Macular response to supplementation with differing xanthophyll formulations in subjects with and without age-related macular degeneration

  • David I. Thurnham
  • John M. Nolan
  • Alan N. Howard
  • Stephen Beatty
Retinal Disorders



Our aim was to investigate the macular response to three different supplements containing lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ) in normal subjects and those with age-related macular degeneration (AMD).

Materials and Methods

Macular pigment optical density (MPOD) and serum xanthophyll concentrations were measured in normal (n = 31) and AMD subjects (n = 32), randomly assigned to: group 1 (20 mg L, 2 mg Z, 0.3 mg MZ), group 2 (10 mg L, 2 mg Z, 10 mg MZ) or group 3 (3 mg L, 2 mg Z, 17 mg MZ). MPOD was measured at baseline, 2, 4, 6 and 8 weeks and at 0.25°, 0.5°, 1.0° and 1.75° of eccentricity using customised heterochromatic flicker photometry and serum xanthophylls by HPLC.


MPOD increased significantly at all eccentricities in each group (p < 0.05), except at 1.75° in group 3 (p = 0.242). There was no difference in MPOD measurements between AMD and normal subjects, except for group 2, where AMD subjects exhibited a greater response at 1.75° (p = 0.012). Final serum concentrations of MZ were positively and significantly related to final MPOD values at each eccentricity in all subjects. Targeted analysis of those subjects receiving the MZ-containing supplements exhibited stronger relationships between serum MZ concentrations and MPOD at 0.25° in group 3 than group 2; in group 2 all associations were positive, but only significant at 1.75°.


Serum concentrations of MZ were strongly correlated with MPOD after 8 weeks of supplementation with the group 3 formulation, but the inclusion of L in the group 2 formulation may result in greater MPOD augmentation across the spatial profile.


Age-related macular degeneration Macular pigment Lutein Zeaxanthin Meso-zeaxanthin 



Age-related macular degeneration








Macular pigment optical density



The authors acknowledge financial support given by the Howard Foundation, Cambridge UK. The authors also acknowledge Professor Ronald Klein and his team at the Fundus Photography Reading Center, University of Wisconsin, USA, for grading the fundus images. The authors are grateful to Ms Katie A. Meagher, who analysed the serum carotenoids and assisted in drafting the manuscript, and to Dr J Stack, who assisted with the statistical analysis. D. I. T. drafted the final manuscript, helped with data interpretation and statistical analysis. S. B. helped to draft the manuscript and interpret the data. A. N. H. helped with the design of the trial and to draft the manuscript. J. M. N. designed and supervised the study, helped with data interpretation and statistical analysis, and helped to draft the manuscript. All authors have read and approved the final manuscript.

Declarations of Interest

J. M. N. and S. B. do consultancy work for nutraceutical companies, in a personal capacity, and as directors of Nutrasight Consultancy Ltd. D. I. T. is a consultant to the Howard Foundation and receives consulting fees for same. A. N. H., D. I. T., S. B. and J. M. N. are named inventors on a patent application for “Improvements in or relating to visual performance and/or macular pigmentation”, application number: PCT/GB2012/051567 held by the Howard Foundation, which is a UK charity established to support biomedical research.

Grant Information

This clinical trial was funded by the Howard Foundation, Cambridge, UK


  1. 1.
    Beatty S, Chakravarthy U, Nolan JM, Muldrew KA, Woodside JV, Denny F, Stevenson MR (2013) Secondary outcomes in a clinical trial of carotenoids with coantioxidants versus placebo in early age-related macular degeneration. Ophthalmology 120:600–606PubMedCrossRefGoogle Scholar
  2. 2.
    Bressler NM (2004) Age-related macular degeneration is the leading cause of blindness. JAMA 291:1900–1901PubMedCrossRefGoogle Scholar
  3. 3.
    Kvansakul J, Rodriguez-Carmona M, Edgar DF, Barker FM, Kopcke W, Schalch W, Barbur JL (2006) Supplementation with the carotenoids lutein or zeaxanthin improves human visual performance. Ophthalmic Physiol Opt 26:362–371PubMedCrossRefGoogle Scholar
  4. 4.
    Stringham JM, Hammond BR (2008) Macular pigment and visual performance under glare conditions. Optom Vis Sci 85:82–88PubMedCrossRefGoogle Scholar
  5. 5.
    Loughman J, Akkali MC, Beatty S, Scanlon G, Davison PA, O’Dwyer V, Cantwell T, Major P, Stack J, Nolan JM (2010) The relationship between macular pigment and visual performance. Vision Res 44:131–139Google Scholar
  6. 6.
    Loughman J, Davison PA, Nolan JM, Akkali MC, Beatty S (2010) Macular pigment and its contribution to visual performance and experience. J Optom 3:74–90PubMedCentralCrossRefGoogle Scholar
  7. 7.
    Loughman J. Nolan JM. Howard AN. Connolly E. Meagher K. Beatty S 2012 The impact of macular pigment augmentation on visual performance using different carotenoid formulations. Invest Ophthalmol Vis Sci :7871–7880.Google Scholar
  8. 8.
    Hammond BR Jr, Wooten BR, Engles M, Wong JC (2012) The influence of filtering by the macular carotenoids on contrast sensitivity measured under simulated blue haze conditions. Vision Res 63:58–62PubMedCrossRefGoogle Scholar
  9. 9.
    Krinsky NI, Landrum JT, Bone RA (2003) Biologic mechanisms of the protective role of lutein and zeaxanthin in the eye. Annu Rev Nutr 23:171–201PubMedCrossRefGoogle Scholar
  10. 10.
    Renzi LM. Hammond BR. Coleman HD. 2013 Use of xanthophyll carotenoids to improve visual performance and neural efficiency. PCT/US2012/035766. 2012.Ref Type: PatentGoogle Scholar
  11. 11.
    Maoka T, Arai A, Shimizu M, Matsuno T (1986) The first isolation of enantiomeric and meso-zeaxanthin in nature. Comp Biochem Physiol B 83:121–124PubMedCrossRefGoogle Scholar
  12. 12.
    Johnson EJ, Neuringer M, Russell RM, Schalch W, Snodderly DM (2005) Nutritional manipulation of primate retinas, III: effects of lutein or zeaxanthin supplementation on adipose tissue and retina of xanthophyll-free monkeys. Investig Ophthalmol Vis Sci 46:692–702CrossRefGoogle Scholar
  13. 13.
    Bhosale P, Serban B, Zhao DY, Bernstein PS (2007) Identification and metabolic transformations of carotenoids in ocular tissues of the Japanese quail coturnix japonica. Biochemistry 46:9050–9057PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Bone RA, Landrum JT, Friedes LM, Gomez CM, Kilburn MD, Menendez E, Vidal I, Wang WL (1997) Distribution of lutein and zeaxanthin stereoisomers in the human retina. Exp Eye Res 64:211–218PubMedCrossRefGoogle Scholar
  15. 15.
    Bhosale P, Zhao DY, Bernstein PS (2007) HPLC measurement of ocular carotenoid levels in human donor eyes in the lutein supplementation era. Invest Ophthalmol Vis Sci 48:543–549PubMedCrossRefGoogle Scholar
  16. 16.
    Chew E, The AREDS2 Study Group (2013) Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the age-related eye disease study 2 (AREDS2) randomized clinical trial. JAMA 309:2005–2015CrossRefGoogle Scholar
  17. 17.
    Trieschmann M, Beatty S, Nolan JM, Hense HW, Heimes B, Austermann U, Fobker M, Pauleikhoff D (2007) Changes in macular pigment optical density and serum concentrations of its constituent carotenoids following supplemental lutein and zeaxanthin: the LUNA study. Exp Eye Res 84:718–728PubMedCrossRefGoogle Scholar
  18. 18.
    Ma L, Dou HL, Huang YM, Lu XR, Xu XR, Qian F, Zou ZY, Pang HL, Dong PC, Xiao X, Wang X, Sun TT, Lin XM (2012) Improvement of retinal function in early age-related macular degeneration after lutein and zeaxanthin supplementation: a randomized, double-masked, placebo-controlled trial. Am J Ophthalmol 154(4):625–634PubMedCrossRefGoogle Scholar
  19. 19.
    Koh HH, Murray IJ, Nolan D, Carden D, Feather J (2004) Serum and macular responses to lutein supplement in subjects with and without age-related maculopathy: a pilot study. Exp Eye Res 79:21–27PubMedCrossRefGoogle Scholar
  20. 20.
    Li B, Ahmed F, Bernstein PS (2010) Studies on the singlet oxygen scavenging mechanism of human macular pigment. Arch Biochem Biophys 504:56–60PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Nolan JM, Akkali MC, Loughman J, Howard AN, Beatty S (2012) Macular carotenoid supplementation in subjects with atypical spatial profiles of macular pigment. Exp Eye Res 504:56–60Google Scholar
  22. 22.
    Meagher KA, Thurnham DI, Beatty S, Howard AN, Connolly E, Cummins W, Nolan JM (2012) Serum response to supplemental macular carotenoids in subjects with and without age-related macular degeneration. Br J Nutr 110:289–300PubMedCrossRefGoogle Scholar
  23. 23.
    Kirby ML, Beatty S, Loane E, Akkali M, Connolly EE, Stack J, Nolan JM (2010) A central dip in the macular pigment spatial profile is associated with age and smoking. Invest Ophthalmol Vis Sci 51:6722–6728PubMedCrossRefGoogle Scholar
  24. 24.
    Perry A, Rasmussen H, Johnson EJ (2009) Xanthophyll (lutein, zeaxanthin) content in fruits, vegetables and corn and egg products. J Food Compos Anal 22:9–15CrossRefGoogle Scholar
  25. 25.
    Wooten BR, Hammond BR, Land RI, Snodderly DM (1999) A practical method for measuring macular pigment optical density. Invest Ophthalmol Vis Sci 40:2481–2489PubMedGoogle Scholar
  26. 26.
    Connolly EE, Beatty S, Thurnham DI, Loughman J, Howard AN, Stack J, Nolan JM (2010) Augmentation of macular pigment following supplementation with all three macular carotenoids: an exploratory study. Curr Eye Res 35:335–351PubMedCrossRefGoogle Scholar
  27. 27.
    Barker FM, Snodderly DM, Johnson EJ, Schalch W, Koepcke W, Gerss J, Neuringer M (2011) Nutritional manipulation of primate retinas. V: effects of lutein, zeaxanthin and n-3 fatty acids on retinal sensitivity to blue light damage. Invest Ophthalmol Vis Sci 52:3934–3942PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Schalch W, Cohn W, Barker FM, Kopcke W, Mellerio J, Bird AC, Robson AG, Fitzke FF, van Kuijk FJ (2007) Xanthophyll accumulation in the human retina during supplementation with lutein or zeaxanthin - the LUXEA (lutein xanthophyll eye accumulation) study. Arch Biochem Biophys 458:128–135PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • David I. Thurnham
    • 1
  • John M. Nolan
    • 2
  • Alan N. Howard
    • 3
    • 4
  • Stephen Beatty
    • 5
  1. 1.Northern Ireland Centre for Food and Health (NICHE)University of UlsterColeraineUK
  2. 2.Macular Pigment Research Group, Department of Chemical and Life SciencesWaterford Institute of TechnologyWaterfordIreland
  3. 3.Howard FoundationCambridgeUK
  4. 4.Downing CollegeUniversity of CambridgeCambridgeUK
  5. 5.Institute of Vision researchWhitfield ClinicWaterfordIreland

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