Effects of lutein supplementation in age-related macular degeneration

Autoři: Liwen Feng aff001;  Kailai Nie aff001;  Hui Jiang aff001;  Wei Fan aff001
Působiště autorů: Department of Ophthalmology, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China aff001;  Research Laboratory of Ophthalmology and Vision Sciences, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China aff002
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0227048


The purpose of this meta-analysis was to evaluate the effects of lutein supplementation on macular pigment optical density (MPOD) in randomized controlled trials involving patients with age-related macular degeneration (AMD). A comprehensive search of the literature was performed in PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and Wan Fang database through December 2018. Nine randomized controlled trials involving 920 eyes (855 with AMD) were included. Meta-analysis suggested that lutein supplementation (10 or 20 mg per day) was associated with an increase in MPOD (mean difference (MD) 0.07; 95% confidence interval (CI) 0.03 to 0.10), visual acuity (MD 0.28; 95%CI 0.06 to 0.50) and contrast sensitivity (MD 0.26; 95%CI 0.22 to 0.30). Stratified analyses showed the increase in MPOD to be faster and greater with higher dose and longer treatment. The available evidence suggests that dietary lutein may be beneficial to AMD patients and the higher dose could make MPOD increase in a shorter time.

Klíčová slova:

Antioxidants – Carotenoids – Eyes – Macular degeneration – Pigments – Randomized controlled trials – Visual acuity


1. van Lookeren Campagne M, LeCouter J, Yaspan BL, Ye W. Mechanisms of age-related macular degeneration and therapeutic opportunities. The Journal of pathology. 2014;232(2):151–64. Epub 2013/10/10. doi: 10.1002/path.4266 24105633.

2. Wald G. HUMAN VISION AND THE SPECTRUM. Science (New York, NY). 1945;101(2635):653–8. Epub 1945/06/29. doi: 10.1126/science.101.2635.653 17777531.

3. Bone RA, Landrum JT, Tarsis SL. Preliminary identification of the human macular pigment. Vision research. 1985;25(11):1531–5. Epub 1985/01/01. doi: 10.1016/0042-6989(85)90123-3 3832576.

4. Johnson EJ. Role of lutein and zeaxanthin in visual and cognitive function throughout the lifespan. Nutrition reviews. 2014;72(9):605–12. Epub 2014/08/12. doi: 10.1111/nure.12133 25109868.

5. Bone RA, Landrum JT, Dixon Z, Chen Y, Llerena CM. Lutein and zeaxanthin in the eyes, serum and diet of human subjects. Experimental eye research. 2000;71(3):239–45. Epub 2000/09/07. doi: 10.1006/exer.2000.0870 10973733.

6. Snodderly DM, Auran JD, Delori FC. The macular pigment. II. Spatial distribution in primate retinas. Investigative ophthalmology & visual science. 1984;25(6):674–85. Epub 1984/06/01. 6724837.

7. Bernstein PS, Li B, Vachali PP, Gorusupudi A, Shyam R, Henriksen BS, et al. Lutein, zeaxanthin, and meso-zeaxanthin: The basic and clinical science underlying carotenoid-based nutritional interventions against ocular disease. Progress in retinal and eye research. 2016;50:34–66. Epub 2015/11/07. doi: 10.1016/j.preteyeres.2015.10.003 26541886; PubMed Central PMCID: PMC4698241.

8. Eggersdorfer M, Wyss A. Carotenoids in human nutrition and health. Archives of biochemistry and biophysics. 2018;652:18–26. Epub 2018/06/10. doi: 10.1016/j.abb.2018.06.001 29885291.

9. Kijlstra A, Tian Y, Kelly ER, Berendschot TT. Lutein: more than just a filter for blue light. Progress in retinal and eye research. 2012;31(4):303–15. Epub 2012/04/03. doi: 10.1016/j.preteyeres.2012.03.002 22465791.

10. Ozawa Y, Shigeno Y, Nagai N, Suzuki M, Kurihara T, Minami S, et al. Absolute and estimated values of macular pigment optical density in young and aged Asian participants with or without age-related macular degeneration. BMC Ophthalmol. 2017;17(1):161. Epub 2017/08/31. doi: 10.1186/s12886-017-0557-5 28851319; PubMed Central PMCID: PMC5576241.

11. Loane E, Kelliher C, Beatty S, Nolan JM. The rationale and evidence base for a protective role of macular pigment in age-related maculopathy. British Journal of Ophthalmology. 2008;92(9):1163–8. doi: 10.1136/bjo.2007.135566 18669545

12. Sabour-Pickett S, Nolan JM, Loughman J, Beatty S. A review of the evidence germane to the putative protective role of the macular carotenoids for age-related macular degeneration. Molecular nutrition & food research. 2012;56(2):270–86. Epub 2011/11/29. doi: 10.1002/mnfr.201100219 22121091.

13. Puell MC, Palomo-Alvarez C, Barrio AR, Gomez-Sanz FJ, Perez-Carrasco MJ. Relationship between macular pigment and visual acuity in eyes with early age-related macular degeneration. Acta ophthalmologica. 2013;91(4):e298–303. Epub 2013/04/12. doi: 10.1111/aos.12067 23575039.

14. Korobelnik JF, Rougier MB, Delyfer MN, Bron A, Merle BMJ, Savel H, et al. Effect of Dietary Supplementation With Lutein, Zeaxanthin, and omega-3 on Macular Pigment: A Randomized Clinical Trial. JAMA ophthalmology. 2017;135(11):1259–66. Epub 2017/10/04. doi: 10.1001/jamaophthalmol.2017.3398 28973076; PubMed Central PMCID: PMC5710391.

15. Arslan S, Kadayifcilar S, Samur G. The Potential Role of Dietary Antioxidant Capacity in Preventing Age-Related Macular Degeneration. Journal of the American College of Nutrition. 2018:1–9. Epub 2018/12/21. doi: 10.1080/07315724.2018.1538830 30570376.

16. Rinninella E, Mele MC, Merendino N, Cintoni M, Anselmi G, Caporossi A, et al. The Role of Diet, Micronutrients and the Gut Microbiota in Age-Related Macular Degeneration: New Perspectives from the Gut(-)Retina Axis. Nutrients. 2018;10(11). Epub 2018/11/08. doi: 10.3390/nu10111677 30400586; PubMed Central PMCID: PMC6267253.

17. Wong WL, Su X, Li X, Cheung CM, Klein R, Cheng CY, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. The Lancet Global health. 2014;2(2):e106–16. Epub 2014/08/12. doi: 10.1016/S2214-109X(13)70145-1 25104651.

18. Hyttinen JMT, Viiri J, Kaarniranta K, Blasiak J. Mitochondrial quality control in AMD: does mitophagy play a pivotal role? Cellular and molecular life sciences: CMLS. 2018;75(16):2991–3008. Epub 2018/05/20. doi: 10.1007/s00018-018-2843-7 29777261.

19. Chung RWS, Leanderson P, Gustafsson N, Jonasson L. Liberation of lutein from spinach: Effects of heating time, microwave-reheating and liquefaction. Food chemistry. 2019;277:573–8. Epub 2018/12/07. doi: 10.1016/j.foodchem.2018.11.023 30502187.

20. Chew EY, Clemons TE, Agron E, Launer LJ, Grodstein F, Bernstein PS. Effect of Omega-3 Fatty Acids, Lutein/Zeaxanthin, or Other Nutrient Supplementation on Cognitive Function: The AREDS2 Randomized Clinical Trial. Jama. 2015;314(8):791–801. Epub 2015/08/26. doi: 10.1001/jama.2015.9677 26305649; PubMed Central PMCID: PMC5369607.

21. Tan JS, 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):334–41. Epub 2007/08/01. doi: 10.1016/j.ophtha.2007.03.083 17664009.

22. Fujimura S, Ueda K, Nomura Y, Yanagi Y. Preliminary analysis of the relationship between serum lutein and zeaxanthin levels and macular pigment optical density. Clinical ophthalmology (Auckland, NZ). 2016;10:2149–55. Epub 2016/11/09. doi: 10.2147/opth.s119251 27826180; PubMed Central PMCID: PMC5096749.

23. Sasamoto Y, Gomi F, Sawa M, Tsujikawa M, Nishida K. Effect of 1-year lutein supplementation on macular pigment optical density and visual function. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 2011;249(12):1847–54. Epub 2011/08/19. doi: 10.1007/s00417-011-1780-z 21850440.

24. Kanis MJ, Wisse RP, Berendschot TT, van de Kraats J, van Norren D. Foveal cone-photoreceptor integrity in aging macula disorder. Investigative ophthalmology & visual science. 2008;49(5):2077–81. Epub 2008/01/29. doi: 10.1167/iovs.07-1181 18223244.

25. Dieguez HH, Romeo HE, Alaimo A, Gonzalez Fleitas MF, Aranda ML, Rosenstein RE, et al. Oxidative stress damage circumscribed to the central temporal retinal pigment epithelium in early experimental non-exudative age-related macular degeneration. Free radical biology & medicine. 2019;131:72–80. Epub 2018/12/07. doi: 10.1016/j.freeradbiomed.2018.11.035 30502459.

26. Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Systematic Reviews. 2015;4(1):1. doi: 10.1186/2046-4053-4-1 25554246

27. Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ (Clinical research ed). 2011;343:d5928. Epub 2011/10/20. doi: 10.1136/bmj.d5928 22008217; PubMed Central PMCID: PMC3196245.

28. Zwetsloot PP, Van Der Naald M, Sena ES, Howells DW, IntHout J, De Groot JA, et al. Standardized mean differences cause funnel plot distortion in publication bias assessments. eLife. 2017;6. Epub 2017/09/09. doi: 10.7554/eLife.24260 28884685; PubMed Central PMCID: PMC5621838.

29. Xudong GRZJSXH. Clinical observation of macular pigment optical density changes on visual functions in patients with age-related macular degeneration. BMU Journal. 2018;41(3):185–7,240.

30. Sui CLWRYJ. Effect of lutein intervention on visual function in patients with early age-related macular degeneration. Int Eye Sci. 2017.

31. Richer SP, Stiles W, Graham-Hoffman K, Levin M, Ruskin D, Wrobel J, et al. 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 (St Louis, Mo). 2011;82(11):667–80.e6. Epub 2011/10/27. doi: 10.1016/j.optm.2011.08.008 22027699.

32. 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 (St Louis, Mo). 2007;78(5):213–9. Epub 2007/05/05. doi: 10.1016/j.optm.2006.10.019 17478338.

33. Weigert G, Kaya S, Pemp B, Sacu S, Lasta M, Werkmeister RM, et al. Effects of lutein supplementation on macular pigment optical density and visual acuity in patients with age-related macular degeneration. Investigative ophthalmology & visual science. 2011;52(11):8174–8. Epub 2011/08/30. doi: 10.1167/iovs.11-7522 21873668.

34. Arnold C, Winter L, Frohlich K, Jentsch S, Dawczynski J, Jahreis G, et al. Macular xanthophylls and omega-3 long-chain polyunsaturated fatty acids in age-related macular degeneration: a randomized trial. JAMA ophthalmology. 2013;131(5):564–72. Epub 2013/03/23. doi: 10.1001/jamaophthalmol.2013.2851 23519529

35. Garcia-Layana A, Recalde S, Alaman AS, Robredo PF. Effects of lutein and docosahexaenoic Acid supplementation on macular pigment optical density in a randomized controlled trial. Nutrients. 2013;5(2):543–51. Epub 2013/02/26. doi: 10.3390/nu5020543 23434908; PubMed Central PMCID: PMC3635211.

36. 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. Investigative ophthalmology & visual science. 2013;54(3):1781–8. Epub 2013/02/07. doi: 10.1167/iovs.12-10715 23385792.

37. Huang YM, Dou HL, Huang FF, Xu XR, Zou ZY, Lu XR, et al. Changes following supplementation with lutein and zeaxanthin in retinal function in eyes with early age-related macular degeneration: a randomised, double-blind, placebo-controlled trial. The British journal of ophthalmology. 2015;99(3):371–5. Epub 2014/09/18. doi: 10.1136/bjophthalmol-2014-305503 25228440.

38. Ma L, Yan SF, Huang YM, Lu XR, Qian F, Pang HL, et al. Effect of lutein and zeaxanthin on macular pigment and visual function in patients with early age-related macular degeneration. Ophthalmology. 2012;119(11):2290–7. Epub 2012/08/04. doi: 10.1016/j.ophtha.2012.06.014 22858124.

39. Ma L, Dou HL, Huang YM, Lu XR, Xu XR, Qian F, et al. Improvement of retinal function in early age-related macular degeneration after lutein and zeaxanthin supplementation: a randomized, double-masked, placebo-controlled trial. American journal of ophthalmology. 2012;154(4):625–34.e1. Epub 2012/07/28. doi: 10.1016/j.ajo.2012.04.014 22835510.

40. Azar G, Quaranta-El Maftouhi M, Masella JJ, Mauget-Faysse M. Macular pigment density variation after supplementation of lutein and zeaxanthin using the Visucam((R)) 200 pigment module: Impact of age-related macular degeneration and lens status. Journal francais d'ophtalmologie. 2017;40(4):303–13. Epub 2017/03/25. doi: 10.1016/j.jfo.2016.11.009 28336284.

41. Akuffo KO, Nolan JM, Peto T, Stack J, Leung I, Corcoran L, et al. Relationship between macular pigment and visual function in subjects with early age-related macular degeneration. The British journal of ophthalmology. 2017;101(2):190–7. Epub 2016/04/20. doi: 10.1136/bjophthalmol-2016-308418 27091854; PubMed Central PMCID: PMC5293853.

42. Madhavan J, Chandrasekharan S, Priya MK, Godavarthi A. Modulatory Effect of Carotenoid Supplement Constituting Lutein and Zeaxanthin (10:1) on Anti-oxidant Enzymes and Macular Pigments Level in Rats. Pharmacognosy magazine. 2018;14(54):268–74. Epub 2018/05/04. doi: 10.4103/pm.pm_340_17 29720843; PubMed Central PMCID: PMC5909327.

43. Yanai R, Chen S, Uchi SH, Nanri T, Connor KM, Kimura K. Attenuation of choroidal neovascularization by dietary intake of omega-3 long-chain polyunsaturated fatty acids and lutein in mice. PloS one. 2018;13(4):e0196037. Epub 2018/04/26. doi: 10.1371/journal.pone.0196037 29694386; PubMed Central PMCID: PMC5919067.

44. Tuzcu M, Orhan C, Muz OE, Sahin N, Juturu V, Sahin K. Lutein and zeaxanthin isomers modulates lipid metabolism and the inflammatory state of retina in obesity-induced high-fat diet rodent model. BMC Ophthalmol. 2017;17(1):129. Epub 2017/07/26. doi: 10.1186/s12886-017-0524-1 28738845; PubMed Central PMCID: PMC5525211.

45. Chae SY, Park SY, Park G. Lutein protects human retinal pigment epithelial cells from oxidative stressinduced cellular senescence. Molecular medicine reports. 2018;18(6):5182–90. Epub 2018/10/16. doi: 10.3892/mmr.2018.9538 30320359.

46. Zareba M, Widomska J, Burke JM, Subczynski WK. Nitroxide free radicals protect macular carotenoids against chemical destruction (bleaching) during lipid peroxidation. Free radical biology & medicine. 2016;101:446–54. Epub 2016/11/15. doi: 10.1016/j.freeradbiomed.2016.11.012 27840316; PubMed Central PMCID: PMC5154825.

47. Mettu PS, Wielgus AR, Ong SS, Cousins SW. Retinal pigment epithelium response to oxidant injury in the pathogenesis of early age-related macular degeneration. Mol Aspects Med. 2012;33(4):376–98. Epub 2012/05/12. doi: 10.1016/j.mam.2012.04.006 22575354.

48. 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 ophthalmology & visual science. 2001;42(1):235–40. Epub 2001/01/03. 11133874.

49. Gopinath B, Liew G, Tang D, Burlutsky G, Flood VM, Mitchell P. Consumption of eggs and the 15-year incidence of age-related macular degeneration. Clinical nutrition (Edinburgh, Scotland). 2019. Epub 2019/03/28. doi: 10.1016/j.clnu.2019.03.009 30914217.

50. Li S, Liu N, Lin L, Sun ED, Li JD, Li PK. Macular pigment and serum zeaxanthin levels with Goji berry supplement in early age-related macular degeneration. International journal of ophthalmology. 2018;11(6):970–5. Epub 2018/07/07. doi: 10.18240/ijo.2018.06.12 29977809; PubMed Central PMCID: PMC6010398.

51. Papudesu C, Clemons TE, Agron E, Chew EY. Association of Mortality with Ocular Diseases and Visual Impairment in the Age-Related Eye Disease Study 2: Age-Related Eye Disease Study 2 Report Number 13. Ophthalmology. 2018;125(4):512–21. Epub 2017/11/21. doi: 10.1016/j.ophtha.2017.10.028 29153456; PubMed Central PMCID: PMC5866182.

52. Wang X, Jiang C, Zhang Y, Gong Y, Chen X, Zhang M. Role of lutein supplementation in the management of age-related macular degeneration: meta-analysis of randomized controlled trials. Ophthalmic research. 2014;52(4):198–205. Epub 2014/11/02. doi: 10.1159/000363327 25358528.

53. Evans JR, Lawrenson JG. Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration. The Cochrane database of systematic reviews. 2017;7:Cd000254. Epub 2017/08/02. doi: 10.1002/14651858.CD000254.pub4 28756618; PubMed Central PMCID: PMC6483465.

54. Ravikrishnan R, Rusia S, Ilamurugan G, Salunkhe U, Deshpande J, Shankaranarayanan J, et al. Safety assessment of lutein and zeaxanthin (Lutemax 2020): subchronic toxicity and mutagenicity studies. Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association. 2011;49(11):2841–8. Epub 2011/08/30. doi: 10.1016/j.fct.2011.08.011 21872637.

55. Shao A, Hathcock JN. Risk assessment for the carotenoids lutein and lycopene. Regulatory toxicology and pharmacology: RTP. 2006;45(3):289–98. Epub 2006/07/04. doi: 10.1016/j.yrtph.2006.05.007 16814439.

56. Yonova-Doing E, Hysi PG, Venturini C, Williams KM, Nag A, Beatty S, et al. Candidate gene study of macular response to supplemental lutein and zeaxanthin. Experimental eye research. 2013;115:172–7. Epub 2013/07/31. doi: 10.1016/j.exer.2013.07.020 23891863; PubMed Central PMCID: PMC3819993.

57. Koo E, Neuringer M, SanGiovanni JP. Macular xanthophylls, lipoprotein-related genes, and age-related macular degeneration. The American journal of clinical nutrition. 2014;100 Suppl 1:336s–46s. Epub 2014/05/16. doi: 10.3945/ajcn.113.071563 24829491; PubMed Central PMCID: PMC4144106.

58. Kirby ML, Beatty S, Stack J, Harrison M, Greene I, McBrinn S, et al. Changes in macular pigment optical density and serum concentrations of lutein and zeaxanthin in response to weight loss. The British journal of nutrition. 2011;105(7):1036–46. Epub 2010/12/15. doi: 10.1017/S0007114510004721 21144093.

59. Tudosescu R, Alexandrescu CM, Istrate SL, Vrapciu AD, Ciuluvica RC, Voinea L. Correlations between internal and external ocular factors and macular pigment optical density. Romanian journal of ophthalmology. 2018;62(1):42–7. Epub 2018/05/26. 29796433; PubMed Central PMCID: PMC5959024.

60. Putnam CM. Clinical imaging of macular pigment optical density and spatial distribution. Clinical & experimental optometry. 2017;100(4):333–40. Epub 2016/11/26. doi: 10.1111/cxo.12500 27885710.

61. Sharifzadeh M, Obana A, Gohto Y, Seto T, Gellermann W. Autofluorescence imaging of macular pigment: influence and correction of ocular media opacities. Journal of biomedical optics. 2014;19(9):96010. Epub 2014/09/17. doi: 10.1117/1.JBO.19.9.096010 25223707.

62. Bartlett H, Howells O, Eperjesi F. The role of macular pigment assessment in clinical practice: a review. Clinical & experimental optometry. 2010;93(5):300–8. Epub 2010/07/16. doi: 10.1111/j.1444-0938.2010.00499.x 20629669.

63. Li B, Ahmed F, Bernstein PS. Studies on the singlet oxygen scavenging mechanism of human macular pigment. Archives of biochemistry and biophysics. 2010;504(1):56–60. Epub 2010/08/04. doi: 10.1016/j.abb.2010.07.024 20678467; PubMed Central PMCID: PMC2957523.

64. Meagher KA, Thurnham DI, Beatty S, Howard AN, Connolly E, Cummins W, et al. Serum response to supplemental macular carotenoids in subjects with and without age-related macular degeneration. The British journal of nutrition. 2013;110(2):289–300. Epub 2012/12/06. doi: 10.1017/S0007114512004837 23211762.

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