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AstaPure® Astaxanthin
Dr Nina Bailey BSc MSc, PhD RNutr
1
Introducing
Astaxanthin
Astaxanthin belongs to a family of naturally occurring pigments called
carotenoids
There are over 600 known carotenoids and they all have at least nine
conjugated double bonds, which absorb specific wavelengths of visible light
and thus provide carotenoids with their characteristic colours
Carotenes are non-polar molecules, which contain only carbon and
hydrogen atoms
• α-carotene, β-carotene & lycopene
Xanthophylls are polar carotenoids, which contain at least one oxygen atom
• Lutein, zeaxanthin & astaxanthin
•Haematococcus pluvialis (H. pluvialis), a single-celled green algae, is believed to have
the highest capacity to accumulate astaxanthin in nature – it does so under
environmental stresses such as starvation, high salt, elevated temperature, or
irradiation
•Astaxanthin produced from H. pluvialis is the primary
natural source of astaxanthin and is the source of
astaxanthin used in AstaPure®
Source:
•Astaxanthin is found in abundance in marine animals such as salmon, crab and
crustaceans that live on astaxanthin-containing plankton and micro algae and is
responsible for their pink-red colour.
Light microscopic images of H. pluvialis cells in life cycle
(A) Green vegetative motile cell; (B) Green vegetative palmella cell; (C) Astaxanthin accumulating palmella
cell in transition to aplanospore; (D) Astaxanthin accumulated aplanospore cell. Scale bar: 10 μm.
Md. Mahfuzur R. Shah, Yuanmei Liang, Jay J. Cheng, Maurycy Daroch Astaxanthin-Producing Green Microalga Haematococcus pluvialis:
From Single Cell to High Value Commercial ProductsFront Plant Sci. 2016; 7: 531
Factors that influence astaxanthin
efficacy/benefits
• Stereochemistry • Source
• Configuration • Safety*
• Esterification • Efficacy
• Synergy • Dosage
* USDA, Notification of GRAS Determination for Natural Astaxanthin Complex (AstaPure),a Haematococcus pluvialis extract characterized by component
astaxanthin esters of common edible fatty acids
Park JS, Chyun JH, Kim YK, Line LL, Chew BP. Astaxanthin decreased oxidative stress and inflammation and enhanced immune response in humans. Nutr Metab
(Lond). 2010 Mar 5;7:18.
Polar end
Stereochemistry
There are three distinct shapes (enantiomers) [3S,3 S], [3R,3 R] and [3R,3 S] and while natural and′ ′ ′
synthetic astaxanthin share the same molecular formula, 75% of the molecules are shaped differently,
meaning that natural and synthetic astaxanthin molecules are stereochemically different
Polar end Non polar polyene chainNatural astaxanthin is 100% [3S,3 S]′
Synthetic astaxanthin is:
ο 25% as [3S,3 S]′
ο 50% as [3R,3 S]′
ο 25% as [3R,3 R]′
It is the [3S,3 S] form found in′ AstaPure® that
offers unprecedented antioxidant activity.
It is estimated that the synthetic form
would need to be provided in doses 20–50
times greater than the natural form to
achieve the same benefits
Capelli, B., Bagchi, D. & Cysewski, G.R. Synthetic astaxanthin is significantly inferior to algal-based astaxanthin as an antioxidant and may not be suitable as a human nutraceutical
supplement Nutrafoods 2013 (12) 145.
Esterification
In nature, astaxanthin it is found either conjugated with proteins
(e.g., salmon muscle or lobster exoskeleton) or esterified by
hydroxyl reaction with one (monoester) or two (diester) fatty
acids, which stabilise the molecule
•The predominant form of astaxanthin in H. pluvialis is mono-ester
•In its free form (including synthetic), astaxanthin is considerably
unstable and particularly susceptible to oxidation
Zuluaga M, Gueguen V, Letourneur D, Pavon-Djavid G. Astaxanthin antioxidant impact on excessive reactive oxygen
species generation induced by ischemia and reperfusion injury. Chem Biol Interact. 2018 Jan 5;279:145-158.
Astaxanthin can be:
• straight chained (E-isomer)
OR
• bent chained (Z-isomer) of which there
are 3 (9Z, 13Z & 15Z)
The E configurations are predominant in
nature, better absorbed and span the
membrane more efficiently than Z-
isomers
AstaPure® contains a very high content of
esterified astaxanthin (>95%, w/w) of
which the E-isomer is the dominant
form
Carotenoid %
E-Astaxanthin 70-90
9Z-Astaxanthin 5-20
13Z-Astaxanthin 2-10
Total Astaxanthin <95
β-Carotene 0.05-0.2
Lutein 0.7-1.2
Canthaxanthin 0.2-0.6
Total Other Carotenoids >2
Configuration
Synergy
AstaPure® astaxanthin is concentrated astaxanthin oil, naturally containing the
algae oil, the carotenoid complex, amino acids and fatty acids (43% of which is
omega-9 oleic acid)
The mono- and di- esterified astaxanthin molecules in AstaPure® provide increased
stability and bioavailability over the ‘free’ molecules in synthetic products
Odeberg JM, Lignell Å, Petterson A, Höglund. Oral bioavailability of the antioxidant astaxanthin in humans is enhanced by incorporation of lipid based
formulations. Eur J Pharm Sci. 2003; 19(4):299-304.
AstaPure® is mixed with cold-pressed olive oil which significantly enhances the
bioavailability of astaxanthin
Synergy:
Natural, but not synthetic, astaxanthin provides a natural carotenoid complex
containing approximately:
70% monoesterified astaxanthin
10% diesterified astaxanthin
5% free astaxanthin
6% beta-carotene
5% canthaxanthin
4% lutein
The presence of the additional antioxidant carotenoids in AstaPure® enhance its therapeutic
potential
AstaPure® summary
• Source  H. pluvialis (natural)
• Stereochemistry 100% [3S,3 S]′
• Configuration Predominantly E-isomer
• Esterification Mono- and di-esterified
• Synergy Natural carotenoid complex
AstaPure® cultivation process
Growth Apparatus of the “Green Stage” Growth Apparatus of the “Red Stage”
Cultivation stages of Haematococcus pluvialis microalgae
Advantages of closed system cultivation
Closed System Open System
Adopting a ‘closed system’ technology
eliminates microbial, chemical or any other
outdoor contaminations
Difficult to control contamination which can
be in the form of general air pollution, to
animal & bird excrement
Astaxanthin
mechanisms of action
Free radicals initiate disease
The free radicals are derived from
•endogenous sources - as part of normal metabolic processes
•exogenous sources - pollution, alcohol, tobacco smoke, heavy metals, solvents,
pesticides, radiation, UV light and certain drugs
all of which can damage all classes of biological molecules including nucleic acids,
carbohydrate, proteins and lipids
Antioxidants (both consumed and synthesised endogenously) act to keep free radical
levels (and subsequent damage) in check
Oxidative stress arises when there is an imbalance between free radical production
and antioxidant production/intake
The regulation of reducing and oxidising (redox) state is critical for essential cellular
homeostasis
Guerin M, Huntley ME, Olaizola M. Haematococcus astaxanthin: applications for human health and nutrition. Trends Biotechnol. 2003 May;21(5):210-6.
Review.
Picture source: http://www.milesonveggies.com/wellness/nutrition/why-antioxidants-are-important/
Free radicals initiate disease
An antioxidant with unique benefits
Astaxanthin’s hydroxyl (OH) and ketone (C=O) oxygen-containing groups are
responsible for its high antioxidant activity and ability to span and stabilise cell
membranes
The ability of carotenoids to act as antioxidants is related to the number of double
bonds within the polar polyene chain region. Those with ≥9 double bonds (such as
astaxanthin) are the best quenchers of singlet oxygen molecules.
Furthermore, astaxanthin (as with all carotenoids) is not destroyed during the process
of neutralising free radicals, meaning that it can repeatedly quench singlet oxygen
molecules. This is reflected by its superior ORAC score of ~25,000 μmole TE/g
Nishida Y., Yamashita E., Miki W. Quenching activities of common hydrophilic and lipophilic antioxidants against singlet oxygen using
chemiluminescence detection system. Carotenoid Science. 2007;11(6):16–20.
Astaxanthin's polar end groups overlap the polar boundary zones of the membrane, while the non-polar middle
fits the membrane’s non-polar interior. The dashed red line speculatively indicates “lightning-rod” conduction of
electrons along the astaxanthin molecule, possibly to vitamin C or other antioxidants located outside the
membrane.
Pashkow FJ, Watumull DG, Campbell CL. Astaxanthin: a novel potential treatment for oxidative stress and inflammation in cardiovascular disease. Am J Cardiol
2008;101(suppl):58D-68D
Kidd P. Astaxanthin, cell membrane nutrient with diverse clinical benefits and anti-aging potential. Altern Med Rev. 2011 Dec;16(4):355-64. Review
Astaxanthin’s multiple conjugated double bonds allows it to
act as a strong antioxidant by electron donation and by
reacting with free radicals:
Free radical scavenging
Free radicals are neutralised by antioxidants either by donating an electron to
the free radical to ensure electrons in the outer ring of the atom are paired or
by incorporating the unpaired electron into its own molecule
Quenching
Antioxidants take the energy from the charged singlet oxygen molecule
thereby de-charging it, making it harmless and terminating a potentially
harmful oxidative stress chain-reaction
The ORAC (Oxygen Radical Absorbance Capacity) unit, ORAC value, or “ORAC score” is a method
of measuring the in vitro antioxidant capacity of different foods and supplements
•It is theorised that foods that are higher on the ORAC scale may be more effective at neutralising
free radicals
•Thus the ORAC value of a nutrient is a useful indicator of its antioxidant potential and ability to
slow the oxidative processes and free radical damage that can contribute to age-related
degeneration and disease
Nishida Y., Yamashita E., Miki W. Quenching activities of common hydrophilic and lipophilic antioxidants against singlet oxygen using chemiluminescence
detection system. Carotenoid Science. 2007;11(6):16–20.
• Astaxanthin’s ROS-scavenging capacity
has been shown to be 6000x more than
vitamin C, 800x more than coenzyme
Q10, 550x more than vitamin E, 200x
more than polyphenols, 150x more than
anthocyanins, and 75x more than alpha
lipoic acid
Astaxanthin - the ‘king of the antioxidants’?
Unique molecular structure that enables its superior position in the membrane: The
general ‘rule’ of antioxidants is that lipid-soluble antioxidants protect the lipid-soluble
part of cells, and water-soluble antioxidants protect the water-soluble part of cells, yet
astaxanthin’s unique structure allows it to span the cell membrane fulfilling both roles
while also providing cell membrane stability
Direct antioxidant action: Quenches singlet oxygen and scavenges free radicals to
prevent or terminate chain reactions
Indirect antioxidant action: Astaxanthin activates antioxidant enzymes
Astaxanthin is a ‘pure’ antioxidant: Unlike other antioxidants, astaxanthin never turns
into a pro-oxidant. Vitamins C & E, and other carotenoid antioxidants such as lycopene
and zeaxanthin can all become pro-oxidants under certain conditions
Mechanisms of action - astaxanthin
Acts as COX-2 inhibitor
Inhibits iNOS enzyme activity, which decreases production of nitric oxide
Reduces C-reactive protein (CRP), one of the acute-phase proteins that increase
during systemic inflammation
Suppresses inflammatory gene expression by suppressing I(kappa)B kinase-
dependent NF-kappaB activation
Suppresses inflammatory agents such as prostaglandin E2, IL-1β, TNFα– the key
proinflammatory mediators, which promote inflammatory responses
Inhibits the enzyme 5-α-reductase with anti-androgen effects
Crosses the blood-brain and blood-retinal barriers (promoting brain and eye health)
MUSCLE & JOINTS:
•Improves endurance & performance
•Decreases inflammation & muscle soreness
EYE HEALTH:
•Protects against light induced retinal damage
•Increases UV protection
ENERGY:
•Reduces tiredness & fatigue
•Benefits for endurance & recovery after exercise
GUT HEALTH:
•Reduces Helicobacter pylori inflammation
•Protects against gastric ulceration
•Reduces acid reflux & heart burn
LIVER HEALTH:
•Decreases inflammation
•Protects against fatty liver disease
METABOLIC SYNDROME & DIABETES:
•Improves insulin sensitivity;
•Protects against the development of insulin resistance
•Improves insulin-glucose balance
Whilst research into astaxanthin is still in its relative infancy some human, as well
as animal and mechanistic studies have found it to be highly beneficial to the
following systems and conditions:
SKIN:
•Reduces UV damage
•Improves moisture & elasticity
•Reduces wrinkles
IMMUNE SYSTEM:
•Improves immune defences
•Reduces inflammation
CARDIOVASCULAR HEALTH:
•Improves blood flow
•Lowers blood pressure
•Lowers lipids (cholesterol & triglycerides)
BRAIN:
•Improves cognitive function, memory and learning
•Protects the brain from ischemic stroke
•Benefits for Parkinson & Alzheimer's disease
FERTILITY:
•Improves sperm and oocyte quality
•Improves fertility
CANCER:
•Suppresses cell growth, proliferation and metastasis
Whilst research into astaxanthin is still in its relative infancy some human, as well
as animal and mechanistic studies have found it to be highly beneficial to the
following systems and conditions:
mg of astaxanthin in a typical 85g
portion of different species of salmon
Farmed Rainbow Trout 2.1
Wild Sockeye Salmon 3.2
Farmed Rainbow Trout 2.1
Wild Coho Salmon 1.8
Farmed Atlantic Salmon 0.8
Wild Arctic Char 0.7
Farmed Arctic Char 0.7
Wild Pink Salmon 0.6
Chinook Salmon 0.5
Source
Astaxanthin
concentration ppm
Salmonids (salmon) 5
Plankton 60
Krill 120
Arctic Shrimp
(Pandalus borealis)
1,200
Phaffia Yeast
(Xanthophyllomyces dendrorhous)
10,000
Green Algae
(Haematococcus pluvialis)
40,000
Biswal S. Oxidative stress and astaxanthin: The novel supernutrient carotenoid. Int J Health Allied Sci 2014;3:147-53
Supplements vs food
To achieve 4mg intake you would need to consume
•1.25 portions of wild sockeye salmon
•1.9 portions of farmed rainbow trout
•6.7 portions of wild pink salmon
AstaPure® compared
Products claiming to deliver
4mg of astaxanthin often only
contain 4mg of the bulk oil,
with a 10% concentration of
active astaxanthin. Therefore,
these products only deliver
0.4mg of active Astaxanthin
Igennus AstaPure® pure delivers 42mg of oil per
capsule and 4mg active astaxanthin
Absorption and digestion of astaxanthin
The absorption of astaxanthin is similar to that of dietary lipids or fat-soluble vitamins:
1.the ester forms are hydrolysed in the gastro-intestinal tract prior to absorption
2.the incorporation into mixed lipid micelles in the lumen composed of phospholipids,
lipids, cholesterol, and bile salts and absorbed into the enterocyte through passive and
facilitated diffusion
3.the uptake into intestinal mucosa
4.the incorporation into chylomicrons
5.the release into the lymph
6.chylomicrons are digested by lipoprotein lipase which releases astaxanthin
7.astaxanthin is distributed mostly by low and very low density lipoproteins
The presence of dietary fat is known to affect the degree of astaxanthin absorption in the
small intestine.
Astaxanthin absorption is higher when emulsified with olive oil (as is the case with AstaPure®
) and taking astaxanthin supplements with additional fat significantly enhances bioavailability (Odeberg
et al., 2003)
Kotake-Nara E, Nagao A. Absorption and metabolism of xanthophylls. Mar Drugs. 2011;9(6):1024-37; Fiedor J, Burda K. Potential role of carotenoids as antioxidants in human health and
disease.Nutrients. 2014 Jan 27;6(2):466-88.
Odeberg JM, Lignell Å, Petterson A, Höglund. Oral bioavailability of the antioxidant astaxanthin in humans is enhanced by incorporation of lipid based formulations. Eur J Pharm Sci.
2003; 19(4):299-304.
Pharmacokinetics
Pharmacokinetic studies are limited; however, in an open labeled study, three middle-
aged male volunteers (41-50 years) ingested a single meal containing first a 10-mg dose
of astaxanthin followed by a dose of 100 mg after 4 weeks
Coral-Hinostroza GN, 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.
The plasma astaxanthin concentration-time
curves were measured over 76 hours.
Maximum levels of astaxanthin (Cmax
) for the
low dose was 0.08 mg/l and 0.28 mg/L for
the high dose, these were reached 11.5 h
after administration and the plasma
astaxanthin elimination half-life was 52 ± 40h
Okada Y, Ishikura M, Maoka T Bioavailability of astaxanthin in Haematococcus algal extract: the effects of timing of diet and smoking habits.
Biosci Biotechnol Biochem. 2009 Sep;73(9):1928-32.
Furthermore, in a separate study, taking astaxanthin after food rather than before food
improved the bioavailability of astaxanthin supplements by 2-fold
An open-label clinical study of the toxicity and efficacy of an astaxanthin-rich H.
pluvialis extract was conducted with 127 healthy adults who received a single, daily
dose of 4, 8 or 20mg of astaxanthin for 4 weeks
•Blood pressure and other parameters were collected before and after 4 weeks of
supplementation
•A significant decrease in systolic blood pressure and fasting blood glucose was
observed in the subjects who ingested 4mg of astaxanthin
•No significant differences were noted from baseline to end treatment for the other
parameters
•There were no adverse effects or changes in the biochemical parameters of the
supplemented groups
The decreases in systolic blood pressure, triglyceride, and fasting glucose values
observed in the present study may support that the product has a beneficial effect in
patients with borderline diabetes mellitus or persons at risk for metabolic syndrome
Satoh A, Tsuji S, Okada Y, Murakami N, Urami M, Nakagawa K, et al. Preliminary clinical evaluation of toxicity and efficacy of a new astaxanthin-
rich Haematococcus pluvialis extract. J Clin Biochem Nutr. 2009; 44(3):280-4.
In a randomised double-blind, placebo-controlled study, 14 young (average age = 21.5 years)
free-living healthy females received 0, 2, or 8 mg astaxanthin daily for 8 weeks
Measures included cytokine production, plasma concentrations of 8-epi-prostaglandin F2α (8-
isoprostane) as a measure of lipid peroxidation, C-Reactive protein (CRP), as a well-
established marker of inflammatory status and oxidative DNA damage was assessed by
measuring plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG)
Park JS, Chyun JH, Kim YK, Line LL, Chew BP. Astaxanthin decreased oxidative stress and inflammation and enhanced immune response in humans. Nutr Metab (Lond). 2010 Mar 5;7:18.
A dose of as low as 2 mg/day, given orally to a human subject for a period of four
weeks, is sufficient to reduce measurable endogenous oxidative DNA damage by about
40%
Overall, this study shows that dietary
astaxanthin, at relatively low doses 2-8 mg
daily over an 8-week period enhanced
immune response, and decreased a DNA
oxidative damage biomarker and
inflammation in young healthy females
“Astaxanthin confers multiple neuroprotective effects in various experimental
models of neurological diseases, which includes both acute injuries and chronic
neurodegenerative disorders. The protective effects of astaxanthin are associated
with its anti-oxidative, anti-inflammatory, anti-apoptotic effects. Astaxanthin is a
safe nutrient, with no toxic effects when it is consumed with food. Furthermore, as
a fat-soluble compound, astaxanthin is able to effectively pass through the BBB.
Therefore, astaxanthin is an excellent candidate for treating neurological diseases.”
Wu H, Niu H, Shao A, Wu C, Dixon BJ, Zhang J, Yang S, Wang Y. Astaxanthin as a Potential Neuroprotective Agent for Neurological Diseases.
Mar Drugs. 2015 Sep 11;13(9):5750-66.
“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.”
Fassett RG, Coombes JS. Astaxanthin in cardiovascular health and disease. Molecules. 2012 Feb 20;17(2):2030-48. doi:
10.3390/molecules17022030. Review.
“The effects of a dietary supplement containing astaxanthin on the accommodation
function and subjective symptoms of the eyes were investigated in 22 middle-aged
and older people (mean age: 53.9 years) with complaints of eye strain.
Astaxanthin was administered to subjects at a daily dose of 6 mg for 4 weeks, and
the pupillary constriction ratio before and after astaxanthin supplementation was
measured by TriIRIS C9000. The change in subjective symptoms after
supplementation was examined by a questionnaire.
The results showed a significant increase in pupillary constriction ratio after
supplementation of astaxanthin, thereby suggesting that astaxanthin may also
improve the accommodation function of the eye and some subjective symptoms
related to presbyopia in middle-aged and older people with complaints of eye
strain”
Kajita M, et al. The Effects of a Dietary Supplement Containing Astaxanthin on the Accommodation Function of the Eye in Middle-aged
and Older People. Medical Consultation & New Remedies. 2009 Mar;46(3):89-93.
Dosing guidance
NUTRITIONAL INFORMATION Per capsule % RI*
AstaPure® Haematococcus pluvialis
microalgae (10% astaxanthin complex)
42 mg n/a
of which astaxanthin 4 mg
of which lutein 36µg
of which cantaxanthin 20µg
of which zeaxanthin 3µg
of which violaxanthin 0.5µg
of which beta-carotene 0.5µg
DIRECTIONS FOR USE
The majority of the research to date used between 2 mg and 24 mg of astaxanthin daily
No general dosage recommendations or standardised guidelines currently exist for astaxanthin
INGREDIENTS:
Cold-pressed extra-virgin olive oil; AstaPure® from Haematococcus pluvialis (H. pluvialis) microalgae
(10% astaxanthin); capsule shell (gelatine, glycerol, beta-carotene, caramel E150a).
This product should not be used as a substitute for a balanced diet. Pregnant or breastfeeding women
should consult their doctor before taking any food supplement. Keep out of the reach of children and
away from sunlight. Free from: dairy, gluten, lactose, soya, wheat, yeast, artificial colours and flavours;
not tested on animals; non-GMO; halal & kosher.
*% Reference Intake
For adults and children aged 12+: take 1-2
capsules daily. For intensive support, the
dose can be increased to 4 capsules daily. For
optimal absorption, astaxanthin should be
taken with fats and immediately after meals.
Do not exceed the above doses unless
advised by a healthcare practitioner.
41
AstaPure® advantages:
Environmentally friendly, controlled, closed microalgae cultivation system
Advanced & controlled down-stream processing of the biomass
Sealed system eliminates the risk of foreign objects, agricultural residue and
microbial or chemical contamination
Green technology, energised by natural sunlight
Reliable and consistent production
Highest commercial concentration of natural astaxanthin
Super-critical CO2 extraction – No organic solvent residues
ISO 9001:2000, HACCP, GMP, Kosher, Halal
High stability
Supporting studies
Provided by AstaPure®
Effect of astaxanthin on the cardiovascular system
Pre-clinical/clinical Effect followed Main outcome Reference
Normal rats
Insulin-resistant rats
Obese rats
level
Dyslipidemia
Adiponectin levels
Increased
Improved
Improved
Murillo 1992
Hussein 2007,
Ikeuchi 2007
Hypertensive rats Hypertension
Stroke incidence
Artery wall thickness
Reduced
Reduced
Reduced
Yanai 2008
Rats
Rabbits
Dogs
Myocardial ischemia-
reperfusion damage
Reduced
Reduced
Gross 2004
Lauver 2005
Gross 2005
Dogs Rethrombosis Reduced Krötz 2004
61 mildly
hyperlipidemic subjects
Dyslipidemia
Adiponectin
level
Improved
Increased
Yoshida 2010
Effect of astaxanthin on various physiological systems
System Pre-clinical/clinical Effect followed Main outcome Reference
Skin Hairless UV-irradiated mice Wrinkles formation Reduction Arakane 2002
Healthy subjects Erythema Reduction Yamashita, 1995
46 healthy women Skin elasticity and
moisture
Improved Yamashita 2002,
Yamashita 2007,Seki
2001
Immune response Mice Humoral responses to
T-dependent antigens
Improved Jyonouchi 1994,
Bennedsen 1999,
Chew 1999
14 healthy women Oxidative stress
markers
Inflammation markers
Immune response
Reduced
Reduced
Improved
Park 2010
Inflammation Rats Inflammation of paw Reduced Kurashige 1990
Mice injected with
inflammation inducers
Inflammation markers
in plasma
Reduced Lockwood 2006
Gastric ulcers H. pylori-infected mice Gastric mucus
Bacterial load
Immune response
Reduced
Reduced
Improved
Bennedsen 1999,
Wang 2000
Chemically - induced gastric
ulcers in rats
Gastric ulcer markers Reduced Kim 2005a, Kamath
2008, Kim 2005b,
Yang 2009
Effect of astaxanthin on eye health
Pre-clinical/clinical Effect followed Main outcome Reference
Rats Light damage to
retina
Reduction Tso 1996
Rats Uveitis Reduction Ohgami 2003
Suzuki 2006
Rats Selenite-induced
cataract
Inhibition Liao 2009
Diabetic patients Humoral superoxide
scavenging activity
Increased Hashimoto 2009
15 subjects with
nonadvanced
Central retina
function
Improved Parisi 2008
18 healthy men Deep vision Improved Sawaki 2002
10 healthy men Eye function Improved Iwasaki 2006
40 asthenopia patients Accommodation
power
Improved Kenji 2005
49 healthy men Uncorrected far
visual acuity
Improved Nakamura 2004
87 visual display terminal
(VDT) workers
Accommodation
amplitude
improved Nagaki 2002
Nagaki 2006
Effect of astaxanthin on muscle endurance
Pre-clinical/clinical Effect followed Main outcome Reference
Exercising mice Muscle lipid metabolism
Oxidative damage
Fatigue
Improved
Reduced
Reduced
Aoi 2008
Aoi 2003
Ikeuchi 2006
16 non trained men Lactic acid accumulation
after run
Reduced Sawaki 2002
19 non trained men Respiratory and sympathetic
nervous system activities
Improved Nagata 2006
20 non trained men Strength/explosiveness
test
Strength/endurance
test
Improved Lignell 2001
Effect of astaxanthin on the central nervous system
Pre-clinical/clinical Effect followed Main outcome Reference
Mice subjected to
transient cerebral
ischemia
Learning and
memory skills
Improved Hussein 2005a
Rats subjected to
transient cerebral
ischemia
Locomotor activity
Cerebral infarction
Improved
Reduced
Shen 2009
Rats chronically fed with
alcohol
Alcohol-induced
neural marker
Reduced Abadie-Guedes 2008
Healthy mice Memory Improved Zhang 2007
10 healthy men (50-69
years old)
Response time and
accuracy of several
tasks
Improved Satoh 2008
AstaPure® summary
» AstaPure® manufacturing:
– Environmentally friendly, controlled, closed microalgae cultivation system
– Sealed system eliminates the risk of foreign objects, agricultural residue and
microbial or chemical contamination
– Green technology, energised by natural sunlight
– Super-critical CO2 extraction: No organic solvent residues
» AstaPure® provides natural 100% [3S,3 S] astaxanthin′ from H. pluvialis,
predominantly as the straight-chained (E-isomer) that efficiently spans the
membrane for unprecedented antioxidant support
» AstaPure® astaxanthin is 95% esterified offering a natural carotenoid complex of
amino acids and fatty acids that enhances both stability and bioavailability
» Safety: this natural form of astaxanthin has over 15 years of safe use as a
commercially sold nutritional supplement with no adverse side-effects
» Efficacy: Natural astaxanthin has been shown to have diverse health benefits in
numerous in vitro, animal and human clinical trials
» Dosage: Benefits observed from as little as 2mg daily
Education Technical
Sophie Tully
Nutrition Education Manager
sophiet@igennus.com
Dr Nina Bailey
Head of Nutrition
ninab@igennus.com
Get in touch

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Introducing Astaxanthin – nature’s most potent antioxidant

  • 1. AstaPure® Astaxanthin Dr Nina Bailey BSc MSc, PhD RNutr 1 Introducing
  • 2. Astaxanthin Astaxanthin belongs to a family of naturally occurring pigments called carotenoids There are over 600 known carotenoids and they all have at least nine conjugated double bonds, which absorb specific wavelengths of visible light and thus provide carotenoids with their characteristic colours Carotenes are non-polar molecules, which contain only carbon and hydrogen atoms • α-carotene, β-carotene & lycopene Xanthophylls are polar carotenoids, which contain at least one oxygen atom • Lutein, zeaxanthin & astaxanthin
  • 3. •Haematococcus pluvialis (H. pluvialis), a single-celled green algae, is believed to have the highest capacity to accumulate astaxanthin in nature – it does so under environmental stresses such as starvation, high salt, elevated temperature, or irradiation •Astaxanthin produced from H. pluvialis is the primary natural source of astaxanthin and is the source of astaxanthin used in AstaPure® Source: •Astaxanthin is found in abundance in marine animals such as salmon, crab and crustaceans that live on astaxanthin-containing plankton and micro algae and is responsible for their pink-red colour.
  • 4. Light microscopic images of H. pluvialis cells in life cycle (A) Green vegetative motile cell; (B) Green vegetative palmella cell; (C) Astaxanthin accumulating palmella cell in transition to aplanospore; (D) Astaxanthin accumulated aplanospore cell. Scale bar: 10 μm. Md. Mahfuzur R. Shah, Yuanmei Liang, Jay J. Cheng, Maurycy Daroch Astaxanthin-Producing Green Microalga Haematococcus pluvialis: From Single Cell to High Value Commercial ProductsFront Plant Sci. 2016; 7: 531
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  • 6. Factors that influence astaxanthin efficacy/benefits • Stereochemistry • Source • Configuration • Safety* • Esterification • Efficacy • Synergy • Dosage * USDA, Notification of GRAS Determination for Natural Astaxanthin Complex (AstaPure),a Haematococcus pluvialis extract characterized by component astaxanthin esters of common edible fatty acids Park JS, Chyun JH, Kim YK, Line LL, Chew BP. Astaxanthin decreased oxidative stress and inflammation and enhanced immune response in humans. Nutr Metab (Lond). 2010 Mar 5;7:18.
  • 7. Polar end Stereochemistry There are three distinct shapes (enantiomers) [3S,3 S], [3R,3 R] and [3R,3 S] and while natural and′ ′ ′ synthetic astaxanthin share the same molecular formula, 75% of the molecules are shaped differently, meaning that natural and synthetic astaxanthin molecules are stereochemically different Polar end Non polar polyene chainNatural astaxanthin is 100% [3S,3 S]′ Synthetic astaxanthin is: ο 25% as [3S,3 S]′ ο 50% as [3R,3 S]′ ο 25% as [3R,3 R]′ It is the [3S,3 S] form found in′ AstaPure® that offers unprecedented antioxidant activity. It is estimated that the synthetic form would need to be provided in doses 20–50 times greater than the natural form to achieve the same benefits Capelli, B., Bagchi, D. & Cysewski, G.R. Synthetic astaxanthin is significantly inferior to algal-based astaxanthin as an antioxidant and may not be suitable as a human nutraceutical supplement Nutrafoods 2013 (12) 145.
  • 8. Esterification In nature, astaxanthin it is found either conjugated with proteins (e.g., salmon muscle or lobster exoskeleton) or esterified by hydroxyl reaction with one (monoester) or two (diester) fatty acids, which stabilise the molecule •The predominant form of astaxanthin in H. pluvialis is mono-ester •In its free form (including synthetic), astaxanthin is considerably unstable and particularly susceptible to oxidation Zuluaga M, Gueguen V, Letourneur D, Pavon-Djavid G. Astaxanthin antioxidant impact on excessive reactive oxygen species generation induced by ischemia and reperfusion injury. Chem Biol Interact. 2018 Jan 5;279:145-158.
  • 9. Astaxanthin can be: • straight chained (E-isomer) OR • bent chained (Z-isomer) of which there are 3 (9Z, 13Z & 15Z) The E configurations are predominant in nature, better absorbed and span the membrane more efficiently than Z- isomers AstaPure® contains a very high content of esterified astaxanthin (>95%, w/w) of which the E-isomer is the dominant form Carotenoid % E-Astaxanthin 70-90 9Z-Astaxanthin 5-20 13Z-Astaxanthin 2-10 Total Astaxanthin <95 β-Carotene 0.05-0.2 Lutein 0.7-1.2 Canthaxanthin 0.2-0.6 Total Other Carotenoids >2 Configuration
  • 10. Synergy AstaPure® astaxanthin is concentrated astaxanthin oil, naturally containing the algae oil, the carotenoid complex, amino acids and fatty acids (43% of which is omega-9 oleic acid) The mono- and di- esterified astaxanthin molecules in AstaPure® provide increased stability and bioavailability over the ‘free’ molecules in synthetic products Odeberg JM, Lignell Å, Petterson A, Höglund. Oral bioavailability of the antioxidant astaxanthin in humans is enhanced by incorporation of lipid based formulations. Eur J Pharm Sci. 2003; 19(4):299-304. AstaPure® is mixed with cold-pressed olive oil which significantly enhances the bioavailability of astaxanthin
  • 11. Synergy: Natural, but not synthetic, astaxanthin provides a natural carotenoid complex containing approximately: 70% monoesterified astaxanthin 10% diesterified astaxanthin 5% free astaxanthin 6% beta-carotene 5% canthaxanthin 4% lutein The presence of the additional antioxidant carotenoids in AstaPure® enhance its therapeutic potential
  • 12. AstaPure® summary • Source  H. pluvialis (natural) • Stereochemistry 100% [3S,3 S]′ • Configuration Predominantly E-isomer • Esterification Mono- and di-esterified • Synergy Natural carotenoid complex
  • 13. AstaPure® cultivation process Growth Apparatus of the “Green Stage” Growth Apparatus of the “Red Stage” Cultivation stages of Haematococcus pluvialis microalgae
  • 14. Advantages of closed system cultivation Closed System Open System Adopting a ‘closed system’ technology eliminates microbial, chemical or any other outdoor contaminations Difficult to control contamination which can be in the form of general air pollution, to animal & bird excrement
  • 16. Free radicals initiate disease The free radicals are derived from •endogenous sources - as part of normal metabolic processes •exogenous sources - pollution, alcohol, tobacco smoke, heavy metals, solvents, pesticides, radiation, UV light and certain drugs all of which can damage all classes of biological molecules including nucleic acids, carbohydrate, proteins and lipids Antioxidants (both consumed and synthesised endogenously) act to keep free radical levels (and subsequent damage) in check Oxidative stress arises when there is an imbalance between free radical production and antioxidant production/intake The regulation of reducing and oxidising (redox) state is critical for essential cellular homeostasis Guerin M, Huntley ME, Olaizola M. Haematococcus astaxanthin: applications for human health and nutrition. Trends Biotechnol. 2003 May;21(5):210-6. Review.
  • 18. An antioxidant with unique benefits Astaxanthin’s hydroxyl (OH) and ketone (C=O) oxygen-containing groups are responsible for its high antioxidant activity and ability to span and stabilise cell membranes The ability of carotenoids to act as antioxidants is related to the number of double bonds within the polar polyene chain region. Those with ≥9 double bonds (such as astaxanthin) are the best quenchers of singlet oxygen molecules. Furthermore, astaxanthin (as with all carotenoids) is not destroyed during the process of neutralising free radicals, meaning that it can repeatedly quench singlet oxygen molecules. This is reflected by its superior ORAC score of ~25,000 μmole TE/g Nishida Y., Yamashita E., Miki W. Quenching activities of common hydrophilic and lipophilic antioxidants against singlet oxygen using chemiluminescence detection system. Carotenoid Science. 2007;11(6):16–20.
  • 19. Astaxanthin's polar end groups overlap the polar boundary zones of the membrane, while the non-polar middle fits the membrane’s non-polar interior. The dashed red line speculatively indicates “lightning-rod” conduction of electrons along the astaxanthin molecule, possibly to vitamin C or other antioxidants located outside the membrane. Pashkow FJ, Watumull DG, Campbell CL. Astaxanthin: a novel potential treatment for oxidative stress and inflammation in cardiovascular disease. Am J Cardiol 2008;101(suppl):58D-68D Kidd P. Astaxanthin, cell membrane nutrient with diverse clinical benefits and anti-aging potential. Altern Med Rev. 2011 Dec;16(4):355-64. Review
  • 20. Astaxanthin’s multiple conjugated double bonds allows it to act as a strong antioxidant by electron donation and by reacting with free radicals: Free radical scavenging Free radicals are neutralised by antioxidants either by donating an electron to the free radical to ensure electrons in the outer ring of the atom are paired or by incorporating the unpaired electron into its own molecule Quenching Antioxidants take the energy from the charged singlet oxygen molecule thereby de-charging it, making it harmless and terminating a potentially harmful oxidative stress chain-reaction
  • 21. The ORAC (Oxygen Radical Absorbance Capacity) unit, ORAC value, or “ORAC score” is a method of measuring the in vitro antioxidant capacity of different foods and supplements •It is theorised that foods that are higher on the ORAC scale may be more effective at neutralising free radicals •Thus the ORAC value of a nutrient is a useful indicator of its antioxidant potential and ability to slow the oxidative processes and free radical damage that can contribute to age-related degeneration and disease Nishida Y., Yamashita E., Miki W. Quenching activities of common hydrophilic and lipophilic antioxidants against singlet oxygen using chemiluminescence detection system. Carotenoid Science. 2007;11(6):16–20. • Astaxanthin’s ROS-scavenging capacity has been shown to be 6000x more than vitamin C, 800x more than coenzyme Q10, 550x more than vitamin E, 200x more than polyphenols, 150x more than anthocyanins, and 75x more than alpha lipoic acid
  • 22. Astaxanthin - the ‘king of the antioxidants’? Unique molecular structure that enables its superior position in the membrane: The general ‘rule’ of antioxidants is that lipid-soluble antioxidants protect the lipid-soluble part of cells, and water-soluble antioxidants protect the water-soluble part of cells, yet astaxanthin’s unique structure allows it to span the cell membrane fulfilling both roles while also providing cell membrane stability Direct antioxidant action: Quenches singlet oxygen and scavenges free radicals to prevent or terminate chain reactions Indirect antioxidant action: Astaxanthin activates antioxidant enzymes Astaxanthin is a ‘pure’ antioxidant: Unlike other antioxidants, astaxanthin never turns into a pro-oxidant. Vitamins C & E, and other carotenoid antioxidants such as lycopene and zeaxanthin can all become pro-oxidants under certain conditions
  • 23. Mechanisms of action - astaxanthin Acts as COX-2 inhibitor Inhibits iNOS enzyme activity, which decreases production of nitric oxide Reduces C-reactive protein (CRP), one of the acute-phase proteins that increase during systemic inflammation Suppresses inflammatory gene expression by suppressing I(kappa)B kinase- dependent NF-kappaB activation Suppresses inflammatory agents such as prostaglandin E2, IL-1β, TNFα– the key proinflammatory mediators, which promote inflammatory responses Inhibits the enzyme 5-α-reductase with anti-androgen effects Crosses the blood-brain and blood-retinal barriers (promoting brain and eye health)
  • 24. MUSCLE & JOINTS: •Improves endurance & performance •Decreases inflammation & muscle soreness EYE HEALTH: •Protects against light induced retinal damage •Increases UV protection ENERGY: •Reduces tiredness & fatigue •Benefits for endurance & recovery after exercise GUT HEALTH: •Reduces Helicobacter pylori inflammation •Protects against gastric ulceration •Reduces acid reflux & heart burn LIVER HEALTH: •Decreases inflammation •Protects against fatty liver disease METABOLIC SYNDROME & DIABETES: •Improves insulin sensitivity; •Protects against the development of insulin resistance •Improves insulin-glucose balance Whilst research into astaxanthin is still in its relative infancy some human, as well as animal and mechanistic studies have found it to be highly beneficial to the following systems and conditions:
  • 25. SKIN: •Reduces UV damage •Improves moisture & elasticity •Reduces wrinkles IMMUNE SYSTEM: •Improves immune defences •Reduces inflammation CARDIOVASCULAR HEALTH: •Improves blood flow •Lowers blood pressure •Lowers lipids (cholesterol & triglycerides) BRAIN: •Improves cognitive function, memory and learning •Protects the brain from ischemic stroke •Benefits for Parkinson & Alzheimer's disease FERTILITY: •Improves sperm and oocyte quality •Improves fertility CANCER: •Suppresses cell growth, proliferation and metastasis Whilst research into astaxanthin is still in its relative infancy some human, as well as animal and mechanistic studies have found it to be highly beneficial to the following systems and conditions:
  • 26. mg of astaxanthin in a typical 85g portion of different species of salmon Farmed Rainbow Trout 2.1 Wild Sockeye Salmon 3.2 Farmed Rainbow Trout 2.1 Wild Coho Salmon 1.8 Farmed Atlantic Salmon 0.8 Wild Arctic Char 0.7 Farmed Arctic Char 0.7 Wild Pink Salmon 0.6 Chinook Salmon 0.5 Source Astaxanthin concentration ppm Salmonids (salmon) 5 Plankton 60 Krill 120 Arctic Shrimp (Pandalus borealis) 1,200 Phaffia Yeast (Xanthophyllomyces dendrorhous) 10,000 Green Algae (Haematococcus pluvialis) 40,000 Biswal S. Oxidative stress and astaxanthin: The novel supernutrient carotenoid. Int J Health Allied Sci 2014;3:147-53 Supplements vs food To achieve 4mg intake you would need to consume •1.25 portions of wild sockeye salmon •1.9 portions of farmed rainbow trout •6.7 portions of wild pink salmon
  • 27. AstaPure® compared Products claiming to deliver 4mg of astaxanthin often only contain 4mg of the bulk oil, with a 10% concentration of active astaxanthin. Therefore, these products only deliver 0.4mg of active Astaxanthin Igennus AstaPure® pure delivers 42mg of oil per capsule and 4mg active astaxanthin
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  • 29. Absorption and digestion of astaxanthin The absorption of astaxanthin is similar to that of dietary lipids or fat-soluble vitamins: 1.the ester forms are hydrolysed in the gastro-intestinal tract prior to absorption 2.the incorporation into mixed lipid micelles in the lumen composed of phospholipids, lipids, cholesterol, and bile salts and absorbed into the enterocyte through passive and facilitated diffusion 3.the uptake into intestinal mucosa 4.the incorporation into chylomicrons 5.the release into the lymph 6.chylomicrons are digested by lipoprotein lipase which releases astaxanthin 7.astaxanthin is distributed mostly by low and very low density lipoproteins The presence of dietary fat is known to affect the degree of astaxanthin absorption in the small intestine. Astaxanthin absorption is higher when emulsified with olive oil (as is the case with AstaPure® ) and taking astaxanthin supplements with additional fat significantly enhances bioavailability (Odeberg et al., 2003) Kotake-Nara E, Nagao A. Absorption and metabolism of xanthophylls. Mar Drugs. 2011;9(6):1024-37; Fiedor J, Burda K. Potential role of carotenoids as antioxidants in human health and disease.Nutrients. 2014 Jan 27;6(2):466-88. Odeberg JM, Lignell Å, Petterson A, Höglund. Oral bioavailability of the antioxidant astaxanthin in humans is enhanced by incorporation of lipid based formulations. Eur J Pharm Sci. 2003; 19(4):299-304.
  • 30. Pharmacokinetics Pharmacokinetic studies are limited; however, in an open labeled study, three middle- aged male volunteers (41-50 years) ingested a single meal containing first a 10-mg dose of astaxanthin followed by a dose of 100 mg after 4 weeks Coral-Hinostroza GN, 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. The plasma astaxanthin concentration-time curves were measured over 76 hours. Maximum levels of astaxanthin (Cmax ) for the low dose was 0.08 mg/l and 0.28 mg/L for the high dose, these were reached 11.5 h after administration and the plasma astaxanthin elimination half-life was 52 ± 40h Okada Y, Ishikura M, Maoka T Bioavailability of astaxanthin in Haematococcus algal extract: the effects of timing of diet and smoking habits. Biosci Biotechnol Biochem. 2009 Sep;73(9):1928-32. Furthermore, in a separate study, taking astaxanthin after food rather than before food improved the bioavailability of astaxanthin supplements by 2-fold
  • 31. An open-label clinical study of the toxicity and efficacy of an astaxanthin-rich H. pluvialis extract was conducted with 127 healthy adults who received a single, daily dose of 4, 8 or 20mg of astaxanthin for 4 weeks •Blood pressure and other parameters were collected before and after 4 weeks of supplementation •A significant decrease in systolic blood pressure and fasting blood glucose was observed in the subjects who ingested 4mg of astaxanthin •No significant differences were noted from baseline to end treatment for the other parameters •There were no adverse effects or changes in the biochemical parameters of the supplemented groups The decreases in systolic blood pressure, triglyceride, and fasting glucose values observed in the present study may support that the product has a beneficial effect in patients with borderline diabetes mellitus or persons at risk for metabolic syndrome Satoh A, Tsuji S, Okada Y, Murakami N, Urami M, Nakagawa K, et al. Preliminary clinical evaluation of toxicity and efficacy of a new astaxanthin- rich Haematococcus pluvialis extract. J Clin Biochem Nutr. 2009; 44(3):280-4.
  • 32. In a randomised double-blind, placebo-controlled study, 14 young (average age = 21.5 years) free-living healthy females received 0, 2, or 8 mg astaxanthin daily for 8 weeks Measures included cytokine production, plasma concentrations of 8-epi-prostaglandin F2α (8- isoprostane) as a measure of lipid peroxidation, C-Reactive protein (CRP), as a well- established marker of inflammatory status and oxidative DNA damage was assessed by measuring plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG) Park JS, Chyun JH, Kim YK, Line LL, Chew BP. Astaxanthin decreased oxidative stress and inflammation and enhanced immune response in humans. Nutr Metab (Lond). 2010 Mar 5;7:18. A dose of as low as 2 mg/day, given orally to a human subject for a period of four weeks, is sufficient to reduce measurable endogenous oxidative DNA damage by about 40% Overall, this study shows that dietary astaxanthin, at relatively low doses 2-8 mg daily over an 8-week period enhanced immune response, and decreased a DNA oxidative damage biomarker and inflammation in young healthy females
  • 33. “Astaxanthin confers multiple neuroprotective effects in various experimental models of neurological diseases, which includes both acute injuries and chronic neurodegenerative disorders. The protective effects of astaxanthin are associated with its anti-oxidative, anti-inflammatory, anti-apoptotic effects. Astaxanthin is a safe nutrient, with no toxic effects when it is consumed with food. Furthermore, as a fat-soluble compound, astaxanthin is able to effectively pass through the BBB. Therefore, astaxanthin is an excellent candidate for treating neurological diseases.” Wu H, Niu H, Shao A, Wu C, Dixon BJ, Zhang J, Yang S, Wang Y. Astaxanthin as a Potential Neuroprotective Agent for Neurological Diseases. Mar Drugs. 2015 Sep 11;13(9):5750-66.
  • 34. “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.” Fassett RG, Coombes JS. Astaxanthin in cardiovascular health and disease. Molecules. 2012 Feb 20;17(2):2030-48. doi: 10.3390/molecules17022030. Review.
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  • 38. “The effects of a dietary supplement containing astaxanthin on the accommodation function and subjective symptoms of the eyes were investigated in 22 middle-aged and older people (mean age: 53.9 years) with complaints of eye strain. Astaxanthin was administered to subjects at a daily dose of 6 mg for 4 weeks, and the pupillary constriction ratio before and after astaxanthin supplementation was measured by TriIRIS C9000. The change in subjective symptoms after supplementation was examined by a questionnaire. The results showed a significant increase in pupillary constriction ratio after supplementation of astaxanthin, thereby suggesting that astaxanthin may also improve the accommodation function of the eye and some subjective symptoms related to presbyopia in middle-aged and older people with complaints of eye strain” Kajita M, et al. The Effects of a Dietary Supplement Containing Astaxanthin on the Accommodation Function of the Eye in Middle-aged and Older People. Medical Consultation & New Remedies. 2009 Mar;46(3):89-93.
  • 40. NUTRITIONAL INFORMATION Per capsule % RI* AstaPure® Haematococcus pluvialis microalgae (10% astaxanthin complex) 42 mg n/a of which astaxanthin 4 mg of which lutein 36µg of which cantaxanthin 20µg of which zeaxanthin 3µg of which violaxanthin 0.5µg of which beta-carotene 0.5µg DIRECTIONS FOR USE The majority of the research to date used between 2 mg and 24 mg of astaxanthin daily No general dosage recommendations or standardised guidelines currently exist for astaxanthin INGREDIENTS: Cold-pressed extra-virgin olive oil; AstaPure® from Haematococcus pluvialis (H. pluvialis) microalgae (10% astaxanthin); capsule shell (gelatine, glycerol, beta-carotene, caramel E150a). This product should not be used as a substitute for a balanced diet. Pregnant or breastfeeding women should consult their doctor before taking any food supplement. Keep out of the reach of children and away from sunlight. Free from: dairy, gluten, lactose, soya, wheat, yeast, artificial colours and flavours; not tested on animals; non-GMO; halal & kosher. *% Reference Intake For adults and children aged 12+: take 1-2 capsules daily. For intensive support, the dose can be increased to 4 capsules daily. For optimal absorption, astaxanthin should be taken with fats and immediately after meals. Do not exceed the above doses unless advised by a healthcare practitioner.
  • 41. 41 AstaPure® advantages: Environmentally friendly, controlled, closed microalgae cultivation system Advanced & controlled down-stream processing of the biomass Sealed system eliminates the risk of foreign objects, agricultural residue and microbial or chemical contamination Green technology, energised by natural sunlight Reliable and consistent production Highest commercial concentration of natural astaxanthin Super-critical CO2 extraction – No organic solvent residues ISO 9001:2000, HACCP, GMP, Kosher, Halal High stability
  • 43. Effect of astaxanthin on the cardiovascular system Pre-clinical/clinical Effect followed Main outcome Reference Normal rats Insulin-resistant rats Obese rats level Dyslipidemia Adiponectin levels Increased Improved Improved Murillo 1992 Hussein 2007, Ikeuchi 2007 Hypertensive rats Hypertension Stroke incidence Artery wall thickness Reduced Reduced Reduced Yanai 2008 Rats Rabbits Dogs Myocardial ischemia- reperfusion damage Reduced Reduced Gross 2004 Lauver 2005 Gross 2005 Dogs Rethrombosis Reduced Krötz 2004 61 mildly hyperlipidemic subjects Dyslipidemia Adiponectin level Improved Increased Yoshida 2010
  • 44. Effect of astaxanthin on various physiological systems System Pre-clinical/clinical Effect followed Main outcome Reference Skin Hairless UV-irradiated mice Wrinkles formation Reduction Arakane 2002 Healthy subjects Erythema Reduction Yamashita, 1995 46 healthy women Skin elasticity and moisture Improved Yamashita 2002, Yamashita 2007,Seki 2001 Immune response Mice Humoral responses to T-dependent antigens Improved Jyonouchi 1994, Bennedsen 1999, Chew 1999 14 healthy women Oxidative stress markers Inflammation markers Immune response Reduced Reduced Improved Park 2010 Inflammation Rats Inflammation of paw Reduced Kurashige 1990 Mice injected with inflammation inducers Inflammation markers in plasma Reduced Lockwood 2006 Gastric ulcers H. pylori-infected mice Gastric mucus Bacterial load Immune response Reduced Reduced Improved Bennedsen 1999, Wang 2000 Chemically - induced gastric ulcers in rats Gastric ulcer markers Reduced Kim 2005a, Kamath 2008, Kim 2005b, Yang 2009
  • 45. Effect of astaxanthin on eye health Pre-clinical/clinical Effect followed Main outcome Reference Rats Light damage to retina Reduction Tso 1996 Rats Uveitis Reduction Ohgami 2003 Suzuki 2006 Rats Selenite-induced cataract Inhibition Liao 2009 Diabetic patients Humoral superoxide scavenging activity Increased Hashimoto 2009 15 subjects with nonadvanced Central retina function Improved Parisi 2008 18 healthy men Deep vision Improved Sawaki 2002 10 healthy men Eye function Improved Iwasaki 2006 40 asthenopia patients Accommodation power Improved Kenji 2005 49 healthy men Uncorrected far visual acuity Improved Nakamura 2004 87 visual display terminal (VDT) workers Accommodation amplitude improved Nagaki 2002 Nagaki 2006
  • 46. Effect of astaxanthin on muscle endurance Pre-clinical/clinical Effect followed Main outcome Reference Exercising mice Muscle lipid metabolism Oxidative damage Fatigue Improved Reduced Reduced Aoi 2008 Aoi 2003 Ikeuchi 2006 16 non trained men Lactic acid accumulation after run Reduced Sawaki 2002 19 non trained men Respiratory and sympathetic nervous system activities Improved Nagata 2006 20 non trained men Strength/explosiveness test Strength/endurance test Improved Lignell 2001
  • 47. Effect of astaxanthin on the central nervous system Pre-clinical/clinical Effect followed Main outcome Reference Mice subjected to transient cerebral ischemia Learning and memory skills Improved Hussein 2005a Rats subjected to transient cerebral ischemia Locomotor activity Cerebral infarction Improved Reduced Shen 2009 Rats chronically fed with alcohol Alcohol-induced neural marker Reduced Abadie-Guedes 2008 Healthy mice Memory Improved Zhang 2007 10 healthy men (50-69 years old) Response time and accuracy of several tasks Improved Satoh 2008
  • 48. AstaPure® summary » AstaPure® manufacturing: – Environmentally friendly, controlled, closed microalgae cultivation system – Sealed system eliminates the risk of foreign objects, agricultural residue and microbial or chemical contamination – Green technology, energised by natural sunlight – Super-critical CO2 extraction: No organic solvent residues » AstaPure® provides natural 100% [3S,3 S] astaxanthin′ from H. pluvialis, predominantly as the straight-chained (E-isomer) that efficiently spans the membrane for unprecedented antioxidant support » AstaPure® astaxanthin is 95% esterified offering a natural carotenoid complex of amino acids and fatty acids that enhances both stability and bioavailability » Safety: this natural form of astaxanthin has over 15 years of safe use as a commercially sold nutritional supplement with no adverse side-effects » Efficacy: Natural astaxanthin has been shown to have diverse health benefits in numerous in vitro, animal and human clinical trials » Dosage: Benefits observed from as little as 2mg daily
  • 49. Education Technical Sophie Tully Nutrition Education Manager sophiet@igennus.com Dr Nina Bailey Head of Nutrition ninab@igennus.com Get in touch