ASTAXANTHIN REVIEW - BENEFITS, SIDE EFFECTS, DOSAGES, USES

Updated on February 09, 2012

Astaxanthin Review Astaxanthin ([3S,3'S]-3,3'-dihydroxy-p,p-carotene4,4'-dionCeA,S Registry Number 472-61-7 has molecular weight of 596.8 daltons. Astaxanthin esters are available as dark red viscous oils. Astaxanthin is practically insoluble in water, it is partially soluble in ethanol, soluble in acetone and n-hexane. Two popular extraction methods are used for astaxanthin and they are supercritical CO2 extraction and acetone extraction method. Compositional analysis of astaxanthin esters manufactured by both methods is similar, but the acetone extracted product has higher values for tocopherols and phospholipids. The slightly higher levels of tocopherol and phospholipids may be related to the polarity of the solvent use. [GRN 0294] Astaxanthin is a naturally occurring carotenoid pigment, it is also a powerful biological antioxidant. Astaxanthin has strong free radical scavenging activity and protects against lipid peroxidation and oxidative damage of LDL-cholesterol, cell membranes, cells, and tissues. Astaxanthin is believed to have many health benefits. Chemicially, astaxanthin has two chiral atoms and several double bonds. Though structurally similar to beta-carotene, astaxanthin is polar and more anti-oxidative, and the structural attributes of astaxanthin have been purported to enhance its membrane function activities and thus provide a benefit or a protective effect against degenerative conditions. Astaxanthin can be found in many of seafoods such as salmon, trout, seabream and shrimps. Astaxanthin cannot be synthesized by animals and must be provided in the diet. The main or richest commercial source for natural astaxanthin is Haematococcus pluvialis microalgae. Manufacturers have the advanced biotechnology process to cultivate large amount of enriched algae cells for mass production and eliminate the issues of contaminations and salinity. Haematococcus microalgae is cultivated in an environmental conditions using the natural sun light as the energy source all year round. Thus, the process is cost-effective and users enjoy the low price of astaxanthin supplements. For last 2 decades, 300 articles and patents or more have been published about astaxanthin. Astaxanthin is a small lipid soluble molecule, it can cross the blood brain and retina barriers easily. Because of its antioxidant activities and its blood brain/retina permeability, astaxanthin was found to have benefits on inflammation, diabetics, certain cardiovascular, vision and neuronal conditions. The uses of astaxanthin esters are for addition to foods as a nutrient. Astaxanthin has been shown to protect the cellular and mitochondrial membranes and ocular tissues against oxidative damage. Addition of astaxanthin to certain food is intended for populations that do not consume marine foods. Astaxanthin is also commonly used as an

color additive in the feed of salmonid fish to enhance the color of the flesh. [GRN 0294] _________________________________________________________________________________ ________________________________ Astaxanthin Benefits Astaxanthin is a powerful antioxdative agent. In a study, astaxanthin was added to rat liver microsomes undergoing radical-initiated lipid peroxidation, astaxanthin is more effective than beta-carotene in inhibiting the process. [2] In another study, large unilamellar liposomes comprising of egg yolk phosphatidylcholine was exposed to photoirradiation in the presence of photosensitizers. Astaxanthin decreased the process much slower than beta-carotene, lycopene, and alpha-carotene. [4] Another early study showed that astaxanthin was able to protect against UV-induced oxidative stress in rat kidney fibroblasts. [7] With such strong anti-oxidative effects, one may expect that astaxanthin carries many benefits. The following section discusses about astaxanthin's potential benefits. Cancers Astaxanthin showed potential benefits against various cancer cells in animal studies or test-tube studies. Clinical studies are needed to support its beneficial claims on its potential application on chemotherapy. Cardiovascular Events Astaxanthin may have protective benefits on heart. A study of mice has shown that astaxanthin attenuated exercise-induced damage in mouse skeletal muscle and heart, including an associated neutrophil infiltration that induces further damage. In the study, the researchers required the mice to perform vigorous exercise and they found the protection of astaxanthin on the cardiac muscle. [11] Another study has demonstrated that astaxanthin significantly prolonged the LDL oxidation lag time. [12] Diabetes Astaxanthin may have benefits on diabetic patients. Oxidative stress induced by hyperglycemia possibly causes the dysfunction of pancreatic beta-cells and various forms of tissue damage in patients with diabetes mellitus. Astaxanthin elicited beneficial effects on the progressive destruction of pancreatic beta-cells in db/db mice--a well-known obese model of type 2 diabetes. [10] Astaxanthin was also found to have a protective effect on endothelial dysfunction of aortas in diabetic rats and the possible molecular mechanism involved. [Zhao ZW et al;. Arzneimittelforschung. 2011;61(4):239-46] Hypertension Astaxanthin may benefit users at risk of hypertension. A study of spontaneously hypertensive rats has shown the antihypertensive effects of astaxanthin. Oral administration of astaxanthin for 14 days induced a significant

reduction in the arterial blood pressure. The long-term administration of astaxanthin (50 mg/kg) for 5 weeks in stroke prone rats induced a significant reduction in the blood pressure. [16] Immunity Astaxanthin may benefit user's immune system by enhancing antibody production. Astaxanthin enhanced in vitro antibody production to sheep red blood cells in normal B6 mice. [3] When the actions of carotenoids were tested in normal strains of mice, astaxanthin enhanced in vitro antibody production to T cell-dependent antigen. And, astaxanthin exerted maximum enhancing actions when it was present at the initial period of antigen priming. [3] Astaxanthin Safety Issue and Astaxanthin Side effects Astaxanthin is probably safe at low oral doses, with no side effects when it is consumed in amounts found in food. A rat study also supports the claim that astaxanthin is sate without side effects at low doses. [1] A study showed here were no adverse side effects resulting from the administration of astaxanthin 6 mg/day for 10 days. [3] High doses of astaxanthin do have side effects. A study shows the main site of astaxanthin accumulation, indeed, was the hairless skin of the tail, this was associated with red coloration. Potential adverse side effects such as lesions in the kidneys of three animals and a slight (n.s.) change in the leucogram were also noted. Furthermore, astaxanthin accumulated in the eyes in the same magnitude as it is known for canthaxanthin in the eyes of rats. It is also unknown how it affects the skin, when it is used in topical applications. _________________________________________________________________________________ ___________ Astaxanthin Dosage Astoxanthin Dosages Used in Studies A study of spontaneously hypertensive rats has shown the antihypertensive effects of astaxanthin. Oral administration of astaxanthin for 14 days induced a significant reduction in the arterial blood pressure. The long-term administration of astaxanthin (dosage 50 mg/kg) for 5 weeks in stroke prone rats induced a significant reduction in the blood pressure. [16] Another study has demonstrated that astaxanthin significantly prolonged the LDL oxidation lag time (31.5, 45.4, 65.0 min) compared with the control (19.9 min) in a doseproportionality manner. In the same study, the researchers dosed 24 volunteers with astaxanthin at doses of 1.8, 3.6,14.4 and 21.6 mg per day for 14 days. They also found the a longer LDL oxidation lag time. [12] Finally, a study (of 35 healthy adults) reveals that 6 mg of astaxanthin per day can be safely consumed by healthy adults. [2] One study of the effects of astaxanthin on human blood rheology were investigated in 20 adult men with a single-blind method. A blood rheology test that measures whole blood transit time was conducted using heparinized blood of the

volunteers. After administration of astaxanthin 6 mg/day for 10 days. _________________________________________________________________________________ __________ Fuji GRAS notice GRN 000294 cites studies which have shown that no adverse effects of astaxanthin have been noted at doses of up to 40 mg/day in humans, and up to 465 and 557 astaxanthin/kg/day (highest dosage tested) in male and female rats, respectively. Given that the daily intake of astaxanthin from the intended uses of Natural Astaxanthin Complex at the 90th percentile of 5.4 mg/person (0.1 mg/kg body weight/day) is approximately seven-fold lower than the demonstrated safe levels of human intake of at least 40 mg astaxanthin per day (0.67 mg/kg body weight/day), the estimated daily intake in humans is from 500 to 5000-fold lower than the demonstrated safe level. The safety of astaxanthin has been as evidenced by its use as a dietary supplement for over more 10 years in the United States without any adverse side effects. Typical recommended doses of these astaxanthin extracts are approximately 6mg/day (dosage range: 2 to 12 mg/day). At 6 mg/day, the daily estimated 90th percentile intake dosage is 5 4 mg astaxanthin per day. [Reference: Notification of GRAS Determination for Natural Astaxanthin Complex (AstaPure), TC Associates, Inc. 13 September 2010] _________________________________________________________________________________ _________

There are always new information. Please, send me an email (zhion@zhion.com) to correct my mistake(s). Reasonable care has been taken in preparing this document and the information provided herein is believed to be accurate. The information is not intended to be a substitute for professional medical advice. It is important to seek the advice of a physician about any medical condition or symptom or the benefits and side effects of an astaxanthin supplement or a drug product. Finally, please, do not transfer the article to other website. Thank you. ALL RIGHTS RESERVED. _________________________________________________________________________________ __ Astaxanthin Benefits / Astaxanthin Side Effects / Astaxanthin Dosage / Astaxanthin Cancer / Astaxanthin Reference

_________________________________________________________________________________ __ Company Product(s) Description Cyanotech Corp. BioAstinB 4mg algal meal in gelatin capsules (I<ailua-Kona, HI) Gel Caps 5% astaxanthin SCF-CO2 extract SCE5 7% astaxanthin SCF-C02 extract SCE7 1.35% astaxanthin gelatin beadlets Beadlets Mera Pharmaceuticals (I<ailua-Kona, HI) FUJI Health Science BioReal (Maui, HI) BioReal (Sweden) Valensa International :Eustis, FL) AstaFactoa 5 mg astaxanthin algal meal in soft gels SCF-C02 extract of algal meal 2 mg astaxanthin gelatin capsules 10% astaxanthin oleoresin 2% astaxanthin water dispersible SCF-CO2 extract of algal meal 5 mg astaxanthin gelcap 2.5% astaxanthin complex 2.0% astaxanthin complex SCF-CO2 extract of algal meal 10 to 25% Astaxanthin oleoresin 4 mg astaxanthin gelatin capsules 2 to 2.5% astaxanthin granules

AstaRealB Gel Caps L-I 0 P2AF ZanthinB Complex Vegetarian softgel Beadlets AstaPure Oleoresin Capsules Beadlets

Algatechnologies Ltd Kibbutz Ketura Israel

Astaxanthin as anti-cancer agent Astaxanthin is as effective as alpha-tocopherol in inhibiting radical-initiated lipid peroxidation in rat liver microsomes. In this system, beta-carotene appears to be a much less potent antioxidant. [2] In another study, large unilamellar liposomes comprising of egg yolk phosphatidylcholine was exposed to photoirradiation in the presence of photosensitizers. Without sensitizers, astaxanthin decreased the process much slower than beta-carotene, lycopene, and alpha-carotene. [4] Research also shows that astaxanthin is an immunomolulator, astaxanthin enhances in vitro antibody production to sheep red blood cells in normal B6 mice. [3] Because of its immulomodulatory and anti-oxidative activities, astaxanthin may offer benefits to patients suffered from cancers. Bladder cancer In a study, mice were given drinking water with a carcinogen for 20 weeks then, water containing astaxanthin. It was found astaxanthin administration significantly reduced the chance of bladder cancer. Treatment with astaxanthin also decreased the number/nucleus of silver-stained nucleolar organizer region proteins, an index of cell proliferation. Astaxanthin may suppress cell proliferation. [5] And then, it may benefit people at risk of certain bladder cancers. Colon Cancer Dietary astaxanthin was found to significantly inhibit the occurrence of colonic mucosal ulcers, dysplastic crypts, and colonic adenocarcinoma at week 20 in a study of mice. [Yasui Y et al, Chem Biol Interact. 2011 Aug 15;193(1):79-87.] Oral carcinogenesis

In another study, researchers fed the animals with 100 ppm astaxanthin during the initiation or postinitiation phase of 4-NQO-induced oral carcinogenesis. It was found the incidences of preneoplastic lesions and neoplasms in the oral cavity of rats fed with astaxanthin were significantly smaller than those without astaxanthin treatment. In particular, no oral neoplasms developed in rats fed with astaxanthin during the 4-NQO exposure. [6] Mammary tumor cells One early study demonstrated the anticancer activities of astaxanthin against the growth of mammary tumors in mice. In the study, the mice were fed with a synthetic diet containing 0, 0.1 or 0.4% astaxanthin. After 3 weeks, all mice were inoculated tumor cells into the mammary fat pad. 45 days later, animals were killed and it was found that astaxanthin decreased mammary tumor volume in a dose-dependent fashion. [8] Prostate cancer cells In a study, astaxanthin demonstrated 98% inhibition of 5alpha-reductase at 300 microg/mL in vitro. Inhibition of 5alpha-reductase has been reported to decrease the symptoms of benign prostate hyperplasia (BPH) and possibly inhibit or help treat prostate cancer. [14] Liver cancer cells Astaxanthin showed anticancer effect in rat hepatocellular carcinoma CBRH-7919 cells by inducing cell apoptosis through the regulation of mitochondrial-dependent manner. [Song XD, et al, Biol Pharm Bull. 2011;34(6):839-44]. Discussion and Conclusion Astaxanthin appears to be a potent anti-cancer agent, and astaxanthin may benefit people at risk or even suffered from different types of cancers. However, its support is limited to in vitro and animal studies. Clinical studies are needed to further explore this application. Infertility A double blind, randomized trial of 30 men suffered from infertility showed that astaxanthin increased the sperm linear velocity and decreased reactive oxygen species and Inhibin B. [13] Thus, astaxanthin may benefit users at risk of certain types of infertility. Liver Issues Astaxanthin may benefit users at risk of certain liver issues. Astaxanthin was found to protect liver from damage in presence of CCl4, via inhibition of lipid peroxidation and stimulation of the cellular antioxidant system. In the study, astaxanthin subsided the increased glutamate-oxalacetate transaminase and glutamate-pyruvate transaminase activities in response to carbon tetrachloride, while causing an increase in glutathione levels and superoxide dismutase activities in the CCl4-treated rat liver. [9] Ulceration Astaxanthin may benefit users from certain types of ulcers. Researchers supplemented rats suffered from naproxen-induced gastric antral ulceration with astaxanthin. The oral administration of astaxanthin (dosage 1, 5, and 25 mg/kg of body weight) showed a significant protection against naproxen (80 mg/kg of body weight)-induced gastric antral ulcer and inhibited elevation of the

lipid peroxide level in gastric mucosa. They also found that pretreatment of astaxanthin resulted in a significant increase in the activities of radical scavenging enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. The acute gastric mucosal lesion induced by naproxen nearly disappeared after the pretreatment of astaxanthin. [15] GRN No. 294 Haematococcus pluvialis extract containing astaxanthin esters FDA has no questions Applicant: Fuji Chemical Industry Co., Ltd. 55 Yokohoonji, Kamiichi, Toyama 930-0397, JAPAN Substance: Haematococcus pluvialis extract containing astaxanthin esters Intended Use: Ingredient in baked goods, beverages, cereals, chewing gum, coffee and tea, dairy product analogs etc. at a use level to provide 0.1 milligrams of astaxanthin per serving Date of filing: 10-JUL-09