Mar. Drugs 2011, 9, 447-465; doi:10.3390/md9030447
Astaxanthin: A Potential Therapeutic Agent in
Robert G. Fassett 1,2,* and Jeff S. Coombes 2
1 Renal Research Royal Brisbane and Women’s Hospital and The University of Queensland School
of Medicine, Level 9 Ned Hanlon Building, Butterfield Street, Brisbane, Queensland 4029, Australia
2 School of Human Movement Studies, The University of Queensland, St. Lucia, Brisbane,
Queensland 4072, Australia; E-Mail: email@example.com
* Author to whom correspondence should be addressed; E-Mail: firstname.lastname@example.org;
Tel.: +61-419399571; Fax: +61-736368572.
Received: 7 February 2011; in revised form: 14 March 2011 / Accepted: 18 March 2011 /
Published: 21 March 2011
Abstract: Astaxanthin is a xanthophyll carotenoid present in microalgae, fungi, complex
plants, seafood, flamingos and quail. It is an antioxidant with anti-inflammatory properties
and as such has potential as a therapeutic agent in atherosclerotic cardiovascular disease.
Synthetic forms of astaxanthin have been manufactured. The safety, bioavailability and
effects of astaxanthin on oxidative stress and inflammation that have relevance to the
pathophysiology of atherosclerotic cardiovascular disease, have been assessed in a small
number of clinical studies. No adverse events have been reported and there is evidence of a
reduction in biomarkers of oxidative stress and inflammation with astaxanthin
administration. Experimental studies in several species using an ischaemia-reperfusion
myocardial model demonstrated that astaxanthin protects the myocardium when
administered both orally or intravenously prior to the induction of the ischaemic event. At
this stage we do not know whether astaxanthin is of benefit when administered after a
cardiovascular event and no clinical cardiovascular studies in humans have been completed
and/or reported. Cardiovascular clinical trials are warranted based on the physicochemical
and antioxidant properties, the safety profile and preliminary experimental cardiovascular
studies of astaxanthin.
Keywords: antioxidants; xanthophyll carotenoid; inflammation; Haematococcus pluvialis;
Mar. Drugs 2011, 9
Astaxanthin is a xanthophyll carotenoid of predominantly marine origin, with potent antioxidant
and anti-inflammatory effects demonstrated in both experimental and human studies. Oxidative stress
and inflammation are common pathophysiological features of atherosclerotic cardiovascular disease
hence astaxanthin may have a potential therapeutic role in this condition. This review will summarise
the available evidence suggesting astaxanthin may be of therapeutic value in cardiovascular disease.
2. Oxidative Stress and Inflammation
Oxidative stress and inflammation are established non-traditional risk factors for atherosclerosis
associated cardiovascular morbidity and mortality . Dietary antioxidants can reduce the oxidation of
lipids and proteins and have the potential to protect from the development of arterial stiffening and
atherosclerosis [2–4]. Cross-sectional and prospective observational studies have demonstrated an
association between the intake of dietary antioxidants and/or their plasma levels and a reduction of
cardiovascular events [5–10]. This supports the theory that oxidative stress is a pathophysiological
process involved in atherosclerotic vascular damage. Also, a reduced dietary antioxidant intake is
associated with oxidative stress and inflammation . Newer more potent dietary antioxidants such
as astaxanthin have yet to be studied in this setting. Studies that have assessed the intake of -carotene
or dietary -carotene supplementation have shown higher -carotene consumption is associated with a
reduction in cardiovascular disease [6,12–17]. Other than a few studies [18–20], cardiovascular
intervention trials using antioxidants have not demonstrated benefits [21–23]. This may be because
study participants did not have oxidative stress and/or the antioxidants used were insufficiently potent.
In addition, it is becoming recognized that there is communication between oxidative stress and
inflammatory processes leading to the additional hypothesis that antioxidants may be able to modify
both deleterious events. Further research is needed studying antioxidants with different biological
actions in patients with demonstrated oxidative stress.
Carotenoids are ubiquitous, and found in high concentrations in plants, algae and microorganisms.
Humans and other animals cannot synthesize them and therefore are required to source them in
their diet . Carotenoids are classified, according to their chemical structure, into carotenes and
xanthophylls. The carotene carotenoids include -carotene and lycopene and the xanthophyll
carotenoids include lutein, canthaxanthin, zeaxanthin, violaxanthin, capsorubin and astaxanthin [25,26].
The effects of carotenoids vary dependent on how they interact with cell membranes . The
effects of astaxanthin, zeaxanthin, lutein, -carotene and lycopene on lipid peroxidation have been
assessed using a polyunsaturated fatty acid enriched membrane model [25,27]. Non-polar carotene
carotenoids such as lycopene and -carotene caused membrane disorder and lipid peroxidation in
contrast to the polar xanthophyll carotenoid astaxanthin, which preserved membrane structure .
Contrasting effects of different carotenoids may be responsible for the differing biological effects seen
in clinical studies. For instance, in some studies the non-polar carotenoid, -carotene has been shown
to have no benefit on cardiovascular disease [28–32] and in fact it may be pro-oxidant at high
Mar. Drugs 2011, 9
doses . In contrast, the polar carotenoid astaxanthin has protective effects on the cardiovascular
system demonstrated in animal studies. However, this has not been studied in human clinical
trials [34–36]. -carotene at physiological levels may act in differing ways when ultraviolet A light A
(UVA) acts on keratinocytes including vitamin A-independent pathways . Astaxanthin,
canthaxanthin and -carotene had differential effects on UVA-induced oxidative damage .
In addition, carotenoids may also alter the immune response  and transcription .
Astaxanthin contains two oxygenated groups on each ring structure (see Figure 1), which is
responsible for its enhanced antioxidant features . It is found in living organisms particularly in the
marine environment where it is present in microalgae, plankton, krill and seafood. It gives salmon,
trout, and crustaceans such as shrimp and lobster their distinctive reddish coloration . It is
also present in yeast, fungi, complex plants and the feathers of some birds including flamingos and
quail . In 1987, the United States Food and Drug Administration approved astaxanthin as a feed
additive for use in the aquaculture industry and in 1999 it was approved for use as a dietary
supplement (nutraceutical) . The microalgae Haematococcus pluvialis produces the astaxanthin
isomer (3S, 3S′), which is the same as the form found in wild salmon. Synthesis of astaxanthin is not
possible in humans and it cannot be converted to vitamin A, which means excess intake will not cause
hypervitaminosis A toxicity [43,44]. Astaxanthin and canthaxanthin are scavengers of free radicals,
chain-breaking antioxidants and potent quenchers of reactive oxygen and nitrogen species including
singlet oxygen, single and two electron oxidants [45–47]. They (astaxanthin and canthaxanthin) have
terminal carbonyl groups that are conjugated to a polyene backbone  and are more potent
antioxidants and scavengers of free radicals than carotene carotenoids such as -carotene [47,48]. For
these reasons dietary supplementation with astaxanthin has the potential to provide antioxidant
protection of cells and from atherosclerotic cardiovascular disease .
Figure 1. Molecular structure of astaxanthin.
5. Astaxanthin Formulations
5.1. Astaxanthin of Marine Origin
Astaxanthin used in nutritional supplements is usually a mixture of configurational isomers
produced by Haematococcus pluvialis, a unicellular microalga . Astaxanthin can be produced
in its natural forms on a large scale . The initial production of astaxanthin from
Haematococcus pluvialis uses closed culture systems followed by a 5–7 day, “reddening” cycle,
Mar. Drugs 2011, 9
conducted in open culture ponds. At each production stage, the cultures are closely monitored by
microscopic examination to ensure they remain free of contamination. After the reddening cycle,
Haematococcus pluvialis cultures are harvested, washed and dried. The final step for the production of
astaxanthin is extraction of dried Haematococcus pluvialis biomass using supercritical carbon dioxide
to produce a purified oleoresin, which is free of any contamination. Other sources used for the
commercial production of astaxanthin include cultures of Euphausia pacifica (Pacific krill),
Euphausia superba (Antarctic krill), Pandalus borealis (shrimp) and Xanthophyllomyces dendrorhous,
formerly Phaffia rhodozyma (yeast). Astaxanthin from natural sources varies considerably from one
organism to another. For instance, the astaxanthin found in seafood will depend on the stereoisomer
ingested. Astaxanthin produced by haematococcus pluvialis, consists of the (3-S,3′-S) stereoisomer
which is most commonly used in aquaculture. It is therefore the form most commonly consumed
5.2. Synthetic Astaxanthin
There are three stereoisomers of astaxanthin; (3-R,3′-R), (3-R,3′-S) and (3-S,3′-S). Disodium
disuccinate astaxanthin (DDA) is a synthetic astaxanthin containing a mixture of all three
stereoisomers, in the proportions 1:2:1. DDA was manufactured by Cardax Pharmaceuticals and used
in animal studies investigating the myocardial ischemia-reperfusion injury models [34–36,52–54]. This
form of astaxanthin was touted to have better aqueous solubility, unlike other carotenoids, and this
enabled both oral and intravenous administration. DDA is no longer available but the same company
now produces a second synthetic astaxanthin compound; Heptax/XanCor, CDX-085. The company
claims that it is developed for thrombotic protection, triglyceride reduction, metabolic syndrome, and
inflammatory liver disease. In addition, it has increased water dispersibility and enhanced
bioavailability compared to natural astaxanthin and DDA. The synthetic forms are metabolized via
hydrolysis in the intestine yielding free astaxanthin for intestinal absorption. CDX-085 has been used
in one study, discussed below .
It is not yet clear which form of astaxanthin should be administered in clinical studies, the natural
form from the marine environment or a synthetic form. As the proportions of stereoisomers, vary
between these different forms of astaxanthin they may not be therapeutically equivalent . Thus
synthetic astaxanthin could result in different outcomes when assessed clinically .
6. Astaxanthin-Experimental Studies
Experimental studies undertaken with astaxanthin specifically relevant to the cardiovascular system
are summarised in Table 1. Astaxanthin attenuates mediators of oxidative stress and inflammation and
has shown beneficial effects in non-cardiovascular models of disease [58–69]. In addition, astaxanthin
has decreased markers of lipid peroxidation , inflammation [61,62,67,68] and thrombosis .
Mar. Drugs 2011, 9
Table 1. Animal studies investigating the cardiovascular effects of astaxanthin.
Study Model Dosage
30 min after
Effects of astaxanthin
Lauver et al.
Dog with occlusive
carotid artery thrombus
DDA 10, 30, or
50 mg/kg/body weight IV
- Reduced incidence of secondary thrombosis
Aoi et al.
C57BL/6 mice Diet supplemented with
weight/weight and food
- Attenuation of exercise increased 4-hydroxy-2-
nonenal-modified protein and 8-hydroxy-2′-
deoxyguanosine in cardiac and gastrocnemius muscle
- Attenuation of exercise increases in creatine kinase
and myeloperoxidase activity in cardiac and
- Astaxanthin accumulated in cardiac and gastrocnemius
- Myocardial infarct size significantly reduced Gross and
DDA 25/50/75 mg/kg
4 days prior to
5 weeks Hussein et al.
Rabbit model of
Astaxanthin 50 mg/kg
- Significant blood pressure reduction
- Delayed incidence of stroke
Lauver et al.
DDA 50 mg/kg
DDA 50 mg/kg
5 days - Significant reduction in complement activation
- Significant reduction in myocardial infarct size
Gross et al.
Canine model of
2 h or daily for
- Significant reduction in myocardial infarct size
- Two of three dogs treated for four days had 100%
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Table 1. Cont.
Gross et al.
Left anterior descending
DDA 125 or 500 mg/kg
body weight/day orally
7 days - Astaxanthin loading of myocardium indicating good
- Trends in lowering of lipid peroxidation products
- Significant reduction in myocardial infarct size
Hussein et al.
Astaxanthin 5% in olive
oil (5 mg/kg/day orally)
7 days - Significant reduction in nitric oxide end products
- Significant reduction in elastin bands in aorta
- Significant reduction in wall/lumen arterial ratio in coronary
Astaxanthin increased fat utilization during exercise and prolonged
Astaxanthin prevented increase in hexanoyl-lysine modification of
CPT I with exercise
- No change in blood glutathione concentration
- No change in lymphocyte mitochondrial membrane potential
- Higher myocardial mitochondrial membrane potential and
- CDX-085 administered orally to C57BL/6 mice was associated
with presence of free astaxanthin in the plasma, heart, liver and
- Mice fed astaxanthin had significantly increased basal arterial
blood flow and delay in occlusive thrombosis after endothelial
- Human umbilical vein endothelial cells and platelets from
Wistar-Kyoto rats treated with free astaxanthin has significantly
increased release of nitric oxide and decreased peroxynitrite levels
Aoi et al.
ICR mice Astaxanthin 0.02% w/w 4 weeks
Nakao et al.
BALC/c mice Astaxanthin 0, 0.02,
Khan et al.
Human umbilical vein
endothelial cells and
CDX-085 500 mg/kg
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6.1. Cardiovascular Studies
A series of experiments have been conducted to assess the efficacy of DDA in protecting the
myocardium using the myocardial ischemia-reperfusion model in rats, rabbits and dogs [35,36,53,54].
Prior treatment for four-days with intravenous DDA using doses of 25, 50 and 75 mg/kg body weight
in Sprague-Dawley rats significantly reduced myocardial infarct size . The degree of cardiac
protection correlated with the dose of DDA administered. In a study in rabbits using a myocardial
ischaemia-reperfusion model prior intravenous treatment with 50 mg/kg/day of DDA for four days
resulted in a significant decrease in the size of the myocardial infarction and an improvement in
myocardial salvage . Animals treated with DDA had an attenuation of inflammation and
complement activation suggesting there was a reduction in tissue inflammation . In another study
using a dog model intravenous DDA was administered daily for four-days prior to occlusion of the left
anterior descending coronary artery or two hours prior to coronary artery occlusion . After an hour
of coronary occlusion and three hours of reperfusion there was a significant reduction in myocardial
infarct size in the dogs treated with DDA. In the four-day treatment group, two out of three dogs had
complete cardiac protection . In a rat study, the effects of seven days of pre-treatment with oral
DDA, 125 and 500 mg/kg/day on the concentrations of free astaxanthin in myocardial tissue . The
astaxanthin concentration in the myocardium was 400 nM after oral DDA at a dose of 125 mg/kg/day
for seven-days and it was 1634 nM after 500 mg/kg/day. There was also a reduction of multiple lipid
peroxidation products. The doses of DDA used in these experiments were quite high and at this stage it
is not known whether such doses would be safe to use in humans.
The effects of astaxanthin on blood pressure (BP) were assessed in spontaneously hypertensive
rats (SHR). There was a significant reduction in BP after 14-days of oral astaxanthin administration
whereas this did not occur in normotensive Wistar Kyoto rats . Astaxanthin administered orally for
five-weeks in stroke prone SHR also resulted in a significant BP reduction . Oral astaxanthin also
enhanced nitric oxide induced vascular relaxation in the rat aortas  In experiments in SHR, oral
astaxanthin significantly decreased nitric oxide end products indicating that it may be exerting its BP
effects via this pathway . Studies using the SHR aorta and coronary arteries demonstrated that
astaxanthin reduced the wall/lumen ratio in coronary arteries and decreased elastin bands in the
aorta . This suggests that astaxanthin may beneficially mediate atherosclerotic CVD processes.
Recently, a series of two experiments were reported in the one article, one using the synthetic
astaxanthin (CDX-085) and the other using free astaxanthin . CDX-085 administered orally to
C57BL/6 mice resulted in the presence of free astaxanthin in the plasma, heart, liver and platelets.
Mice that were fed astaxanthin had significantly increased basal arterial blood flow and a delay in
occlusive thrombosis after endothelial injury. Also, in an in vitro study, human umbilical vein
endothelial cells and platelets isolated from Wistar-Kyoto rats that were treated with free astaxanthin
has significantly increased nitric oxide release and a decrease in peroxynitrite levels . The authors
concluded the results support the potential of astaxanthin as a potential therapy to prevent thrombosis
associated with cardiovascular disease.
Astaxanthin administered to C57BL/6 mice resulted in a reduction in exercise-induced increases in
the oxidative stress biomarkers 8-hydroxy-2′-deoxyguanosine and 4-hydroxy-2-nonenal-modified
protein in both cardiac and gastrocnemius muscle . Increases in myeloperoxidase and creatinine
Mar. Drugs 2011, 9
kinase activity in cardiac and gastrocnemius muscle were also reduced by astaxanthin. After
three-weeks of astaxanthin supplementation there was evidence of accumulation of astaxanthin in
gastrocnemius and cardiac muscle. Astaxanthin given to female BALB/c mice for eight-weeks resulted
in a dose dependent increase in plasma astaxanthin but no significant changes in blood glutathione or
change in lymphocyte mitochondrial membrane potential and cardiac contractility index measured on
echocardiography. The mice that were fed 0.08% astaxanthin in the diet had higher cardiac
mitochondrial membrane potential and contractility index compared with control animals . This
suggests dietary astaxanthin provides cardiac protection. Astaxanthin administered for four weeks to
eight week old ICR mice resulted in increased exercised induced fat utilization and prevention of
increased hexanoyl-lysine modification of carnitine palmitoyltransferase I (CTP I) . In a canine
carotid artery thrombosis model, administration of DDA resulted in a dose-dependent reduction in
carotid artery re-thrombosis and a reduction of re-thrombosis after thrombolysis but there was no
effect on hemostasis .
6.2. Diabetes Studies
Diabetes mellitus and its associated nephropathy is a common cause of chronic kidney disease and
is complicated by accelerated atherosclerotic cardiovascular disease . In studies involving diabetic
db/db mice, supplementation with astaxanthin produced a reduction in the levels of blood glucose .
In the kidney there was significantly decreased relative mesangial area in the animals supplemented
with astaxanthin. Also proteinuria and urinary excretion of 8-OHdG were attenuated. Mice
supplemented with astaxanthin had less glomerular 8-OHdG immunoreactive cells .
Hyperglycemia induced reactive oxygen species production, activation of transcription factors, and
cytokine expression and production by normal human mesangial cells was suppressed significantly by
7. Astaxanthin Studies in Humans
Although no cardiovascular outcomes studies using astaxanthin have been reported in humans there
have been clinical studies that have investigated the effects of astaxanthin in human health and other
diseases (Table 2). The majority of these have been conducted in healthy participants who volunteered
to assess astaxanthin dose, bioavailability, safety and oxidative stress, which are all potentially relevant
to the cardiovascular system. Studies have also been conducted in other medical conditions such as
reflux oesophagitis, where measurements of oxidative stress and/or inflammation have been included.
Human clinical studies have used oral astaxanthin in a dose that ranges from 4 mg up to
100 mg/day, given from a one off dose up to durations of one-year (Table 2).
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Table 2. Clinical studies investigating the safety, bioavailability and effects of astaxanthin on oxidative stress.
(n = subject numbers)
Volunteers (n = 24)
Dosage Study design
Effects of astaxanthin
Iwamoto et al.
Open labelled 2 weeks - Reduction of LDL oxidation
Osterlie et al.
Mercke Odeberg et al.
Middle aged male
volunteers (n = 3)
volunteers (n = 32)
Open labelled Single dose - Astaxanthin taken up by VLDL chylomicrons
- Enhanced bioavailability with lipid based
- Demonstrated safety assessed by measures of
blood pressure and biochemistry
Spiller et al.
Healthy adults (n = 35) 6 mg/day
(3 × 2 mg
Open labelled Single dose or
Coral-Hinostroza et al.
Healthy adult males
(n = 3)
10 mg and
100 mg 4 weeks
- Cmax 0.28 mg/L at 11.5 h at high dose and
0.08 mg/L at low dose
- Elimination half life 52 ± 40 h
- z-isomer selectively absorbed
- Intestinal absorption adequate with capsules
- Reduced levels of plasma 12 and 15 hydroxy
- Decreased oxidation of fatty acids
Karppi et al.
Finnish males (n = 40)
8 mg/day Randomised,
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Table 2. Cont.
Parisi et al.
(n = 27)
4 mg/day Randomised
open labelled no
12 months - Improved central retinal dysfunction in age
related macular degeneration when administered
with other antioxidants
Miyawaki et al.
(n = 20)
6 mg/day Single blind,
10 days - Decreased whole blood transit time (improved
Rufer et al.
(n = 28)
5 g/g salmon
flesh (wild vs.
4 weeks - Bioavailability initially better with ingestion of
aquacultured salmon but equivalent at day 28.
Isomer (3S, 3′S) greater in plasma compared with
isomer proportion in salmon flesh
Park et al.
(n = 14)
0, 2, 8 mg/day
8 weeks - Decreased plasma 8-hydroxy-2′-deoxyguanosine
after week four in those taking astaxanthin.
- Lower CRP after week four in those taking
2 mg/day astaxanthin
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Astaxanthin bioavailability from the marine environment was assessed in a randomised double
blind trial in 28 volunteers . Participants were given either 250 g of wild salmon or aquaculture
salmon (5 µg/g) to eat. Wild salmon ingest astaxanthin naturally from krill whereas aquacultured
salmon acquire it from fish that are fed astaxanthin that might be derived from a synthetic source.
Plasma levels of astaxanthin were higher at 3, 6, 10 and 14 days during ingestion of the aquacultured
compared with the wild salmon. Plasma levels of the (3-S, 3′-S) isomer of astaxanthin appeared at
higher levels than its proportionate level in the flesh of the salmon. This suggests that isomers of
astaxanthin might have different bioavailability. The plasma isomers of astaxanthin have also been
studied after ingestion of single oral dose of 10mg and also 100 mg over four-weeks. Astaxanthin
plasma elimination half-life was 52 (SD 40) h and there was a non-linear dose response and selective
absorption of z-isomers .
The safety of astaxanthin administered orally was assessed in a double-blind, randomised
placebo-controlled trial undertaken in healthy adults . Volunteers took either 6 mg/day of
astaxanthin or placebo for eight-weeks. BP and biochemistry measured after four and eight weeks of
therapy revealed no significant differences in these parameters between treatment and placebo groups
and these did not differ from baseline. The authors concluded that healthy adults could safely consume
6 mg/day of astaxanthin derived from a Haematococcus pluvialis algal extract. Measuring whole blood
transit time in 20 healthy males was used to assess the effects of astaxanthin on blood rheology in
humans. Six milligrams of oral astaxanthin per day for ten days improved blood rheology as evidenced
by decreased whole blood transit time . Escalating concentrations of astaxanthin were tested
in vitro with blood taken from volunteers, 8 of whom were taking asprin and 12 who were not .
Even supra-therapeutic concentrations of astaxanthin had no adverse effects on indices of platelet,
coagulation and fibrinolytic function. These results support the safety profile of astaxanthin for future
clinical trials. No significant side effects have been reported so far in published human studies in
which astaxanthin was administered to humans.
7.4. Oxidative Stress and Inflammation
Oral supplementation with astaxanthin in studies in healthy human volunteers and patients with
reflux oesophagitis demonstrated a significant reduction in oxidative stress, hyperlipidemia and
biomarkers of inflammation [70,80,86]. In a study involving 24 healthy volunteers who ingested
astaxanthin in doses from 1.8 to 21.6 mg/day for two weeks, LDL lag time, as a measure of
susceptibility of LDL to oxidation, was significantly greater in astaxanthin treated participants
indicating inhibition of the oxidation of LDL . Plasma levels of 12- and 15-hydroxy fatty acids
were significantly reduced in 40 healthy non-smoking Finnish males given astaxanthin  suggesting
astaxanthin decreased the oxidation of fatty acids . The effects of dietary astaxanthin in doses of
0, 2 or 8 mg/day, over 8 weeks, on oxidative stress and inflammation were investigated in a double
blind study in 14 healthy females . Although these participants did not have oxidative stress or
Mar. Drugs 2011, 9
inflammation those taking 2 mg/day had lower CRP at week eight. There was also a decrease in DNA
damage measured using plasma 8-hydroxy-2′-deoxyguanosine after week four in those taking
astaxanthin. Astaxanthin therefore appears safe, bioavailable when given orally and is suitable for
further investigation in humans.
8. Clinical Trial Using Astaxanthin
A double-blind randomised placebo-controlled clinical trial (Xanthin study) is currently being
conducted to assess the effects of astaxanthin 8mg orally day on oxidative stress, inflammation and
vascular function in patients that have received a kidney transplant . Patients in the study
undertake measurements of surrogate markers of cardiovascular disease including aortic pulse wave
velocity, augmentation index, brachial forearm reactivity and carotid artery intima-media thickness.
Depending on the results from this pilot study a large randomised controlled trial assessing major
cardiovascular outcomes such as myocardial infarction and death may be warranted.
Experimental evidence suggests astaxanthin may have protective effects on cardiovascular disease
when administered prior to an induced ischemia-reperfusion event. In addition, there is evidence that
astaxanthin may decrease oxidative stress and inflammation which are known accompaniments of
cardiovascular disease. At this stage we do not know whether astaxanthin has any therapeutic value in
human cardiovascular disease either in a preventative capacity or when administered after a
cardiovascular insult. It has been proposed that astaxanthin may provide cardiovascular protection
through reducing oxidative stress, which is one of the non-traditional risk factors for the development
of atherosclerotic cardiovascular disease. The role of oxidative stress in cardiovascular disease is
supported by evidence from observational studies that have found associations between antioxidant
intake, oxidative stress and cardiovascular outcomes. Despite this, clinical intervention studies using
antioxidants including vitamin E, -carotene and vitamin C, have not proved successful [22,23]. These
intervention studies may have failed because of flawed design where patients were not included based
on the presence of oxidative stress. Hence, many participants may not have been in a state of oxidative
stress and able to benefit from antioxidant therapy. Also, in those participants where oxidative stress
may have existed there was no way of assessing whether the therapy adequately corrected this. Thus,
the antioxidants used such as vitamin E, -carotene and vitamin C may not have been effective
because insufficient doses were used or an inadequate length of therapy followed to correct the
oxidative stress. Some antioxidants such as -carotene may be pro-oxidant at higher doses, which
could have confounded study results.
Astaxanthin is a potent antioxidant and based on its physicochemical properties and the results of
preliminary experimental studies in ischaemia-reperfusion models of cardiovascular disease, it
warrants consideration for testing in human clinical trials. There have been no safety concerns noted so
far in human clinical studies where astaxanthin has been administered. As astaxanthin is a potent
antioxidant and is associated with membrane preservation, it may protect against oxidative stress and
inflammation and provide cardiovascular benefits.
Mar. Drugs 2011, 9
Cyanotech the manufacturer of BioAstin, a proprietary brand of astaxanthin, is providing financial
support and astaxanthin capsules and placebo for a clinical trial being conducted by the authors. The
sponsor has no role in the study itself.
1. Dzau, V.J.; Antman, E.M.; Black, H.R.; Hayes, D.L.; Manson, J.E.; Plutzky, J.; Popma, J.J.;
Stevenson, W. The cardiovascular disease continuum validated: Clinical evidence of improved
patient outcomes. Part II: Clinical trial evidence (acute coronary syndromes through renal disease)
and future directions. Circulation 2006, 114, 2871–2891.
Ellingsen, I.; Seljeflot, I.; Arnesen, H.; Tonstad, S. Vitamin C consumption is associated with less
progression in carotid intima media thickness in elderly men: A 3-year intervention study. Nutr.
Metab. Cardiovasc. Dis. 2009, 19, 8–14.
Carty, J.L.; Bevan, R.; Waller, H.; Mistry, N.; Cooke, M.; Lunec, J.; Griffiths, H.R. The effects of
vitamin C supplementation on protein oxidation in healthy volunteers. Biochem. Biophys. Res.
Commun. 2000, 273, 729–735.
Carpenter, K.L.; Kirkpatrick, P.J.; Weissberg, P.L.; Challis, I.R.; Dennis, I.F.; Freeman, M.A.;
Mitchinson, M.J. Oral alpha-tocopherol supplementation inhibits lipid oxidation in established
human atherosclerotic lesions. Free Radic. Res. 2003, 37, 1235–1244.
Stampfer, M.J.; Hennekens, C.H.; Manson, J.E.; Colditz, G.A.; Rosner, B.; Willett, W.C.
Vitamin E consumption and the risk of coronary disease in women. N. Engl. J. Med. 1993, 328,
Rimm, E.B.; Stampfer, M.J.; Ascherio, A.; Giovannucci, E.; Colditz, G.A.; Willett, W.C.
Vitamin E consumption and the risk of coronary heart disease in men. N. Engl. J. Med. 1993, 328,
Gey, K.F.; Puska, P. Plasma vitamins E and A inversely correlated to mortality from ischemic
heart disease in cross-cultural epidemiology. Ann. N. Y. Acad. Sci. 1989, 570, 268–282.
Willcox, B.J.; Curb, J.D.; Rodriguez, B.L. Antioxidants in cardiovascular health and disease: Key
lessons from epidemiologic studies. Am. J. Cardiol. 2008, 101, 75D–86D.
Frei, B. Cardiovascular disease and nutrient antioxidants: Role of low-density lipoprotein
oxidation. Crit. Rev. Food Sci. Nutr. 1995, 35, 83–98.
10. Steinberg, D. Antioxidants in the prevention of human atherosclerosis. Summary of the
proceedings of a National Heart, Lung, and Blood Institute Workshop: September 5–6, 1991,
Bethesda, Maryland. Circulation 1992, 85, 2337–2344.
11. Helmersson, J.; Arnlov, J.; Larsson, A.; Basu, S. Low dietary intake of beta-carotene,
alpha-tocopherol and ascorbic acid is associated with increased inflammatory and oxidative stress
status in a Swedish cohort. Br. J. Nutr. 2009, 101, 1775–1782.
12. Osganian, S.K.; Stampfer, M.J.; Rimm, E.; Spiegelman, D.; Manson, J.E.; Willett, W.C.
Dietary carotenoids and risk of coronary artery disease in women. Am. J. Clin. Nutr. 2003, 77,
Mar. Drugs 2011, 9
13. Ford, E.S.; Giles, W.H. Serum vitamins, carotenoids, and angina pectoris: Findings from the
National Health and Nutrition Examination Survey III. Ann. Epidemiol. 2000, 10, 106–116.
14. Klipstein-Grobusch, K.; Geleijnse, J.M.; den Breeijen, J.H.; Boeing, H.; Hofman, A.;
Grobbee, D.E.; Witteman, J.C. Dietary antioxidants and risk of myocardial infarction in the
elderly: The Rotterdam Study. Am. J. Clin. Nutr. 1999, 69, 261–266.
15. Gaziano, J.M.; Manson, J.E.; Branch, L.G.; Colditz, G.A.; Willett, W.C.; Buring, J.E.
A prospective study of consumption of carotenoids in fruits and vegetables and decreased
cardiovascular mortality in the elderly. Ann. Epidemiol. 1995, 5, 255–260.
16. Morris, D.L.; Kritchevsky, S.B.; Davis, C.E. Serum carotenoids and coronary heart disease.
The Lipid Research Clinics Coronary Primary Prevention Trial and Follow-up Study. JAMA
1994, 272, 1439–1441.
17. Knekt, P.; Reunanen, A.; Jarvinen, R.; Seppanen, R.; Heliovaara, M.; Aromaa, A. Antioxidant
vitamin intake and coronary mortality in a longitudinal population study. Am. J. Epidemiol. 1994,
18. Stephens, N.G.; Parsons, A.; Schofield, P.M.; Kelly, F.; Cheeseman, K.; Mitchinson, M.J.
Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart
Antioxidant Study (CHAOS). Lancet 1996, 347, 781–786.
19. Tepel, M.; van der Giet, M.; Statz, M.; Jankowski, J.; Zidek, W. The antioxidant acetylcysteine
reduces cardiovascular events in patients with end-stage renal failure: A randomized, controlled
trial. Circulation 2003, 107, 992–995.
20. Boaz, M.; Smetana, S.; Weinstein, T.; Matas, Z.; Gafter, U.; Iaina, A.; Knecht, A.; Weissgarten, Y.;
Brunner, D.; Fainaru, M.; Green, M.S. Secondary prevention with antioxidants of cardiovascular
disease in endstage renal disease (SPACE): Randomised placebo-controlled trial. Lancet 2000,
21. Steinhubl, S.R. Why have antioxidants failed in clinical trials? Am. J. Cardiol. 2008, 101,
22. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of antioxidant
vitamin supplementation in 20,536 high-risk individuals: A randomised placebo-controlled trial.
Lancet 2002, 360, 23–33.
23. Yusuf, S.; Dagenais, G.; Pogue, J.; Bosch, J.; Sleight, P. Vitamin E supplementation and
cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study
Investigators. N. Engl. J. Med. 2000, 342, 154–160.
24. Sandmann, G. Carotenoid biosynthesis in microorganisms and plants. Eur. J. Biochem. 1994, 223,
25. McNulty, H.; Jacob, R.F.; Mason, R.P. Biologic activity of carotenoids related to distinct
membrane physicochemical interactions. Am. J. Cardiol. 2008, 101, 20D–29D.
26. Jackson, H.; Braun, C.L.; Ernst, H. The chemistry of novel xanthophyll carotenoids. Am. J.
Cardiol. 2008, 101, 50D–57D.
27. McNulty, H.P.; Byun, J.; Lockwood, S.F.; Jacob, R.F.; Mason, R.P. Differential effects of
carotenoids on lipid peroxidation due to membrane interactions: X-ray diffraction analysis.
Biochim. Biophys. Acta 2007, 1768, 167–174.
Mar. Drugs 2011, 9
28. Brown, B.G.; Zhao, X.Q.; Chait, A.; Fisher, L.D.; Cheung, M.C.; Morse, J.S.; Dowdy, A.A.;
Marino, E.K.; Bolson, E.L.; Alaupovic, P.; Frohlich, J.; Albers, J.J. Simvastatin and niacin,
antioxidant vitamins, or the combination for the prevention of coronary disease. N. Engl. J. Med.
2001, 345, 1583–1592.
29. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. The effect of vitamin E
and beta carotene on the incidence of lung cancer and other cancers in male smokers. N. Engl. J.
Med. 1994, 330, 1029–1035.
30. Omenn, G.S.; Goodman, G.E.; Thornquist, M.D.; Balmes, J.; Cullen, M.R.; Glass, A.;
Keogh, J.P.; Meyskens, F.L.; Valanis, B.; Williams, J.H.; Barnhart, S.; Hammar, S. Effects of a
combination of beta carotene and vitamin A on lung cancer and cardiovascular disease.
N. Engl. J. Med. 1996, 334, 1150–1155.
31. Lee, I.M.; Cook, N.R.; Manson, J.E.; Buring, J.E.; Hennekens, C.H. Beta-carotene
supplementation and incidence of cancer and cardiovascular disease: The Women’s Health Study.
J. Natl. Cancer Inst. 1999, 91, 2102–2106.
32. Hennekens, C.H.; Buring, J.E.; Manson, J.E.; Stampfer, M.; Rosner, B.; Cook, N.R.;
Belanger, C.; LaMotte, F.; Gaziano, J.M.; Ridker, P.M.; Willett, W.; Peto, R. Lack of effect of
long-term supplementation with beta carotene on the incidence of malignant neoplasms and
cardiovascular disease. N. Engl. J. Med. 1996, 334, 1145–1149.
33. Burton, G.W.; Ingold, K.U. beta-Carotene: An unusual type of lipid antioxidant. Science 1984,
34. Lauver, D.A.; Driscoll, E.M.; Lucchesi, B.R. Disodium disuccinate astaxanthin prevents carotid
artery rethrombosis and ex vivo platelet activation. Pharmacology 2008, 82, 67–73.
35. Gross, G.J.; Lockwood, S.F. Cardioprotection and myocardial salvage by a disodium disuccinate
astaxanthin derivative (Cardax). Life Sci. 2004, 75, 215–224.
36. Gross, G.J.; Hazen, S.L.; Lockwood, S.F. Seven day oral supplementation with Cardax (disodium
disuccinate astaxanthin) provides significant cardioprotection and reduces oxidative stress in rats.
Mol. Cell. Biochem. 2006, 283, 23–30.
37. Wertz, K.; Hunziker, P.B.; Seifert, N.; Riss, G.; Neeb, M.; Steiner, G.; Hunziker, W.; Goralczyk, R.
beta-Carotene interferes with ultraviolet light A-induced gene expression by multiple pathways.
J. Invest. Dermatol. 2005, 124, 428–434.
38. Camera, E.; Mastrofrancesco, A.; Fabbri, C.; Daubrawa, F.; Picardo, M.; Sies, H.; Stahl, W.
Astaxanthin, canthaxanthin and beta-carotene differently affect UVA-induced oxidative damage and
expression of oxidative stress-responsive enzymes. Exp. Dermatol. 2009, 18, 222–231.
39. Camara, B.; Bouvier, F. Oxidative remodeling of plastid carotenoids. Arch. Biochem. Biophys.
2004, 430, 16–21.
40. Sharoni, Y.; Agbaria, R.; Amir, H.; Ben-Dor, A.; Bobilev, I.; Doubi, N.; Giat, Y.; Hirsh, K.;
Izumchenko, G.; Khanin, M.; Kirilov, E.; Krimer, R.; Nahum, A.; Steiner, M.; Walfisch, Y.;
Walfisch, S.; Zango, G.; Danilenko, M.; Levy, J. Modulation of transcriptional activity by
antioxidant carotenoids. Mol. Asp. Med. 2003, 24, 371–384.
41. Guerin, M.; Huntley, M.E.; Olaizola, M. Haematococcus astaxanthin: Applications for human
health and nutrition. Trends Biotechnol. 2003, 21, 210–216.
Mar. Drugs 2011, 9
42. Hussein, G.; Sankawa, U.; Goto, H.; Matsumoto, K.; Watanabe, H. Astaxanthin, a carotenoid with
potential in human health and nutrition. J. Nat. Prod. 2006, 69, 443–449.
43. Schweigert, F. Metabolism of Carotenoids in Mammals; Birkhauser Verlag: Basel,
44. Jyonouchi, H.; Sun, S.; Tomita, Y.; Gross, M.D. Astaxanthin, a carotenoid without vitamin A
activity, augments antibody responses in cultures including T-helper cell clones and suboptimal
doses of antigen. J. Nutr. 1995, 125, 2483–2492.
45. Shimidzu, N. Carotenoids as singlet oxygen quenchers in marine organisms. Fish. Sci. 1996, 62,
46. Miki, W. Biological functions and activities of animal carotenoids. Pure Appl. Chem. 1991, 63,
47. Krinsky, N.I. Antioxidant functions of carotenoids. Free Radic. Biol. Med. 1989, 7, 617–635.
48. Beutner, S.; Bloedorn, B.; Frixel, S.; Blanco, I.H.; Hoffman, T.; Martin, H.D.; Mayer, B.; Noach, P.;
Rack, C.; Schmidt, M.; et al. Quantitative assessment of antioxidant properties of natural colorants
and phytochemicals; carotenoids. flavonoids, phenols and indigoids: The role of β-carotene in
antioxidant functions. J. Sci. Food Agric. 2001, 81, 559–568.
49. Pashkow, F.J.; Watumull, D.G.; Campbell, C.L. Astaxanthin: A novel potential treatment for
oxidative stress and inflammation in cardiovascular disease. Am. J. Cardiol. 2008, 101, 58D–68D.
50. Kobayashi, M.; Kakizono, T.; Nishio, N.; Nagai, S.; Kurimura, Y.; Tsuji, Y. Antioxidant role of
astaxanthin in the green alga Haematococcus pluvialis. Appl. Microbiol. Biotechnol. 1997, 48,
51. Ernst, H. Recent advances in industrial carotenoid synthesis. Pure Appl. Chem. 2002, 74,
52. Lauver, D.A.; Lockwood, S.F.; Lucchesi, B.R. Disodium Disuccinate Astaxanthin (Cardax)
attenuates complement activation and reduces myocardial injury following ischemia/reperfusion.
J. Pharmacol. Exp. Ther. 2005, 314, 686–692.
53. Lockwood, S.F.; Gross, G.J. Disodium disuccinate astaxanthin (Cardax): Antioxidant and
antiinflammatory cardioprotection. Cardiovasc. Drug Rev. 2005, 23, 199–216.
54. Gross, G.J.; Lockwood, S.F. Acute and chronic administration of disodium disuccinate
astaxanthin (Cardax) produces marked cardioprotection in dog hearts. Mol. Cell. Biochem. 2005,
55. Khan, S.K.; Malinski, T.; Mason, R.P.; Kubant, R.; Jacob, R.F.; Fujioka, K.; Denstaedt, S.J.;
King, T.J.; Jackson, H.L.; Hieber, A.D.; Lockwood, S.F.; Goodin, T.H.; Pashkow, F.J.;
Bodary, P.F. Novel astaxanthin prodrug (CDX-085) attenuates thrombosis in a mouse model.
Thromb. Res. 2010, 126, 299–305.
56. Shargel, L.; Yu, A. Applied Biopharmaceutics and Pharmacokinetics; Appleton-Lange: Stamford,
CT, USA, 1999.
57. Rishton, G.M. Natural products as a robust source of new drugs and drug leads: Past successes
and present day issues. Am. J. Cardiol. 2008, 101, 43D–49D.
58. Kang, J.O.; Kim, S.J.; Kim, H. Effect of astaxanthin on the hepatotoxicity, lipid peroxidation and
antioxidative enzymes in the liver of CCl4-treated rats. Methods Find. Exp. Clin. Pharmacol.
2001, 23, 79–84.
Mar. Drugs 2011, 9
59. Kamath, B.S.; Srikanta, B.M.; Dharmesh, S.M.; Sarada, R.; Ravishankar, G.A. Ulcer preventive
and antioxidative properties of astaxanthin from Haematococcus pluvialis. Eur. J. Pharmacol.
2008, 590, 387–395.
60. Naito, Y.; Uchiyama, K.; Aoi, W.; Hasegawa, G.; Nakamura, N.; Yoshida, N.; Maoka, T.;
Takahashi, J.; Yoshikawa, T. Prevention of diabetic nephropathy by treatment with astaxanthin in
diabetic db/db mice. Biofactors 2004, 20, 49–59.
61. Ohgami, K.; Shiratori, K.; Kotake, S.; Nishida, T.; Mizuki, N.; Yazawa, K.; Ohno, S. Effects of
astaxanthin on lipopolysaccharide-induced inflammation in vitro and in vivo. Invest. Ophthalmol.
Vis. Sci. 2003, 44, 2694–2701.
62. Lee, S.J.; Bai, S.K.; Lee, K.S.; Namkoong, S.; Na, H.J.; Ha, K.S.; Han, J.A.; Yim, S.V.; Chang, K.;
Kwon, Y.G.; Lee, S.K.; Kim, Y.M. Astaxanthin inhibits nitric oxide production and inflammatory
gene expression by suppressing I(kappa)B kinase-dependent NF-kappaB activation. Mol. Cells
2003, 16, 97–105.
63. Aoi, W.; Naito, Y.; Sakuma, K.; Kuchide, M.; Tokuda, H.; Maoka, T.; Toyokuni, S.; Oka, S.;
Yasuhara, M.; Yoshikawa, T. Astaxanthin limits exercise-induced skeletal and cardiac muscle
damage in mice. Antioxid. Redox Signal. 2003, 5, 139–144.
64. Uchiyama, K.; Naito, Y.; Hasegawa, G.; Nakamura, N.; Takahashi, J.; Yoshikawa, T. Astaxanthin
protects beta-cells against glucose toxicity in diabetic db/db mice. Redox Rep. 2002, 7, 290–293.
65. Nakajima, Y.; Inokuchi, Y.; Shimazawa, M.; Otsubo, K.; Ishibashi, T.; Hara, H. Astaxanthin, a
dietary carotenoid, protects retinal cells against oxidative stress in vitro and in mice in vivo.
J. Pharm. Pharmacol. 2008, 60, 1365–1374.
66. Manabe, E.; Handa, O.; Naito, Y.; Mizushima, K.; Akagiri, S.; Adachi, S.; Takagi, T.; Kokura, S.;
Maoka, T.; Yoshikawa, T. Astaxanthin protects mesangial cells from hyperglycemia-induced
oxidative signaling. J. Cell. Biochem. 2008, 103, 1925–1937.
67. Nakano, M.; Onodera, A.; Saito, E.; Tanabe, M.; Yajima, K.; Takahashi, J.; Nguyen, V.C. Effect
of astaxanthin in combination with alpha-tocopherol or ascorbic acid against oxidative damage in
diabetic ODS rats. J. Nutr. Sci. Vitaminol. (Tokyo) 2008, 54, 329–334.
68. Choi, S.K.; Park, Y.S.; Choi, D.K.; Chang, H.I. Effects of astaxanthin on the production of NO
and the expression of COX-2 and iNOS in LPS-stimulated BV2 microglial cells. J. Microbiol.
Biotechnol. 2008, 18, 1990–1996.
69. Liu, X.; Shibata, T.; Hisaka, S.; Osawa, T. Astaxanthin inhibits reactive oxygen species-mediated
cellular toxicity in dopaminergic SH-SY5Y cells via mitochondria-targeted protective mechanism.
Brain Res. 2009, 1254, 18–27.
70. Iwamoto, T.; Hosoda, K.; Hirano, R.; Kurata, H.; Matsumoto, A.; Miki, W.; Kamiyama, M.;
Itakura, H.; Yamamoto, S.; Kondo, K. Inhibition of low-density lipoprotein oxidation by
astaxanthin. J. Atheroscler. Thromb. 2000, 7, 216–222.
71. Hussein, G.; Nakamura, M.; Zhao, Q.; Iguchi, T.; Goto, H.; Sankawa, U.; Watanabe, H.
Antihypertensive and neuroprotective effects of astaxanthin in experimental animals.
Biol. Pharm. Bull. 2005, 28, 47–52.
72. Hussein, G.; Goto, H.; Oda, S.; Sankawa, U.; Matsumoto, K.; Watanabe, H. Antihypertensive
potential and mechanism of action of astaxanthin: III. Antioxidant and histopathological effects in
spontaneously hypertensive rats. Biol. Pharm. Bull. 2006, 29, 684–688.
Mar. Drugs 2011, 9
73. Aoi, W.; Naito, Y.; Takanami, Y.; Ishii, T.; Kawai, Y.; Akagiri, S.; Kato, Y.; Osawa, T.;
Yoshikawa, T. Astaxanthin improves muscle lipid metabolism in exercise via inhibitory effect of
oxidative CPT I modification. Biochem. Biophys. Res. Commun. 2008, 366, 892–897.
74. Nakao, R.; Nelson, O.L.; Park, J.S.; Mathison, B.D.; Thompson, P.A.; Chew, B.P. Effect of
astaxanthin supplementation on inflammation and cardiac function in BALB/c mice. Anticancer
Res. 2010, 30, 2721–2725.
75. Yamamoto, R.; Kanazawa, A.; Shimizu, T.; Hirose, T.; Tanaka, Y.; Kawamori, R.; Watada, H.
Association between atherosclerosis and newly classified chronic kidney disease stage for
Japanese patients with type 2 diabetes. Diabetes Res. Clin. Pract. 2009, 84, 39–45.
76. Osterlie, M.; Bjerkeng, B.; Liaaen-Jensen, S. Plasma appearance and distribution of astaxanthin
E/Z and R/S isomers in plasma lipoproteins of men after single dose administration of astaxanthin.
J. Nutr. Biochem. 2000, 11, 482–490.
77. Mercke Odeberg, J.; Lignell, A.; Pettersson, A.; Hoglund, P. Oral bioavailability of the
antioxidant astaxanthin in humans is enhanced by incorporation of lipid based formulations.
Eur. J. Pharm. Sci. 2003, 19, 299–304.
78. Spiller, G.A.; Dewell, A. Safety of an astaxanthin-rich Haematococcus pluvialis algal extract:
A randomized clinical trial. J. Med. Food 2003, 6, 51–56.
79. Coral-Hinostroza, G.N.; Ytrestoyl, T.; Ruyter, B.; Bjerkeng, B. Plasma appearance of unesterified
astaxanthin geometrical E/Z and optical R/S isomers in men given single doses of a mixture of
optical 3 and 3′R/S isomers of astaxanthin fatty acyl diesters. Comp. Biochem. Physiol. C Toxicol.
Pharmacol. 2004, 139, 99–110.
80. Karppi, J.; Rissanen, T.H.; Nyyssonen, K.; Kaikkonen, J.; Olsson, A.G.; Voutilainen, S.;
Salonen, J.T. Effects of astaxanthin supplementation on lipid peroxidation. Int. J. Vitam. Nutr.
Res. 2007, 77, 3–11.
81. Parisi, V.; Tedeschi, M.; Gallinaro, G.; Varano, M.; Saviano, S.; Piermarocchi, S. Carotenoids and
antioxidants in age-related maculopathy italian study: Multifocal electroretinogram modifications
after 1 year. Ophthalmology 2008, 115, 324–333.e2.
82. Miyawaki, H.; Takahashi, J.; Tsukahara, H.; Takehara, I. Effects of astaxanthin on human blood
rheology. J. Clin. Biochem. Nutr. 2008, 43, 69–74.
83. Rufer, C.E.; Moeseneder, J.; Briviba, K.; Rechkemmer, G.; Bub, A. Bioavailability of astaxanthin
stereoisomers from wild (Oncorhynchus spp.) and aquacultured (Salmo salar) salmon in healthy
men: A randomised, double-blind study. Br. J. Nutr. 2008, 99, 1048–1054.
84. Park, J.S.; Chyun, J.H.; Kim, Y.K.; Line, L.L.; Chew, B.P. Astaxanthin decreased oxidative stress
and inflammation and enhanced immune response in humans. Nutr. Metab. (Lond.) 2010, 7, 18.
85. Serebruany, V.; Malinin, A.; Goodin, T.; Pashkow, F. The in vitro effects of Xancor, a synthetic
astaxanthine derivative, on hemostatic biomarkers in aspirin-naive and aspirin-treated subjects
with multiple risk factors for vascular disease. Am. J. Ther. 2010, 17, 125–132.
86. Andersen, L.P.; Holck, S.; Kupcinskas, L.; Kiudelis, G.; Jonaitis, L.; Janciauskas, D.; Permin, H.;
Wadstrom, T. Gastric inflammatory markers and interleukins in patients with functional dyspepsia
treated with astaxanthin. FEMS Immunol. Med. Microbiol. 2007, 50, 244–248.
Mar. Drugs 2011, 9 Download full-text
87. Fassett, R.G.; Healy, H.; Driver, R.; Robertson, I.K.; Geraghty, D.P.; Sharman, J.E.; Coombes, J.S.
Astaxanthin vs. placebo on arterial stiffness, oxidative stress and inflammation in renal transplant
patients (Xanthin): A randomised controlled trial. BMC Nephrol. 2008, 9, 17.
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