As more studies are demonstrating lately, there is a strong link between proper nutrition and optimal ocular and visual health. Inadequate, unbalanced or excessive food intake has been linked to dry eye, vascular occlusive disease, diabetic retinopathy, age-related macular degeneration (AMD) and cataract formation.


Heres an update on the latest research that links proper diet and nutritional supplementation to yet another ocular condition: glaucoma.

 

Open-Angle Glaucoma

In contrast to all our efforts to treat patients and not simply their conditions, glaucoma remains one of the diseases for which we still break this tenet. The mainstay of glaucoma therapy is to control intraocular pressure (IOP), based on evidence that this tactic provides the best chance of minimizing glaucomatous optic nerve damage.1-2


Measuring Up

The antioxidant capabilities of foods and supplements are evaluated for their antioxidant capability using different methods that aim to determine Total Antioxidant Capacity (TAC). Two common methods are the Oxygen Radical Absorbance Capacity and the Ferric Iron Reducing Antioxidant Power. These methods evaluate different aspects of antioxidant capacity, so there are discrepancies in the TAC scores reported for various foods and supplements. And, differences in growing conditions, harvesting, processing and preparation affect foods actual TAC. This helps to explain some inconsistencies in the information about superfoods disseminated in the popular literature. Despite these apparent differences, however, certain foods, such as walnuts, apples, berries, spinach, dark chocolate, plums and artichokes, consistently rank high in TACno matter which method is used.29,30

But, no matter how many new anti-glaucoma drugs are developed, several peculiarities still exist about the disease itself: Why do some patients with IOPs of 27mm Hg suffer severe nerve damage, while others dont? Why do black patients suffer more severe nerve damage than white patients, even after correcting for central corneal thickness (CCT) differences? Why do some patients have an aggressively progressive form of the disease, while others show a more stable profile? Why do some patients show a reduced IOP in response to topical therapy, yet still experience deterioration of the visual field and loss of nerve fiber layer thickness?3-9


If the connection between IOP and nerve damage was absolute, these discrepancies would not exist. It is probably more accurate to think of high IOP as an important risk factor, but not as the sole etiology, of primary open-angle glaucoma (POAG).10 And, it is possible that at least part of the remaining puzzle might be solved with an understanding of nutritions role in the maintenance of ocular health.


Problem: Nerve Damage

Several processes aside from increased IOP can cause optic nerve damage. Vascular dysregulation, systemic hypotension and other vascular compromise are among the most well understood non-IOP dependent mechanisms associated with glaucoma.11-15


On a cellular level, excitatory neurotransmitters and apoptosis (also known as programmed cell death) have been implicated in the development of glaucomatous damage. Adjunct strategies in glaucoma management are often aimed at preventing or minimizing these factors, along with other methods of neuroprotection.16 In cases of glaucoma, neuroprotection (protecting previously undamaged ganglion cells from the destructive cellular processes resulting from the death of adjacent ganglion cells) deals less with lowering IOP, and more with neutralizing the chemicals and other extracellular substances produced during the original damage.17 This is where nutrition might play a role.

 

Solution: Antioxidants

In their normal functions and processes, cells produce free radicals as byproducts. Stress and environmental toxins, such as tobacco smoke and radiation, also produce free radical molecules.


Structurally, these unstable molecules have incomplete electron shells, making them more chemically reactive than molecules with full electron shells. Free radicals are constantly looking for other molecules from which to take electrons in order to complete their shell. But, those other molecules wont function properly if their electrons are snatched by free radicals. Optic nerve cells are more susceptible in glaucoma patients than in those without glaucoma; the reasons for this are not entirely clear.


In such cases, cellular damage results, and evidence suggests that this cellular damage can translate into several disease processes, including cancer, premature signs of aging, AMD, cataract formation, obesity, mood disorders, memory disorders, and a host of other diseases.18-21 Oxidative stress is also associated with glaucomatous optic nerve damage, because free radicals damage retinal ganglion cell axons.


Antioxidants stabilize those free radical oxygen molecules, rendering them less reactive and presumably less capable of disease promotion.18-21 Antioxidants do this by donating electrons to the unstable free radical, leaving those free radicalsnow with a full electron shellunable to scavenge from other cells. In cases of glaucoma, the ganglion cells are less susceptible to damage when fewer of these scavengers are around, seeking to take any available electrons.18,19


Common dietary sources of antioxidants include vitamins A, C and E; selenium; polyphenols (found in red wine, pomegranate, acai berries, cranberries, dark chocolate, and black and green tea); anthocyanins (found in bilberry); lycopene (tomato products); lutein (dark green leafy vegetables like kale and spinach); and lignan (flax seeds, flaxseed oils and some grains).20


Coenzyme Q10 also has antioxidant properties.21 It is made in the human body and is also available as a supplement. Ginkgo biloba extract (GBE) is an important antioxidant as well, and its unique properties may become very important in the adjunctive therapy of glaucoma.10,22


Whole Food Supplementation

For a healthy patient who currently uses no supplements or energy drinks and relies upon whole (as opposed to engineered) foods for nutrition, it is difficultbut not impossibleto consume the vitamins, minerals, trace elements, antioxidants and fiber recommended for health promotion and disease prevention. At least one study has found a significantly lower risk for glaucoma in women who consume a diet rich in fruits and vegetables.31


Many patients are opting for whole food supplements, either in capsule or liquid form, that claim to have an advantage over the chemical form of individual nutrients due to the proposed synergistic effects of various fruits and vegetables. Caution patients against over-supplementing if this approach is taken. For example, I recently had a patient who was trying to lose weight by eating lots of fruits and vegetables, energy bars (which are often loaded with various vitamins and/or minerals), vitamin-enriched water during workouts, a whole-food liquid supplement and protein shakes. She asked which brand of eye vitamin she should take. It was pretty clear that her intake of vitamins, minerals and macronutrients was already very high, and arguably excessive in some areas. I recommended she continue with her healthy dietary patterns, journal her food intake, and consult with a nutritionist before taking any additional supplements.


Remember, its the total intake that matters, and one standard response to the question, What should I take? isnt sufficient. When it comes to glaucoma patients, whole food supplementation could conceivably provide benefit due to the wide variety of antioxidants available in a variety of fruit- and vegetable-based nutrients.



Problem: Vascular Regulation

One risk factor for normal-tension glaucomatous nerve damage is low blood pressure. This isnt necessarily from a lack of perfusion to the optic nerve, which tends to create non-glaucomatous optic atrophy, characterized by pallor but not excavation.23 Instead, what may cause the trouble is the re-perfusion that occurs as a result of the bodys attempt to regulate the pressure-perfusion ratio at the optic nerve head.23 Reperfusion leads to an increase of oxygen free radicals, and without sufficient levels of antioxidative molecules immediately at hand, cellular damage occurs. Moreover, once cellular damage occurs, a secondary chemical cascade results directly from those cells death and leads to secondary degeneration of ganglion cells that werent originally damaged. It is important to stop this process at the cellular level, and lowering the IOP has no effect on this aspect of the pathogenesis of glaucomatous nerve damage.


This is an example of how nutrition and health are inextricably linked at the cellular level; without sufficient antioxidants, damage is more likely to proceed unchecked.


If low blood pressure is a risk, why not simply raise systemic blood pressure to eliminate that risk? In fact, some patients may benefit from just that type of treatment. Good old table salt is a known blood pressure modulator, but recommending an increase in dietary sodium should not be undertaken lightlyand certainly not without input from the patients other care providers.24


For most patients, focusing on vascular regulation, rather than on overall blood pressure, is a better option.25 One nutrient group believed to improve vascular regulation is dietary fatbut not just any fat. The primary health-promoting fats are the unsaturated fats, particularly omega-3 fatty acids.

 

Ginkgo Biloba Extract

Several years ago, ginkgo biloba became popular because of emerging reports that it may help to reverse or delay the progression of dementia.32-34 Ginkgo biloba extract is likely the best-documented of all the complementary agents being evaluated for a potential role in glaucoma therapy. It may have the most potential value due to its effects on several mechanisms.35-44


We know that ginkgo biloba extract is an antioxidant, but what makes it effective specifically in cases of glaucoma? As it turns out, ginkgo biloba extract has the ability to exert its antioxidative effects at the level of the inner membrane of ganglion cell mitochondriathe most susceptible subcellular component relative to oxidative stress in glaucomatous eyes.35
Further, ginkgo biloba extract inhibits the effects of platelet-activating factor (PAF), which, through a variety of chemical pathways, promotes glaucomatous damage.36,37


Ginkgo biloba extract also improves ocular, peripheral and cerebral blood flow, which may help to combat the vascular dysregulation mechanisms in glaucoma.38 It also has demonstrated neuroprotective properties in several different conditions. Glutamate toxicity, a relatively recent but well-documented proposed factor in the excitatory neurotransmitter-mediated progression of glaucoma, is also inhibited by ginkgo biloba extract.39-44

Side effects of ginkgo biloba extract are few, but the list includes such potentially serious bleeding-related events as hyphema and hematoma.45,46 Reviews classify ginkgo biloba extract as reasonably safe at recommended levels.47 Caution should be exercised for patients with pre-existing bleeding disorders or who are taking anticoagulant preparations.


Solution: Omega-3 Fatty Acids

For years, dietary fat was considered the enemy of a healthy diet. We now recognize that unsaturated fats are essential for health maintenance and promotion, while trans fats and saturated fats are detrimental.


All fats are chemically comprised of carbon, hydrogen and oxygen the same elements found in carbohydratesbut there are more carbon and hydrogen atoms than oxygen atoms in fats vs. carbohydrates. Saturated fats consist only of single chemical bonds between the three elements; no double bonds exist. Double bonds create a more unstable connection and are prone to oxidation, in which the bond comes loose. Because they have no double bonds, saturated fats are stable and structurally firm (e.g., butter or shortening). Saturated fatsand their chemical copycats, known as trans fatsdont offer much in the way of healthy value.


Melatonin

Melatonin may play a dual role in the future of glaucoma management.

Melatonin is naturally formed by the pineal gland, and it has been popularized as an enhancer for regulating sleep cycles. It also has antioxidant properties and may even stimulate other antioxidative enzymes.48 And, melatonin seems to exhibit neuroprotective properties and has an ocular hypotensive effect.49

Unsaturated fats, on the other hand, have one (monounsaturated) or more (polyunsaturated) locations where a double bond exists between two carbon atoms. Where these double bonds exist, the fatty acid is more fluid, unstable and reactive, and it may turn, crimp, curve or bend. The longer the molecule, the more easily it can turn and bend. The presence of these double bonds (and how quickly they break down) explains the unstable nature of fish oil and the fact that flaxseed oil cant be used in high-temperature cooking. Vegetable, olive, nut, fish and flaxseed oils are unsaturated, but of these, fish oilsand to a lesser extent, flaxseed oilare the omega-3 fatty acids that are typically deficient in the Western diet. These are the fats that can play an important role in vascular regulation.


Dont think that other unsaturated oils are unhealthy, though.
We need unsaturated dietary fat for several important processes: vitamin transport, cell membrane structure and the production of key chemicals in our body. But, the balance of the types of fat we eat is critical. Experts agree that a ratio between 1:1 and 4:1 of omega-6 fatty acids (e.g., olive, soybean or sunflower seed oil) to omega-3 fatty acids (e.g., fish oil) is ideal. Our Western diet is typically 20:1 or 30:1!26


Omega-3 fatty acids are thought to be beneficial to several different mechanisms in addition to vascular regulation, though there is still some suggestion to the contrarythe counterargument is that fatty acids do not provide a positive or protective effect.26-28 No specific dosage guidelines are definitely established for use as an adjunctive therapy in cases of glaucoma. However, most patients should completely eliminate trans fats from their diet, significantly reduce intake of saturated fats, and supplement an already-abundant intake of omega-6 fatty acids with an omega-3 fatty acid supplement.


How much to take depends on the patient, his or her associated systemic conditions, and his or her baseline food and supplement intake. For otherwise healthy patients, having oily fish (e.g., salmon) at least twice a week is a minimal goal. For patients with hypertriglyceridemia, pharmaceutical-grade high-dose fish oils can dramatically improve lipid profiles. For everyone else, supplementation should probably fall somewhere in between 1,500mg to 2,500mg of docosahexaenoic acid (DHA) and/ or eicosapentaenoic acid (EPA).


Glaucomatous optic nerve damage is created by more than just high intraocular pressure. As our understanding of the various factors in this disease increases, new treatment options should be considered, and nutrition and supplementation can be an important adjunctive therapy for some glaucoma patients.

Dr. Reed is an associate professor at Nova Southeastern University, where she teaches ocular disease and primary clinical care.

 

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Vol. No: 146:07Issue: 7/15/2009