What Are the Benefits of Astaxanthin?

Astaxanthin is a keto-carotenoid pigment with a chemical name of 3,3,-dihydroxy-4,4,-dione-beta,beta,-carotene and a molecular formula of C40H5204. It is also known as shrimp yellow pigment, lobster shell pigment, and is a non-vitamin A source carotenoid. It is not only highly antioxidant, anti-tumor and immune-enhancing, but also has a bright red color and strong pigment deposition ability. It has been successfully used in high-end aquaculture abroad. Natural astaxanthin is mainly found in some plants and microorganisms. Animals cannot synthesize astaxanthin themselves and must obtain it from food.

Astaxanthin is very similar to other carotenoid pigments such as β-carotene, zeaxanthin and lutein, and therefore they share many metabolic and physiological functions.  In addition, the presence of hydroxyl and keto groups on each of the astaxanthin's chromone rings means that it has some unique properties, such as esterification, higher antioxidant activity than other pigments and a more polar configuration. Free astaxanthin is particularly sensitive to oxidation.

In nature, astaxanthin usually forms complexes with protein molecules to produce a range of colors in different organisms. For example, it is the blue, green, and yellow chromophores in lobsters. In addition, astaxanthin can be simply dissolved in complex molecules, such as the lipid-protein lipid part of egg, or chemically combined with other molecules such as fatty acids to form esters. In nature, astaxanthin has different stereoisomers due to the different configurations of the two hydroxyl groups in the molecule. Astaxanthin from natural sources mainly occurs in the 3S, 3'S, 3R, or 3'R form, and the 3R, 3'S isomer is the most abundant in synthetic astaxanthin [2].

1 Astaxanthin bioavailability and pharmacokinetics

In mammals, the digestion, absorption and plasma transport of carotenoids have been studied at various steps [3]. In plasma, non-polar carotenoids such as β-carotene or lycopene are mostly transported by lipoproteins [4]. Most carotenoids have a very low bioavailability, and a high dose of 100 mg is provided singly.

1.1Antioxidant activity of astaxanthin

In the human body, free radicals and singlet oxygen are produced during normal metabolic processes. At the same time, psychological stress, air pollution, smoking, exposure to chemicals and ultraviolet light can all increase the number of these radicals. Bacterial cells can also produce large amounts of free radicals to prevent being degraded by invaders. Free radicals can damage DNA, proteins and lipid membranes; they are closely related to oxidative damage and aging, atherosclerosis, infantile retinopathy, and cancer [5].

Astaxanthin molecules have long conjugated double bonds, hydroxyl groups and unsaturated ketones at the ends of the conjugated double bond chains, and the hydroxyl and ketone groups form α-hydroxyketones. These structural features give them relatively active electronic effects, which can provide electrons to free radicals or attract unpaired electrons of free radicals, making them extremely reactive with free radicals and scavenging free radicals, thus acting as antioxidants. Miki used hemoglobin containing ferrous ions as the free radical generator, linoleic acid as the acceptor, and thiobarbituric acid to test the antioxidant properties of various carotenoids and α-tocopherol. The results showed that astaxanthin has 10 times the ability to resist lipid oxidation than β-carotene and 100 times the ability than vitamin E, which is why it is also known as super vitamin E.

In vitro and in vivo experiments have shown that astaxanthin can protect the mitochondria of vitamin E-deficient mice from lipid peroxidation catalyzed by divalent iron ions, and its ability is stronger than that of α-tocopherol [6]. Mortensen et al. used endogenous peroxide to produce molecular oxygen to study the ability of various carotenoids to quench molecular oxygen. It was found that the ability to quench molecular oxygen was astaxanthin>α-carotene>β-carotene>canthaxanthin>zeaxanthin>lutein>bilirubin>biliverdin [7]. From the above research results, it can be seen that astaxanthin has strong antioxidant properties and the ability to scavenge free radicals. Therefore, it is clear that astaxanthin transports high-density lipoprotein (HDL) and low-density lipoprotein (LDL). Polar carotenoids such as zeaxanthin or lutein are likely to be transported by LDL and HDL. The only human study to date that has demonstrated the bioavailability of astaxanthin is a high dose of 100 mg given as a single dose, and it was transported in the blood plasma by lipoproteins [4].

2 Antioxidant activity of astaxanthin

In the human body, free radicals and singlet oxygen are produced during normal metabolic processes. At the same time, psychological stress, air pollution, smoking, exposure to chemicals and ultraviolet light can all increase the number of these radicals. Phagocytes can also produce large amounts of free radicals to prevent being degraded by invaders. Free radicals can damage DNA, proteins and lipid membranes; they are closely related to oxidative damage and aging, atherosclerosis, infantile retinopathy, cancer, etc. [5].

Astaxanthin molecules have long conjugated double bonds, hydroxyl groups and unsaturated ketones at the ends of the conjugated double bond chains, and the hydroxyl and ketone groups form α-hydroxyketones. These structural features give them relatively active electronic effects, which can provide electrons to free radicals or attract unpaired electrons of free radicals, making them extremely reactive with free radicals and able to scavenge them, thus acting as antioxidants. Miki used hemoglobin containing ferrous ions as the free radical generator, linoleic acid as the acceptor, and thiobarbituric acid to test the antioxidant properties of various carotenoids and α-tocopherol. The results showed that astaxanthin has 10 times the ability to resist lipid oxidation than β-carotene and 100 times the ability than vitamin E, which is why it is also known as super vitamin E.

In vitro and in vivo experiments have shown that astaxanthin can protect the mitochondria of vitamin E-deficient mice from lipid peroxidation catalyzed by divalent iron ions, and its ability is stronger than that of α-tocopherol [6]. Mortensen et al. used endogenous peroxide to produce molecular oxygen to study the oxygen-quenching ability of various carotenoids and found that the oxygen-quenching ability was astaxanthin>α-carotene>β-carotene>canthaxanthin>zeaxanthin>lutein>bilirubin>biliverdin [7]. From the above research results, it can be seen that astaxanthin has strong antioxidant properties and the ability to scavenge free radicals. Therefore, it is clear that astaxanthin plays an extremely important role in human health and can effectively prevent oxidative damage to tissues, cells, and DNA [2].

3 Health benefits of astaxanthin

3.1 Astaxanthin as a unique photoprotector

Exposing lipids and tissues to sunlight, especially ultraviolet light, can lead to the production of singlet oxygen and free radicals, which can cause photooxidative damage to these lipids and tissues [8]. Carotenoids in nature play an important role in protecting tissues from photooxidation caused by ultraviolet light and are often found in tissues directly exposed to sunlight.  Astaxanthin has a more significant effect than β-carotene and lutein in preventing lipid UV photo-oxidation [9]. The oxidative damage caused by UV light to the eyes and skin has been widely reported [8]. Therefore, astaxanthin's unique UV protection properties are important for eye and skin health.

3.2 Astaxanthin and eye health

The two main causes of visual impairment and blindness are age-related macular degeneration (AMD) and cataracts. Both diseases are associated with photoinduced oxidative processes in the eye [7, 10]. A high intake of carotenoids, especially lutein and zeaxanthin, can reduce the risk of cataracts and AMD [10]. The two carotenoid pigments lutein and zeaxanthin are very similar to astaxanthin and are found in high concentrations in the macular region of the eye [11]. Astaxanthin is very similar in structure to lutein and zeaxanthin, but it has stronger antioxidant activity and UV protection [9]. Astaxanthin has not yet been isolated from the human eye, but animal studies have shown that astaxanthin can cross the blood-brain barrier and, similar to lutein, deposit in the mammalian retina. Astaxanthin-fed mice had less damage to their retinal photoreceptors from ultraviolet light and recovered more quickly than mice that were not fed astaxanthin [12]. It can therefore be inferred that astaxanthin deposition in the eye can better protect the eye from ultraviolet damage and retinal tissue oxidation, indicating the efficacy of astaxanthin in maintaining eye health.

3.3 Astaxanthin and skin health

Prolonged exposure of unprotected skin to sunlight can lead to sunburn, but it can also cause photo-induced oxidation, inflammation, suppression of immune responses, aging, and even carcinogenic effects on skin cells. Clinical studies have shown that consumption of typical antioxidants such as α-tocopherol, ascorbic acid or β-carotene can reduce these damages [13]. Astaxanthin has been shown to protect salmon skin and eggs against UV-induced photo-oxidation [14], and astaxanthin supplementation protects retinal photoreceptors in the eyes of mice exposed to intense UV light [12]. Astaxanthin is more effective than β-carotene and lutein in protecting against UV-induced photo-oxidation in vivo [9]. These studies suggest that astaxanthin has great potential as an oral photoprotectant. Although dietary supplementation with β-carotene and astaxanthin has been shown to be beneficial in other cancers, animal or clinical studies with these two compounds have been inconclusive in relation to skin cancer [13, 15]. More research is needed to better understand the possible interactions between various antioxidants and their potential antioxidant roles in order to determine under what circumstances astaxanthin supplementation may help reduce the carcinogenic effects of skin cells.

3.4 Astaxanthin and inflammation

In clinical cases associated with inflammation, the release of toxic reactive oxygen species (ROS) by phagocytes at the site of inflammation (intestinal mucosa and lumen), combined with the increasing concentration of neutrophils at the site of inflammation, causes a decrease in the antioxidant vitamin content and an increase in oxidative stress and lipid peroxidation [16]; and oxidants are directly related to the stimulation of inflammatory factors in damaged cells [17]. Studies have found that astaxanthin can reduce the swelling of the paw of mice caused by inflammation, while VE cannot [18]. It has recently been found that dietary astaxanthin can help heal ulcers caused by Helicobacter pylori, and astaxanthin can reduce the symptoms of gastritis and is also associated with changes in the inflammatory response [19]. Although it can be inferred that the anti-inflammatory properties of astaxanthin explain its anti-inflammatory properties, further research is needed to better understand the specific way in which astaxanthin combats inflammation.

3.5 Astaxanthin and heart health

The level of low-density lipoprotein (LDL) cholesterol in the blood is positively correlated with coronary atherosclerosis, while the level of high-density lipoprotein (HDL) cholesterol is negatively correlated with coronary heart disease, which can be used as an indicator of atherosclerosis. Normally, low-density lipoprotein (LDL) in the blood is not oxidized, but oxidation of LDL is thought to contribute to the development of atherosclerosis [20]. Epidemiological and clinical data suggest that the intake of antioxidants may prevent cardiovascular disease [21].

In human blood, astaxanthin is transported via LDL and HDL. In vitro experiments and human studies have shown that a daily intake of a constant amount (3.6 mg/day) of astaxanthin for two weeks can prevent the oxidation of LDL-cholesterol in the body [22]. In animal studies, astaxanthin supplementation caused an increase in blood HDL concentrations [23]. Thus, astaxanthin may be beneficial for heart health by altering blood LDL and HDL cholesterol levels. Finally, astaxanthin may also be beneficial for heart health by reducing inflammation that may be associated with coronary heart disease [24].

3.6 Astaxanthin and cellular health

In mitochondria, multiple oxidative chain reactions generate energy for cellular needs, but at the same time produce a large number of free radicals that need to be suppressed to maintain normal mitochondrial function. If mitochondria are constantly damaged, it is a major cause of cellular aging, which in turn is the main cause of aging [25].

Astaxanthin is 100 times more effective than VE in preventing intracellular peroxidation in liver cells from mice [18]. This further demonstrates astaxanthin's unique ability to maintain mitochondrial function and its potential for anti-aging. Astaxanthin's outstanding performance in protecting cell membranes is thought to stem from its ability to protect the inner membrane and prevent oxidation of the outer surface [26]. Antioxidants, especially carotenoids, are essential for cellular health, not only because they prevent oxidative damage to cellular components, but also because they play an important role in regulating gene expression and inducing intercellular communication [27]. It has recently been reported that astaxanthin plays an important role in regulating CYP genes in mouse liver cells, although it does not seem to have this effect on human liver cells [28].

3.7 Anticancer properties of astaxanthin

Many studies have shown that astaxanthin has anticancer effects in mammals. Astaxanthin can prevent bladder carcinogenesis in mice by reducing the incidence of chemically induced bladder cancer. Compared with feeding mice with carcinogens only, feeding mice with carcinogens and astaxanthin supplements can significantly reduce the growth of different types of cancer cells in the mouth, and this protective effect of astaxanthin is even more significant than that of β-carotene [29].

It has also been found that astaxanthin can significantly reduce the incidence of induced colon cancer (p<0.001)[30]. Astaxanthin in the diet is also effective in the treatment of breast cancer, with an effect 50% higher than that of β-carotene and canthaxanthin [31]. Astaxanthin can inhibit the activity of 5-alpha-reductase, which causes prostate growth, so astaxanthin supplementation has been proposed as a way to treat benign prostatic hyperplasia and prostate cancer [32]. Recent studies on the mechanism of action of astaxanthin in influencing cancer-related pathways include the ability of this carotenoid to enhance membrane stability and promote the synthesis of genes encoding intercellular junction proteins. Changes in these proteins will effectively affect intercellular communication, which may be related to slowing cancer cell growth [27] or to regulating immune responses against cancer cells [29].

3.8 Astaxanthin and detoxification and liver function

The liver is a complex organ that is constantly engaged in anabolic and catabolic processes. Liver functions include lipoprotein oxidation for energy production, detoxification of pollutants, destruction of pathogenic bacteria and viruses, and destruction of dead red blood cells. These functions can lead to the production of large amounts of free radicals and oxidative by-products. Therefore, it is important to have a substance to prevent oxidative damage to liver cells. Astaxanthin is more effective than VE in protecting the mitochondria of mouse liver cells from lipid peroxidation [18]. Astaxanthin can also induce enzymes in mouse liver cells that cause metabolic changes caused by drugs, pesticides, carcinogens, etc. This process may help prevent cancer [33].

3.9 Astaxanthin and the immune response

Immune response cells are particularly sensitive to oxidative stress and membrane damage caused by free radicals, as they are particularly dependent on intercellular communication via membrane receptors. Moreover, some of these cells, such as phagocytes, function by releasing free radicals in order to rapidly destroy these cells if they are not inhibited by antioxidants [34]. Many studies have shown that astaxanthin can enhance antibody responses and increase humoral immune function. By studying the immunomodulatory effects of the two carotenoids astaxanthin and β-carotene on an in vitro mouse lymphoid tissue culture system, the results showed that the immunomodulatory effect of carotenoids was independent of the presence of vitamin A activity, and astaxanthin exhibited a stronger effect [35].

Overall experimental observations also found that carotenoids such as astaxanthin significantly promote antibody production in response to thymus-dependent antigen (TD-Ag) stimulation, and the number of IgM and IgG secreting cells increases [36]. Supplementation with astaxanthin can partially restore antibody production in response to TD-Ag in aged B mice, which helps to restore the humoral immunity of aged animals. In vitro experiments have also found that astaxanthin can significantly promote antibody production in B6 mouse splenocytes in response to TD-Ag, and enhance humoral immune responses that depend on T-specific antigens [35]. In addition, in vitro experiments on human blood cells have shown that astaxanthin can increase the amount of immunoglobulin in response to T-specific antigens [37].

3.10 Astaxanthin and neurodegenerative diseases

The nervous system is rich in unsaturated fatty acids and iron, and the constant aerobic metabolic activity in nervous system tissue and the large number of blood vessels running through it make it particularly susceptible to oxidative damage [38]. Studies have shown that oxidative stress is a major factor or at least a contributing factor in the pathogenesis of most neurodegenerative diseases, and that a diet high in antioxidants can reduce the associated risk [39]. The aforementioned study of mice fed natural astaxanthin showed that astaxanthin can cross the blood-brain barrier in mammals and produce an antioxidant effect on the other side of the barrier [12]. Astaxanthin can therefore be used as an excellent substitute for testing neurological diseases.

4 Safety of astaxanthin

Many everyday foods contain high levels of astaxanthin. Farmed Atlantic salmon contains 4–10 mg/kg of astaxanthin, wild sockeye salmon contains an average of 14 mg/kg, and coho salmon contains up to 40 mg/kg of astaxanthin [40]. No adverse reactions were observed in humans taking doses of 3.6 mg/d, 7.2 mg/d, and 14.4 mg/d astaxanthin, and the plasma LDL oxidation rate slowed with increasing dose [22]. Recently, Mera Pharmaceuticals conducted the following experiment: 33 healthy adult volunteers took 3.85 mg or 19.25 mg of natural astaxanthin (derived from dried Haematococcus pluvialis) daily for 29 days. A comprehensive physical examination was conducted before, during and after the experiment, including body weight, skin tone, appearance, blood pressure, vision, color perception, depth perception, eyes, ears, nose, mouth, throat, teeth, chest, lungs, urine sample analysis, blood sample analysis, no toxic side effects of astaxanthin were found [41], and other research results also indicate that astaxanthin is safe [22].

5 Conclusion

A series of research results in recent years by scientific researchers have led to the inference that supplementing with astaxanthin will be a practical and effective strategy for maintaining human health. This inference is supported by the strong antioxidant activity of astaxanthin. Astaxanthin has a wide range of biological sources. The production of astaxanthin using microorganisms such as yeast and algae has the advantages of a short production cycle, mild culture conditions and being environmentally friendly, and therefore has very broad prospects. Astaxanthin has numerous physiological functions and can be widely used in the food, pharmaceutical, chemical and feed industries. It has great potential, especially in the functional food and pharmaceutical markets.

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