Study shows no benefit with fish oil
Age-related macular degeneration (AMD) remains the leading cause of central vision loss or severe visual impairment in patients over the age of 65 (Ophthalmology. 2008;115:116–126). In fact, advanced AMD is the cause of greater than half of severe vision impairment in the U.S. (Arch Ophthalmol. 2004;122:477-485). There are several stages of the disease: early-stage, or dry; intermediate; and advanced (either geographic atrophy or wet) AMD.
Fortunately, there are drugs that help treat the vision loss, and options are expanding. These involve vascular endothelial growth factors, including ranibizumab, off-label bevacizumab and the newest, aflibercept. There is also a combination drug therapy in development that may improve vision further; it involves the current medications, plus a potential new class, a platelet-derived growth factor (PDGF) inhibitor.
However, there is no cure for AMD. In fact, there is no treatment for the early, or dry, form of AMD. Therefore, identifying factors that may help decrease the risk of progression to advanced disease should be front and center. The goal of the Age-Related Eye Disease Study 2 (AREDS2) was just this – to reduce progression by identifying the optimal supplement formulation.
Just as important is identifying factors that may increase overall risk of developing AMD. We know that smoking, family history and age are contributing factors, and potentially iron (Am J Epidemiol. 2009;169:867-876). In addition, sunlight may play a role. Also, there have been three recent studies with conflicting results regarding aspirin’s potential to raise AMD risk.
Let’s look at the evidence.
Age-Related Eye Disease Study 2
The purpose of AREDS2 was to improve a multivitamin identified in the original AREDS study that illustrated a 25 percent reduction in progression from early-stage to advanced AMD. The multivitamin was composed of zinc, copper, beta-carotene and vitamins C and E, all considered to enhance antioxidant defenses.
AREDS2 researchers compared multiple formulations of the original AREDS multivitamin, adding omega-3 fatty acids — fish oil including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) — and/or lutein/zeaxanthin. They also compared variations with and without beta-carotene. In this randomized controlled trial (RCT), the gold standard of studies, the results with fish oil were disappointing (JAMA. 2013;309:2005-2015). There was no risk reduction — a stark contrast to an observational study I mentioned in my May 3, 2011 article. RCTs always trump observational trials.
AREDS2 showed a modest decrease in risk with lutein/zeaxanthin in a certain population. Beta-carotene deletion decreased the risk of lung cancer, mostly in previous smokers, but it did not affect progression to late AMD. It may also have had a role in preventing the absorption of lutein/zeaxanthin.
The lutein/zeaxanthin group saw an additional 5 percent reduction in risk in the group that had the lowest levels of these compounds from their diet at the trial’s start. Those patients who ate more foods with lutein and zeaxanthin, such as green, leafy vegetables and red, orange and yellow fruits and vegetables, did not see this small but significant beneficial effect. The reason may be that the patients eating a higher nutrient-dense diet already have sufficient levels of lutein and zeaxanthin. The duration of AREDS2 was five years and involved 4203 AMD patients between 50 to 85 years of age with the possibility of progression to advanced disease.
Aspirin effect conflicting
It is essential to discuss the role of aspirin, since approximately 20 percent of patients take this drug on a chronic basis (ahrq.gov). There are three recent studies: two were observational and one meta-analysis included observational studies. As I mentioned, observational studies are not the best types of studies.
In the Beaver Dam Eye Study, results showed there was a significant, yet small, increased risk of developing advanced, but not early-stage, AMD when taking aspirin (JAMA. 2012;308:2469-2478). The data can be subdivided even further: those with advanced AMD – neovascular (wet) and geographic atrophy groups – saw vastly different results, with increased risk for the former and decreased risk for the latter. Negative effects only occurred if patients had been taking aspirin for at least 10 years. Those at the five-year mark did not see a difference compared to nonusers. Chronic use was defined as at least two times weekly. Aspirin dosage did not have any impact.
In a second study, aspirin was associated with an increased risk of early AMD (Br J Ophthalmol. 2013 June;97:785-788). However, it became nonsignificant when patients with cardiovascular disease were factored into the mix. The authors concluded that there was no association, though caution and further study may be needed of patients who have cardiovascular disease and take aspirin, which make up a substantial number of aspirin users.
In the third and most recent study, a meta-analysis (group of 10 studies), there was no association between aspirin use and AMD. Risk levels were the same in early and advanced disease. The moral of the story is to speak with your doctor when considering taking aspirin if you have AMD.
On a more upbeat note, it seems that rosemary extract or oil plus zinc decreases the risk of developing retinal damage in rats that is similar to advanced AMD (Molecular Vision. 2013;19:1433-1445).Rats were exposed to damaging lights to try to induce detrimental effects. Zinc alone and rosemary alone were not nearly as effective as the combination. These two substances together decreased the damaging effects of the green light to the retina (back of the eye). Interestingly, the current AREDS multivitamin was not found to be as beneficial as the combination of zinc and rosemary. These are encouraging possibilities for a multivitamin of the future that prevents AMD progression.
We know that aspirin’s benefit outweighs its risk in cardiovascular disease; therefore, do not consider stopping aspirin until talking to your physician. Until well-designed RCTs are done, it is not clear that aspirin elevates AMD risk.
Unfortunately, the ideal formulation for a multivitamin to prevent AMD progression has not been perfected. The AREDS2 formulation with the addition of lutein/zeaxanthin and the deletion of beta-carotene is not commercially available yet. If you don’t have a smoking history, then taking the original AREDS multivitamin formulation is beneficial, plus lutein/zeaxanthin or foods containing these substances. However, if you do smoke, you may want to talk to your doctor about using the AREDS formulation that contains lutein instead of beta-carotene.
Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to www.medicalcompassmd.com and/or consult your personal physician.