A highly-anticipated study, published “online first” in the May 2013 issue of The Journal of the American Medical Association has concluded that adding omega-3 fatty acids (such as those found in fish oil) had no effect on the formulation, while the addition of lutein and zeaxanthin together appeared to offer a safe and effective alternative to the beta-carotene that was contained in the original AREDS formulation) commonly recommended for the treatment of age-related macular degeneration (AMD).
The Journal of the American Medical Association (JAMA) is an international peer-reviewed general medical journal published 48 times per year by the American Medical Association and is part of the JAMA Network of journals. The primary objective of JAMA is “to promote the science and art of medicine and the betterment of the public health.”
About the Research
The study, entitled Lutein + Zeaxanthin and Omega-3 Fatty Acids for Age-Related Macular Degeneration: The Age-Related Eye Disease Study 2 (AREDS2) Randomized Clinical Trial, was authored by the Age-Related Eye Disease Study 2 (AREDS2) Research Group, headed by lead investigator Emily Y. Chew, M.D., deputy director of the Division of Epidemiology and Clinical Applications and deputy clinical director at the National Eye Institute (NEI). According to Paul A. Sieving, M.D., Ph.D., the NEI director, “Millions of older Americans take nutritional supplements to protect their sight without clear guidance regarding benefit and risk. This study clarifies the role of supplements in helping prevent advanced AMD.”
What Is the AREDS Study? A Short History of the Research
Here is a good explanation from Massachusetts Eye and Ear, a Harvard Medical School teaching hospital:
The [original] Age-Related Eye Disease Study (AREDS) was designed to determine if daily intake of certain vitamins and minerals could reduce the risk of cataract and advanced AMD. The study included a placebo-controlled trial, launched in 1992, to evaluate a combination of vitamins E and C, beta-carotene, and zinc—known as the AREDS formulation. (Note: “Placebo” refers to an inactive substance that is provided to participants in place of the active drug or intervention that is being tested.
In 2001, the investigators reported that the AREDS formulation reduced the risk of advanced AMD by about 25 percent over a five-year period. There was no effect on cataract. After completion of the AREDS trial, all participants were given the option to receive the AREDS formulation as part of a five-year follow-up study.
In 2006, the investigators began a separate clinical trial called AREDS2. The primary goal was to determine if adding omega-3 fatty acids or the antioxidants lutein and zeaxanthin to the original AREDS formulation would make it more effective for reducing the risk of advanced AMD or cataract.
In prior observational studies, increased dietary intake of some or all of these nutrients had been linked to a reduced risk of advanced AMD and cataract. The omega-3 fatty acids tested in AREDS2 were docosahexanoic acid (DHA) and its precursor eicosapentanoic acid (EPA). There were four main treatment arms to the trial: (1) control/AREDS formulation only, (2) lutein/zeaxanthin added to the formulation, (3) DHA/EPA added, (4) lutein/zeaxanthin and DHA/EPA added.
The original AREDS trial involved 4,757 participants, age 55-80 at the time of enrollment. Of 4,203 surviving participants, 3,549 (about 84 percent) took part in the follow-up study.
AREDS2 enrolled 4,203 participants, age 50-85. Because the original AREDS trial established that the formulation does not benefit people with no AMD or early AMD, the AREDS2 trial was limited to people with intermediate AMD in both eyes, or intermediate AMD in one eye and advanced AMD in the other eye.
The Study Results
From the JAMA article, which summarized the results as follows:
Addition of lutein + zeaxanthin, DHA + EPA, or lutein + zeaxanthin and DHA + EPA to the AREDS formulation in primary analyses did not further reduce risk of progression to advanced AMD. Comparison of low-dose zinc vs high-dose zinc showed no evidence of a statistically significant effect, and there is insufficient evidence to provide a clinical recommendation.
There was no apparent effect of beta carotene elimination or lower-dose zinc on progression to advanced AMD. More lung cancers were noted in the beta carotene vs. no beta carotene group, mostly in former smokers. Based on apparent risks of beta carotene and possible benefits that are only evident within exploratory subgroup analyses, lutein + zeaxanthin requires further investigation for potential inclusion in the AREDS supplements.
The limitations of this study include a complicated study design …, which may have affected our ability to evaluate the role of adding lutein + zeaxanthin and DHA + EPA to the AREDS formulation. Not all participants were taking the original AREDS formulation, with some taking only certain components of the AREDS formulation. This formulation was given as a mixture of antioxidant vitamins and minerals. It is not known whether a single specific ingredient is important or if the combination is essential for its therapeutic effect.
More AREDS News
There is good news about AREDS supplements, however. NEI’s AREDS Research Group has provided additional, and more encouraging, results in Long-Term Effects of Vitamins C, E, Beta-Carotene and Zinc on Age-Related Macular Degeneration, published online in the April 11, 2013 issue of the journal Ophthalmology. Here is a summary of that research from an NEI news release:
[The report] shows the beneficial effects of taking the AREDS vitamins are long-lasting. The report describes a follow-up study of AREDS participants. Those who took the AREDS formulation during the initial five-year trial were 25 to 30 percent less likely to develop advanced AMD over the next five years, compared with participants who took placebo during AREDS.
“Long-term use of AREDS supplements appears safe and protective against advanced AMD,” said [Doctor Emily] Chew. “While zinc is an important component of the AREDS formulation, based on evidence from AREDS2 it is unclear how much zinc is necessary. Omega-3 fatty acids and beta-carotene clearly do not reduce the risk of progression to advanced AMD; however, adding lutein and zeaxanthin in place of beta-carotene may further improve the formulation.”
You can read an AREDS2 update from Lylas G. Mogk, M.D at What Is the Age-Related Eye Disease Study? at VisionAware.org.