10-Year Data Support Supplements for Macular Degeneration

Laird Harrison

June 08, 2022

The Age-Related Eye Disease Study 2 (AREDS2) formula of vitamins and minerals remains safe and effective in treating age-related macular degeneration (AMD) over 10 years, researchers say.

Replacing beta carotene with lutein and zeaxanthin appeared to eliminate the increased risk of lung cancer seen with the original AREDS formula while achieving an increase in effectiveness, said Emily Chew, MD, director of the Division of Epidemiology and Clinical Applications at the U.S. National Eye Institute in Bethesda, Maryland.

She recommended that everyone with intermediate- or late-macular degeneration take the AREDS2 supplements, which are available over the counter. “I think that really confirms that this is the right formulation for safety and for beneficial effects,” she told Medscape Medical News.

The increased lung cancer risk with beta carotene mostly applies to smokers and former smokers, Chew said.

Launched in 1996, the original AREDS study was the largest trial of dietary supplements ever conducted for macular degeneration.

Chew and her colleagues concluded that the formulation (500 mg vitamin C, 400 international units vitamin E, 2 mg copper, 80 mg zinc, and 15 mg beta carotene) could significantly slow the progression of AMD from moderate to late disease.

But while the researchers were working on the AREDS trial, studies published on beta carotene for the prevention of cancer and cardiovascular disease showed that the vitamin increased the risk of cancer in smokers.

In a new trial, AREDS2, Chew and her team replaced the beta carotene in their formulation with 10 mg lutein and 2 mg zeaxanthin. Like beta carotene, lutein and zeaxanthin are antioxidants that help protect the retina from damage caused by exposure to light.

Lower Risk, More Protection

For AREDS2, launched in 2006, the researchers gave the formulation with beta carotene only to participants who were not current smokers or had stopped smoking for at least 1 year.

At the end of the 5-year AREDS2 study, the researchers concluded that lutein and zeaxanthin did not increase risk for lung cancer, and that the new formulation could reduce the risk of AMD progression by about 25%.

On the other hand, those participants taking the formulation with beta carotene had twice the risk of lung cancer, with most of the cases in former smokers.

The researchers then offered all participants the AREDS2 formulation that included lutein and zeaxanthin instead of beta carotene.

For their latest report, Chew and her colleagues analyzed who among these participants had progressed to late AMD and who had been diagnosed with lung cancer over the 5 years after AREDS2 concluded in 2011.

They were able to collect data on 3882 of the original 4203 AREDS2 participants. All the participants had switched to lutein and zeaxanthin. Yet among those who had originally taken the beta carotene, the incidence of lung cancer was 2.8% vs 1.5% among those who did not take beta carotene (odds ratio 1.82; 95% CI, 1.06-3.12).

And in the group originally assigned to receive lutein and zeaxanthin, the rate of progression to late AMD was 20% lower than in the group originally assigned to receive beta carotene (hazard ratio 0.80; 95% CI, 0.68-0.92).

The researchers also looked at the effects of adding two omega-3 fatty acids to the formulation: docosahexaenoic acid and eicosapentaenoic acid. They found no effect on the progression to late AMD.

Other Dietary Protection

“The results are good, because they will improve the way that physicians can provide some cue to patients by saying that they should take the AREDS2 formulation, including lutein and zeaxanthin instead of beta carotene,” said Serge Camelo, PhD, who researches treatments for macular degeneration at Biophytis, a pharmaceutical company in Paris, France. He was not involved in this study.

On the other hand, he pointed out, about half the study participants progressed from moderate to late AMD even while taking the AREDS2 formulation. “So on one hand, it's a good thing that they improved the formulation that they give to patients, and it's safer and better,” he told Medscape. “But there is still a lot of progress to be done in the field.”

One way people with AMD can further slow the progression of AMD is by adhering to the Mediterranean diet, which includes a high proportion of fruits, vegetables, and fish. Fish appeared particularly important, Chew said, citing a separate study.

The diet and the supplements appear to complement each other, she said. While the supplements are most effective in slowing progression to the wet form of AMD, the diet is most effective in slowing progression to the dry form, Chew said.

And unlike the supplements, which are only effective in moderate and late-stage AMD, the Mediterranean diet can reduce the risk of AMD in people without AMD and people in early stages, she said.

The amount of beta carotene in food is not enough to pose a risk of cancer, Chew said.

Chew reported no relevant financial interests. Camelo reported researching treatments for macular degeneration. The study was funded by the National Institutes of Health, which has a royalty-bearing license issued to Bausch and Lomb for the AREDS2 supplements. Bausch and Lomb provided the supplements for the 5-year follow-up study.

JAMA Ophthalmology. Published online June 2, 2022. Abstract.

Laird Harrison writes about science, health and culture. His work has appeared in national magazines, in newspapers, on public radio, and on websites. He is at work on a novel about alternate realities in physics. Harrison teaches writing at The Writers Grotto. Visit him at www.lairdharrison.com or follow him on Twitter: @LairdH.

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