Limited Benefit for Yellow Carotenoids in Macular Degeneration

MADISON, Wis., Aug. 14 -- Diets rich in the yellow carotenoids lutein and zeaxanthin may protect against intermediate-stage age-related macular degeneration in healthy women younger than 75.

So found an observational study of 1,787 women, ages 50 to 79, in Iowa, Wisconsin, and Oregon, originally from the Women's Health Initiative Observational Study. The women were recruited four to seven years later into the Carotenoids in Age-Related Eye Disease Study (CAREDS).

However, no significant difference between high and low intake of the plant pigments was found in the overall group of women, ages 50 to 79, Suzen Moeller, Ph.D., of the University of Wisconsin here, and colleagues, reported in the August issue of Archives of Ophthalmology.

Lutein and zeaxanthin are found in leafy green vegetables, corn, egg yolks, squash, broccoli, and peas. These compounds are the only carotenoids that concentrate in the macula. They may protect by absorbing harmful blue light from the sun, by quenching free radicals, and by increasing membrane stability, said Dr. Moeller.

The women had an intake of lutein plus zeaxanthin either above the 78^th percentile (high) and or below the 28^th percentile (low). At the start of the study, the women filled out questionnaires evaluating their diets in the past 15 years. Blood samples were taken as well as fundus photographs.

In the primary analysis, the prevalence of intermediate age-related macular degeneration was not statistically different between the high and low lutein plus zeaxanthin groups, after adjusting for age (odds ratio, 0.96; 95% confidence interval, 0.75-1.23), the researchers reported.

However, the odds ratio (0.57; CI 0.34-0.95) was significantly lower when analyses were limited to women younger than 75 years with a stable intake of lutein plus zeaxanthin and without a history comorbid conditions such as cardiovascular disease, diabetes, hypertension, or previously diagnosed macular degeneration that might alter dietary habits.

Finally, exploratory analyses of advanced macular disease in 34 participants resulted in protective, but statistically nonsignificant associations in the overall sample as well as in women younger than 75.

Despite evidence from experimental and observational studies suggesting a protective relationship for these pigments, epidemiological studies of early and intermediate disease do not support a beneficial role, the researchers wrote. "Indeed, the null association we observed . . . in our primary analyses is consistent with the few previous studies that have examined these relationships," Dr. Moeller and colleagues said.

Discussing the failure to find a benefit in the overall group of women, the researchers said that diet instability plus selective mortality bias (levels of consumption in older women may have been higher than that of older women who had died), may have explained the inability to detect a benefit.

Among the study's limitations, the researchers said that non-participation was a possible source of bias, as 36% of those eligible to participate declined. Also, because healthier people are more likely to participate in health studies, the associations may have been biased toward the null if those who did not participate had more age-related macular degeneration.

It is also important to note, they said, that the estimates of dietary intake of lutein and zeaxanthin represent diets high or low in these pigments, and therefore everything else that goes along with such diets, including vitamins, minerals, and nutritive and non-nutritive compounds such as phytochemicals and food additives. Many nutrients may work together to provide protection, and the study may not have measured other dietary deficits that influence the risk.

Further studies are needed to fully understand how food components interact as they are absorbed in the diet and metabolized in the body, as well as how they act with other environmental and genetic factors, the researchers wrote.

Although this study's findings of benefit for the women younger than 75 is consistent with evidence from observational and experimental studied, given the numerous analyses in this study, the results still could have been due to chance," Dr. Moeller wrote.

More conclusive evidence from long-term prospective studies and clinical trials is needed, Dr. Moeller said, to determine whether the macular carotenoids themselves, or as markers of broader dietary patterns, can protect against intermediate disease or delay progression of early-stage disease.