Due the their high antioxidant properties and other function, many astaxanthin containing

nutraceuticals with potent effect on human health are coming onto the market
STRUCTURE AND SOURCE OF ASTAXANTHIN
The astaxanthin molecule has a symmetric configuration and two chiral centers ; two carbon
atoms adjacent to hydroxyl functional group are chiral. There are three enantiometric isomer of
astaxanthin, 3S 3S, 3R 3R, and 3R 3S. chemically synthesized astaxanthin is a mixture of
1:2:1 of 3s 3s 3r 3r and 3r 3r enantiomer, respectively. This is mainly used in the field of
aquaculture as a reviver and is not used as an ingredient in human neutraceuticals. A green
microalga ( H. pluvialis), a red yeast (phaffia rhodozyma), and crustacean by product are
commercially available as natural sources of the astaxanthin pigment. These sources are often
used in the nutraceutical industry because of recent natural food trends and safety concerns. The
form of astaxanthin in these natural sources are slightly different from each other. Astaxanthin
from haematococcus is the 3s 3s isomer and is almost esterified with fatty acid to form mono or
diester. In contrast, phaffia rhodozyma is reported to synthesize the 3R, 3R isomer, which is
mainly unesterified. Haematococcus alga is considered to be the most efficient natural source of
astaxanthin and is presently used as the main source of natural astaxanthin.
ANTIOXIDATIVE ACTIVITY OF ASTAXANTHIN
Carotenoids are generally known to possess powerful antioxidative activity, thought to be
because of their long conjugated polyene system. The stable structure and strong antioxidative
activity of astaxanthin is considered to be due to the conjugation of the oxo group to the polyene
system. Astaxanthin is reported to show a strong quenching effect against singlet oxygen, with
potency more than 100-fold higher than that of a-tocopherol. This same study also reports that
astaxanthin shows strong activity against lipid peroxidation. In addition, astaxanthin is reported
to have no pro-oxidative properties; other carotenoids, such as b-catorene, lycopene, and
zeaxanthin, under certain conditions, are considered to possess pro-oxidative properties.
HEMATOCOCCUS ALGAE
H. pluvialis, Flotow, Volvocales, Chlorophyceae, is a unicellular freshwater green microalgae. In
response to environmental condition, the green flagellated cells (vegetative cells) gradually
transform into cyst cells without flagellae ( the aplanospores), accompanied by a marked
accumulation of astaxanthin, resulting in the formation of red-colored cells. The size of
vegetative cell is less than 10micrometer in diameter, although is gradually increases to over 4050 nm after transforming into cist cells. In oxygenic photosynthetic organisms, carotenoids play
importany roles in the light-harvesting complex and in the protection of photosynthetic
machinery, by dissipating axcess light energy. These types of carotenoids are referred to as
primary carotenoids and are essential in metabolism. These carotenoids are localized in thylakoid

membranes of rge chloroplast. In contrast, secondary carotenoids such as astaxanthin are not
functionally obligatory for photosynthesis. Astaxanthin in H. pluvialis accumulates in
cytoplasmic lipid globules of the cells: accumulation occurs in response to environmental
stimuli, such as high light intensity and oligotrophic conditions. In H.pluvialis, it is considered
that astaxanthin acts as sunshade , to provide protection from photodamage, or to minimize
oxidation of storage lipids.
BENEFITS OF ASTAXANTHIN FOR HUMAN HEALTH MANAGEMENT
As a company which supplies functional food ingredients, it is important that we invedtigate the
effectiveness of the ingredient we produce. It is generally accepted that oxidative stress is
involved not only in the normal aging process but also in the pathogenesis of many acute,
chronic, and agerelated diseases, including inflammation, cancer, cardiovascular disease,
neurodegenetarive disease, lung disease, and eye disease. Naturals antioxidants are scavengers of
reactive oxygen species including free radicals, and therefore have broad implications in
antiaging and human health management. As described in the previous section, astaxanthin has a
strong antioxidative activity and hence various physiological efficacies. In the next section, we
present out clinica evidence for the efficacy of our astaxanthin-rich H.pluvialis oil on oxidative
stress-related diseases/aging, especially atopic dermatitis, brain health, and metabolic syndrome.
ASTAXANTHIN AND ATOPIC DERMATITIS
There are many lines of evidence suggesting that allergic disorders, such as atopic dermatitis,
asthma, and rhinitis, are mediated by oxidative stress. We observed that the administration of
astaxanthin significantly suppressed ear swelling in NC/Nga mice which had been previously
sensitized by intradermal injections of mite antigen into the ear pinnae, inducing atopic
dermatitis like lesions. We further investigated the effect of astaxanthin intake on atopic
dermatitis by a double-blind, randomized, placebo-controlled clinical trial.
In this study, patients (aged 19-51 years) with mild to moderate atopic dermatitis ingested
astaxanthin-rich H.pluvialis oil, equivalent to 12 mg of astaxanthin dialcohol (Ax group, six men
and eight woman) or corn oil (placebo group , six men and seven women) contained of soft
capsules, once daily for 4 weeks. Before and after administration, evaluations were made on
severity (scoring atopic dermatitis, SCORAD), pruritus (visual analog scale; VAS), quality of
life (Skindex-16 and state trait anxiety inventory, STAI), immune function (Th1/Th2 and blood
catecholamines), and antioxidative status (urine 8-OHdG and isoprostane). No significant
difference in severity and pruritus was apparent between the Ax and placebo groups. However,
the Ax group showed significant amelioration of symptoms evaluated by skindex-16 and on
anxiety state evaluated by STAI. The ameliorating effect on anxiety by astaxanthin was
supported by the level of the stress hormone, dopamine, which was significantly decreased in the
Ax group. The level of urine 8-OHdG,which is reported to be high in patient with atopic
dermatitis, decreased significantly in the Ax group, indicating that astaxanthin intake has an

antioxidative efficacy. Furthermore, the study revealed that there was a statistically significant
shift in the Th1/Th2 balance toward Th1 in the Ax group. Atopic dermatitis is characterized by
Th2-dominated allergic skin inflammation. It is known that higher anxiety in patients enhances
the Th2-type response, due to dysregulation of the neuro immune system, leading to worsening
of the allergic symptoms. The finding of this study, which showed that patients in the Ax group
showed reduced anxiety accompanied by a shift in the Th1/Th2 balance toward Th1, strongly
suggests that astaxanthin is a promising food factor in the management of atopic dermatitis.
ASTAXANTHIN AND BRAIN HEALTH
Brain aging, either natural or in neurodegenerative disorders, is also closely associated with
oxsidative stress, subsenquent damage to cellular components (DNA oxidation/mutation, protein
modification/aggregation, and lipid peroxidation), inflammation, and other factors, including
excess calorie intake, insulin resistance, and mitochondrial dysfunction leading to neuron death.
In connection with the effect to astaxanthin on the factors involved in brain aging, we have
observed the following findings; 1. Astaxanthin protects neuroblastoma cells from oxidativestress induced apoptosis in vitro. 2. In dopaminergic neuron-specific manganese superoxide
dismutase (MnSOD)-deficient mice which display parkinsonian symptons, oral administration of
astaxanthin resulted in improvement of body weight loss and behavior function and hence an
increase in life span. 3. Astaxanthin improves mitochondrial function by maintaining a high
mitochondrial membrane potential, stimulating respiration , maintaining mitochondria in a
reduced state even under oxidative challenge. In addition, a memory improving effect of
astaxanthin in mice has been reported by other research groups. However, there had been no
studies investigating the effect of astaxanthin on the higher cognitive function of the human
brain.
We therefore conducted a preliminary clinical evaluation, an open-label trial using 10 otherwise
healthy male subjects (50-69 years of age) who complained of age related forgetfulness. Age
associated memory impairment is a common condition characterized by very mild symptoms of
cognitive decline that occur as part of the normal aging process (NYU medical center / NYU
school of medicine) in our study, subject ingested astaxanthin-rich H.pluvialis oil, equivalent to
12 mg of astaxanthin dialcohol, contained in soft capsules, once daily for 12 weeks. Cognitive
function was evaluated before administration (at baseline) and again every six weeks during the
study, using either the CogHealth tool (Cogstage, Melbourne, Australia) or the event-related
P300 recognition response elicited by an auditory task. Coghealth is a cognitive function test
specifically designed to detect changes in healthy or mildly impaired subjects at an early date.
The trial revealed significant reduction in response time on all tasks in Coghealth ; phychomotor
speed, impulse control, working memory, episodic learning, and attention, after 12 weeks intake
of astaxanthin. The accuracy on the working memory task in coghealth was also significantly
improved after 12 weeks of treatment. The P300 peak amplitude tended to increase after 12
weeks astaxanthin administration, indicating that astaxanthin might increase patient informasion
processing capacity and selective attention. All tasks investigationby coghealth and P300 are

indispensable for a skilful performance in daily like activities such as driving, which is a
complex form of activity involving specific cognitive and phychomotor functions. Age-related
decreases in these task are therefore a serious problem, causing an increased number of traffic
accident and deaths in older people. double-blind, randomized, placebo-controlled clinical trial
investigation the effect of astaxanthin on coghealth tasks and driving performance are currently
in progress.
ASTAXANTHIN AND METABOLIC SYNDROME
Metabolic syndrome is characterized by a clustering of metabolic risk factors for cardiovascular
disease in one person. The risk factors include abdominal obesity; insulin resistance, elevated
blood glucose, atherogenic dysplidemia and hypertension. Metabolic syndrome is closely
associated with oxidative stress and adipose tissue inflammation, and the improving effects of
astaxanthin on metabolic syndrome have been suggested in several animal models.
We attemted to confirm the clinical efficacy of astaxanthin in an open label uncontrolled study
using volunteers at risk of metabolic syndrome. In this trial, a total of 17 volunteers between 12
and 65 years of age (13 men and 4 women) at risk of developing metabolic syndrome were
administered with astaxanthin-rich H.pluvialis oil, equivalent to 8 mg of astaxanthin dialcohol,
twice daily for 12 weeks. A significant increase in adiponectin levels and a significant decrease
in tumor necrosis factors (TNF) a levels were onserved. In addition, a significant decrease in
glycohemoglobin (HbAIc), a diagnostic marked of diabetes, was observed. Adiponectin has an
antidiabetic effect; it decreaed blood glucose as a good indicator of metabolic syndrome. While
TNF-a increases insulin resistance. It is generally accepted that the reduced secretion of
adiponectin and increased secretion of TNF-a in dysfunctional adipose tissue (inflamed adipose
with enlarged adipocytes and impaired preadipocyte differentiation) increase insulin resistance in
the phatogenesis of metabolic syndrome. Our result showed that astaxanthin intake increased
adiponectin levels and decreased TNF-a levels, which strongly suggest that astaxanthin has a
positive effect on the proin flammatory state of dysfunctional adipose tissue and hence on
elevated blood glucose. This is confirmed by a significant decrease in glycohemoglobin (HbAIc)
in humans at risk of metabolic syndrome.

CONCLUDING REMARKS
In this chapter, we discussed our indoor photobioreactor, a highly controlled microalgal
cultivation technology, with high sterility, light illumination efficiency, and therefore high and
stable biomass productivity on a commercial scale. Although microalgae have been recognized
as promising organism to provide sourced of natural product in functional foods in the
nutraceutical and pharmaceutical industry, only a few algal strains and their products have been

successfully marketed so far, as described in section 18.2. our microalgal cultivation technology,
using an indoor photobioreactor, is considered to be competitive in the production of high-value
bioactive metabolites with low cellular content. The use of sterilized, high density algal
suspensions can be advantageous in downstream processing such as concentration and extraction
processes, particularly for neutraceticals and pharmaceuticals obtained from microalgae which
are difficult to culture outdoors. Another possible application of our technology seems to be the
cultivation of genetically engineered microalgae that will most likely be banned from outdoor
cultivation systems, transgenic algal strains that express good concentrations of several
recombinant therapeutic proteins have already been successfully generated. Further improvement
of our cultivation technology, as well as innovations of other important technologies such as
solar electricity and low-cost reactor materials, are needed to develop more competitive and
economically feasible algal biomass production systems. Together with finding useful algal
strains and their metabolites, he innovations of our cultivation technology and other cultivationrelated technologies will bring advancement and expansion to microalgal business opportunities
in the human health industry.