Do vitamin supplements really prevent progression of AMD?

Net benefits and risks of vitamin supplements must await completion of appropriate trials, ophthalmologists say.

Issue: October 1, 1999

The jury is still out on whether or not vitamin supplements delay the succession of the age-related macular degeneration (AMD) damage. Many ophthalmologists concur that there is not sufficient data to confirm what observational studies have suggested.

Since AMD is prevalent and therapy is limited, several studies are focusing on prevention. Studies on vitamins and their effects on eye disease have been small and observational. Ophthalmologists agree the Age-Related Eye Disease Study, the largest AMD and vitamin study thus far, should bear out concrete data on the prevention of the sight-threatening disease. And a majority of eye care professionals agree that while they do not know for sure if vitamins are advantageous, they probably do not hurt a patient if taken correctly. However, most physicians advocate a healthy diet before recommending vitamin supplements.

Lack of stats

“The problem is epidemiologically there isn’t a lot of data that has validated that vitamin supplements make a big difference,” Paul S. Bernstein, MD, PhD, told Ocular Surgery News. “I think, among ophthalmologists, the question of nutrition and macular degeneration has left a lot of ophthalmologists rather skeptical.” Eye health practitioners agree that more studies need to be performed. “In an effort to offer some treatment, many ophthalmologists will not discourage nutritional supplements, reasoning that they don’t know if they help, but they probably don’t cause harm,” retinal specialist Thomas Ciulla, MD, told Ocular Surgery News. “But whether they will benefit the patients with advanced macular degeneration is doubtful.”

Observational studies have shown that patients with a family history of AMD or have early signs of AMD may be able to slow down the formation, or any visual loss associated with the disease, by eating healthy, not smoking, avoiding sunlight and taking vitamin supplements. But the reversal of damage is unlikely.

According to David Boyer, MD, many of his AMD patients are already taking a multivitamin. But the problem is these multivitamins do not always contain the vitamins and/or antioxidants that are helpful to the eye based on observational studies. But the vitamin marketplace is shifting to include lutein and zeaxanthin in multivitamins, Dr. Boyer said.

“In the beginning, the only supplement that was shown to be helpful was zinc,” Dr. Boyer told Ocular Surgery News. “We know that high levels of zinc may compete with the body’s copper and cause copper deficiency anemia. I think it is important to know what our patients are taking to better advise them.” Dr. Boyer promotes a healthy diet first to try to slow down AMD damage, and then recommends patients look for specific vitamin supplements.

All ophthalmologists interviewed for this article were concerned about the toxicity effects of some vitamins.

Carontenoids

“I think lutein and zeaxanthin are probably the best up and coming nutritional supplements,” Dr. Bernstein said. “I think there is biological plausibility that they are good antioxidants, [of which] the highest concentrations anywhere in the body is found directly in the macula.”

Dr. Bernstein has personal research interests in lutein and zeaxanthin, the pigments in the eye, and their possible roles in preventing macular degeneration. According to Dr. Bernstein, the Eye Disease Control Study Group has produced very interesting and provocative data linking patients who consumed a lot of foods containing lutein and zeaxanthin and who had high blood levels of those two carotenoids to having a much lower rate of exudative or wet AMD.

“I encourage patients to try to consume foods that are high in lutein and zeaxanthin,” Dr. Bernstein said. “If not, certainly many of my patients do take supplements that contain lutein.” Lutein and zeaxanthin are closely related carotenoids. It has been proposed that lutein is converted to zeaxanthin in the retina. The typical daily dose of lutein ranges from 6 mg to 20 mg per daily dose, as said by Dr. Bernstein. Zeaxanthin, however, is still not available in pure form. The lutein supplements that list zeaxanthin only contain small amounts of zeaxanthin, around 3% to 5%.

Lutein and zeaxanthin are the major determinants that explain macular pigment density differences between individuals, but the amount of variance explained is limited, according to a study presented by Dr. Ciulla at the Association for Research in Vision and Ophthalmology. These carotenoids are concentrated in the macula and accumulation is thought to be dependent on dietary intake. The macular pigment is thought to possibly filter out harmful blue light that damages the macula. It also may act as a free radical scavenger that prevents further damage.

Good dietary habits remain the first-line therapy for progression prevention in AMD patients. But supplements alone are not bad, Robert Abel Jr., MD, told Ocular Surgery News. Dr. Abel recommends magnesium at bedtime because it dilates blood vessels at a time when blood pressure is reduced and allows more perfusion.

Dr. Abel recommends vitamin supplements to his patients. “The key is to try to make it cost effective for people,” Dr. Abel told Ocular Surgery News. “You can’t give patients a list of 40 things that are said to help eyes.”

Dr. Abel recommends his patients take a multivitamin once in the morning and once at night. Vitamin A also is added in the morning for day vision and vitamin E at dinner to prevent lipid peroxidation. Dr. Abel also advises the omega-3 fatty acid, DHA, in the morning and at night with meals.

AREDS

AREDS, funded by The National Eye Institute, is a randomized study evaluating antioxidants, vitamins C and E, beta-carotene and zinc. AREDS has 4,754 patients enrolled that are randomly assigned to antioxidants alone, antioxidants plus zinc, zinc alone or placebo. The study is in its fifth year of follow up and is to be completed by 2001. According to the study’s chairman, Frederick L. Ferris, MD, at the start of the study about 1,000 patients had no or very few small drusen, about 1,000 had many small or just a few intermediate drusen, about 1,000 had lost vision in one eye from AMD, and the remainder had several intermediate or some large drusen.

“I think it is probably reasonable to think that at best vitamin supplements might make a difference in the small to moderate range,” Dr. Ferris told Ocular Surgery News. “But they are not likely to be penicillin for AMD. If you could reduce the risk of progressing in AMD the same way aspirin reduces the risk of cardiovascular disease, that would be important.” Dr. Ferris said eye care professionals should sit tight and wait for this clinical trial data to know whether taking supplements is the same as what the observational studies have concluded.

Dr. Ferris does not recommend to his AMD patients that they take vitamins. Dr. Ferris explains the observational study data and tells patients that whether they help or not still remains to be proven. He believes many ophthalmologists recommend vitamins on the basis of the observational studies that are available. Dr. Ferris continued to say that the general feeling could be that vitamins are likely to be helpful and unlikely to be harmful and the ophthalmologists desire to do something for patients.

“Sometimes in an effort to do something, we do something wrong,” Dr. Ferris said. “That is why we are doing this clinical trial to make sure that when we do recommend something, that we’ve got good reason.”

For Your Information:

Robert Abel Jr., MD, can be reached at Concord Plaza Naamans Building, 3501 Silverside Road, Wilmington, DE 19810; (302) 479-3937; fax: (302) 477-2650. Dr. Abel has no direct financial interest in any of the products mentioned in this article, nor is he a paid consultant for any companies mentioned.

Paul S. Bernstein, MD, PhD, can be reached at Moran Eye Center, 50 N. Medical Drive, Salt Lake City, UT 84132; (801) 585-7385; fax: (801) 581-3357. Dr. Bernstein has no direct financial interest in any of the products mentioned in this article, nor is he a paid consultant for any companies mentioned.

David Boyer, MD, can be reached at 1127 Wilshire Blvd., Ste. 1620, Los Angeles, CA 90017; (213) 483-8810; fax: (213) 481-1503. Dr. Boyer has no direct financial interest in any of the products mentioned in this article, nor is he a paid consultant for any companies mentioned.

Thomas Ciulla, MD, can be reached at Indiana University, Department of Ophthalmology, 702 Rotary Circle, Indianapolis, IN 46202; (317) 274-3821; fax: (317) 274-1288. Dr. Ciulla has no direct financial interest in any of the products mentioned in this article, nor is he a paid consultant for any companies mentioned.

Frederick L. Ferris, MD, can be reached at 31 Center Drive, MSC 2510, Bldg. 31, Room 6A52, Bethesda, MD 20892-2510; (301) 496-6583; fax: (301) 496-2297. Dr. Ferris has no direct financial interest in any of the products mentioned in this article, nor is he a paid consultant for any companies mentioned.