Study confirms the benefit of dietary supplements in slowing down age-related macular degeneration


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Summary: The AREDS2 dietary supplement, which replaces beta-carotene with the antioxidants lutein and zeaxanthin, reduces the risk of progressive age-related macular degeneration, a new study shows.

Source: NIH

The Age-Related Eye Disease Studies (AREDS and AREDS2) found that dietary supplements may slow the progression of age-related macular degeneration (AMD), the leading cause of blindness in older Americans. In a new report, scientists analyzed 10 years of AREDS2 data.

They show that the AREDS2 formula, which replaced beta-carotene with the antioxidants lutein and zeaxanthin, not only reduced the risk of lung cancer due to beta-carotene, but was also more effective at reducing the risk of AMD progression compared to the original formula.

A report on the study funded by the National Institutes of Health, published in JAMA Ophthalmology.

“Because beta-carotene increased the risk of lung cancer for current smokers in two NIH-supported studies, our goal with AREDS2 was to develop an equally effective dietary supplement formula that could be used by anyone, whether they smoke or not,” said Emily Chew, MD, director of the Division of Epidemiology and Clinical Applications at the National Eye Institute (NEI) and lead author of the study report.

“This 10-year data confirms that the new formula is not only safer, but also better at slowing the progression of AMD.”

AMD is a degenerative disease of the retina, the light-sensitive tissue at the back of the eye. The progressive death of retinal cells in the macula, the part of the retina that provides clear central vision, eventually leads to blindness. Treatment can slow or reverse vision loss; however, there is no cure for AMD.

The original AREDS study, started in 1996, showed that a dietary supplement formulation (500 mg vitamin C, 400 international units vitamin E, 2 mg copper, 80 mg zinc, and 15 mg beta-carotene) significantly slowed the progression of moderate AMD until late illness.

However, two concurrent studies also showed that people who smoked and took beta-carotene had a significantly higher than expected risk of lung cancer.

In AREDS2, started in 2006, Chew and colleagues compared the beta-carotene formulation to one with 10 mg lutein and 2 mg zeaxanthin instead. Like beta-carotene, lutein and zeaxanthin are antioxidants with activity in the retina. The beta-carotene-containing formation was given only to participants who had never smoked or had quit smoking.

At the end of the five-year AREDS2 study period, the researchers concluded that lutein and zeaxanthin did not increase the risk of lung cancer and that the new formation could reduce the risk of AMD progression by approximately 26%.

Upon completion of the five-year study period, all study participants were offered the final AREDS2 formation, which contained lutein and zeaxanthin in place of beta-carotene.

In this new report, researchers followed 3,883 of the original 4,203 AREDS2 participants for another five years after the end of the AREDS2 study in 2011, collecting information on whether their AMD had progressed to late-onset disease and whether they had been diagnosed with lung cancer .

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AMD is a degenerative disease of the retina, the light-sensitive tissue at the back of the eye. The image is in the public domain

Although all participants switched to the lutein and zeaxanthin formula after the end of the study period, the follow-up study continued to show that beta-carotene almost doubled the risk of lung cancer for people who had ever smoked.

There was no increased risk of lung cancer in patients receiving lutein/zeaxanthin.

In addition, the group originally assigned to receive lutein/zeaxanthin had an additional 20% reduced risk of developing late AMD at 10 years compared to those originally assigned to receive beta-carotene .

“These results confirmed that switching our formula from beta-carotene to lutein and zeaxanthin was the right choice,” said Chew.

Financing: The study was supported by the NEI Intramural Program (EY000546) and by contracts (AREDS2 contract HHS-N-260-2005-00007-C; ADB contract NO1-EY-5-0007; AREDS contract NOI-EY-0 -2127, and contract HHS-N-263-2013-00005-C).

The AREDS2 contracts were supported by the NIH Office of Dietary Office of Dietary Supplements, the National Center for Complementary and Integrative Health, the National Institute on Aging, the National Heart, Lung, and Blood Institute, and the National Institute of Neurological Disorders and Stroke.

The study took place at the NIH Clinical Center.

There is news from research about this age-related macular degeneration

Author: Lesley Earl
Source: NIH
Contact: Lesley Earl—NIH
Picture: The image is in the public domain

Original research: Closed access.
“Long-term results of adding lutein/zeaxanthin and ω-3 fatty acids to AREDS supplements on the progression of age-related macular degeneration” by Chew EY, et al. JAMA Ophthalmology


Long-term results of adding lutein/zeaxanthin and ω-3 fatty acids to AREDS supplements on the progression of age-related macular degeneration


Following the Age-Related Eye Disease Study 2 (AREDS2), the beta-carotene component was replaced with lutein/zeaxanthin for the development of the revised AREDS supplement. However, it is not known if the increased risk of lung cancer observed in those given beta-carotene will persist beyond the completion of the AREDS2 study and if there is a benefit of adding lutein/zeaxanthin to the original AREDS supplement , which can be observed over the long term.


See also

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Assessing the 10-year risk of developing lung cancer and late age-related macular degeneration (AMD).

Design, setting and participants

This was a multi-centre follow-up epidemiological study to the AREDS2 clinical study conducted from December 1, 2012 to December 31, 2018. Participants with bilateral or unilateral intermediate AMD were included in the analysis for an additional 5 years after the clinical study. Eyes/participants were censored at time of late AMD development, death, or loss of follow-up care. Data was analyzed from November 2019 to March 2022.


During the clinical study, participants were randomized to primary lutein/zeaxanthin and/or ω-3 fatty acids or placebo and secondarily no beta-carotene vs. beta-carotene and low vs. high doses of zinc. In the epidemiological follow-up study, all participants received AREDS2 supplements containing lutein/zeaxanthin, vitamins C and E, and zinc plus copper. Results were assessed on 6-month phone calls. Analyzes of AMD progression and lung cancer development were performed using proportional hazards regression and logistic regression, respectively.

Main results and actions

Self-reported lung cancer and late AMD validated with medical records.


This study included 3882 participants (mean [SD] Baseline age, 72.0 [7.7] Years; 2240 women [57.7%]) and 6351 eyes. At 10 years, the odds ratio (OR) of having lung cancer was 1.82 (95% CI, 1.06-3.12; P= 0.02) for those randomly assigned beta-carotene and 1.15 (95% CI, 0.79-1.66; P= 0.46) for lutein/zeaxanthin.

The hazard ratio (HR) for progression to late AMD comparing lutein/zeaxanthin to no lutein/zeaxanthin was 0.91 (95% CI, 0.84-0.99; P= 0.02) and the comparison of ω-3 fatty acids with no ω-3 fatty acids was 1.01 (95% CI, 0.93-1.09; P= 0.91).

When the main analysis of effects of lutein/zeaxanthin was restricted to those randomly assigned to beta-carotene, the HR was 0.80 (95% CI, 0.68-0.92; P= 0.002).

A direct analysis of lutein/zeaxanthin vs. beta-carotene showed that the HR for late AMD was 0.85 (95% CI, 0.73-0.98; P= 0.02). The HR for low vs. high zinc was 1.04 (95% CI, 0.94-1.14; P= 0.49) and the HR for no beta-carotene vs. beta-carotene was 1.04 (95% CI, 0.94-1.15; P= 0.48).

Conclusions and Relevance

The results of this long-term epidemiological follow-up study of the AREDS2 cohort suggest that lutein/zeaxanthin is a viable replacement for beta-carotene in AREDS2 supplements. Taking beta-carotene almost doubled the risk of lung cancer, while there was no statistically significant increased risk with lutein/zeaxanthin. Compared to beta-carotene, lutein/zeaxanthin had a potentially beneficial association with late AMD progression.

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