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Associations between Antioxidant and Zinc Intake and the 5-Year Incidence of Early Age-related Maculopathy in the Beaver Dam Eye Study
Abstract
Associations between antioxidants and zinc and the 5-year incidence of early, age-related maculopathy (ARM) were investigated in a population-based cohort of middle-aged and older adults participating in the Beaver Dam Eye Study in Beaver Dam, Wisconsin. A food-frequency questionnaire was administered at baseline (1988-1990) to collect dietary information for that time period and a period of time 10 years earlier (1978-1980) from a 50 percent random sample of persons participating in this study. The incidence of the specific lesions of larger drusen (>125 microns) and pigmentary abnormalities and the incidence of any ARM were assessed by masked grading of stereoscopic color fundus photographs in 1,709 persons who participated in 5-year follow-up eye examinations. Significant, but modest, inverse associations (p < 0.05) were observed between intakes of pro-vitamin A carotenoids and dietary vitamin E and the incidence of large drusen and between zinc and the incidence of pigmentary abnormalities. No significant inverse associations were found between antioxidant or zinc intake and the incidence of overall early ARM. If ARM, which is characterized by a broad spectrum of lesions, involves a number of different underlying pathophysiologic processes, then associations between specific antioxidants and the incidence of distinct macular lesions may be biologically important. However, because there were too few incident late ARM cases in this cohort, the authors were unable to assess whether antioxidant intake is associated with the progression of early ARM to late-stage macular degeneration. Clinical trials and longer-term prospective studies are needed to elucidate further the impact of antioxidants and zinc on the development and progression of ARM.
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“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 [93]
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Jager, R. D., Mieler, W. F., & Miller, J. W. (2008) · New England Journal of Medicine · doi:10.1056/nejmra0801537 · Cited by 1,379
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Zarbin, M. A. (2004) · Archives of Ophthalmology · doi:10.1001/archopht.122.4.598 · Cited by 1,006
Age-related macular degeneration: etiology, pathogenesis, and therapeutic strategies
Ambati, J., Ambati, B. K., Yoo, S. H., Ianchulev, S., & Adamis, A. P. (2003) · Survey of Ophthalmology · doi:10.1016/s0039-6257(03)00030-4 · Cited by 959
B IOLOGIC M ECHANISMS OF THE P ROTECTIVE R OLE OF L UTEIN AND Z EAXANTHIN IN THE E YE
Krinsky, N. I., Landrum, J. T., & Bone, R. A. (2003) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.23.011702.073307 · Cited by 779
“However, a later study from this group reported a significant relationship between the intake of pro-vitamin A carotenoids ( α-carotene,β-carotene and β-cryptoxanthin) and the incidence of large drusen, frequently used as a marker of early AMD (149).”
BackgroundAge-related macular degeneration
Coleman, H. R., Chan, C.-C., Ferris, F. L., & Chew, E. Y. (2008) · The Lancet · doi:10.1016/s0140-6736(08)61759-6 · Cited by 542
Seddon, J. M. (2005) · Archives of Ophthalmology · doi:10.1001/archopht.123.3.321 · Cited by 446
“Although our results indicate a relatively larger role for genetic factors, to date the evidence for environmental risk factors in the etiology of AMD has been more clearly delineated, including behavioral, lifestyle, and medical factors such as cigarette smoking,(14-16) overall obesity and abdominal adiposity,(17) sy…”
BackgroundAge-Related Macular Degeneration
Fine, S. L., Berger, J. W., Maguire, M. G., & Ho, A. C. (2000) · New England Journal of Medicine · doi:10.1056/nejm200002173420707 · Cited by 424
Progression of Age-Related Macular Degeneration
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Prevention of age related macular degeneration
Hall, N. F., & Galé, C. R. (2002) · BMJ · doi:10.1136/bmj.325.7354.1 · Cited by 396
Risk factors for progression of age‐related macular degeneration
Heesterbeek, T. J., Lorés‐Motta, L., Hoyng, C. B., Lechanteur, Y. T. E., & den Hollander, A. I. (2020) · Ophthalmic and Physiological Optics · doi:10.1111/opo.12675 · Cited by 399
“Higher levels of a-carotene and b-carotene were associated with decreased risk of early and late AMD in some studies,(194,201,202) but most studies did not find any association.(189,192,194,195) Two studies reported even an increased risk of developing late AMD in those consuming higher levels of dietary b-carotene.”
InfluentialDietary Antioxidants and the Long-term Incidence of Age-Related Macular Degeneration
Tan, J. S. L., Wang, J. J., Flood, V., Rochtchina, E., Smith, W., & Mitchell, P. (2008) · Ophthalmology · doi:10.1016/j.ophtha.2007.03.083 · Cited by 381
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Self-citationDietary intake of antioxidants and risk of age-related macular degeneration
van Leeuwen, R. (2005) · JAMA · doi:10.1001/jama.294.24.3101 · Cited by 345
Risk Factors for Age-related Macular Degeneration
Evans, J. R. (2001) · Progress in Retinal and Eye Research · doi:10.1016/s1350-9462(00)00023-9 · Cited by 340
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Self-citationDry Age-Related Macular Degeneration: Mechanisms, Therapeutic Targets, and Imaging
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ResultLutein and Zeaxanthin Status and Risk of Age-Related Macular Degeneration
Galé, C. R., Hall, N. F., Phillips, D. I. W., & Martyn, C. (2003) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.02-0929 · Cited by 258
“In the Beaver Dam Eye Study, there were no statistically significant correlations between intake of lutein and zeaxanthin and the prevalence of early or late age-related macular degeneration(21) or the incidence of early macular degeneration.(22) Lutein and zeaxanthin may have different functions in the retina.”
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Antioxidant vitamin and mineral supplements for preventing age-related macular degeneration
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Moeller, S. M. (2006) · Archives of Ophthalmology · doi:10.1001/archopht.124.8.1151 · Cited by 257
“We did not observe any statistically significant associations in the overall sample or in the subsample of all women younger than 75 years, which is consistent with the null or weak associations observed in other studies of early and intermediate stages of AMD.(35,37,43) One small”
ResultMiller, J. W. (2012) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2012.10.018 · Cited by 254
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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
“[33] followed subjects from the Beaver Dam cohort who were free of late stage AMD at baseline for five years and found no significant association between specific macular lesions and lutein and zeaxanthin intake either 10 years before study enrollment or at baseline.”
BackgroundEisenhauer, B., Natoli, S., Liew, G., & Flood, V. M. (2017) · Nutrients · doi:10.3390/nu9020120 · Cited by 240
“Van den Langenberg 1998 Beaver Dam Eye Study [29] 5-year follow-up of 1709 US men and women aged 43–84 years Median intake (μg per 1000 kcal): Quintile 1: 294 μg Quintile 5: 1006 μg FFQ (100 item) No significant association between L/Z intake and early AMD.”
BackgroundWu, J., Cho, E., Willett, W. C., Sastry, S. M., & Schaumberg, D. A. (2015) · JAMA Ophthalmology · doi:10.1001/jamaophthalmol.2015.3590 · Cited by 231
Trieschmann, M., Beatty, S., Nolan, J. M., Hense, H. W., Heimes, B., Austermann, U., Fobker, M., & Pauleikhoff, D. (2006) · Experimental Eye Research · doi:10.1016/j.exer.2006.12.010 · Cited by 220
“…and/or serum levels of L and Z were associated with subtypes of AMD in some, (Gale et al., 2003; Mares-Perlman et al., 2001; Seddon et al., 1994; Snellen et al., 2002), but not all (Cardinault et al., 2005; Dasch et al., 2005; Mares-Perlman et al., 1995; VandenLangenberg et al., 1998), studies.”
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“However, in several studies, these associations were not observed [56,72] or were observed only in population subgroups [71].”
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“In addition, nutritional factors are related to AMD (Seddon et al. 1994, 2001b; Mares-Perlman et al. 1995; VandenLangenberg et al. 1998).”
BackgroundNutritional antioxidants and age-related cataract and maculopathy
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“Some studies did indeed find an inverse association between zinc intake and ARM [103], while others did not [110, 111, 113, 114].”
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“The Beaver Dam Eye study indicated a correlation between low vitamin E intake and developing large drusen [47], whereas the Eye Disease Case-control Study Group did not identify a significant interaction between the risk of AMD and vitamin E [48].”
Iyengar, S. K., Song, D., Klein, B. E. K., Klein, R., Schick, J. H., Humphrey, J., Millard, C., Liptak, R., Russo, K., Jun, G., et al. (2004) · The American Journal of Human Genetics · doi:10.1086/380912 · Cited by 173
“…ARMD development is associated with numerous environmental factors, such as smoking (Klein et al. 1993, 1998b, 2002b; DeBlack 2003), sunlight exposure (Cruickshanks et al. 1993), and diet (Seddon et al. 1994; Mares-Perlman et al. 1996; VandenLangenberg et al. 1998; Jacques 1999; Anonymous 2002).”
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“A recent prospective population-based cohort study demonstrated no relationship between incidence of early ARMD and dietary intake of zinc, whereas a modest inverse association was observed between dietary zinc and development of retinal pigmentary abnormalities [115].”
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Age-related Macular Degeneration and Antioxidant Status in the POLA Study
Delcourt, C. (1999) · Archives of Ophthalmology · doi:10.1001/archopht.117.10.1384 · Cited by 158
Decanini, A., Nordgaard, C. L., Feng, X., Ferrington, D. A., & Olsen, T. W. (2007) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2006.12.006 · Cited by 157
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Ugarte, M., Osborne, N. N., Brown, L. A., & Bishop, P. N. (2013) · Survey of Ophthalmology · doi:10.1016/j.survophthal.2012.12.002 · Cited by 161
Healthy Lifestyles Related to Subsequent Prevalence of Age-Related Macular Degeneration
Mares, J. A. (2010) · Archives of Ophthalmology · doi:10.1001/archophthalmol.2010.314 · Cited by 156
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Lutein Supplementation for Eye Diseases
Li, L. H., Lee, J. C.-Y., Leung, H. H., Lam, W. C., Fu, Z., & Lo, A. C. Y. (2020) · Nutrients · doi:10.3390/nu12061721 · Cited by 152
“VandenLangenberg 1998 [82] Beaver Dam Study Population based cohort study, 5-year incidence 1709 adults in USA Too few incidence, unable to show association of lutein with age-related maculopathy”
BackgroundAge-Related Macular Degeneration: Advances in Management and Diagnosis
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Meyers, K. J., Mares, J. A., Igo, R. P., Truitt, B. J., Liu, Z., Millen, A. E., Klein, R., Johnson, E. J., Engelman, C. D., Karki, C. K., et al. (2013) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.13-13216 · Cited by 136
Self-citationOxidative stress and its downstream signaling in aging eyes
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“The Beaver Dam Eye Study 104 found an inverse association between vitamin A and E intake and the incidence of large drusen, and between zinc intake and the incidence of macropigmentary changes in early AMD.”
BackgroundThe Age-Related Eye Disease 2 Study: Micronutrients in the Treatment of Macular Degeneration
Gorusupudi, A., Nelson, K., & Bernstein, P. S. (2017) · Advances in Nutrition · doi:10.3945/an.116.013177 · Cited by 130
“(53) 1709 R, cross-sectional, Beaver Dam Eye Study Photograph grading, dietary intake assessment Significant modest associations were observed between provitamin A carotenoid and vitamin E intake and incidence of large drusen (P , 0.”
BackgroundAge‐Related Macular Degeneration
Cheung, L. K., & Eaton, A. (2013) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1002/phar.1264 · Cited by 130
Production of O/W Emulsions Containing Astaxanthin by Repeated Premix Membrane Emulsification
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Age-Related Macular Degeneration
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“[140,141] The Australian Blue Mountains Eye Study[142] did not find significant associations betweenARM/AMDand serum levels of zinc, vitamin E or β-carotene.”
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Review of nutrient actions on age-related macular degeneration
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“75, which was obtained by pooling the results from two studies: the Rotterdam eye study [46] and the Beaver Dam eye study [40,47].”
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“Previous research has also supported the importance of analyzing diet and disease relations in the appropriate temporal sequence (30).”
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Cho, E., Hankinson, S. E., ROSNER, B. A., Willett, W. C., & Colditz, G. A. (2008) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/87.6.1837 · Cited by 94
“Three cohort studies with early AMD cases only or with mostly early AMD cases found no inverse association (27,28, 30).”
BackgroundLutein, Zeaxanthin, andmeso-Zeaxanthin in the Clinical Management of Eye Disease
Scripsema, N. K., Hu, D., & Rosen, R. B. (2015) · Journal of Ophthalmology · doi:10.1155/2015/865179 · Cited by 98
“They analyzed six longitudinal cohort studies [68–72] and found that early and late AMD have different relationship with the intake of L and Z.”
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Hogg, R. E., Woodside, J. V., McGrath, A. J., Young, I. S., Vioqué, J., Chakravarthy, U., de Jong, P. T. V. M., Rahu, M., Seland, J. H., Soubrane, G., et al. (2016) · Ophthalmology · doi:10.1016/j.ophtha.2016.09.019 · Cited by 98
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Weikel, K., Chiu, C., & Taylor, A. (2012) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2012.03.005 · Cited by 89
“…of the Beaver Dam Eye Study indicated that there was a decrease in risk for pigment abnormalities 5 years after baseline for those with past zinc intake (food and supplements) in the highest quintile (OR = 0.38; 95% CI: 0.20, 1.00; p = 0.03 for trend) (VandenLangenberg et al., 1998) (Fig.”
BackgroundMethodInfluentialAge-Related Maculopathy in a Randomized Trial of Low-Dose Aspirin Among US Physicians
Christen, W. G. (2001) · Archives of Ophthalmology · doi:10.1001/archopht.119.8.1143 · Cited by 88
Sabour‐Pickett, S., Nolan, J. M., Loughman, J., & Beatty, S. (2011) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201100219 · Cited by 85
“A large number of studies have investigated the relationship between dietary intake of the macular carotenoids and AMD (Table 2) [72, 132–138].”
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Vishwanathan, R., Chung, M., & Johnson, E. J. (2013) · Investigative Ophthalmology and Visual Science · doi:10.1167/iovs.12-11552 · Cited by 85
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Lem, D. W., Davey, P. G., Gierhart, D. L., & Rosen, R. B. (2021) · Antioxidants · doi:10.3390/antiox10081255 · Cited by 85
“For instance, the Beaver Dam Eye Study found that neither dietary intake nor serum carotenoid levels were significantly correlated with AMD [193,201], while the Muenster Aging and Retina Study (MARS), in Germany, also observed a non-statistically significant association between plasma concentrations and age-related ma…”
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Risk Factors for Five-Year Incident Age-related Macular Degeneration: The Reykjavik Eye Study
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“lutein Prospective cohort studies Vandenlandgenberg et al, 1998 (16) Beaver Dam, 1709 subjects; 5-y”
BackgroundProspective Study of Zinc Intake and the Risk of Age-Related Macular Degeneration
Cho, E., Stampfer, M. J., Seddon, J. M., Hung, S., Spiegelman, D. L., Rimm, E. B., Willett, W. C., & Hankinson, S. E. (2001) · Annals of Epidemiology · doi:10.1016/s1047-2797(01)00217-4 · Cited by 75
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Self-citationDose-Ranging Study of Lutein Supplementation in Persons Aged 60 Years or Older
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Zn2+ Enhances the Molecular Chaperone Function and Stability of α-Crystallin
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AMD and micronutrient antioxidants
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Evidence for the Use of Nutritional Supplements and Herbal Medicines in Common Eye Diseases
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The Antioxidant Vitamins C and E
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An ideal ocular nutritional supplement?*
Bartlett, H. E., & Eperjesi, F. (2004) · Ophthalmic and Physiological Optics · doi:10.1111/j.1475-1313.2004.00218.x · Cited by 59
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“Many physicians suggest that 15 to 30 mg of zinc per day is necessary for a healthy vision [37].”
BackgroundMillen, A. E. (2003) · American Journal of Epidemiology · doi:10.1093/aje/kwg116 · Cited by 56
“Am J Epidemiol 2003;158:225–233 other studies of diet and age-related eye disease have shown that assessment of past dietary intake, or intake prior to incident disease, may be more influential then recent dietary intake on eye disease development (42, 43).”
BackgroundGenetics of age-related macular degeneration
Ting, A., Lee, T. K. M., & MacDonald, I. M. (2009) · Current Opinion in Ophthalmology · doi:10.1097/icu.0b013e32832f8016 · Cited by 58
Nutrition Effects on Ocular Diseases in the Aging Eye
Chew, E. Y. (2013) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs13-12914 · Cited by 51
Alcohol consumption and the 5-year incidence of age-related maculopathy
Moss, S. E., Klein, R., Klein, B. E. K., Jensen, S. C., & Meuer, S. M. (1998) · Ophthalmology · doi:10.1016/s0161-6420(98)95016-3 · Cited by 49
Self-citationRisk Factors for Age-Related Maculopathy
Connell, P., Keane, P. A., O’Neill, E. C., Al‐Taie, R., Loane, E., Neelam, K., Nolan, J. M., & Beatty, S. (2009) · Journal of Ophthalmology · doi:10.1155/2009/360764 · Cited by 49
“Cross-sectional data from the Beaver Dam Eye Study also showed that a high dietary intake of vitamin C was negatively associated with early ARM, but this finding was not statistically significant [229, 237].”
BackgroundInfluentialPrevention of age-related macular degeneration
Wong, I. Y., Koo, S., & Chan, C. W. N. (2010) · International Ophthalmology · doi:10.1007/s10792-010-9397-5 · Cited by 51
“These ingredients were thought to exert a protective effect on retinal cells by counteracting oxidative stresses [10–15].”
BackgroundNutritional supplements in age‐related macular degeneration
Schmidl, D., Garhöfer, G., & Schmetterer, L. (2015) · Acta ophthalmologica · doi:10.1111/aos.12650 · Cited by 97
Five Heavy Metallic Elements and Age-Related Macular Degeneration
Park, S. J., Lee, J. H., Woo, S. J., et al. (2014) · Ophthalmology · doi:10.1016/j.ophtha.2014.07.039 · Cited by 46
Serum levels of macular carotenoids in relation to age-related maculopathy
Dasch, B., Fuhs, A., Schmidt, J. G. H., Behrens, T., Meister, A., Wellmann, J., Fobker, M., Pauleikhoff, D., & Hense, H. (2005) · Graefe s Archive for Clinical and Experimental Ophthalmology · doi:10.1007/s00417-005-1176-z · Cited by 42
“However, not all observational studies could confirm these results [13, 18, 28, 29, 43].”
ResultVitamin E and Age-Related Macular Degeneration in a Randomized Trial of Women
Christen, W. G., Glynn, R. J., Chew, E. Y., & Buring, J. E. (2010) · Ophthalmology · doi:10.1016/j.ophtha.2009.10.043 · Cited by 43
Mitotropic Compounds for the Treatment of Age-Related Macular Degeneration
Fehér, J., Papale, A., Mannino, G., Gualdi, L., & Gabrieli, C. B. (2003) · Ophthalmologica · doi:10.1159/000071351 · Cited by 41
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
“Similarly, past or present intake of lutein did not affect the five year incidence of pigment abnormalities in the Beaver Dam Eye study [94].”
BackgroundInfluentialDiet and risk factors for age-related maculopathy
O’Connell, E., Nolan, J. M., Stack, J., Greenberg, D. C., Kyle, J., Maddock, L.-A., & Beatty, S. (2008) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/87.3.712 · Cited by 35
Simple and objective method for routine detection of the macular pigment xanthophyll
Schweitzer, D., Jentsch, S., Dawczynski, J., Hammer, M., Wolf-Schnurrbusch, U. E., & Wolf, S. (2010) · Journal of Biomedical Optics · doi:10.1117/1.3526358 · Cited by 36
Metadata
- Authors
- VandenLangenberg, G. M., Mares-Perlman, J. A., Klein, R., Klein, B. E. K., Brady, W. E., & Palta, M.
- Affiliations
- University of Wisconsin–Madison (US)
- Corresponding author
- Mares-Perlman, J. A.
- ORCID
- Palta, M.
- Venue
- American Journal of Epidemiology
- Publisher
- Oxford University Press (OUP)
- Published
- 1998-07-15
- Volume
- 148
- Issue
- 2
- Pages
- 204-214
- ISSN
- 0002-9262 (ISSN-L)
- 1476-6256
- OpenAlex
- W2036317458
- Cited by
- 234
- References
- 0
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 2 · 2022: 4 · 2021: 2 · 2020: 3 · 2019: 1 · 2018: 8 · 2017: 7 · 2016: 5 · 2015: 11 · 2014: 9 · 2013: 13 · 2012: 13
- FWCI
- 7.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Epidemiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Eye Institute (EY O6594, EYO8012)
- 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
- age-related maculopathy, antioxidants, dietary zinc, vitamin E, carotenoids, drusen, pigmentary abnormalities, macular degeneration, dietary intake, Beaver Dam Eye Study
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Antioxidants, Diet, Female, Humans, Macular Degeneration, Male, Middle Aged, Pigment Epithelium of Eye, Prospective Studies, Wisconsin, Zinc, Confounding Factors, Epidemiologic, Incidence, Logistic Models
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