Serum levels of macular carotenoids in relation to age-related maculopathy

The Muenster Aging and Retina Study (MARS)
  • Burkhard Dasch
  • Andrea Fuhs
  • Joachim Schmidt
  • Thomas Behrens
  • Astrid Meister
  • Juergen Wellmann
  • Manfred Fobker
  • Daniel Pauleikhoff
  • Hans-Werner Hense
Clinical Investigation

Abstract

Background

It has been hypothesized that the macular carotenoids, lutein and zeaxanthin, may protect against age-related maculopathy. We evaluated the association between blood concentrations of lutein (L) and zeaxanthin (Z) and age-related maculopathy (ARM) in a case-control analysis of the baseline examination of the Muenster Ageing and Retina Study (MARS).

Methods

Of the 1060 participants aged 59–82 years at baseline, 910 (85.9%) with bilateral gradable fundus photographs and complete data for the carotenoids and potential confounders were included. The Rotterdam classification system was used for definition of ARM stages. Multivariate linear regression methods were applied to model the relationship between macular carotenoids and the presence of ARM.

Results

The participants’ mean age was 70.9+5.5 years, 59.9% were female, 20.8% had a normal bilateral fundus, and 48.5% showed signs of early ARM (uni- or bilateral) and 30.7% of late ARM (in at least one eye). In study participants with L and/or Z supplementation (15.6%), the median serum levels for L (Z) were approximately 2 times (1.5 times) higher than in subjects with no supplementation. After exclusion of subjects with L and/or Z supplementation, no statistically significant bivariate relationship was observed between the serum levels of L or Z and the presence of ARM. Multivariate regression models, adjusting for age, gender, smoking, body-mass index, and HDL-cholesterol blood levels, produced adjusted mean serum levels of 0.124, 0.112, and 0.131 μg/ml for L and 0.019, 0.020, and 0.022 μg/ml for Z in subjects with normal fundus, early ARM, and late ARM, respectively.

Conclusion

In this large study, the serum concentrations of L and Z were not related to the prevalence of ARM. However, the large proportion of study participants taking L and/or Z supplementation may have affected these results.

Keywords

Age-related maculopathy Age-related macular degeneration Macular carotenoids Lutein Zeaxanthin 

Notes

Acknowledgements

The study was supported by Deutsche Forschungsgemeinschaft grants HE 2293/5-1 and 2293/5-2, the ProRetina foundation and the IMF fund of the University of Muenster. We thank Ada Hooghart and Corina Brussee from the Rotterdam Study team for enthusiastically supporting our efforts to achieve a high quality of fundus grading.

References

  1. 1.
    Age-Related Eye Disease Study Research Group (2001) A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol 119:1417–1436Google Scholar
  2. 2.
    Beatty S, Boulton M, Henson D, Koh HH, Murray IJ (1999) Macular pigment and age related macular degeneration. Br J Ophthalmol 83:867–877PubMedGoogle Scholar
  3. 3.
    Beatty S, Koh HH, Henson D, Boulton M (2000) The role of oxidative stress in the pathogeneseis of age-related macular degeneration. Surv Ophthalmol 45:115–134CrossRefPubMedGoogle Scholar
  4. 4.
    Beatty S, Murray IJ, Henson DB, Carden D, Koh H, Boulton ME (2001) Macular pigment and risk for age-related macular degeneration in subjects from a Northern European population. Invest Ophthalmol Vis Sci 42:439–446PubMedGoogle Scholar
  5. 5.
    Beatty S, Nolan J, Kavanagh H, O’Donovan O (2004) Macular pigment optical density and its relationship with serum and dietary levels of lutein and zeaxanthin. Arch Biochem Biophys 430:70–76CrossRefPubMedGoogle Scholar
  6. 6.
    Berendschot TT, Goldbohm RA, Klopping WA, van-de-Kraats J, van-Norel J, van-Norren D (2000) Influence of lutein supplementation on macular pigment, assessed with two objective techniques. Invest Ophthalmol Vis Sci 41:3322–3326PubMedGoogle Scholar
  7. 7.
    Bhosale P, Larson AJ, Frederick JM, Southwick K, Thulin CD, Bernstein PS (2004) Identification and characterization of a Pi Isoform of glutathione S-transferase (GSTP1) as a zeaxanthin-binding protein in the macula of the human eye. J Biol Chem 279(47):49447–49454CrossRefPubMedGoogle Scholar
  8. 8.
    Bird AC, Bressler NM, Bressler SB, Chisholm IH, Coscas G, Davis MD, de Jong PT, Klaver CC, Klein BE, Klein R, et al (1995) An international classification and grading system for age- related maculopathy and age-related macular degeneration. The International ARM Epidemiological Study Group. Surv Ophthalmol 39:367–374PubMedCrossRefGoogle Scholar
  9. 9.
    Bone RA, Landrum JT, Dixon Z, Chen Y, Llerena CM (2000) Lutein and zeaxanthin in the eyes, serum and diet of human subjects. Exp Eye Res 71:239–245CrossRefPubMedGoogle Scholar
  10. 10.
    Bone RA, Landrum JT, Fernandez L, Tarsis SL (1988) Analysis of the macular pigment by HPLC: retinal distribution and age study. Invest Ophthalmol Vis Sci 29:843–849PubMedGoogle Scholar
  11. 11.
    Bone RA, Landrum JT, Mayne ST, Gomez CM, Tibor SE, Twaroska EE (2001) Macular pigment in donor eyes with and without AMD: a case-control study. Invest Ophthalmol Vis Sci 42:235–240PubMedGoogle Scholar
  12. 12.
    Broekmans WM, Berendschot TT, Klopping-Ketelaars IA, de Vries AJ, Goldbohm RA, Tijburg LB, Kardinaal AF, van Poppel G (2002) Macular pigment density in relation to serum and adipose tissue concentrations of lutein and serum concentrations of zeaxanthin. Am J Clin Nutr 76:595–603PubMedGoogle Scholar
  13. 13.
    Cho E, Seddon JM, Rosner B, Willett WC, Hankinson SE (2004) Prospective study of intake of fruits, vegetables, vitamins, and carotenoids and risk of age-related maculopathy. Arch Ophthalmol 122:883–892CrossRefPubMedGoogle Scholar
  14. 14.
    Clevidence BA, Bieri JG (1993) Association of carotenoids with human plasma lipoproteins. Methods Enzymol 214:33–46PubMedCrossRefGoogle Scholar
  15. 15.
    Cruickshanks KJ, Klein R, Klein BE (1993) Sunlight and age-related macular degeneration. The Beaver Dam Eye Study. Arch Ophthalmol 111:514–518PubMedGoogle Scholar
  16. 16.
    Dachtler M, Glaser T, Kohler K, Albert K (2001) Combined HPLC-MS and HPLC-NMR on-line coupling for the separation and determination of lutein and zeaxanthin stereoisomers in spinach and in retina. Anal Chem 73:667–674CrossRefPubMedGoogle Scholar
  17. 17.
    Davies NP, Morland AB (2004) Macular pigments: their characteristics and putative role. Prog Retin Eye Res 23:533–559CrossRefPubMedGoogle Scholar
  18. 18.
    Flood V, Smith W, Wang JJ, Manzi F, Webb K, Mitchell P (2002) Dietary antioxidant intake and incidence of early age-related maculopathy: the Blue Mountains Eye Study. Ophthalmology 109:2272–2278CrossRefPubMedGoogle Scholar
  19. 19.
    Gale CR, Hall NF, Phillips DI, Martyn CN (2003) Lutein and zeaxanthin status and risk of age-related macular degeneration. Invest Ophthalmol Vis Sci 44:2461–2465CrossRefPubMedGoogle Scholar
  20. 20.
    Gruber M, Chappell R, Millen A, LaRowe T, Moeller SM, Iannaccone A, Kritchevsky SB, Mares J (2004) Correlates of serum lutein + zeaxanthin: findings from the Third National Health and Nutrition Examination Survey. J Nutr 134:2387–2394PubMedGoogle Scholar
  21. 21.
    Hammond BR Jr, Ciulla TA, Snodderly DM (2002) Macular pigment density is reduced in obese subjects. Invest Ophthalmol Vis Sci 43:47–50PubMedGoogle Scholar
  22. 22.
    Hammond BR Jr, Curran Celentano J, Judd S, Fuld K, Krinsky NI, Wooten BR, Snodderly DM (1996) Sex differences in macular pigment optical density: relation to plasma carotenoid concentrations and dietary patterns. Vision Res 36:2001–2012CrossRefPubMedGoogle Scholar
  23. 23.
    Hammond BR Jr, Wooten BR, Snodderly DM (1996) Cigarette smoking and retinal carotenoids: implications for age- related macular degeneration. Vision Res 36:3003–3009CrossRefPubMedGoogle Scholar
  24. 24.
    Klein R, Klein BE, Tomany SC, Meuer SM, Huang GH (2002) Ten-year incidence and progression of age-related maculopathy: The Beaver Dam eye study. Ophthalmology 109:1767–1779CrossRefPubMedGoogle Scholar
  25. 25.
    Landrum JT, Bone RA (2001) Lutein, zeaxanthin, and the macular pigment. Arch Biochem Biophys 385:28–40CrossRefPubMedGoogle Scholar
  26. 26.
    Landrum JT, Bone RA, Joa H, Kilburn MD, Moore LL, Sprague KE (1997) A one year study of the macular pigment: the effect of 140 days of a lutein supplement. Exp Eye Res 65:57–62CrossRefPubMedGoogle Scholar
  27. 27.
    Mangione CM, Lee PP, Gutierrez PR, Spritzer K, Berry S, Hays RD (2001) Development of the 25-item National Eye Institute Visual Function Questionnaire. Arch Ophthalmol 119:1050–1058PubMedGoogle Scholar
  28. 28.
    Mares Perlman JA, Brady WE, Klein R, Klein BE, Bowen P, Stacewicz Sapuntzakis M, Palta M (1995) Serum antioxidants and age-related macular degeneration in a population-based case-control study. Arch Ophthalmol 113:1518–1523PubMedGoogle Scholar
  29. 29.
    Mares Perlman JA, Klein R, Klein BE, Greger JL, Brady WE, Palta M, Ritter LL (1996) Association of zinc and antioxidant nutrients with age-related maculopathy. Arch Ophthalmol 114:991–997PubMedGoogle Scholar
  30. 30.
    Mares-Perlman JA, Fisher AI, Klein R, Palta M, Block G, Millen AE, Wright JD (2001) Lutein and zeaxanthin in the diet and serum and their relation to age-related maculopathy in the third national health and nutrition examination survey. Am J Epidemiol 153:424–432CrossRefPubMedGoogle Scholar
  31. 31.
    Mitchell P, Wang JJ, Foran S, Smith W (2002) Five-year incidence of age-related maculopathy lesions: the Blue Mountains Eye Study. Ophthalmology 109:1092–1097CrossRefPubMedGoogle Scholar
  32. 32.
    Noell WK, Walker VS, Kang BS, Berman S (1966) Retinal damage by light in rats. Invest Ophthalmol 5:450–473PubMedGoogle Scholar
  33. 33.
    Seddon JM, Ajani UA, Sperduto RD, Hiller R, Blair N, Burton TC, Farber MD, Gragoudas ES, Haller J, Miller DT, et al (1994) Dietary carotenoids, vitamins A, C, and E, and advanced age- related macular degeneration. Eye Disease Case-Control Study Group. JAMA 272:1413–1420CrossRefPubMedGoogle Scholar
  34. 34.
    Semba RD, Dagnelie G (2003) Are lutein and zeaxanthin conditionally essential nutrients for eye health? Med Hypotheses 61:465–472CrossRefPubMedGoogle Scholar
  35. 35.
    Smith W, Assink J, Klein R, Mitchell P, Klaver CC, Klein BE, Hofman A, Jensen S, Wang JJ, de Jong PT (2001) Risk factors for age-related macular degeneration: pooled findings from three continents. Ophthalmology 108:697–704CrossRefPubMedGoogle Scholar
  36. 36.
    Snellen EL, Verbeek AL, Van Den Hoogen GW, Cruysberg JR, Hoyng CB (2002) Neovascular age-related macular degeneration and its relationship to antioxidant intake. Acta Ophthalmol Scand 80:368–371PubMedCrossRefGoogle Scholar
  37. 37.
    Snodderly DM, 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 25:660–673PubMedGoogle Scholar
  38. 38.
    Taylor HR, West S, Munoz B, Rosenthal FS, Bressler SB, Bressler NM (1992) The long-term effects of visible light on the eye. Arch Ophthalmol 110:99–104PubMedGoogle Scholar
  39. 39.
    The Eye Disease Case-Control Study Group (1992) Risk factors for neovascular age-related macular degeneration. The Eye Disease Case-Control Study Group. Arch Ophthalmol 110:1701–1708Google Scholar
  40. 40.
    The Eye Disease Case-Control Study Group (1993) Antioxidant status and neovascular age-related macular degeneration. Eye Disease Case-Control Study Group. Arch Ophthalmol 111:104–109Google Scholar
  41. 41.
    Trieschmann M, Spital G, Lommatzsch A, van Kuijk E, Fitzke F, Bird AC, Pauleikhoff D (2003) Macular pigment: quantitative analysis on autofluorescence images. Graefes Arch Clin Exp Ophthalmol 241:1006–1012CrossRefPubMedGoogle Scholar
  42. 42.
    van Leeuwen R, Klaver CC, Vingerling JR, Hofman A, de Jong PT (2003) The risk and natural course of age-related maculopathy: follow-up at 6 1/2 years in the Rotterdam study. Arch Ophthalmol 121:519–526CrossRefPubMedGoogle Scholar
  43. 43.
    VandenLangenberg GM, Mares Perlman JA, Klein R, Klein BE, Brady WE, Palta M (1998) Associations between antioxidant and zinc intake and the 5-year incidence of early age-related maculopathy in the Beaver Dam Eye Study. Am J Epidemiol 148:204–214PubMedGoogle Scholar
  44. 44.
    West SK, Rosenthal FS, Bressler NM, Bressler SB, Munoz B, Fine SL, Taylor HR (1989) Exposure to sunlight and other risk factors for age-related macular degeneration. Arch Ophthalmol 107:875–879PubMedGoogle Scholar
  45. 45.
    Winkler BS, Boulton ME, Gottsch JD, Sternberg P (1999) Oxidative damage and age-related macular degeneration. Mol Vis 5:32PubMedGoogle Scholar
  46. 46.
    Young AJ, Lowe GM (2001) Antioxidant and prooxidant properties of carotenoids. Arch Biochem Biophys 385:20–27CrossRefPubMedGoogle Scholar
  47. 47.
    Young RW (1988) Solar radiation and age-related macular degeneration. Surv Opthalmol 32(4):252–269CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Burkhard Dasch
    • 1
  • Andrea Fuhs
    • 1
  • Joachim Schmidt
    • 1
  • Thomas Behrens
    • 1
  • Astrid Meister
    • 1
    • 2
  • Juergen Wellmann
    • 1
  • Manfred Fobker
    • 3
  • Daniel Pauleikhoff
    • 2
  • Hans-Werner Hense
    • 1
  1. 1.Institute of Epidemiology and Social MedicineUniversity of MuensterMuensterGermany
  2. 2.Department of OphthalmologySt. Franziskus Hospital MuensterMuensterGermany
  3. 3.Institute of Clinical Chemistry and Laboratory MedicineUniversity of MuensterMuensterGermany

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