What Are the Uses and Benefits of Astaxanthin in Animal Feeding?

Astaxanthin is a carotenoid extracted mainly from aquatic animals. It has various physiological functions and is therefore a research hotspot in the animal husbandry industry. Due to its extremely strong antioxidant activity, which is more than 10 times that of other carotenoids and more than 550 times that of vitamins, astaxanthin is also known as the “super vitamin”. Astaxanthin can effectively inhibit oxidative damage and cancerous changes in cells, as well as prevent ultraviolet radiation, enhance the body's resistance, and resist cardiovascular and cerebrovascular diseases. It is playing an increasingly important role in industries such as healthcare and feed farming[1]. This paper reviews the physical and chemical properties, structural characteristics, sources of production, application in animal husbandry and safety of astaxanthin, with a view to providing theoretical reference for the application of astaxanthin in China's animal husbandry industry.

1 Physicochemical properties and structural characteristics of astaxanthin

1.1 Physicochemical properties

Astaxanthin, also known as shrimp yellow protein or shrimp yellow substance, is a kind of purplish red crystalline substance first extracted from lobsters by German chemist Richard Kuhn. It is therefore called astaxanthin. Later, astaxanthin was determined to be a carotenoid closely related to shrimp red pigment. Beta-carotene , lutein , canthaxanthin , lycopene, etc. are all synthetic intermediates of carotenoids, and astaxanthin is the product with the highest level of synthesis among carotenoids. It is also currently the substance with the strongest antioxidant activity discovered by humans in nature, with antioxidant properties that far exceed those of existing antioxidants. The chemical name of astaxanthin is 3,3'-dihydroxy-4,4'-dione-beta,beta'-carotene, with the molecular formula C40H52O4 and  relative molecular mass 596.84, melting point 215~216℃, boiling point 774℃, red solid powder, fat-soluble, insoluble in water.

1.2 Structural characteristics

The molecular structure of astaxanthin is shown in Figure 1. The middle structure is composed of a conjugated double bond consisting of four isoprene units, and the end structures are composed of α-hydroxy-perillene hexaheterocycles. The C-3 and C-3' of the end ring structures are two chiral centers. The conjugated double bond in the middle structure can attract the unpaired electrons of free radicals or provide electrons to free radicals, thereby removing free radicals and playing an antioxidant role. Due to the special structure of the conjugated double bond chain, unsaturated ketone group and hydroxyl group, astaxanthin is prone to degradation reactions with light, heat and oxygen, forming astaxanthin.

Astaxanthin has two conformations for each chiral center, and each chiral carbon atom can exist in the form of R or S. Therefore, astaxanthin has three isomers: (3S, 3'S), (3R, 3'R) and  (3R, 3'S) There are a total of 3 isomers, of which (3S, 3'S) and (3R, 3'R) are enantiomers. Astaxanthin exists in trans and cis structures due to the different ways in which the carbon-carbon double bond groups are linked. Natural astaxanthin is almost entirely trans, and both are chemically synthesized. Among them, the natural trans-form of astaxanthin has higher biological activity, while the cis-form of astaxanthin has extremely low biological activity. Animals have weak absorption of cis-form astaxanthin. Therefore, the trans-form of astaxanthin is generally selected in the animal husbandry industry [2].

2 Production methods of astaxanthin

In the early 20th century, natural astaxanthin was mainly extracted from shrimp, crab and other organisms using natural purification methods. With the progress of science and technology, chemically synthesized astaxanthin quietly came out, but due to differences in molecular structure and other aspects, its effect and safety are far lower than that of naturally purified astaxanthin.

2.1 Synthetic astaxanthin

The main synthetic route for astaxanthin is to use the carotenoid β-carotene as a starting point, introduce two hydroxyl groups and a ketone group on the 3rd and 4th carbons of the aromatic ring of β-carotene, and finally form astaxanthin. At present, the most widely used method for synthesizing astaxanthin is the Wittig reaction, while the semi-synthesis method uses carotenoids such as canthaxanthin, zeaxanthin and lutein as raw materials to prepare astaxanthin. The main features of chemically synthesizing astaxanthin are its simple preparation process and low cost. However, it exists in the form of three stereoisomers and contains by-products, and its stability, safety and antioxidant activity are not satisfactory [3]. In particular, in practical production applications, the bioavailability of natural astaxanthin in animals is stronger than that of synthetic astaxanthin. When the feeding concentration is low, the concentration of natural astaxanthin in the blood of rainbow trout is significantly higher than that of synthetic astaxanthin, and synthetic astaxanthin cannot be converted into the natural configuration in animals. The biological efficacy and coloring ability are much lower than those of natural astaxanthin of the same concentration [4]. In view of this, the global management of chemically synthesized astaxanthin is becoming increasingly strict, and countries have also made corresponding management regulations. The US Food and Drug Administration (FDA) has banned the use of chemically synthesized astaxanthin in the health food market.

2.2 Natural astaxanthin

Natural astaxanthin mainly exists in the form of 3S, 3'S, which has higher biological activity. There are two main production methods: one method is to extract it from krill, lobster, trout, salmon, algae, yeast, bacteria and aquatic processing waste [5]. At present, there are about millions of tons of aquatic product waste worldwide each year. Natural astaxanthin can be obtained by crushing, breaking the cell wall, hydrolyzing, and extracting. This method can promote the healthy development of the aquaculture industry and reduce the pressure on the ecological environment.

However, these waste aquatic products contain impurities such as chitin and ash. How to maximize the extraction of astaxanthin and remove impurities is the key to solving the problems of product quality and production costs. Another method is to produce it through microbial fermentation of Rhodotorula glutinis, Chlorella pyrenoidosa, unicellular microorganisms such as red yeast, Chlorella vulgaris, Haematococcus pluvialis, Saccharomyces cerevisiae, Gluconobacter and so on. This method has the advantages of low environmental pressure, clear products and few by-products[6] and is currently the main method of astaxanthin production. However, this method has high requirements for the culture conditions and strains. Chi et al. [7] used genetic engineering to modify the high-yielding red yeast MK19, and the astaxanthin production was increased by 17 times compared to the wild type. The method of fermenting astaxanthin using red yeast fermentation has the advantages of short culture time and high-density culture that can be achieved by mass propagation. Yeast is also a good feed protein raw material, and the selection of high-yield red yeast strains has therefore attracted much attention. If a high-yield strain of red yeast can be selected, it will definitely further facilitate the large-scale production of astaxanthin and promote its application in animal husbandry.

3 Application of astaxanthin in animal husbandry

3.1 Effect of astaxanthin on the quality of livestock and poultry products

Color and water retention are important indicators of the quality of livestock and poultry products. Factors affecting these indicators include the pigment content and antioxidant enzyme activity of the product. Astaxanthin has innate advantages in terms of coloring and antioxidant properties, and is the preferred coloring agent in aquatic and poultry feeds. As the final step in carotenoid synthesis, astaxanthin can be directly stored and deposited in muscle tissue after entering the animal's body, and can non-specifically bind to myoglobin [8]. Therefore, adding astaxanthin to feed can effectively improve the color of livestock and poultry products, enhance their nutritional value and market competitiveness.

Conradie et al. [9] found that adding astaxanthin to the feed can make the feet, skin, beaks, and feathers of laying hens appear in varying degrees of red or golden yellow, increase the weight of whole eggs and egg yolks, promote poultry growth, and increase egg production. Liu Bing [10] found that the antioxidant enzyme activity of the muscle tissue and egg yolk of laying hens increased with the increase of the amount of astaxanthin added to the diet. Fu Xingzhou et al. [11] found that astaxanthin can significantly increase the a* and L* values of the redness and brightness of chicken meat after slaughter. There has also been a gradual increase in research on astaxanthin in livestock animals. Carballo et al. [12] found that when studying the meat quality of lambs, adding astaxanthin to a commercial butylated hydroxytoluene-containing milk powder can increase the a* redness value of the post-slaughter lamb and fat, thereby improving the lipid stability of frozen meat. Li Xinjie et al. [13] found that adding astaxanthin to the diet of fattening pigs can reduce the brightness value L* and yellowness value b* of the loin muscle, deepen the color of the meat, and the quality is better.

3.2 Effect of astaxanthin on the reproductive performance of livestock and poultry

Astaxanthin can quench singlet oxygen and scavenge free radicals. It can also improve the defense function of the endogenous antioxidant enzyme system by reducing membrane permeability and limiting the penetration of oxidants into cells. Astaxanthin can improve semen quality by continuously reducing the level of oxidative damage to livestock and poultry sperm, and improve the reproductive performance of female animals by increasing the superoxide dismutase activity of thermally shocked cumulus cells [14]. Studies have shown that adding astaxanthin to chicken semen can significantly enhance the superoxide dismutase and glutathione peroxidase activities in the semen and improve the integrity of the sperm plasma membrane [15]. In in vitro experiments, adding astaxanthin to the maturation medium of porcine oocytes improved growth and development at all stages to varying degrees [14]. Hu Yamei [16] found that the appropriate amount of astaxanthin can significantly improve the quality of pig semen at room temperature. Kamada et al. [17] found that the addition of low concentrations of astaxanthin to the culture medium of bovine luteal cells can increase the progesterone content in the culture medium. Therefore, the addition of astaxanthin to the feed has the potential to improve luteal function.

3.3 Effect of astaxanthin on the production performance of livestock and poultry

As a new type of feed additive, astaxanthin can improve the feed utilization rate and growth rate of livestock and poultry. Some studies have shown that adding astaxanthin to the diet of laying hens can improve the storage stability of DHA eggs and increase egg production. Kumar et al. [18] found that adding astaxanthin to the diet of calves can significantly improve the feed conversion rate and increase body weight. Lin et al. [19] found that a combination of astaxanthin and sodium diacetate in piglet feed can improve the antioxidant capacity and nutrient digestibility of piglets, thereby improving their performance. Perenlei et al. [20] found that astaxanthin can increase the daily weight gain and abdominal fat percentage of broilers. However, other studies have shown that adding natural astaxanthin to the diet of laying hens has no effect on production performance [21,22].

3.4 Effect of astaxanthin on the immunity of livestock and poultry

The level of immunity in livestock and poultry directly affects their health and growth rate. The effect of astaxanthin on the immunity of livestock and poultry is mainly reflected in the following three aspects: first, its antioxidant effect. Astaxanthin has strong antioxidant properties, can scavenge free radicals, inhibit oxidative stress, protect immune cells, and prevent the immune system from damage. Second, it enhances the number and activity of immune cells. Astaxanthin can increase the number of immune cells such as lymphocytes, neutrophils and macrophages, thereby enhancing the body's immune capacity.

Third, it promotes the production of immunoglobulins. Astaxanthin can promote the vitality of B cells in the immune system, increase the production of immunoglobulins (IgG, lgA and IgM), and enhance the ability of humoral immune response.

In summary, astaxanthin can be used as an effective antioxidant and immune enhancer in animal husbandry to improve the immunity and disease resistance of livestock and poultry. However, astaxanthin cannot replace any drug in treating diseases. At the same time, the absorption and utilization of astaxanthin by different species of animals may also differ, and appropriate adjustments and choices need to be made in actual application.

4 Safety of astaxanthin in animal husbandry

Astaxanthin is safe and has no toxic side effects. It is widely used in animal feed and, in moderate amounts, can promote animal growth and development without adversely affecting animal health. This has been demonstrated in many experiments. Jin Wei et al. [23] conducted a 30-day astaxanthin feeding experiment on rats, and found that there were no abnormalities in the growth and development of the rats, and they generally performed well. There were no significant abnormal changes in the results of various indicators or histopathological examinations. Lin et al. [24] showed that, compared with the control group, no significant biological differences were found in clinical parameters such as body weight, hematology, urinalysis, and organ weight in mice that had been continuously administered astaxanthin for 13 weeks. Shi Lili et al. [25] used toxicological evaluation methods such as acute toxicity tests, genotoxicity tests, and a 30-day rat feeding test to evaluate the safety of astaxanthin consumption. No significant toxic side effects of astaxanthin were observed. Lin Feiliang et al. [26] also revealed that Haematococcus pluvialis extract was safe in a 90-day feeding test and teratology test in rats.

Worldwide, astaxanthin is used in a wide range of applications. In North America, in April 2009, the FDA approved astaxanthin as a component of a mixed coloring agent for use in fish feed. In 2000, Haematococcus pluvialis powder and Rhodopseudomonas palustris were approved for use in fish feed to color salmon, and achieved the desired feeding results. In the European Union, astaxanthin is approved as a new ingredient for dietary supplements. In 2009, China approved astaxanthin for use as a feed additive, and Haematococcus pluvialis was approved as a new food resource in 2010. In general, the use of astaxanthin in animal feed is safe, but it should be avoided if the animal is allergic to astaxanthin, carotenoids, the source of astaxanthin, or drugs that inhibit 5-alpha reductase. In addition, attention should be paid to the amount used and the combination with other feed ingredients to avoid affecting the health of the animal.

5 Summary

Astaxanthin is one of the most important carotenoids in nature. It has attracted the attention of animal nutritionists because of its important role in improving the growth performance, survival rate, reproductive performance, and disease resistance of livestock and poultry. Due to its significant effect on improving the color, reproductive performance, production performance, and immunity of livestock and poultry, the amount of astaxanthin used in animal husbandry has increased rapidly, and it has great application value and development potential. However, there is not much research on the application of astaxanthin in the breeding of livestock and poultry, especially ruminants, and many of its mechanisms of action are still unclear. With the increasing market demand for astaxanthin, the large-scale production of astaxanthin through synthetic biology, molecular biology, metabolic engineering and other new technological methods is the focus of research. The screening, extraction and purification of high-yield astaxanthin strains are key points and difficulties. In short, the production and application of astaxanthin is an extremely attractive and challenging field. It is expected that with the help of new biotechnology, the large-scale production and application of astaxanthin will see new developments.

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