ASTAXANTHIN REVIEW - BENEFITS, SIDE EFFECTS, DOSAGES, USES
Updated on August 13, 2013
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]
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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 t
he 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.
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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 dose-proportionality 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.
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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]
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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.

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Astaxanthin
Benefits / Astaxanthin Side Effects / Astaxanthin Dosage / Astaxanthin Cancer / Astaxanthin Reference
___________________________________________________________________________________
Company
Product(s)
Description
Cyanotech Corp.
(I<ailua-Kona, HI)
BioAstinB
Gel Caps
SCE5
SCE7
Beadlets
4mg algal meal in gelatin capsules
5% astaxanthin SCF-CO2 extract
7% astaxanthin SCF-C02 extract
1.35% astaxanthin gelatin beadlets
Mera
Pharmaceuticals
(I<ailua-Kona, HI)
AstaFactoa
5 mg astaxanthin algal meal in soft
gels
FUJI Health Science
BioReal (Maui, HI)
BioReal (Sweden)
AstaRealB
Gel Caps
L-I 0
P2AF
SCF-C02 extract of algal meal
2 mg astaxanthin gelatin capsules
10% astaxanthin oleoresin
2% astaxanthin water dispersible
Valensa International
:Eustis, FL)
ZanthinB Complex
Vegetarian softgel
Beadlets
SCF-CO2 extract of algal meal
5 mg astaxanthin gelcap
2.5% astaxanthin complex
2.0% astaxanthin complex
Algatechnologies Ltd
Kibbutz Ketura
Israel
AstaPure
Oleoresin
Capsules
Beadlets
SCF-CO2 extract of algal meal
10 to 25% Astaxanthin oleoresin
4 mg astaxanthin gelatin capsules
2 to 2.5% astaxanthin granules
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 post-initiation 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] , A study using hamster buccal pouch carcinogenesis model demonstrates that astaxanthin exerts chemopreventive effects by
concurrently inhibiting phosphorylation of transcription factors and signaling kinases and inducing intrinsic apoptosis. In the study, astaxanthin
inhibits NF-κB, an oncogenic transcription factor, signaling by downregulating the key regulatory enzymes IKKβ and GSK-3β. Astaxanthin also
induced caspase-mediated mitochondrial apoptosis. [17]

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].

Skin Cancer
At 200 μg/kg bw, Astaxanthin diesters and Astaxanthin monoesters reduced UV-7,12-dimethylbenz(a)anthracene-induced tumor incidences up to
96 and 88%, respectively, when compared to astaxanthin (66%) and total carotenoids (85%). UV-DMBA has been known to generate high levels of
free radicals and tyrosinase enzyme, leading to characteristic symptoms of skin pigmentation and tumor initiation. Intriguingly, ∼7-fold increase in
tyrosinase and 10-fold decrease in antioxidant levels were normalized by Astaxanthin diesters and Astaxanthin monoesters as opposed to only ∼1.
4-2.2-fold by astaxanthin and total carotenoids, respectively. [18]

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