2005 Contents 1 1 9 13 19 19 28 37 45 53 53 57
2005 Contents 2005 3 02-2655-8233 ext.338 02-2655-8362 Http://agbio.coa.gov.tw/ 115 3 F 16 1 TEL: 02-2732-1234 GPN: 2009401406 ISSN: 18154379 017 62 66 FAO GMO GM Israeli Jaffa Sweetie 70 4% 7~10 30
IFT (Institute of Food Technologists) functional safety nutritional nutraceutical functional foods nutraceuticals 2002~2005 IFT 2005 2004 2003 2002 Functional 341 393 284 236 Safety 289 356 292 314 Nutritional 212 189 172 141 Antioxidant 188 193 134 129 Weight 182 230 166 150 Nutraceutical 156 195 132 107 Soy 146 163 139 137 Bioactive 119 97 46 37 Aging 93 92 75 76 Soybean 59 99 76 91 Cardiovascular 56 32 26 17 Peptide 52 51 25 38 Tea 50 35 23 27 Obesity 49 59 24 13 Genetic 46 62 33 54 Gene 39 65 42 38 Diabetes 32 28 21 14 Polyphenol 18 18 13 13 Isoflavone 10 22 19 14 www.ift.org 2005 2005 1
2005 2 Functional Foods Nutraceuticals EPA DHA 45 42 36 31 25 25 24 24 23 22 18 16 15 13 12 12 11 11 11 10 9 10 9 8 2 18-29 64 60 35 10 7 9 23 24 6 31 18 23 1 15 2 24 4 5 10 22 8 12 14 7 1 30-39 53 52 41 15 13 20 17 18 10 23 16 16 4 11 3 13 6 8 14 14 7 6 8 7 1 40-49 49 50 35 24 18 26 21 21 14 24 16 21 22 13 6 11 8 10 8 7 7 11 9 8 1 50-64 39 37 41 39 33 30 25 28 30 22 19 15 34 13 17 11 14 14 12 7 8 12 9 10 2 65 30 19 29 54 42 30 31 25 44 12 19 9 5 14 27 7 20 17 9 5 13 9 6 8 2 HealthFocus 2005 ITIS %
( ) 261.8 246.4 192.5 What an ingredient does -- How an ingredient works Ordinary foods ( ) Nutrition labeling and Education Act (1990) ILSI-Europe opinion (CODEX Alimentarius) Food for Specific Health Use Act (1991) Dietary supplements ( ) Dietary Supplement Health and Education Act (1994) Health food Manufactures Association (bar) (Cereal) Nutrition business Journal, 2005 Food Technology, Vol.59, No.5, May 2005 ITIS (functional foods) Nutrition Business Journal 2005 770 34% 32%25% 2005 261.8 246.4 192.5 64% 21% 5,000 Market standard Healthy for you Natural/Organic Functional food Market standard Healthy for you Natural/Organic Functional food E 2003 Market standard 82% Healthy for you 11% Natural/Organic 3% Functional food 4% Mark K. Schmidl (Fresh produce) (Healthy Snacks and Meal Replacements) / ( Herbs) (Medical Foods) 750 400 250 200 100 1209080 3010 2,030 2010 Market standard 76% Healthy for you 13% Natural/Organic 5% Functional food 6% Datamonitor 6-7% 2005 3
sterol sterol esters Danone sterol esters 2005 2 Minute Maid Tesco Lactobacillus acidophilus inulin Semper (novel probiotic delivery system) Paul Yamaguchi and Associates Inc. 2004 160 2003 12% FOSHU 400 50 31.25% FOSHU FOSHU FOSHU 63% 50 FOSHU 29% 110 corroborative project (biomarker of fatigue) (alternative medications) (dietary supplements) 2005 1802010 250 R (blueberry) (collagen) (hyaluronic acid) (ceramide) (lotus germ extract)(rose petal extract) (conjugated linoleic acid CLA) (L-carnitine) 2004 2002 2002 1 2 3 4 5 6 4 7 9 10 11 12 13 14 15 16 17 CoQ10 18 CoQ10 19 20 α- 21 β- 22 23 24 25 2005 9 8 4 2005
(estrogen-like) (probiotics) (Morinaga) (lactoferrin yogurt) (Koiwai)Lactobacillus yogurt (Meiji) LG 21 Pylori yogurt (pylori bacteria) R (Calpis) R Daizu Peptide Nysankin 4,000 R Powerade Toraku 8,000 R The Peptide Tokiwa R (sardine peptide) Lapis Support (Kao) Healthya Green Tea 36% (therapeutic) (liquid) 2080 2000 500 2001175 2002 200 2003300 2004 500 2004 500 306 2000 2004 2004 2004 3/5 300 1997 15 2002 2004 170 1996 FOSHU a Mize-Mizu-Shia Suntory ( b ) Resistant starch Blenry Coffee with Oligosaccharide Ajinomoto General Foods Coffee (manno-) oligosaccharide c Van Hou Ten Milk Cocoa Fiber Plus Kataoka Trading Cocoa mix Mine-zu Mitsukan Prety-o Gamma amino butyric acid Healthia Oolong Tea Re-setta Soft Margarine MCT a:from Asahi Shimbun(Japanese daily newspaper), March 26, 2005. b: c: Bifidobacterium Food Technology, Vol.59, No.5, May 2005 ITIS 2005 5
2004 7 2004 7 6,000 9 2005 8 11 6861 AB ) 35.3% 24 / 9 32.4% 22 7 β-glucan HMG- CoA EPA DHA 10.3% 7 4 G G Daidzein nystose 8.8% 6 4 ab N 2.9% 2 2.9% 2 (Healthy Resetta Diet Oil) 1999 68 1999 12000 11 2001 9 2002 8 2003 112004 122005 8 11 16 2000 AB 2001 ABC / 2001 2002 2003 2005 LGG 85 54 3 (Econa Cooking Oil) OilliO (Healthy Resetta Diet Oil) Econa 1998 1999 2 OilliO 2002 12 6 6 2005
10 AMIRU-S Econa Health 100 83 1,600 Econa Health 1998 (Banso-reicya) AMIRU-S 80-100 FOSHU 100 FOSHU 1999 Survival food Convenience food Engineered food 150-300 2004 93% 89% 10 Functional food Nutraceutical Nutrigenetic food 18th 19th 20th 21th Century Fi Asia -China Conference, 2005 3 1-2 ITIS (Nutrigenetic Food Age) 2005 7
Nutrigenetic (Survival food) (Convenience food) (Functional food) (Nutrigenetic food) 8 2005
2005 9 88 2 38 3 100
dietary supplement (Food for Specific Health Use, FOSHU) dietary supplement 80 83 84 88 dietary supplement (This statement has not been evaluated by the FDA. This product is not intended to diagnose, treat, cure or prevent any disease.) (medical claim) (1) 10 2005
(2) (3) (structure/function claim) (health claim) (medical claim) 88 1. 2. 28 90 90 2005 11
94 11 74 (http://www.doh.gov.tw) (http://food.doh. gov.tw) 12 2005
68 (94) 8 28 Flavonoids allyl sulfides carotenoids monoterpenes isothiocyanates phytosterols 88 8 2,, 28, 90, 90 28 (Genotoxicity study) (1) (2) 2005 13
(Ames test) S. typhimurium TA98 S. typhimurium TA100 S. typhimurium TA1535 S. typhimurium TA1537 TA97 TA97a S. typhimurium TA102 E. coli WP2 uvr A E. coli WP2 uvr A (pkm101) (1)(In vitro Chromosomal aberration test with mammalian cells in culture) : (2) tk (In vitro mouse lymphoma tk assay) tk cell cell (1) (Chromosomal aberrations in bone marrow cells of rodents) : (2) (Micronuclei in bone marrow cells of rodents) : (3) (Micronuclei in peripheral blood of rodents) : 24-76 Acridine orange (1000X) (1000X) 5/1000 20-90/1000 2.1 0.1 28 (5g/kg 10ml/kg) SD 28 28 (no-observed-adverse-effect level, NOAEL) 28 5 (w/w) 1000 mg/kg 14 2005
28 28 (NOAEL) NOAEL (acceptable daily intake, ADI) 10 5 WORLDNUTRA 2004 (1) Oligonol Polyphenols Chitosan Soy protein Fish oil Sea algae Anthocyanins Probiotics Phytoestrogens Lutein CoQ10 Lycopene Blueberries CLnA (Isomers of Conjugated Linolenic Acid) Galactooligosacchrides Vitamin Ginseng Noni Sterols Dietary Supplements (2) (3) (4) (5) (6) (7)(8) (9) 250g 250g Cy3xGG Cy3xSGG 500g Cy3xGG Cy3xSGG (1) GMO (2)(3) (4) (5) (1) (2) / / Dr. Ruckmany GRAS DHEA Novel Foods Food Supplements directive (1) Ames test metaphase analysis mammalian cell mutation assay Gastrointestinal study(2)single dose oral study 4/8-week oral repeat dose study 90-day oral repeat dose study St. John's Wort (Hypericum perforatum L.) MAO COMT Cortisol 5-HTGABA-A Beta-adrenoceptors 5-HT-2 23 21 1/3 Cadmium 2005 15
3 FDA Dr. Blumenthal 6 (1) EphedraFDA 2004 4 12 (2)Bitter orange Synephrine ephedrine (3)black cohosh CSPI FDA 32 (4) Kava FDA 20028 (5)St. John's wort P450 (6)Comfrey CO2 (7)scullcapgermander (8)Asian ginseng 1979 JAMA caffeine (9) Magnolia bark 1990 Aristolochic acid Tubocurarine Magnocurarine10 Aristolochia Magnolia bark Aristolochic acid Magnolia bark Magnocurarine Magnolia bark Tubocurarine lobelia 4 (1) 1 (2) 2 (3) 3 (4) 4 1480 5280 77 Dr. Stohs ( Citrus Aurantium) synephedra (CNS) Dr. Pujari PCB(EPA 8082 SDIRaPID Assay ) Dioxin(EPA 625) Pb Cd Hg As (EPA 6020/200.8) (AOAC991.39) Dr. Tauscher 500 16 2005
(EWG-no. 209/91) Dr. Kumii 7 100 200 300 mg Isoflavone (IF)1 HPLC-ECD 644 ng/ml Daidzein 295 ng/ml Equol 287 ng/ml Genistein 7 4 EquolIF WBC RBC Hb Ht Thyroid steroid IF 1 Dr. Kim (Ca) (Pb) 6.7 mg/g 1.1 mg/g 2.3 mg/g FAO/WHO : (1) (2) (3) : 1. 2. 3.4. 5. (ADME) 6. Flavonoids allyl sulfides carotenoids monoterpenes isothiocyanates phytosterols 1000 2005 17
10 4 II I (Naringin) anti-cd71-fitc 10 2 10 3 4012 48 10 1 III IV 10 0 10 0 10 1 10 2 10 3 10 4 Propidium lodide I - II III IV 5000 in vitro Caco-2 cell line 3R 18 2005
Probiotics Prebiotics prebiotics synbiotics B 1. 2. (1) (2) ph (3) 3. K 4. Obradovic 1996 17 2005 19
200 ml 12 1.5 mmol/l 20 L. para. subsp. paracasei NTU 101 26.4 3. 4. A - 88 8 3 71 24 7124 68 24 34 22 31 9 13 7 10 3 4 2 3 2 3 1 1 1 1 19 synbiotic 3 (prebiotic) 1 ( ) + 20 2005
synbiotics Lactobacillus sporogenes (Bacillus coagulans) 8908-8912 3 AB (prebiotic) Bifidobacterium longum 9001-9006 3 Lactobacillus acidophilus ( ) Lactobacillus bulgaricus Bifidobacterium bifidum Bifidobacterium longum Streptococcus thermophilus 9007-9012 9101-9106 3 2 ABC / (Daidzein 9107-9112 2 nystose) 9201-9206 3 9208-9212 1 1-3 9301-9306 9307-9312 9401-9406 9407-9410 2 2 2 1 TCELL-1 LGG (synbiotic) (synbiotic) (synbiotic) 4 3 ABC / 3 3 1 1 1 1 1 1 1 1 1 1 1 AB TCELL-1 LGG 2005 21
11 LGG ABC / AB TCELL-1 (Lactobacillus) (Bifidobacterium) Lactobacillus acidophilus Lactobacillus casei Lactobacillus delbrueckii Lactobacillus paracasei Lactobacillus casei sp. Rhamnosus Lactobacillus rhamnosus Lactobacillus bulgaricus Lactobacillus fermentum Bifidobacte-rium longum Bifidobacterium lactis Bb-12 Bifidobacterium bifidum Enterococcus faecium Streptococcus thermophilus AB 2 2 Lactobacillus acidophilus La-5 Bifidobacterium lactis Bb-12 1 1 Bifidobacterium longum BB536 + Bifidus 2 2 Bifidobacterium longum Lactobacillus acidophilus 1 1 Bifidobacterium lactis HN019 3 5 Bifidobacterium longum Lactobacillus acidophilus Bifidobacterium lactis Bb-12 Lactobacillus casei Enterococcus faecium 2 2 Streptococcus thermophillus Lactobacillus delbrueckii 3 3 DR10TM Bifidobacterium longum Streptococcus thermophillus Lactobacillus delbrueckii 22 2005
/ ABC 3 5 Streptococcus thermophillus Lactobacillus delbrueckii Lactobacillus acidophilus Bifidobacterium longum Lactobacillus paracasei 1 1 Bifidobacterium longum 2 3 Bifidobacterium lactis Lactobacillus acidophilus Lactobacillus casei 3 4 Bifidobacterium lactis Lactobacillus acidophilus Enterococcus faecium Lactobacillus paracasei 1 1 Lactobacillus casei sp. rhamnosus GG 2 3 Bifidobacterium lactis Lactobacillus acidophilus Lactobacillus casei 1 1 Lactobacillus casei Shirota 2 2 Bifidobacterium longum Lactobacillus acidophilus 2 3 Bifidobacterium lactis Lactobacillus acidophilus Lactobacillus casei Bifidus TCELL-1 1 1 Lactobacillus rhamnosus Tcell-1 2 2 Lactobacillus sporogenes (Bacillus coagulans) Bifidobacterium longum powder 3 5 Lactobacillus acidophilus Lactobacillus bulgaricus Bifidobacterium bifidum Bifidobacterium longum Streptococcus thermophilus LGG 3 7 Lactobacillus bulgaricus Streptococcus thermophilus Lactobacillus rhamnosus GG Lactobacillus bulgaricus Bifidobacterium bifidum Lactobacillus acidophilus Lactobacillus casei (Daidzein 1 1 Lactobacillus fermentum nystose) 2005 23
46 52 T-cell 38 Lactobacillus rhamnosus Tcell-1 4 8 12 4 (GOT GPT) (RBC HGB HCT MCV MCH MCHC PLT WBC) 28 (28-day feeding toxicity study)spf620 10 16 83 166 L. rhamnosus Tcell-1 28 Wistar 20 1 g/kg (7x10 11 CFU) 0.5 g/kg (3.5x10 11 ) 0.1 g/kg (7x10 10 CFU) 1 2 3 4 L. rhamnosus Tcell-1 L. rhamnosus Tcell-1 HPRT (S9) 6(S9) 3.125, 6.25, 12.5, 25, 50, 100 µl/ml 0.1 µl/ml methanesulfonic acid, ethyl ester 18~24 (S9) 1.5625, 3.125, 6.25, 12.5, 25, 50 µl/ ml 100 µg/ml N- nitroso-dimethylamine 18~24 HPRT ICR25 35 25 50 100 20 ml/kg mitomycin C 1 mg/kg 36~48 ICR S9 3 S9 20 5 -S9, 3 +S9, 3 -S9, 20 24 2005
5 (µl/ml) 6.25, 12.5, 25, 50, 100-S9 mitomycin C 1 µm +S9 cyclophosphamide 40 µm SD 4865 10 20 ml/kg (20 ml/kg) 14 SD 14 28 SD 80 10 1.5 5 15 ml/kg/day (15 ml/kg/day) 28 23 22 1 400 (1) 1971-1974 Streptococcus type Lactobacillus type (2) 1987-1991 23 1991 Lactobacillus acidophilus 2004 (3) (L. reuteri) Co-culture/overlayer (RPLR) 0-76 2001L. GG Caco-2 2003 Clostridium difficile Caco-2 (4) 1987 91 L. acidophilus L. bulga- 2005 25
ricus Streptococcus lactis SK2 1993L. plantarum L. plantarum Escherichia coli, Pseudomonas aeruginosa Bacillus cereus (5) 1995 Bifidobacterium -D- 2~3 B. longum B. bifidum (6) 1995 Bacillus coagulans Leuconostoc mensenteroides Pediococcus cerevisiae L. brevis L. plantarum (7) L. plantarum Pediococcus acidilacici Pediococcus pentosaceus (8) 1995 L. bulgaricus L. acidophilus Streptococcus thermophilus Lactococcus lactis -18 C -3l C 5 7 log CFU/mL (9) 1995 glutathione 2003 2000 2002 Lactobacillus paracasei subsp. paracasei NTU 101 Bifidobacterium longum BCRC 11847 1:2 2575 12 10 15 0.44 0.42 5 4 C 14 10 9 CFU/mL L. para. subsp. paracasei NTU 101L. plantarum NTU 102 L. para. subsp. paracasei NTU 101 L. plantarum NTU 102 L. para. subsp. paracasei NTU 101 26.4 L. plantarum NTU 102 23.5 LDL HDL L. plantarum NTU 102 L. para. subsp. paracasei NTU 101 (10) 1986 26 2005
1994 (probiotics) 2000 35 (11) 1994 15 C 3 30 ppm 0 ppm ethyl carbamate 7 ppb 35 ppb 130 ppb (12) 1995 L. acidophilus B. bifidum (13) 1989 Streptococcus lactis 12267 Bacillus subtilis 51166 4 nisin 1986 Leuconostoc sp. TMB4440 2.5 Ca-alginate gel 11 1993 1998 2001 2002 2004 pnlp1 p203 2002 (14) 1995 Streptococcus faecium 132003 (1) (Helicobacter pylori) (rotavirus diarrhoea) (gastritis) (2) 2005 27
(Monascus)van Tieghem 1884 (septa) (ascocarp) (Fungi) (Ascomycota) (Ascomycetes) (Eurotiales) (Monascaceae) 1908 Monascus purpureus 1930 Monascus anka Anka 30 C 7 1. 2. (monascidin) 3. (monacolins) 4. (GABA) 5. (flavonoids) 6. 28 2005
(monacolins) 51 (19.2 ) 2000 23,884 1979 Monascus ruber monacolin K HMG-CoA reductase (3-hydroxy-3-methylglutaryl coenzyme A reductase) mevalonic acid (low density lipoprotein cholesterol, LDL-C) Monacolin K (isoprene) Monacolin K 1993 0.2~0.3 200 mmhg 180 mmhg γ- (γaminobutyric acid, GABA) (glucosamine) 1987 Kohama (spontaneously hypertensive rats SHR) 1992 Tsuji (Monascus pilosus IFO 4520) γ- 2005 29
300 µg 27 g (monascidin) M. purpureus 1977 Wong Bau monascidin A Monascidin A Bacillus Streptococcus Pseudomonas monascidin ABlanc 1995 GC-MS NMR IR monascidin A citrinin monascorubrin rubropunctatin (ammoniemia) Yasukawa 12-o-tetradecanoyl-phorbol-13-acetate (TPA) (inflammatory) monascorubrin 1988 0.2~ 0.3% 23~33% 19~29% (ergosterol) D 2 1995 (Monascus) 1999 Aniya α α -diphenyl-β - picrylhydrazyl (DPPH) Aniya dimerumic acid Juzlova 1996 C 14 ~C 24 GC-MS 39 22 iso anteiso 14 (monoenoic acid) 2 (dienoic acid) 1 α- (α-linolenic acid) (superoxide dismutase SOD) (ribonuclease) α- N (α-galactosidase) (pectinase) citrinin (monascidin A) (hepatonephrotoxic mycotoxin) Citrinin Citrinin Penicillium citrinum Aspergillium spp. Monascus spp. Citrinin C 13 H 14 O 5 alcohol dioxane dilute alkali 250.331 nm LD 50 35 mg/kg (mouse) 67 mg/kg (rat) 217.1 O OH HOOC O O CH 3 CH 3 CH 3 Citrinin 30 2005
Citrinin gram-positive Bacillus Streptococcus Pseudomonas citrinin (nephrotoxin and hepatotoxin)monascus ruber citrinin citrinin citrinin Blanc 1995 Monasus purpureus Monascus ruber citrinin 100~400 mg/l citrinin citrinin citrinin citrinin citrinin citrinin 1999 Monica citrinin 0.2~17.1 µg/kg Ames Salmonella-microsome assay Salmonella-hepatocyte assay citrinincitrinin 1. - 2. 1. 2. 3. 4. 5. monacolin K/- 6. monacolin K/ - monacolin K 7. -- 1. (II) 2. 2005 31
3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 81,200 1. azaphilones 2. 3. pravastatin (HMG-CoA reductase inhibitor) 4. 5. 6. 7. M9011 1. 2. citrinin 32 2005
3. HPLC CE citrinin 4. citrinin 5. citrinin 6. citrinin 1. citrinin 2. 1. monacolin K citrinin monacolin K citrinin HPLC C18 citrininmonacolin K monacolin K 1 g 100 ethanol (10 ml) 60 C 30 min citrinin monacolin K monacolin K 859594 HPLC acetonitrile-water-trifluoacetate (550:450:0.5) citrinin monacolin K monacolin K LC-MS J. AOAC International 2. -γ- monacolin K Monascus γ- (γ-aminobutyric acid, GABA) monacolin K M. purpureus BCRC31615 NaNO 3 GABA monacolin K monacolin K 378 mg/ kg GABA 368 mm GABA K 2 HPO 4 430 mm (J. Industrial Microbiology and Biotechnology) 3. monacolin K GABA citrinin M. purpureus 0.5 ethanol citrinin 813.10 ppb 561.05 ppb monacolin K 136.03 mg/kg 383.62 mg/kg GABA 1.06 mg/g 7.45 mg/g 30 C 0.3 ethanol 145 ml monacolin K 530.61 mg/kg citriinin 460.08 ppb GABA 5.00 mg/g citrinin 0.25 M NaHCO 3 30 citrinin 70.07 monacolin K 93.14 (J. Industrial Microbiology and Biotechnology) 4. citrinin monacolin K GABA citrinin monacolin K GABA Monascus purpureus NTU 601 2005 33
Monascus citrinin Bacillus subtilis Monascus Bacillus subtilis citrinin monacolin K citrinin 301 citrinin 230.13 ppb wild type 50 monacolin K 481.29 mg/kg 90 GABA 5.25 mg/g wild type monacolin K9500 mg/kg monacolin K (J. Agriculture and Food Chemistry) 5. - monacolin K monascin Monascus purpureus NTU3012584 mg/kg monacolin K 5.37Monascin monacolin K monascin (J. Industrial Microbiology and Biotechnology) 6. α α-diphenyl-βpicrylhydrazyl (DPPH) Monascus sp. NiA M. anka M-13 77.0 73.10 M. purpureus BCRC31615 M. anka M-13 71.52 67.52 monacolin K (J. Agriculture and Food Chemistry) 7. Monascus purpureus NTU 568 (total cholesterol) (triglyceride) (LDL-C) HDL-C 31.2 30.1 36.0 LDL-C/HDL-C 39.1 11.5 citrinin GOT (glutamic-oxaloacetic transaminase) GPT (glutamic-pyruvic transaminase) (Applied Microbiology and Biotechnology) 8. 16 Wistar Monascus purpureus NTU 568 28 5 g/kg 1 g/kg 33.59 65.90 29.52 1.44 34 2005
mg/dl27.72 0.99 mg/dl 27.63 1.17 mg/dl (p 0.05) 45.00 0.90 mg/dl 31.41 1.80 mg/ dl 28.89 1.62 mg/dl 52.44 13.31 4.56 (Applied Microbiology and Biotechnology) 9. Monacolin K 48(Hy-line)48 12 2.05.08.0 HDL LDL (0 : 194.14 8.30, 2 : 167.17 4.34, 5 : 168.93 9.38, 8 : 183.02 7.63 mg/egg; p 0.05) (0 : 1494 178, 2 :1280 174, 5 : 1189 248, 8 : 1381 218 mg/dl; p 0.05) LDL (0 : 36.81 5.53, 2 : 32.25 7.93, 5 : 30.06 4.39, 8 : 28.81 4.16 mg/dl; p 0.05) HDL (0 : 36.06 3.96, 2 : 36.25 5.39, 5 : 33.13 3.68, 8 : 31.44 4.29 mg/dl; p 0.05) MDA (0 : 27.42 0.53, 2 : 25.62 0.76, 5 : 24.35 0.59, 8 : 23.63 0.48 µm; p 0.05) HPLC monacolin K (J. Agriculture and Food Chemistry) 100 Science News 092130380 10. LDL-C5.0 LDL-C 16.83 2.0 15.35 5.0 14.48 (p 0.05) 39.57 2 36.84 523.01 8% 5 31.76 24.54 (Applied Microbiology and Biotechnology) 11. (mechanical attrition method) 26 µm 1 10 30 200 ml (10 ) 600 g 2005 35
100 ml 3000 rpm 3 hr(dynamic light scattering, DLS) 20152.4 nm 3 401.1 nm (Scanning electron microscope SEM) monacolin K citrinin1310 6.05 mg/ kg 1171 2.41 mg/kg monacolin K citrinin (1) citrinin citrinin citrinin citrinin polyketide citrinin citrinin NTG citrinin citrinin (2) (intron) (gene cluster) polyketide 36 2005
1993 1950 1970 1993 20012005 25 (Chang, 2005) 1980 1987 1990 1999 2000 2001 1. 1971 Sasaki(G. applanatum) (Sasaki et al, 1971) -2(IL-2) T (Lai and Lin, 1992) T α DNAT (Lai and Lin, 1991) IL-1,IL-2,IL-6,INF-α,INF-γ (Lieu et al, 1992) 2005 37
(AIDS) β (1-3) β (1-6) G. applanatum G. lucidum G. tsugae (G. applanatum) G. lucidum G. tsugae (Wang et al,1993) T TNF-α IFN-γ (Wang et al, 1997) F3, GLPS, PS-G -1(IL-1) TLR4 (Toll-like receptor-4) (Hsu et al, 2004, Lin et al, 2005) 2-1-2 1982Kubota G. lucidum A.B. (ganoderic acid A. B.) (Kobota et al,1982) 1999 Kim HIV (Kim and Kim,1999) 1989 Kino G. lucidum LZ- (Ling Zhi-8) LZ-8 110 12,420 Da (Tanaka, 1989) LZ-8 (homodimmer) (systemic anaphylaxis reaction) (Arthus reaction) LZ-8 (Kino, 1989) LZ-8 β-d β-b α-a β-a α-b β-f β-g β-e β-c t-a 1 10 20 30 SDTALIFRLAWDVKKLSFDYTPNWGRGNPN 31 40 50 60 NFIDTVTFPKVLTDKAYTYRVAVSGRNLGV 61 70 80 90 KPSYAVESDGSQKVNFLEYNSGYGIADTNT 91 100 110 IQVFVVDPDTNNDFIIAQWN LZ-8 (Lin, 1997) 38 2005
FIP-gts FIP-fve FIP-vvo (Lin et al. 1997) 1989 Kino LZ-8 LZ-8 (nonobese diabetic, NOD) (Kino, 1990) LZ-8 (immunomodulatory drug) : CsA (cyclosporin A) R FK506 tacrolimus LZ-8 (ven der Hem, 1995) LZ-8 (G. tsugae) 13 kd FIP-gts (fungal immunomodulatory protein-gts) LZ-8 LZ-8 (human peripheral lymphocytes) 3 H-thymidine 5 µg/ml RT-PCR LZ-8 (IL-2, IL-4) (IFN-γ)(TNF-α) 1997 FIP-gts LZ-8 2003 13 kd FIP-fve (Ko et al. 1995) FIP-vvo (Hsu et al. 1997) LZ-8 FIP-fve FIP-vvo 51 2005 G. applanatum G. boninense G. formosamun G. fornicatum G. lucidum G. microsporum G. neojaponicum G. oerstedii G. resinaceum G. sinense G. tropicum G. tsugae G. valesiacum G. weberianum LZ-8 lz-8 LZ-8 genome walking G. microsporum G. fornicatum gmi gfo-1 gfo-2 lz-8 gmi gfo-1 Pichia pastoris KM71 replz regmi regfo-1 MALDI- TOF 2005 39
300 mg/l BALB/c (dendritic cells, DCs) IL-12 J774A.1 TNF-α T Jurkat cells IL-2reGMI 5 µg/ml DCs IL-12 replz 2005 Pichia pastoris (laccase, 1.10.3.2) (manganese peroxidase, 1.11.1.13) (lignin peroxidase, 1.11.1.14) (Servili et al., 2000) (Leonowicz et al., 2001) (Abadulla et al., 2000) (Mougin et al., 2000) S. cerevisiae S. cerevisiae (Larsson et al., 2001) Li Steffens (Li and Steffens, 2002) 1990 Ko (G. lucidum 7071-10) (isozymes) Galc3 ph3-ph10 (Ko et al., 2001) D'souza LZ-8 ( 2005) 40 2005
Veratryl alcohol 0.2U/ml (D'souza et al., 1999) 26 (intron) G. lucidum G. tsugae G. fornicatum RZ.lac4 0814.lac1 1109.lac1 2121 bp 2019 bp 2110bp 9 intron 520 521 521 21 signal peptide Cysteine Phenylalanine AOX1 1109.lac1 Pichia pastoris KM71 ph 3.0 65 C BMMHY 30 C 0.5 662 607 965 AY450404 (Pleurotus ostreatus ) AY176230 (Polyporous ciliatus lcc3) 36146.lac2 933 974 0814.lac1 AY485825 577 1109.lac1 997 998 1109.lac2 947 RZ.lac2 975 999 RZ-2.lac1 RZ-3.lac1 0815.lac1 997 RZ.lac1 RZ-34a.lac1 995 36291.lac1 1.5K 999 36291.lac2 909 0109.lac1 1000 521 615 989 AY364841 (G.sp.BS-1 lac2) 0109.lac2 977 0705.lac1 AF185275 963 0815.lac2 987 RZ.lac3 RZ.lac4 RS.lac1 974 566 864 976 36146.lac1 999 AY414807 (T. pubescens lap2) AY081188 (T. Versicolr lcc3) AY364840 (G.sp.BS-1 lac1) 0109.lac3 997 36291.lac3 1.5K 0705.lac2 0705.lac3 574 36122.lac2 RS.lac3 2005 41
6.6U/ml 81.7U/mg re1109.lac1 55 C 24 100 2005 1970 1995 Global Industry Analysis 2000 27 21 2004 30 2010 6011.2% 1995 2002 2003 2010 β 2010 (Molecular pharming, biopharming pharming) 80(Aspergillus spp.) (chymosin) B (virus-like particle) (Burns et al, 2005, Chen et al, 2000) (green fluorescent protein) (Hirano et al, 2000) pan7-1 hygromycin Bhph - hygromycin B(1998) 2001 GPD promoter (2001 Sun et al,) 2004 restriction enzyme-mediated integration (2004 Kim et al,) 42 2005
1. 2001 2. 1966 3. 2005 GMI GFO-1 Pichia pastoris 4. 1993. 5. 1990 6. 1998 7. 2005 8. 2003 9. Abadulla E, Tzanov T, Costa S, Robra K.H., Cavaco-Paulo A, Gubitz G.M. 2000. Decolorization and detoxification of textile dyes with a laccase from Trametes hirsuta. Appl Environ Microbiol 66(8):3357-62. 10. Burns, C., K. E. Gregory, M. Kirby, M. K. Cheung, M. Riquelme, T. J. Elliott, M. P. Challen, A. Bailey, Foster G. D. 2005. Efficient GFP expression in the mushrooms Agaricus bisporus and Coprinus cinereus requires introns. Fungal Genet Biol 42:191-9. 11. Chang S.T. 2005. Ganoderma lucidum A prominent source for the healthcare market in the 21th century. Proceedings of the first Symposium on development of China's medicinal fungi industry. 15-27. 12. Chen, X., M. Stone, C. Schlagnhaufer, Romaine C. P. 2000. A fruiting body tissue method for efficient Agrobacterium-mediated transformation of Agaricus bisporus. Appl Environ Microbiol 66:4510-3. 13. D'Souza T.M., Merritt C.S., Reddy C.A. 1999. Lignin-modifying enzymes of the white rot basidiomycete Ganoderma lucidum. Appl Environ Microbiol 65(12):5307-13. 14. Frendscho M.H., Kino, Sone T. and Jardieu P. 1993. Ling Zhi-8:A novel T cell mitogen includes cytokine production and upregulation of ICAM-1 expression. Cell immunol.150,101-133. 15. Hirano, T., T. Sato, K. Yaegashi, Enei H. 2000. Efficient transformation of the edible basidiomycete Lentinus edodes with a vector using a glyceraldehyde-3-phosphate dehydrogenase promoter to hygromycin B resistance. Mol Gen Genet 263:1047-52. 16. Hsu H.C., Hsu C.I., Lin R.H., Kao C.L., Lin J.Y.. 1997. Fip-vvo, a new fungal immunomodulatory protein isolated from Volvariella volvacea. Biochem J 323 (Pt 2):557-65. 17. Hsu H.Y., HUA K.F., Lin C.C., Hsu J., Wong C.H. 2004. Extract of Reishi polysaccharides induces cytokine expression via TLR4-modulated protein kinase signaling pathways. J Immunol. 173(10): 5989-5999. 18. Janusz M.J., Austen K.F. and Czop J.K 1989. Isolation of a yeast heptaglucoside that inhibets monocyte phagocytosis of zymosan particles. J. Immunol. 142: 959-965. 19. Kim S., Song J., Choi H.T. 2004. Genetic transformation and mutant isolation in Ganoderma lucidum by restriction enzymemediated integration. FEMS Microbiology letters 233: 201-204. 20. Kim H.W. and Kim B. K 1999. Biomedicinal triterpenoids of Ganoderma lucidum (Curt.:Fr.)P Karst. (Aphyllophoromycetideae). Intl. J. Med. Mushrooms 1:121-138. 21. Ko E.M., Leem Y.E., Choi H.T. 2001. Purification and characterization of laccase isozymes from the white-rot basidiomycete Ganoderma lucidum. Appl Microbiol Biotechnol 57(1-2):98-102. 2005 43
22. Kino K., Yamsshita A., Yamaoka K., Watanabe J., Tanaka S., Ko K. and Tsunoo H. 1989. Isolation and characterization of a new immunomodulatory protein, Ling Zhi-8(LZ-8),form Ganiderma lucidum. J.Biol. Chem. 264, 472-478. 23. Kino K., Mizumoto K., Sone T., Yamaoka J., Watanabe A., Yamashita K., Yamaoka K., Ko K., Tsunoo H. 1990. An immunomodulatory protein, Ling Zhi-8, prevents insulitis in non-obese diabetic mice. Diabetologia. 33, 713. 24. Ko J.L., Hsu C.I., Lin R.H., Kao C.L., Lin J.Y. 1995. A new fungal immunomodulatory protein, FIP-fve isolated from the edible mushroom, Flammulina velutipes and its complete amino acid sequence. Eur J Biochem 228(2):244-9. 25. Kubota T., Asaka Y., Miura I. and Mori H. 1982. Structures of ganoderic acids A and B, two new lanostane type bitter triterpenes from Ganoderma lucidum(fr.)karst. Helv Chim Acta, 65, 611-619. 26. Larsson S, Cassland P, Jonsson L.J. 2001. Development of a Saccharomyces cerevisiae strain with enhanced resistance to phenolic fermentation inhibitors in lignocellulose hydrolysates by heterologous expression of laccase. Appl Environ Microbiol 67(3):1163-70 27. Leonowicz A, Cho N.S., Luterek J, Wilkolazka A, Wojtas-Wasilewska M, Matuszewska A, Hofrichter M, Wesenberg D, Rogalski J. 2001. Fungal laccase: properties and activity on lignin. J Basic Microbiol 41(3-4):185-227. 28. Lei L.S. and Lin Z.B. 1992. Effect of Ganoderma polysaccharides on T cell subpopulations and production and production of interleukin2 in mixed lymphocyte response. Acta Pharmaceuica Sinica 27(5): 331-335. 29. Lei L.S. and Lin Z.B. 1991. Effect of Ganoderma polysaccharides on the activity of DNA polymerase in -spleen cells stimulated by alloantigens in mice in vitro. T. Beijing Medical University 23(4): 329-333. 30. Li L, Steffens J.C. 2002. Overexpression of polyphenol oxidase in transgenic tomato plants results in enhanced bacterial disease resistance. Planta 215(2):239-47 31. Lieu C.W., Lee S.S. and Wang S.Y. 1992. The effect of Ganoderma lucidum on induction of differentiation in leulsemic U937 cells Anticancer Research 12:1211-1216. 32. Lin Y.L., Liang Y.C., Lee S.S., Chiang B.L. 2005 Polysaccharide purified from Ganoderma lucidum induced activation and maturation of human monocyte-derived dendritic cells by the NF-kappaB and p38 mitogen-activated protein kinase pathways. J Leukoe Biol.78(2):533-543. 33. Miyasaka N., Inoue H., Sone T. and Jardieu P. 1993 Ling Zhi-8:facilitates cellular interaction through modulation of adhesion molecules. Biochem. Biophys. Res. Commun. 186,358-390. 34. Mizuno T., Sakai T. and Chihara G. 1995. Health foods and medicinal usages of mushrooms. Food Review International 11 (1) 69-81. 35. Mougin C, Boyer F.D., Caminade E, Rama R. 2000. Cleavage of the diketonitrile derivative of the herbicide isoxaflutole by extracellular fungal oxidases. J Agric Food Chem 48(10):4529-34. 36. Servili M, DeStefano G, Piacquadio P, Sciancalepore V. 2000. A novel method for removing phenols from grape must. Am. J. Enol. Vitic. 51:357-361. 37. Sun L., Cai H.Q., Xu W.H., Hu Y.L., Gao Y., Lin Z.P. 2001. Efficient transformation of the medicinal mushroom Ganoderma lucidum. Plant Molecular Biology Reporter 19: 383a-383j. 38. van der Hem L.G., van der Vliet J.A., Bocken C.F., Kino K, Hoitsma A.J., Tax W.J. 1995. Ling Zhi-8: studies of a new immunomodulating agent. Transplantation 60(5):438-43. 39. Wang G., Zhang J., Mizuno T., Zhuang C., Ito H., Mayuzumi H., Okamoto H. and Li J. 1993. Antitumor active polysaccharides from the Chinese mushroom Song Shan Lingzhi, the fruiting body of Ganoderma tsugae. Biosci.Biotech. Biochem. 57 (6):894-900. 40. http://www.americamember.org/usa/agriculture.htm 44 2005
(Bacillus subtilis) (Bacillus natto spore) 2000 B 1 B 2 E K 2 2300 754 1286 B1 B2 K2 kcal g g g g mg mg mg mg mg mg mg U/g 180 16 9 7.6 2.1 70 2 1 570 0.22 0.09 41 200 16.5 10 9.8 2.3 90 3.3 2 660 0.07 0.56 870 500 2005 45
1600 100 2 21 1982 E 1995 Angiotension K K SOD K 2 Catalase 1967 KMD1126 1987 B2 1996 0-157 0-157 1 0-157 (LDL) : 1986 K 2 O-157 (Helicobacter pylori) 3 46 2005
angiotensin converting enzyme (ACE) K2 3 200 NHK 4,5 (nattokinase) 12 50 100 1. DNA 275 27728 2. 8.6 0.3 3. ph4 ~12 ph7~9 Nattokinase Enzyme Ralph E. Holsworth: Nattokinase and Cardiovascular Health, http://www.nutrimart.com/pdf/nattoreport.pdf, 2002 (urokinase) 20 1 1600 (FU) (thiol reductant) 6,7 FDATulane 25 74 1,100 1 4 20 50~60 B 6 E K 2 8 2005 47
(reactive oxygen species, ROS) 9 KMD1126 KMD1126 Ehrlich ascites carcinoma (interferon) 30 (edamame therapy) (purine) K 2 (osteoclast calcium) Gla 10 K 2 (coagulation) K 2 K 2 K 2 K 2 11,12 48 2005
13 (probiotics) (endospore) (γ-poly-glutamic acid, γ- PGA) 14,15 - (urokinase) (tissue plasminogen activator, t-pa) (ACE inhibitor) K 2 17,18,19 (100 C) (vegetative cells) D 2005 49
2005 50 2002 (2000-2002) (2002-2004) (2005) (nutraceuticals) Nutrition Pharmaceutical Nutraceutical Science Safety LDL
R(peptides)(glycopeptides) 6 -O-succinyl 19 PPQ (pyrroloquinoline quinone) (Bifidus) (natto micronutrients) (amylase) (Protease) (natural antioxidative factors) 20 Euromonitor 13.5 2006 600 4030 (1998-2004) 1. Zuber, P., M. M. Nakano, and M. A. Marahiel. 1993. Peptide antibiotics, p. 897-916. In A. L. Sonenshein, J. A. Hoch, and R. Losick (ed.), Bacillus subtilis and other gram-positive bacteria: biochemistry, physiology, and molecular genetics. American Society for Microbiology, Washington, D.C. 2. T. Yamashita, E. Oda a, J.C. Giddings, J. Yamamoto: The effect of dietary Bacillus natto productive protein on in vivo endogenous thrombolysis, Pathophysiology of Haemostasis and Thrombosis 2003; 33:138-143. 3. Kudva, I. T., P. S. Evans, N. T. Perna, T. J. Barrett, F. M. Ausubel, F. R. Blattner, and S. B. Calderwood. Strains of Escherichia coli O157:H7 differ primarily by insertions or deletions, not single-nucleotide polymorphisms. J. Bacteriol. 2002; 184:1873-1879. 4. Fujita M, Hong K, Ito Y, Fujii R, Kariya K, Nishimuro S: Thrombolytic effect of nattokinase on a chemically induced thrombosis model in rat. Biol Pharm Bull 1995; 18:1387-1391. 5. Kim W, Choi K, Kim Y, Park H, Choi J, Lee Y, Oh H, Kwon I, Lee S: Purification and characterization of a fibrinolytic enzyme produced from Bacillus sp. strain CK 11-4 screened from Chungkook-Jang. Appl Environ Microbiol 1996; 62: 2482-2488. 2005 51
6. Yamamoto, K. et al. Plasminogen activator inhibitor-1 is a major stress-regulated gene: implications for stress-induced thrombosis in aged individuals. Proceedings of the National Academy of Sciences. 2002; 99(2): 890-895. 7. Urano T, Ihara H, Umemura K, Suzuki Y, Oike M, Akita S, Tsukamoto Y, Suzuki I, Takada A: The profibrinolytic enzyme subtilisin NAT purified from Bacillus subtilis cleaves and inactivates plasminogen activator inhibitor type 1. J Biol. Chem. 2001; 276:24690-24696. 8. Pesce, Noel ; Eyster, Kathleen M.; Williams, John L. ; Wixon, Regina ; Wang, Chunyang ; Martin, Doug S.: Effect of Genistein on Cardiovascular Responses to Angiotensin II in Conscious Unrestrained Rats, Journal of Cardiovascular Pharmacology. 2000; 36(6): 806-809. 9. Iwai K, Nakaya N, Kawasaki Y, Matsue H: Antioxidative functions of natto, a kind of fermented soybeans: Effect on LDL oxidation and lipid metabolism in cholesterol-fed rats. J Agric Food Chem 2002; 50:3597-3601. 10. Kaneki M, Hedges SJ, Hosoi T, et al. Japanese fermented soybean food as the major determinant of the large geographic difference in circulating levels of vitamin K2: possible implications for hip-fracture risk. Nutrition 2001 Apr; 17(4): 315-21. 11. Tsukamoto Y, Ichise H, Kakuda H, Yamaguchi M: Intake of fermented soybean (natto) increases circulating vitamin K 2 (menaquinone-7) and gamma-carboxylated osteocalcin concentration in normal individuals. J Bone Miner Metab 2000; 18/4: 216-222. 12. Katsuyama H, Ideguchi S, Fukunaga M, Saijoh K, Sunami S: Usual dietary intake of fermented soybeans (Natto) is associated with bone mineral density in premenopausal women. J Nutr Sci Vitaminol (Tokyo) 2002; 48/3:207-215. 13. Tomohiro Hosoi, Akio Ametani, Kan Kiuchi, and Shuichi Kaminogawa: Improved growth and viability of lactobacilli in the presence of Bacillus subtilis (natto), catalase, or subtilisin, 2000: Can. J. Microbiol./Rev. can. Microbiol. 46(10): 892-897. 14. Ashiuchi, M., C. Nawa, T. Kamei, J. J. Song, S. P. Hong, M. H. Sung, K. Soda, and H. Misono. 2001. Physiological and biochemical characteristics of poly-γ-glutamate synthetase complex of Bacillus subtilis. Eur. J. Biochem. 268:5321-5328. 15. Ashiuchi, M., and H. Misono. Biochemistry and molecular genetics of poly-γ-glutamate synthesis. Appl. Microbiol. Biotechnol, 2002; 59:9-14. 16. Liu BY, Song HY: Molecular cloning and expression of nattokinase gene in Bacillus subtilis. Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai) 2002; 34: 338-340. 17. Chang CT, Fan MH, Kuo FC, Sung HY: Potent fibrinolytic enzyme from a mutant of Bacillus subtilis IMR-NK1. J Agric Food Chem 2000; 48:3210-3216. 18. Yamaguchi M, Ma Z J. Inhibitory effect of menaquinone-7 (vitamin K 2 ) on osteoclast-like cell formation and osteoclastic bone resorption in rat bone tissues in vitro. Mol Cell Biochem 2001; 228(1-2): 39-47 19. Toda T, Uesugi T, Hirai K, Nukaya H, Tsuji K, Ishida H. New 6-O-acyl isoflavone glycosides from soybeans fermented with Bacillus subtilis (natto). I. 6-O-succinylated isoflavone glycosides and their preventive effects on bone loss in ovariectomized rats fed a calcium-deficient diet. Biol Pharm Bull 1999; 22(11): 1193-2011. 20. Mentor-Marcel R, Lamartiniere CA, Eltoum IA, Greenberg NM, Elgavish A. Dietary genistein improves survival and reduces expression of osteopontin in the prostate of transgenic mice with prostatic adenocarcinoma (TRAMP). 2005: J Nutr; 135(5): 989-95. 52 2005
2001 1 3 (Original Design Manufactures ODM) 2005 cgmp (Small Business Innovation Research SBIR) LP33Aller Relief(Nu Skin) ODM... Q1 A1 Pediatric Allergy and Immunology 2005 53
- Q2 A2 1. 2. 3. 4. DNA PCR DNA API CH50 Q3 A3 600 cgmp LP33 (Lactobacillus paracasei33) 54 2005
396 (ph2.5) (0.3%) CTL Th NK B (helper T) Th1 γ (IFN-γ) B G IgG Th2 IL-4 IL-5 E(IgE) (humoral immunity) Older sibs: many infections (Th1 stimuli) LP33 Th1 No allergies Birth Th2 Allergen exposure GOT Only child: few infections Still Th2 Allergies GTP T Th2 IgE Th1 Th2 LP33 IgE IFN γ (antihistamine) Q4 LP33 A4 2 3 10 20 LP33LP33 IgE LP33 80 60 20 LP33 LP33 IgE IFN γ 2005 55
LP33 Q5 A5 Q6 A6 1. 2. Q7 A7 SBIR cgmp 56 2005
1971 1982 1991 50%2000 1984 G.M.P 1991 1994 1997 995 2001 Q1 A1 3-6 6 2005 57
1.55 % 1.55 % 5.43 % 120 200 90 120 6 12 1997 2001 2004 A00043 T Q2 A2 1998 copy Q3 A3 A00043 2002 2003 2004 (A) 1072 1200 1284 (B) 35.4 30.9 33.4 (C) 152 147 146 (D) 34 33 34 (E) 17 20 20 17 13 14 (B/A) 3.3% 3.15 2.60 (D/C) 22.3% 22.44 23.28 58 2005
Q4 A4 1 2 995 3 2 10 1998 4 50 10 3 2 Antrodia Q5 A5 14% 3% 24% 2001 2002 2003 2004 23,284 31,823 93,346 152,022 300,475 59% 2004 10 2005 59
14 5-6 1/2 93 2/3 Q6 A6 1994 1996 12 WTO Q7 A7 100 300 2 5 20 40 50 200 5 ODM OEM 8 Shaker 14 100L 3 200L 2 300L 1 500L 6-1 60 2005
2 Ton 1 2.5 Ton 1 5 Ton 1 20 Ton 1 40 Ton 1 50 Ton 1 15 2 4-2 2005 61
20 1000 Bacillus subtilis natto 62 2005
Q1 A1(B. subtilis Natto)40 C (Natto- Kinase) (C) (A) (B) (C) (A) (B) Pyrazines Q2 A2 K2 2005 63
PUB Q3 A3 Q4 A4 know-how Q5 A5 Q6 A6 60 Q7 A7 70% Amgen (Epogen)Amgen Amgen 64 2005
Amgen Q8 A8 25% SBIR Q9 25% A9 Q10 A10 Q11 A11 1 Q12 A12 20 Nutrition Business Journal 2005 770 34% 32%25% 21 2005 65
Bt 1000 Gerard Barry Bt AGBIOS.COM 2005/04/16 110 10-12 90% 1960 12000 110 100 350 2006 140-150 20 ISNA Tehran Times 2005/05/17 66 2005
FAO GMO (FAO) (GMOs) Monsanto 90% 650 FAO GM GMOs 115 250 (Consumers International)2000 GM GM 652004 (WFP) GM GMOs GM FAO GMOs Tehran Times 2005/05/17 GM 1997 2000 (GM) T25 Syngenta Bt176 Monsanto ]MON810, Topas 19/2 MS1xRF1 20 GM 1998 2004 AGBIOS BBC News 2005/06/27 2005 67
Frost & Sullivan GI GI (pure glucose)100 2 (GI =100) 2 Frost & Sullivan AGBIOS 2005/09/06 20 30 (luciferrin) (luciferase)(adenosine triphosphate ATP) (bio-luminescence testing method) AGBIOS 2005/09/27 68 2005
Israeli Jaffa Sweetie pomelit Israeli Jaffa Sweetie pomelit pomelit72 43 71 (bypass surgery) 2430 100 pomelit 200 pomelit pomelit (low-density lipoprotein, LDL) (blood albumin) (blood fibrinogen) pomelit pomelit Science Daily AGBIOS 2005 69
4% ITIS 4.6% 2% 2.6% 3% 4% 5.9% WTO 2003 230 2008 370 ITIS IT ERP CRM SCM KM GMP CAS HACCP ISO 9000 94/02/28 1920 zerumbone humulene α-curcumene gingerol 2002 94/03/25 70 2005
94/05/05 7 10 3-4 7-10 6 200 (1 3) -β-d-glucan 3-4 7-10 94/06/02 2005 71
10,256 WTO 2005/06/16 7 1 7 1 19 3 15 94/06/22 72 2005
30 182 30 50 35 100 94/07/09 3000 B 94/07/28 2005 73
60 genistin daidzin 94/08/13 74 2005