Natural Products Expo Asia 2005 Hong Kong
Astaxanthin:
A Radical Approach to
Vitality & Beauty From
Within
Natural Products Expo Asia 2005
Vincent Wood PhD, Manager
International Business Dept/Marketing
NOV2004
Natural Products Expo Asia 2005 Hong Kong
TO DAY’S
PR E S E NTATI O N
OUTLINE
• What is Astaxanthin?
• Why is it so potent compared to other carotenoid
antioxidants?
• The Research & Impact on Health
• Summary of Recent Advances
– Supplement use in Muscle Endurance, Eye health and Cosmetic benefit
• Retail Examples in Japan
• Regulatory, Production Technology & Supply
NOV2004
Natural Products Expo Asia 2005 Hong Kong
A MEMBER OF THE
CAROTENOID FAMILY
– Lutein
– Astaxanthin
-Carotene
OH
OH
• 600 known carotenoids*
• Humans cannot synthesise
carotenoids.
• Need to obtain carotenoids
from food.
• <25 obtained from food.
• Basic carotene structure
• Xanthophyll Class
Lutein
O
OH
HO
O
Astaxanthin
Molecular Formula:
Molecular Weight:
CAS No:
C40H52O4
596.82
472-61-7
*Parker RS.,1997
NOV2004
Natural Products Expo Asia 2005 Hong Kong
ASTAXANTH I N BAC K G R O U N D
1938
Lobster
Present Day
Other Sources
Microalgae
Yeast
Bacteria
Higher Plants
Crustaceans
Fish
Birds
(Astacus gammarus) Discovered
by Nobel Laureate Dr Kuhn
(Haematococcus pluvialis)
(Phaffia rhodozyma)
(Agrobacterium aurantiacum)
(Adonis aestivalis)
(Euphasia supurba)
(Salmon) Typically 1mg per 200g
(Flamingo, Cockerel)
NOV2004
Natural Products Expo Asia 2005 Hong Kong
Haematococcus pluvialis
Haemato (Blood) coccus (Seed)
Microalgae family – includes Spirulina
Harsh Environment – Dormant / Hibernates
Astaxanthin
“Astaxanthin efficiently functions as an
antioxidant agent in both cytoplasmic and
membraneous regions to protect cells in Powerful Antioxidant
vivo against environmental oxidative
Defence Against Free Radicals
stress.”
Protects Plant Cell Contents
(1999 Kobayashi, M., Okada, T. Protective Role of Astaxanthin to
Protect Against UVB Radiation in the Green Alga Haematococcus
pluvialis.)
Microalgae 15,000 ppm Yeast 8,000 ppm Krill 1,500 ppm.
NOV2004
Natural Products Expo Asia 2005 Hong Kong
ASTAXANTH I N M EAN S M O R E
HENS FOR THE ROOSTER!
COME HERE GIRLS!
NOV2004
Natural Products Expo Asia 2005 Hong Kong
ASTAXANTH I N & CAR OTE N O I D
PERCEPTIONS
Low level of consumer and
retail awareness
Contradictory carotenoid
evidence. Not enough science
-carotene>lycopene>lutein>astaxanthin
Natural vs Synthetic
Microalgae vs Yeast
Perceived to be expensive!
Unstable supply in the past,
Intense competition
Too many antioxidants on
the market
A functional based product is
being developed based on
microalgal astaxanthin
only small amounts are
required. Can complements
existing formulations
‘Wait and see” attitude on
market developments
“Frost & Sullivan estimates that astaxanthin is now one of the fastest growing carotenoids in Europe.
European carotenoids were worth $348.5 million in 2003, with 17 per cent of this coming from
supplements. But currently less than 1 ton of astaxanthin is going into supplements per year, compared
to up to 150 tons for the aquaculture industry.” Source: Nutraingredients.com 22/03/04
NOV2004
Natural Products Expo Asia 2005 Hong Kong
ANTIOXIDANT MECHANISMS
Physical Quenching
1O
2
+ 1Carotenoid → 3O2 + 3Carotenoid*
3Carotenoid* → 1Carotenoid + thermal energy*
↓
ASTAXANTHIN ELIMINATES FREE RADICALS EXTREMELY
FAST BY ENERGY TRANSFER**
Chemical Reaction (e.g. -Carotene)
1O
2
+ Carotenoid → Carotenoid RADICAL → OXIDIZED
*B.R.Nielsen, K.Jorgensen and L.H.Skibsted : Triplet-triplet extinction coefficients, rate constants of triplet decay and rate
constants of anthracene triplet sensitization by laser flash photolysis of astaxanthin, β-carotene, canthaxanthin and zeaxanthin in
deaerated toluene at 298K, J.Photochem.Photobio.A:Chem., 112, 127-133 (1998).
“The energy of the singlet state oxygen is quickly transferred to the carotenoid by direct contact, and the carotenoid in the triplet
state relaxes to the singlet state very quickly by the transformation of the potential energy into thermal energy through the vibration
of conjugated double bonds in the polyene chain.” (Miki, M., Biological Functions and Activities of Animal Carotenoids. Pure Appl.
Chem. 63. 141-146. 1991.)
NOV2004
Natural Products Expo Asia 2005 Hong Kong
SCAVENGING EFFECT OF DIFFERENT
ANTIOXIDANTS IN A LIPOPHILLIC
IN VITRO MODEL
3500
ED 50 value (nM)
3000
2500
2000
1500
1000
500
0
Astaxanthin
Zeaxanthin
Cantaxanthin
Lutein
ß-Carotene
Vitamin E
Antioxidant
Scavenging: Carotenoids with oxygen groups most efficient against lipid peroxidation.
Astaxanthin was the most efficient scavenger. Miki, W. Pure & Appl. Chem. 63(1);141-46
NOV2004
Natural Products Expo Asia 2005 Hong Kong
N E U T RA L I Z I N G R O S
SOD
３O
2
e－
→
e－
→ H2O2
→
(Hydroxy radicals)
・OH
(Singlet oxygen radical)
O２
↓
LH →
↓
L・
→
↓
Astaxanthin
LH
H2O
↓
LOO・
→
LOOH
↓
L・
QUENCHING
550 x Vitamin E*
40 x -carotene*
(Peroxide
radicals)
Astaxanthin
(Superoxide radical)
↓
１O
2
・O －
2
Ascorbic Acid
Catalase
Vitamin E
(tocopherol)
INHIBITS
PEROXIDATION
1000 x Vitamin E**
*N.Shimizu et al.: Carotenoids as singlet oxygen quenchers in marine organisms, Fisheries Science, 62, 134-137 (1996).
**Miki, W. Pure & Appl. Chem. 63(1);141-46. (ROS: Reactive Oxygen Species)
NOV2004
Natural Products Expo Asia 2005 Hong Kong
ASTAXANTH I N - I S TH E PU R E ANTI O X I DANT
β-Carotene
Anti- and
Pro-oxidants
Lycopene
Zeaxanthin
Pure
Anti-oxidant
Astaxanthin
0
1
2
3
4
Normalized relative oxidation rates
H.D.Martin, et al. : Chemistry of carotenoid oxidation and free radical reactions,
Pure Appl. Chem., 71(12), 2253-2262 (1999).
NOV2004
Natural Products Expo Asia 2005 Hong Kong
THE ASTAXANTHIN SHIELD
Lignell A., & Wood V., Astaxanthin: Radical Cellular Defense. May 2004 Innovations in Food Technology.
NOV2004
Natural Products Expo Asia 2005 Hong Kong
ASTAXANTH I N D I STR I B UTI O N I N RATS AFTE R
3 WEEKS ON SUPPLEMENTED DIET
( 1 0 0 m g A x / k g f e e d ).
80
70
ASTAXANTHIN SHIELD
µg astaxanthin/kg
60
50
40
30
20
10
0
Blood
Brain
Heart
Kidney
Liver
Lung
Muscle
Skin
Organ
US Pat 6,245,818 Medicament for improvement of duration of muscle function or treatment of muscle disorders or
diseases.
NOV2004
Natural Products Expo Asia 2005 Hong Kong
PR O PE RTI E S O F ASTAXANTH I N
Antioxidant Potency
Powerful singlet oxygen quenching
and free radical scavenging activity.
Protects against lipoperoxidation.
Solubility
Spans the membrane bi-lipid layer –
comprehensive protection and
strengthens rigidity
Protection
Forms a protective shield and
defends against continuous free
radical attack at the cellular level.
Safety
Defined as a pure antioxidant unlike
other well known antioxidants that can
become pro-oxidants.
NOV2004
Natural Products Expo Asia 2005 Hong Kong
CATERGORIZED
CATE R G O RY
LITERATURE
PU B LI CATI O N S
General Nutrition
Antioxidant potency, Synergies.
Stomach & Gut Health*
Helicobacter, dyspepsia
Eye Health**
Visual Fatigue, Diabetic Cataract
Sports Nutrition*
Muscle Endurance and damage,
Visual Acuity, anti-inflammatory.
Fertility, muscle endurance, antiinflammatory
UVR damage, photoprotectant,
anti-inflammatory.
Vetinary Health*
Cosmecuticals
*Patent Protected **Patent Applied
NOV2004
Natural Products Expo Asia 2005 Hong Kong
• Sports nutrition & supplement
– Major market potential. Continues positive growth.
• Strenuous physical activity generates free radicals
– up to 12 times more than at rest
• Activation of the inflammation response
– Important factor for post strenuous exercise & recovery
• Feel oxidative damage
– Muscle pain, tiredness, need for recovery
NOV2004
Natural Products Expo Asia 2005 Hong Kong
Dietary supplementation with astaxanthin improves
muscle endurance.
A randomised double blind placebo controlled study on healthy male subjects.
Protocol
40 young healthy male students, age 17 - 19, were included. Standardized
exercise tests were carried out at baseline and after three and six months of
supplementation with 4 mg astaxanthin per day or placebo.
Inclusion
Randomisation
4 mg astaxanthin
Placebo
3 months
Parameters measured:
- Fitness
- Strength / endurance
- Strength / explosivity
3 months
(In Press) Investigator
Curt L. Malmsten, PhD, MD,
Räddningshälsan AB,
Sweden.
NOV2004
Natural Products Expo Asia 2005 Hong Kong
RESULTS: CHANGES IN STRENGTH/ENDURANCE
80
No difference in
fittness.
No difference in
muscle explosivity.
75
Placebo
70
No. of knee bendings/person
Significant increase
of muscle
endurance.
Astaxanthin
65
60
55
50
45
40
35
30
1
Baseline
Baseline
2
3
3 months
6 months
p < 0.05
NOV2004
Natural Products Expo Asia 2005 Hong Kong
CONCLUSIONS
Astaxanthin may be effective for:
 Endurance Levels (4 mg daily dose)
 Maintains Antioxidant Protection Levels
 Reduces Recovery Time to Training
 2002 Sawaki K., et al., reported a 28.5%
(P<0.05%) reduction in lactic acid build up
after 1200m supplemented subjects.
 On-going US and Swedish clinical trials.
Results Due 1st QTR 2005.
Muscle endurance US Pat 6,245,818
NOV2004
Natural Products Expo Asia 2005 Hong Kong
Astaxanthin Limits Exercise-Induced Skeletal and
Cardiac Muscle Damage in Mice
Protocol
１wk
3wk
Acclimatization
24hr
Training Program
・Control (N=8)
・Exercise Control (N=8)
・Exercise Supplemented (N=8)
Exercise Euthanized
Damage Markers
Muscle cell staining – Cell membrane damage
Creatine kinase (CK) – Damaged muscle cells
8-hydroxy-2’-deoxyguanosine (OHdG) – DNA damage
Myeloperoxidase (MPO) - Inflammation
Aoi, W. et al. 2003, Antioxidants & Redox Signalling, 5:(1) 139-144.
NOV2004
Natural Products Expo Asia 2005 Hong Kong
MUSCLE CELL MEMBRANE
Heart
CONTROL
EXERCISE CONTROL
EXERCISE + AX
EXERCISE CONTROL
EXERCISE + AX
Gastrocnemius
CONTROL
NOV2004
Natural Products Expo Asia 2005 Hong Kong
R E S U LT S
Production of 8-OHdG (DNA Damage)
Inflammation in Gastrocnemius and Heart
1.50
3.00
p< 0.05
*P<0.05
MPO Activity (mU/mg protein)
1.00
5
8-OHdG/10 xdG
p< 0.05
0.50
*P<0.05
*P<0.05
*P<0.05
2.50
2.00
1.50
1.00
0.50
0.00
0.00
Control
Exercised
Gastrocnemius
Ax+ Exercised
Control
Exercised
Ax+Exercised
Control
Exercised
Ax+Exercised
Control
Gastrocnemius
Heart
Exercised
Ax+Exercised
Heart
Creatine Kinase in Plasma
 Overall Reduction of DNA damage
3500
p<0.05
p<0.05
3000
 Reduction of Inflammatory Response
 New Research to Mechanism using
Gene Chip Analysis - 2005
2000
U/L
 Reduction of Muscle Cell Damage
2500
1500
1000
500
0
Control
Exercised
Ax+Exercised
NOV2004
Natural Products Expo Asia 2005 Hong Kong
I N F LAM MAT O R Y R E S P O N S E –
I N A C T I V A T I O N OF N F – K B
Lignell A., & Wood V., Astaxanthin: Radical Cellular Defense. May 2004 Innovations in Food Technology.
NOV2004
Natural Products Expo Asia 2005 Hong Kong
NOV2004
Natural Products Expo Asia 2005 Hong Kong
EYE H EALTH - FAT I G U E
 Visual Display Terminals (VDT) at work and leisure.
 Increased Risk of developing glaucoma for heavy
computer use combined with short sightedness*.
 Eye Disorders – Blurring, Occular & Visual Asthenopia,
Headache
 Visual Acuity, Accommodation, Critical flicker fusion, Depth
Perception, Pattern Evoked Potential
 Deteriorates on Daily Basis & Fatigue Accumulates
 Age Related Macular Degeneration**
 No Data on Astaxanthin on VDT Induced Visual Fatigue
*Source: BBC News 16 Nov 2004 Japanese research 10,000 Japanese workers: Computer link to eye disease.
**US Patent 5,527,533, Tso & Lam, “Method of Retarding and Ameliorating Central Nervous System and Eye
Damage”
NOV2004
Natural Products Expo Asia 2005 Hong Kong
C LI N I CAL PARAM ETE R S
Visual Acuity (Landolt Ring) 5m & 35 cm
Accommodation Amplitude = Ciliary Muscle Function
Critical Flicker Fusion (CFF) = Central Nervous System (CNS)
Pattern Evoked Potention (PEVP) = Visual Nerve connection
the to brain
Patient Questionnaire (Subject monitoring devised by
Ophthalmologists)
*Nagaki Y., et al., 2002 Journal of Traditional Medicines 19(5):170-173.
**Koide R., et al., 1994 Effects of Whortleberry extract on ocular function. J. Eye 11:117-121.
***Sawaki K., et al., 2002. Sports Performance Benefits from Taking Natural Astaxanthin Characterized by Visual Acuity
and Muscle Fatigue in Humans. J. Clin. Ther. Med. 18(9):73-88.
****Nakamura A., et al., 2004. Changes in Visual Function Following Peroral Astaxanthin. 57th Congress of Clinical
Opthalmology of Japan 58(6):1051-1054 (Japanese).
NOV2004
Natural Products Expo Asia 2005 Hong Kong
EYE FATI G U E C O N C LU S I O N
14
No. of Subje cts w ith Eye Strain
 Questionnaire revealed a 54% reduction
of eye strain symptoms* at 5 mg/day after
4 weeks (N=26) and better accomodation
(P<0.01).
 Agree with Whortleberry**
 Hypofunction of Ciliary Body
 6mg/day*** for 4 weeks (n=18) showed
better depth perception and CFF (P<0..05)
 Accomodation improved at 4 mg (P<0.05)
and 12 mg/day (P<0.1) (n=49)****
 FOSHU Planned
 Mid 2005 Agent for improving
accommodation blood flow in the eye.
12
10
8
6
4
2
0
Bef ore
A f te r
G r o u p B ( T r e a te d )
Bef ore
A f te r
G r o u p C ( Pla c e b o )
V DT S u b je c t s w it h Ey e S t r a in S y m p t o m s b e f o r e
a n d a f t e r a s t a x a n t h in s u p p le m e n t a t io n
*Nagaki Y., et al., 2002 Journal of Traditional Medicines 19(5):170-173.
**Koide R., et al., 1994 Effects of Whortleberry extract on ocular function. J. Eye 11:117-121.
***Sawaki K., et al., 2002. Sports Performance Benefits from Taking Natural Astaxanthin Characterized by Visual Acuity
and Muscle Fatigue in Humans. J. Clin. Ther. Med. 18(9):73-88.
****Nakamura A., et al., 2004. Changes in Visual Function Following Peroral Astaxanthin. 58(6):1051-1054 (Japanese).
NOV2004
Natural Products Expo Asia 2005 Hong Kong
Wrinkles where do you
have them?
Eyes>Forehead>Mouth
UNAVOIDABLE. It’s all part of the
aging process.
Causes of aging can be partially
counteracted.
By improving nutrition and
minimizing phototic injury.
NOV2004
Natural Products Expo Asia 2005 Hong Kong
Astaxanthin
 Early studies in mice models
revealed significant long terms
protection against premature
wrinkle formation caused by UVA
and UVB exposure*
 Topical application lowers the
UVB induced inflammatory
process that may lead to
hyperpigmentation**
BEAUTY FROM WITHIN –
The Next Hot Market Segment
L’Oreal & Nestle – “Innévo” 2002 Targeting women >40 y.o.***
*Arakane K., 2002. Superior protection via astaxanthin. Carotenoid Science, Vol 5.
**Yamashita E., 1995. Suppression of Post UVB hyperpigmentation by Topical astaxanthin from krill.
Fragrance Journal 14:180-185. ***Times, March 2004 (US) L’Oreal innovations - Beauty foods.
NOV2004
Natural Products Expo Asia 2005 Hong Kong
Cosmetic benefit of a Dietary Supplement
Containing Astaxanthin & Tocotrienol
on Human Skin
A Randomized Double Blind Placebo Controlled Study
Supplemented group - Astaxanthin 2mg from Haematococcus pluvialis
- Tocotrienol 40mg from palm fruit
- Canola oil
Subjects
- Healthy female with dry skin conditions
- n=8 (supplemented group) + 8 (placebo)
- Mean age: 40 years old
Methods
- 1 capsule per day in the evening for 4 weeks
- Parameters measured at start, 2 and 4 weeks
Parameters
- Standardized questionnaire
- Dermatologist inspection/palpation
- Skin moisture & sebum content
- Magnified skin surface inspection
Yamashita, E. 2002, FOOD Style 21, 6:(6) 112-117.
NOV2004
Natural Products Expo Asia 2005 Hong Kong
NOV2004
Treated
Placebo
3.0
p<0.05
2.0
1.0
0.0
-1.0
Total
Sag
4 Weeks
Pouch
Wrinkle
Fine wrinkle
Dullness
Spots/Freckles
Redness
Acne/Pimples
Complexion
Oiliness
Elasticity
Moisture
Smoothness
Changes of skin condition (-worse/+better)
Total
Sag
2 Weeks
Pouch
Wrinkle
Fine wrinkle
Dullness
Spots/Freckles
Redness
Acne/Pimples
Complexion
Oiliness
Elasticity
Moisture
Smoothness
Changes of skin condition (-worse/+better)
RESULTS 1
Natural Products Expo Asia 2005 Hong Kong
• Skin condition by individual assessment
Treated
Placebo
3.0
p<0.05
2.0
1.0
0.0
-1.0
NOV2004
2
Week 2
Traeted
Placebo
3
p<0.1
p<0.1
1
0
-1
-2
-3
3
2
Skin color
Spots/Freckles
Dullness
Dark rings around eyes
Oiliness
Complexion
Acne/Pimples
Redness
Fine wrinkle
Wrinkle
Skin texture
Pouch
Sag
Smoothness
Moisture
Pulpfree
Elasticity
Tough
Changes of skin condition (-worse/+better)
Skin color
Spots/Freckles
Dullness
Dark rings around eyes
Oiliness
Complexion
Acne/Pimples
Redness
Fine wrinkle
Wrinkle
Skin texture
Pouch
Sag
Smoothness
Moisture
Pulpfree
Elasticity
Tough
Changes of skin condition (-worse/+better)
RESULTS 2
Natural Products Expo Asia 2005 Hong Kong
• Dermatologist inspection/palpation
Week 4
Treated
Placebo
p<0.05
p<0.01
p<0.1
1
0
-1
-2
-3
NOV2004
RESULTS 3
Natural Products Expo Asia 2005 Hong Kong
• Skin moisture content
Cheek
Placebo
50
15
40
10
30
20
10
0
-10
2 Weeks
4 Weeks
Variation (microS)
Variation (microS)
Eye Region
Treated
Treated
Placebo
5
0
-5
2 Weeks
4 Weeks
-10
-15
-20
-20
p<0.05
NOV2004
RESULTS 4
Natural Products Expo Asia 2005 Hong Kong
• Skin sebum content
Cheek
6
6
4
4
2
2
0
0
-2
-4
-6
2 Weeks
4 Weeks
Variation
Variation
Brow
Treated
Placebo
-2
2 Weeks
Treated
Placebo
4 Weeks
-4
-6
-8
-8
-10
-10
-12
-12
NOV2004
RESULTS 5
Natural Products Expo Asia 2005 Hong Kong
• Magnified skin surface inspection
M4
Start
2 weeks
4 weeks
NOV2004
Possible Mechanism of Action
- Visual Wrinkle Reduction -
Natural Products Expo Asia 2005 Hong Kong
1
1
1
O2
O2
Singlet oxygen
induced UVA
oxidizes collagen
O2
Tocotrienol
Astaxanthin
Astaxanthin
Tocotrienol
New Collagen
Thank you !!
→ WRINKLE
NOV2004
Natural Products Expo Asia 2005 Hong Kong
CONCLUSION
Astaxanthin & Tocotrienol supplementation resulted in
• Increased moisture levels
• Consistent natural oils
• Reduction of fine wrinkles and pimples
• Improved elasticity
• Reduced swelling under the eyes
NOV2004
Natural Products Expo Asia 2005 Hong Kong
JAPAN E S E R ETAI L PR O D U CTS
Astaxanthin +
Tocotrienol & SOD
60 soft cap
3,800 JPY/month
37 USD or 287 HKD
Astaxanthin & Blueberry
Astaxanthin
1mg/day +
DHA+ARA
Pure
Astaxanthin
Astaxanthin & Natto Kinase
6,300 JPY/month
61 USD or 477 HKD
Astaxanthin 2mg/day+ pomegranate juice
500mL. 6,000 JPY/month, 58 USD or 453 HKD
NOV2004
Natural Products Expo Asia 2005 Hong Kong
JAPAN E S E R ETAI L PR O D U CTS
CO SM ECEUTICALS & BEAUTY SUPPLEM ENTS
NatuReal Corp.
Astaxanthin, Tocotrienol &
Collagen
Supplement 7,000 JPY/month
Cream 9000 JPY
Essence 10,000 JPY
68-97 USD or 529-755 HKD
Shiseido: Pure White
Astaxanthin 0.5 mg/day plus
multivitamins.
Drink 250 JPY 250 mL/day,
2.40 USD or 18.9 HKD
Tablet 4000 JPY/ month,
39 USD or 302 HKD
NOV2004
Natural Products Expo Asia 2005 Hong Kong
R E G U LAT O R Y I N F O R MAT I O N
US
DSHEA granted for 2 mg/day – 4
mg/day.
No GRAS status
CFTA/INCI Listed
Japan
Listed under Food Additives &
Colouring
JP Cosmetic Listed
Europe
Only biomass approved
EU approvals not yet harmonised
Requires EU Novel Foods
Approval
Country Specific
China/Hong Kong
Rquires “Bao Jian Shipin” or
Health Enchaning Foods approval
No information available
NOV2004
Natural Products Expo Asia 2005 Hong Kong
C O NTAC T
I NTE R NATI O NAL MAR K ETI N G S E CTI O N
3rd F L R H A L I F A X O N A R I M O N B L D.
3 – 2 4 –1 0 N I S H I S H I N B A S H I
M I NATO – K U
TO KYO 1 0 5 –0 0 0 3 JAPAN
(T) +81–3–3437–2353
(F) +81–3–3437–2347
www.fujichemical.co.jp/english
Email: info@fujichemical.co.jp
Thank you for your kind attention!
For more information vist Booth E17
NOV2004