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Dietary Carotenoids, Vitamins A, C, and E, and Advanced Age-Related Macular Degeneration
Abstract
Objective. —To evaluate the relationships between dietary intake of carotenoids and vitamins A, C, and E and the risk of neovascular age-related macular degeneration (AMD), the leading cause of irreversible blindness among adults. Design. —The multicenter Eye Disease Case-Control Study. Setting. —Five ophthalmology centers in the United States. Patients. —A total of 356 case subjects who were diagnosed with the advanced stage of AMD within 1 year prior to their enrollment, aged 55 to 80 years, and residing near a participating clinical center. The 520 control subjects were from the same geographic areas as case subjects, had other ocular diseases, and were frequency-matched to cases according to age and sex. Main Outcome Measures. —The relative risk for AMD was estimated according to dietary indicators of antioxidant status, controlling for smoking and other risk factors, by using multiple logistic-regression analyses. Results. —A higher dietary intake of carotenoids was associated with a lower risk for AMD. Adjusting for other risk factors for AMD, we found that those in the highest quintile of carotenoid intake had a 43% lower risk for AMD compared with those in the lowest quintile (odds ratio, 0.57; 95% confidence interval, 0.35 to 0.92;Pfor trend=.02). Among the specific carotenoids, lutein and zeaxanthin, which are primarily obtained from dark green, leafy vegetables, were most strongly associated with a reduced risk for AMD (Pfor trend=.001). Several food items rich in carotenoids were inversely associated with AMD. In particular, a higher frequency of intake of spinach or collard greens was associated with a substantially lower risk for AMD (Pfor trend<.001). The intake of preformed vitamin A (retinol) was not appreciably related to AMD. Neither vitamin E nor total vitamin C consumption was associated with a statistically significant reduced risk for AMD, although a possibly lower risk for AMD was suggested among those with higher intake of vitamin C, particularly from foods. Conclusion. —Increasing the consumption of foods rich in certain carotenoids, in particular dark green, leafy vegetables, may decrease the risk of developing advanced or exudative AMD, the most visually disabling form of macular degeneration among older people. These findings support the need for further studies of this relationship. (JAMA. 1994;272:1413-1420)
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“analyses have revealed protective effects from antioxidants, nuts, fish, and omega-3 polysaccharide unsaturated fatty acids (AREDS, 2001; Cho et al., 2001; Seddon et al., 1994, 2001; Smith et al., 2000).”
From Molecular pathology of age-related macular degeneration (2009) · cites this paper as Seddon et al., 1994
In the citing paper
“Results from observational studies that assessed the effect of dietary antioxidants on risk for age-related macular degeneration have been inconsistent.90–95”
From Age-related macular degeneration (2008) · cites this paper as [90]
In the citing paper
“Some case-control studies have found evidence of decreasing risk of neovascular age-related macular degeneration among individuals who reported the highest intake of dietary lutein and zeaxanthin, the major macular carotenoids98 that are found mostly in green leafy vegetables such as spinach, collard greens, and kale.90,91,99,100”
From Age-related macular degeneration (2008) · cites this paper as [90]
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Effects of Season and Postharvest Storage on the Carotenoid Content of Solanum phureja Potato Tubers
Griffiths, D. W., Dale, M. F. B., Morris, W. L., & Ramsay, G. (2006) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf0620822 · Cited by 43
Effect of 1-year lutein supplementation on macular pigment optical density and visual function
Sasamoto, Y., Gomi, F., Sawa, M., Tsujikawa, M., & Nishida, K. (2011) · Graefe s Archive for Clinical and Experimental Ophthalmology · doi:10.1007/s00417-011-1780-z · Cited by 42
Horvath, M. P., George, E. W., Trần, Q. T. L., Baumgardner, K., Zharov, G., Lee, S., Sharifzadeh, H., Shihab, S., Mattinson, T., Li, B., et al. (2016) · Acta Crystallographica Section F Structural Biology Communications · doi:10.1107/s2053230x16010694 · Cited by 42
“…shown that dietary intake and supplementation with lutein and zeaxanthin increase the likelihood of avoiding age-related macular degeneration (AMD), a leading cause of blindness (Seddon et al., 1994; Age-Related Eye Disease Study 2 Research Group, 2014; Wu et al., 2015; Bernstein et al., 2016).”
BackgroundJeon, S., Ranard, K. M., Neuringer, M. D., Johnson, E. E., Renner, L. M., Kuchan, M. J., Pereira, S. L., Johnson, E. J., & Erdman, J. W. (2018) · Journal of Nutrition · doi:10.1093/jn/nxx023 · Cited by 42
“Epidemiologic and large-scale clinical studies have shown that increased intake of lutein and zeaxanthin is associated with a decreased risk of age-related macular degeneration, a leading cause of irreversible visual loss in older adults (11, 12).”
Backgroundde Kinkelder, R., van der Veen, R. L. P., Verbaak, F. D., et al. (2010) · Eye · doi:10.1038/eye.2010.164 · Cited by 42
McCarty, M. F. (2000) · Medical Hypotheses · doi:10.1054/mehy.2000.1075 · Cited by 43
Spirulina is an effective dietary source of zeaxanthin to humans
Yu, B., Wang, J., Suter, P. M., Russell, R. M., Grusak, M. A., Wang, Y., Wang, Z., Yin, S., & Tang, G. (2012) · British Journal Of Nutrition · doi:10.1017/s0007114511005885 · Cited by 40
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de Carvalho, T. C. L., & Nunes, C. A. (2021) · Journal of Food Composition and Analysis · doi:10.1016/j.jfca.2021.104164 · Cited by 41
Oxidation of carotenoids by heat and tobacco smoke
Hurst, J. S., Contreras, J. E., Siems, W. G., & van Kuijk, F. J. G. M. (2004) · BioFactors · doi:10.1002/biof.5520200103 · Cited by 41
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Diminishing Risk for Age-Related Macular Degeneration with Nutrition: A Current View
Schleicher, M. M., Weikel, K., Garber, C., & Taylor, A. (2013) · Nutrients · doi:10.3390/nu5072405 · Cited by 42
“Case-control analysis of patients in the Beaver Dam Eye Study, EDCC and three additional studies did not find any association between serum levels of alpha-carotene and any stage of AMD or any difference in blood levels of alpha-carotene between AMD patients and controls [69,85,86,90,98,102].”
BackgroundInfluentialTamura, H., Goto, R., Akune, Y., Hiratsuka, Y., Hiragi, S., & Yamada, M. (2015) · PLoS ONE · doi:10.1371/journal.pone.0133628 · Cited by 43
Ong, F. S.-C., Kuo, J. Z.-C., Wu, W., Cheng, C., Blackwell, W.-L. B., Taylor, B. L., Grody, W. W., Rotter, J. I., Lai, C., & Wong, T. Y. (2013) · Journal of Personalized Medicine · doi:10.3390/jpm3010040 · Cited by 39
Vitamin A-aldehyde adducts: AMD risk and targeted therapeutics
Sparrow, J. R. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1600474113 · Cited by 40
Xavier, A. A. O., Carvajal-Lérida, I., Garrido‐Fernández, J., et al. (2017) · Journal of Food Composition and Analysis · doi:10.1016/j.jfca.2017.01.015 · Cited by 39
“A low intake of lutein food sources is related with the risk of developing AMD (Dwyer et al., 2001; Seddon et al., 1994; Shao, 2001).”
BackgroundInfluentialPhillips, K. M., Tarragó‐Trani, M. T., McGinty, R. C., Rasor, A. S., Haytowitz, D. B., & Pehrsson, P. R. (2018) · Journal of the Science of Food and Agriculture · doi:10.1002/jsfa.8941 · Cited by 40
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“caused by complications of metabolic disorders such as diabetes (Hankinson et al., 1992; Seddon et al., 1994; Brown et al., 1999; Chasan-Taber et al., 1999; Lyle et al., 1999; MaresPerlman et al., 2001; Gale et al., 2001).”
Noninvasive detection of macular pigments in the human eye
Gellermann, W., & Bernstein, P. S. (2004) · Journal of Biomedical Optics · doi:10.1117/1.1628240 · Cited by 39
“It has also been demonstrated that MP levels are lower in autopsy eyes from patients with AMD.8,9 In order to advance our understanding of MPs with a view to preventing AMD, more reliable data on carotenoid levels in the living human eye are needed.”
BackgroundBeta-Carotene and the Carotenoids: Beyond the Intervention Trials
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Phenotypic Heterogeneity in Families with Age-related Macular Degeneration
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“Evidence for lutein and zeaxanthin contributing to AMD prevention has been shown in case–control studies((4)) and cohort studies((2,18)).”
Development and characterization of lutein-loaded SNEDDS for enhanced absorption in Caco-2 cells
Niamprem, P., Rujivipat, S., & Tiyaboonchai, W. (2013) · Pharmaceutical Development and Technology · doi:10.3109/10837450.2013.829092 · Cited by 37
Use of a 13C tracer to quantify the plasma appearance of a physiological dose of lutein in humans
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Gayathri, S., Radhika, S., Suman, T. Y., & Aranganathan, L. (2018) · Biomass Conversion and Biorefinery · doi:10.1007/s13399-018-0331-9 · Cited by 37
Grčević, M., Kralik, Z., Kralik, G., et al. (2018) · Journal of the Science of Food and Agriculture · doi:10.1002/jsfa.9425 · Cited by 37
Longitudinal Study of Visual Function in Dry Age-Related Macular Degeneration at 12 Months
Hsu, S. T., Thompson, A. C., Stinnett, S. S., et al. (2019) · Ophthalmology Retina · doi:10.1016/j.oret.2019.03.010 · Cited by 37
Serum Lutein is related to Relational Memory Performance
Cannavale, C. N., Hassevoort, K. M., Edwards, C., Thompson, S. V., Burd, N. A., Holscher, H. D., Erdman, J. W., Cohen, N. J., & Khan, N. A. (2019) · Nutrients · doi:10.3390/nu11040768 · Cited by 39
“In the retina, lutein is protective against age-related macular degeneration by reducing oxidative stress [13,14].”
BackgroundBritten‐Jones, A. C., Singh, S., Craig, J. P., & Downie, L. E. (2020) · Nutrients · doi:10.3390/nu12041179 · Cited by 43
Diet and risk factors for age-related maculopathy
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Zeaxanthin inhibits PDGF‐BB‐induced migration in human dermal fibroblasts
Wu, N., Chiang, Y.-C., Huang, C., Fang, J., Chen, D., & Hung, C. (2010) · Experimental Dermatology · doi:10.1111/j.1600-0625.2009.01036.x · Cited by 37
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Why Is Zeaxanthin the Most Concentrated Xanthophyll in the Central Fovea?
Widomska, J., SanGiovanni, J. P., & Subczynski, W. K. (2020) · Nutrients · doi:10.3390/nu12051333 · Cited by 37
Wang, Y., Connor, S. L., Wang, W., Johnson, E. J., & Connor, W. E. (2007) · Experimental Eye Research · doi:10.1016/j.exer.2006.11.013 · Cited by 36
Bisretinoids of the Retina: Photo-Oxidation, Iron-Catalyzed Oxidation, and Disease Consequences
Kim, H. J., Montenegro, D., Zhao, J., & Sparrow, J. R. (2021) · Antioxidants · doi:10.3390/antiox10091382 · Cited by 35
Unhealthy behaviours and risk of visual impairment: The CONSTANCES population-based cohort
Merle, B. M. J., Moreau, G., Ozguler, A., Srour, B., Cougnard‐Grégoire, A., Goldberg, M., Zins, M., & Delcourt, C. (2018) · Scientific Reports · doi:10.1038/s41598-018-24822-0 · Cited by 40
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“Epidemiology studies were starting to show that high blood levels and high dietary consumption of L and Z were associated with decreased risk of advanced AMD, while β-carotene was not (29, 30).”
BackgroundCarotenes and xanthophylls as antioxidants
Rodriguez–Amaya, D. B. (2015) · Elsevier eBooks · doi:10.1016/b978-1-78242-089-7.00002-6 · Cited by 42
Kim, J., Ahn, J., Ha, T. Y., et al. (2011) · Korean Journal of Food Science and Technology · doi:10.9721/kjfst.2011.43.5.564 · Cited by 34
“는데, β-carotene은 눈 건강 및 암 예방 효과(8,9), lutein과 zeaxanthin은 노인성 황반변증과 초기 동맥경화 예방 효과(10,11), capsanthin은 동맥경화 및 심장질환의 위험 감소 효과(12,13) 등이 보고되고 있다.”
Liquid antisolvent precipitation: an effective method for ocular targeting of lutein esters
Wu, M., Feng, Z., Deng, Y., et al. (2019) · International Journal of Nanomedicine · doi:10.2147/ijn.s194068 · Cited by 34
“Therefore, daily intake of 6 mg of lutein from food can reduce the risk of developing AMD.(13) Lutein can also effectively inhibit gastric cancer,(14) breast cancer,(15) esophageal cancer,(16) and oral epithelial cancer.”
BackgroundClark, R. M., Herron, K. L., Waters, D. D., & Fernández, M. L. (2006) · Journal of Nutrition · doi:10.1093/jn/136.3.601 · Cited by 34
Peter, I., Huggins, G. S., Ordovás, J. M., Haan, M. N., & Seddon, J. M. (2011) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2011.05.016 · Cited by 34
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Retinal and Choroidal Blood Flow in Health and Disease
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Isolation, Characterization, and Diversity of Novel Radiotolerant Carotenoid-Producing Bacteria
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Effect of Dietary Carotenoid on Egg Yolk Color and Singlet Oxygen Quenching Activity of Laying Hens
Kojima, S., Koizumi, S., Kawami, Y., Shigeta, Y., & Osawa, A. (2021) · The Journal of Poultry Science · doi:10.2141/jpsa.0210032 · Cited by 41
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Genotype × Environment Interactions for Potato Tuber Carotenoid Content
Haynes, K. G., Clevidence, B. A., Rao, D., Vinyard, B. T., & White, J. M. (2010) · Journal of the American Society for Horticultural Science · doi:10.21273/jashs.135.3.250 · Cited by 33
Physiology of Light Tolerance in Plants
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“Various observational studies suggest a protective effect of lutein against eye diseases such as age-related macular degeneration [1–4] and cataract [5,6].”
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Electrospray tandem mass spectrometric analysis of zeaxanthin and its oxidation products
PRASAIN, J. K., Moore, R., Hurst, J. S., et al. (2005) · Journal of Mass Spectrometry · doi:10.1002/jms.868 · Cited by 32
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Enzymes and Mechanisms for Violaxanthin-zeaxanthin Conversion
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Antioxidant vitamin and mineral supplements for age-related macular degeneration.
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“…environmental risk factors or subphenotypes could account for our findings, we compared environmental risk factors (smoking and body mass index) 16 , 17 and the two main subtypes of AMD, advanced dry (geographic atrophy) and wet (choroidal neovascularization) AMD, in families whose genotypic…”
Self-citationChew, E. Y. (2020) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2020.05.042 · Cited by 33
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“Seddon et al. (1994) reported that lutein and zeaxanthin are prominent macular pigments that can reduce the risk of age-related macular degeneration.”
BackgroundThe role of omega-3 and micronutrients in age-related macular degeneration
Querques, G., & Souied, E. H. (2014) · Survey of Ophthalmology · doi:10.1016/j.survophthal.2014.01.001 · Cited by 31
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“…and filtering capability of MP translates to a significantly reduced risk of developing diseases that are brought on by cumulative tissue damage, including agerelated macular degeneration (AMD; e.g. Seddon et al., 1994), the leading cause of blindness in the Western world (Klaver et al., 1998).”
BackgroundThoene, M. K., Anderson‐Berry, A., Ormer, M. V., Furtado, J. D., Soliman, G. A., Goldner, W. S., & Hanson, C. (2019) · Nutrients · doi:10.3390/nu11010134 · Cited by 30
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“With respect to ocular health, lutein and zeaxanthin are now believed to play a quasi-essential role in the retinal macula, protecting this key region from light-generated free radicals, and thereby diminishing risk for age-related macular degeneration [31–35].”
BackgroundBhosale, P., & Bernstein, P. S. (2005) · Analytical Biochemistry · doi:10.1016/j.ab.2005.07.006 · Cited by 31
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“Low systemic and retinal levels of lutein and zeaxanthin are adversely associated with the risk of age-related macular disease (AMD) and diabetic retinopathy [7–10].”
BackgroundAbsorption of Carotenoids and Mechanisms Involved in Their Health-Related Properties
Cervantes‐Paz, B., Victoria-Campos, C. I., & Ornelas‐Paz, J. D. J. (2016) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-3-319-39126-7_16 · Cited by 36
Simple Raman Instrument for in vivo Detection of Macular Pigments
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“It has been suggested that carotenoids through these biological functions and actions may protect against degenerative diseases, for example, cardiovascular disease (16,17), cancer (16,18) and age-related macular degeneration (15,16).”
BackgroundCurrent and Future Treatment Options for Nonexudative and Exudative Age-Related Macular Degeneration
Comer, G., Ciulla, T., Criswell, M., & Tolentino, M. (2004) · Drugs & Aging · doi:10.2165/00002512-200421150-00002 · Cited by 33
Antioxidants in Age-Related Macular Degeneration: Lights and Shadows
Parmar, U. P. S., Surico, P. L., Mori, T., Singh, R. B., Cutrupi, F., Premkishore, P., Afflitto, G. G., Zazzo, A. D., Coassin, M., & Romano, F. (2025) · Antioxidants · doi:10.3390/antiox14020152 · Cited by 32
“This five-year trial involved over 4000 participants with intermediate AMD and sought to assess whether these changes could further reduce the progression to advanced AMD [120].”
InfluentialFatty Acids and Bioactive Lipids of Potato Cultivars: An Overview
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Genetic Susceptibility, Diet Quality, and Two-Step Progression in Drusen Size
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The growth and development of cress (Lepidium sativum) affected by blue and red light
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“Vitamins and green pigments (high chlorophyll) are valuable compounds in this plant which play an important role in human health (Curran-Celentano et al., 2001; Giovannucci, 1999; Humphrey et al., 1992; Mayne, 1996; Seddon et al., 1994).”
BackgroundLutein Is Stable in Strawberry Yogurt and Does Not Affect its Characteristics
Aryana, K. J., Barnes, H. T., Emmick, T. K., et al. (2006) · Journal of Food Science · doi:10.1111/j.1750-3841.2006.00080.x · Cited by 30
Molecular Genetics of Age-Related Macular Degeneration: Current Status
Allikmets, R. (1999) · European Journal of Ophthalmology · doi:10.1177/112067219900900401 · Cited by 29
Role of flavonoids in age-related macular degeneration
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“In the multicenter Eye Disease CaseControl Study (Seddon et al., 1994), vegetables, particularly GLV such as spinach and collard greens (B. oleracea var. acephala L.), were strongly associated with a lower AMD risk (P-trend <0.001).”
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“The exact mechanismunderlying the role of obesity in AMD is uncertain, but it seems that some metabolic features of obesity, including elevated oxidative stress (Zarbin, 2004), decreased carotenoid intake (Seddon et al., 1994) and systemic inflammation (Seddon et al.”
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Storage Stability of Lutein During Ripening of Cheddar Cheese
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Inside out: Relations between the microbiome, nutrition, and eye health
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Sharan, S. (2005) · British Journal of Ophthalmology · doi:10.1136/bjo.2005.070839 · Cited by 28
Metadata
- Authors
- Seddon, J. M.
- Corresponding author
- Seddon, Johanna M.
- ORCID
- Seddon, Johanna M.
- Venue
- JAMA: The Journal of the American Medical Association
- Publisher
- American Medical Association (AMA)
- Published
- 1994-11-09
- Volume
- 272
- Issue
- 18
- Pages
- 1413
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- OpenAlex
- W4296976934
- Cited by
- 993
- References
- 0
- Citations by year
- 2026: 10 · 2025: 17 · 2024: 48 · 2023: 27 · 2022: 30 · 2021: 30 · 2020: 39 · 2019: 44 · 2018: 35 · 2017: 35 · 2016: 37 · 2015: 41 · 2014: 38 · 2013: 41 · 2012: 56
- FWCI
- 21.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JAMA (publishedVersion)
- Funders
- National Eye Institute (EY09972)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
- Keywords
- neovascular age-related macular degeneration, dietary carotenoids, lutein, zeaxanthin, vitamin A, vitamin C, vitamin E, antioxidant intake, dark green leafy vegetables, spinach, collard greens, AMD risk factors, dietary intake, older adults, blindness prevention, retinol, dietary supplements
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