Dietary Carotenoids, Vitamins A, C, and E, and Advanced Age-Related Macular Degeneration Johanna M. Seddon, MD; Umed A. Ajani, MBBS; Robert D. Sperduto, MD; Rita Hiller, MS; Norman Blair, MD; Thomas C. Burton, MD; Marilyn D. Farber, PhD; Evangelos S. Gragoudas, MD; Julia Haller, MD; Dayton T. Miller, PhD; Lawrence A. Yannuzzi, MD; Walter Willett, MD; for the Eye Disease Case-Control Study Group Objective.\p=m-\To evaluate the relationships between dietary intake of carotenoids and vitamins A, C, and E and the risk of neovascular age-related macular degen- eration (AMD), the leading cause of irreversible blindness among adults. Design.\p=m-\The multicenter Eye Disease Case-Control Study. Setting.\p=m-\Fiveophthalmology centers in the United States. Patients.\p=m-\Atotal 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 re- siding 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.\p=m-\Therelative risk for AMD was estimated accord- ing to dietary indicators of antioxidant status, controlling for smoking and other risk factors, by using multiple logistic-regression analyses. Results.\p=m-\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 high- est 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; P for trend=.02). Among the specific carotenoids, lutein and zeaxanthin, which are pri- marily obtained from dark green, leafy vegetables, were most strongly associated with a reduced risk for AMD (P for 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 (P for trend<.001). The intake of preformed vitamin A (retinol) was not ap- preciably 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.\p=m-\Increasing the consumption of foods rich in certain carotenoids, in particular dark green, leafy vegetables, may decrease the risk of developing ad- vanced or exudative AMD, the most visually disabling form of macular degenera- tion among older people. These findings support the need for further studies of this relationship. (JAMA. 1994;272:1413-1420) From the Epidemiology Unit (Drs Seddon and Ajani) and the Retina Service (Drs Seddon and Gragoudas), the Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, and the Channing Laboratory (Dr Willett), Harvard Medical School, Boston, Mass; the Department of Epidemiology (Drs Seddon and Willett) and the Department of Nutrition (Dr Willett), Harvard School of Public Health, Boston; the National Eye Insti- tute, Bethesda, Md (Dr Sperduto and Ms Hiller); the Department of Ophthalmology, University of Illinois at Chicago (Drs Blair and Farber); the Department of Ophthalmology, Medical College of Wisconsin, Mil- waukee (Dr Burton); the Wilmer Eye Institute, Baltimore, Md (Dr Haller); the Division of Environmental Health Laboratory Sciences, Centers for Disease Control and Prevention, Atlanta, Ga (Dr Miller); the Manhattan Eye, Ear, and Throat Hospital, New York, NY (Dr Yannuzzi); and the Brigham and Women's Hospital, Boston, Mass (Dr Willett). A complete list of the participants in the Eye Disease Case-Control Study Group was published in the follow- ing article: The Eye Disease Case-Control Study Group. Risk factors for neovascular age-related macular de- generation. Arch Ophthalmol. 1992;110:1701-1708. Presented in part at the annual meeting of the Asso- ciation for Research in Vision and Ophthalmology, Sarasota, Fla, May 5, 1993. Reprint requests to the Epidemiology Unit, Massa- chusetts Eye and Ear Infirmary, 243 Charles St, Boston, MA 02114 (Dr Seddon). AGE-RELATED macular degeneration (AMD) is the leading cause of irrevers¬ ible blindness among persons older than 65 years.1-2 Activities essential for inde¬ pendent living, including reading, driv¬ ing, and writing, are most impaired by the loss of central vision due to this dis¬ ease that affects the macula, the small central part of the retina. The preva¬ lence of AMD and the associated social and economic consequences of blindness from AMD are increasing as the num¬ ber of older people in our population continues to increase. However, despite the significance of this disease, there are no available means to prevent it, and effective treatment is limited to only a small fraction of patients. Strategies to prevent or retard the onset of AMD are needed so that the burden of blind¬ ness and visual impairment due to this disease can be reduced. See also pp 1439 and 1455. There is increasing speculation that dietary factors, particularly antioxi- dants, may prevent or impede the pro¬ gression of AMD.3"11 The theory is bio¬ logically plausible. The outer retina, rich in polyunsaturated fatty acids, may be altered adversely by free-radical pro¬ duction and oxidation and, conversely, may be protected by nutrients that block this oxidative damage. Antioxidants may also help to maintain the integrity of the choroidal blood vessels that supply the macular region of the retina. Basic and clinical research suggest that nutritional factors may be associ¬ ated with AMD. Animals of several species, including primates, that are de¬ prived of nutrients with antioxidant po¬ tential are more prone than those not deprived of such nutrients to develop retinal degeneration, an effect that is enhanced by bright light. Animals that are given nutrients that have antioxi¬ dant potential are less likely to demon- DownloadedFrom:http://jama.jamanetwork.com/byaTuftsUniv.HirshHealthSciencesLibraryUseron10/24/2013