The effect of lutein and zeaxanthin supplementation on metabolites of these carotenoids in the serum of persons aged 60 or older.

PURPOSE To investigate the effect of lutein supplementation at doses of 2.5, 5.0, and 10 mg/d for 6 months on distribution of these carotenoids and their metabolites in the serum of elderly human subjects, with and without age-related macular degeneration. To determine whether supplementation with lutein can interact with the serum levels of other dietary carotenoids, retinol, and alpha-tocopherol. METHODS Forty-five subjects received daily supplements of lutein (containing 5% zeaxanthin) for 6 months and were followed up for another 6 months after supplementation. Blood was collected at various intervals and lutein, zeaxanthin, and their metabolites in the sera were quantified by normal-phase high-performance liquid chromatography (HPLC)-UV/visible detection. Other dietary carotenoids, retinol, and alpha-tocopherol were identified and quantified on a C18 reversed phase HPLC column. RESULTS After 6 months of supplementation with 10 mg of lutein, the increases in the mean serum levels from baseline were: 210 to 1000 nM/L (P < 0.0001) for lutein and 56 to 95 nM/L (P < 0.0001) for zeaxanthin. Similarly, the mean concentrations (nM/L) of carotenoid metabolites increased from 49 to 98 (P < 0.0001) for 3-hydroxy-beta,epsilon-caroten-3'-one (3'-oxolutein); 31 to 80 (P < 0.0001) for 3'-hydroxy-epsilon,epsilon-caroten-3-one; and 19 to 25 (P < 0.0001) for epsilon,epsilon-carotene-3,3'-dione. The serum levels of these carotenoids gradually decline within 6 months after supplementation. CONCLUSIONS The increase in the serum levels of lutein/zeaxanthin correlates with increases in the serum levels of their metabolites that have previously been identified in the ocular tissues. Elderly human subjects with and without AMD can safely take supplements of lutein up to 10 mg/d for 6 months with no apparent toxicity or side effects.

[1]  C. Djerassi,et al.  Selective Preparation of Lutein Monomethyl Ethers. , 1966 .

[2]  TECHNICAL PROCEDURES FOR THE SYNTHESIS OF CAROTENOIDS AND RELATED COMPOUNDS FROM 6-OXOISOPHORONE. VII. SYNTHESIS OF RHODOXANTHIN AND (3RS,3′RS)-ZEAXANTHIN FROM THE C15-RING COMPONENT , 1982 .

[3]  E. Widmer,et al.  Technische Verfahren zur Synthese von Carotinoiden und verwandten Verbindungen aus 6‐Oxo‐isophoron. VII. Synthese von Rhodoxanthin und (3RS,3RS)‐Zeaxanthin aus der C15‐Ringkomponente , 1982 .

[4]  Isolation and structural elucidation of the geometrical isomers of lutein and zeaxanthin in extracts from human plasma. , 1992, Journal of chromatography.

[5]  W. Schalch Carotenoids in the retina--a review of their possible role in preventing or limiting damage caused by light and oxygen. , 1992, EXS.

[6]  J. C. Smith,et al.  Separation and identification of carotenoids and their oxidation products in the extracts of human plasma. , 1992, Analytical chemistry.

[7]  R. Bone,et al.  Stereochemistry of the human macular carotenoids. , 1993, Investigative ophthalmology & visual science.

[8]  Antioxidant status and neovascular age-related macular degeneration. Eye Disease Case-Control Study Group. , 1993, Archives of ophthalmology.

[9]  Lawrence A. Yannuzzi,et al.  Dietary Carotenoids, Vitamins A, C, and E, and Advanced Age-Related Macular Degeneration , 1994 .

[10]  R. Klein,et al.  Serum antioxidants and age-related macular degeneration in a population-based case-control study. , 1995, Archives of ophthalmology.

[11]  D M Snodderly,et al.  Evidence for protection against age-related macular degeneration by carotenoids and antioxidant vitamins. , 1995, The American journal of clinical nutrition.

[12]  J. C. Smith,et al.  Lutein, lycopene, and their oxidative metabolites in chemoprevention of cancer , 1995, Journal of cellular biochemistry. Supplement.

[13]  H. Ohigashi,et al.  Food Factors for Cancer Prevention , 1997, Springer Japan.

[14]  F. Khachik,et al.  Identification of lutein and zeaxanthin oxidation products in human and monkey retinas. , 1997, Investigative ophthalmology & visual science.

[15]  J. C. Smith,et al.  Identification, quantification, and relative concentrations of carotenoids and their metabolites in human milk and serum. , 1997, Analytical chemistry.

[16]  F. Khachik,et al.  Bioavailability, Metabolism, and Possible Mechanism of Chemoprevention by Lutein and Lycopene in Humans , 1997 .

[17]  K. E. Sprague,et al.  A one year study of the macular pigment: the effect of 140 days of a lutein supplement. , 1997, Experimental eye research.

[18]  W. Bidlack Phytochemicals : a new paradigm , 1998 .

[19]  F. Khachik,et al.  Partial Synthesis and Structural Elucidation of the Oxidative Metabolites of Lycopene Identified in Tomato Paste, Tomato Juice, and Human Serum , 1998 .

[20]  Isolation and structural elucidation of (13Z,13'Z,3R,3'R,6'R)-lutein from marigold flowers, kale, and human plasma. , 1999, Journal of agricultural and food chemistry.

[21]  R. Klein,et al.  Lutein and zeaxanthin in the diet and serum and their relation to age-related maculopathy in the third national health and nutrition examination survey. , 2001, American journal of epidemiology.

[22]  F. Khachik,et al.  Identification and quantitation of carotenoids and their metabolites in the tissues of the human eye. , 2001, Experimental eye research.

[23]  Da-You Zhao,et al.  Transformations of selected carotenoids in plasma, liver, and ocular tissues of humans and in nonprimate animal models. , 2002, Investigative ophthalmology & visual science.

[24]  R. Bone,et al.  Lutein and zeaxanthin dietary supplements raise macular pigment density and serum concentrations of these carotenoids in humans. , 2003, The Journal of nutrition.

[25]  F. Khachik An efficient conversion of (3R,3'R,6'R)-lutein to (3R,3'S,6'R)-lutein (3'-epilutein) and (3R,3'R)-zeaxanthin. , 2003, Journal of natural products.

[26]  J. Humphries,et al.  Distribution of lutein, zeaxanthin, and related geometrical isomers in fruit, vegetables, wheat, and pasta products. , 2003, Journal of agricultural and food chemistry.

[27]  R. Bone,et al.  Biologic mechanisms of the protective role of lutein and zeaxanthin in the eye. , 2003, Annual review of nutrition.

[28]  G. Barja Free radicals and aging , 2004, Trends in Neurosciences.

[29]  R. Klein,et al.  Causes and prevalence of visual impairment among adults in the United States. , 2004, Archives of ophthalmology.

[30]  S. Beatty,et al.  Plasma and macular responses to lutein supplement in subjects with and without age-related maculopathy: a pilot study. , 2004, Experimental eye research.

[31]  D. Snodderly,et al.  Nutritional manipulation of primate retinas, III: Effects of lutein or zeaxanthin supplementation on adipose tissue and retina of xanthophyll-free monkeys. , 2005, Investigative ophthalmology & visual science.

[32]  F. Ferris,et al.  Dose-ranging study of lutein supplementation in persons aged 60 years or older. , 2006, Investigative ophthalmology & visual science.