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Role of antioxidants in slowing progression of AMD still subject of debate
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Exactly why age-related macular degeneration (AMD) develops is not known, and no treatment thus far has been steadily effective. Disputed theories suggest that supplemental vitamins, minerals and antioxidants may slow the progression of the dry form of AMD and stabilize the eye.
Researchers have found evidence proposing that people who consume the highest quantity of foods rich in carotenoids and antioxidants and low in fat - such as spinach, collard greens and other dark green leafy vegetables, carrots, sweet potatoes and mangos - are less likely to have the advanced form of macular degeneration, compared with people who eat the least amounts of these foods.
Some, however, encourage nutrient supplementation, saying it is impossible to get the recommended amounts of these substances from diet alone. Other research findings suggest that people should not rely on vitamin supplements as their main source for vitamins, minerals and nutrients due to toxicity possibilities, but instead should eat a balanced diet that includes a wide range of vegetables.
Although some investigators have linked low vitamin and mineral serum levels to the risk of AMD, the lack of specific nutrients is not the only element influencing the disease. Light exposure, smoking and pollution have also been linked to AMD onset and progression.
Diet and vitamins
"By reducing our exposure to risk factors, such as smoking, sunlight, diets rich in meats, processed foods and saturated fats, and increasing our antioxidants, green leafy vegetable intake and exercise, we can slow the progression of macular degeneration and maybe prevent its onset," said Alexander M. Eaton, MD, an ophthalmologist and retina/vitreous specialist with the Eye Centers of Florida. "The earlier we get started the better."
Doctors have long advised patients to consume a balanced diet and to exercise for overall good health. Vitamin and mineral supplements are commonly recommended in addition to diet in amounts determined by the recommended daily allowances. These supplementary dosages cause no apparent harm and are commonly available.
The macula area of the retina is primarily composed of cone cells containing high levels of the carotenoids zeaxanthin and lutein, which are derived through dietary intake. The macula pigment is believed to protect the retina from ultraviolet light. This protective effect is due to the antioxidant activity of zeaxanthin and lutein. Macular pigment density differs from person to person. When macular degenerative changes begin, they start with a migration of the macular pigment, leaving some areas less pigmented than others. AMD develops in response to this cumulative oxidative damage.
Phytochemicals, or plant chemicals, defend the eye from this damage, according to Spencer P. Thornton, MD, FACS, an ophthalmologist and refractive surgeon. "These plant materials are common components of [the] human diet," Dr. Thornton said, "but it isn't always possible to get a balanced diet. Nutritional supplements, particularly those containing phytochemicals, ... play a role in increasing circulation and are high in antioxidants." Dr. Thornton said it is the antioxidant activity that produces a protective effect for the macula.
"There is evidence, ranging across multiple studies, of positive relationships between dietary intake of and/or serum levels of vitamins A, E and C, the antioxidants, and lowered risk of AMD," said Donald R. Sanders, MD, PhD, an ophthalmologist and pharmacologist in Elmhurst, Ill. "With respect to ocular wellness, I believe the evidence [exists] for the value of dietary carotenoids - dietary or through the use of supplements. However, there is ample evidence that nutrition is not optimal in many people, particularly the elderly, and use of carefully formulated supplements is, I believe, warranted."
It has been argued, however, that large doses of vitamins called therapeutic doses - amounts many times greater than the daily recommended allowances - may not be entirely safe. On occasion, these seemingly benign nutrients can be harmful when taken inappropriately, especially nutrients that accumulate in body fat. Also, whether supplements con fer the same nutritional benefits as do food sources rich in antioxidants is debatable.
Evidence lacking?
The current dispute centers on whether scientific evidence links vitamins and minerals to macular degeneration. Numerous nutritional research projects are in progress. If dietary supplements prove effective, this could have a huge impact on AMD treatment and reduce the need for low vision services and devices for older Americans.
Frederick L. Ferris, III, MD, a retina/vitreous specialist and director of the Division of Biometry and Epidemiology at the National Institutes of Health (NIH) in Rockville, Md., said currently there are no reliable data that could influence a practitioner to prescribe vitamin and mineral supplements for AMD.
"All of the data that suggests that vitamin intake or serum levels are associated with macular degeneration are from what are called observational studies," Dr. Ferris said. "Observational studies aren't enough. They are great for hypothesis generation, but they are poorly suited to establish cause and effect."
Dr. Ferris referred to the Finnish study, Alpha-Tocopherol, Beta-Carotene Lung Cancer Prevention Study (ATBC). The study investigated vitamin E alone, beta-carotene alone or a combination of the two compounds in preventing lung cancer in more than 29,000 male cigarette smokers. Unexpectedly, the study showed an increase of 16% in the incidence of lung cancer in the beta-carotene group. The beta-carotene group also had a higher risk of total deaths, primarily due to deaths from lung cancer and ischemic heart disease.
Consuming supplements is not the same as taking mega-doses of vitamins. Common sense dictates that if one is going to use supplements at all, products providing nutrients in the range of the recommended dietary allowances remain the best choice.
"I think we have to evaluate the risk-to-benefit ratio and realize that it is quite low," Dr. Sanders said. "Antioxidants prevent the free-radical damage, carotenoids help maintain macular pigment density and zinc plays a role, probably as a co-factor for the enzymes involved in antioxidant activity." Dr. Sanders said that in supplements an appropriate mix of nutrients are given to promote optimal levels, and well-formulated products are not given in dangerous mega-doses.
Dr. Eaton agreed: "As for vitamin and mineral supplements, there is little data that, if you take them as I propose, there are any deleterious effects." Dr. Eaton said he does not advocate taking supplements in place of dietary intake of foods rich in vitamins and minerals.
To complete the regimen, Dr. Eaton suggests his patients take one multivitamin with minerals, and supplement vitamin E (400 IU) and vitamin C (1,000 IU). Dr. Eaton does not recommend adjusting the supplement intake for dietary intake for patients who eat a normal diet.
"There is a great deal of scientific evidence that nutritional supplements containing phytochemicals are effective in reversing and slowing down the processes of degeneration," said Dr. Thornton, "particularly macular degeneration. You can't reverse the damage that has already been done, but you can reverse the progression of currently occurring damage."
A study that appeared in the December 1995 issue of Archives of Ophthalmology (Serum antioxidants and age-related macular degeneration in a population-based case-control study), concluded that people with the lowest levels of lycopene, a carotenoid, were twice as likely to have AMD.
How free radicals work
The body needs free radicals, or unstable oxygen, to fight infections and stop inflammation. Free radical scavengers produced by the body eliminate extra free radicals that prevent damage to the eye. When the amount of free radicals in the body exceeds the capacity of the free radical scavengers, the aging and injurious processes begin and vision is reduced. This degeneration is called oxidative stress.
Environmental factors, such as sunlight, smoking, pollution, and contaminants in food can produce free radicals because the human body is not equipped with an adequate natural defense mechanism to protect itself. The free radicals cause damage to the lens and retina, leading to the development of cataract and macular degeneration.
The retina is vulnerable to this damage due to the high flow of oxygen through it. In addition, retinal photoreceptors contain high levels of polyunsaturated fat, which is predisposed to damage from free radicals. It is the retinal photoreceptors and retinal pigment epithelium that are damaged by oxidative stress.
Smoking and AMD
Several studies suggest that smoking may be associated with AMD. The Rotterdam Study noted the link between smoking and AMD (Age-related Macular Degeneration is Associated With Atherosclerosis: The Rotterdam Study). Results from this study indicated that current and former smokers had an increased risk of neovascular AMD.
The causes of the association, however, are still unclear. According to the study, it is probable that by decreasing levels of serum antioxidants smoking lowers the levels of retinal antioxidants, thus leaving the eye open to free radical damage. Another reason for the association may be alteration of choroidal blood flow.
Dr. Eaton noted that many of the same factors that lead to atherosclerosis also contribute to the development of macular degeneration, such as smoking, high blood pressure and elevated cholesterol. "Evidence was found in a study of Dutch seniors," Dr. Eaton said, "that people with fat deposits in their arteries are more likely to have AMD than those with clean arteries."
He said hardening of the arteries de creases the flow of blood and nutrients through the portion of the choroidal blood vessels that supply the retinal pigment epithelium, which becomes damaged. Cells are eventually lost, photo receptors become damaged and vision is lost.
The NEI is currently sponsoring several studies to establish the specific causes of AMD and how it can be prevented and treated. The NEI's Age-Related Eye Disease Study involves researchers at 11 clinical centers in the United States who are assessing the aging process, potential visual risk factors and quality of life in 4,700 patients. The study includes clinical trials that will assist in determining the effects of certain vitamins and minerals, especially vitamins C and E, beta-carotene and zinc, in preventing or slowing the progress of AMD.
These vitamins and minerals will be closely examined to determine whether they can provide the macula with greater protection, thereby preventing or slowing progression of the disorder. The study is due to be completed in the next 2 years. It also aims to determine whether any of these vitamin and mineral combinations are effective and safe therapy for macular degeneration.
For Your Information:
- Alexander M. Eaton, MD, can be reached at (941) 939-3456.
- Frederick L. Ferris, III, MD, can be reached at (301) 496-6583.
- Donald R. Sanders, MD, PhD, may be reached at (630) 530-9700. Drs. Eaton, Ferris and Sanders have no direct financial interest in any products mentioned in this article, nor are they paid consultants for any companies mentioned.
- Spencer P. Thornton, MD, FACS, can be reached at (615) 329-7890. Dr. Thornton did not disclose if he has a direct financial interest in the products mentioned in this article or if he is a paid consultant for any companies mentioned.