NEI recommends change based on AREDS2 results

June 20, 2013
A scene as it might be viewed by a person with age-related macular degeneration. Credit: National Eye Institute, National Institutes of Health

A scene as it might be viewed by a person with age-related macular degeneration.
Credit: National Eye Institute, National Institutes of Health

Author presentation discusses subject groups and additive effects on AMD

National Eye Institute Deputy Clinical Director Emily Chew, M.D., Ph.D., presented the results from the second Age-Related Eye Disease Study (AREDS2) at the Association for Research in Vision and Ophthalmology (ARVO) annual meeting in May. Her presentation expanded upon the results published in the Journal of the American Medical Association (JAMA).

The primary analysis of the study tested whether adding FloraGLO Lutein and Optisharp Zeaxanthin, DHA + EPA, or a combination of the two to the AREDS formulation reduced the risk of progression to advanced age-related macular degeneration (AMD) by an additional 25 percent as compared to study subjects taking the original AREDS supplement, which was the study control arm. The data did not demonstrate a significant reduction in progression to advanced AMD in any of the three treatment arms as compared to the control group.

Lutein and zeaxanthin

Analysis by Kemin, the makers of FloraGLO Lutein, reflected on the impact of dietary intake of lutein and zeaxanthin.

“These results come at a critical time when our population is aging and eye health is a growing concern for many Americans,” said Heather Richardson of Kemin. “The number of people diagnosed with early AMD is projected to double by 2020, and a clinical research trial of this size and scope provides eye care professionals and their patients with peace of mind that there are effective treatments available.”

For those in the lowest quintile of dietary L/Z intake, comparison of L/Z vs. no L/Z resulted in a 26 percent reduction in progression to advanced AMD, which was significant.

Paul Chous, O.D., AOA Health Promotions Committee member, said it is also critically important to note that baseline nutritional status of AREDS2 subjects was better than nationally representative samples and better than that of the original AREDS subjects.

The AREDS2 Research Group that authored the JAMA article state the AREDS2 participants were very well-nourished based tested levels of lutein/zeaxanthin and DHA/EPA that were significantly greater than others.

In the United States, dietary intake of lutein and zeaxanthin is typically less than 1 mg per day, which is similar to the dietary intake of the participants who showed the greatest reduction in risk in this study.

These data support a recommendation for lutein and zeaxanthin to be added to an AREDS supplement as the general population has a dietary intake of L/Z more in line with the subjects in the lowest quintile.

“The JAMA paper abstract clearly misstates some of the most important points made at the live presentation,” said Dr. Chous. “The addition of lutein and zeaxanthin (L/Z) to the AREDS formula resulted in a statistically significant 10 percent reduction in conversion from AREDS grade 3 or 4 AMD to advanced AMD (p = 0.04) and an 11 percent risk reduction for CNVM (p = 0.05), with the confidence interval presented during the live ARVO presentation reported as ‘less than 1.0’ (meaning there is NO chance that L/Z worsened outcomes and a high probability it improved them). However, and unfortunately, the JAMA paper reports the confidence interval ranged from 0.76-1.07 (p = 0.12). This discrepancy is crucial and is reflected in Tables 3 and 4 of the JAMA paper, with the statistics reported at ARVO by the lead investigator (what everyone in the world who watched assumed was the primary analysis) being reported as ‘secondary analysis’ in the JAMA paper.”

Effects of smoking

Comparison of lutein and zeaxanthin-containing AREDS supplements without beta-carotene vs. original AREDS supplement with beta carotene resulted in an 18 percent reduction in progression to advanced AMD, which was significant.

Participants who were former smokers showed more lung cancers in the beta-carotene group than in the no beta-carotene group.

The JAMA publication shows 50 percent of the AREDS2 subjects were former smokers. These data suggest that half of individuals suffering from AMD may be at greater risk for developing lung cancer if they are taking an AREDS supplement containing 15 mg beta carotene.

“The addition of beta-carotene to AREDS worsened outcomes compared to AREDS plus L/Z , suggesting competitive inhibition of carotenoid uptake,” said Dr. Chous. “Beta-carotene also more than doubled the risk of lung cancer in previous smokers (current smokers were excluded from the B-carotene groups). Fifty percent of patients who develop AMD have a history of smoking, so this is really important.”

“The NEI has issued a recommendation to modify the original AREDS formulation by adding 10 mg lutein and 2 mg zeaxanthin while removing beta carotene,” said Diane Alexander, Ph.D., of Kemin. “This recommendation is based upon the significant findings of the AREDS2 study showing a 10 percent reduction in progression to advanced AMD in subjects receiving lutein/zeaxanthin. This reduction was even more profound when beta carotene was removed from the formulation. Because of the safety issues associated with beta carotene in former smokers and competition among lutein/zeaxanthin and beta carotene for absorption into the blood, the data strongly support the addition of lutein and zeaxanthin in place of beta carotene in an AREDS supplement.”

“These statistics will undoubtedly be crunched in a number of different ways over the next 10 years, just as they were for the original AREDS trial with publication of multiple other analyses,” said Dr. Chous. “For instance, subsequent analysis of AREDS data showed a strong effect of dietary glycemic index on rates of progression, something still rarely talked about. Stratification of treatment effect by presence or absence of genetic markers for advanced AMD is another example (e.g., CFH Y402H polymorphism)—something not done in AREDS (it wasn’t available) but eventually will be done with AREDS2 blood samples, I suspect. This is really important since 70 percent of AMD risk is thought to be genetic.”

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