Combination of Specific Dietary Supplements Can Slow Macular Degeneration Progression

Age-related macular degeneration (AMD) is a leading cause of vision loss in older adults.[1] The condition involves progressive, age-related damage to the macula of the retina (light-sensitive tissue in the back of the eye that controls sharp, straight-ahead vision).

In the July 2022 issue of the Journal of the American Medical Association Ophthalmology (JAMA Ophthalmology) researchers published 10-year follow-up data on subjects who had been enrolled in a clinical trial that evaluated various combinations of dietary supplements for reducing the risk of AMD progression.[2] This new research confirmed the benefits and safety of a specific combination of supplements for slowing the progression of AMD.

Background on AMD and dietary supplements

The National Eye Institute (NEI) estimates that 11 million people in the U.S. have AMD.[3] It can occur in one or both eyes, and the presence of advanced AMD in one eye increases the risk of developing severe disease in the other eye. AMD progresses at different rates in different individuals.

AMD typically has three stages: early (no symptoms), intermediate (mild symptoms including trouble seeing in low light) and late (increasing central-vision blurriness or blank spots, seeing straight lines as wavy and colors appearing less bright).[4] There is currently no treatment for early AMD except monitoring the disease in case it progresses; healthy eating, regular exercise and smoking cessation can help.[5] However, a combination of specific dietary supplements (vitamins, minerals and antioxidants) may slow the progression of intermediate AMD.

The randomized Age-Related Eye Disease Study (AREDS), which was funded by the National Institutes of Health (NIH) and published in 2001, demonstrated that compared with placebo, the daily use of a combination of three antioxidants — vitamin C, vitamin E and beta carotene — plus zinc with copper reduced the risk of progression to late AMD in eyes with intermediate AMD by 25% over five years.[6]

Importantly, while AREDS was ongoing, two unrelated randomized clinical trials showed that beta carotene increased the risk of lung cancer in smokers.[7],[8]

A subsequent NIH-funded randomized clinical trial, called “AREDS2,” evaluated the effect of adding the antioxidants lutein and zeaxanthin, omega-3 fatty acids or both to the AREDS supplement formula — with or without beta carotene — in AMD patients.[9] The AREDS2 results, which were published in 2013, found that after a median follow-up of five years, the addition of lutein/zeaxanthin, omega-3 fatty acids or both to the original AREDS formula did not further reduce the risk of progression to advanced AMD, but they did confirm that beta carotene increased the risk of lung cancer, particularly in smokers.[10]

Based on the AREDS2 data, the formula for marketed AREDS supplements were modified by replacing the beta carotene with lutein/zeaxanthin. The current AREDS2 supplements, which are taken daily, contain the following: vitamins C (500 milligrams [mg]) and E (400 international units), copper (2 mg), zinc (80 mg), lutein (10 mg) and zeaxanthin (2 mg).

AREDS2 long-term follow-up analysis[11]

For the 2022 JAMA Ophthalmology study, the AREDS2 researchers collected an additional five years of follow-up data on 3,883 (92%) of the original 4,203 subjects who had participated in AREDS2. The follow-up subjects had completed the five-year randomized AREDS2 and were subsequently encouraged to take an AREDS2 supplement daily (91% complied with this recommendation).

The follow-up subjects were contacted by telephone every six months from 2012 to 2018 and asked about any new diagnosis of late AMD or lung cancer. A subset of the follow-up subjects also had a clinic visit for an eye exam to document AMD progression five years after the end of the original five-year randomized trial.

The follow-up study found that use of lutein/zeaxanthin resulted in an approximately 10% reduction in the risk of AMD progression from intermediate stage to late stage after 10 years. Moreover, the 10-year incidence of lung cancer with beta carotene use for subjects who formerly smoked nearly doubled (from 2.3% in subjects who had been randomly assigned to a supplement formula without beta carotene to 4.5% in those who had been randomly assigned to receive a supplement formula with beta carotene). No increased risk of cancer was seen in subjects who had received lutein/zeaxanthin during the five-year randomized AREDS2.

Dr. Emily Chew, the lead AREDS2 researcher and director of the Division of Epidemiology and Clinical Application at the NEI, stated, “These results confirmed that switching our [AREDS] formula from beta-carotene to lutein and zeaxanthin was the right choice.”[12]

What You Can Do

If you experience central vision blurring or other vision symptoms, consult with an eye doctor as soon as possible. If you receive the diagnosis of intermediate AMD, discuss with your doctor the use of an AREDS2 dietary supplement to slow the progression of your AMD.

Before you begin AREDS2 supplements, check the ingredient list to make sure it conforms with the NEI-recommended formulation.

Avoid beta carotene because of the lung cancer risk, especially if you have a history of smoking.
 

References

[1] National Eye Institute. Age-related macular degeneration (AMD). June 22, 2021. https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/age-related-macular-degeneration. Accessed October 30, 2022.

[2] Chew EY, Clemons TE, Agrón E, et al. Long-term outcomes of adding lutein/zeaxanthin and ω-3 fatty acids to the AREDS supplements on age-related macular degeneration progression: AREDS2 report 28. JAMA Ophthalmol. 2022;140(7):692-698.

[3] National Eye Institute. Age-related macular degeneration (AMD). June 22, 2021. https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/age-related-macular-degeneration. Accessed October 30, 2022.

[4] Ibid.

[5] Ibid.

[6] Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS Report no. 8. Arch Ophthalmol. 2001;119(10):1417–1436.

[7] Omenn GS, Goodman GE, Thornquist MD, et al. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med. 1996:334(18):1150-1155.

[8] Al banes D, Heinonen OP, Taylor PR, et al. Alpha-tocopherol and beta-carotene supplements and lung cancer incidence in the alpha-tocopherol, beta-carotene cancer prevention study: effects of base-line characteristics and study compliance. J Natl Cancer Inst. 1996;88(21): 1560-1570.

[9] Age-Related Eye Disease Study 2 (AREDS2) Research Group. Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: The Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA. 2013;309(19):2005–2015.

[10] Age-Related Eye Disease Study 2 (AREDS2) Research Group. Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: The Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA. 2013;309(19):2005-2015.

[11] Chew EY, Clemons TE, Agrón E, et al. Long-term outcomes of adding lutein/zeaxanthin and ω-3 fatty acids to the AREDS supplements on age-related macular degeneration progression: AREDS2 report 28. JAMA Ophthalmol. 2022;140(7):692-698.

[12] National Institutes of Health. NIH study confirms benefit of supplements for slowing age-related macular degeneration. June 2, 2022. https://www.nih.gov/news-events/news-releases/nih-study-confirms-benefit-supplements-slowing-age-related-macular-degeneration. Accessed November 8, 2022.