin Health. Antioxidants 2026, 15, 575. https://doi.org/10.3390/antiox15050575
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