What Is the Age-Related Eye Disease Study (AREDS and AREDS2)?

By Lylas G. Mogk, M.D.
Edited by Maureen A. Duffy, M.S., CVRT

The First Age-Related Eye Disease Study (AREDS)

The first Age-Related Eye Disease Study (AREDS) was a major clinical trial sponsored by the National Eye Institute to:

  • Learn more about the history of, and risk factors for, age-related macular degeneration (AMD) and cataract;
  • Evaluate the effect of high doses of antioxidants and zinc on the progression of AMD and cataract.

Results from the first AREDS trial, which were reported in October 2001, indicated that five years of supplementation with high doses of antioxidant vitamins, copper, and zinc reduced the risk of developing advanced AMD in 30% of individuals in the study who took the supplements and had already-existing moderate to advanced dry or wet AMD.

The original AREDS formulation included:

  • 500 milligrams (mg) of vitamin C
  • 400 international units of vitamin E
  • 15 mg beta-carotene (for non-smokers only)
  • 80 mg zinc as zinc oxide
  • 2 mg copper as cupric oxide (to avoid anemia with high zinc intake)

The Second Age-Related Eye Disease Study (AREDS2)

In May 2013, The National Eye Institute concluded the Age-Related Eye Disease Study 2, which tested several changes to the original AREDS formulation:

  • The primary goal of the AREDS2 study was to determine if (a) adding omega-3 fatty acids or (b) lutein and zeaxanthin (the anti-oxidants found in dark green leafy vegetables) to the original AREDS formulation would make it more effective for reducing the risk of advanced AMD and cataract.
  • The AREDS2 research group also substituted lutein and zeaxanthin for beta-carotene, which prior studies had associated with an increased risk of lung cancer in smokers.

The researchers concluded that while omega-3 fatty acids had no effect on the formulation, lutein and zeaxanthin together appeared to be a safe and effective alternative to beta-carotene. Therefore, the addition of lutein and zeaxanthin to, and the subtraction of beta carotene from, the original AREDS supplement formula was recommended by AREDS2.

The AREDS2 formulation now includes:

  • 500 milligrams (mg) of vitamin C
  • 400 international units of vitamin E
  • 80 mg zinc as zinc oxide
  • 2 mg copper as cupric oxide (to avoid anemia with high zinc intake)
  • 10 mg lutein
  • 2 mg zeaxanthin

Be sure to talk with your doctor before adding any nutritional or vitamin supplements to your diet. If you don't have AMD and wish to take nutritional supplements, take a good multiple vitamin/mineral combination with additional lutein and omega-3 fatty acids. The AREDS formula is not recommended for persons who do not have macular degeneration because it contains a high dose of zinc.

Please note: There is some new evidence that individuals whose AMD progression is slowed by the supplements were of a particular genetic makeup and that the supplements may speed its progression in those with a different genetic makeup. This has prompted some scientists to call for genetic testing on everyone with macular degeneration before prescribing supplements, but the evidence is not sufficient for all scientists to agree on this. Individuals should discuss this with their ophthalmologists.

Something New: Mesoxanthin and MacuHealth

John Nolan, Ph.D., came from Ireland to speak at our hospital by invitation of the MacuHealth company and I found his research to be very solid and convincing. While the MacuHealth company paid for his research, Dr. Nolan stated that he agreed to do the research only on the basis that he would publish his findings no matter what they were.

What he showed was that another cousin of lutein and zeaxanthin named "mesoxanthin" is actually the most active of the three specifically in the macula and that the combination of lutein, zeaxanthin, and mesoxanthin is what's needed. That's what the MacuHealth supplement contains.

Mesoxanthin has not heretofore been commercially available and the MacuHealth company now has the sole right to manufacture and distribute it. It has not been subjected to a randomized, masked study so whether – and to what degree – it may be helpful is unknown. It is unlikely to do harm, however, and the research suggests that it may help.

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