EyeWorld is the official news magazine of the American Society of Cataract & Refractive Surgery.
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March 2013 EW RETINA 77 Pharmaceutical focus Supplement strategies to forestall AMD by Maxine Lipner EyeWorld Senior Contributing Writer Eye on best vitamins A ge-related macular degeneration (AMD) has the dubious distinction of being the leading cause of new cases of blindness in older Americans, according to William G. Christen, Ph.D., epidemiologist, Brigham and Williams Hospital, Boston. To help stave off this sight-threatening disease, as well as minimize progression, practitioners often steer their patients toward the supplement aisle of the drug store. But which supplements should they be encouraging patients to put on their lists? Beginning the list Dr. Christen sees a range of vitamins as potentially playing a pivotal role here and pegs the best data to shine a light on key nutritional supplementation as coming from the original Age-Related Eye Disease Study (AREDS). "That showed that among people who have intermediate AMD or advanced AMD in one eye, a combination of vitamin E, C, and beta-carotene plus zinc appeared to slow the progression to advanced AMD," he said. Meanwhile, a trial his own group worked on, published in the February 2009 issue of the Archives of Internal Medicine, showed value to supplementing with vitamins B6 and B12 as well as folic acid. "It indicated that there was a benefit on early AMD in people who received those supplements over an average of about seven years of follow-up," Dr. Christen said. Investigators found that of those taking supplements, just 55 AMD cases were reported compared with 82 cases in the placebo group, something that surprised Dr. Christen. "We were surprised because it had been investigated in a number of trials of cardiovascular disease prevention with no benefits observed," he said. Off the omega-3 shelf Dr. Christen said there are a number of other possible supplements being evaluated in randomized trials right now. "There's a lot of current excitement about fish oil—omega-3 fatty acids," he said. "They're being investigated in a couple of ongoing trials including one that we're conducting here and also the NEI AREDS2." Omega-3 fatty acids are rich in DHA, he observed. "They're found in the retina and they're part of some of the constituents of the retina," he said. So the thinking is, based on observational data that suggest a benefit for those people who have a high intake of fish, that omega-3 might be the oft-sought magic bullet, he explained. Likewise, Johanna M. Seddon, M.D., professor of ophthalmology, director of ophthalmic epidemiology and genetics service, and macular degeneration specialist, New England Eye Center, Tufts Medical Center, Boston, touts the benefits of omega-3 fatty acid in forestalling AMD. "We've done some of the early work in the 1990s on omega-3 fatty acids in the diet and have shown beneficial effects in a sample of twins," she said. In this study of identical twins, published in the July 2011 issue of Ophthalmology, investigators found that the twin who ate the most fish, high in omega-3 fatty acids, tended to have an earlier stage of AMD than the identical sibling. While the difference was not found to be significant here, her earlier studies, one published in the July 2006 issue of Archives of Ophthalmology, showed a beneficial effect of omega-3 fatty acids on both onset and progression to advanced stages of AMD. In addition, other dietary factors were shown to be important in slowing AMD in this twin population. "We found that other nutrients were related, including intake of methionine and betaine," she said. She pointed out that vitamin D might also be helpful. This was found to be inversely associated with AMD drusen size and area in the twin study. "General recommendations for older individuals are between 1,000 and 2,000 IU of vitamin D3," Dr. Seddon said. New must-haves Other nutrients showing promise in forestalling AMD are lutein and zeaxanthin. "Foods rich in lutein and zeaxanthin like spinach, collard greens, green leafy vegetables and foods rich in omega-3 fatty acids, especially the fatty-type fish like salmon, mackerel, and sardines, have been shown to be beneficial in many studies for reducing the rate of (AMD) progression, beginning with our Dietary Ancillary study published in [Journal of the American Medical Assosciation] in 1994," Dr. Seddon said. Over the years, lutein, zeaxanthin, and omega-3 fatty acids have all become pivotal players. "I think that's why supplements now that are in the new [AREDS2] have taken out some of the old ingredients from the [original] AREDS and substituted with these new ingredients," Dr. Seddon said. "It remains to be seen what the results are, but there is a lot of evidence pointing to the beneficial effects of lutein instead of betacarotene, only because there is no beta-carotene in the retina, but there is an abundance of lutein and zeaxanthin." She warned that for smokers, beta-carotene should actually be avoided. "There were a couple of clinical trials that showed that betacarotene increased the risk of lung cancer in smokers," she said. "So beta-carotene is contraindicated in anyone who smokes or who smoked in the recent past." For her patients, Dr. Seddon recommends maintaining healthy habits including avoiding smoking and exposure to heavy smoke, as well as eating a healthy diet with foods rich in lutein, zeaxanthin, and omega-3 fatty acids. This includes consuming a lot of fruits and vegetables and eating fish a couple of times a week. Her supplement strategy builds on this. "If people want to take supplements, I recommend lutein and zeaxanthin and omega-3 fatty acid supplements, as well as vitamin C, modest doses of vitamin E, and some zinc" she said. Jeffrey B. Morris, M.D., Encinitas, Calif., likewise touts the importance of lutein and zeaxanthin, which are part of the yellow luteal pigment filter protecting the macula. This nutrient filter is made up of three carotenoids: lutein, zeaxanthin, and meso-zeaxanthin, he said. "Recent studies out of the Waterford Institute in Ireland have revealed that meso-zeaxanthin may be even more important than the other two carotenoids, especially with regard to visual performance," Dr. Morris said. Dr. Morris uses a new technology called MAPCATsf (Guardion Health Sciences, San Diego) to gauge the status of a patient's protective macular pigment optical density (MPOD). "MPOD has been associated inversely with the incidence of AMD; additional denser MPOD levels have been definitively linked to better visual performance in areas such as contrast sensitivity, glare reduction, and faster photostress recovery times," he said. "I strongly recommend that all of my patients set up an appointment with our staff's ocular nutritionist to have their MPOD tested in our Visual Performance Clinic and to have nutritional counseling." Dr. Morris finds that about 75% of patients follow through on this. At the clinic, the nutritionist analyzes the patient's current diet and supplement intake and recommends ways to increase lutein, zeaxanthin, and meso-zeaxanthin levels, he explained. "At this stage our primary goal is for patients to obtain favorable levels of these three essential carotenoids for maintaining ocular health, either through diet or food supplements," Dr. Morris said. While there are many supplements that contain two of the three ingredients that he deems essential, Dr. Morris says that his preference is for Lumega-Z (Guardion Health Sciences). "It is the only supplement on the market to contain liquid mesozeaxanthin as well as lutein and zeaxanthin," he said. Meso-zeaxanthin, a metabolite of lutein and not found in foods, can be deficient in individuals who do not metabolize lutein properly. Overall, Dr. Morris urges other practitioners to keep ocular nutrition and possible need for supplements high on the agenda. "As a cataract surgeon my tendency is to focus on the anterior segment, however, the usual excellent results from cataract surgery can be even more potentiated by improving the macular health," he said. "Being involved in prevention creates favorable outcomes for my patients and my practice." EW Editors' note: Dr. Morris has financial interests with Guardion Health Sciences. Drs. Christen and Seddon have no financial interests related to this article. Contact information Christen: 617-278-0795, wchristen@partners.org Morris: 760-631-3500, drmorris@morriseyegroup.com Seddon: 617-636-9000, Johanna_seddon@yahoo.com