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NOV2004 Natural Products Expo Asia 2005 Hong Kong Astaxanthin: A Radical Approach to Vitality & Beauty From Within Natural Products Expo Asia 2005 Vincent.

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Presentation on theme: "NOV2004 Natural Products Expo Asia 2005 Hong Kong Astaxanthin: A Radical Approach to Vitality & Beauty From Within Natural Products Expo Asia 2005 Vincent."— Presentation transcript:

1 NOV2004 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

2 NOV2004 Natural Products Expo Asia 2005 Hong Kong What is Astaxanthin?What is Astaxanthin? Why is it so potent compared to other carotenoid antioxidants?Why is it so potent compared to other carotenoid antioxidants? The Research & Impact on HealthThe Research & Impact on Health Summary of Recent AdvancesSummary of Recent Advances –Supplement use in Muscle Endurance, Eye health and Cosmetic benefit Retail Examples in JapanRetail Examples in Japan Regulatory, Production Technology & SupplyRegulatory, Production Technology & Supply 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

3 NOV2004 Natural Products Expo Asia 2005 Hong Kong 600 known carotenoids*600 known carotenoids* Humans cannot synthesise carotenoids.Humans cannot synthesise carotenoids. Need to obtain carotenoids from food.Need to obtain carotenoids from food. <25 obtained from food. <25 obtained from food. Basic carotene structureBasic carotene structure Xanthophyll ClassXanthophyll Class –Lutein –Astaxanthin Molecular Formula: C 40 H 52 O 4 Molecular Weight:596.82 CAS No: 472-61-7 *Parker RS.,1997 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 Astaxanthin Lutein  -Carotene OH OH

4 NOV2004 Natural Products Expo Asia 2005 Hong Kong 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) A S T A X A N T H I N B A C K G R O U N D

5 NOV2004 Natural Products Expo Asia 2005 Hong Kong Haematococcus pluvialis Astaxanthin Powerful Antioxidant Defence Against Free Radicals Protects Plant Cell Contents Haemato (Blood) coccus (Seed) Microalgae family – includes Spirulina Harsh Environment – Dormant / Hibernates “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.) Microalgae 15,000 ppm Yeast 8,000 ppm Krill 1,500 ppm.

6 NOV2004 Natural Products Expo Asia 2005 Hong Kong 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 NOV2004 Natural Products Expo Asia 2005 Hong Kong 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 Low level of consumer and retail awareness Too many antioxidants on the market Contradictory carotenoid evidence. Not enough science  -carotene>lycopene>lutein>astaxanthin A functional based product is being developed based on microalgal astaxanthin Natural vs Synthetic Microalgae vs Yeast Perceived to be expensive! only small amounts are required. Can complements existing formulations Unstable supply in the past, Intense competition ‘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

8 NOV2004 Natural Products Expo Asia 2005 Hong Kong Physical Quenching 1 O 2 + 1 Carotenoid → 3 O 2 + 3 Carotenoid* 3 Carotenoid* → 1 Carotenoid + thermal energy * ↓ ASTAXANTHIN ELIMINATES FREE RADICALS EXTREMELY FAST BY ENERGY TRANSFER** Chemical Reaction (e.g.  -Carotene) 1 O 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). A N T I O X I D A N T M E C H A N I S M S “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 NOV2004 Natural Products Expo Asia 2005 Hong Kong 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 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

10 NOV2004 Natural Products Expo Asia 2005 Hong Kong e - e - 3 O 2 → ・ O 2 - → H 2 O 2 → ・ OH O 2 LH 1 O 2 LH → L ・ → LOO ・ → LOOH H 2 O L ・ SOD Catalase Ascorbic Acid Astaxanthin ↓ ↓ ↓ ↓ ↓ ↓ QUENCHING 550 x Vitamin E* 40 x  -carotene* INHIBITSPEROXIDATION 1000 x Vitamin E** N E U T RA L I Z I N G R O S (Superoxide radical) (Singlet oxygen radical) (Hydroxy radicals) (Peroxide radicals) *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) Astaxanthin Vitamin E (tocopherol)

11 NOV2004 Natural Products Expo Asia 2005 Hong Kong H.D.Martin, et al. : Chemistry of carotenoid oxidation and free radical reactions, Pure Appl. Chem., 71(12), 2253-2262 (1999). PureAnti-oxidant Anti- and Pro-oxidants 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

12 NOV2004 Natural Products Expo Asia 2005 Hong Kong 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 NOV2004 Natural Products Expo Asia 2005 Hong Kong 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 NOV2004 Natural Products Expo Asia 2005 Hong Kong P R O P E R T I E S O F A S T A X A N T H 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.

15 NOV2004 Natural Products Expo Asia 2005 Hong Kong C A T E R G O R I Z E D L I T E R A T U R E C A T E R G O R YP U B L I C A T I O N S General Nutrition Stomach & Gut Health* Eye Health** Sports Nutrition* Vetinary Health* Cosmecuticals Antioxidant potency, Synergies. Helicobacter, dyspepsia Visual Fatigue, Diabetic Cataract Muscle Endurance and damage, Visual Acuity, anti-inflammatory. Fertility, muscle endurance, anti- inflammatory UVR damage, photoprotectant, anti-inflammatory. *Patent Protected **Patent Applied

16 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

17 NOV2004 Natural Products Expo Asia 2005 Hong Kong 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. Parameters measured: - Fitness - Strength / endurance - Strength / explosivity 3 months Dietary supplementation with astaxanthin improves muscle endurance. A randomised double blind placebo controlled study on healthy male subjects. (In Press) Investigator Curt L. Malmsten, PhD, MD, Räddningshälsan AB, Sweden.

18 NOV2004 Natural Products Expo Asia 2005 Hong Kong 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 Baseline 6 months 3 months Baseline p < 0.05 Significant increase of muscle endurance. No difference in fittness. No difference in muscle explosivity.

19 NOV2004 Natural Products Expo Asia 2005 Hong Kong 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 C O N C L U S I O N S

20 NOV2004 Natural Products Expo Asia 2005 Hong Kong Damage Markers Muscle cell staining – Cell membrane damage Creatine kinase (CK) – Damaged muscle cells 8-hydroxy-2’-deoxyguanosine (OHdG) – DNA damage Myeloperoxidase (MPO) - Inflammation Acclimatization ・ Control (N=8) ・ Exercise Control (N=8) ・ Exercise Supplemented (N=8) Training Program Exercise Protocol 1 wk 3wk Euthanized 24hr Astaxanthin Limits Exercise-Induced Skeletal and Cardiac Muscle Damage in Mice Aoi, W. et al. 2003, Antioxidants & Redox Signalling, 5:(1) 139-144.

21 NOV2004 Natural Products Expo Asia 2005 Hong Kong M U S C L E C E L L M E M B R A N E Gastrocnemius Heart CONTROLEXERCISE CONTROLEXERCISE + AX CONTROLEXERCISE + AX EXERCISE CONTROL

22 NOV2004 Natural Products Expo Asia 2005 Hong Kong 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 NOV2004 Natural Products Expo Asia 2005 Hong Kong 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 NOV2004 Natural Products Expo Asia 2005 Hong Kong

25 NOV2004 Natural Products Expo Asia 2005 Hong Kong  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” E Y E H E A L T H - F A T I G U E

26 NOV2004 Natural Products Expo Asia 2005 Hong Kong 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) C L I N I C A L P A R A M E T E R S *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).

27 NOV2004 Natural Products Expo Asia 2005 Hong Kong  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. E Y E F A T I G U E C O N C L U S I O 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).

28 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.

29 NOV2004 Natural Products Expo Asia 2005 Hong Kong Astaxanthin BEAUTY FROM WITHIN – The Next Hot Market Segment L’Oreal & Nestle – “Innévo” 2002 Targeting women >40 y.o.***  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** *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.

30 NOV2004 Natural Products Expo Asia 2005 Hong Kong Cosmetic benefit of a Dietary Supplement Containing Astaxanthin & Tocotrienol on Human Skin Yamashita, E. 2002, FOOD Style 21, 6:(6) 112-117. 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

31 NOV2004 Natural Products Expo Asia 2005 Hong Kong

32 NOV2004 Natural Products Expo Asia 2005 Hong Kong Skin condition by individual assessment R E S U L T S 1 Total Sag Pouch Fine wrinkle Wrinkle Redness Spots/Freckles Dullness Acne/Pimples Complexion Elasticity Oiliness Smoothness Moisture Total Sag Pouch Fine wrinkle Wrinkle Redness Spots/Freckles Dullness Acne/Pimples Complexion Elasticity Oiliness Smoothness Moisture Changes of skin condition (-worse/+better) p<0.05

33 NOV2004 Natural Products Expo Asia 2005 Hong Kong Dermatologist inspection/palpation R E S U L T S 2 Week 2 Tough Elasticity Smoothness Sag Pouch Fine wrinkle Wrinkle Redness Spots/Freckles Dullness Acne/Pimples Complexion Oiliness Skin texture Moisture Pulpfree Dark rings around eyes Skin color Week 4 Smoothness Sag Pouch Fine wrinkle Wrinkle Redness Spots/Freckles Dullness Acne/Pimples Complexion Oiliness Skin texture Moisture Tough Pulpfree Dark rings around eyes Skin color Elasticity p<0.05 p<0.01 p<0.1 Changes of skin condition (-worse/+better)

34 NOV2004 Natural Products Expo Asia 2005 Hong Kong Skin moisture content R E S U L T S 3 p<0.05

35 NOV2004 Natural Products Expo Asia 2005 Hong Kong Skin sebum content R E S U L T S 4

36 NOV2004 Natural Products Expo Asia 2005 Hong Kong Magnified skin surface inspection R E S U L T S 5 M4 4 weeks2 weeks Start

37 NOV2004 Natural Products Expo Asia 2005 Hong Kong Possible Mechanism of Action - Visual Wrinkle Reduction - 1O21O2 1O21O2 1O21O2 UVA Singlet oxygen induced UVA oxidizes collagen → WRINKLE Astaxanthin New Collagen Thank you !! Tocotrienol

38 NOV2004 Natural Products Expo Asia 2005 Hong Kong Increased moisture levelsIncreased moisture levels Consistent natural oilsConsistent natural oils Reduction of fine wrinkles and pimplesReduction of fine wrinkles and pimples Improved elasticityImproved elasticity Reduced swelling under the eyesReduced swelling under the eyes Astaxanthin & Tocotrienol supplementation resulted in C O N C L U S I O N

39 NOV2004 Natural Products Expo Asia 2005 Hong Kong J A P A N E S E R E T A I L P R O D U C T S Astaxanthin & Blueberry Astaxanthin & Natto Kinase Astaxanthin + Tocotrienol & SOD 60 soft cap 3,800 JPY/month 37 USD or 287 HKD Pure Astaxanthin Astaxanthin 1mg/day + DHA+ARA 6,300 JPY/month 61 USD or 477 HKD Astaxanthin 2mg/day+ pomegranate juice 500mL. 6,000 JPY/month, 58 USD or 453 HKD

40 NOV2004 Natural Products Expo Asia 2005 Hong Kong 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 NatuReal Corp. Astaxanthin, Tocotrienol & Collagen Supplement 7,000 JPY/month Cream 9000 JPY Essence 10,000 JPY 68-97 USD or 529-755 HKD J A P A N E S E R E T A I L P R O D U C 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

41 NOV2004 Natural Products Expo Asia 2005 Hong Kong R E G U L A T O R Y I N F O R M A T 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

42 NOV2004 Natural Products Expo Asia 2005 Hong Kong 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 3 rd 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 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 C O N T A C T Thank you for your kind attention! For more information vist Booth E17


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