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280 89 2014 11 AREDS I AREDS I AMD AREDS I AMD AMD AREDS I DHA EPA AMD AREDS II 2006-2012 1 2 AREDS II GRAS Generally Recognized as a Safe FAO/WHO JECFA 1 2 mg/kg 2006 OSL Observed Safety Level 20 mg/ 3 C40H56O2 568.87 2 Eye Disease Case-Control Study EDCCS 1986 1990 / 6 mg/ AMD 43 AMD Lutein Antioxidant Supplementation Trial LAST 1999 2001 2 AMD 90 MPOD Macular Pigment Optical Density Age-Related Eye Disease Study1 AREDS1 AMD Tagetes erecta Linne 80-3 LCPFA

5 6 6 2015 281 AREDS1 1 4 4 / 10 mg/ 2 mg/ -3 LCPFA 1 g/ / 3 AREDS1 3 AMD AMD AREDS II 2006 3 4 AREDS1 4000 AMD 1 2 AREDS II AREDS1 AREDS1 - - - - 4203 55-80 74 AMD 3 4 1 5 2006-2012 82 89 Centrum Silver 0.275mg AREDS DHA EPA 2 AREDS AREDS AMD 25 0.013 3 AMD AMD / DHA EPA AREDS1 AMD AREDS - AREDS AMD AREDS 3 AMD AREDS 3 AMD 25 1 AMD

282 89 3 AREDS / AREDS / DHA/ EPA AREDS DHA/EPA AREDS / AREDS AMD 10 AREDS DHA/EPA AMD AREDS AMD 26HR 0.74 P 0.01 1 32 30 36 - vs. / - AREDS / - AREDS AREDS - 2 3

5 6 6 2015 283 1 O2 3 O2 3 3 8-11 1 12-14 2 15 4 / AMD 18HR 0.82 p 0.02 4 AREDS FGL / AREDS AMD 10 AREDS II 10 mg/ 2 mg 1 AREDS II C 500 mg E 400 IU / 10 mg/2 mg 80 mg 2 mg 10 2 2 1 O2 3 4-7 2 16 3- - --3-3 - 17 18 19 StARD3 20 GSTP1 S- Pi GSTP1 21 StARD3 400-500 nm 446 nm 22 ROS 23 24

284 89 25-27 in vitro in vivo AMD / ips 1 AMD Key Words AREDS II (Age-Related Eye Diseases Study II), AMD (Age-Related Macular Degeneration), Randomized Clinical Trial, Lutein, Zeaxantin 1 The General Incorporated Association of International Foods & Nutrition (AIFN) Chief Executive Of cer 2 Kemin Japan KK Representative Director Kazuo Sueki 1, Masafumi Hashimoto 2 1 AIFN 2 1 2 27.1.7 1 Chew E, Age-Related Eye Diseases Study II Research Group. AREDS II. Retina, Subspecialty Day 5-6, 2005. 2 http://www.nei.nih.gov/neitrials/viewstudyweb.aspx?id=120. Clinical Studies Database. Age Related Eye Diseases Study II (AREDS II). Last update 2/3/2006. pp. 1-6. 3 Alves-Rodrigues A, Shao A (2004) The Science Behind Lutein, Toxicol Lett 150, 57-83 4 Stahl W, Sies H (2003) Antioxidant activity of carotenoids. Mol Aspect Med 24, 345-351 5 Semba RD, Dagnelie G (2003) Are lutein and zeaxanthin conditionally essential nutrients for eye health? Med Hypotheses 61, 465-472 6 Stahl W, Sies H (2005) Bioactivity and protective effects of natural carotenoids. Biochim Biophys Acta 1740, 101-107 7 De Spirt S, Lutter K, Stahl W (2010) Carotenoids in photooxidative stress. Curr Nutr Food Sci 6, 36-43 8 Semba RD, Dagelie G (2003) Are lutein and zeaxanthin conditionally essential nutrients for eye health? Med Hypotheses 61, 465-472 9 Stahl W, Sies H (2005) Bioactivity and protective effects of natural carotenoids. Biochim Biophys Acta 1740, 101-107 10 De Spirt S, Lutter K, Stahl W (2010) Carotenoids in photooxidative stress. Curr Nutr Food Sci 6, 36-43 11 Stahl W, Sies H (2003) Antioxidant activity of carotenoids. Mol Aspects Med 24, 345-351 12 Stahl W, Sies H (2005) Bioactivity and protective effects of natural carotenoids. Biochim Biophys Acta 1740, 101-107 13 Stahl W, Sies H (2003) Antioxidant activity of carotenoids. Mol Aspects Med 24, 345-351 14 Kim SR, Nalanishi K, Itagaki Y, Sparrow JR (2006) Photooxidation of A2-PE, a photoreceptor outer segment fluorophore, and protection by lutein and zeaxanthin. Exp Eye Res 82, 828-839 15 Thammanina GSS, Dinesha R, Harsha R, Srinivas L (2010) Free radical scavenging activity of lutein - isolated from methi leaves (Trigonella foenum graecum). Int J Pharm Pharm Sci 2, 113-117 16 Trevithick-Sutton CC, Foote CS, Collins M, Trevthick JR (2006) The retinal carotenoids zeaxanthin and lutein scavenge superoxide and hydroxyl radicals: A chemiluminescence and ESR study. Mol Vis 12, 1127-1135 17 Landrum JT, Bone RA (2001) Lutein, zeaxanthin, and the macular pigment. Arch Biochem Biophys 385, 28-40 18 Khachik F, Bernstein PS, Garland DL (1997) Identi cation of lutein and zeaxanthin oxidation products in human and monkey retinas. Invest Ophthalmol Vis Sci 38, 1802-1811 20 Li B, Vachali P, Berstein PS. (2010) Human ocular carotenoidbinding proteins. Photochem Photobiol Sci 9, 1418-1425 21 Bhosale P, Berstein PS (2005) Synergistic effects of zeaxanthin and its binding protein in the prevention of lipid membrane oxidation. Biochim Biophys Acta 1740, 116-121 22 SnoeeerlyDM, Brown PK, Delori FC, Auran JD (1984) The macular pigment. I. Absorbance spectra, localization, and discrimination from other yellow pigments in primate retinas. Invest Ophthalmol Vis Sci 25, 660-673 23 Krinsky NI, Landrum JT, Bone RA. (2003) Biologic mechanisms of the protective role of lutein and zeaxanthin in the eye. Ann Rev Nutr 23, 171-201 24 Semba RD, Dagnelie G (2003) Are lutein and zeaxanthin condi-

5 6 6 2015 285 tionally essential nutrients for eye health? Med Hypotheses 61, 465-472 25 Krinsky NI, Landrum JT, Bone RA (2003) Biologic mechanisms of the protective role of lutein and zeaxanthin in the eye. Ann Rev Nutr 23, 171-201 26 Stahl W, Sies H (2003) Antioxidant activity of carotenoids. Mol Aspects Med 24, 345-351 27 Kim SR, Nakanishi K, Itagaki Y, Sparrow JR (2006) Photooxidation of A2-PE, a photoreceptor outer segment fluorophore, and protection by lutein and zeaxanthin. Exp Rye Res 82, 828-839