Table 2.

Summary of epidemiological evidence of dietary lutein/zeaxanthin intake and age-related macular degeneration.

Cohort Studies
Study	Length of follow-up Study participant details	Dietary Lutein and Zeaxanthin Intake	Dietary Assessment Method	Association between lutein and zeaxanthin consumption and Early or Intermediate Age-Related Macular Disease	Association between lutein and zeaxanthin consumption and Late Age-Related Macular Disease
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.	Not reported
Van Leeuwen et al. 2005 The Rotterdam Study [28]	8-year follow-up of 4170 Dutch men and women aged ≥ 55 years	Mean intake mg/day: Quartile 1:1.4 mg Quartile 4:3.6 mg	FFQ (170 item)	No significant association between L/Z intake and incident AMD.	Not reported
Moeller et al. 2006 Carotenoids in Age-Related Eye Disease Study [33]	7-year follow-up of 1787 US women aged 50−79 years	Low (<28th percentile): 792 ± 169 µg/day vs. High (>78th percentile): 2868 ± 919 µg/day Median intake (µg per 1000 kcal): Low: 618 µg High: 1438 µg	FFQ (122 item)	No association between dietary L/Z and prevalence of intermediate AMD in high vs. low intake. Significant, protective association (OR: 0.57; 95% CI 0.34−0.95) in women <75 years with stable L/Z intake and no history of CVD, diabetes, hypertension and/or AMD.	No significant association between dietary L/Z levels and late AMD in overall sample ORs in protective direction in younger women.
Tan et al. 2008 Blue Mountains Eye Study [34]	10-year follow-up of 2454 Australian men and women aged 45−93 years	Median intake µg/day: 743 µg (SD: 482 µg) Top tertile: ≥ 942 µg/day	FFQ (145 item)	Those with above-median intakes had a reduced risk of indistinct soft or reticular drusen (RR: 0.66; 95% CI, 0.48−0.92).	Top tertile of L/Z intake had a reduced risk of incident neovascular AMD (RR: 0.35, 95% CI 0.13–0.92).
Cho et al. 200 The Health Professionals Follow-Up Study [35]	16-year follow-up of 41,564 US male health professionals aged 50−79 years	Quintile 1: 1209 ± 317 µg/day Quintile 5: 6879 ± 315 µg/day	FFQ (130 item)	No overall association between L/Z intake and early AMD risk.	Top vs. bottom quintiles of L/Z intake and neovascular AMD pooled multivariate RR 0.78 (95% CI: 0.57, 1.06)
Cho et al. 2008 The Nurses’ Health Study [35]	18-year follow-up of 71,494 US female health professionals aged 50−79 years	Quintile 1: 1097 ± 279 µg/day Quintile 5: 5852 ± 2797 µg/day	FFQ (130 item)	No overall association between L/Z intake and early AMD risk.	Top vs. bottom quintiles of L/Z intake and neovascular AMD pooled multivariate RR 0.78 (95% CI: 0.57, 1.06)
Ho et al. 2011 The Rotterdam Study [36]	8.6-year follow-up 2167 individuals (≥ 55 years) from the Rotterdam study at risk of AMD	Tertile 1: 1.45−1.50 mg/day Tertile 3: 3.29−3.39 mg/day	FFQ (170 item)	High dietary intake of L/Z reduced the risk of early AMD in those at high genetic risk.	Not reported
Case-Control Studies
Seddon et al. 1994 The Eye Disease Case-Control Study [31]	Case-control study of 356 subjects aged 55 to 80 years with advanced-stage AMD matched with 520 control subjects	Median intake (IU): Quintile 1: 560.8 Quintile 5: 5757	FFQ (60 item)	Not reported	Highest vs. lowest dietary L/Z was associated with a reduced risk for advanced AMD (OR: 0.43; 95% CI 0.2−0.7).
Snellen et al. 2002 [37]	Case-control study of 72 case and 66 control subjects	Levels not reported.	Dietary habits interview	Not reported	The odds ratio for neovascular AMD with low L/Z vs. high L/Z was OR: 2.4 (95% CI, 1.1−5.1).
SanGiovanni et al. 2007 The Age-Related Eye Disease Study (AREDS) Report 22 [21]	Case-control study of 4519 AREDS participants aged 60 to 80 years at baseline	Median intake (µg per 1000 kcal): Quintile 1: 521 µg Quintile 5: 2095 µg	FFQ (90 item)	Highest quintile vs. lowest quintile dietary L/Z was inversely associated with large or extensive intermediate drusen (OR: 0.73; 95% CI 0.56−0.96).	Highest quintile vs. lowest quintile dietary intake L/Z was inversely associated with neovascular AMD (OR: 0.65; 95% CI 0.45−0.93) and geographic atrophy (OR: 0.45; 95% CI 0.24−0.86).

Abbreviations: FFQ, food frequency questionnaire; OR, odds ratio; CVD, cardiovascular disease; SD, standard deviation.