The role of the carotenoids, lutein and zeaxanthin, in protecting against age-related macular degeneration: A review based on controversial evidence

Nutrition Journal

Andreas Wedrich¹  Stefan Sacu¹  Maneli Mozaffarieh¹ 

[1] Department of Ophthalmology, University of Vienna, Austria

关键词: vitamin supplements;    carotenoids;    age-related macular degeneration (AMD);   

Others  :  1152099
DOI  :  10.1186/1475-2891-2-20

 received in 2003-08-21, accepted in 2003-12-11,  发布年份 2003

【 摘 要 】

Purpose

A review of the role of the carotenoids, lutein and zeaxanthin, and their function in altering the pathogenesis of age-related macular degeneration (AMD).

Methods

Medline and Embase search.

Results

Recent evidence introduces the possibility that lutein and zeaxanthin, carotenoids found in a variety of fruits and vegetables may protect against the common eye disease of macular degeneration. This potential and the lack to slow the progression of macular degeneration, has fueled high public interest in the health benefits of these carotenoids and prompted their inclusion in various supplements. The body of evidence supporting a role in this disease ranges from basic studies in experimental animals to various other clinical and epidemiological studies. Whilst some epidemiological studies suggest a beneficial role for carotenoids in the prevention of AMD, others are found to be unrelated to it. Results of some clinical studies indicate that the risk for AMD is reduced when levels of the carotenoids are elevated in the serum or diet, but this correlation is not observed in other studies. Published data concerning the toxicity of the carotenoids or the optimum dosage of these supplements is lacking.

Conclusion

An intake of dietary supplied nutrients rich in the carotenoids, lutein and zeaxanthin, appears to be beneficial in protecting retinal tissues, but this is not proven. Until scientifically sound knowledge is available we recommend for patients judged to be at risk for AMD to: alter their diet to more dark green leafy vegetables, wear UV protective lenses and a hat when outdoors. Future investigations on the role of nutrition, light exposure, genetics, and combinations of photodynamic therapy with intravitreal steroid (triamcinolone-acetonide) injections hold potential for future treatment possibilities.

【 授权许可】

   
2003 Mozaffarieh et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

【 参考文献 】

• [1]Handelman GJ, Dratz EA, Reay CC, van Kuijk JG: Carotenoids in the human macula and whole retina. Invest Ophthalmol Vis Sci 1988, 29:850-5.
• [2]Bone RA, Landrum JT, Fernandez L, Tarsis SL: Analysis of the macular pigment by HPLC: retinal distribution and age study. Invest Ophthalmol Vis Sci 1988, 29:843-9.
• [3]Khachik F, Beecher GR, Goli MB, Lusby WR, Daitch CE: Seperation and quantification of carotenoids in human plasma. Methods Enzymol 1992, 213:205-219.
• [4]Khachik F, Beecher GR, Goli MB, Lusby WR: Seperation and quantification of carotenoids in foods. Methods Enzymol 1992, 213:347-359.
• [5]Snodderly DM, Handelman GJ, Adler AJ: Distribution of individual macular pigment carotenoids in the central retina of macaque and squirrel monkeys. Invest Ophthalmol Vis Sci 1991, 32:268-279.
• [6]Dichtburn RW: Eye movements and visual perception. Oxford: Claredon Press 1973.
• [7]Bone RA, Landrum JT: Macular pigment in Henle fiber membranes: a model for Haidinger's brushes. Vis Res 1984, 24:103-8.
• [8]Kirschfeld K: Carotenoid pigments: their possible role in protecting against photooxidation in eyes and photoreceptor cells. Proc R Soc Lond 1982, 216:71-85.
• [9]Nussbaum JJ, Pruett RC, Delori FC: Macular yellow pigment. The first 200 years. Retina 1981, 1:296-310.
• [10]Reading VM, Weale RA: Macular pigment and chromatic aberration. J Optom Soc Am 1974, 64:231-4.
• [11]Foote CS, Chang YC, Denny RW: Chemistry of singlet oxygen. X: Carotenoid quenching parallels biological protection. J Am Chem Soc 1970, 92:5216-18.
• [12]Snodderly DM: Evidence for protection against age-related macular degeneration by carotenoids and antioxidant vitamins. Am J Clin Nutr 1995, 62(suppl):1448s-60s.
• [13]Young RW: Solar radiation and age-related macular degeneration. Surv Ophthalmol 1988, 32:252-69.
• [14]De La Paz MA, Anderson RE: Regional and age-dependent variation in susceptibility of the human retina to lipid peroxidation. Invest Ophthalmol Vis Sci 1992, 33:3497-9.
• [15]Landrum JT, Bone RA, Kilburn MD: The macular pigment : a possible role in protection from age-related macular degeneration. Adv Pharm 1997, 38:537-56.
• [16]Moeller SM, Jaques PF, Blumberg JB: The potential role of dietary xanthophylls in cataract and age-related macular degeneration. J Am Coll Nutr 2000, 19:522S-527S.
• [17]Pratt S: Dietary prevention of age-related macular degeneration. J Am Optom Assoc 1999, 70:39-47.
• [18]Jaques PF: The potential preventive effects of vitamins for cataract and age-related macular degeneration. Int J Vitam Nutr Res 1999, 69:198-205.
• [19]Hammond Br Jr, Johnson EJ, Russel RM, Krinsky NI, Yeum KJ, Edwards RB, et al.: Dietary modification of human macular pigment density. Invest Ophthalmol Vis Sci 1997, 38:1795-1801.
• [20]Handelman GJ, Nightingale ZD, Lichtenstein AH, Schaefer EJ, Blumberg JB: Lutein and zeaxanthin concentrations in plasma after dietary supplementation with egg yolk. Am J Clin Nutr 1999, 70:247-251.
• [21]Landrum JT, Bone RA, Joa H, Kilburn MD, Moore LL, Sprague KE: A one year study of the macular pigment: the effect of 140 days of a lutein supplement. Exp Eye Res 1997, 65:57-62.
• [22]Berendschot TTJM, Goldbohm RA, Klopping WAA, van Norel J, van Norren D: Influence of lutein supplementation on macular pigment, assessed with two objective techniques. Invest Ophthalmol Vis Sci 2000, 41:3322-6.
• [23]The International ARM Epidemiological Study Group: An international classification and grading system for grading system for age-related maculopathy and age-related macular degeneration. Surv Ophthalmol 1995, 39:367-74.
• [24]Macular Photocoagulation Study Group: Laser photocoagulation for juxtafoveal choroidal neovascularization. Five-year results for randomized clinical trials. Arch Ophthalmol 1994, 112:500-9.
• [25]Ghafour IM, Allan D, Foulds WS: Common causes of visual handicap in the west of Scotland. Br J Ophthalmol 1983, 67:209-13.
• [26]Ferris FL III: Senile macular degeneration: review of epidemiological features. Am J Epidemiol 1983, 118:132-51.
• [27]Bressler NM, Bressler SB, Fine SL: Age-related macular degeneration. Surv Ophthalmol 1988, 32:375-413.
• [28]Age-Related Eye Disease Study Report Number 3: Risk factors associated with age-related macular degeneration: a case-control study in the age-related eye disease study. Ophthalmology 2000, 107:2224-2232.
• [29]Klein ML, Mauldin WM, Stoumbos VD: Hereditory and age-related macular degeneration: observations in monozygotic twins. Arch Ophthalmol 1994, 112:932-937.
• [30]Smith W, Assink J, Klein R, Mitchell P, Klaver CC, Klein BE, et al.: Risk factors for age-related macular degeneration: pooled findings from three continents. Ophthalmology 2001, 108:697-704.
• [31]Eye Disease Case-Control Study Group: Risk factors for neovascular age-related macular degeneration. Arch Ophthalmol 1992, 110:1701-1708.
• [32]Klein R, Rowland MR, Harris MI: Racial/ethnic differences in age-related maculopathy. Third National Health and Nutrition Examination Survey. Ophthalmology 1995, 102:371-8.
• [33]Mares-Perlman JA, Brady WE, Klein R, VandenLangenberg GM, Klein BEK, Palta M: Dietary fat and age-related maculopathy. Arch Ophthalmol 1995, 113:743-748.
• [34]Holz FG, Piguet B, Minassian DC, Bird AC, Weale RA: Decreasing stromal iris pigmentation as a risk factor for age-related macular degeneration. Am J Ophthalmol 1994, 117:19-23.
• [35]Sandberg MA, Gaudio AR, Miller S, Weiner A: Iris pigmentation and extent of disease in patients with neovascular age-related macular degeneration. Invest Ophthalmol Vis Sci 1994, 35:2734-40.
• [36]Blumenkranz MS, Russel SR, Robey MG, Kott-Blumenkranz Penneys N: Risk factors in age-related maculopathy complicated by choroidal neovascularization. Ophthalmology 1986, 93:552-6.
• [37]Gibson JM, Shaw DE, Rosenthal AR: Senile cataract and senile macular degeneration. An investigation into possible risk-factors. Trans Ophthalmol Soc UK 1986, 105:463-9.
• [38]Votruba M, Zdenek G: Neovascular age-related macular degeneration: present and future treatment options. Eye 2001, 15:424-429.
• [39]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.
• [40]Sommerburg O, Keunen JEE, Bird AC, van Kuijk FJGM: Fruits and vegetables that are sources of lutein and zeaxanthin: the macular pigment in human eye. Br J Ophthalmol 1998, 82:907-910.
• [41]Leung IYF, Ngai J, Lam KW, Tso MOM: Absorption of zeaxanthin in rats after feeding with purified zeaxanthin or a traditional Chinese medicine, gou chi zi. [ARVO abstract]. Invest Ophthalmol Vis Sci 1999, 40(4):S608. Abstract nr 3196
• [42]Schalch W: Carotenoids in the retina: a review of their possible role in preventing or limiting damage caused by light and oxygen. In Free radicals and ageing. Edited by Emerit I, Chase B. Basel:Birkhauser; 1992.
• [43]West S, Vitale S, Hallfrisch J, Munoz B, Muller D, Bressler S, et al.: Are antioxidants or supplements protective for age-related macular degeneration? Arch Ophthalmol 1994, 112:222-7.
• [44]Johnson EJ, Hammond BR, Yeum KJ, Qin J, Wang XD, Castaneda C, et al.: Relation among serum and tissue concentrations of lutein and zeaxanthin and macular pigment density. Am J Clin Nutr 2000, 71:1555-1562.
• [45]Canfield LM, Giuliano AR, Neilson EM, Yap HH, Graver EJ, Cu HA, et al.: Beta-carotene in breast milk and serum is increased after a single beta-carotene dose. Am J Clin Nutr 1997, 66:52-61.
• [46]Nierenberg DW, Dain BJ, Mott LA, Baron JA, Greenberg ER: Effects of 4 y of oral supplementation with beta-carotene on serum concentrations of retinol, tocopherol, and five carotenoids. Am J Clin Nutr 1997, 66:315-9.
• [47]Fotouhi N, Meydani M, Santos MS, Meydani SN, Hennekens CH, Gaziano JM: Carotenoid and tocopherol concentrations in plasma, peripheral blood mononuclear cells, and red blood cells after long-term supplementation in men. Am J Clin Nutr 1996, 63:533-8.
• [48]Ribaya-Mercado JD, Ordovas JM, Russell RM: Effect of beta-carotene supplementation on the concentrations and distribution of carotenoids, vitamin E, vitamin A and cholesterol in plasma lipoprotein and non-lipoprotein fractions in healthy older women. J Am Coll Nutr 1995, 14:614-20.
• [49]Micozzi MS, Brown ED, Edwards BK, Bieri JG, Taylor PR, Khachik F, et al.: Plasma carotenoid response to chronic intake of selected foods and beta-carotene supplements in men. Am J Clin Nutr 1992, 55:1120-5.
• [50]Albanes D, Virtamo J, Taylor PR, Rautalahti M, Pietinen P, Heinonen OP: Effects of supplemental beta-carotene, cigarette smoking, and alcohol consumption on serum carotenoids in the Alpha-Tocopherol, Beta-carotene Cancer Prevention Study. Am J Clin Nutr 1997, 66:366-72.
• [51]Faulks RM, Hart DJ, Scott KJ, Southon S: Changes in plasma carotenoid and vitamin E profile during supplementation with oil palm fruit carotenoids. J Lab Clin Med 1998, 132:507-11.
• [52]The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group: The effect of vitamin E and beta-carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med 1994, 330:1029-1035.
• [53]Peterson K: 'Natural' cancer prevention trial halted. Science 1996, 271:441.
• [54]Bendich A: The safety of beta-carotene. Nutr Cancer 1988, 11:207-14.
• [55]Newsome DA, Swartz M, Leone NC, Elston RC, Miller E: Oral zinc in macular degeneration. Arch Ophthalmol 1988, 106:192-198.
• [56]Mares-Perlman JA, Klein R, Klein BE, Greger JL, Brady WE, Palta M, Ritter LL: Association of zinc and antioxidant nutrients with age-related maculopathy. Arch Ophthalmol 1996, 114:991-997.
• [57]AREDS report Nn. 8: 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. Arch Ophthalmol 2001, 119:1417-36.
• [58]Clevidence BA, Bieri JG: Association of carotenoids with human plasma lipoproteins. Methods Enzymol 1993, 214:33-46.
• [59]Bernstein PS, Balashov NA, Tsong ED, Rando RR: Retinal tubulin binds macular carotenoids. Inv Ophthalmol Vis Sci 1997, 38:167-75.
• [60]Lakshman Mr, Okoh C: Carotenoid-protein compexes. Methods Enzymol 1993, 214:74-86.
• [61]Reddy KJ, Bullerjahn GS, Sherman LA: Characteristics of membrane-associated carotenoid-binding proteins in cyanobacteria and prochlorophytes. Methods Enzymol 1993, 214:390-401.
• [62]Yemelyanov AYU, Katz NB, Bernstein PS: Ligand-binding characterization of xantophyll carotenoids to solubilized membrane proteins derived from human retina. Exp Eye Res 2001, 72:381-392.
• [63]van den Berg H: Carotenoid interactions. Nutr Rev 1999, 57:1-10.
• [64]Bone RA, Landrum JT, Friedes LM, Gomez CM, Kilburn MD, Menendez E, et al.: Distribution of lutein and zeaxanthin stereoisomers in the human retina. Exp Eye Res 1997, 64:211-218.
• [65]Khachik F, Bernstein PS, Garland DL: Identification of lutien and zeaxanthin oxidation products in human and monkey retinas. Invest Ophthalmol Vis Sci 1997, 38:1802-1811.
• [66]Bone RA, Landrum JT, Hime GW, Cains A, Zamor J: Stereochemistry of the human macular carotenoids. Invest Ophthalmol Vis Sci 1993, 34:2033-2040.
• [67]The Eye-Disease Case Control Study Group: Antioxidant status and neovascular age-related macular degeneration. Arch Ophthalmol 1993, 111:104-109.
• [68]Seddon JM, Ajani UA, Sperduto RD, Hiller R, Blair N, Burton TC, et al.: Dietary carotenoids, vitamin A, C, and E, and advanced age-related macular degeneration. JAMA 1994, 272:1413-1420.
• [69]Mares-Perlman JA, Brady WE, Klein R, Klein BE, Bowen P, Stacewicz-Sapuntzakis M, et al.: Serum antioxidants and age-related macular degeneration in a population-based case control study. Arch Ophthalmol 1995, 113:1518-1523.
• [70]Goldberg J, Flowerdew J, Smith E, Brody JA, Tso MOM: Factors associated with age-related macular degeneration: an analysis of data from the First National Health and Nutrition Examination Survey. Am J Epidemiol 1988, 128:700-710.
• [71]Mares-Perlman JA, Fisher A, 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.
• [72]Vandenlangenberg GM, Mares-Perlman JA, Klein R, Klein BEK, Brady WE, Palta M: 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 1988, 148:204-214.
• [73]Ziegler RG, Colavito EA, Hartge P, Mc Adams MJ, Schoenberg JB, Mason TJ, et al.: Importance of alpha-carotene, beta-carotene, and other phytochemicals in the etiology of lung cancer. J Natl Cancer Inst 1996, 88:612-5.
• [74]Omenn GS, Goodman GE, Thornquist MD, Balmes J, Cullen MR, Glass A, et al.: Effects of a combination of beta-carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med 1996, 334:1150-5.
• [75]Malinow MR, Feeney-Burns L, Peterson LH, Klein ML, Neuringer M: Diet-related macular anomalies in monkeys. Invest Ophthalmol Vis Sci 1980, 19:857-863.
• [76]Leung IYF, Tso MOM, Li WWY, Lam TT: Absorption and tissue distribution of zeaxanthin and lutein in rhesus monkeys after taking fructus lycii (Gou Qi Zi) extract. 2001, 42:466-471.
• [77]Snodderly DM, Shen B, Land RI, Krinsky NI: Dietary manipulation of plasma carotenoid concentrations of squirrel monkeys (Saimiri Sciureus). JNutr 1997, 127:122-9.
• [78]Toyoda Y, Sapunztkis M, Nichols C, Cheng K, Dorey C: Preferential accumulation of lutein and zeaxanthin in the quail retina, an experimental model of the primate macula [ARVO Abstract]. Invest Ophthalmol Vis Sci 1996, 36(3):S802. Abstract nr 3692
• [79]Toyoda Y, Thomson L, Langner A, Craft NE, Garnett KM, Nichols CR, et al.: Effect of dietary zeaxanthin on tissue distribution of zeaxanthin and lutein in quail. Invest Ophthalmol Vis Sci 2002, 43:1210-1221.
• [80]Fite KV, Bengston L: Aging and sex-related changes in the outer retina of the Japanese quail. Curr Eye Res 1989, 8:1039-1048.
• [81]Goldsmith TH, Collins JS, Licht S: The cone oil droplets of avian retinas. Vision Res 1984, 24:1661-1671.
• [82]Thomsom LR, Toyoda Y, Langner A, Delori FC, Garnett KM, Craft N, et al.: Elevated retinal zeaxanthin and prevention of light-induced photoreceptor cell death in quail. Invest Ophthalmol Vis Sci 2002, 43:3538-49.
• [83]Organisciak DT, Want HM, Li Z, Tso MOM: The protective effect of ascorbate in retinal light damage of rats. Invest Ophthalmol Vis Sci 1985, 26:1580-88.
• [84]Leure-duPree AE, Mc Clain CJ: The effect of severe zinc deficiency on the morphology of the rat retinal pigment epithelium. Invest Ophthalmol Vis Sci 1982, 23:425-434.
• [85]Ursin G, Ziegler RG, Subar AF, Graubard BI, Haile RW, Hoover R: Dietary pattern associated with low-fat diet in the national health examination follow-up study: identification of potential confounders for epidemiologic analyses. Am J Epidemiol 1993, 137:916-27.
• [86]Sanders TAB, Haines AP, Wormald R, Wright LA, Obeid O: Essential fatty acids, plasma cholesterol, and fat soluble vitamins in subjects with age-related maculopathy and matched control subjects. Am J Clinc Nutr 1993, 57:428-433.
• [87]Beatty S, Murray IJ, Henson DB, Carden D, Koh HH, 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.
• [88]Bone RA, Landrum JT, Mayne ST, Gomez CM, Tibor SE, Tweiska EE: Macular pigment in donor eyes with and without AMD: a case-control study. Invest Ophthalmol Vis Sci 2001, 42:235-240.
• [89]Sanders TAB, Haines AP, Wormald R, Wright LA, Obeid O: Essential fatty acids, plasma cholesterol, and fat soluble vitamins in subjects with age-related maculopathy and matched control subjects. Am J Clinc Nutr 1993, 57:428-433.
• [90]Hammond BR Jr, Curran-Celentano J, Judd S, Fuld K, Krinsky NI, Wooten BR, et al.: Sex differences in macular pigment optical density: relation to plasma carotenoid concentrations and dietary patterns. Vision Res 1996, 36:2001-12.
• [91]Hammond BR, Wooten BR, Snodderly DM: Cigarette smoking and retinal carotenoids: implications for age-related macular degeneration. Vision Res 1996, 36:3003-9.
• [92]Borges J, Li ZY, Tso MOM: Effects of repeated public exposures on the monkey macula. Arch Ophthalmol 1990, 108:727-733.
• [93]West SK, Rosenthal FS, Bressler NM, Bressler SB, Munoz B, Fine SL, et al.: Exposure to sunlight and other risk factors for age-related macular degeneration. Arch Ophthalmol 1989, 107:875-859.
• [94]Taylor HR, West S, Munoz B, et al.: The long-term effects of visible light on the eye. Arch Ophthalmol 1992, 110:99-104.
• [95]Cruickshanks KJ, Klein R, Klein BE: Sunlight and age-related macular degeneration. The Beaver Dam Eye Study. Arch Ophthalmol 1993, 111:514-518.
• [96]Dayhow-Barker P: Ocular photosensitization. Photochem Photobiol 1986, 46:1051-55.
• [97]McCarty C, Taylor HR: Light and risk for age-related eye diseases. In Nutritional and environmental influences on the eye. Edited by Taylor A. CRC Press, Boca Raton, FL; 1999:135-160.
• [98]Seddon AJ, Ajani UA, Mitchell BD: Familial aggregation of age-related maculopathy. Am J Ophthalmol 1997, 123:199-206.
• [99]Gottfredsdottir MS, Sverrisson T, Musch DC, Steffanson E: Age-related macular degeneration in monozygotic twins and their spouses in Iceland. Acta Ophthalmol Scand 1999, 77:422-425.
• [100]Meyers SM, Greene T, Gutman FA: A twin study of age-related macular degeneration. Am J Ophthalmol 1995, 120:757-766.
• [101]Heiba IM, Elston RC, Klein BE, Klein R: Sibling correlations and segregation analysis of age-related maculopathy: the Beaver Dam Eye Study. Genet Epidemiol 1994, 11:51-67.
• [102]Allikmets R, Shroyer NF, Singh N, Seddon JM, Lewis RA, Bernstein PS, et al.: Mutation of the Stargate disease (ABCR) in age-related macular degeneration. Science 1997, 277:1805-7.
• [103]Stone EM, Webster AR, Vandenburg K, Streb LM, Hockey RR, Lotery AJ, et al.: Allelic variation in ABCR associated with Stargate disease but not age-related macular degeneration. Nat Genet 1998, 20:328-9.
• [104]Danis R, Bingaman DP, Yang Y, Ladd B: Inhibition of preretinal and optic nerve head neovascularization in pigs by intravitreal triamcinolone acetonide. Ophthalmology 1996, 103:2099-2104.
• [105]Ciulla TA, Criswell MH, Danis RP, Hill TE: Intravitreal triamcinolone acetonide inhibits choroidal neovascularization in a laser-treated rat model. Arch Ophthalmol 2001, 119:399-404.
• [106]Mares-Perlman JA: Too soon for lutein supplements. Am J Clin Nutr 1999, 70:431-432.