Astaxanthin - a superb natural antioxidant
ASTAXANTHIN, a member of the carotenoid family, is a dark-red
pigment which is the main carotenoid found in the marine world of
algae and aquatic animals. ASTAXANTHIN is present in many types
of seafood, including salmon, trout, red sea bream, shrimp and lobster,
as well as in birds such as flamingo and quail. This pigment is
commercially produced from the microalga Haematococcus pluvialis,
the richest known natural source for
Carotenoids are lipid-soluble pigments and antioxidants, which
participate as accessory pigments in the light-absorption process
of photosynthetic organisms. To date, over 600 natural carotenoids
have been identified. They are responsible for the orange and red
colors in plants and algae, and for the wide range of blue, purple
and reddish colors in aquatic animals. Only phytoplankton, algae,
plants and certain bacteria and fungi synthesize carotenoids. Animals,
including humans, must consume carotenoids as part of their diet
and rely on this external supply.
Recent scientific findings indicate that ASTAXANTHIN is a powerful
antioxidant and can serve as a potent free-radical scavenger. Moreover,
ASTAXANTHIN has been found to provide many essential biological
functions, including protection against lipid-membrane peroxidation
of essential polyunsaturated fatty acids and proteins, DNA damage
and UV light effects; it also plays an important role in immunological
Oxygen is necessary for the metabolic production of energy in our
bodies. Mitochondria, through the electron-transport chain, use
oxygen to oxidize certain molecules and generate energy in the
form of ATP. During this process, oxygen is reduced to water, producing
several oxygen-derived free radicals or reactive oxygen species
(ROS) which play an important role in various diseases. Normally,
oxygen free radicals are neutralized by natural antioxidants such
as vitamin E, or enzymes such as superoxide dismutase (SOD). However,
ROS become a problem when either a decrease in their removal or
their overproduction occurs, resulting in oxidative stress. This
stress, and the resultant damage, have been implicated in many
diseases, and a wealth of preventative drugs and treatments are
currently being studied.
ASTAXANTHIN’s powerful antioxidant activity has been demonstrated
in numerous studies showing the detrimental
effects of free-radical-induced oxidative stress (2-4)
and ASTAXANTHIN’s potential to target many important health
There is increasing testimonial evidence that ASTAXANTHIN may be
effective in enhancing general well-being, improving the quality
of life and enhancing the immune system. Recent studies have shown
enhanced immune response and decreased DNA damage in human subjects
following ASTAXANTHIN administration (5).
ASTAXANTHIN is capable of crossing the blood-brain
barrier in mammals (6), a unique and
important property in the realm of antioxidants. This characteristic
allows ASTAXANTHIN to extend its superior antioxidant activity to
the central nervous system, which, being rich in unsaturated fatty
acids is highly susceptible to oxidative damage
by ROS (7).
The efficacy of ASTAXANTHIN in limiting the damage produced by ROS-induced
oxidative stress and improving health parameters in the tissues
and the body was demonstrated in a series of in-vitro experiments,
in pre-clinical studies and in human models. The following is a
list of diseases and conditions for which ASTAXANTHIN
has been shown to have beneficial effects, as described in numerous
medical articles, patents and excellent reviews (8,9)
over the last 10 years:
· Age-Related Macular Degeneration: the leading cause of
blindness in the aging population
Alzheimer's and Parkinson's Diseases: two of the most important neurodegenerative
Cholesterol Disease: ameliorates the effects of LDL, the "bad" cholesterol
Inflammatory, chronic viral and autoimmune diseases
Semen fertility improvement
Sunburn from UV light
Normalization of cardiac rhythm
Benign Prostatic Hyperplasia (BPH)
Stroke: repairs damage caused by lack of oxygen.
A demand for natural ASTAXANTHIN is now emerging in the fast-growing,
multi-billion dollar nutraceutical market; in particular, increasing
evidence suggests that ASTAXANTHIN was shown to be a much more powerful
antioxidant than vitamins C and E, or than other carotenoids such
as beta-carotene, lycopene, lutein and zeaxanthin, among others.
The enhanced activity of ASTAXANTHIN may stem from its molecular
structure. ASTAXANTHIN belongs to the xanthophyll group of carotenoids,
or the oxygenated carotenoids (see other members of the group
in Fig. 1). The hydroxyl and keto functional groups (see
Fig. 1) present in the ending ionone ring of ASTAXANTHIN may
be responsible for its uniquely powerful antioxidant activity and
for its ability to span the membrane bilayers as a direct
result of its more polar configuration relative to other carotenoids
Carotenoids with polar end groups like ASTAXANTHIN span the lipid
membrane bilayer with their end groups located near the hydrophobic-hydrophilic
interface, where free-radical attack first occurs.
Haematococcus pluvialis is believed to accumulate the highest levels
of ASTAXANTHIN in nature. Commercially grown Haematococcus pluvialis
can accumulate more than 40 g of ASTAXANTHIN per kilo of dry biomass
(see Table 1).
TABLE 1 - NATURAL SOURCES OF ASTAXANTHIN
|The primary use
of synthetic ASTAXANTHIN today is as an animal feed additive to impart
coloration to salmonids (salmon and trout), as well as to red sea
bream and tai. In natural habitats, salmonids obtain their coloration
from natural food sources, including algae and crustaceans. However
in fish farms, the absence of natural pigmentation sources results
in salmonids with off-white coloration, imparting an artificial and
unattractive look for consumers and making the fish difficult to
Today, essentially all commercial ASTAXANTHIN for aquaculture
is produced synthetically from petrochemical sources, with an annual
turnover of over $200 million, and a selling price of ~$2000 per
kilo of pure ASTAXANTHIN.
Other developing applications for synthetic ASTAXANTHIN include
poultry and egg production.
In recent years, there has been a growing trend toward using natural
ingredients in all forms of food nutrients, resulting from increasing
concerns for consumer safety and regulatory issues over the introduction
of synthetic chemicals into the human food chain. This is also
true for the nutraceutical and cosmeceutical markets.
Good examples of commercially important naturally derived carotenoids
are beta-carotene, lycopene, lutein and zeaxanthin, commercial carotenoids
with antioxidant properties which have become popular ingredients
in many vitamin and mineral supplements. Beta-carotene and lycopene
can be produced both synthetically (from petrochemicals) and naturally.
A decade ago, natural beta-carotene accounted for a tiny percentage
of the total world market. Since then, that market has increased
several-fold and today, natural beta-carotene accounts for 15 to
20% of world demand (15). Virtually
all nutraceutical producers use natural rather than synthetic carotenoids,
and pay premium prices as much as five times that of the synthetic
The demand for natural ASTAXANTHIN is now emerging in the multi-billion
dollar nutraceutical market, and increasingly, medical researchers
believe that ASTAXANTHIN may have significant pharmaceutical applications.
While only a negligible part of today's market, the demand for
such applications is expected to grow significantly in the near
term as a result of numerous medical studies performed during the
last 5 years in the area of ASTAXANTHIN applications.
More and more research supports the conviction that a daily dose
of ~5 mg of ASTAXANTHIN is of tremendous importance for health
management, by protecting cells and body tissues from the oxidative
stress caused by free radicals, among others.
ASTAXANTHIN producers have conducted several studies in recent
years to demonstrate the safety of natural ASTAXANTHIN
derived from Haematococcus (16-18).
A randomized, double-blind, placebo-controlled, 8-week trial designed
to determine the safety of ASTAXANTHIN in 35 healthy
adults was published recently (19).
Results revealed that healthy adults can safely consume 6 mg of
ASTAXANTHIN per day from Haematococcus pluvialis algal extract.
Based on recent findings, we believe that a daily dose of ASTAXANTHIN
will have an important influence in preventing a broad array of
age related diseases. Moreover, small daily doses of ASTAXANTHIN
may prevent or delay the onset of some diseases, thus saving society
significant sums of money.
NATURAL vs. SYNTHETIC ASTAXANTHIN
The chemical difference between natural and synthetic ASTAXANTHIN
lies in the stereochemical orientation of the molecules in space
(those different molecules are called “enantiomers”).
ASTAXANTHIN exists in three main enantiomeric forms, termed 3S-3’S,
3R-3’S, and 3R-3’R, depending on the spatial orientation
of the hydroxyl (OH) groups in chiral carbon number 3 (see
Quite simply stated, chirality and stereo differentiation are crucial
factors in biological activity because in nature, at a molecular
level, asymmetry dominates biological processes, such as enzymatic
and most immunological reactions. Chirality is not a prerequisite
for bioactivity but in bioactive molecules where one or more chiral
centers are present, great differences are usually observed in
the activities of the different enantiomers. This is a general
phenomenon that applies to many bioactive substances, such as drugs,
flavors, fragrances and food additives.
A recent study showed that farmed salmon, like most of the salmon
sold in supermarkets, can be easily distinguished from wild salmon
in its ASTAXANTHIN isomers, because farmed salmon
are fed synthetic ASTAXANTHIN (20).
The pigment in wild salmon is found overwhelmingly in the 3S-3’S
enantiomeric form, the same form as that found in Haematococcus.
Synthetic ASTAXANTHIN from petrochemical sources contains a mixture
of all the enantiomers of ASTAXANTHIN, as a direct result of its
chemical synthesis, primarily (~50%) the 3R-3’S enantiomer
(the meso form). Indeed, in an elegant human study, Østerlie
and co-workers (74-76)
found that humans selectively absorb the different isomers and their
relative concentrations were found to differ in various organs.
It is important to note that nearly all studies showing ASTAXANTHIN's
health-beneficial effects in humans were performed on the stereoisomer
found in Haematococcus, 3S-3’S. Although the other stereoisomers
may not be harmful, no significant biological effect has been established.
Moreover, natural ASTAXANTHIN exists in algae and fish as mono-
and di-esters of fatty acids, while synthetic ASTAXANTHIN is produced
and sold for salmon farming as free hydroxy ASTAXANTHIN. In nutraceutical
applications as well, scientists have proven that one of
the main advantages of natural ASTAXANTHIN esters is that the esterified
form is inherently more stable than the free form, providing for
a significantly longer shelf life without being oxidized. Several
recent studies clearly showed the positive effect of ASTAXANTHIN
esters mixed with fat formulations on the oral bioavailability of
ASTAXANTHIN in humans (21,22).
|Astaxanthin 3S, 3’S
|Astaxanthin 3S, 3’S
|Fig. 1. Members of the xanthophyll family
THE PRODUCTION OF NATURAL ASTAXANTHIN BY HAEMATOCOCCUS
The microalga Haematococcus pluvialis synthesizes and accumulates
ASTAXANTHIN to relatively high levels. The commercial production
process is based on two distinct cultivation stages. The first is
called the "Green Stage," which starts indoors with a
single-cell colony of the microalga, and continues outdoors in solar-powered
photobioreactors. The aim of this stage is to produce plenty of
viable, unstressed "green" algal cells by normal cell-division
process (see Fig. 2). The "Green Stage" provides
optimal growth conditions in order to achieve maximal biomass production
rate. The second cultivation stage is the "Red Stage"
(see Fig. 2), in which the algal cells synthesize and accumulate
the pigment ASTAXANTHIN. This stage starts by subjecting the cells
to severe stress conditions, mainly high radiation intensity and
changes in growth media. As a result, the Haematococcus cells start
to form cysts by producing thick cell walls, and to synthesize and
accumulate ASTAXANTHIN in its esterified form. Cultivating the algal
culture in closed systems allows an environmentally controlled process
with less biological and chemical contamination. Following the "Red"
process, the level of ASTAXANTHIN in the "red cells" may
reach up to ~4% of their dry weight. The ASTAXANTHIN content of
the "red cells" is correlated to the severity of the stress
conditions, mainly to the light flux through the culture. In due
time, the "red" culture is pumped to the down-processing
area, where the cells are cracked (to render the pigment bioavailable),
dried, and vacuum-packed. Haematococcus oleoresin is produced in
an additional step, using the CO2 Supercritical Fluid Extraction
process. Increasingly, both consumers and regulatory agencies are
requiring extracts that contain no residual solvents. U.S. Nutra
of Eustis, FL, has the technology to extract Haematococcus with
CO2 and without any co-solvents.
Very few companies commercially produce ASTAXANTHIN from Haematococcus
pluvialis. The Hawaiian companies Cyanotech Corporation and Mera
Pharmaceuticals cultivate the algae using an open pond system for
the "Red Stage." The Japanese company Fuji Chemicals operates
an indoor facility in Sweden and its "dome-shaped" bioreactors
Algatech uses tubular solar-powered photobioreactors for both the
"Green" and "Red" stages in closed, strictly
controlled systems (see Figs. 3 and 4). Algatech produces
its ASTAXANTHIN from the microalga Haematococcus pluvialis according
to its patented biocontrolled growing process
(1). The plant is located in the southern part of Israel, in
the Negev Desert, near the resort city of Eilat, thus exploiting
the area's high solar radiation year-round.
The major parameters used to assess high-quality commercial Haematococcus
biomass and oleoresins are high ASTAXANTHIN content in the product,
low levels of biological and chemical contamination, and excellent
stability of the ASTAXANTHIN in the product. Producing ASTAXANTHIN
in a closed system throughout the entire process ("Green"
and "Red") in an area with high solar-radiation intensity
year-round, as in the case of Algatech, yields high-quality ASTAXANTHIN
products (see Fig. 5). This algal biomass contains ~4%
of its dry weight as ASTAXANTHIN. The production of the algal biomass
in flake form (as with Algatechnologies’ dry biomass), offers
additional clear advantages when an extraction process is required
for the production of high-quality oleoresin with ~ 10% ASTAXANTHIN
|Fig. 2. Red stage of Haematococcus pluvialis
culture (under the red half of the photo). Green stage of Haematococcus
pluvialis culture (under the green half of the photo).
|Fig. 3. General view of Algatechnologie's
production plant in the heart of the Negev desert in Israel.
|Fig. 4. "Red-stage" solar photobioreactors
- general view.
|Fig. 5. Cracked and dried Haematococcus
pluvialis algal biomass
- Medical and Nutraceutical Applications
- Conclusions and Product Future
- Articles and Scientific References
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