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Dietary Carotenoids, Vitamins A, C, and E, and Advanced Age-Related Macular Degeneration FREE

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
[+] Author Affiliations

A complete list of the participants in the Eye Disease Case-Control Study Group was published in the following article: The Eye Disease Case-Control Study Group. Risk factors for neovascular age-related macular degeneration. Arch Ophthalmol. 1992;110:1701-1708.

Presented in part at the annual meeting of the Association for Research in Vision and Ophthalmology, Sarasota, Fla, May 5, 1993.

Reprint requests to the Epidemiology Unit, Massachusetts Eye and Ear Infirmary, 243 Charles St, Boston, MA 02114 (Dr Seddon).


JAMA. 1994;272(18):1413-1420. doi:10.1001/jama.1994.03520180037032
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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; P for 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 (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 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)

REFERENCES

National Advisory Eye Council, Report of the Retinal and Choroidal Diseases Panel. Vision Research—A National Plan: 1983-1987 . Bethesda, Md: US Dept of Health and Human Services; 1984;. National Institutes of Health publication 83-2471.
Klein R, Klein B, Linton KLP.  Prevalence of age-related maculopathy: the Beaver Dam Study. Ophthalmology . 1992;;99:933-943.
Organisciak DT, Wang HM, Li Z, Li ZY, Tso MOM.  The protective effect of ascorbate in retinal light damage of rats. Invest Ophthalmol Vis Sci . 1985;;26:1580-1588.
Tso MOM, Woodford BJ, Lam KW.  Distribution of ascorbate in normal primate retina and after photic injury: a biochemical, morphological correlated study. Curr Eye Res . 1984;;3:181-191.
Ham WT, Mueller HA, Ruffolo JJ, et al.  Basic mechanisms underlying the production of photochemical lesions in the mammalian retina. Curr Eye Res . 1984;;3:165-174.
Katz ML, Parker KR, Handelman GJ, Bramel TL, Dratz EA.  Effects of antioxidant nutrient deficiency on the retina and retinal pigment epithelium of albino rats: a light and electron microscopic study. Exp Eye Res . 1982;;34:339-369.
Hayes KC.  Retinal degeneration in monkeys induced by deficiencies of vitamin E or A. Invest Ophthalmol Vis Sci . 1974;;13:499-510.
Young RW.  Solar radiation and age-related macular degeneration. Surv Ophthalmol . 1988;;32:252-269.
Goldberg J, Flowerdew G, 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.
The Eye Disease Case-Control Study Group.  Antioxidant status and neovascular age-related macular degeneration. Arch Ophthalmol . 1993;;111:104-109.
Blumenkranz MS, Russell SR, Robey MG, Blumenkranz RK, Penneys N.  Risk factors in age-related maculopathy complicated by chroroidal neovascularization. Ophthalmology . 1986;;96:552-558.
West S, Vitale S, Hallfrisch J, et al.  Are antioxidants or supplements protective of age-related macular degeneration? Arch Ophthalmol . 1994;;112: 222-227.
Newsome DA, Swartz M, Leone NC, Elston RC, Miller E.  Oral zinc in macular degeneration. Arch Ophthalmol . 1988;;106:192-198.
Willett W. Nutritional Epidemiology . New York, NY: Oxford University Press; 1990;.
Blackman BC, White P, Tsou W, Finkel D.  Peroxidation of plasma and platelet lipids in chronic smokers and insulin-dependent diabetics. Ann N Y Acad Sci . 1984;;435:385-387.
Chow CK, Thacker RR, Changchit C, et al.  Lower levels of vitamin C and carotenes in plasma of cigarette smokers. J Am Coll Nutr . 1986;;5:305-312.
Stryker WS, Kaplan LA, Stein EA, Stampfer MJ, Sober A, Willett WC.  The relation of diet, cigarette smoking, and alcohol consumption to plasma beta carotene and alpha tocopherol levels. Am J Epidemiol . 1988;;127:283-291.
The Eye Disease Case-Control Study Group.  Risk factors for neovascular age-related macular degeneration. Arch Ophthalmol . 1992;;110:1701-1708.
Willett WC, Sampson L, Stampfer MJ, et al.  Reproducibility and validity of a semiquantitative food frequency questionnaire. Am J Epidemiol . 1985;;122:51-65.
Ajani U, Willett W, Seddon J, the Eye Disease Case-Control Study Group.  Reproducibility of a food frequency questionnaire for use in ocular research. Invest Ophthalmol Vis Sci . 1994;;35:2725-2733.
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.
Willett WC, Stampfer MJ.  Total energy intake: implications for epidemiologic analyses. Am J Epidemiol . 1986;;124:17-27.
Foote CS.  Photosensitized oxidation and singlet oxygen: consequences in biological systems.  In: Pryor WA, ed. Free Radicals in Biology . New York, NY: Academic Press; 1976;;2:85-133.
Krinsky NI.  Antioxidant function of carotenoids. Free Radic Biol Med . 1989;;7:617-635.
Schalch W.  Carotenoids in the retina: a review of their possible role in preventing or limiting damage caused by light and oxygen.  In: Emerit I, Chance B, eds. Free Radicals and Aging . Basel, Switzerland: Birkhauser Verlag; 1992;:280-298.
Handleman GJ, Snodderly DM, Adler AJ, Russett MD, Oratz EA.  Measurements of carotenoids in human and monkey retinas.  In: Packer L, ed. Methods in Epidemiology . San Diego, Calif: Academic Press; 1992;:220-230.
Seddon JM, Hennekens CH.  Vitamins, minerals, and macular degeneration: promising but unproven hypotheses. Arch Ophthalmol .1994;;112:176-179.

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National Advisory Eye Council, Report of the Retinal and Choroidal Diseases Panel. Vision Research—A National Plan: 1983-1987 . Bethesda, Md: US Dept of Health and Human Services; 1984;. National Institutes of Health publication 83-2471.
Klein R, Klein B, Linton KLP.  Prevalence of age-related maculopathy: the Beaver Dam Study. Ophthalmology . 1992;;99:933-943.
Organisciak DT, Wang HM, Li Z, Li ZY, Tso MOM.  The protective effect of ascorbate in retinal light damage of rats. Invest Ophthalmol Vis Sci . 1985;;26:1580-1588.
Tso MOM, Woodford BJ, Lam KW.  Distribution of ascorbate in normal primate retina and after photic injury: a biochemical, morphological correlated study. Curr Eye Res . 1984;;3:181-191.
Ham WT, Mueller HA, Ruffolo JJ, et al.  Basic mechanisms underlying the production of photochemical lesions in the mammalian retina. Curr Eye Res . 1984;;3:165-174.
Katz ML, Parker KR, Handelman GJ, Bramel TL, Dratz EA.  Effects of antioxidant nutrient deficiency on the retina and retinal pigment epithelium of albino rats: a light and electron microscopic study. Exp Eye Res . 1982;;34:339-369.
Hayes KC.  Retinal degeneration in monkeys induced by deficiencies of vitamin E or A. Invest Ophthalmol Vis Sci . 1974;;13:499-510.
Young RW.  Solar radiation and age-related macular degeneration. Surv Ophthalmol . 1988;;32:252-269.
Goldberg J, Flowerdew G, 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.
The Eye Disease Case-Control Study Group.  Antioxidant status and neovascular age-related macular degeneration. Arch Ophthalmol . 1993;;111:104-109.
Blumenkranz MS, Russell SR, Robey MG, Blumenkranz RK, Penneys N.  Risk factors in age-related maculopathy complicated by chroroidal neovascularization. Ophthalmology . 1986;;96:552-558.
West S, Vitale S, Hallfrisch J, et al.  Are antioxidants or supplements protective of age-related macular degeneration? Arch Ophthalmol . 1994;;112: 222-227.
Newsome DA, Swartz M, Leone NC, Elston RC, Miller E.  Oral zinc in macular degeneration. Arch Ophthalmol . 1988;;106:192-198.
Willett W. Nutritional Epidemiology . New York, NY: Oxford University Press; 1990;.
Blackman BC, White P, Tsou W, Finkel D.  Peroxidation of plasma and platelet lipids in chronic smokers and insulin-dependent diabetics. Ann N Y Acad Sci . 1984;;435:385-387.
Chow CK, Thacker RR, Changchit C, et al.  Lower levels of vitamin C and carotenes in plasma of cigarette smokers. J Am Coll Nutr . 1986;;5:305-312.
Stryker WS, Kaplan LA, Stein EA, Stampfer MJ, Sober A, Willett WC.  The relation of diet, cigarette smoking, and alcohol consumption to plasma beta carotene and alpha tocopherol levels. Am J Epidemiol . 1988;;127:283-291.
The Eye Disease Case-Control Study Group.  Risk factors for neovascular age-related macular degeneration. Arch Ophthalmol . 1992;;110:1701-1708.
Willett WC, Sampson L, Stampfer MJ, et al.  Reproducibility and validity of a semiquantitative food frequency questionnaire. Am J Epidemiol . 1985;;122:51-65.
Ajani U, Willett W, Seddon J, the Eye Disease Case-Control Study Group.  Reproducibility of a food frequency questionnaire for use in ocular research. Invest Ophthalmol Vis Sci . 1994;;35:2725-2733.
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.
Willett WC, Stampfer MJ.  Total energy intake: implications for epidemiologic analyses. Am J Epidemiol . 1986;;124:17-27.
Foote CS.  Photosensitized oxidation and singlet oxygen: consequences in biological systems.  In: Pryor WA, ed. Free Radicals in Biology . New York, NY: Academic Press; 1976;;2:85-133.
Krinsky NI.  Antioxidant function of carotenoids. Free Radic Biol Med . 1989;;7:617-635.
Schalch W.  Carotenoids in the retina: a review of their possible role in preventing or limiting damage caused by light and oxygen.  In: Emerit I, Chance B, eds. Free Radicals and Aging . Basel, Switzerland: Birkhauser Verlag; 1992;:280-298.
Handleman GJ, Snodderly DM, Adler AJ, Russett MD, Oratz EA.  Measurements of carotenoids in human and monkey retinas.  In: Packer L, ed. Methods in Epidemiology . San Diego, Calif: Academic Press; 1992;:220-230.
Seddon JM, Hennekens CH.  Vitamins, minerals, and macular degeneration: promising but unproven hypotheses. Arch Ophthalmol .1994;;112:176-179.
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