POSTED 30 JUN 2005
Originally posted 1996.
If a high-fat diet seems to contribute to age-related macular degeneration (AMD), can antioxidants prevent this blinding disease? These chemicals, including vitamins A, C and E, detoxify "free radicals" -- highly reactive molecular fragments that trigger chemical degradation of the body.
Due to exposure to the ultraviolet radiation in sunlight, and to metabolic activity, the macula contains a lot of free radicals. The tips of the light-sensitive rods and cones must be reformed every day, says ophthalmologic researcher Julie Mares. That produces a dollop of free radicals, which can damage the delicate rods and cones.
The experimental evidence for antioxidants against AMD is limited. Several studies of antioxidants (at doses no higher than the U.S. Department of Agriculture's recommended daily allowance) show no benefit against AMD, Mares says. And high-dose antioxidant supplements are not only unproven, but also risky. Notably, in the Finnish Smoker's Trial, beta carotene increased the rates of lung cancer and hemolytic stroke (caused when red blood cells break up). In other studies, a high dose of vitamin E seemed to reduce the cholesterol-lowering activity of statin drugs, or to increase heart failure.
Still, there are reasons to think antioxidants can help the delicate macula. The largest study to date, the Age Related Eye Disease (AREDS), found some benefit from a supplement mix with 500 milligrams ascorbic acid (a form of vitamin C) 400 IU of vitamin E, 15 milligrams of beta-carotene (a vitamin A relative), 80 milligrams of zinc oxide and 2 milligrams of copper.
The AREDS brew reduced visual loss in people with intermediate or advanced AMD by 29 percent. As National Eye Institute director Paul Sieving said in 2001, "This is an exciting discovery because, for people at high risk for developing advanced AMD, these nutrients are the first effective treatment to slow the progression of the disease." Unfortunately, the supplements did not help people who started the study without intermediate AMD in both eyes or advanced AMD in one eye. It's possible, Mares suggests, that a longer or larger study might have found a benefit among these milder cases.
In 2005 we asked Mares, who studies diet and vision, to update us on AMD and diet. "Many -- but not all -- studies show that people who eat more leafy greens have lower AMD," she told us. The identity of the helpful fruit or vegetable can differ in various studies, and some studies find no benefit from leafy greens -- perhaps, she says, because they count as fruits or vegetables "highly sugared drinks like Hi-C, which contains little actual fruit, or iceberg lettuce, which has few nutrients."
(Beyond AMD, antioxidants may also protect against cataracts, a clouding of the eye's lens that is the biggest cause of blindness worldwide. Vitamin A also seems to slow the decline in retinitis pigmentosa, a hereditary disease that typically destroys vision during middle age.)
Hold the capsules. Pass the broccoli!
Recent evidence suggests that two yellow plant pigments, which are seldom found in supplements, might help fight AMD. Lutein and zeaxthanthin are carotenoids found in many fruits and vegetables, including spinach and corn. Unlike beta-carotene, they gather in the center of the retina, making them particularly interesting in terms of AMD.
In 1994, Johanna Seddon of Harvard Medical School, and colleagues, showed that people who ate more lutein and zeaxthanthin had less "wet" macular degeneration (see "Dietary Carotenoids..." in the bibliography). Lower rates of AMD have been associated with eating lutein and zeathanthin in several other populations. Although some epidemiological studies have found no benefit, monkeys that don't get these carotenoids have retinal disease.
Eye need advice
The dynamic duo of lutein and zeaxthanthin also gather in the lens, where their antioxidant actions may protect against cataract, the most common eye disease of aging. Five studies have found that people with high dietary levels of zeathanthin and lutein have fewer cataracts. Although the connection remains suggestive, the National Eye Institute is about to start a clinical trial of zeathanthin and lutein against AMD and cataracts.
From "Doctor, What..." in the bibliography
If you worry about AMD, what should you do in the meantime? To answer this question, Mares leafed through the scientific literature on supplements and eye disease (see "Doctor, What Vitamins..." in the bibliography) and cooked up some suggestions:
Bad: The dose of zeathanthin and lutein in some multivitamin supplements is not high enough to be helpful. Good: Take several antioxidants together, at the doses typically found in foods.
Good: Spill that fat-free salad dressing down the drain. Moderate amounts of salad dressing containing oils from olive, nuts or canola will help your body absorb zeathanthin and lutein.
Best: Eat your veggies, especially leafy greens. Add a few tablespoons of spinach or kale to your diet each day.
Caution: Because leafy greens contain vitamin K, which speeds blood clotting, tell your doctor if you dramatically increase your intake of leafy greens while taking prescription blood thinners. You may have to adjust your medicine dose.
The larger picture is bright. The evolutionary history of plants suggests that we may be living in a sea of antioxidants. Plants, Mares notes, have evolved antioxidants as protection against the sun's ultraviolet light, yet we have only a skimpy understanding of plant chemistry. "There are many classes of foods that have an antioxidant capacity, that influence our health," she says, "but we have just scratched the surface. We know that many compounds in onions, garlic, chocolate, wine, fruits and vegetables can act as antioxidants. So when you eat your veggies, you are not only getting the few nutrients we know that can fight free radicals. You are also getting the many things we don't know about that can lower oxidative stress."
As we age, we may need to enlarge our view of essential micronutrients, Mares adds. "Scientists had thought that all essential food vitamins and minerals needed to sustain human life had already been identified. But as we think about the nutrients necessary to maintain health into old age, it's possible that lutein and its sister compound, zeaxthanthin, might be essential as well."
We've talked a lot about epidemiology -- the study of populations and diseases. What makes a solid conclusion in the world of epidemiology?