The relation between serum lipids and lutein and zeaxanthin in the serum and retina: results from cross-sectional, case-control and case study designs

Lipids in Health and Disease

Richard Roberts³  Melissa Dengler²  Billy R Hammond¹  Lisa M Renzi⁴ 

[1] Vision Sciences Laboratory and Human Biofactors Laboratory, The University of Georgia, 520 Psychology Building, Athens, GA 30602-3013, USA;Vision Sciences Laboratory, The University of Georgia, 501 Psychology Building, Athens, GA 30602-3013, USA;Kemin Health, L.C., 600 E. Court Ave, Suite A, DesMoines, IA 50309, USA;Human Biofactors Laboratory and Vision Sciences Laboratory, The University of Georgia, 601 Psychology Building, Athens, GA 30602-3013, USA

关键词: Zeaxanthin;    Lutein;    Statins;    Lipoproteins;    Macular pigment;   

Others  :  1160343
DOI  :  10.1186/1476-511X-11-33

 received in 2011-11-14, accepted in 2012-02-29,  发布年份 2012

【 摘 要 】

Background

The xanthophyll carotenoids lutein (L) and zeaxanthin (Z) are found in and around the macula of the primate retina, where they are termed macular pigment (MP). Dietary L and Z are absorbed with fat in the gut and transported on lipoproteins to the retina. Both MP and serum lipoproteins have been related to risk for neurodegenerative diseases such as age-related macular degeneration (AMD). L and Z are carried on both HDL (related to reduced risk of AMD) and LDL (related to increased risk). The purpose of this set of studies was to analyze the relation between L and Z in the serum and retina with the circulating lipid profile.

Methods

In all experiments, lipoproteins were measured enzymatically from plasma, and MP optical density (MPOD) was measured using customized heterochromatic flicker photometry. Experiment 1: Relations between serum L and Z, MPOD and lipoprotein levels. 108 young, healthy subjects (M = 23.2, SD = 4.12 years) participated. Lipoprotein levels and MPOD were measured. In a subset of 66 participants, serum L and Z levels were also measured using high-performance liquid chromatography. Experiment 2: Relations between lipoprotein levels and MPOD in statin users. 20 subjects (M = 58.05, SD = 11.08 years) taking statin medication and 20 subjects (M = 57.95, SD = 11.03 years) not taking satin were recruited for participation. MPOD and lipoprotein levels were measured. Experiment 3: lowering lipoprotein levels to impact MPOD. One individual (aged 41 years) with high MP density adhered first to an atorvastatin regimen, then, after a wash-out period, to a rosuvastatin regimen.

Results

Experiment 1: HDL were significantly (p < 0.05) related to MPOD (r = 0.33), to serum L (r = 0.36) and to serum Z (r = 0.26). MPOD was also significantly related to total cholesterol (r = 0.19). Experiment 2: MPOD was not lower in statin users when compared to matched non-statin users, but MPOD decreased significantly with increased duration of statin use (r = −0.63). Experiment 3: Administration of a statin regimen reduced MPOD with atorvastatin (p < 0.05) but not with rosuvastatin.

Conclusions

Serum xanthophylls, retinal xanthophylls and lipoprotein concentrations are significantly related, and changing lipoprotein levels may impact levels of retinal xanthophylls.

【 授权许可】

   
2012 Renzi et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]Maoka T: Recent progress in structural studies of carotenoids in animals and plants. Archives Biochem Biophys 2009, 483(2):191-195.
• [2]Demmig-Adams B, Gilmore AM, Adams WW 3rd: Carotenoids 3: in vivo function of carotenoids in higher plants. The FASEB J: Official Publ Federation Am Soc Exp Biol 1996, 10(4):403-412.
• [3]Vershinin A: Biological functions of carotenoids--diversity and evolution. Biofactors (Oxford, England) 1999, 10(2-3):99-104.
• [4]Namitha KK, Negi PS: Chemistry and biotechnology of carotenoids. Crit Rev Food Sci Nutr 2010, 50(8):728-760.
• [5]Chew BP, Park JS: Carotenoid action on the immune response. The J Nutr 2004, 134(1):257S-261S.
• [6]Handelman GJ: The evolving role of carotenoids in human biochemistry. Nutr (Burbank, Los Angeles County, Calif) 2001, 17(10):818-822.
• [7]Izumi-Nagai K, Nagai N, Ohgami K, Satofuka S, Ozawa Y, Tsubota K, Umezawa K, Ohno S, Oike Y, Ishida S: Macular pigment lutein is antiinflammatory in preventing choroidal neovascularization. Arteriosclerosis, Thrombosis, Vasc Biol 2007, 27(12):2555-2562.
• [8]Krinsky NI: Effects of carotenoids in cellular and animal systems. The Am J Clin Nutr 1991, 53(1 Suppl):238S-246S.
• [9]Krinsky NI: Mechanism of action of biological antioxidants. Proc Soc Exp Biol Med Soc Expe Biol Med (New York, NY) 1992, 200(2):248-254.
• [10]Renzi LM, Hammond BR Jr: The relation between the macular carotenoids, lutein and zeaxanthin, and temporal vision. Ophthalmic & Physiological Optics: The J British Coll Ophthalmic Opticians (Optometrists) 2010, 30(4):351-357.
• [11]Schmitz HH, Poor CL, Wellman RB, Erdman JW: Concentrations of selected carotenoids and vitamin A in human liver, kidney and lung tissue. J Nutr 1991, 121:1613-1621.
• [12]Yeum KJ, Shang FM, Schalch WM, Russell RM, Taylor A: Fat-soluble nutrient concentrations in different layers of human cataractous lens. Curr Eye Res 1999, 19(6):502-505.
• [13]Yeum KJ, Taylor A, Tang G, Russell RM: Measurement of carotenoids, retinoids, and tocopherols in human lenses. Invest Ophthalmol Vis Sci 1995, 36(13):2756-2761.
• [14]Bone RA, Landrum JT, Tarsis SL: Preliminary identification of the human macular pigment. Vision Res 1985, 25(11):1531-1535.
• [15]Bone RA, Landrum JT, Friedes LM, Gomez CM, Kilburn MD, Menendez E, Vidal I, Wang W: Distribution of lutein and zeaxanthin stereoisomers in the human retina. Exp Eye Res 1997, 64(2):211-218.
• [16]Bone RA, Landrum JT, Mayne ST, Gomez CM, Tibor SE, Twaroska EE: Macular pigment in donor eyes with and without AMD: a case-control study. Investigative Ophthalmol Vis Sci 2001, 42(1):235-240.
• [17]Beatty S, Murray IJ, Henson DB, Carden D, Koh H, Boulton ME: Macular pigment and risk for age-related macular degeneration in subjects from a Northern European population. Investigative Ophthalmol Vis Sci 2001, 42(2):439-446.
• [18]Falsini B, Piccardi M, Iarossi G, Fadda A, Merendino E, Valentini P: Influence of short-term antioxidant supplementation on macular function in age-related maculopathy: a pilot study including electrophysiologic assessment. Ophthalmology 2003, 110(1):51-60.
• [19]Richer S, Stiles W, Statkute L, Pulido J, Frankowski J, Rudy D, Pei K, Tsipursky M, Nyland J: Double-masked, placebo-controlled, randomized trial of lutein and antioxidant supplementation in the intervention of atrophic age-related macular degeneration: the Veterans LAST study (Lutein Antioxidant Supplementation Trial). Optometry (St Louis, Mo) 2004, 75(4):216-230.
• [20]Cangemi FE: TOZAL Study: an open case control study of an oral antioxidant and omega-3 supplement for dry AMD. BMC Ophthalmol 2007, 7:3-3. BioMed Central Full Text
• [21]Klaver CC, Ott A, Hofman A, Assink JJ, Breteler MM, de Jong PT: Is age-related maculopathy associated with Alzheimer's Disease? The Rotterdam Study. Am J Epidemiol 1999, 150(9):963-968.
• [22]Johnson LV, Leitner WP, Rivest AJ, Staples MK, Radeke MJ, Anderson DH: The Alzheimer's A beta -peptide is deposited at sites of complement activation in pathologic deposits associated with aging and age-related macular degeneration. Proc Natl Acad Sci USA 2002, 99(18):11830-11835.
• [23]Dentchev T, Milam AH, Lee VMY, Trojanowski JQ, Dunaief JL: Amyloid-beta is found in drusen from some age-related macular degeneration retinas, but not in drusen from normal retinas. Mol Vis 2003, 9:184-190.
• [24]Delcourt C, Michel F, Colvez A, Lacroux A, Delage M, Vernet MH: Associations of cardiovascular disease and its risk factors with age-related macular degeneration: the POLA study. Ophthalmic Epidemiol 2001, 8(4):237-249.
• [25]Hyman L, Schachat AP, He Q, Leske MC: Hypertension, cardiovascular disease, and age-related macular degeneration. Age-Related Macular Degeneration Risk Factors Study Group. Archives Ophthalmol 2000, 118(3):351-358.
• [26]Snow KK, Seddon JM: Do age-related macular degeneration and cardiovascular disease share common antecedents? Ophthalmic Epidemiol 1999, 6(2):125-143.
• [27]Tan JSL, Mitchell P, Smith W, Wang JJ: Cardiovascular risk factors and the long-term incidence of age-related macular degeneration: the Blue Mountains Eye Study. Ophthalmology 2007, 114(6):1143-1150.
• [28]Sun C, Klein R, Wong TY: Age-related macular degeneration and risk of coronary heart disease and stroke: the Cardiovascular Health Study. Ophthalmology 2009, 116(10):1913-1919.
• [29]Wong TY, Tikellis G, Sun C, Klein R, Couper DJ, Sharrett AR: Age-related macular degeneration and risk of coronary heart disease: the Atherosclerosis Risk in Communities Study. Ophthalmology 2007, 114(1):86-91.
• [30]Nowak M, Swietochowska E, Marek B, Szapska B, Wielkoszynski T, Kos-Kudla B, Karpe J, Kajdaniuk D, Sieminska L, Glogowska-Szelag J, et al.: Changes in lipid metabolism in women with age-related macular degeneration. Clin Exp Med 2005, 4(4):183-187.
• [31]Reynolds R, Rosner B, Seddon JM: Serum lipid biomarkers and hepatic lipase gene associations with age-related macular degeneration. Ophthalmology 2010, 117(10):1989-1995.
• [32]Sabbagh M, Zahiri HR, Ceimo J, Cooper K, Gaul W, Connor D, Sparks DL: Is there a characteristic lipid profile in Alzheimer's disease. J Alzheimer's Disease: JAD 2004, 6(6):585-589.
• [33]Cagnin A, Zambon A, Zarantonello G, Vianello D, Marchiori M, Mercurio D, Miccichè F, Ermani M, Leon A, Battistin L: Serum lipoprotein profile and APOE genotype in Alzheimer's disease. J Neural Transmission Supplementum 2007, 72:175-179.
• [34]Chakravarthy U, Wong TY, Fletcher A, Piault E, Evans C, Zlateva G, Buggage R, Pleil A, Mitchell P: Clinical risk factors for age-related macular degeneration: a systematic review and meta-analysis. BMC Ophthalmol 2010, 10:31-31. BioMed Central Full Text
• [35]Tomany SC, Wang JJ, Van Leeuwen R, Klein R, Mitchell P, Vingerling JR, Klein BEK, Smith W, De Jong PTVM: Risk factors for incident age-related macular degeneration: pooled findings from 3 continents. Ophthalmology 2004, 111(7):1280-1287.
• [36]Wang W, Shinto L, Connor WE, Quinn JF: Nutritional biomarkers in Alzheimer's disease: the association between carotenoids, n-3 fatty acids, and dementia severity. J Alzheimer's Dis: JAD 2008, 13(1):31-38.
• [37]Rinaldi P, Polidori MC, Metastasio A, Mariani E, Mattioli P, Cherubini A, Catani M, Cecchetti R, Senin U, Mecocci P: Plasma antioxidants are similarly depleted in mild cognitive impairment and in Alzheimer's disease. Neurobiol Aging 2003, 24(7):915-919.
• [38]Lidebjer C, Leanderson P, Ernerudh J, Jonasson L: Low plasma levels of oxygenated carotenoids in patients with coronary artery disease. Nutr, Metab, Cardiovasc Dis: NMCD 2007, 17(6):448-456.
• [39]Moeller SM, Parekh N, Tinker L, Ritenbaugh C, Blodi B, Wallace RB, Mares JA: Associations between intermediate age-related macular degeneration and lutein and zeaxanthin in the Carotenoids in Age-related Eye Disease Study (CAREDS): ancillary study of the Women's Health Initiative. Archives Ophthalmol 2006, 124(8):1151-1162.
• [40]SanGiovanni JP, Chew EY, Clemons TE, Ferris FL, 3 rd, Gensler G, Lindblad AS, Milton RC, Seddon JM, Sperduto RD: The relationship of dietary carotenoid and vitamin A, E, and C intake with age-related macular degeneration in a case-control study: AREDS Report No. 22. Archives Ophthalmol 2007, 125(9):1225-1232.
• [41]Tan JSL, Wang JJ, Flood V, Rochtchina E, Smith W, Mitchell P: Dietary antioxidants and the long-term incidence of age-related macular degeneration: the Blue Mountains Eye Study. Ophthalmology 2008, 115(2):334-341.
• [42]Michikawa T, Ishida S, Nishiwaki Y, Kikuchi Y, Tsuboi T, Hosoda K, Ishigami A, Iwasawa S, Nakano M, Takebayashi T: Serum antioxidants and age-related macular degeneration among older Japanese. Asia Pacific J Clin Nutr 2009, 18(1):1-7.
• [43]Parker RS: Absorption, metabolism, and transport of carotenoids. The FASEB J: Official Publ Federation Am Soc Exp Biol 1996, 10(5):542-551.
• [44]Goulinet S, Chapman MJ: Plasma LDL and HDL subspecies are heterogenous in particle content of tocopherols and oxygenated and hydrocarbon carotenoids. Relevance to oxidative resistance and atherogenesis. Arteriosclerosis, Thrombosis, Vasc Biol 1997, 17(4):786-796.
• [45]Wang W, Connor SL, Johnson EJ, Klein ML, Hughes S, Connor WE: Effect of dietary lutein and zeaxanthin on plasma carotenoids and their transport in lipoproteins in age-related macular degeneration. The Am J Clin Nutr 2007, 85(3):762-769.
• [46]Gross M, Yu X, Hannan P, Prouty C, Jacobs DR Jr: Lipid standardization of serum fat-soluble antioxidant concentrations: the YALTA study. The Am J Clin Nutr 2003, 77(2):458-466.
• [47]Wooten BR, Hammond BR Jr, Land RI, Snodderly DM: A practical method for measuring macular pigment optical density. Investigative Ophthalmol & Vis Sci 1999, 40(11):2481-2489.
• [48]Vine AK, Stader J, Branham K, Musch DC, Swaroop A: Biomarkers of cardiovascular disease as risk factors for age-related macular degeneration. Ophthalmology 2005, 112(12):2076-2080.
• [49]Broekmans WMR, Berendschot TTJM, Klöpping-Ketelaars IAA, de Vries AJ, Goldbohm RA, Tijburg LBM, Kardinaal AFM, van Poppel G: Macular pigment density in relation to serum and adipose tissue concentrations of lutein and serum concentrations of zeaxanthin. The Am J Clin Nutr 2002, 76(3):595-603.
• [50]Gruber M, Chappell R, Millen A, LaRowe T, Moeller SM, Iannaccone A, Kritchevsky SB, Mares J: Correlates of serum lutein + zeaxanthin: findings from the Third National Health and Nutrition Examination Survey. The J Nutr 2004, 134(9):2387-2394.
• [51]Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report Circulation 2002, 106(25):3143-3421.
• [52]Hammond BR Jr, Wooten BR, Snodderly DM: Cigarette smoking and retinal carotenoids: implications for age-related macular degeneration. Vis Res 1996, 36(18):3003-3009.
• [53]Kirby ML, Beatty S, Loane E, Akkali MC, Connolly EE, Stack J, Nolan JM: A central dip in the macular pigment spatial profile is associated with age and smoking. Investigative Ophthalmol Vis Sci 2010, 51(12):6722-6728.
• [54]Loane E, Nolan JM, Beatty S: The respective relationships between lipoprotein profile, macular pigment optical density, and serum concentrations of lutein and zeaxanthin. Investigative Ophthalmol Vis Sci 2010, 51(11):5897-5905.
• [55]Saheki A, Terasaki T, Tamai I, Tsuji A: In vivo and in vitro blood-brain barrier transport of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors. Pharmaceutical Res 1994, 11(2):305-311.
• [56]Panz VR, Raal FJ, Paiker J, Immelman R, Miles H: Performance of the CardioChek PA and Cholestech LDX point-of-care analysers compared to clinical diagnostic laboratory methods for the measurement of lipids. Cardiovasc J South Africa: Official J Southern Africa Cardiac Soc [And] South African Soc Cardiac Practitioners 2005, 16(2):112-117.
• [57]Santee J: Accuracy and precision of the Cholestech LDX System in monitoring blood lipid levels. Am J Health-System Pharmacy: AJHP: Official J The Am Soc Health-System Pharmacists 2002, 59(18):1774-1779.
• [58]Hartmann D, Thürmann PA, Spitzer V, Schalch W, Manner B, Cohn W: Plasma kinetics of zeaxanthin and 3'-dehydro-lutein after multiple oral doses of synthetic zeaxanthin. The Am J Clin Nutr 2004, 79(3):410-417.
• [59]Burke JD, Curran-Celentano J, Wenzel AJ: Diet and Serum carotenoid concentrations affect macular pigment optical density in adults 45 years and older. The J Nutr 2005, 135(5):1208-1214.
• [60]Stringham JM, Hammond BR, Nolan JM, Wooten BR, Mammen A, Smollon W, Snodderly DM: The utility of using customized heterochromatic flicker photometry (cHFP) to measure macular pigment in patients with age-related macular degeneration. Exp Eye Res 2008, 87(5):445-453.
• [61]Hammond BR Jr, Wooten BR, Smollon B: Assessment of the validity of in vivo methods of measuring human macular pigment optical density. Optometry Vis Sci: Official Publ Am Acad Optometry 2005, 82(5):387-404.
• [62]Thomson LR, Toyoda Y, Langner A, Delori FC, Garnett KM, et al.: Elevated retinal zeaxanthin an prevention of light-induced photoreceptor cell death in quail. Investigative Ophthalmol Vis Sci 2002, 43(11):3538-3549.
• [63]Connor WE, Duell PB, Kean R, Wang Y: The prime role of HDL to transport lutein into the retina: evidence from HDL-deficient WHAM chicks having a mutant ABCA1 transporter. Investigative Ophthalmol Vis Sci 2007, 48(9):4226-4231.
• [64]Vishwanathan R, Goodrow-Kotyla EF, Wooten BR, Wilson TA, Nicolosi RJ: Consumption of 2 and 4 egg yolks/d for 5 wk increases macular pigment concentrations in older adults with low macular pigment taking cholesterol-lowering statins. The Am J Clin Nutr 2009, 90(5):1272-1279.