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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Antioxidants, nuts, fish, and omega-3 polyunsaturated fatty acids have protective effects against AMD.
“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
Results from observational studies that assessed the effect of dietary antioxidants on risk for age-related macular degeneration have been inconsistent.
“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]
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.
“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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Mares, J. A. (2016) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071715-051110 · Cited by 243 · see citing works
“The lowest rates of AMD have been reported in persons consuming 5 to 6 mg/day (118, 131, 165, 191).”
BackgroundBioavailability of lutein from vegetables is 5 times higher than that of β-carotene
Hof, K. H. V. H., Brouwer, I. A., West, C. E., Haddeman, E., Steegers‐Theunissen, R. P. M., van Dusseldorp, M., Weststrate, J. A., Eskes, T. K. A. B., & HAUTVAST, J. G. A. J. (1999) · American Journal of Clinical Nutrition · doi:10.1093/ajcn.70.2.261 · Cited by 243 · see citing works
Bian, Q., Gao, S., Zhou, J., Qin, J., Taylor, A., Johnson, E. J., Tang, G., Sparrow, J. R., Gierhart, D. L., & Shang, F. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.06.024 · Cited by 241 · see citing works
“Epidemiological evidence for these protective effects was first obtained from a large case-control study, which showed that individuals with high dietary intakes and high serum levels of lutein and zeaxanthin have a much lower rate of exudative AMD [3].”
BackgroundMa, L., Dou, H.-L., Wu, Y.-Q., Huang, Y.-M., Huang, Y.-B., Xu, X.-R., Zou, Z.-Y., & Lin, X.-M. (2012) · British Journal of Nutrition · doi:10.1017/s0007114511004260 · Cited by 237 · see citing works
The Potential Role of Dietary Xanthophylls in Cataract and Age-Related Macular Degeneration
Moeller, S. M., Jacques, P. F., & Blumberg, J. B. (2000) · Journal of the American College of Nutrition · doi:10.1080/07315724.2000.10718975 · Cited by 236 · see citing works
Violet and blue light blocking intraocular lenses: photoprotection versus photoreception
Mainster, M. A. (2006) · British Journal of Ophthalmology · doi:10.1136/bjo.2005.086553 · Cited by 236 · see citing works
Health Benefits of Polyphenols and Carotenoids in Age-Related Eye Diseases
BUNGAU, S. G., Abdel‐Daim, M. M., Ţiţ, D. M., Ghanem, E., Sato, S., Maruyama-Inoue, M., Yamane, S., & Kadonosono, K. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/9783429 · Cited by 241 · see citing works
Bhosale, P., & Bernstein, P. S. (2005) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-005-0032-8 · Cited by 234 · see citing works
“Oxidative damage of the retina may underlie the development of age-related macular degeneration and hence the presence of the antioxidants lutein and zeaxanthin may be protective (Seddon et al. 1994; Mares-Perlman et al. 2002).”
BackgroundEisenhauer, B., Natoli, S., Liew, G., & Flood, V. M. (2017) · Nutrients · doi:10.3390/nu9020120 · Cited by 240 · see citing works
Zinkernagel, M. S., Zysset-Burri, D. C., Keller, I., Berger, L. E., Leichtle, A. B., Largiadèr, C. R., Fiedler, G. M., & Wolf, S. (2017) · Scientific Reports · doi:10.1038/srep40826 · Cited by 229 · see citing works
- 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 › 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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