Nutrition's Emerging Role in  Ocular Disease
More studies demonstrate a beneficial link between supplements and eye health.
BY JOHN PARKINSON, ASSOCIATE EDITOR

Years ago, many physicians were reluctant to discuss nutrition and recommend vitamins or supplements to patients. Nutrition was often a small part of the curriculum in medical schools, according to Johanna M. Seddon, M.D., a leading researcher. A paucity of research demonstrated the connection between nutrition and disease prevention. As a result, doctors did not consider nutrition as a major contributor to health with regard to preventing illness.

More recently, scientific evidence may have some doctors reconsidering their stance on nutrition, especially as it applies to ocular ailments. Clinical studies are proving nutrition is one significant element in helping to prevent or retard progression of ocular disease; this is most evident in the fight against AMD with the Age-Related Eye Disease Study (AREDS) trial findings.

Along with AMD, cataract and glaucoma studies related to nutrition research are being conducted, as scientists look for ways to prevent the onset of — or delay — the progression of these debilitating and blinding diseases. This article will provide physicians' and researchers' analysis about ongoing nutrition studies and how it might be applied in practices.

Why Ocular Supplementation?

Some physicians may not see a strong argument for implementing ocular supplementation into their treatment armamentaria, but the physiological nature of the eye offers a contrary opinion, says Hannah Bartlett, MCOptom., a research fellow with the Ophthalmic Research Group, Aston University, Birmingham, England.

"Ocular tissues are particularly susceptible to oxidative damage. The transparency of the cornea, aqueous humor, lens and retina allow continuous exposure to light, which along with aging, inflammation, air pollutants and cigarette smoke, has been shown to increase production of reactive oxygen species (ROS).1-3 The use of antioxidants in an attempt to prevent the onset and progression of age-related ocular disease appears to be indicated," says Dr. Bartlett.

While this may be true, another researcher, John Veach, O.D., says there continues to be a disparity between the small amount of research on nutrition and disease as compared to the enormous amount of physiological research about the role such diseases play on the body's anatomy and processes. Dr. Veach decided to determine how certain vitamins and antioxidants can play a role in primary open angle glaucoma (POAG) patients.

"There had been very little research concerning the role of nutrition in POAG. On the other hand, there was a great deal of physiological research taking place all over the world when I began studying this subject about 7 years ago," says Dr. Veach. "I was surprised and excited to be able to fit the pieces of the glaucoma puzzle together as new research emerged. In this way, I was able to use available scientific research to validate a role for nutrition in glaucoma."

This lack of finite scientific evidence on how vitamins and minerals work in the eye suggests much remains to be discovered about possible supplementation therapy.

Cautionary Advice

For physicians who want to recommend supplements to patients, Dr. Seddon, who is associate professor of Ophthalmology at the Harvard Medical School, associate professor of Epidemiology at the Harvard School of Public Health, and a principal investigator for AREDS I, suggests doctors find out if their patients are currently taking any vitamins or minerals before recommending any further supplements.

For example, when she recommends the AREDS formula to patients with AMD, she tells them to discontinue the use of other supplements that contain vitamin E. She also asks patients about cigarette smoking, because smokers should not take beta-carotene.

Upon taking a history, physicians should establish a guideline for patients, describing what supplements they should ingest and how much. While this leaves concerns such as toxicity and daily dosage in the physician's lap, guidance about such issues can be found on the Institute of Medicine's (IOM) Web site. The site can be accessed at www.iom.edu. The Institute lists recommended daily intakes and tolerable upper intake levels for individual vitamins and minerals; however, it does not outline how much should be ingested for persons who are suffering ocular ailments.

AMD

While nutritional research has been branching out into various ocular diseases and ailments, AMD, arguably, receives the most attention, especially with the federal government's financial support and active participation. The National Eye Institute (NEI) has led the way with its first Age-Related Eye Disease Study (AREDS I), which looked at nutritional supplements and the effect they would have on the incidence and progression of AMD.

As the AREDS I trial comes to a close this month after several years, researchers have accumulated significant data from the randomized, multicenter trial.

"The AREDS clinical trial demonstrated a beneficial effect in a rigorous well-done study. I think it is very important in delaying the progression of the disease," says Dr. Seddon.

In persons with a moderate risk of AMD or advanced AMD in one eye, high doses of antioxidant vitamins and minerals reduced the risk of developing advanced AMD by 25% in 5 years.4 Additionally, the risk of moderate vision loss (15 or more letter decrease compared to baseline visual acuity measured on the logMAR chart) was also reduced by 19% at 5 years in those patients assigned to the combination of antioxidant vitamins and minerals compared to participants assigned to placebo.5

Dr. Seddon also points to the ability of patients to have some autonomy in treating their disease. "It's something people can do for themselves that we didn't have before."

The first AREDS trial used a nutritional formula that included vitamins C and E, beta-carotene, zinc and copper. However, in a new study (AREDS II), researchers will
modify the formula to reflect concerns that were raised in the first AREDS trial. Beta-carotene will be taken out of some of the treatment arms because studies have linked the carotenoid with greater incidences of lung cancer among smokers.

Additionally, a relationship between zinc and Alzheimer's disease was reported in vitro, so for AREDS II some of the patients will be given a daily dose of 80 mg of zinc — which was used in AREDS I — and others will receive a lower dosage. Other nutrients that will be added to the study include the carotenoids, lutein (10 mg) and zeaxanthin (2 mg) taken together and omega-3 long-chain polyunsaturated fatty acids plus eicosapentaenoic acid at a total of 1 g.6,7 Along with AREDS supplementation, Dr. Seddon recommends AMD patients eat a balanced diet, specifically spinach and broccoli to get lutein, and a daily multivitamin as well. "Some older individuals are not eating well-balanced meals. I think it is good to get a well-balanced intake of vitamins and minerals and at least the minimum daily requirements."

Glaucoma

Whereas the AREDS II trial will be investigating whether omega-3s decrease the risks of AMD, there are some POAG studies linking omega-3s to glaucoma and an increase in IOP. Jae Hee Kang, Sc.D., along with a group of researchers found a suggestive positive association that a higher ratio of omega-3 to omega-6 appears to increase the risk of POAG, specifically high-tension POAG.8

Another paper suggests a similar dietary link saying, "the dietary ratio of omega-3/omega-6 [polyunsaturated fatty acids] PUFA could influence cyclooxygenase competition. A diet with increased omega-3 and decreased omega-6 could thus favor an increase in intraocular pressure, reducing synthesis of [prostaglandin F (2 alpha)] PG-F2, leading to a decrease in uveoscleral outflow."9

While the researchers in both papers concluded that further studies were needed, the theory that dietary fat intake may influence the risk of POAG and an IOP increase illustrates a new aspect of nutritional advice for glaucoma specialists to consider.

Along with studies on polyunsaturated fats, Dr. Veach's paper discussed the role nutritional components — specifically vitamin E and glutathione — play in the aetiology of POAG. Published in the British Journal of Nutrition, Dr. Veach's paper discussed two physiologic changes in the trabecular meshwork that cause IOP to rise and optic nerve atrophy. "Compelling evidence suggests that collagen trabecular meshwork extracellular matrix (ECM) remodeling is correlated to increased intraocular pressure in POAG. Elastin trabecular meshwork ECM remodeling is correlated to POAG optic nerve atrophy," wrote Dr. Veach. "There appear to be two different pathways for collagen remodeling and apoptosis induction in POAG. The pathway for collagen remodeling and apoptosis induction seems to be exogenously influenced by water-soluble antioxidants, for example glutathione. The pathway for elastin remodeling and apoptosis induction seems to be influenced by endogenous lipid-soluble antioxidants, for example vitamin E."10 Dr. Veach concluded that antioxidants are important in maintaining cellular homeostasis in the aetiology of primary open angle glaucoma.

Dr. Veach does not see present research validating the use of vitamin E and glutathione supplements. "Unfortunately, I do not believe that there is enough scientific evidence to answer this question with any authority. I do not challenge the status quo by recommending specific nutritional remedies to my patients," explains Dr. Veach.

He foresees glaucoma nutritional research focusing on halting the progression of the disease as opposed to preventing it. He also says a market for novel antioxidants is the most likely development in glaucoma supplementation. "Novel antioxidants can be patented so that those willing to make the investment can recapture the research expenditures," predicts Dr. Veach.

Cataracts

Vitamins and minerals that have been highlighted for use in the prevention of onset or progression of lens opacities include vitamins A,C, E and lutein, although there is conflicting evidence for each. When asked about adverse reactions and contraindications of ocular supplements,
Dr. Bartlett commented that, "practitioners should be particularly aware of potential relationships between vitamin A and reduced bone mineral density. High-dose vitamin A supplements should be avoided by women who may become pregnant, in those with liver disease and those who drink alcohol heavily. There are a couple of case reports detailing anticoagulant and antiplatelet effects of vitamin E and ginkgo biloba respectively."

The chart in the upper right column gives the IOM's recommendations for daily intake and the upper tolerable limits of the antioxidants used for cataract prevention.

Dr. Bartlett also says following the food pyramid can be helpful to patients who are at risk of developing cataracts. "The dietary guidelines set out for maintenance of general well-being may be recommended, i.e., consumption of at least five portions of fruits and vegetables per day," explains Dr. Bartlett. "More specifically, increasing intake of foods rich in lutein such as spinach and kale has been associated with a moderate decrease in the risk of cataract."11

Supplementation's Role

Overall, there are many ongoing nutritional studies suggesting an emerging role for supplementation in the future. With this in mind, ophthalmologists have an opportunity to continue discussing the benefits of a healthy diet with patients, and as more developments of supplementation research become available, recommendations for supplementation usage may someday play a definitive role in all physicians' discussions about ocular health. OM

References   

1. Borish E, Prior W., and Venuugopal, S. DNA synthesis is blocked by cigarette tar-induced DNA single strand breaks. Carcinogenesis. 1987;8:1517-1520.

2. Machlin L, Bendich A. Free radical tissue damage: protective role of antioxidant nutrients. Faseb Journal. 1987;1: 441-445.

3. Seddon JM, Ajani UA, Sperduto RD, et al. Dietary carotenoids, vitamins A,C, and E and advanced age-related macular degeneration. JAMA. 1994;272:1413-1420.

4. The Age-Related Eye Disease Study Group. A randomized, placebo-controlled, clinical trial of high dose supplementation with vitamins C and E, beta-carotene, and zinc for age-related macular degeneration and vision loss. AREDS Report No. 8. Archives of Ophthalmology. 2001;119:1417-1436.

5. Chew EY. Dietary Supplements: What we should and should not be recommending for our patients. Retinal Physician. 2005; 3: 45-47

6. Seddon JM, Rosner B, Sperduto RD, et al. Dietary fat and risk for advanced age-related macular degeneration. Arch Ophthalmol. 2001;119:1191-99.

7. Seddon JM, Cote J, Rosner B. Progression of age-related macular degeneration: association with dietary fat, transunsaturated fat, nuts, and fish intake. Arch Ophthalmol. 2003;121:1728-1737.

8. Kang JH, et al. Dietary fat consumption and primary open-angle glaucoma. American Journal of Clinical Nutrition. 2004;79:755-764.

9. Desmettre T, Rouland JF. Hypothesis on the role of nutritional factors in ocular hypertension and glaucoma. Journal of French Ophthalmology. 2005;28:312-316.

10. Veach J. Functional dichotomy: glutathione and vitamin E in homeostasis relevant to primary open-angle glaucoma. British Journal of Nutrition. 2004;91:809-829.

11. Chasen-Taber L, et al. A prospective study of carotenoid and vitamin A intakes and risk of cataract extraction in U.S. women. American Journal of Clinical Nutrition. 1999;70:509-516.