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Astaxanthin as a Medical Food

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Astaxanthin is a red pigment that belongs to the carotenoid family like β-carotene. And it’s found in seafood such as crustaceans: shrimp and crabs and fish: salmon and sea bream. Recently, astaxanthin has been reported to have antioxidant activity up to 100 times more potent than that of vitamin E against lipid peroxidation and about 40 times more potent than that of β-carotene on singlet oxygen quenching. Astaxanthin does not show any pro-oxidant activity and its main sight of action is on/in the cell membrane. Various important benefits to date have suggested for human health such as immunomodulation, anti-stress, anti-inflammation, LDL cholesterol oxidation suppression, enhanced skin health, improved semen quality, attenuating eye fatigue, sport performance and endurance, limiting exercised induced muscle damage, suppressing the development of life-style related diseases such as obesity, atherosclerosis, diabetes, hyperlipidemia and hypertension. Nowadays, the research and demand for natural astaxanthin in human health application are explosively growing worldwide. Especially, the clinicians use the astaxanthin extracted from the microalgae, Haematotoccus pluvialis as an add-on supplementation for the patients who are unsatisfied with the current medications or who can’t receive any medications because of their serious symptom. For example, the treatment enhances their daily activity levels or QOL in heart failure or benign prostatic hypertrophy/lower urinary tract symptom patients Other studies and trials are under way on chronic diseases such as non-alcoholic steatohepatitis, diabetes and CVD. We may call astaxanthin “a medical food” in the near future.Keywords: astaxanthin, medical food, Haematococcus, add-on supplementation
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Functional Foods in Health and Disease 2013; 3(7):254-258 Page 254 of 258
Review Article Open Access
Astaxanthin as a Medical Food
Eiji Yamashita
Department of Research & Development, Medical Nutrition Division, AstaReal Co., Ltd.,
Tokyo, Japan
Corresponding author: Eiji Yamashita, 2-6-3-12F, Shibakoen, Minato-ku, Tokyo 105-0011,
Japan
Submission date: April 28, 2013; Acceptance date: July 3, 2013; Publication date: July 3, 2013
ABSTRACT:
Astaxanthin is a red pigment that belongs to the carotenoid family like β-carotene. And it’s found
in seafood such as crustaceans: shrimp and crabs and fish: salmon and sea bream. Recently,
astaxanthin has been reported to have antioxidant activity up to 100 times more potent than that
of vitamin E against lipid peroxidation and about 40 times more potent than that of β-carotene on
singlet oxygen quenching. Astaxanthin does not show any pro-oxidant activity and its main sight
of action is on/in the cell membrane. Various important benefits to date have suggested for
human health such as immunomodulation, anti-stress, anti-inflammation, LDL cholesterol
oxidation suppression, enhanced skin health, improved semen quality, attenuating eye fatigue,
sport performance and endurance, limiting exercised induced muscle damage, suppressing the
development of life-style related diseases such as obesity, atherosclerosis, diabetes,
hyperlipidemia and hypertension. Nowadays, the research and demand for natural astaxanthin in
human health application are explosively growing worldwide. Especially, the clinicians use the
astaxanthin extracted from the microalgae, Haematotoccus pluvialis, as an add-on
supplementation for the patients who are unsatisfied with the current medications or who can’t
receive any medications because of their serious symptom. For example, the treatment enhances
their daily activity levels or QOL in heart failure or benign prostatic hypertrophy/lower urinary
tract symptom patients. Other studies and trials are under way on chronic diseases such as non-
alcoholic steatohepatitis, diabetes and CVD. We may call astaxanthin “a medical food” in the
near future.
Keywords: astaxanthin, medical food, Haematococcus, add-on supplementation
BACKGROUND:
Astaxanthin is widely and naturally distributed in marine organisms including crustaceans such
as shrimps and crabs and fish such as salmon and sea bream. In fact, it is one of the oldest
carotenoids isolated and identified from lobster, Astacus gammarus [1]. Astaxanthin was first
Functional Foods in Health and Disease 2013; 3(7):254-258 Page 255 of 258
commercially used for pigmentation only in the aquaculture industry. Later in 1991, when the
biological activity of potent antioxidative property was reported [2], astaxanthin as a food
supplement started gaining acceptance. Nowadays, the research and demand for natural
astaxanthin in human health application are explosively growing worldwide. In this article the
underlying basis to astaxanthin’s bioactivity and health promotional effects of natural
astaxanthin extracted from the microalgae, Haematotoccus pluvialis, are reviewed. And the
practical medical applications of natural astaxanthin are disclosed with the cases and reports by
the clinicians using the astaxanthin as an add-on supplementation for the patients who are
unsatisfied with the current medications or who can’t receive any medications because of their
serious symptom.
Uunderlying basis to astaxanthin’s bioactivity: Astaxanthin is a totally unique antioxidant,
because it possesses three novel distinctions at once.
Powerful antioxidant: The inhibitory activity of astaxanthin on the peroxyl radical mediated
lipid peroxidation was more than 100 times greater than that of α-tocopherol in the homogenate
of rat mitochondria [2]. Among twenty seven common hydrophilic and lipophilic antioxidants
such as polyphenols, toco-pherols, carotenoids, ascorbic acid, coenzyme Q10 and α-lipoic acid
astaxanthin showed the strongest singlet oxygen (1O2) quenching activity under the same test
condition of the chemilu-minescence detection system for direct 1O2 counting using the
thermodissociable endoperoxides of 1,4-dimethylnaphthalene as 1O2 generator in DMF : CDCl3
(9 : 1) [3]. Hydroxyl radical scavenging ability of astaxanthin encapsulated in liposomes was
more potent than that of α-tocopherol [4].
Safe antioxidant: Martin divided seventeen investigated carotenoids into three classes ; i)
without significant antioxidative properties, ii) anti- and pro-oxidants and iii) pure anti-oxidants.
Astaxanthin was classified as “pure anti-oxidants” not possessing any pro-oxidative properties
like β-carotene and lycopene [5]. Non-polar carotenoids such as lycopene and β-carotene
disordered the membrane bilayer enriched with polyunsaturated fatty acids and showed a potent
pro-oxidant effect (>85% increase in lipid hydroperoxide (LOOH) levels) while astaxanthin
preserved membrane structure and exhibited significant antioxidant activity (40% decrease in
LOOH levels) [6]. The photostability of the three carotenoids in the human dermal fibroblasts
was astaxanthin > canthaxanthin >> β-carotene. Only astaxantin efficiently abrogated the
apoptotic response to UVA. β-Carotene dose-dependently induced caspase-3 activity following
UVA exposure [7].
Superior position in cell membrane: Astaxanthin traps radicals not only at the conjugated
polyene chain but also in the terminal ring moiety, in which the hydrogen atom at the C3 methine
is suggested to be a radical trapping site. Owing to the equivalent amounts of the hydrophobic
intramolecular hydrogen-bonded ring and intermolecular hydrogen bonding with phospholipid
polar heads, and the interconversion between the two hydrogen bond formations, the terminal
ring of astaxanthin is able to scavenge radicals both at the surface and in the interior of the
phospholipid membrane, although its unsaturated polyene chain trapped radicals only in the
Functional Foods in Health and Disease 2013; 3(7):254-258 Page 256 of 258
membrane [8]. Figure 1 shows astaxanthin’s unique ability to span through the double layer cell
membrane. β-carotene and vitamin C only reside inside and outside the lipid bilayer membrane
respectively. The astaxanthin molecule is exposed both in- and outside of the cell giving better
overall protection.
Figure 1. Superior position in cell membrane. No other antioxidants possess the three unique
characters at once. This should be associated with its potent bioactivity.
Health promotional effects of natural astaxanthin: Numerous studies have shown that
astaxanthin has potential health-promoting effects in the prevention and treatment of various
diseases, such as cancers, chronic inflammatory diseases, metabolic syndrome, diabetes, diabetic
nephropathy, cardiovascular diseases, gastrointestinal diseases, liver diseases, neurodegenerative
diseases, eye diseases, skin diseases, exercise-induced fatigue, male infertility as reviewed by
Yuan [9]. It has been proven in over 65 clinical studies, featured in over 300 peer-reviewed
publications. Figure 2 shows the main benefits for human health. “Eye fatigue relieve” [10],
“skin aging defense” (anti-photoaging) [11] and “muscle resilience” (sports performance
enhancement) [12, 13] have been most clinically substantiated.
Functional Foods in Health and Disease 2013; 3(7):254-258 Page 257 of 258
©AstraReal 2012
Figure 2. Health promotional effects of astaxanthin
Practical medical applications of natural astaxanthin: Mostly two soft gel capsules of the
dietary supplement containing 12 mg of AstaREAL® astaxanthin extracted from the microalgae,
Haematotoccus pluvialis were used by the clinicians. Add-on supplementations of AstaREAL®
astaxanthin dramatically exhibited improvements in the patients who were unsatisfied with the
Functional Foods in Health and Disease 2013; 3(7):254-258 Page 258 of 258
current medications or who couldn’t receive any medications because of their serious symptom.
There were the cases that the administration improved the cardiac function in the heart failure
patients who is difficult to control with drug therapy and in the patients whose activity levels
were reduced because of chronic heart failure resulting in enhancing their daily activity levels
and QOL. The add-on effects of astaxanthin for treatment of benign prostatic hypertrophy/lower
urinary tract symptom (BPH/LUTS) were reported as an open-label preliminary study. A total of
thirty patients who had been treated with a1-blockers for more than 12 weeks and still had LUTS
intook the astaxanthin for eight weeks. The subjective symptoms and objective voiding
parameters were improved including QOL. Other studies and trials are under way on chronic
diseases such as non-alcoholic steatohepatitis, diabetes and CVD as well as infertility, atopic
dermatitis and androgenetic alopecia.
CONCLUSION:
A practical medical application of astaxanthin from Haematococcus will expand into medical
institution worldwide not only into the consumer space. We may call astaxanthin “a medical
food” at the moment.
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... And that the reason for the low level of ALT enzyme in the astaxanthin addition treatments may be due to the effective role in enhancing the activity of antioxidants and the possession of astaxanthin to the polyene chain, which is a double bond system that is responsible for the activity of antioxidants by quenching the oxygen atom and getting rid of free radicals to end the oxidation reactions. Thus, the structure of the cell membrane is preserved by extending through the cell membrane (the double layer), preventing oxidation and preserving the manufacturing function of the liver [34,49]. The reason for the superiority of the glutathione peroxidase enzyme in the treatments of adding astaxanthin is due to the positive role in improving the balancing of antioxidant status by enhancing the role of antioxidants in the cell [50]. ...
... As for the significant improvement in the level of HSP 70 in the treatments of adding astaxanthin, it may be due to the effectiveness of astaxanthin, which enhances antioxidants in the body of broiler chickens, by increasing the activity of antioxidant enzymes that have an effect in resisting oxidation and eliminating free radicals, and thus have great importance in protecting cells, proteins and nucleic acids. DNA from oxidation caused by free radicals, thus protecting proteins from oxidation and damage [49,51]. ...
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From February 15, 2022, until March 22, 2022, researchers from the Al-Anwar Poultry Company in Babil Governorate carried out the experiment on their areas to examine the effect of adding annatto seed powder (Bixa orellana) and astaxanthin to the diet on physiological traits of broiler, using 225 unsexed one-day-old Ross-308 chickens, Chickens were randomly assigned to one of 15 cages containing one of five treatments (totaling 45 birds in all), with three replicates of 15 birds in each cage. Here’s how the experiment goes down: T1 control treatment / standard diet without addition, T2 addition powder annatto seeds (0.5 g / kg feed), T3 add powder annatto seeds (1 g / kg feed), T4 addition astaxanthin (50 mg / kg feed), T5 addition astaxanthin (100 mg / kg feed), the results showed in terms of blood cellular characteristics in relation to the number of red blood cells, we note a significant superiority (p ≤ 0.05) for the treatment T3, while the number of white blood cells improved significantly (p ≤ 0.05) for the two treatments T2 and T4, and with regard to hematocrit The blood (pcv) was significantly superior (p≤ 0.05) for the two treatments T1 and T3, as for hemoglobin trait the T1 treatment was significantly (p≤ 0.05), and the H/L ratio was significantly improved (p≤ 0.05) for the T2 treatment. with regard to blood biochemical characteristics for glucose we note a significant improvement (p≤ 0.05) for T2 treatment, as for the total protein we see a highly significant superiority (p≤ 0.01) for the treatments T2, T4 and T5, and in the form of albumin we notice a significant superiority (p≤ 0.05) for the treatment T5, and in the of globulin we notice a significant superiority (p≤ 0.05) for the two treatments T2 and T4, as for uric acid we see a significant improvement (p ≤ 0.05) for the two treatments T2 and T5. with regard to protein lipids in relation to cholesterol we see a significant improvement (p≤ 0.05) for treatments T3 and T5, and for triglycerides it improved significantly (p≤ 0.05) for treatment T2, and for high-density lipoproteins (HDL) we notice a significant superiority (p≤ 0.05) for treatment T2, and for low-density lipoproteins (LDL) we see an improvement Significant (p ≤ 0.05) for T5 treatment, and very low density lipoproteins (VLDL) improved significantly (p ≤ 0.05) for T2 treatment. As for the indicators of oxidative stress in the blood, we see a significant improvement (p≤ 0.05) for the (AST) enzyme for T3 treatment, and for the (ALT) enzyme we notice a significant improvement (p≤ 0.05) for the T4 treatment, while for the (GPX) enzyme we see a highly significant superiority (p≤ 0.01) for the T2 and T4 treatments, and for the Heat shock protein (HSP 70) We notice a significant improvement (p ≤ 0.05) for the two treatments T3 and T4.
... Whereas, β-carotene and vitamin C only reside inside and outside the lipid bilayer membrane, respectively. Thus, AST can take a transmembrane alignment in biological membranes, helping to maintain membrane structure and decrease membrane fluidity, and acting as an antioxidant that provides better overall protection (Yamashita 2013;Park et al. 2010;Mcnulty et al. 2007;Goto et al. 2001). The antioxidant activities of AST are believed to have a key role in several other properties such as protection against UV-light photooxidation, inflammation, cancer, ulcers, aging, and age-related diseases, or the promotion of the immune response, liver function and heart, and eye health (Sheikhzadeh et al. 2011). ...
... Superior position of astaxanthin in cell membrane(Yamashita 2013) ...
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... Conjugated double bonds at the center give red color to this compound and act as strong antioxidants. With hydrophilic and lipophilic characteristics, astaxanthin can easily cross the cell membrane without compromising its structure or components, providing an antioxidant potential at both the inner and outer sides of the tissue ( Figure 1(A)) [2,4,5]. That's why astaxanthin has potent antioxidant activity as compared to other antioxidants, such as Vitamin E, tea polyphenols, α-tocopherol, vitamin C, grape seed, and carotenoids, including β-carotene, zeaxanthin, canthaxanthin, and lutein [1,6,7]. ...
... only astaxanthin can link both the outside and inside of the cell membrane. the figure is drawn based on the idea from yamashita [2]. (B) H. pluvialis cell stages during normal growth and astaxanthin production. in the presence of adequate nutrients, green cells keep growing and dividing. ...
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... The carotenoid astaxanthin (Ax), a potent herbal antioxidant, known as 3,30-dihydroxy-β,β-carotene-4,40-dione, has enormous profitable usages in the medicinal sectors and it has been widely used in the food and medical fields [1,2]. Hydrocarbon carotenoids like β-carotene and oxygenreplaced carotenoids (also known as "xanthophylls," like astaxanthin) make up the family of carotenoids with a deep red, yellow, or orange color [3]. ...
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... The position in cell membrane can be seen in figure 3, the terminal ring is able to scavenge radicals at the surface and in the interior of phospholipids membrane. Its membrane insertion is due to its linear molecular appearance and extends across the entire width of the lipid membrane [199,200]. It is a red pigment found naturally in shrimp, crab, and salmon, is insoluble in water but soluble in most organic solvents. ...
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Carotenoids are used for systemic photoprotection in humans. Regarding mechanisms underlying photoprotective effects of carotenoids, here we compared the modulation of UVA-related injury by carotenoids. Human dermal fibroblasts (HDF) were exposed to moderate doses of UVA, which stimulated apoptosis, increased levels of reactive oxygen species and thiobarbituric acid reactive substances, decreased antioxidant enzymes activities, promoted membrane perturbation, and induced the expression of heme oxygenase-1 (HO-1). The carotenoids astaxanthin (AX), canthaxanthin (CX) and beta-carotene (betaC) were delivered to HDF 24 h before exposure to UVA. Astaxanthin exhibited a pronounced photoprotective effect and counteracted all of the above-mentioned UVA-induced alterations to a significant extent. beta-Carotene only partially prevented the UVA-induced decline of catalase and superoxide dismutase activities, but it increased membrane damage and stimulated HO-1 expression. Moreover, betaC dose-dependently induced caspase-3 activity following UVA exposure. In contrast, CX had no effect on oxidative damage, except for HO-1 expression, which was augmented. Uptake of AX by fibroblasts was higher than that of the other two carotenoids. The photostability of the three compounds in fibroblasts was AX > CX > betaC. The data indicate that the oxo-carotenoid AX has a superior preventive effect towards photo-oxidative changes in cell culture.
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Astaxanthin is a naturally occurring carotenoid in a wide variety of living organisms such as salmon, shrimp, crab, and red snapper. Approximately 90% of the astaxanthin in krill is found in the eye. Asthenopia, or eye fatigue, is an ophthalmological condition with nonspecific symptoms such as eye pain, eye strain, blurred vision, headache, and shoulder stiffness. Symptoms often occur after reading, computer work, or other activities that involve visual display terminals (VDT). More recently, the advances of information technology (IT), software, and electronics have led to the widespread and habitual use of VDT resulting in higher visual fatigue complains and more sufferers. There is, however, no effective therapeutic approach to date. Eye fatigue is usually caused by straining the ciliary body, the eye muscle responsible for accommodation. We previously reported a randomized double-blind placebo controlled study using VDT workers (n=25 treated vs. 23 placebo). 6mg/day astaxanthin supplementation for 4-weeks significantly improved eye fatigue measuring ocular accommodation by the objective instrument and subjective individual assessment. Here we report further 4 clinical studies with the different measurements and an animal study. The same source of astaxanthin, extract derived from the microalgae Haematococcus pluvialis, was used for all of the studies. The first clinical study was performed under randomized double-blind placebo controlled cross-over conditions using 10 healthy subjects. After a 20-minute near visual task, accommodation contraction and relaxation times were extended in both the astaxanthin and placebo groups. However, accommodation relaxation time in the placebo was significantly longer than in the astaxanthin group, and accommodative contraction and relaxation times after a 10-minute rest in the placebo were also significantly longer those in the astaxanthin group. In the second study, the effects of astaxanthin on accommodative recovery derived from a rest after VDT work were studied using 10 healthy volunteers. 6mg/day astaxanthin supplementation for 2-weeks led to a significant relief in accommodative fatigue induced by 30-minutes of IT work (Nintendo Game Boy). In the third study, 22 middle-aged and elder subjects (mean age: 53.9 years) with complaints of eye strain received 6mg/day astaxanthin. Results showed that the pupillary constriction ratio at week 4 was significantly increased compared to that at week 0. The forth clinical study, using 10 healthy subjects, was performed to investigate the effects of visual fatigue on reaction times. Visual fatigue significantly increases reaction time; however 6 mg/day astaxanthin supplementation for 4-weeks was shown to significantly decrease reaction time. We also investigated the intraocular pharmacokinetics of astaxanthin in an albino rabbit. After 100mg/kg astaxanthin administration in a single dose, astaxanthin was detected in the ciliary body as well as the serum at Tmax of 24h and 9h and Cmax of 79.3ng/g and 61.3ng/ml, respectively. Based on the studies it is suggested that astaxanthin supplementation might be a practical and beneficial approach for eye fatigue relief.
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Astaxanthin (Asx) is known to be a potent quencher of singlet oxygen and an efficient scavenger of superoxide anion. Therefore, Asx would be expected to be a useful antioxidant for the prevention of oxidative stress, a causative factor in severe diseases such as ischemic reperfusion injury. However, it is still unclear whether Asx has scavenging capability against the most potent reactive oxygen species (ROS), hydroxyl radical, because the hydrophobicity of Asx prevents analysis of hydroxyl radical scavenging ability in aqueous solution. In this study, to solve this problem, liposomes containing Asx (Asx-lipo), which could be dispersed in water, were prepared, and the scavenging ability of Asx-lipo for the hydroxyl radical was examined. The liposomal formulation enabled encapsulation of a high concentration of Asx. Asx-lipo gave a dose-dependent reduction of chemiluminescence intensity induced by hydroxyl radical in aqueous solution. Hydroxyl radical scavenging of Asx was more potent than α-tocopherol. The absorbance of Asx in the liposome decreased after reduction of hydroxyl radicals, indicating the direct hydroxyl radical scavenging by Asx. Moreover, Asx-lipo prevented hydroxyl radical-induced cytotoxicity in cultured NIH-3T3 cells. In conclusion, Asx has potent scavenging capability against hydroxyl radicals in aqueous solution, and this paper is the first report regarding hydroxyl radial scavenging by Asx.
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When oxygenic photosynthesis evolved, one of the key functions of carotenoids was to protect aerobic photosynthetic organisms against destruction by photodynamic sensitization. Aerobic photosynthesis would not exist without the coevolution of carotenoids alongside the chlorophylls. As carotenoids are abundant in nature, in many fruits and vegetables, they are able to react with excited states of appropriate energy and quench them, and they can react with free radicals according to their reactivity, redox potentials, and XÐH bond energies. This report concerns the bimolecular reactions of carotenoids with oxygen species, such as 3 O 2 , 1 O 2 , H , HO , À 2 , etc.
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Two human clinical studies were performed. One was an open-label non-controlled study involving 30 healthy female subjects for 8 weeks. Significant improvements were observed by combining 6 mg per day oral supplementation and 2 ml (78.9 μM solution) per day topical application of astaxanthin. Astaxanthin derived from the microalgae, Haematococcus pluvialis showed improvements in skin wrinkle (crow's feet at week-8), age spot size (cheek at week-8), elasticity (crow's feet at week-8), skin texture (cheek at week-4), moisture content of corneocyte layer (cheek in 10 dry skin subjects at week-8) and corneocyte condition (cheek at week-8). It may suggest that astaxanthin derived from H. pluvialis can improve skin condition in all layers such as corneocyte layer, epidermis, basal layer and dermis by combining oral supplementation and topical treatment. Another was a randomized double-blind placebo controlled study involving 36 healthy male subjects for 6 weeks. Crow's feet wrinkle and elasticity; and transepidermal water loss (TEWL) were improved after 6 mg of astaxanthin (the same as former study) daily supplementation. Moisture content and sebum oil level at the cheek zone showed strong tendencies for improvement. These results suggest that astaxanthin derived from Haematococcus pluvialis may improve the skin condition in not only in women but also in men.
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The ketocarotenoid astaxanthin can be found in the microalgae Haematococcus pluvialis, Chlorella zofingiensis, and Chlorococcum sp., and the red yeast Phaffia rhodozyma. The microalga H. pluvialis has the highest capacity to accumulate astaxanthin up to 4-5% of cell dry weight. Astaxanthin has been attributed with extraordinary potential for protecting the organism against a wide range of diseases, and has considerable potential and promising applications in human health. Numerous studies have shown that astaxanthin has potential health-promoting effects in the prevention and treatment of various diseases, such as cancers, chronic inflammatory diseases, metabolic syndrome, diabetes, diabetic nephropathy, cardiovascular diseases, gastrointestinal diseases, liver diseases, neurodegenerative diseases, eye diseases, skin diseases, exercise-induced fatigue, male infertility, and HgCl₂-induced acute renal failure. In this article, the currently available scientific literature regarding the most significant activities of astaxanthin is reviewed.