The Application of Astaxanthin and its Commercial Production

GAO Qing-tan, CUI Zhi-qiang

(Salt Research Institute of China National Salt Industry Corp., Tianjin 300450,China)

Classification number: S965

Document identification yard: A

Article serial number: 1001-2214( 2004) 06-0033-05

Abstract: Astaxanthin a kind of oxygenated carotene,is widely employed in aquaculture and poultry raising as pigmentation sourcc,In addition,due to its strong antioxidative activity,astaxanthin also has promising potential in neutraceutical and healthy food markeet.The major market of astaxanthin is as a pigment in aquaculture and poultry feed,which is derived from synthetic source.Although the production of astaxanthin with microalgac Haematococcus is challenged by some technological production of astaxanthin from massive cultivation of microalgae now became a reality and will became a promising industry.

Key words:astaxanthin;haematococcus; -carotene;

1.      Distribution of Astaxanthin

Astaxanthin is a kind of carotenoids; its structure is similar to carotenoid which is familiar to us. It's a kind of oxidative beta-carotene. The slight diversity between them makes the great difference in their chemical and biological characteristics. Astaxanthin is a kind of natural carotenoids which is distributed widely in nature. Although we may not refer to astaxanthin everyday, we always ingest astaxanthin in our daily diet. In nature, astaxanthin exist in salmon, shrimp, crab, spectator fish, roe, leaves, flower and fruit. Many crustaceans are tinted red by accumulated astaxanthin. Besides, astaxanthin also exist in birds. In most time, astaxanthin has a bright red color. Burt it turns duck-blue or green in many crustaceans, as it combines with protein ? The machining process of heating destroys the combination between them and astaxanthin renew its original color ( Weesie,1999 ) .






Fig. 1 Molecular Structure of Astaxanthin


2. Apply of Astaxanthin

As the same of other carotenoids, animals cannot synthesize astaxanthin by themselves. Besides, another animal also cannot transform other carotenoids which they ingested into astaxanthin. Therefore, all animals must obtain astaxanthin from their food. In the environment of ocean, astaxanthin is generally provided by the green algae in food chain or other microorganisms. Compared with other carotenoids, astaxanthin is easier passive absorption and accumulation. It can obtain the widespread application as one kind of natural carotene in the aquaculture, because of the following main function: 1. Anti-oxidability; 2. Certain hormones precursors; 3. Enhances the immune function; 4. It has the activeness of vitamin A; 5. It can improve the ability of breeding; 6. promote the develop; 7.Proper growth; 8.The light protective function. At present, many countries in the world put astaxanthin as animal feed additives for development.

  2.1 Aquaculture

   2.1.1  Salmon

Astaxanthin make the flesh of salmon remain pink. People have to add some astaxanthin to keep its bright color in the artificial breeding .The conclusion obtained through the research by FDA indicate that the salmon or the wild red trout and artificial feeding products can be distinguish by Analysis its astaxanthin composition . Because the wild red trout mainly contains 3S, 3.S isomer, the 3S, 3.S isomer appeared only by increased this isomer in the animal feed. So, it shows that the salmon can not change 3R, 3.S isomer into 3S; 3.S isomer .The investigation demonstrated that the consumers incline toward the natural red one ( Turujman , 1997 ) . Many researches have shown that astaxanthin can not only increase or keep the color of fish but also improve production and keep healthy. In some types of fish especially salmon, astaxanthin is essential for their proper growth and survival. At present, it is a potential market for astaxanthin as feed additives of salmon. The salmon's output which increases continuously impulse the market demand of fish. The astaxanthin bring salmon a bright red color. A research which carried on in Norway in 2000 showed that the content of astaxanthin in feedstuff is closely related with growth and survival of Atlantic salmon. The fry cannot grow normally if the content of astaxanthin below   3.5mg/kg, it can't keep the proper growth and the Lipid content also rises obviously if the content above 5.3mg/kg. The livability will declines to 20% when the livability of matched control is 90%, the content blow 1mg/kg. So, the astaxanthin is regarded as something that has the activity of Vitamin A (Christiansen , 1995) . It is particularly important to the farming fish which can not absorb other carotinoids completely. Research expresses that the content of astaxanthin as a basic nutritional elements in bait may maintains in 5mg/kg at least in order to keep the farming fish's proper and bright color (Lorenz and Cysewski , 2000) .  

    2.1.2 Sea bream

They often have a high price if their skin are bright red. The research proves that bright colors mainly due to astaxanthin and the color would be light if reduce the content of astaxanthin. If add carotinoid in feed, such as carotinoid, zeaxanthin, lutein and canthaxanthin, we will find that it have no obvious exaltation function and the color would be light because of the astaxanthin exhaust slowly. Researches also proved that the lipidic astaxanthin can be easier absorbed than the liberal elements ( Nakazoe , 1984 ) .

  2.1.3 Spectacular fish

Tropical spectacular fish have bright color due to their internal carotinoid. The color is the key of identification and mating signal, it's important for their physiological function. They commonly ingest astaxanthin from benthos, such as algae, coral and other plants including carotinoid. At present, the biggest challenge for the tropical fish industry is how to keep their natural bright colors. Although many businesses have made great success in the breeding, they are failing because they can't keep natural color of fish when the market sells. So, people carried on a great deal of research, the conclusion is only to increase astaxanthin especially add the heamatococcus pluvialiaflotow in the feeding process. The scholar discovered that the species luster will be improved if increase 30mg/kg astaxanthin in the feed. In a research that announced recently, added 100mg/kg astaxanthin in spectacular fish's feeds, after a week, majority of species colors improve obviously, and in some categories even grow faster. Although the sugar recruitment is high in the laboratory, most of the enterprises are inclined to take this way to improve the color quickly before selling.


3  The Medicine Health Cares Function of Astaxanthin

The strongest antioxidant  in world --natural astaxanthin, which comes from Hawaii's function food ingredient, is the natural heamatococcus pluvialia's extract, and has the pure natural vegetative quality. The clinical trial proved that natural astaxanthin has 500 times the antioxidant effect of vitamin E and 10 times of -carotene. America FDA had attested the security. A great deal of clinical trial has proved the function of astaxanthin :  ? eliminate the free radical eternal efficient ; ? defer decrepitude ; ? super radiation hardening capability ; ? improve immune ; ? protect the skin against Uv ; ? alleviate sport fatigue quickly ; ? diminish inflammation effectively . At present, the natural astaxanthin had acquired three patents : protecting the skin against Uv, treating the carpal tunnel syndrome, easing the ache of inflammation and ulcer . The medicine health cares function of astaxanthin mainly manifested in the following aspects:

3 .1 Antioxidant Properties of Astaxanthin

The human body produces a great deal of free radical, which accumulates more if getting in touch with pollution and harmful chemistry material or exposing in UV radiation. It will be also produced by phagocyte in the course of the immune response. Some nitrogen compound such as N-2-O, N-2-O-3 is harmful to the human body. They damage macromolecules by chemical reaction occurred in macromolecules distributing around and carbohydrate and lipid, which creates the serious consequence to the organism. We are constantly exposed to the descent of free radical which be called oxidative stress. This oxidative stress would bring many diseases, for example: caducity, syndrome symptom complex, AD, bacterial meningitis, cerebrovascular disease, PD, visual meningitis, Neurological disease. Because we are constantly exposed to the descent of free radical, human being had produced to moderate free radical during the period of evolving which had become the mechanism to prevent the outbreak of diseases. Although any enzyme which have the repair function can eliminate the injury which the free radical produces.  The antioxidant can perish it to ensure the survival, which depends upon avoiding function before it appears.  They can not only alleviate the above diseases, but also prevent the occurrence of these diseases. Many chemical substances have antioxidation, such as vita-C, vita-E and carotinoid and so on. The research indicated that Astaxanthin has from 80 to 100 times the antioxidant capacity of Vitamin E and 10 times the antioxidant capacity of beta-carotene. At the same time, the astaxanthin can pass through protein film of biomembrane, which achieves its antioxidation functions.

  3.2 Astaxanthin's Inhibitory Effect on Cancer

      Astaxanthin is a super antioxidant, it could prevent harm from ultraviolet radiation, enhances in vitro antibody production, and it also have inhibitory effect on cancer, It can improve immunity ability; even regulate the activity of some genes to inhibit cancer metastasis. Chew (1999) studied the activeness of resisting breas carcinoma of astaxanthin, -carotene and horny yellow by chmice. The result leaded to that astaxanthin is the best one which has the highest success rate about inhibiting cancer. It also has the best performance in transforming the tumour's dioxygenase, and horny yellow has no activity. The result is similar to the research about astaxanthin's knub inhibition of bladder carcinoma. Tanaka (1994)'s study proved that astaxanthin can inhibit carcinogen effectively, such as flavacino, chloroform, 4-quonoline 212 oxide. The scientific researcher recently propose the astaxanthin anti- cancer mechanism, which has respected to stability of cell film and the gene of promote gap junction protein "conexin-43". It adjusts correspondence between the cell and the cell through the change of conexin-43's quantity to improve the capacity of stability and maintain the normal function of cell. In addition, a study of chmice's liver cells has shown that astaxanthin can induce the enzyme's synthesis of xenobiotic metabolism; this process also has a close role in the prevention of cancer. NK cell plays an important role in the inhibition of tumor metastasis. Kurihara(2002) thought through research : Astaxanthin can inhibit the injuring of NK-cell's ability against cancer caused by oxidative stress, so, It can repress the tumor metastasis .

  3 .3 Cardiovascular Diseases

LDL is called bad phospholipoprotein, so, the cholesterol in it is called bad cholesterin . On the contrary, the cholesterol in HDL is called good cholesterol. If the density of LDL in the human body is very high, the risk of suffering from AD is higher, and will injure artery wall. Especially, because the deposition of the blood platelets makes the blood vessel become thin, this will ultimately impede blood flow through arteries, thus cause heart disease and apoplexy . On the other hand, if the density of HDL in the human body is very high, the risk of suffering from coronary artery disease will be descended, thus can prevent the occurrence of AD. The researcher firmly believes that AD has respect to Oxidizing of LDL. The epidemiology and clinic proved that it can prevent from a cardiovascular diseases if take in more oxidation. In recent decades, many cultural heritages had reported the prevention function of carotinoid. People's attention mainly concentrated at the carotinoid for different levels of cholesterol in lipoprotein. Murillo(1992) made a research on mice to prove that astaxanthin including other carotinoid  could reduce the HDL level in blood obviously.  Ingesting vitamin A, vitamin E, -carotene and most carotinoid could reduce the possibility of LDL oxygenated. It indirectly proved that astaxanthin can prevent AD by expressing the action, which protects the cholesterol in LDL from oxygenated. The last of reason is that astaxanthin can alter the level of LDL cholesterol and HDL cholesterol .On the other hand, the probability of cardiopathy will reduce when there is a low level of LDL and a low ratio of LDL/HDL. An experiment proved that the trier take the 3.8mg or 19mg astaxanthin coming from heamatococcus pluvialia  every day, after a period of time ,the analysis shows that the ratio of LDL/HDL and LDL has decreased significantly .

3.4 Astaxanthin and Immunity Function

Because the immune cells communicate through a receptor in the membrane of the cell, the immune cells are sensitive to the injury of oxidative stress and the free radical. In the immunity process, some phagocyte activity releases the free radical actually; if the free radical cannot obtain promptly in vivo neutral, it will harm the cell membrane of immune cell rapidly. It had Already observed that astaxanthin in many aquatic product animals can increase animal's immunity function and disease resistivity. Take salmon for example, astaxanthin is essential for parr's proper growth and survival; therefore, some researchers thought that it is equal to chum salmon's vitamin. Whether in vivo or in vitro tests, it has already confirmed that astaxanthin can obviously improve mammal's immunity system function. In vitro experiments of mouse spleen cell, Jyonouchi (1991) discovered that astaxanthin can stimulate the spleen cell to produce the immune body. The further research discovered that this kind of stimulation is stimulates through the T- cell, especially T-helper cells at least .Because the mammal cannot transform astaxanthin into vitamin A, therefore, the immunity function of astaxanthin has nothing to do with the vitamin A's activeness. The vitro experiments of blood cells showed that astaxanthin can also enhance immunoglobulin production. Moreover, in the human body trial test, takes 5 times of astaxanthin every day (8MG),  all patients gastritis symptom remarkably reduces after 3 weeks, although the bacterium inspection still assumed the masculine gender(Wangetal.,2000). 

3.5 Astaxanthin and Nervous System Diseases

The nervous system includes the cerebrum, the vertebra and the peripheral nervous system, rich in unsaturated fatty acid which is easy to be oxidized, and the strong oxidizing iron. The strong oxygen metabolism activeness, adequately contacting with blood vessel and high ion, therefore the oxidant is easy to damage nerve tissue. Some massive evidence indicated that oxidative stress is the pathogenesis of neurodegenerative diseases, or at least a subsidiary factor. Many separation researches show that people take the antioxidant such as vitamins and carotenoids may protect nerve tissue from the damage of oxidative stress. Many living specimens' experiments and the clinical research indicated that astaxanthin can help resist the nervous system diseases. Tso (1996) carried on a research indicated that comparing with other antioxidants, astaxanthin is easier to pass through mammal's blood barrier. It can be predicted that astaxanthin can extend its antioxidant capacity to the brain. Its antioxidant capacity goes far beyond vitamin E and the B-carotene; therefore it is the candidate in treatment of diseases of the nervous system and Meniere's disease.

3.6 Other Functions of Astaxanthin

Besides the above medicine health care function, the massive researches
indicated that, it also has the anti- inflammation, the disintoxicating, the promotion liver function, protection of mitochondrial cells,  protects the eye and the skin, the light protection, enhances the cell health. Many tissues and organs are frequently exposed to the ree radical environment because of their physiological functions or have a large number of free radicals in the metabolic process, so they are harmed by the free radicals .Because ataxanthin is a very strong antioxidant, and can easily pass through the blood barrier to achieve each tissue and organ. But the antioxidant must contact with the tissue and organ which it protects in order to achieve its protective function. Many questionnaire surveys and the medicine experiment have also proven these above functions of astaxanthin ( Guerin,2002 ) .


4. The Commercial Production of Astaxanthin

Animals cannot synthesize astaxanthin by themselves. Besides, most animal also cannot transform other carotenoids. Therefore, all animals must obtain astaxanthin from their food. In 2000, the estimated capacity of astaxanthin on the market has reached 200 million dollars a year. Mainly used in aquaculture, and some part in the health product. The current price is about 2500 US dollar/kg, which is more than 95% of chemical synthesis products, mainly comes from Switzerland. Because the consumer favors the natural product more and more, it has provided the latent market using the microorganism to product natural astaxanthin .

At present, the crustacean saccharomycetes and the micro algae are the natural origin of astaxanthin. Because the content of astaxanthin in crustacean and fungus is very low, which just from 0.15% to 0.4%. But very many green algae in the culture conditions can be determined accumulation of carotenoids, thus the production of natural astaxanthin from micro algae have broad prospects, and aroused national scientific researchers ' great interest. It has been found algae can accumulate a lot of astaxanthin, especially haematococcus pluvialis, they can reach more than 2% of the dry content, which is the highest level of astaxanthin found in the biological, it's considered to be one of the most prospective green algae. The large scale production of haematococcus pluvialis' cell main components and the content generally are: astaxanthin : 1.5%,thick protein 24%, crude fat 14%, carbohydrate 38%, thick ash 14%, moisture 6% - 9%.

Haematococcus pluvialis belongs to the green alga gate in the taxonomy, chlorophyceae, volvocales, haematococcecae, haematococcus, Ag.Haematococcus pluvialis is a single-cell freshwater algae which has the double flagella. The most suitable temperature for the growth of haematococcus pluvialis is 25-28 degrees Celsius, most suits PH is the neutrality to the alkalescency. Haematococcus pluvialis is a single-cell freshwater algae. Under the normal growth condition, the cell is green, has two flagellas, extracellulars the ellipse to the egg circle , the cell front was ended by a thinner cell wall. Under the certain growth condition, the dormant spores become zoospores lose their ability. As a result of astaxanthin's massive accumulation, the dormancy spore turns red.

As the medium neutral Haematococcus pluvialis is very neutrality. The growth of haematococcus pluvialis is slow, they could very easily polluted by other fungus and protozoa, and this restricts haematococcus pluvialis 'commercial production. Therefore Haematococcus pluvialis algae's large scale production requires higher technology and careful operation. At present, Commercial production of algal biomass liquid is lower. There are two methods of production: photoreactor production and production of astaxanthin from Haematococcus pluvialis in open ponds

 5. Conclusion

  Because astaxanthin is a very powerful antioxidant, it has huge application prospect in feed additive and the medicine. At present, researchers have made important progress in biosynthesis physiological and environmental factors of astaxanthin. Although there are some technical aspects of the large-scale cultivation of technical problems, along with the biological reactor unceasing progress, raising technical, unceasing discovery of the new species  , especially the identification of astaxanthin biosynthetic enzymes and the breakthrough of genetic technology, producing natural astaxanthin from microalgae become a prospect industry.