Supplements Slow the Course of Macular Degeneration

Our eyesight changes as we get older. We squint to bring words into focus or find ourselves holding reading material at varying lengths from our eyes. These problems may be annoying (and require a first pair of glasses), but their impact pales in comparison to that of blurry vision at the center of the eye -- the hallmark of age-related macular degeneration (AMD).

The most common cause of vision loss in people over age 55, AMD now affects an estimated 10 million Americans. In the coming years, because of increased life expectancy and the aging of the baby boomers, more people than ever will be living with this disease.

AMD is incurable, and treatment options are limited. But new research indicates that high doses of selected antioxidants and the mineral zinc can slow the march toward advanced AMD and possible blindness. These long-awaited findings answer some important questions while raising new ones about where studies should go from here.

WHAT IS AMD?
AMD is the breakdown of cells of the macula, the small area on the retina (see diagram, page 2) that gives us color vision and the sharp eyesight we need to read, drive, recognize faces, or see anything directly ahead. No one knows the exact cause of AMD, but risk factors include age, family history, cigarette smoking, exposure to bright sunlight or UV radiation, farsightedness, hypertension, high cholesterol, and coronary artery disease. Because women are twice as likely as men to develop AMD in later years, some researchers speculate that estrogen plays a role. A study investigating this possibility has been added to the large, ongoing Women's Health Initiative, with results expected in about five years.

A growing body of research has also found links between AMD and dietary intake of antioxidants found in fruits and vegetables, including vitamins A, C, and E.

AMD has two forms, dry and wet. Dry AMD, which accounts for 90% of cases, is identified by the presence of drusen, small, whitish-yellow deposits that accumulate in the retina and break down the light-sensing cells of the macula. Although it's normal to have a few small drusen after age 50, AMD can occur if their size or number increases. Early symptoms include distorted outlines and blurry or blank spots in the center of the visual field. Dry AMD worsens with age, but usually progresses slowly, causing mild to moderate visual loss. Wet AMD, the more damaging form, is characterized by an overgrowth of blood vessels in the macula, possibly in response to growth-promoting compounds released by drusen. Most wet AMD occurs in people who already have dry AMD. It usually progresses to blindness.

Treating dry AMD is pretty much limited to watchful waiting and close monitoring of drusen. For wet AMD, treatments include laser procedures and experimental surgeries and medications.

THE NUTRITIONAL APPROACH
Nutritional research on AMD has focused on the group of antioxidants called carotenoids, substances that give fruits and vegetables their deep green and yellow-orange colors. The carotenoids lutein and zeaxanthin (but not beta-carotene) are found in high concentrations in the retina. Harvard researchers have shown that these two substances are associated with a reduced risk for macular degeneration. In one study, people who consumed the most lutein and zeaxanthin -- an average of about 5.8 mg, or 5,800 micrograms, per day -- had a risk for macular degeneration 57% lower than that of subjects who ate the least of them. Research suggests that lutein and zeaxanthin help to protect the retina from various harmful processes, including certain damaging wavelengths of sunlight.

Zinc is also concentrated in the retina, and high doses have been linked to visual improvement in people with AMD. Many ophthalmologists already recommend supplements of antioxidants and zinc, but in the absence of direct evidence of their effectiveness, they have not had official support.

The Age-Related Eye Disease Study (AREDS) reported in the October 2001 Archives of Ophthalmology is the largest clinical trial to have tested the impact of nutritional supplements on AMD and cataracts. AREDS involved nearly 5,000 women and men, ages 55-80, at 11 clinical centers nationwide. Participants in the macular degeneration portion of the study were divided into groups depending upon the severity of their condition. They received one of the following daily regimens: 1) antioxidants (500 mg vitamin C, 400 IU vitamin E, 15 mg beta-carotene), 2) zinc (80 mg, plus 2 mg copper to prevent anemia), 3) a combination of the antioxidants and zinc, or 4) a placebo. Participants were evaluated every six months for vision loss and annually for retinal changes.

RESULTS ENCOURAGING
Over the seven-year study, combined antioxidants and zinc reduced the risk for progression to advanced AMD by 25%, compared with placebo, among those who already had extensive intermediate or large drusen or advanced AMD in one eye. This treatment also reduced the AMD-related loss of visual acuity by about 19%. Antioxidants or zinc alone reduced the risk, but to a lesser extent. AREDS subjects with early or no AMD got no measurable benefit from the supplements. In the companion study of cataract development, antioxidants and zinc (separately or in combination) had no beneficial effect.

WHAT NOW?
This research suggests that for people with established AMD, antioxidant and zinc supplements are a good idea. AREDS also reinforces the importance of having eye exams to detect the condition.

Although participants reported no major side effects during the study, we don't know about longer-term consequences. Taking nutrients at levels above the Recommended Dietary Allowance (RDA), as AREDS participants did, may not be completely harmless. For example, beta-carotene at comparably elevated doses has been associated in other trials with an increased risk for lung cancer among smokers.

At the same time, AREDS tells us little about the potential of lutein and zeaxanthin. When the study began, neither was available in a form suitable for research. Preliminary studies are now under way. Meanwhile, your dietary intake of carotenoids should include plenty of these two nutrients.

Sources of Lutein and Zeaxanthin
Legend for Chart:

A - Vegetable (100 grams, about 1/2 cup)
B - Lutein/Zeaxanthin (micrograms)

A B

Kale 21,900

Collard greens 16,300

Cooked spinach 12,600

Swiss chard 11,000

Parsley 10,200

Mustard greens 9,900

Red pepper 6,800

Celery 3,600

Broccoli 1,900

Romaine lettuce 1,800

Dry AMD starts with drusen deposits beneath
the macula. In wet AMD, unwanted blood vessels
grow behind the retina toward the macula,
where they leak blood and damage tissue.