Lutien/zeaxanthin associated with decreased risk of AMD

In a multivariate analysis with subjects divided into quintiles by lutein/zeaxanthin intake, persons with the highest intake had a 66% reduced likelihood of having geographic atrophy compared with those in the lowest intake quintile and a 36% reduced likelihood of having neovascular AMD.

"These findings on the relationship of lutein/zeaxanthin intake to advanced AMD are consistent with the existing published evidence base consisting of observational studies. However, because we ascertained our outcome variable at enrollment and also collected demographic, life-style, and medical data at the same time, factors such as misclassification of exposure and unmeasured confounding constrain us from making causal inferences," said Dr. SanGiovanni, who is currently a staff scientist at the National Eye Institute and the AREDS Project Officer.

Examining nutrient intake Information on nutrient intake during the year preceding enrollment was derived from the results of a semi-quantitative validated food frequency questionnaire completed at enrollment; the data for each subject were energy-adjusted using the nutrient density model. Subjects and controls were then divided into quintiles of nutrient intake.

Potential relationships were also investigated with other major dietary carotenoids, including alpha- and beta-carotene, lycopene, and beta-cryptoxanthin, and the various AMD categories at enrollment. However, in the multivariate analyses that con- trolled for non-nutritional and nutritional cofactors, only lutein/zeaxanthin intake had independent predictive value, and these associations were observed only for neovascular AMD and geographic atrophy.

"Of approximately 50 carotenoids present in the Western diet, lutein and zeaxanthin are the major carotenoids concen- trated in the macula; of the eight possible isomeric forms of lutein and three of zeaxanthin, the all-trans configurations of both compounds are the most prevalent in diet and retina," noted Dr. SanGiovanni.

The question on the relationship of dietary carotenoids to risk for prevalent AMD was predicated by concepts similar to those that guided planning of the AREDS clinical trial, he said.

"Current pharmacologic and surgical treatment options for AMD are of limited scope and efficacy; they are costly, and may result in complications as severe as end-stage disease. Therefore, our efforts are directed at identifying modifiable factors associated with AMD. Available evidence indicates dietary nutrients represent one element of this set, and modulation of nutrient intake may also offer a well-tolerated intervention," Dr. SanGiovanni said.

Importantly, with regard to lutein and zeaxanthin, there is also compelling evidence that their retinal tissue status is affected by diet, and that acting via multiple mechanisms, those compounds have the capacity to protect the retina from age-related pathogenic factors.

"The biophysical and biochemical nature of macular xanthophylls, as well as their retinotopic and laminar distribution, support the idea that these compounds may modulate processes implicated in AMD pathogenesis. Because retinal tissue status of lutein and zeaxanthin is modifiable by intake, there is reasonable basis for examining diet-AMD relationships," Dr. SanGiovanni said.OT