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Review
. 2023 Sep 28;21(10):514.
doi: 10.3390/md21100514.

Astaxanthin: Past, Present, and Future

Yasuhiro Nishida  1 , Pernilla Christina Berg  2 , Behnaz Shakersain  2 , Karen Hecht  3 , Akiko Takikawa  4 , Ruohan Tao  5 , Yumeka Kakuta  5 , Chiasa Uragami  5 , Hideki Hashimoto  5 , Norihiko Misawa  6 , Takashi Maoka  7
Affiliations
Review

Astaxanthin: Past, Present, and Future

Yasuhiro Nishida et al. Mar Drugs. .

Abstract

Astaxanthin (AX), a lipid-soluble pigment belonging to the xanthophyll carotenoids family, has recently garnered significant attention due to its unique physical properties, biochemical attributes, and physiological effects. Originally recognized primarily for its role in imparting the characteristic red-pink color to various organisms, AX is currently experiencing a surge in interest and research. The growing body of literature in this field predominantly focuses on AXs distinctive bioactivities and properties. However, the potential of algae-derived AX as a solution to various global environmental and societal challenges that threaten life on our planet has not received extensive attention. Furthermore, the historical context and the role of AX in nature, as well as its significance in diverse cultures and traditional health practices, have not been comprehensively explored in previous works. This review article embarks on a comprehensive journey through the history leading up to the present, offering insights into the discovery of AX, its chemical and physical attributes, distribution in organisms, and biosynthesis. Additionally, it delves into the intricate realm of health benefits, biofunctional characteristics, and the current market status of AX. By encompassing these multifaceted aspects, this review aims to provide readers with a more profound understanding and a robust foundation for future scientific endeavors directed at addressing societal needs for sustainable nutritional and medicinal solutions. An updated summary of AXs health benefits, its present market status, and potential future applications are also included for a well-rounded perspective.

Keywords: SDGs; anti-aging; astaxanthin; commercial production; microalgae; mitochondria; slow-aging.

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Conflict of interest statement

Y.N. is employed by Fuji Chemical Industries, Co., Ltd. P.B. and B.S. are employed by AstaReal AB. K.H. is employed by AstaReal, Inc. All other authors declare that there is no duality of interest associated with this manuscript.

Figures

Figure 9
Figure 9
Life cycle of Haematococcus algae. (A) Three different cell morphologies of a typical Haematococcus algae. (B) Life cycle: When old cultures are transplanted into fresh medium, coccoid palmelloid cells undergo cell division to form flagellated cells within the mother cell wall. After germination, flagellated cells settle and form palmelloid cells. Environmental stress such as strong light, nutrient depletion, and/or high salinity accelerates the accumulation of astaxanthin during encystment. This figure was reproduced with some additional information, citing ref [247] under the terms of the Creative Commons Attribution License.
Figure 1
Figure 1
Number of scientific papers on astaxanthin (AX) by the end of 2022. Number of articles in PubMed (https://pubmed.ncbi.nlm.nih.gov/, accessed on 30 June 2023) by year. The keyword query “astaxanthin” was used to search the PubMed database. Note that “clinical trial” and “review” articles were selected as article type tags on PubMed, resulting in differences from the actual number of clinical reports shown in Section 3.3.1.
Figure 2
Figure 2
Astaxanthin; structure, optical isomers and major geometric isomers.
Figure 3
Figure 3
Oak Ridge Thermal Ellipsoid Program (ORTEP) diagram of a single molecule and the crystal structure obtained from a crystalline sample of all-trans astaxanthin. This figure was prepared based on reference [18].
Figure 4
Figure 4
Predicted representative forms of astaxanthin aggregates in hydrated polar solvents. Reproduced from Ref. [74] with permission from the Royal Society of Chemistry.
Figure 5
Figure 5
Steady-state absorption spectra of astaxanthin (AX) in acetone when different amounts of FeCl3 solutions (1 mM acetone solution) were added. According to the addition of the FeCl3 solution, the intensity of S0 → S2 absorption of AX around 500 nm decreases, and the new absorption bands appear in the 600–950 nm spectral region (see inset of Figure 5). With the small amount of FeCl3 solution added, the absorption band that is associable to the radical cation of AX appears to peak around 850 nm. With more addition of the FeCl3 solution, the radical cation of AX transforms to dication, peaking around 700 nm. The absorption band below 400 nm is due to the absorption of FeCl3.
Figure 6
Figure 6
The steady-state resonance Raman spectrum of astaxanthin (AX) in acetone recorded with 532 nm excitation laser light at room temperature (solid red line in the left panel) and the resonance Raman spectra of radical species of AX recorded with 808 nm excitation laser light at room temperature (solid red line in the right panel). The results of DFT calculations of the ground (S0) species, radical cation, and dication of AX are also shown in each panel (solid black lines).
Figure 7
Figure 7
Comparison of the bond lengths of the ground (S0) state, radical cation, and dication of astaxanthin predicted theoretically by DFT calculations.
Figure 8
Figure 8
Biosynthetic pathway of astaxanthin from β-carotene with bacterial enzymes. β-Carotene (β-carotenoid) 3,3′-hydroxylase and 4,4′-ketolase are shown with blue and orange letters, respectively. In this figure, the maximal levels of catalytic activities are shown concerning CrtR and CrtO. Generally, the catalytic activity from adonixanthin to astaxanthin is weak, even with CrtW. This pathway is based on bacterial enzymes. However, the functions of green algal BHY and BKT are the same as those of CrtZ and CrtW, respectively.
Figure 10
Figure 10
Biosynthetic pathway of carotenoids in the leaves of higher plants. Plant-type enzymes are shown with green letters, while bacterial enzymes and fungal enzymes that can catalyze in this pathway are written in pink and red, respectively.
Figure 11
Figure 11
Conversion routes from β-ring to 3-hydroxy-4-keto-β-ring in AX-biosynthesizing organisms. ASY, also called CrtS, from Xanthophyllomyces dendrorhous; CrtW and CrtZ, from bacteria; BKT and BHY, from green algae; CBFD and HBFD, from Adonis aestivalis.
Figure 12
Figure 12
Cell morphology of Haematococcus algae at each stage. Transmission electron micrographs of (A) a green palmelloid cell, (B) an intermediate palmelloid cell, and (C) a mature aplanospore of Haematococcus algae during encystoment. In green palmellod cells, the cell wall is surrounded by an extracellular matrix (arrowheads). Arrows indicate AX granules. Cut-away image of 3D TEM images of whole cell of a green palemellod (D) and a cyst cell (E). This figure was adapted from the ref. [247,250] under the terms of the Creative Commons Attribution License. C, chloroplast; CW, cell wall; N, nucleus; OD, oil droplet; SC, starch capsule; SG, starch grain; P, pyrenoid. Scale bars: 5 µm.
Figure 13
Figure 13
Pathways and localization of astaxanthin biosynthesis and esterification in Haematococcus algae. ACCase, acetyl CoA carboxylase; DGAT, diacylglycerol acyltransferase; FAS, fatty acid synthase; FA, fatty acid; SAD, stearoyl acyl carrier protein desaturase; TAG, triacylglycerol. Other enzyme abbreviations are listed in the main text. This figure was reproduced from ref. [410] with the permission of the publisher.
Figure 14
Figure 14
Relationship between food chain and metabolic conversion to astaxanthin in animals [280].
Figure 15
Figure 15
Industrial synthesis route for astaxanthin.
Figure 16
Figure 16
Summary of health benefits of astaxanthin in humans The inner circle summarizes the health benefits with substantial clinical evidence. The outer circle includes the areas with preliminary but promising pre-clinical and clinical data, suggesting potential future directions for clinical research on the beneficial effects of natural astaxanthin. References are discussed in more detail in Section 3, Table 4, and Section 5.
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