Objective: The conduct of this meta-analysis aimed at examining the individual role of lutein as a dietary supplement in improving conditions of age-related macular degeneration (AMD) from the data generated from randomized controlled trials (RCTs). Method: The literature search was made in multiple electronic databases. Eligibility criteria were RCTs that recruited AMD patients or individuals at risk and evaluated lutein supplementation efficacy against placebo. The quality of the trials was assessed by using the Jadad scale. The meta-analysis was conducted under the fixed effect model with RevMan software by calculating the mean differences of the changes from baseline of both lutein and placebo groups. Parameters of interest were macular pigment optical density (MPOD) and visual acuity (VA) in logMAR (minimum angle of resolution). Heterogeneity was determined by χ2 and I2 and publication bias was assessed by visual examination of funnel plots. Results: After following predetermined inclusion and exclusion criteria, five RCTs that recruited 445 participants were selected for the meta-analysis. It has been found that lutein treatment was associated with a significant improvement in MPOD, with mean differences between lutein and placebo groups in the changes from baseline of 0.09 (95% CI: 0.06, 0.12; p < 0.00001). VA also improved with a mean difference between lutein and placebo groups in the changes from baseline of −0.04 (95% CI−0.07, 0.00; p = 0.05). Statistical heterogeneity was not apparent. Conclusion: A statistically highly significant effect of lutein supplementation has been observed for improving the MPOD, whereas the improvement in VA was milder. A daily dose of 10 mg was found as effective as higher doses in this meta-analysis. However, the number of input studies is not adequate for conclusive evidence.

1.
Congdon N, O'Colmain B, Klaver CC, Klein R, Munoz B, Friedman DS, Kempen J, Taylor HR, Mitchell P; Eye Diseases Prevalence Research Group: Causes and prevalence of visual impairment among adults in the United States. Arch Ophthalmol 2004;122:477-485.
2.
National Eye Institute: Age-related macular degeneration. Statistics and data. http://www.nei.nih.gov/eyedata/amd.asp (accessed July 29, 2013).
3.
Friedman DS, O'Colmain BJ, Muñoz B, Tomany SC, McCarty C, de Jong PT, Nemesure B, Mitchell P, Kempen J; Eye Diseases Prevalence Research Group: Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol 2004;122:564-572.
4.
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. Invest Ophthalmol Vis Sci 2001;42:439-446.
5.
Zeimer M, Dietzel M, Hense HW, Heimes B, Austermann U, Pauleikhoff D: Profiles of macular pigment optical density and their changes following supplemental lutein and zeaxanthin: new results from the LUNA study. Invest Ophthalmol Vis Sci 2012;53:4852-4859.
6.
Landrum JT, Bone RA, Joa H, Kilburn MD, Moore LL, Sprague KE: A one year study of macular pigment modification: the effect of 140 days of lutein supplement. Exp Eye Res 1997;65:57-62.
7.
Palozza P, Krinsky NI: Antioxidant effects of carotenoids in vivo and in vitro: an overview. Methods Enzymol 1992;213:403-420.
8.
Khachik F, Bernstein PS, Garland DL: Identification of lutein and zeaxanthin oxidation products in human and monkey retinas. Invest Ophthalmol Vis Sci 1997;38:1802-1811.
9.
Mangels AR, Holden JM, Beecher GR, Forman MR, Lanza E: Carotenoid content of fruits and vegetables: an evaluation of analytic data. J Am Diet Assoc 1993;93:284-296.
10.
Landrum JT, Bone RA, Kilburn MD: The macular pigment: a possible role in protection from age-related macular degeneration. Adv Pharmacol 1997;38:537-556.
11.
Hammond BR Jr, Johnson EJ, Russell RM, Krinsky NI, Yeum KJ, Edwards RB, Snodderly DM: Dietary modification of human macular pigment density. Invest Ophthalmol Vis Sci 1997;38:1795-1801.
12.
Bone RA, Landrum JT, Guerra LH, Ruiz CA: Lutein and zeaxanthin dietary supplements raise macular pigment density and serum concentrations of these carotenoids in humans. Bone J Nutr 2003;133:992-998.
13.
Dawczynski J, Jentsch S, Schweitzer D, Hammer M, Lang GE, Strobel J: Long term effects of lutein, zeaxanthin and omega-3-LCPUFAs supplementation on optical density of macular pigment in AMD patients: the LUTEGA study. Graefes Arch Clin Exp Ophthalmol 2013;251:2711-2723.
14.
Berendschot TT, Goldbohm RA, Klopping WA, van de Kraats J, van Norel J, van Norren D: Influence of lutein supplementation on macular pigment, assessed with two objective techniques. Invest Ophthalmol Vis Sci 2000;41:3322-3326.
15.
Rosenthal JM, Kim J, de Monasterio F, Thompson DJ, Bone RA, Landrum JT, de Moura FF, Khachik F, Chen H, Schleicher RL, Ferris FL 3rd, Chew EY: Dose-ranging study of lutein supplementation in persons aged 60 years or older. Invest Ophthalmol Vis Sci 2006;47:5227-5233.
16.
Mares-Perlman JA, Fisher AI, Klein R, Palta M, Block G, Millen AE, Wright JD: 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 2001;153:424-432.
17.
Snellen EL, Verbeek AL, Van Den Hoogen GW, Cruysberg JR, Hoyng CB: Neovascular age-related macular degeneration and its relationship to antioxidant intake. Acta Ophthalmol Scand 2002;80:368-371.
18.
Gale CR, Hall NF, Phillips DI, Martyn CN: Lutein and zeaxanthin status and risk of age-related macular degeneration. Invest Ophthalmol Vis Sci 2003;44:2461-2465.
19.
Moeller SM, Parekh N, Tinker L, Ritenbaugh C, Blodi B, Wallace RB, Mares JA; CAREDS Research Study Group: 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. Arch Ophthalmol 2006;124:1151-1162.
20.
Delcourt C, Carriere I, Delage M, Barberger-Gateau P, Schalch W: Plasma lutein and zeaxanthin and other carotenoids as modifiable risk factors for age-related maculopathy and cataract: the POLA Study. Invest Ophthalmol Vis Sci 2006;47:2329-2335.
21.
SanGiovanni JP, Chew EY, Clemons TE, Ferris FL 3rd, Gensler G, Lindblad AS, Milton RC, Seddon JM, Sperduto RD; Age-Related Eye Disease Study Research Group: 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. Arch Ophthalmol 2007;125:1225-1232.
22.
Mares-Perlman JA, Brady WE, Klein R, Klein BE, Bowen P, Stacewicz-Sapuntzakis M, Palta M: Serum antioxidants and age-related macular degeneration in a population-based case-control study. Arch Ophthalmol 1995;113:1518-1523.
23.
Flood V, Smith W, Wang JJ, Manzi F, Webb K, Mitchell P: Dietary antioxidant intake and incidence of early age-related maculopathy: the Blue Mountains Eye Study. Ophthalmology 2002;109:2272-2278.
24.
Simonelli F, Zarrilli F, Mazzeo S, Verde V, Romano N, Savoia M, Testa F, Vitale DF, Rinaldi M, Sacchetti L: Serum oxidative and antioxidant parameters in a group of Italian patients with age-related maculopathy. Clin Chim Acta 2002;320:111-115.
25.
van Leeuwen R, Boekhoorn S, Vingerling JR, Witteman JC, Klaver CC, Hofman A, de Jong PT: Dietary intake of antioxidants and risk of age-related macular degeneration. JAMA 2005;294:3101-3107.
26.
Dasch B, Fuhs A, Schmidt J, Behrens T, Meister A, Wellmann J, Fobker M, Pauleikhoff D, Hense HW: Serum levels of macular carotenoids in relation to age-related maculopathy: the Muenster Aging and Retina Study (MARS). Graefes Arch Clin Exp Ophthalmol 2005;243:1028-1035.
27.
Cardinault N, Abalain JH, Sairafi B, Coudray C, Grolier P, Rambeau M, Carre JL, Mazur A, Rock E: Lycopene but not lutein nor zeaxanthin decreases in serum and lipoproteins in age-related macular degeneration patients. Clin Chim Acta 2005;357:34-42.
28.
Chow E, Hankinson SE, Rosner B, Willet WC, Colditz GA: Prospective study of lutein/zeaxanthin intake and risk of age-related macular degeneration. Am J Clin Nutr 2008;87:1837-1843.
29.
Age-Related Eye Disease Study 2 Research Group: Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degenera- tion: the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA 2013;309:2005-2015.
30.
Age-Related Eye Disease Study 2 (AREDS2) Research Group, et al: Secondary analyses of the effects of lutein/zeaxanthin on age-related macular degeneration progression: AREDS2 report No. 3. JAMA Ophthalmol 2014;132:142-149.
31.
Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ: Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996;17:1-12.
32.
Beck RW, Moke PS, Turpin AH, Ferris FL III, Sangiovanni JP, Johnson CA, Birch EE, Chandler DL, Cox TA, Blair RC, Kraker RT: A computerized method of visual acuity testing: adaptation of the early treatment of diabetic retinopathy study testing protocol. Am J Ophthalmol 2003;135:194-205.
33.
Murray IJ, Makridaki M, van der Veen RL, Carden D, Parry NR, Berendschot TT: Lutein supplementation over a one-year period in early AMD might have a mild beneficial effect on visual acuity: the CLEAR study. Invest Ophthalmol Vis Sci 2013;54:1781-1788.
34.
Huang YM, Yan SF, Ma L, Zou ZY, Xu XR, Dou HL, Lin XM: Serum and macular responses to multiple xanthophyll supplements in patients with early age-related macular degeneration. Nutrition 2013;29:387-392.
35.
Ma L, Yan SF, Huang YM, Lu XR, Qian F, Pang HL, Xu XR, Zou ZY, Dong PC, Xiao X, Wang X, Sun TT, Dou HL, Lin XM: Effect of lutein and zeaxanthin on macular pigment and visual function in patients with early age-related macular degeneration. Ophthalmology 2012;119:2290-2297.
36.
Richer S, Devenport J, Lang JC: LAST II: differential temporal responses of macular pigment optical density in patients with atrophic age-related macular degeneration to dietary supplementation with xanthophylls. Optometry 2007;78:213-219.
37.
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 2004;75:216-230.
38.
Weigert G, Kaya S, Pemp B, Sacu S, Lasta M, Werkmeister RM, Dragostinoff N, Simader C, Garhofer G, Schmidt-Erfurth U, Schmetterer L: Effects of lutein supplementation on macular pigment optical density and visual acuity in patients with age-related macular degeneration. Invest Ophthalmol Vis Sci 2011;52:8174-8178.
39.
Johnson EJ, Chung HY, Caldarella SM, Snodderly DM: The influence of supplemental lutein and docosahexaenoic acid on serum, lipoproteins, and macular pigmentation. Am J Clin Nutr 2008;87:1521-1529.
40.
Ma L, Dou HL, Wu YQ, Huang YM, Huang YB, Xu XR, Zou ZY, Lin XM: Lutein and zeaxanthin intake and the risk of age-related macular degeneration: a systematic review and meta-analysis. Br J Nutr 2012;107:350-359.
41.
Garcia-Layana A, Recalde S, Alamán AS, Robredo PF: Effects of lutein and docosahexaenoic acid supplementation on macular pigment optical density in a randomized controlled trial. Nutrients 2013;5:543-551.
42.
Richer SP, Stiles W, Graham-Hoffman K, Levin M, Ruskin D, Wrobel J, Park DW, Thomas C: Randomized, double-blind, placebo-controlled study of zeaxanthin and visual function in patients with atrophic age-related macular degeneration: the Zeaxanthin and Visual Function Study (ZVF) FDA IND #78, 973. Optometry 2011;82:667-680.e6
43.
Arnold C, Winter L, Fröhlich K, Jentsch S, Dawczynski J, Jahreis G, Böhm V: Macular xanthophylls and ω-3 long-chain polyunsaturated fatty acids in age-related macular degeneration: a randomized trial. JAMA Ophthalmol 2013;131:564-572.
44.
Seddon JM, Willett WC, Speizer FE, Hankinson SE: A prospective study of cigarette smoking and age-related macular degeneration in women. JAMA 1996;276:1141-1146.
45.
Johnson EJ: Obesity, lutein metabolism, and age-related macular degeneration: a web of connections. Nutr Rev 2005;63:9-15.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.