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Astaxanthin and health

By Njaal Meland, M.D., Medical Advisor, Igene

Astaxanthin - a carotenoid

Carotenoids are a family of over 700 natural lipid soluble pigments. They provide, in nature, a wide variety of colors ranging from yellow to orange and red, giving color to aquatic life, fruits and birds. Only phytoplankton, algae and plants produce carotenoids. Their native function in algae and plants are as light harvesting molecules and as antioxidants. Animals have adapted to exploit these properties. A well known example is retinal (vitamin A), an essential nutrient for humans and for the function of human vision.

Astaxanthin as an antioxidant

Astaxanthin is another member of the carotenoid family. It has been shown to be a powerful quencher of singlet oxygen activity and a strong scavenger of oxygen free radicals. Its antioxidant properties are at least ten times stronger than that of vitamin A, and a hundred times stronger than vitamin E.

These properties have caused great interest in this substance, and there is a growing scientific literature on astaxanthin.

Astaxanthin in nature

In marine environments, astaxanthin is biosynthesized in yeast, microalgea and phytoplankton. The yeast Phaffia rhodozyma and the algae Haematococcus pluvalis provide the most concentrated natural source of astaxanthin. When nutrients become limiting, or when its environments begin to dry in, the algae and the yeast produces massive amounts of astaxanthin. The algae then encysts. It can thus enter a dormant stage until the next influx of water and nutrients. A cell can remain viable in this stage for decades. Cells with a high concentration of astaxanthin are more resistant to environmental hazards such as light than cells with a low concentration. This strongly suggests a protective role of the antioxidant astaxanthin.

Astaxanthin accumulates in the aquatic food chain. Algea and plankton are consumed by zooplankton and crustaceans, which in turn are ingested by fish, such as salmon or trout. It is deposited and concentrated in the muscles of the salmon, probably protecting its lipid tissue from peroxidation. It is essential for growth, survival and immune response in salmon (24).

Wild salmon has high concentrations of astaxanthin, some 40 mg/kg. Farmed salmon is given astaxanthin as an artificially produced supplement in its diet. Farmed salmon thus reaches concentrations around 5 mg/kg.

Astaxanthin in preclinical studies

Oxygen is required for metabolic functions, but it also presents challenges to cells. The human organism has a vide range of metabolic enzymes and antioxidants to rid its cells of oxygen derived molecules. This oxidative stress is supposed to be a contributing factor in conditions such as rheumatoid arthritis, ischemic heart disease and stroke, Alzheimer`s dementia, cancer and ageing. Astaxanthin is an extremely effective antioxidant protector (1,2,3,4,5,6), and therefore has the potential to protect against such a wide spectre of disease. Being well tolerated and safe it is therefore a promising substance in future prevention and treatment. Unlike beta-carotene it readily crosses the blood-brain/retina barrier, and therefore also has a potential to protect from diseases of the brain and the eyes (14).

Though lots of research has been done, one should notice that apart from human studies carried out to establish the safety of astaxanthin, most studies are either in vitro studies or animal studies. Caution should be carried out when interpreting such studies on humans.

There are, nevertheless, preclinical studies suggesting effects such as: - Inhibited carcinogenesis in bladder, colon, liver, mammary and oral cavity (7,8,9,10,11).

- There is evidence that astaxanthin can protect the retina of the eye from oxidative damage. This suggests effect against age related macular disease (12,13,14).

- Increased activity of the immune system (T-helper cell and antibody secreting cells of the spleen) (16,17).

- Protection of skin from ultraviolet (UV) light damage (18).

- Suppression of the bacterium H. pylori, the cause of gastric ulcer (19,20).

- Inhibition of LDL (bad cholesterol) oxidation (23). Oxidation is probably an important step in development of atherosclerosis and cardiovascular disease (22). Increased levels of HDL (good cholesterol) (21).

- One pilot study carried out on healthy males showed increased muscle endurance in the astaxanthin group (15).

Astaxanthin and human consumption

Astaxanthin naturally occurs in human diet when seafood such as krill, shrimp, lobster, pacific cod, flounder, mackerel, salmon and other red fishes is eaten. In several human populations, including traditional Oriental diet rich in seafood, intake of high amounts of astaxanthin is routine. In fact, Eskimos with a high consumption of salmon show a low rate of ischaemic heart disease and also a high blood concentration of omega-3 fatty acids. A daily ingestion of 4 mg astaxanthin corresponds to a daily ingestion of 100 gram of wild salmon or 400 gram of farmed Atlantic salmon.

Astaxanthin - a safety concern

Astaxanthin and its safety for consumption by humans has been extensively demonstrated. The substance naturally occurs in food, especially seafood. It is permitted by FDA as an artificial additive in farmed salmon and as a nutriceutical in doses up to 2mg a day. Studies have been carried out on animals and humans ingesting high amounts of astaxanthin failing to prove any harmful effects. There are no known side effects.

Absorption of Astaxanthin

Astaxanthin is available in to different forms, as free astaxanthin and as esterified astaxanthin (like astaxanthin dipalmitate).

- Free astaxanthin is available either as a synthetic substance produced by chemical industry based on crude oil, or as a natural product made by the yeast phaffia rhodozyma (AstaBioCareï).

- Esterified astaxanthin is available as an algae based meal produced by the algae haematococcus pluvalis.

No studies have been conducted on humans to establish in which form astaxanthin is most efficiently absorbed in the diet. But investigations has been performed on salmon and trout. In these studies, fish is given the same amount of astaxanthin (as carotenoid equivalents) either as free astaxanthin or as esterified astaxanthin.

The results indicate a better absorption of free astaxanthin as indicated by flesh pigmentation, astaxanthin concentration and measured digestibility. The latter is calculated by comparing amount of astaxanthin in feed and in faeces (25,26,27).

Astaxanthin from Phaffia Rhodozyma - production Our astaxanthinÊproduced by fermentationusing a proprietary process technology. Igene Biotechnology inc has developed this technology and the product during the last 12 years. More than $30 million has been spent in research and development of this product. The production is done in accordance with cGMP regulations in a GMP approved pharmaceutical facility.

Astaxanthin as a dietary supplement

Astaxanthin from Phaffia Rhodozyma is permitted by FDA as a dietary supplement in dosages of 2mg a day. It can be manufactured as the sole ingredient in capsule form, or as an ingredient in a mixture with other antioxidants or vitamins. Astaxanthin contains free astaxanthin produced by yeast, and as such is available in the most absorbable form.

Astaxanthin and consumer promotion

Astaxanthin is a naturally occurring antioxidant. Its safety is well documented. It has a proven protective role in aquatic life. It exhibits the same antioxidant properties in humans. Scientific studies suggests effects against most of the plagues of western society, diseases witch sooner or later will affect most of us.

Astaxanthin - summary of papers

Presented here are short summaries of articles in the text. We will also recommend a search on ÒastaxanthinÓ on Internet seeking engines or in any medical database.

Antioxidative effect

(1) Mike W. 1991. Biological functions and activities of animal carotenoids. Pure and applies Chem. 63: 141-146. Summary: Quenching effect against singlet oxygen against free radicals for a variety of substances is examined. It is found to be 10 times stronger in astaxanthin than in other carotenoids, and 100 times greater than vitamin E.

(2) Nakagawa, K., Kang SD, Park DK, Handelman GJ, Miyazawa T 1997. Inhibition of beta careotene and astaxanthin of NADPH dependent microsomal phospholipid peroxidation. J Nutr Sci Vitaminol June; 43(3): 345-55. Summary: A study demonstrating the protective role of carotenoids when a lipid membrane is exposed to oxidative stress.

(3) O`Connor I., O`Brian N., Modulation of UVA light-induced oxidative stress by beta-carotene, lutein and astaxanthine in cultured fibroblasts. J. Dermatol. Sci. 1998 Mar; 16(3): 226-30. Summary: Rat kidney fibroblasts are in this study exposed to UVA-light. Levels of oxidative stress is measured and compared in cells protected by beta-carotene, lutein and astaxanthin, with astaxanthin exhibiting superior protective properties.

(4) Terao J 1989. Antioxidant activity of beta-carotene-related carotenoids in solutions. Lipids 1989 Jul; 24(7): 659-61. Summary: Canthaxananthin and astaxanthin are more effective antioxidants than beta-carotene in stabalizing trapped radicals.

(5) Rengel D, Diez-Navajas A, Serna-Rico A, Veiga P, Muga A, Milicua JC 2000. Exogenously incorporatec ketocarotenoids in large unilamellar vesicles. Protective activity against peroxidation. Biochim Biophys Acta 2000 Jan 15; 1463(1): 179-87. Summary: The ability of cantacanthaxanthin and astaxanthin as chain breaking antioxidants in a membranous vesicle is examined. Both xantophylls are interspersed among phospholipid membranes. Astaxanthin showed the strongest antioxidant activity.

(6) Jorgensen K, Skibsted LH 1993. Crotenoid scavenging of free radicals. Effect of carotenoid structure and oxygen partial pressure on antioxidant activity. Lebensm Unters Forsch 1993 May; 196(5): 423-9. Summary: Four different carotenoids examined suppress peroxidation of lipids. Astaxanthin is the most stable compound and therefore the most efficient suppressor of peroxidation.

Cancer

(7) Tanaka T. et al. 1995a. Suppression of azomethane-induced rat colon carcinogenesis by dietary administration of naturally occurring xantophylls astaxanthin and cantaxanthin during the postinition phase. Carcinogenesis 15 (1). Summary: Rats are fed a cancer inducing agent. During the study some of the rats are given astaxanthin or the related compound cantaxanthin. At the end of the study the incidence of neoplasms was significantly smaller in rats fed on astaxanthin or cantaxanthin than in the rats given the cancer inducing agent alone.

(8) Tanaka T et al 1995. Chemoprevention of rat oral carcinogenesis by naturally occurring xanthophylls, astaxanthin and cantaxanthin. Cancer Res 1995 Sep 15; 55(18): 4059-64. Summary: Rats given cancer inducing agents are protected by astaxanthin and canthaxanthin from cell proliferation and oral carcinogenesis.

(9) Tanaka T et al 1994. Chemoprevention of mouse urinary bladder carcinogenesis by the naturally occurring carotenoid astaxanthin. Carcinogenesis 1994 Jan;15(1): 15-9. Summary: Rats given cancer inducing agents are protected by astaxanthin (not by canthaxanthin) from urinary bladder cell proliferation and carcinogenesis. Astaxanthin is a possible chemopreventive agent.

(10) Chew BP, Park JS, Wong MW, Wong TS. A comparision of the anticancer activities of dietary beta-carotene, cantaxanthin and astaxanthin in mice in vivo. Anticancer Res. 1999, May-June (19) 3a 1849-53. Summary: Mice inoculated with mammary tumor cells were fed carotenoids. Tumor growth vas inhibited especially by astaxanthin.

(11) Jyonouchi, H., Sun S., Iijima K., Gross MD. Antitumor activity of astaxanthin and its mode of action. Nutr. Cancer 2000 36(1) 59-65. Summary: Rats are inoculated with subcutaneous fibrosarcoma tumor cells. Cells in rats fed astaxanthin had significantly lover tumor size and weight than controls. The authors also discuss the mechanisms of this action, concluding that their results indicate that dietary astaxanthin suppress tumor cell growth and stimulate immunity against tumor antigen. This potent antitumor activity is present at physiologically achievable concentrations.

Vision

(12) Seddon JM et al. 1994, Dietary carotenoids, vitamins A, C and E, and advanced age related macular degeneration. JAMA 272 (18): 1413-1420. Summary: This is a review article arguing that antioxidant molecules like carotenoids reduces oxidative damage and therefore protects against age related macula degeneration.

(13) Snodderly DM. Evidence for protection against age-related macular degeneration by carotenoids and antioxidant vitamins. 1995 Am J Clin Nutr 62 (suppl): 1448S-1461S. Summary: This is an epidemiological study comparing patients with and without macular degeneration (the most common cause of blindness). Conclusion: Increased intake of food rich in carotenoids decreases risk of developing age related macular disease.

(14) Tso MOM, and Lam TT 1996. Method of retarding and ameliorating central nervous system and eye damage. US patent # 5527533. See http://www.uspto.gov/patft/ Summary: The ability of astaxanthin to cross the blood brain barrier is proven. Damage to the retinas of albino rats exposed to ultraviolet light is measured. Feeding the rats astaxanthin protects the photoreceptor cells from photic injury. Muscle strength (15) Lignell, � (1999) Medicament for improvement of duration of muscle function or treatment of muscle disorders or diseases, Patent Coorperation Treaty application #9911251. AstaCarotene AB, Sweeden. Summary: A double blind placebo controlled study including 40 young healthy male students randomly divided in a group given 4 mg a day of astaxanthin and a group given placebo. The average number of knee-bendings increased significantly more in the supplement group during a six months exercise period.

Immune system

(16) Okai Y., K. Higshi-Okai. 1997, Possible immunomodulating activities of carotenoids in in vitro cell culture experiments. Int. J. Immunopharmac. Vol. 18. No. 12. Summary: Astaxanthin stimulates the production of antibodies in spleen cells.

(17) Jyonouchi H., S. Sun and G. Myron, 1995. Astaxanthin stimulates antibody production in spleen cells. Effect of carotenoids on in vitro immunoglobulin production by human peripheral blood mononuclear cells: Astaxanthin, a carotenoid without vitamin A activity, enhances in vitro immunoglobulin production in response to a T-dependant stimulant and antigen. Nutr. Cancer 23(2): 171-183. Summary: Using human blood it is shown that astaxanthin enhances production of antibodies in response to T-dependant stimuli. Other carotenoids (Beta-carotene) were not found to have this effect.

Skin

(18) Savoure N., et al. Vitamin A status and metabolism of cutaneous plyamines in the hairless mouse after UV irradiation: action of beta-carotene and astaxanthin. Int. journal for vitamin and nutrition research. 1995; 65 (2) 79-86. Summary: Hairless mice are exposed to UV irradiation. After exposure, damage to skin is measured. Mice treated with astaxanthin showed less damage than untreated mice. To quote the authors; Òastaxanthin was remarkably effective in preventing damage.Ó

H. pylori infection

(19) Wang X., Willen R., Wadstrom T. Astaxanthin-Rich Algeal Meal and Vitamin C Inhibit Helicobakter pylori Infection in BALB/ cA Mice. Antimicrob. Agents Chemoter. 2000 sep 44 (9), 2452-2457. Summary: H. pylori infected mice treated with astaxanthine-rich algal meal or with vitamin C show significantly lower colonization levels and lower inflammation score than untreated animals.

(20) Bennedsen M et.al. 1999 Treatment of H. Pylori infected mice with antioxidant astaxanthin reduces gastric inflammation, bacterial load and modulates cytokine release by splenocytes. Summary: The bacterium Helicobacter pylori is affecting about half the population of the world, causing gastritis, and in some patients gastric ulcer, duodenal ulcer, gastric cancer or MALT lymfoma. In the present study infected mice fed astaxanthin show significantly reduced levels of colonisation and inflammation.

Cholesterol and atherosclerosis

(21) Murillo E, 1992. Efecto hipercolesterol�mico de la cant astaxanthina y la Astaxanthin en ratas. Arch. Latinoamericanos Nutr. 42: 409-413. Summary: When rats are fed astaxanthin, cholesterol levels incrase, mainly due to an increase in the HDL-fraction of the lipoproteins.

(22) Chisolm GM, Steinberg D. The oxidative modification hypothesis of atherogenesis: an overview. Free Radic Biol Med 2000 june 15;28(12):1815-1826. Summary: An overview article on the theory that oxidative modification of LDL is of importance in the development of atherosclerotic disease. The authors conclude that data in support of this theory is mounting, but many questions still remain unanswered.

(23) Carpenter KLH et. al: 1997, The carotenoids beta-carotene, canthaxanthine and zeaxanthin inhibit macrophage-mediated LDL oxidation FEBS Letters 401: 262-266 Summary: Experimental data confirming that carotenoids might inhibit the oxidation of LDL.

Astaxanthin in salmon

(24) R. Christiansen, ¯.Lie, O. J. Torrissen: Effect of astaxanthin and Vitamin A on growth and survival during first feeding of Atlantic salmon Salmo salar L Aquaculture and Fisheries Management 1994, 25, 903-914. Summary: Poor growth and low survival rates are observed in Salmon fed diets without astaxanthin, including salmon given sufficient vitamin A. This suggests a specific function of astaxanthin, and establishes it as an essential nutrient during first-feed period.

Absorption of astaxanthin

(25) Storebakken T. Foss P. Schiedt K. Austreng E. Liaaen-Jensen S. Manz U. Carotenoids in Diets for Salmonids IV Pigmentation of Atlantic Salmon with Astaxantin, Astaxantin Dipalmitate and Canthaxantin, Aquaculture 65 (1987) 279-292. Summary: Different concentrations and forms of astaxanthin is given in the diet of Salmon. Digestibility is determined by measurement of faecal content of astaxanthin. It is determined to be 64% for free astaxanthin and 47% for astaxanthin dipalmitate. Also, the flesh concentration of astaxanthin is significantly higher in the group of fish fed free astaxanthin. In the discussion this is said to confirm the findings in most earlier studies.

(26)Foss P. Storebakken T. Austreng E. Liaaen-Jensen S. Carotenoids in Diets for Salmonids. V. Pigmentation of Rainbow Trout and Sea Trout with Astaxanthin and Astaxanthin Dipalmitate in Comparision with Canthaxanthin. Aquaculture 65 (1987) 293-305. Summary: Trout and seatrout are fed carotenoids as free astaxanthin, esterified astaxanthin (astaxanthin dipalmitate) and canthaxanthin. Flesh pigmentation is compared. Results support earlier findings indicating that hydrolysis of the ester linkage is a limiting step in the utilization of astaxanthin esters by salmonids.

(27) Storebakken T. S¿rensen M. Bjerkeng B. Effects of degrees of enzymatic cell wall digestion of the red yeast, Phaffia rhodozyma, and feed extrusion temperatures on astaxanthin availability in rainbow trout, Oncorhynchus mykiss. AKVAFORSK-Report 15/00. Summary: The experiment performed in this article is not relevant to the discussion above. But the authors compare in their discussion absorption of free astaxanthin as produced by yeast to esterified astaxanthin as produced by algae. According to the discussion yeast is the best source due to more effective uptake and utilization. Esterified astaxanthin is not so beneficial due to limited capacity of intestinal esterase to hydrolyse the astaxanthin esters.