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Original Investigation |

Intakes of Lutein, Zeaxanthin, and Other Carotenoids and Age-Related Macular Degeneration During 2 Decades of Prospective Follow-up

Juan Wu, MS1; Eunyoung Cho, ScD2,3,4; Walter C. Willett, MD, MPH, DrPH1,4,5; Srinivas M. Sastry, MD, MPH6; Debra A. Schaumberg, ScD, OD, MPH5,7
[+] Author Affiliations
1Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
2Department of Dermatology, Warren Alpert Medical School, Brown University, Providence, Rhode Island
3Department of Epidemiology, Brown School of Public Health, Providence, Rhode Island
4Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
5Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
6Bethesda Retina, Bethesda, Maryland
7Moran Center for Translational Medicine, John A. Moran Eye Center, Department of Ophthalmology and Visual Sciences, University of Utah School of Medicine, Salt Lake City
JAMA Ophthalmol. 2015;133(12):1415-1424. doi:10.1001/jamaophthalmol.2015.3590.
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Importance  Despite strong biological plausibility, evidence from epidemiologic studies and clinical trials on the relations between intakes of lutein and zeaxanthin and age-related macular degeneration (AMD) has been inconsistent. The roles of other carotenoids are less thoroughly investigated.

Objective  To investigate the associations between intakes of carotenoids and AMD.

Design, Setting, and Participants  Prospective cohort study, with cohorts from the Nurses’ Health Study and the Health Professionals Follow-up Study in the United States. A total of 63 443 women and 38 603 men were followed up, from 1984 until May 31, 2010, in the Nurses’ Health Study and from 1986 until January 31, 2010, in the Health Professionals Follow-up Study. All participants were aged 50 years or older and were free of diagnosed AMD, diabetes mellitus, cardiovascular disease, and cancer at baseline.

Main Outcomes and Measures  Predicted plasma carotenoid scores were computed directly from food intake, assessed by repeated food frequency questionnaires at baseline and follow-up, using validated regression models to account for bioavailability and reporting validity of different foods, and associations between predicted plasma carotenoid scores and AMD were determined.

Results  We confirmed 1361 incident intermediate and 1118 advanced AMD cases (primarily neovascular AMD) with a visual acuity of 20/30 or worse by medical record review. Comparing extreme quintiles of predicted plasma lutein/zeaxanthin score, we found a risk reduction for advanced AMD of about 40% in both women and men (pooled relative risk comparing extreme quintiles = 0.59; 95% CI, 0.48-0.73; P for trend < .001). Predicted plasma carotenoid scores for other carotenoids, including β-cryptoxanthin, α-carotene, and β-carotene, were associated with a 25% to 35% lower risk of advanced AMD when comparing extreme quintiles. The relative risk comparing extreme quintiles for the predicted plasma total carotenoid index was 0.65 (95% CI, 0.53-0.80; P for trend < .001). We did not identify any associations of carotenoids, either as predicted plasma score or calculated intake, with intermediate AMD.

Conclusions and Relevance  Higher intake of bioavailable lutein/zeaxanthin is associated with a long-term reduced risk of advanced AMD. Given that some other carotenoids are also associated with a lower risk, a public health strategy aimed at increasing dietary consumption of a wide variety of fruits and vegetables rich in carotenoids may reduce the incidence of advanced AMD.

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Figure 1.
Dose-Response Relationship Between Predicted Plasma Carotenoid Scores and the Relative Risk of Advanced Age-Related Macular Degeneration (AMD)

Dose-response relationships were calculated for predicted plasma lutein/zeaxanthin score (A) and predicted plasma total carotenoid index (B) with the risk of advanced AMD. Multivariate models were adjusted for age (continuous), body mass index (≥30; calculated as weight in kilograms divided by height in meters squared), current aspirin use (≥1 tablet/wk), history of hypertension, pack-years of smoking, physical activity, and modified alternative healthy eating index (all in categories). Solid lines represent relative risks; dashed lines, 95% CIs.

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Figure 2.
Relative Risks of Age-Related Macular Degeneration (AMD) According to Primary Carotenoid-Containing Foods

Bars surrounding point estimates indicate 95% CIs. Multivariate models were adjusted for the same variables as in Table 2.

aP for linear trend < .05.

bCooked spinach (0.5 cup) is approximately equivalent to 2.5 × raw spinach (1 cup); total spinach (1 cup) = raw spinach (1 cup) + 2.5 × cooked spinach (0.5 cup).

cP for linear trend < .10

dP for heterogeneity between the Nurses’ Health Study and the Health Professionals Follow-up Study < .05.

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Figure 3.
Independent Associations of Predicted Plasma Carotenoid Scores With Advanced Age-Related Degeneration

Bars surrounding point estimates indicate 95% CIs. Multivariate models were adjusted for the same variables as in Table 2. P for heterogeneity between the Nurses’ Health Study and the Health Professionals Follow-up Study > .10 for all the relative risks.

aAll other carotenoids were a composite score derived by totaling the quintile score of each carotenoid.

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