Macular Degeneration (Age-related)

NUTRITIONAL THERAPY

Recommended Foods

Foods Containing Lutein and Zeaxanthin The phytochemicals that protect against wet macular degeneration are lutein and zeaxanthin.38-43 Lutein is a pigment found in dark green leafy vegetables, including spinach, kale, broccoli, and collard greens. Zeaxanthin is found in fruits and vegetables with yellow hues, such as corn, peaches, persimmons, and mangoes. Meso-zeaxanthin is not found in foods but is produced in the retina from ingested lutein.

Because lutein and zeaxanthin have the tissue-specific characteristic of all carotenoids, their natural tendency is to concentrate in the macula and retina. Consumption of foods rich in these substances is especially important, as they have a direct effect on macular pigment density: The denser the pigment, the less likely a retinal tear or degeneration will occur. Some improvement has been seen in subjects after only one month of supplementation.23,43

Soy Soy contains the phytochemical genistein, which has antiangiogenesis properties.44 This property of inhibiting blood vessel growth is important in limiting abnormal ingrowth of choroidal blood vessels. Those with neovascular macular degeneration may take two Ultra Soy Extract capsules 2 times per day to obtain enough genistein to possibly inhibit blood vessel growth in the eye.

Oily Fish Oily fish like salmon, tuna, and mackerel are important sources of omega-3 fatty acids, essential for protection against macular degeneration and other diseases.25,45 More frequent consumption of fish protects against late age-related macular degeneration. The greatest benefit was seen in those who ate one serving a week; more fish did not offer more protection.45

Dietary Supplements

Bilberry Extract Positive results have been noted in studies using bilberry for macular degeneration, and other eye disorders, including, diabetic retinopathy, retinitis pigmentosa, glaucoma, and cataracts. Bilberry contains anthocyanidins, a blue plant pigment, which protect and regenerate retinal purple (rhodopsin).46 There may be additional benefits by adding vitamin E.47 The anthocyanidins in bilberry decrease vascular permeability by interacting with blood vessel collagen so as to slow down enzymatic attack on the blood vessel wall. This may prevent leakage from capillaries; prevalent in neovascular AMD.

Ginkgo Biloba Ginkgo biloba improves microcapillary circulation in the eye and slows down deterioration of the macula.48 It increases blood flow by inhibiting platelet aggregation and regulating blood vessel elasticity; improving blood flow through major blood vessels and capillaries. Ginkgo is a powerful antioxidant.49

Note: For more information see the Safety Appendix

Grape Seed Extract Grape seed extract is a powerful antioxidant, classified as one of the bioflavonoids. Bioflavonoids derived from plants are readily assimilated into our body when consumed. Bioflavonoids have the ability to strengthen blood vessel walls within a short time after ingesting them.50

Recommended Antioxidants

Glutathione and Vitamin C Glutathione and vitamin C are antioxidants found in high concentrations in the healthy eye and in diminished quantities in AMD patients. Vitamin C aids in glutathione synthesis in the eye. When it is combined with cysteine, an amino acid antioxidant, cysteine remains stable in aqueous solutions and is a precursor to glutathione synthesis. Vitamin C is important because it absorbs ultraviolet radiation and prevents cataracts.18

L-Carnosine L-carnosine is a naturally occurring antioxidant and anti-glycation agent. Topically applied N-acetyl-carnosine prevented light-induced DNA strand breaks and repaired damaged DNA strands.51

Riboflavin, Taurine, and Lipoic Acid Other antioxidants for protection against AMD are riboflavin monophosphate, taurine, and R-dihydro-lipoic acid. Riboflavin monophosphate is a B complex vitamin that reduces oxidized glutathione and helps to prevent sensitivity to light, loss of visual acuity, and burning and itching in the eyes.52 Taurine is an amino acid found in high concentrations in the retina. A deficiency of this amino acid alters the structure and function of the retina.53 R-dihydro-lipoic acid is considered a “universal antioxidant” because of the fact that it is fat and water soluble.54

Selenium Selenium, an essential trace mineral, is a component of the antioxidant enzyme, glutathione peroxidase, important in slowing the progression of AMD and other eye disorders including, cataracts and glaucoma.55,56

Note: For more information see the Safety Appendix

Coenzyme Q10 Coenzyme Q10 (CoQ10) is an important antioxidant that may be beneficial in protecting against free radical damage within the eye.57 In one study a mix of antioxidants including CoQ10, acetyl-L-carnitine, polyunsaturated fatty acids and vitamin E improved the function of mitochondria in retinal pigment epithelium.58 Mitochondrial dysfunction in the eye and throughout the body produces damaging reactive oxygen species, believed to be the cause of many diseases and aging.59

Age-Related Eye Disease Study: Supplement Recommendations

The largest and most important study on the relationship of nutritional supplements and AMD is the Age-Related Eye Disease Study (AREDS). AREDS was the first large study to show a benefit of anti-oxidant and zinc supplementation on the progression of AMD and associated vision loss. Thousands of patients were followed for over six years. AREDS revealed significant improvements for patients with AMD and recommended antioxidants plus zinc (with copper) for most patients with AMD, except for advanced cases in both eyes. The AREDS recipe consists of the following daily: Vitamin A (Beta Carotene), Vitamin C, Vitamin E, Zinc and Copper.60

Note: For more information see the Safety Appendix

FUNCTIONAL AND PRACTICAL MEDICINE

The Importance of the Macular Pigments: Lutein, Zeaxanthin, and Meso-zeaxanthin
The relation between the density of macular pigment and the onset of AMD is well-established. Ocular pigments are essential in the healthy functioning of the eye, and specifically in protecting and maintaining the macula. These pigments are central to the photoreceptor mechanism that picks up the light focused on the macula. They are found in the cone and rod cells within the macula, retina pigment epithelium (which first absorbs the light entering the retina), and surrounding tissues, including blood vessels and capillaries of the choroid which nourish the retina.42

Lutein and zeaxanthin ensure proper functioning of the macula by filtering out harmful blue and ultraviolet light and by acting as antioxidants.38,39 During the aging process, there is a decrease in levels of lutein and zeaxanthin. Low levels of macular pigments are linked to AMD. Inadequate concentrations of lutein and zeaxanthin are associated with development of abnormal pigment deposits under the macula (large drusen); the consequent thinning of the macula; and with choroidal neovascularization, which can lead to very serious and rapid visual impairment.43

It is important to raise macular concentrations of lutein and zeaxanthin with foods rich in these carotenoids or dietary supplements containing them. Intake of lutein and zeaxanthin is an important preventative measure, but may also reverse the degeneration process when it is ongoing.24 Fruits with a yellow or orange color, like mangoes, kiwis or oranges, and vegetables of the dark green leafy variety and orange and yellow types are food sources of lutein and zeaxanthin.40 Egg yolk is a good dietary source of these carotenoids.

If all people had to do was consume adequate zeaxanthin and lutein, then macular degeneration would theoretically disappear as an age-related disorder. Regrettably, macular degeneration still occurs in aging individuals, even in some of those who regularly eat fruits, vegetables, and eggs. In what may be a breakthrough in the prevention of the blinding epidemic of macular degeneration, scientists have discovered a compound called meso-zeaxanthin that is naturally produced in the retina and is needed to maintain youthful macular density.62 They now know that the macular pigment is comprised of the following three carotenoids: 50% lutein, 25% zeaxanthin, and 25% meso-zeaxanthin.

Unlike lutein and zeaxanthin, meso-zeaxanthin is not found in the diet, but is converted in the retina from ingested lutein.62 If taken as a supplement, meso-zeaxanthin is absorbed into the blood stream and effectively increases macular pigment levels.63 Patients with macular degeneration have been shown to have 30% less meso-zeaxanthin in their macula compared to healthy eyes.64 One reason for this deficiency of meso-zeaxanthin is lack of ingested lutein. Another explanation for the missing meso-zeaxanthin observed in macular degeneration may be the inability to adequately convert lutein to meso-zeaxanthin in the retina.

An autopsy study on donated eyes was done to measure levels of lutein, zeaxanthin, and meso-zeaxanthin in the retina of those with and without macular degeneration. As expected, levels of all three carotenoids (lutein, zeaxanthin, and meso-zeaxanthin) were reduced in those with macular degeneration compared to control subjects. The most significant finding, however, was the sharp decrease in meso-zeaxanthin in relation to zeaxanthin in the macula of macular degeneration subjects.65 This postmortem study helped confirm other studies indicating the importance of all three carotenoids (lutein, zeaxanthin, and meso-zeaxanthin) in maintaining the structural integrity of the macula.66,67 These carotenoids protect the macula and the photoreceptor cells beneath via their antioxidant properties and light-filtering capabilities.68

Scientists believe that people who have a high intake of lutein and zeaxanthin (from either diet or dietary supplements) and take supplemental meso-zeaxanthin will have a very low incidence of macular degeneration.

Free Radicals and Antioxidants
Antioxidants are vital components in maintaining the health of the eye and the body. Antioxidants work by scavenging free radicals from the body. Free radicals are simply oxygen atoms that have lost an electron through the body's normal metabolic processes. The free radicals quickly attach nearby body tissues to stabilize themselves. This consequently takes an electron from that tissue, producing yet another free radical which perpetuates the chain reaction. This cascade of oxidation is a process known as oxidative stress.

Antioxidants are chemically structured so that they are able to donate electrons freely without altering their valence (since their electrons are not paired). This means that antioxidants can stabilize or trap free radicals without themselves becoming dangerous free radicals themselves. Antioxidants will donate electrons until they have no more. Because many of these antioxidants can be regenerated (reduced) through the acceptance of free electrons available during normal metabolism, one antioxidant molecule is able to neutralize many free radicals.

While free radicals are produced during normal metabolism, this production is accelerated by smoking and exposure to second-hand smoke16 and by diets high in saturated fats, cholesterol, and low in the “good fats” found in fish such as salmon and tuna, whole grains, and legumes.25 Smoking and a high-fat diet are associated with AMD.

AMD is associated with decreased levels of natural antioxidants in the healthy eye. These include glutathione and vitamin C, and the carotenoids, lutein and zeaxanthin.18,42 Dietary supplementation with these antioxidants is important in slowing the progression of AMD. Other recommended antioxidants beneficial to the macula and retina are vitamin A, vitamin E, L-carnosine, taurine, lipoic acid, selenium, zinc (with copper) and grape-seed extract, and coenzyme Q10.

Note: For more information see the Safety Appendix

Protection against Ocular Atherosclerosis
Many experts believe the underlying cause of AMD occurs in the choroids.7 The choroid lies underneath the retina and provides it with oxygen and nutrients. The retina contains very few blood vessels. The onset of AMD is associated with choroidal blood vessel damage, frequently due to atherosclerotic plaque. This raises blood pressure within these vessels and results in an abnormal production of protein and fats that are deposited underneath the macula as pigment deposits called drusen. There is an associated problem of fracturing and loss of natural elasticity in the barrier between the retina and choroid, which facilitates abnormal growth of choroidal blood vessels into the retina, called choroidal neovascularization (CNV).

To protect against the deterioration of the blood circulatory network within the eye, a number of dietary supplements are beneficial. These include bilberry extract, Ginkgo biloba, grape-seed extract, and genistein. Bilberry helps protect blood vessel walls and leakage of capillaries, very common in neovascular AMD.46 Ginkgo biloba improves blood flow through major blood vessels and capillaries, improving microcapillary circulation in the choroid by inhibiting plaque accumulation and maintaining elasticity of blood vessels.49 Grape-seed extract strengthens blood vessels, even shortly after ingestion.50 The phytochemical, genistein, found in large concentrations in soy, inhibits blood vessel growth necessary for the progression of neovascular AMD.44

Hydergine and thalidomide control blood vessel deterioration. Hydergine is beneficial in treating dry macular degeneration due to its ability to keep blood vessels open.32 Thalidomide inhibits blood vessel growth, counteracting the progression of neovascularization in neovascular (wet) AMD. It is legal for doctors to prescribe thalidomide to treat wet macular degeneration even though it is only officially approved to treat leprosy.33 It should be noted that thalidomide causes severe birth defects and must not be used by pregnant women or women who may become pregnant.

Lucentis® and Macugen® inhibit the action of vascular endothelial growth factor (VEGF), thus prevent the formation of abnormal blood vessels, reduce swelling in the macula, and help preserve vision. Another promising VEGF-inhibitor, Avastin®, is undergoing clinical trials for use in wet macular degeneration.

Supplement and Drug Recommendations
To ensure that adequate concentrations of the essential macular pigments lutein, zeaxanthin, and meso-zeaxanthin are maintained, the following are suggested:

• Lutein Plus with high potencies of lutein, zeaxanthin, and other carotenoids may help slow the progression of advanced AMD into blindness.
• Super Zeaxanthin with Lutein and Meso-zeaxanthin

To protect and preserve the macular pigments from potentially damaging blue and ultraviolet radiation, the following protective eyewear is recommended:

• Life Extension’s Solarshield sunglasses

To protect against the damaging effects of free radicals on the retina, and the macula in particular, the following antioxidants and antioxidant mixes are suggested:

• Vitamin A (Beta Carotene)
• Vitamin C
• Vitamin E
• Zinc
• Copper
• Lipoic acid
• Selenium
• Riboflavin
• Taurine
• Coenzyme Q10
• Life Extension Mix
• Life Extension Booster
• Brite Eyes II eye drops for antioxidant (vitamins A and E), anti-glycating protection (N-acetyl- carnosine)
• Super EPA/DHA with Sesame Lignans

To help protect against the onset and progression of blood vessel damage in the eye that leads to AMD, the following are recommended:

• Ginkgo biloba extract
• Grape seed-skin extract
• Bilberry extract
• Super Absorbable Soy Isoflavones for genistein
• Hydergine (prescription only)
• Lucentis® (prescription only)
• Macugen® (prescription only)
• Avastin® (prescription only)

SUMMARY

Scientific Summary
This protocol has provided background on age-related macular degeneration in terms of its nature, etiology, underlying physiology, pathophysiology, pharmacology, and nutrition. Basic information has been provided on AMD, including newer standard and non-standard approaches to treating this disease. The protocol has focused on the importance of nutritional solutions that prevent or treat AMD. Enough background information has been presented on AMD and its nutritional supplements to enable the reader to make informed decisions on the usefulness of nutrition and its effects on AMD.

There has been limited success within conventional medical treatment protocols to restore lost eyesight from either form of AMD. Leading researchers are documenting the benefits of more holistic approaches to AMD. Patients are encouraged to increase physical fitness, improve nutrition (including a reduction in saturated fats), abstain from smoking, and to protect their eyes from excessive light. Dietary supplementation with trace elements, antioxidants, and vitamins is recommended for improving overall metabolic and vascular functioning. Early screening and patient education offer the most hope for reducing the debilitating effects of the disease.

Functional Summary
The best approach to ensuring protection against the onset of age-related macular degeneration and the possible treatment of the condition involves an understanding of some of the main circumstances under which the condition arises. These are presented below followed by the recommended nutritional therapies for each problem.

1. A reduction in the essential macular pigments lutein, zeaxanthin, and meso-zeaxanthin, critical for the protection and proper functioning of the mechanisms required for the detection and imprinting of the light signals that come into the macula from the outside world.

As lutein, zeaxanthin, and meso-zeaxanthin are the essential pigments within the macula, it is critical to replenish them as they become depleted through the aging process. Consumption of foods rich in these substances is especially important since they have a direct effect on macular pigment density. When the pigment in the macula is denser, retinal tearing or degeneration is less likely. Lutein and zeaxanthin are found in yellow or orange vegetables, in dark leafy greens, and in fruits with yellow or orange hues. Egg yolk is a good source of lutein. Meso-zeaxanthin is not available through dietary sources, but can be manufactured in the retina from ingested lutein. Dietary supplements of lutein, zeaxanthin, and meso-zeaxanthin are recommended.

2. A reduction in antioxidant levels within the retina and surrounding structures that make possible the presence and proliferation of free radicals that damage these structures and keep them from optimal functioning.

An increase in damaging free radical activity occurs through smoking, exposure to second-hand smoke, in diets high in saturated fats, cholesterol, and low in the “good fats” found in fish, whole grains and legumes. Smoking and high-fat diets are associated with AMD.

Decreased levels of natural antioxidants in the healthy eye are associated with AMD. Some of these essential natural antioxidants are glutathione, vitamin C, and the carotenoids, lutein and zeaxanthin. Dietary supplementation with these antioxidants protect against the progression of AMD. Other recommended antioxidants to protect the macula and retina include vitamin A, vitamin E, L-carnosine, taurine, lipoic acid, selenium, zinc (with copper), grape-seed extract, and coenzyme Q10.

3. The onset of ocular atherosclerosis involves blockages in the choroidal blood vessels that adversely affect the functioning of the retina and, particularly, the macula.

Damaged blood vessels in the eye are associated with the onset of AMD. Blockages of these blood vessels, known as ocular atherosclerosis, raises blood pressure, creates deposits under the macula, and abnormal growth of blood vessels into the retina (choroidal neovascularization). The result is severe and debilitating neovascular AMD.

Dietary supplements are beneficial in treating ocular atherosclerosis. These include bilberry extract, ginkgo biloba, grape-seed extract, and genistein. Bilberry protects blood vessel walls and reduces leakage of capillaries, common in neovascular AMD. Ginkgo biloba improves blood flow and inhibits plaque accumulation in the blood vessels of the eye and maintains the elasticity of blood vessels. Grape-seed extract strengthens blood vessel walls, even shortly after ingestion. The phytochemical genistein, found in soy, inhibits blood vessel growth, slowing the progression of neovascular AMD.

Hydergine and thalidomide help with ocular atherosclerosis. Hydergine dilates blood vessels, stimulates mental functioning, and is effective in treating atrophic AMD. Thalidomide inhibits blood vessel growth and counteracts the progression of neovascularization in AMD patients.

Lucentis® and Macugen® are approved for the treatment of wet macular degeneration. By inhibiting the action of vascular endothelial growth factor (VEGF), they prevent the formation of abnormal blood vessels, reduce swelling in the macula, and help preserve vision. Another promising VEGF-inhibitor, Avastin®, is undergoing clinical trials.

General Precautions
Dietary supplements do not always positively affect health due to the systemic imbalances. Increasing evidence indicates that supplementation with one carotenoid may reduce serum levels of other carotenoids.61 Because there are more than 50 naturally occurring carotenoids, it is important that the correct supplement or combination of supplements be chosen. Mega-doses, beyond the prescribed dosage, are generally discouraged. Consult with healthcare professionals knowledgeable in the uses, dosages, and interactive effects of supplements to ensure the best nutritional therapy is utilized.

About the Author
Robert Sachs, Ph.D. is a medical writer specializing in the therapeutic area of ophthalmology. He has prepared FDA submissions for new ophthalmologic devices and drugs and has worked in cutting-edge technology companies developing a range of products in the medical and environmental fields.

Direct your questions to the Life Extension Health Advisory staff at (800) 544-4440.