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ASTAXANTHIN
44 ABSTRACTS
PubMed search of:
Astaxanthin, therapeutic = 16 hits
Astaxanthin, deficiency = 7 hits
Astaxanthin, human = 24 hits
Astaxanthin, animal = 143 hits
Astaxanthin, benefit = 1 hits
MESH search of:
Astaxanthin, therapeutic = 0 hits
Astaxanthin, deficiency = 0 hits
Astaxanthin Overview
Astaxanthin is a fat-soluble, oxygenated pigment called a xanthophyll and a member of
the carotenoid family. It has a unique molecular structure that gives it powerful
antioxidant function. It is extracted from salmon, microalgae, and Pfaffia, a yeast.
Current research shows that due to astaxanthin’s potent antioxidant activity, it may be
beneficial in cardiovascular, immune, anti-inflammatory, and neurodegenerative diseases.
Specifically it inhibits lipid peroxidation at the cell level; crosses the blood-brain barrier,
effecting treatment of ocular, and neurodegenerative diseases such as glaucoma and
Alzheimer's; provides significantly more antioxidant capacity than other carotenoids and
antioxidants such as beta-carotene and Vitamin E; entraps free radicals by adding them to
its long, double-bonded chain rather than donating an electron; stabilizes the cell
membrane like a bridge because its polar end groups span the cell membrane, thus
increasing its rigidity and mechanical strength; neutralizes singlet and triplet oxygen (de-
charges) generated by UVA and UVB radiation and other sources; binds to a lipoprotein,
an efficient transport vehicle, making it more bioavailable; increases immune system
function including heightened production of antibody-secreting cells and Interleukin 2
and suppression of Interferon-gamma; inhibits reactive oxygen species that cause
inflammation; enhances the antioxidant actions of Vitamin E and Vitamin C and
encourages the release of Vitamin A from the liver when needed.
Astaxanthin has 100-500 times the antioxidant capacity of Vitamin E and 10 times the
antioxidant capacity of beta-carotene. Many laboratory studies also indicate astaxanthin
is a stronger antioxidant than lutein, lycopene and tocotrienols.
Dosage: The recommended dosage of 1 mg twice per day is similar on a weight basis to
current doses for beta-carotene and alpha-tocopherol.
Side Effects: There are no known side effects.
(Source: http://www.beta-glucan-info.com/astaxanthin-questions-answers.htm)
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Research Overview
1. Interferes with proinflammatory substances
2. Blocks nitric oxide enzyme activity
3. Is a powerful antioxidant
4. Astaxanthin bioavailability is increased by some long chain triglycerides
5. Protects beta-cell function in diabetes
6. Reduces glucose toxicity
7. Limits exercise-induced cardiac and skeletal damage in mice
8. Protects against DNA damage from UVA rays
9. Reduces stress-induced lipid peroxidation
10. Helps prevent atherosclerosis
11. Slows growth of H pylori infection
12. Inhibits tumor growth
13. Controls cancer cell proliferation in colon cancer
14. Controls cancer cell proliferation in bladder cancer
ASTAXANTHIN: 44 ABSTRACTS
1. Mol Cells. 2003 Aug 31;16(1):97-105.
Astaxanthin inhibits nitric oxide production and inflammatory gene expression by
suppressing I(kappa)B kinase-dependent NF-kappaB activation.
Lee SJ, Bai SK, Lee KS, Namkoong S, Na HJ, Ha KS, Han JA, Yim SV, Chang K, Kwon
YG, Lee SK, Kim YM.
Vascular System Research Center and Department of Molecular and Cellular
Biochemistry, Kangwon National University Biology, Chunchon 200-701, Korea.
Astaxanthin, a carotenoid without vitamin A activity, has shown anti-oxidant and
anti-inflammatory activities; however, its molecular action and mechanism have
not been elucidated. We examined in vitro and in vivo regulatory function of
astaxanthin on production of nitric oxide (NO) and prostaglandin E2 (PGE2) as
well as expression of inducible NO synthase (iNOS), cyclooxygenase-2, tumor
necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta). Astaxanthin
inhibited the expression or formation production of these proinflammatory
mediators and cytokines in both lipopolysaccharide (LPS)-stimulated RAW264.7
cells and primary macrophages. Astaxanthin also suppressed the serum levels of
NO, PGE2, TNF-alpha, and IL-1beta in LPS-administrated mice, and inhibited
NF-kappaB activation as well as iNOS promoter activity in RAW264.7 cells
stimulated with LPS. This compound directly inhibited the intracellular
accumulation of reactive oxygen species in LPS-stimulated RAW264.7 cells as well
as H2O2-induced NF-kappaB activation and iNOS expression. Moreover, astaxanthin
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blocked nuclear translocation of NF-kappaB p65 subunit and I(kappa)B(alpha)
degradation, which correlated with its inhibitory effect on I(kappa)B kinase
(IKK) activity. These results suggest that astaxanthin, probably due to its
antioxidant activity, inhibits the production of inflammatory mediators by
blocking NF-kappaB activation and as a consequent suppression of IKK activity
and I(kappa)B-alpha degradation.
2. Biochem Biophys Res Commun. 2003 Aug 1;307(3):704-12.
Direct superoxide anion scavenging by a disodium disuccinate astaxanthin
derivative: Relative efficacy of individual stereoisomers versus the statistical
mixture of stereoisomers by electron paramagnetic resonance imaging.
Cardounel AJ, Dumitrescu C, Zweier JL, Lockwood SF.
Davis Heart and Lung Research Institute, 473 West 12th Avenue, Columbus, OH
43210-1252, USA.
Carotenoids are a related group of greater than 600 natural compounds,
irrespective of geometric- and stereoisomers, with demonstrated antioxidant
efficacy. The carotenoids are broadly divided into "carotenes," or non-oxygen
substituted hydrocarbon carotenoids, and "xanthophylls," oxygen-substituted
carotenoids. The natural compounds are excellent singlet oxygen quenchers as
well as lipid peroxidation chain-breakers; this dual antioxidant capacity is
generally attributed to the activity of the polyene chain, and increases with
the number of conjugated double bonds along the polyene chain length. However,
the poor aqueous solubility of most carotenes and the vast majority of
xanthophylls limits their use as aqueous-phase singlet oxygen quenchers and
direct radical scavengers. A variety of introduction vehicles (e.g., organic
solvents, cyclodextrins) have been used to introduce the insoluble carotenoids
into aqueous test systems. Hawaii Biotech, Inc. (HBI) successfully synthesized a
novel carotenoid derivative, the disodium disuccinate derivative of astaxanthin
(3,3(')-dihydroxy-beta,beta-carotene-4,4(')-dione) in all-trans (all-E) form.
The novel derivative is a water-dispersible symmetric chiral molecule with two
chiral centers, yielding four stereoisomeric forms: 3R,3(')R and 3S,3(')S
(enantiomers), and the diastereomeric meso forms (3R,3(')S and 3(')R,3S). The
individual stereoisomers were synthesized at high purity (>90% by HPLC) and
compared directly for efficacy with the statistical mixture of stereoisomers
obtained from the synthesis from the commercial source of astaxanthin (1:2:1
ratio of 3S,3(')S, meso, and 3R,3(')R, respectively). Direct scavenging of
superoxide anion was evaluated in a standard in vitro isolated human neutrophil
assay by electron paramagnetic resonance (EPR) imaging, employing the spin-trap
DEPMPO. Each novel derivative was tested in pure aqueous formulation and in
ethanolic formulation shown to completely disaggregate the compounds in
solution. In each case, the ethanolic formulation was a more potent scavenging
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vehicle. No significant differences in scavenging efficiency were noted among
the individual stereoisomers and the statistical mixture of stereoisomers,
suggesting that the polyene chain alone was responsible for superoxide
scavenging. Dose-ranging revealed that the statistical mixture of stereoisomers
of the novel derivative, at millimolar (mM) concentrations, could nearly
completely eliminate the superoxide anion signal generated in the activated
human neutrophil assay. All ethanolic formulations of the novel derivatives
exhibited increased scavenging efficiency over equimolar concentrations of
non-esterified astaxanthin delivered in a dimethyl sulfoxide (DMSO) vehicle.
These novel compounds will likely find utility in applications requiring aqueous
delivery of a highly potent direct radical scavenger.
3. Eur J Pharm Sci. 2003 Jul;19(4):299-304.
Oral bioavailability of the antioxidant astaxanthin in humans is enhanced by
incorporation of lipid based formulations.
Mercke Odeberg J, Lignell A, Pettersson A, Hoglund P.
Department of Clinical Pharmacology, Lund University Hospital, S-221 85 Lund,
Sweden. johanna.odeberg@klinfarm.lu.se
Astaxanthin is a carotenoid with antioxidant properties, synthesised by plants
and algae, and distributed in marine seafood. Astaxanthin is also available as a
food supplement, but, like other carotenoids, is a very lipophilic compound and
has low oral bioavailability. However, bioavailability can be enhanced in the
presence of fat. There is not much information in the literature about the
pharmacokinetics of oral astaxanthin in humans. In this open parallel study,
healthy male volunteers received a single dose of 40 mg astaxanthin, as lipid
based formulations or as a commercially available food supplement, followed by
blood sampling for further analysis of plasma concentrations. Pharmacokinetic
parameters were calculated to evaluate the extent and rate of absorption from
each formulation. The elimination half-life was 15.9+/-5.3 h (n=32), and showed
a mono-phasic curve. Three lipid based formulations: long-chain triglyceride
(palm oil) and polysorbate 80 (formulation A), glycerol mono- and dioleate and
polysorbate 80 (formulation B), and glycerol mono- and dioleate, polysorbate 80
and sorbitan monooleate (formulation C), all showed enhanced bioavailability,
ranging from 1.7 to 3.7 times that of the reference formulation. The highest
bioavailability was observed with formulation B, containing a high content of
the hydrophilic synthetic surfactant polysorbate 80.
4. J Med Food. 2003 Spring;6(1):51-6.
Safety of an astaxanthin-rich Haematococcus pluvialis algal extract: a
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randomized clinical trial.
Spiller GA, Dewell A.
Health Research and Studies Center, Los Altos, CA 94023, USA. spiller@sphere.org
A growing body of scientific literature indicates that astaxanthin is a more
powerful antioxidant than other carotenoids and vitamin E and may confer
numerous health benefits. The purpose of this investigation was to conduct a
human safety study with a Haematococcus pluvialis algal extract with high levels
of astaxanthin. Thirty-five healthy adults age 35-69 years were enrolled in a
randomized, double-blind, placebo-controlled trial of 8 weeks' duration. All
participants took three gelcaps per day, one at each meal. Nineteen participants
received gelcaps with an algal extract in safflower oil, containing 2 mg of
astaxanthin each (treatment); 16 participants received gelcaps containing
safflower oil only (placebo). Blood pressure and blood chemistry tests,
including a comprehensive metabolic panel and cell blood count, were conducted
at the beginning of the trial and after 4 and 8 weeks of supplementation. No
significant differences were detected between the treatment and the placebo
groups after 8 weeks of supplementation with the algal extract in the parameters
analyzed, except for serum calcium, total protein, and eosinophils (P <.01).
Although the differences in these three parameters were statistically
significant, they were very small and are of no clinical importance. These
results reveal that 6 mg of astaxanthin per day from a H. pluvialis algal
extract can be safely consumed by healthy adults.
5. Invest Ophthalmol Vis Sci. 2003 Jun;44(6):2694-701.
Effects of astaxanthin on lipopolysaccharide-induced inflammation in vitro and
in vivo.
Ohgami K, Shiratori K, Kotake S, Nishida T, Mizuki N, Yazawa K, Ohno S.
Department of Ophthalmology and Visual Sciences, Hokkaido University Graduate
School of Medicine, Sapporo, Japan. kohgami@med.hokudai.ac.jp
PURPOSE: Astaxanthin (AST) is a carotenoid that is found in marine animals and
vegetables. Several previous studies have demonstrated that AST exhibits a wide
variety of biological activities including antioxidant, antitumor, and
anti-Helicobacter pylori effects. In this study, attention was focused on the
antioxidant effect of AST. The object of the present study was to investigate
the efficacy of AST in endotoxin-induced uveitis (EIU) in rats. In addition, the
effect of AST on endotoxin-induced nitric oxide (NO), prostaglandin E2 (PGE2),
and tumor necrosis factor (TNF)-alpha production in a mouse macrophage cell line
(RAW 264.7) was studied in vitro. METHODS: EIU was induced in male Lewis rats by
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a footpad injection of lipopolysaccharide (LPS). AST or prednisolone was
administered intravenously at 30 minutes before, at the same time as, or at 30
minutes after LPS treatment. The number of infiltrating cells and protein
concentration in the aqueous humor collected at 24 hours after LPS treatment was
determined. RAW 264.7 cells were pretreated with various concentrations of AST
for 24 hours and subsequently stimulated with 10 microg/mL of LPS for 24 hours.
The levels of PGE2, TNF-alpha, and NO production were determined in vivo and in
vitro. RESULTS: AST suppressed the development of EIU in a dose-dependent
fashion. The anti-inflammatory effect of 100 mg/kg AST was as strong as that of
10 mg/kg prednisolone. AST also decreased production of NO, activity of
inducible nitric oxide synthase (NOS), and production of PGE2 and TNF-alpha in
RAW264.7 cells in vitro in a dose-dependent manner. CONCLUSIONS: This study
suggests that AST has a dose-dependent ocular anti-inflammatory effect, by the
suppression of NO, PGE2, and TNF-alpha production, through directly blocking NOS
enzyme activity.
6. Trends Biotechnol. 2003 May;21(5):210-6.
Haematococcus astaxanthin: applications for human health and nutrition.
Guerin M, Huntley ME, Olaizola M.
Mera Pharmaceuticals Inc., 73-4460 Queen Kaahumanu Hwy, Suite 110, Kailua-Kona,
96740, Hawaii, USA
The carotenoid pigment astaxanthin has important applications in the
nutraceutical, cosmetics, food and feed industries. Haematococcus pluvialis is
the richest source of natural astaxanthin and is now cultivated at industrial
scale. Astaxanthin is a strong coloring agent and a potent antioxidant - its
strong antioxidant activity points to its potential to target several health
conditions. This article covers the antioxidant, UV-light protection,
anti-inflammatory and other properties of astaxanthin and its possible role in
many human health problems. The research reviewed supports the assumption that
protecting body tissues from oxidative damage with daily ingestion of natural
astaxanthin might be a practical and beneficial strategy in health management.
7. Redox Rep. 2002;7(5):290-3.
Astaxanthin protects beta-cells against glucose toxicity in diabetic db/db mice.
Uchiyama K, Naito Y, Hasegawa G, Nakamura N, Takahashi J, Yoshikawa T.
First Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto,
Japan.
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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, a carotenoid of marine microalgae, is reported
as a strong anti-oxidant inhibiting lipid peroxidation and scavenging reactive
oxygen species. The aim of the present study was to examine whether astaxanthin
can elicit beneficial effects on the progressive destruction of pancreatic
beta-cells in db/db mice--a well-known obese model of type 2 diabetes. We used
diabetic C57BL/KsJ-db/db mice and db/m for the control. Astaxanthin treatment
was started at 6 weeks of age and its effects were evaluated at 10, 14, and 18
weeks of age by non-fasting blood glucose levels, intraperitoneal glucose
tolerance test including insulin secretion, and beta-cell histology. The
non-fasting blood glucose level in db/db mice was significantly higher than that
of db/m mice, and the higher level of blood glucose in db/db mice was
significantly decreased after treatment with astaxanthin. The ability of islet
cells to secrete insulin, as determined by the intraperitoneal glucose tolerance
test, was preserved in the astaxanthin-treated group. Histology of the pancreas
revealed no significant differences in the beta-cell mass between
astaxanthin-treated and -untreated db/db mice. In conclusion, these results
indicate that astaxanthin can exert beneficial effects in diabetes, with
preservation of beta-cell function. This finding suggests that anti-oxidants may
be potentially useful for reducing glucose toxicity.
8. J Pharm Sci. 2003 Apr;92(4):922-6.
Improved aqueous solubility of crystalline astaxanthin (3,3'-dihydroxy-beta,
beta-carotene-4,4'-dione) by Captisol (sulfobutyl ether beta-cyclodextrin).
Lockwood SF, O'Malley S, Mosher GL.
Hawaii Biotech, Inc., 99-193 Aiea Heights Drive, Suite 200, Aiea, Hawaii 96701,
USA. slockwood@hibiotech.com
Carotenoids are the most widely distributed natural pigments, with over 600
individual compounds identified and characterized from natural sources. A few
are commercially important molecules, having found utility as additions to
animal feed in the aquaculture, poultry, and swine feed industries. The majority
are lipophilic molecules with near zero inherent aqueous solubility. Many
different methods have been developed to make the carotenoids "water
dispersible," as true water solubility has not been described. Astaxanthin
(3,3'-dihydroxy-beta, beta-carotene-4,4'-dione) is a commercially important
oxygenated carotenoid that has gained wide acceptance as a feed additive in the
$50 billion salmon and trout aquaculture industry. Recently, interest in the
human health applications of astaxanthin has increased, with astaxanthin
receiving approval as a dietary supplement in several countries, including the
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United States. Moving astaxanthin into a pharmaceutical application will require
a chemical delivery system that overcomes the problems with parenteral
administration of a highly lipophilic, low molecular weight compound. In the
current study, the ability of sulfobutyl ether beta-cyclodextrin (sodium), as
the Captisol(R) brand, to increase the aqueous water solubility of crystalline
astaxanthin was evaluated. Complexation of crystalline astaxanthin with Captisol
increased the apparent water solubility of crystalline astaxanthin approximately
71-fold, to a concentration in the 2 microg/mL range. It is unlikely that this
increase in solubility will result in a pharmaceutically acceptable chemical
delivery system for humans. However, the increased aqueous solubility of
crystalline astaxanthin to the range achieved in the current study will likely
find utility in the introduction of crystalline astaxanthin into mammalian cell
culture systems that have previously been dependent upon liposomes, or toxic
organic solvents, for the introduction of carotenoids into aqueous solution.
Copyright 2003 Wiley-Liss, Inc. and the American Pharmaceutical Association J
Pharm Sci 92: 922-926, 2003
9. Antioxid Redox Signal. 2003 Feb;5(1):139-44.
Astaxanthin limits exercise-induced skeletal and cardiac muscle damage in mice.
Aoi W, Naito Y, Sakuma K, Kuchide M, Tokuda H, Maoka T, Toyokuni S, Oka S,
Yasuhara M, Yoshikawa T.
Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto,
602-0841.
Dietary antioxidants may attenuate oxidative damage from strenuous exercise in
various tissues. Beneficial effects of the antioxidant astaxanthin have been
demonstrated in vitro, but not yet in vivo. We investigated the effect of
dietary supplementation with astaxanthin on oxidative damage induced by
strenuous exercise in mouse gastrocnemius and heart. C57BL/6 mice (7 weeks old)
were divided into groups: rested control, intense exercise, and exercise with
astaxanthin supplementation. After 3 weeks of exercise acclimation, both
exercise groups ran on a treadmill at 28 m/min until exhaustion.
Exercise-increased 4-hydroxy-2-nonenal-modified protein and
8-hydroxy-2'-deoxyguanosine in gastrocnemius and heart were blunted in the
astaxanthin group. Increases in plasma creatine kinase activity, and in
myeloperoxidase activity in gastrocnemius and heart, also were lessened by
astaxanthin. Astaxanthin showed accumulation in gastrocnemius and heart from the
3 week supplementation. Astaxanthin can attenuate exercise-induced damage in
mouse skeletal muscle and heart, including an associated neutrophil infiltration
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that induces further damage.
10. Comp Biochem Physiol C Toxicol Pharmacol. 2002 Nov;133(3):443-51.
Astaxanthin and canthaxanthin do not induce liver or kidney
xenobiotic-metabolizing enzymes in rainbow trout (Oncorhynchus mykiss Walbaum).
Page GI, Davies SJ.
Fish Nutrition Unit, Department of Biological Sciences, University of Plymouth,
Drake Circus, Plymouth PL4 8AA, UK. pagegi@mapleleaf.ca
This study was designed to assess the effects of dietary carotenoid
supplementation on liver and kidney xenobiotic-metabolizing enzymes in the
rainbow trout. Twelve rainbow trout (mean weight 266+/-10 g) were assigned to
each of three replicate tanks for each of four dietary treatments; astaxanthin,
canthaxanthin, negative control and positive control using beta-naphthoflavone,
at a target dietary inclusion of 100 mg kg(-1) for each additive. Fish were fed
for 3 weeks at a level of 1.2% body wt. day(-1). Serum carotenoid levels were
used as indicators of exposure and were not significantly different (P>0.05)
between carotenoid-fed trout. Livers and kidney were frozen separately in liquid
N(2) by immersion and microsomal fractions from pooled samples (n=3) assayed for
xenobiotic-metabolizing enzyme (cytochrome P450 monoxygenase) activities
including ethoxyresorufin O-deethylase; methoxyresorufin O-demethylase;
pentoxyresorufin O-dealkylase; benzoxyresorufin O-dearylase; and the conjugating
enzymes glucuronosyl transferase; and glutathione-s-transferase. Results
revealed that carotenoid treatment did not significantly (P>0.05) induce any
enzyme system examined. Results are discussed in the context of metabolism of
absorbed carotenoids.
11. J Dermatol Sci. 2002 Oct;30(1):73-84.
Modulatory effects of an algal extract containing astaxanthin on UVA-irradiated
cells in culture.
Lyons NM, O'Brien NM.
Department of Food Science, Food Technology and Nutrition, University College
Cork, Cork, Ireland. nob@ucc.ie
UV radiation from sunlight is the most potent environmental risk factor in skin
cancer pathogenesis. In the present study the ability of an algal extract to
protect against UVA-induced DNA alterations was examined in human skin
fibroblasts (1BR-3), human melanocytes (HEMAc) and human intestinal CaCo-2
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cells. The protective effects of the proprietary algal extract, which contained
a high level of the carotenoid astaxanthin, were compared with synthetic
astaxanthin. DNA damage was assessed using the single cell gel electrophoresis
or comet assay. In 1BR-3 cells, synthetic astaxanthin prevented UVA-induced DNA
damage at all concentrations (10 nM, 100 nM, 10 microM) tested. In addition, the
synthetic carotenoid also prevented DNA damage in both the HEMAc and CaCo-2
cells. The algal extract displayed protection against UVA-induced DNA damage
when the equivalent of 10 microM astaxanthin was added to all three-cell types,
however, at the lower concentrations (10 and 100 nM) no significant protection
was evident. There was a 4.6-fold increase in astaxanthin content of CaCo-2
cells exposed to the synthetic compound and a 2.5-fold increase in cells exposed
to algal extract. In 1BR-3 cells, exposure to UVA for 2 h resulted in a
significant induction of cellular superoxide dismutase (SOD) activity, coupled
with a marked decrease in cellular glutathione (GSH) content. However
pre-incubation (18 h) with 10 microM of the either the synthetic astaxanthin or
the algal extract prevented UVA-induced alterations in SOD activity and GSH
content. Similarly, in CaCo-2 cells a significant depletion of GSH was observed
following UVA-irradiation which was prevented by simultaneously incubating with
10 microM of either synthetic astaxanthin or the algal extract. SOD activity was
unchanged following UVA exposure in the intestinal cell line. This work suggests
a role for the algal extract as a potentially beneficial antioxidant.
12. Life Sci. 2002 Apr 21;70(21):2509-20.
Contribution of the antioxidative property of astaxanthin to its protective
effect on the promotion of cancer metastasis in mice treated with restraint
stress.
Kurihara H, Koda H, Asami S, Kiso Y, Tanaka T.
Institute for Health Care Science, Suntory Ltd., 1-1-1 Wakayamadai,
Shimamoto-cho, Mishima-gun, Osaka 618-8503, Japan.
Hiroshi_Kurihara@suntory.co.jp
We investigated the effects of astaxanthin on the antitumor effector activity of
natural killer (NK) cells suppressed by stress in mice in order to define the
immunological significance of astaxanthin (ASX) when combined with restraint
stress treatment. When the mice were treated with restraint stress alone, the
total number of spleen cells, and the level NK cell activity per spleen were
reduced to a nadir on day 3. The stress also caused a significant increase in
the lipid peroxidation of liver tissue. ASX (100 mg/kg/day, p.o., 4 days)
improved the immunological dysfunction induced by restraint stress. On the other
hand, metastatic nodules were observed in the livers of syngenic DBA/2 mice on
day 12 after inoculation of P815 mastocytoma cells. Hepatic metastasis was
promoted further by restraint stress when applied on day 3 before the
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inoculation of P815. Daily oral administration of ASX (1 mg/kg/day, p.o., 14
days) markedly attenuated the promotion of hepatic metastasis induced by
restraint stress. These results suggested that astaxanthin improves antitumor
immune responses by inhibiting of lipid peroxidation induced by stress.
13. Arch Toxicol. 2002 Jan;75(11-12):665-75.
Metabolism and CYP-inducer properties of astaxanthin in man and primary human
hepatocytes.
Kistler A, Liechti H, Pichard L, Wolz E, Oesterhelt G, Hayes A, Maurel P.
Vitamins and Fine Chemicals, Human Nutrition and Health, F. Hoffmann-La Roche
Ltd, Basel, Switzerland. kistlera@bluewin.ch
Previous investigations in the rat have shown that the non-provitamin A
carotenoid astaxanthin is metabolized into 3-hydroxy-4-oxo-beta-ionone and
3-hydroxy-4-oxo-7,8-dihydro-beta-ionone and, in addition, is a potent CYP1A gene
inducer. Here we investigated the metabolism of this compound as well as its
capacity to induce CYP genes in primary cultures of human hepatocytes. Free
metabolites of 14C-astaxanthin produced in this cellular model were purified by
high pressure liquid chromatography (HPLC) and identified by gas
chromatography-mass spectrometry (GC-MS) analyses as 3-hydroxy-4-oxo-beta-ionol
and 3-hydroxy-4-oxo-beta-ionone. In addition, deconjugation of polar compounds
by glusulase and further analyses with HPLC and GC-MS revealed four radiolabeled
metabolites including: 3-hydroxy-4-oxo-beta-ionol, 3-hydroxy-4-oxo-beta-ionone,
and their reduced forms, 3-hydroxy-4-oxo-7, 8-dihydro-beta-ionol and
3-hydroxy-4-oxo-7,8-dihydro-beta-ionone. The same four metabolites were
identified in human plasma from two volunteers who had orally taken 100 mg
astaxanthin 24 h before blood collection. In cultured hepatocytes, astaxanthin
was a significant inducer of the major cytochrome P450 enzyme, CYP3A4 as well as
of CYP2B6, but not of other CYPs, including those from CYP1A and CYP2C families.
The lack of autoinduction of astaxanthin metabolism in human hepatocytes
suggests that neither CYP3A4 nor CYP2B6 contribute to the formation of
metabolites. We conclude that metabolism of astaxanthin and its CYP-inducing
capacity are different in humans and in rats. The novel methodology used in our
studies could be extended to evaluating the role of metabolites of more
important carotenoids such as beta-carotene in differentiation and
carcinogenicity.
14. J Reprod Fertil Suppl. 2001;57:331-4.
Effect of supplementation with the antioxidant astaxanthin on reproduction,
pre-weaning growth performance of kits and daily milk intake in mink.
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Hansen KB, Tauson AH, Inborr J.
Department of Animal Science and Animal Health, Royal Veterinary and
Agricultural University, Gronnegardsvej 3, 1870 Frederiksberg C, Denmark.
The study comprised two parts. Firstly, the effects of dietary supplementation
with an algal meal (Novasta) with a high astaxanthin content on ovulation rate
(number of corpora lutea, implantation rate, number, mass and length of fetuses)
of breeding female mink were evaluated. Secondly, reproductive outcome (number
of live and stillborn kits), kit growth rate and milk intake were studied. Both
studies were performed on standard brown female mink (n = 20; control (n = 10)
and experimental (n = 10)) housed under conventional farm conditions.
Experimental animals were supplied with 5.35 mg astaxanthin per day (0.25 g
algal meal (Novasta)). The numbers of corpora lutea, implantation sites and
fetuses appeared to be higher in the group that was given astaxanthin but the
effect was not significant. The differences between treated and control mink
were 1.4 (corpora lutea), 0.9 (implantation sites) and 1.2 (litter size). The
percentage of stillborn kits was reduced by 6.3 (P < 0.005). The milk intake as
measured by use of the isotopic water dilution technique was not affected by
treatment group. Milk intake increased from about 19 g in week 1 of lactation to
about 30 g per kit per day in week 4 of lactation. Kit weight gain was not
affected by the experimental treatment.
15. Biochem Biophys Res Commun. 2001 Oct 19;288(1):225-32.
Astaxanthin and peridinin inhibit oxidative damage in Fe(2+)-loaded liposomes:
scavenging oxyradicals or changing membrane permeability?
Barros MP, Pinto E, Colepicolo P, Pedersen M.
Department of Botany, Stockholm University, SE-10691 Stockholm, Sweden.
mpbarros@botan.su.se
Astaxanthin and peridinin, two typical carotenoids of marine microalgae, and
lycopene were incorporated in phosphatidylcholine multilamellar liposomes and
tested as inhibitors of lipid oxidation. Contrarily to peridinin results,
astaxanthin strongly reduced lipid damage when the lipoperoxidation
promoters-H(2)O(2), tert-butyl hydroperoxide (t-ButOOH) or ascorbate-and
Fe(2+):EDTA were added simultaneously to the liposomes. In order to check if the
antioxidant activity of carotenoids was also related to their effect on membrane
permeability, the peroxidation processes were initiated by adding the promoters
to Fe(2+)-loaded liposomes (encapsulated in the inner aqueous solution). Despite
that the rigidifying effect of carotenoids in membranes was not directly
measured here, peridinin probably has decreased membrane permeability to
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initiators (t-ButOOH > ascorbate > H(2)O(2)) since its incorporation limited
oxidative damage on iron-liposomes. On the other hand, the antioxidant activity
of astaxanthin in iron-containing vesicles might be derived from its known
rigidifying effect and the inherent scavenging ability. Copyright 2001 Academic
Press.
16. J Atheroscler Thromb. 2000;7(4):216-22.
Inhibition of low-density lipoprotein oxidation by astaxanthin.
Iwamoto T, Hosoda K, Hirano R, Kurata H, Matsumoto A, Miki W, Kamiyama M,
Itakura H, Yamamoto S, Kondo K.
National Institute of Health and Nutrition, Tokyo, Japan.
Marine animals produce astaxanthin which is a carotenoid and antioxidant. In
this study we determined the in vitro and ex vivo effects of astaxanthin on LDL
oxidation. The oxidation of LDL was measured in a 1 ml reaction system
consisting of increasing concentrations of astaxanthin (12.5, 25.0, 50.0
microg/ml), 400 microM V-70 (2, 2'-azobis(4-methoxy-2,
4-dimethylvaleronitrile)), and LDL (70 microg/ml protein). Astaxanthin dose,
dependently significantly prolonged the oxidation lag time (31.5, 45.4, 65.0
min) compared with the control (19.9 min). For the ex vivo study 24 volunteers
(mean age 28.2 [SD 7.8] years) consumed astaxanthin at doses of 1.8, 3.6,14.4
and 21.6 mg per day for 14 days. No other changes were made in the diet. Fasting
venous blood samples were taken at days 0, +14. LDL lag time was longer (5.0,
26.2, 42.3 and 30.7% respectively) compared with day 0 after consuming
astaxanthin at doses of 1.8, 3.6,14.4 and 21.6 mg for 14 days compared with day
0, but there was no difference in oxidation of LDL between day 0 (lag time
59.9+/-7.2 min) and day 14 (57.2+/-6.0 min) in the control group. Our results
provide evidence that consumption of marine animals producing astaxanthin
inhibits LDL oxidation and possibly therefore contributes to the prevention of
atherosclerosis.
17. Methods Find Exp Clin Pharmacol. 2001 Mar;23(2):79-84.
Effect of astaxanthin on the hepatotoxicity, lipid peroxidation and
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antioxidative enzymes in the liver of CCl4-treated rats.
Kang JO, Kim SJ, Kim H.
Department of Food and Nutrition, College of Human Ecology, Seoul National
University, Korea.
Astaxanthin is one of many carotenoids present in marine animals, vegetables and
fruits. Since carotenoids are known to have antioxidant properties, we tested to
determine if astaxanthin could have protective effects in the CCl4-treated rat
liver by activating the antioxidant system. Astaxanthin blocked the increase of
glutamate-oxalacetate transaminase (GOT) and glutamate-pyruvate transaminase
(GTP) activity and thiobarbituric acid reactive substances (TBARS) in response
to carbon tetrachloride (CCl4), while causing an increase in glutathione (GSH)
levels and superoxide dismutase (SOD) activities in the CCl4-treated rat liver.
These results suggest that astaxanthin protects liver damage induced by CCl4 by
inhibiting lipid peroxidation and stimulating the cellular antioxidant system.
18. Biochim Biophys Acta. 2001 Jun 6;1512(2):251-8.
Efficient radical trapping at the surface and inside the phospholipid membrane
is responsible for highly potent antiperoxidative activity of the carotenoid
astaxanthin.
Goto S, Kogure K, Abe K, Kimata Y, Kitahama K, Yamashita E, Terada H.
Faculty of Pharmaceutical Sciences, University of Tokushima, Japan.
Kogure@ph.tokushima-u.ac.jp
The effects of the carotenoids beta-carotene and astaxanthin on the peroxidation
of liposomes induced by ADP and Fe(2+) were examined. Both compounds inhibited
production of lipid peroxides, astaxanthin being about 2-fold more effective
than beta-carotene. The difference in the modes of destruction of the conjugated
polyene chain between beta-carotene and astaxanthin suggested that the
conjugated polyene moiety and terminal ring moieties of the more potent
astaxanthin trapped radicals in the membrane and both at the membrane surface
and in the membrane, respectively, whereas only the conjugated polyene chain of
beta-carotene was responsible for radical trapping near the membrane surface and
in the interior of the membrane. The efficient antioxidant activity of
astaxanthin is suggested to be due to the unique structure of the terminal ring
moiety.
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19. 0955-2863. 2000 Oct;11(10):482-490.
Plasma appearance and distribution of astaxanthin E/Z and R/S isomers in plasma
lipoproteins of men after single dose administration of astaxanthin(1).
Osterlie M, Bjerkeng B, Liaaen-Jensen S.
HIST, Department of Food Science, N-7004, Trondheim, Norway
Appearance, pharmacokinetics, and distribution of astaxanthin E/Z and R/S
isomers in plasma and lipoprotein fractions were studied in 3 middle-aged male
volunteers (37-43 years) after ingestion of a single meal containing a 100 mg
dose of astaxanthin. The astaxanthin source consisted of 74% all-E-, 9% 9Z-, 17%
13Z-astaxanthin (3R,3'R-, 3R,3'S; meso-, and 3S,3'S-astaxanthin in a 1:2:1
ratio). The plasma astaxanthin concentration--time curves were measured during
72 hr. Maximum levels of astaxanthin (1.3 +/- 0.1 mg/L) were reached 6.7 +/- 1.2
hr after administration, and the plasma astaxanthin elimination half-life was 21
+/- 11 hr. 13Z-Astaxanthin accumulated selectively, whereas the 3 and 3'R/S
astaxanthin distribution was similar to that of the experimental meal.
Astaxanthin was present mainly in very low-density lipoproteins containing
chylomicrons (VLDL/CM; 36-64% of total astaxanthin), whereas low-density
lipoprotein (LDL) and high-density lipoprotein (HDL) contained 29% and 24% of
total astaxanthin, respectively. The astaxanthin isomer distribution in plasma,
VLDL/CM, LDL, and HDL was not affected by time. The results indicate that a
selective process increases the relative proportion of astaxanthin Z-isomers
compared to the all-E-astaxanthin during blood uptake and that astaxanthin E/Z
isomers have similar pharmacokinetics.
20. Antimicrob Agents Chemother. 2000 Sep;44(9):2452-7.
Astaxanthin-rich algal meal and vitamin C inhibit Helicobacter pylori infection
in BALB/cA mice.
Wang X, Willen R, Wadstrom T.
Department of Infectious Diseases and Medical Microbiology, University of Lund,
Sweden.
Helicobacter pylori infection in humans is associated with chronic type B
gastritis, peptic ulcer disease, and gastric carcinoma. A high intake of
carotenoids and vitamin C has been proposed to prevent development of gastric
malignancies. The aim of this study was to explore if the microalga
Haematococcus pluvialis rich in the carotenoid astaxanthin and vitamin C can
inhibit experimental H. pylori infection in a BALB/cA mouse model. Six-week-old
BALB/cA mice were infected with the mouse-passaged H. pylori strain 119/95. At 2
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weeks postinoculation mice were treated orally once daily for 10 days (i) with
different doses of algal meal rich in astaxanthin (0.4, 2, and 4 g/kg of body
weight, with the astaxanthin content at 10, 50, and 100 mg/kg, respectively),
(ii) with a control meal (algal meal without astaxanthin, 4 g/kg), or (iii) with
vitamin C (400 mg/kg). Five mice from each group were sacrificed 1 day after the
cessation of treatment, and the other five animals were sacrificed 10 days after
the cessation of treatment. Culture of H. pylori and determination of the
inflammation score of the gastric mucosae were used to determine the outcome of
the treatment. Mice treated with astaxanthin-rich algal meal or vitamin C showed
significantly lower colonization levels and lower inflammation scores than those
of untreated or control-meal-treated animals at 1 day and 10 days after the
cessation of treatment. Lipid peroxidation was significantly decreased in mice
treated with the astaxanthin-rich algal meal and vitamin C compared with that of
animals not treated or treated with the control meal. Both astaxanthin-rich
algal meal and vitamin C showed an inhibitory effect on H. pylori growth in
vitro. In conclusion, antioxidants may be a new strategy for treating H. pylori
infection in humans.
21. J Nutr. 2000 Jul;130(7):1800-8.
Depletion of alpha-tocopherol and astaxanthin in Atlantic salmon (Salmo salar)
affects autoxidative defense and fatty acid metabolism.
Bell JG, McEvoy J, Tocher DR, Sargent JR.
Institute of Aquaculture, University of Stirling, Stirling FK9 4LA, Scotland,
U.K.
Duplicate groups of Atlantic salmon post-smolts were fed four purified diets
supplemented with both vitamin E and the carotenoid astaxanthin (Ax) (+E, +Ax),
or supplemented with either vitamin E or Ax (-E, +Ax and +E, -Ax) or deficient
in both vitamin E and Ax (-E, -Ax) for 22 wk. There were no effects of diet on
growth rate, but an extensive lipoid liver degenerative lesion was observed in
15% of fish fed diets deficient in vitamin E. Tissue vitamin E concentrations
varied in accordance with dietary vitamin E in liver, muscle, heart, plasma,
brain and eye; levels were reduced to approximately 3% in liver but only to 40%
in eye of fish fed diets deficient in vitamin E compared with those fed diets
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supplemented with vitamin E. An interactive sparing of Ax supplementation on
tissue vitamin E concentration was observed, but only in brain. Dietary
deficiency of both vitamin E and Ax significantly increased the recovery of
desaturated and elongated products of both [1-(14)C] 18:3(n-3) and [1-(14)C]
20:5(n-3) in isolated hepatocytes, suggesting that conversion of fatty acids to
their long-chain highly unsaturated products can be stimulated by a deficiency
of lipid-soluble antioxidants. The antioxidant synergism of vitamin E and Ax was
supported by their ability to reduce malondialdehyde formation in an in vitro
stimulation of microsomal lipid peroxidation and to reduce plasma levels of
8-isoprostane. The results of this study suggest that both vitamin E and the
carotenoid Ax have antioxidant functions in Atlantic salmon.
22. Nutr Cancer. 2000;36(1):59-65.
Antitumor activity of astaxanthin and its mode of action.
Jyonouchi H, Sun S, Iijima K, Gross MD.
Department of Pediatrics, School of Medicine, University of Minnesota,
Minneapolis 55455, USA. jyono001@jyono001.email.umn.edu
Astaxanthin, a carotenoid without vitamin A activity, may exert antitumor
activity through the enhancement of immune responses. Here, we determined the
effects of dietary astaxanthin on tumor growth and tumor immunity against
transplantable methylcholanthrene-induced fibrosarcoma (Meth-A tumor) cells.
These tumor cells express a tumor antigen that induces T cell-mediated immune
responses in syngenic mice. BALB/c mice were fed astaxanthin (0.02%, 40
micrograms/kg body wt/day in a beadlet form) mixed in a chemically defined diet
starting zero, one, and three weeks before subcutaneous inoculation with tumor
cells (3 x 10(5) cells, 2 times the minimal tumorigenic dose). Three weeks after
inoculation, tumor size and weight were determined. We also determined cytotoxic
T lymphocyte (CTL) activity and interferon-gamma (IFN-gamma) production by
tumor-draining lymph node (TDLN) and spleen cells by restimulating cells with
Meth-A tumor cells in culture. The astaxanthin-fed mice had significantly lower
tumor size and weight than controls when supplementation was started one and
three weeks before tumor inoculation. This antitumor activity was paralleled
with higher CTL activity and IFN-gamma production by TDLN and spleen cells in
the astaxanthin-fed mice. CTL activity by TDLN cells was highest in mice fed
astaxanthin for three weeks before inoculation. When the
astaxanthin-supplemented diet was started at the same time as tumor inoculation,
none of these parameters were altered by dietary astaxanthin, except IFN-gamma
production by spleen cells. Total serum astaxanthin concentrations were
approximately 1.2 mumol/l when mice were fed astaxanthin (0.02%) for four weeks
and appeared to increase in correlation with the length of astaxanthin
supplementation. Our results indicate that dietary astaxanthin suppressed Meth-A
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tumor cell growth and stimulated immunity against Meth-A tumor antigen.
23. J Agric Food Chem. 2000 Apr;48(4):1150-4.
Antioxidant activities of astaxanthin and related carotenoids.
Naguib YM.
Phytochem Technologies, Chelmsford, MA 01824, USA.
The antioxidant activities of astaxanthin and related carotenoids have been
measured by employing a newly developed fluorometric assay. This assay is based
on 4,4-difluoro-3,5-bis(4-phenyl-1, 3-butadienyl)-4-bora-3a,4a-diaza-s-indacene
(BODIPY 665/676) as an indicator; 2,2'-azobis-2,4-dimethylvaleronitrile (AMVN)
as a peroxyl radical generator; and 6-hydroxy-2,5,7,
8-tetramethylchroman-2-carboxylic acid (Trolox) as a calibrator in an organic
and liposomal media. By employing this assay, three categories of carotenoids
were examined: namely, the hydrocarbon carotenoids lycopene, alpha-carotene, and
beta-carotene; the hydroxy carotenoid lutein; and the
alpha-hydroxy-ketocarotenoid