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Long-term nutritional supplementation reduces progression of age-related macular degeneration

Long-term nutritional supplementation reduces progression of age-related macular degeneration

Tuesday, April 23, 2013. An article published online on April 10, 2013 in the journal Ophthalmology reports long-term benefit from supplementing with a nutritional formula containing antioxidants and zinc in men and women with age-related macular degeneration. Age-related macular degeneration (AMD) is characterized by the deterioration of the eye's macula, which results in impairment of central vision. Although there is currently no cure, a combination of beta-carotene, vitamins C and E, and zinc were associated with a reduction in the progression of the disease in a trial that concluded in 2001.

For the current investigation, Emily Y. Chew MD of the National Eye Institute and her associates evaluated data from 3,549 follow-up participants in the Age-Related Eye Disease Study (AREDS), which enrolled 4,757 men and women from 1992 through 1998. Subjects were placed into one of four AMD categories according to the extent of drusen in each eye, the presence of advanced disease, and visual acuity. Participants were divided to receive a placebo, antioxidant vitamins (beta-carotene, vitamin C and vitamin E), zinc plus copper, or antioxidants plus zinc and copper until the trial's completion in 2001. The subjects were invited to participate in a follow-up study, during which annual eye examinations were conducted until November, 2005.

Among participants whose macular degeneration was classified as category 2 (early), 3 (intermediate) and 4 (advanced or neovascular disease in one eye, or central geographic atrophy), those who received antioxidants plus zinc in the clinical trial continued to experience a significant reduction in the risk of developing advanced macular degeneration or neovascular age-related macular degeneration (characterized by abnormal blood vessel growth into the retina) by the end of the follow-up study, in comparison with the placebo group. Supplementation with antioxidants alone was also associated with a reduction in the disease's progression. A separate analysis limited the significance of the finding to subjects in category 4, for whom disease progression was evaluated in the eye that did not have advanced disease at the beginning of the study. Subjects in this category who received antioxidants plus zinc in the clinical trial had a 56 percent lower risk of developing advanced macular degeneration in comparison with those in the placebo group. They additionally experienced a reduction in moderate and severe vision loss.

When mortality was analyzed, those who received zinc were found to have a 17 percent lower adjusted risk of dying from any cause over a median follow-up period of 10.5 years in comparison with those who did not receive the mineral. The protective effect was strongest against death from circulatory diseases.

"Participants in the AREDS clinical trial who had been assigned to the antioxidant and zinc formulation continued to show a reduced odds of developing advanced AMD, especially neovascular AMD, 5 years after the clinical trial ended," the authors conclude. "We continue to recommend the use of the AREDS formulation in persons with intermediate AMD or advanced AMD in 1 eye and persons at moderate to high risk of developing advanced AMD."

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Omega-3 fatty acid metabolite inhibits angiogenesis

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In an article published online on April 3, 2013 in the Proceedings of the National Academy of Sciences, researchers from the University of California, Davis report an antiangiogenic effect for a metabolite of the omega-3 fatty acid docosahexaenoic acid (DHA). Angiogenesis occurs when tumors grow new blood vessels, enabling them to grow and spread. The process also occurs during neovascular age-related macular degeneration, in which abnormal blood vessel growth develops within the eye.

Bruce D. Hammock of UC Davis' Department of Entomology and his associates found that epoxydocosopentaenoic acids (EDPs) metabolized from DHA reduce tumor angiogenesis in mice, and that metabolites of the omega-6 acid arachidonic acid known as epoxyeicosatrienoic acids (EETs) slightly increase it. Further research revealed that EDPs additionally suppress endothelial cell migration needed new blood vessel formation.

"Our investigation opens up a new understanding of the pathways by which omega-3 fatty acids exert their biologic effects," noted lead author Guodong Zhang, who is a postdoctoral researcher in Dr Hammock's laboratory. "As far as we know, EDPs are the first signaling lipids that have been discovered to have such potent anticancer effects. Researchers may be able to use EDPs as structural targets to develop stable analogs as anticancer agents."

"Our results designate EDPs and EETs as unique mediators of an angiogenic switch to regulate tumorigenesis," noted study coauthor Katherine W. Ferrara, who is a professor in the UC Davis Department of Biomedical Engineering. "They also implicate a novel mechanistic linkage between omega-3 and omega-6 fatty acids and cancers."

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