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Astaxanthin: A Radical Approach to Vitality & Beauty From Within

Astaxanthin: A Radical Approach to Vitality & Beauty From Within. Natural Products Expo Asia 2005. Vincent Wood PhD, Manager International Business Dept/Marketing. T O D A Y ’ S P R E S E N T A T I O N O U T L I N E. What is Astaxanthin?

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Astaxanthin: A Radical Approach to Vitality & Beauty From Within

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  1. Astaxanthin:A Radical Approach to Vitality & Beauty From Within Natural Products Expo Asia 2005 Vincent Wood PhD, Manager International Business Dept/Marketing

  2. T O D A Y ’ S P R E S E N T A T I O N O U T L I N E • 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

  3. O H O H A M E M B E R O F T H E C A R O T E N O I D F A M I L Y • 600 known carotenoids* • Humans cannot synthesise carotenoids. • Need to obtain carotenoids from food. • <25 obtained from food. • Basic carotene structure • Xanthophyll Class • Lutein • Astaxanthin -Carotene Lutein Astaxanthin Molecular Formula: C40H52O4 Molecular Weight: 596.82 CAS No: 472-61-7 *Parker RS.,1997

  4. A S T A X A N T H I N B A C K G R O U N D 1938 Lobster (Astacus gammarus) Discovered by Nobel Laureate Dr Kuhn Present Day Other Sources Microalgae (Haematococcus pluvialis) Yeast (Phaffia rhodozyma) Bacteria (Agrobacterium aurantiacum) Higher Plants (Adonis aestivalis) Crustaceans (Euphasia supurba) Fish (Salmon) Typically 1mg per 200g Birds (Flamingo, Cockerel)

  5. 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 vivo against environmental oxidative stress.” (1999 Kobayashi, M., Okada, T. Protective Role of Astaxanthin to Protect Against UVB Radiation in the Green Alga Haematococcus pluvialis.) Powerful Antioxidant Defence Against Free Radicals Protects Plant Cell Contents Microalgae 15,000 ppm Yeast 8,000 ppm Krill 1,500 ppm.

  6. A S T A X A N T H I N M E A N S M O R E H E N S F O R T H E R O O S T E R ! COME HERE GIRLS!

  7. A S T A X A N T H I N & C A R O T E N O I D P E R C E P T I O N S “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

  8. A N T I O X I D A N T M E C H A N I S M S Physical Quenching 1O2 + 1Carotenoid →3O2 + 3Carotenoid* 3Carotenoid*→1Carotenoid + thermal energy* ↓ ASTAXANTHIN ELIMINATES FREE RADICALS EXTREMELY FAST BY ENERGY TRANSFER** Chemical Reaction (e.g. -Carotene) 1O2 +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.)

  9. S C A V E N G I N G E F F E C T O F D I F F E R E N T A N T I O X I D A N T S I N A L I P O P H I L L I C I N V I T R O M O D E L ASTAXANTHIN #1 XANTHOPHYLL 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

  10. N E U T RA L I Z I N G R O S e－e－ ３O2→　・O2－→　H2O2→ ・OHO２LH １O2LH→　L・　→　LOO・　→　LOOH H2OL・ SOD Catalase Ascorbic Acid (Hydroxy radicals) Astaxanthin (Superoxide radical) ↓↓　 ↓　　 ↓ (Singlet oxygen radical) (Peroxide radicals) 　　　　　　　　 　　　　　　 ↓　 　　　 ↓ Astaxanthin QUENCHING 550 x Vitamin E* 40 x -carotene* 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)

  11. A S T A X A N T H I N - I S T H E P U R E A N T I O X I D A N T Anti- and Pro-oxidants Pure Anti-oxidant H.D.Martin, et al. : Chemistry of carotenoid oxidation and free radical reactions, Pure Appl. Chem., 71(12), 2253-2262 (1999).

  12. T H E A S T A X A N T H I N S H I E L D Lignell A., & Wood V., Astaxanthin: Radical Cellular Defense. May 2004 Innovations in Food Technology.

  13. A S T A X A N T H I N D I S T R I B U T I O N I N R A T S A F T E R 3 W E E K S O N S U P P L E M E N T E D D I E T ( 1 0 0 m g A x / k g f e e d ). A S T A X A N T H I N S H I E L D US Pat 6,245,818 Medicament for improvement of duration of muscle function or treatment of muscle disorders or diseases.

  14. P R O P E R T I E S O F A S T A X A N T H I N

  15. C A T E R G O R I Z E D L I T E R A T U R E *Patent Protected **Patent Applied

  16. Muscle Endurance • 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

  17. Dietary supplementation with astaxanthin improves muscleendurance. A randomised double blind placebo controlled study on healthy malesubjects. 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. 3 months 3 months Parameters measured: - Fitness - Strength / endurance - Strength / explosivity (In Press) Investigator Curt L. Malmsten, PhD, MD, Räddningshälsan AB, Sweden.

  18. R E S U L T S : C H A N G E S I N S T R E N G T H / E N D U R A N C E Significant increaseof muscle endurance. No difference in fittness. No difference in muscle explosivity. 3 months Baseline 6 months Baseline p < 0.05

  19. C O N C L U S I O N S • 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 enduranceUS Pat 6,245,818

  20. Astaxanthin Limits Exercise-Induced Skeletal and Cardiac Muscle Damage in Mice Protocol １wk 3wk 24hr Acclimatization Training Program Exercise Euthanized ・Control (N=8) ・Exercise Control (N=8) ・Exercise Supplemented (N=8) 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.

  21. M U S C L E C E L L M E M B R A N E Heart EXERCISE CONTROL CONTROL EXERCISE + AX Gastrocnemius CONTROL EXERCISE CONTROL EXERCISE + AX

  22. R E S U LT S • Overall Reduction of DNA damage • Reduction of Inflammatory Response • Reduction of Muscle Cell Damage • New Research to Mechanism using Gene Chip Analysis - 2005

  23. I N F L A M M A T 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.

  24. E Y E H E A L T H - F A T 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”

  25. C L I N I C A L P A R A M E T E 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. 57thCongress of Clinical Opthalmology of Japan 58(6):1051-1054 (Japanese).

  26. E Y E F A T I G U E C O N C L U S I O N • 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. *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).

  27. 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.

  28. 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.

  29. Cosmetic benefit of a Dietary Supplement Containing Astaxanthin & Tocotrienolon 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.

  30. p<0.05 p<0.05 Changes of skin condition (-worse/+better) Changes of skin condition (-worse/+better) Sag Sag Total Total Pouch Pouch Wrinkle Oiliness Wrinkle Moisture Dullness Oiliness Redness Moisture Dullness Redness Elasticity Elasticity Complexion Complexion Fine wrinkle Smoothness Fine wrinkle Smoothness Acne/Pimples Acne/Pimples Spots/Freckles Spots/Freckles R E S U L T S 1 • Skin condition by individual assessment

  31. Week 2 Week 4 p<0.05 p<0.1 p<0.1 p<0.01 p<0.1 Changes of skin condition (-worse/+better) Changes of skin condition (-worse/+better) Sag Sag Pouch Pouch Tough Tough Wrinkle Wrinkle Oiliness Oiliness Dullness Dullness Pulpfree Pulpfree Redness Redness Moisture Moisture Elasticity Elasticity Skin color Skin color Complexion Skin texture Complexion Skin texture Fine wrinkle Fine wrinkle Smoothness Smoothness Acne/Pimples Acne/Pimples Spots/Freckles Spots/Freckles Dark rings around eyes Dark rings around eyes R E S U L T S 2 • Dermatologist inspection/palpation

  32. p<0.05 R E S U L T S 3 • Skin moisture content

  33. R E S U L T S 4 • Skin sebum content

  34. R E S U L T S 5 • Magnified skin surface inspection M4 2 weeks 4 weeks Start

  35. UVA UVA 1O2 1O2 1O2 New Collagen Possible Mechanism of Action- Visual Wrinkle Reduction - Tocotrienol Astaxanthin Astaxanthin Tocotrienol Singlet oxygen induced UVA oxidizes collagen → WRINKLE Thank you !!

  36. C O N C L U S I O N • Increased moisture levels • Consistent natural oils • Reduction of fine wrinkles and pimples • Improved elasticity • Reduced swelling under the eyes Astaxanthin & Tocotrienol supplementation resulted in

  37. J A P A N E S E R E T A I L P R O D U C T S Astaxanthin + Tocotrienol & SOD 60 soft cap 3,800 JPY/month 37 USD or 287 HKD Astaxanthin & Blueberry Astaxanthin 1mg/day + DHA+ARA 6,300 JPY/month 61 USD or 477 HKD Pure Astaxanthin Astaxanthin & Natto Kinase Astaxanthin 2mg/day+ pomegranate juice 500mL. 6,000 JPY/month, 58 USD or 453 HKD

  38. J A P A N E S E R E T A I L P R O D U C T S C O S M E C E U T I C A L S & B E A U T Y S U P P L E M E N T S 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 NatuReal Corp. Astaxanthin, Tocotrienol & Collagen Supplement 7,000 JPY/month Cream 9000 JPY Essence 10,000 JPY 68-97 USD or 529-755 HKD

  39. R E G U L A T O R Y I N F O R M A T I O N

  40. C O N T A C T I N T E R N A T I O N A L M A R K E T I N G S E C T I 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 N A T O – K U T O K Y O 1 0 5 – 0 0 0 3 J A P A N ( T ) + 8 1 – 3 – 3 4 3 7 – 2 3 5 3 ( F ) + 8 1 – 3 – 3 4 3 7 – 2 3 4 7 w w w . f u j i c h e m i c a l . c o . j p / e n g l i s h E m a i l : i n f o @ f u j i c h e m i c a l . c o . j p Thank you for your kind attention! For more information vist Booth E17

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