Clinical Trial Finds Antioxidants and Zinc Beneficial in Reducing Risk of Severe AMD

by Tom Hoglund, Information Officer
Foundation Fighting Blindness
October 2007
Reprinted by permission.

(Updated May 6, 2013)

Patients with advanced cases of dry age-related macular degeneration (AMD) can moderately lower the risk of developing the more severe wet form of the disease and preserve vision by taking a daily dose of antioxidant vitamins and zinc. This finding is the result of the Age-Related Eye Disease Study (AREDS), a randomized, placebo-controlled clinical trial funded by the National Eye Institute. AREDS evaluated over 3600 men and women between the ages of 55 and 80 for an average of 6.3 years. Published in the October 2007 issue of the Archives of Ophthalmology, AREDS also evaluated whether antioxidants and zinc might reduce cataract development but found no beneficial effect.

Dr. Paul Sieving, Director of the National Eye Institute, stated, “Now that we know antioxidants and zinc are helpful in reducing the risk of severe disease, it is even more important for older-age Americans to have regular eye exams. Intervening in at-risk individuals could help reduce severe disease and vision loss in millions of Americans.”

Specifically, the AREDS study found that AMD patients with advanced cases of dry AMD or vision loss due to wet AMD in one eye, who took daily supplements containing vitamin C, vitamin E, beta carotene, and zinc, had a 20% chance of developing wet macular degeneration over a five-year period. By comparison, the control group taking a placebo pill lacking any nutrients had a 28% chance of developing wet macular degeneration over a five-year period. This finding is important because delaying the onset of wet AMD and its accompanying vision loss by several years can prolong the independence and mobility of seniors and preserve their quality of life.

Various vitamin companies are now manufacturing a supplement of antioxidants and zinc containing the dosages used in the AREDS study, or patients can purchase each nutrient separately. The daily therapeutic dosages of each of the nutrients used in the original AREDS study were as follows: Vitamin C (500 mg), Vitamin E (400 IU), Beta Carotene (15 mg), and Zinc (80 mg).

The AREDS study findings are specific to patients with advanced cases of dry macular degeneration or vision loss from wet AMD in one eye. The study did not evaluate patients with early onset forms of macular degeneration such as Stargardt and Best disease. Due to the nature of the severe genetic defects that cause these early onset forms of macular degeneration, there is no evidence to support the use of high doses of antioxidants and zinc. There is also no evidence that antioxidants and zinc would offer benefit to patients with other retinal degenerative diseases such as retinitis pigmentosa. To the contrary, a well-designed clinical trial found that a daily dose of 400 IU of vitamin E resulted in a faster progression of vision loss for patients with common forms of retinitis pigmentosa.

Lutein and Zeaxanthin
Lutein and zeaxanthin are two antioxidant nutrients found highly concentrated in the macula. They give the macula its characteristic yellow appearance. Lutein and zeaxanthin are thought to protect the macula from oxidative stress due to light exposure. Because lutein and zeaxanthin supplements were not available at the start of the AREDS study, these nutrients were not included in the original formula.

UPDATE: Beta-carotene
Since this article was written by Mr. Hoglund, beta-carotene fell into question. Beta-carotene has been shown in one study to have no effect on retinal health, and it has been shown in some studies to increase lung cancer risk in smokers and ex-smokers. For more information, see “Beta-carotene May be Ineffective in Fighting Macular Degeneration” on this site.

From 2011 to 2013, the National Eye Institute sponsored follow-up research studying 6,891 eyes of people with AMD for the second Age-Related Eye Disease Study (AREDS2).

This time, subjects were given a slightly altered formula containing vitamins, minerals, lutein, zeaxanthin and omega-3 fatty acids DHA and EPA. The purpose was to see if the supplements would help even further to slow the progression of AMD to the advanced stages. A secondary goal was to evaluate the effect of eliminating beta carotene, lowering zinc doses, or both in the AREDS formulation.
On May 5, 2013, the AREDS2 research group, led by Emily Y. Chew, M.D., of the National Eye Institute, reported to the annual meeting of the Academy of Research in Vision and Ophthalmology (ARVO) that the new formula did not further reduce risk of progression to advanced AMD. In addition, there was no apparent effect of beta carotene elimination or lower-dose zinc on progression to advanced AMD. The researchers concluded that, even though there was no benefit to adding lutein and zeaxanthin, those ingredients could be an appropriate carotenoid substitute for beta-carotene. The substitution was found to reduce the benefit of slower progression to advanced AMD from 25% to 18%, but it is still considered an effective result.

The new AREDS formula is now Vitamin C (550 mg), Vitamin E (440 IU), Lutein (10mg), Zeaxanthin (2mg), Zinc (80 mg zinc oxide), Copper (2 mg cupric oxide).

Read the abstract from the AREDS2 report