~ Macular Degeneration: The Role of Nutrition
By Dennis L. Gierhard, PhD
Macular degeneration is the leading cause of blindness in people over the age of 55, affecting more than 10 million Americans. The disease occurs when the central portion of the retina (the macula) deteriorates, resulting in impaired vision or blindness. The good news is that leading researchers have identified specific dietary factors that can prevent, and even partially reverse, this devastating ocular disorder.
Zeaxanthin is one of 700 plant pigments called carotenoids that provide much of the color in nature and our diet. The carotenoids derive their name from the fact that the first pigment isolated, beta-carotene, was from carrots. Beta-carotene is an important source of vitamin A, which is critical to vision. Zeaxanthin and its closely related cousin, lutein, are called xanthophylls and are perhaps the third to seventh most prevalent carotenoids in the human diet (depending on fruit and vegetable selection).1,2 Humans cannot synthesize these carotenoids and thus must obtain them from their diet. Zeaxanthin and lutein have been recently called "conditionally essential nutrients" because of their critical protective functions in the eye.3
Guarding Against Light Damage
Plants synthesize zeaxanthin and lutein to harvest light energy and protect against excessive light. It now appears that humans also utilize these pigments to protect the eye from excessive interaction with the damaging effects of light. This function of zeaxanthin is analogous to a set of "nature's sunglasses" for the tissues of the eye. In plants, lutein is most often used to help green leafy tissues harvest light safely.
While plants use zeaxanthin to safely harvest light, they more importantly use zeaxanthin to protect against harmful light levels. Dark green leafy vegetables contain large amounts of both pigments but have much more lutein compared to zeaxanthin. Zeaxanthin is more predominant in many of the yellow, orange, and red fruits and vegetables such as peppers, corn, and peaches.1-6
Both lutein and zeaxanthin absorb the very high-energy and most damaging portions of the light spectrum (ultraviolet blue). This absorption of the high-energy spectrum is critical to the protection of the lens, retina, and macular portions of the eye.1,5,7
Beyond Eye Protection: Other Health Benefits of Xanthophylls
Protecting Against Free Radicals
- Reduced risks of several cancers (lung, prostrate, breast, skin)5,9,12,13
- Inhibition of pre-malignant lesions and increased apoptosis in malignant tumors5,9,12,13
- Immune modulation and reduced risk of infection5,9,12-14
- Skin photo-protection and reduced sunburn (erythema) at high dietary intake levels15
- High levels are correlated with low levels of systemic inflammation markers like C-reactive protein10,11
- Reduction of numerous aging index biomarkers
- Decreased risk of cardiovascular disease, decreased lipoprotein oxidation, and early atheroscle- rosis lesions (possibly by reduced inflammatory response)12
- Decreased risk of type II diabetes progression
- Increased lung function
- Reduced oxidative (and macro-molecule) damage in numerous tissues9,12
Lutein and zeaxanthin are fat-soluble antioxidants. Their structure effectively stops or "quenches" free-radical reactions and their potentially damaging by-products, which collectively are called "reactive oxygen species." Zeaxanthin and lutein have a unique ability to stop light-accelerated or photo-oxidative reactive oxygen species that are particularly selective and damaging to the eye tissues and skin.1,5,7
Like other carotenoids, zeaxanthin is absorbed like a fat and its absorption is aided by the presence of fats in the accompanying meal. Because the bioavailability of carotenoids can be very poor, it is very important that the dietary supplements you consume have proven bioavailability (some sources may be as low as 5% bioavailable for these pigments).8
Zeaxanthin and lutein are transported from the intestine to the liver, where they are packaged for transport on the surface of blood lipoproteins to various body tissues such as the eye. There is good evidence that the xanthophylls protect lipoproteins—such as low-density lipoprotein (LDL)—and may reduce the earliest steps of atherosclerosis via their antioxidant and anti-inflammatory mechanisms.10-12
The xanthophylls are concentrated in the adrenal, prostate, and breast glands and in the kidneys. The largest total quantities are stored in the liver and adipose (or fat) tissues. The xanthophylls' propensity to store in fat means that individuals who are obese or have a high body mass index (BMI) may have lower deposition of the xanthophylls in eye tissues and greater risk of degenerative eye disease. Both animal and human trial data suggest that lutein is affected more by this competition with fatty tissues, which may explain why in obese individuals zeaxanthin shows much greater ability to deposit in the eye than lutein.16 Other health benefits attributable to both zea-xanthin and lutein are supported by data from laboratory, animal, and epidemiological studies, as shown below.
Discovering Lutein and Zeaxanthin in the Eye
Of the 20 or so carotenoids detected in our blood, only zeaxanthin and lutein are used selectively by the eyes.17-21
These two xanthophylls are found in almost all subsections of the eye,18,19 but occur in concentrations nearly 1,000 times greater in the macula section of the retina than in any other tissue in the body.4 This extremely high concentration creates a yellow spot that is visible to the trained professional and is called the "macula lutea." The xanthophylls that give the macula its striking color also are often referred to as the "macular pigments."
The American biochemist Dr. George Wald was the first to connect the xanthophylls with eye health in 1945 when he tentatively identified the macular pigment as lutein. (Dr. Wald later won a Nobel Prize for his research on the role of vitamin A in vision.23,24)
The modern era was initiated in 1985 when two Miami-based researchers, Bone and Landrum, determined that the macular pigment was actually two compounds, lutein and zeaxanthin.17 This group, along with others, demonstrated that zeaxanthin was concentrated in the center of the retina, while lutein was more prominent at the edges.18,19,20 In 1994, DSHEA legislation was passed and a group headed by Dr. Seddon at Harvard Medical School published epidemiological data that strongly suggested that people who consume fruits and vegetables containing zeaxanthin and lutein have reduced risks of advanced macular degeneration, the leading cause of acquired blindness in the elderly.22 In 1997, a group at Tufts identified the same two pigments in the lens of the human eye in nearly equal proportions; at about the same time, epidemiological studies linked the same two pigments with reduced risk of cataract incidence, progression, and severity.25-31,32
Protecting the Eye's Structure
The eye is a highly complex organ that must safely harvest, control, focus, and react to light to produce vision. Light enters the anterior portion of the eye through the clear cornea and fluid-like aqueous humor, and is then focused by the clear lens before entering the gel-like vitreous. It must pass though a nerve layer of ganglions connected to photoreceptors (both rods and cones) where light signals are converted to electrical signals that are transported to the brain. Behind the photoreceptors are the "nursemaids" called retinal pigmented epithelium cells that feed and remove toxic waste from the constantly active photoreceptors. The retinal pigmented epithelium cells rest on a thin, connective, tissue-like support structure called Bruch's membrane, which also serves to create a blood-brain barrier for transport of nutrients, waste products, and critical oxygen. In the macula region of the retina, the choroidal blood supply should stay on its own side of this membrane.
With time, the aging eye accumulates greater photo-oxidative damage from its interaction with light. These events lead to two prevalent eye diseases: cataracts and macular degeneration.2,7,33-35
Cataract is the leading cause of blindness worldwide and is one of the most costly items in the federal Medicare budget. The second serious vision problem is age-related macular degeneration.
Macular degeneration is the leading cause of acquired blindness and vision impairment among elderly Americans. It is estimated that up to 17 million elderly Americans have at least early signs of the disease called age-related maculopathy. The National Eye Institute estimates that nearly 1.7 million elderly Americans have the more advanced stage of macular degeneration, and a new case is diagnosed every three minutes. The prevalence of the disease increases with age, affecting one in six Americans aged 55 to 64 and one in three Americans over 75. Of the 1.7 million currently afflicted, nearly 85% have the most prevalent form of the disease, known as dry macular degeneration.2,33,34
Patients who are affected suffer a gradual loss of central vision due to the death of photoreceptor cells (rods and cones) and their close associates, retinal pigmented epithelium cells. Photoreceptors are the cells in the retina that actually "see" light and are essential for vision. Retinal pigmented epithelium cells are like the "nursemaids" for photoreceptor cells and are necessary for photoreceptor survival. The death of either of these cell types leads to the death of the other. The macula contains the highest concentration of cone-type photoreceptors that are responsible for providing color and fine detail in the center of the visual field. Thus, patients with macular degeneration gradually lose their central vision and with it, the ability to drive, read, and see the faces of loved ones. As bad as this may be, those suffering the disease can function at a reasonable level for many years.
However, another aspect of macular degeneration is even more devastating. As the photoreceptor and retinal pigmented epithelium cells slowly degenerate, blood vessels tend to grow from their normal location in the choroid into an abnormal location beneath the retina. This abnormal new blood vessel growth is called choroidal neovascularization, or wet macular degeneration. Abnormal blood vessels leak and bleed, resulting in sudden and severe loss of central vision. Depending on the location, laser treatment can sometimes be given to destroy the blood vessels. When retinal cells are lost, they are not replaced and central vision loss can be profound. New drugs are currently under development for wet macular degeneration, but their availability may be years away.
Protecting the Lens and Macula
The high specific concentration of zeaxanthin and lutein in the macula gave scientists their first hint that nature has a purpose for these plant pigments in eye health.23,24
Within the retina, a significant portion of the xanthophylls reside in Henle's fiber, a layer of axons in the inner retinal layer where xanthophylls can filter light prior to light striking photoreceptors (rods and cones) and the very important retinal pigmented epithelium cells. This location would suggest a very strong role for the xanthophylls in filtering damaging light, particularly the most damaging blue part of the spectrum.
The exact center of the macula is where the highest concentrations of dietary zeaxanthin and a related isomer, meso-zeaxanthin, are found. In the peripheral retina, lutein dominates.18-21 Current theory suggests that high macular pigment, particularly dietary zea-xanthin, protects the portion of the macula most critical to vision and most exposed to photo-oxidative damage.35 Very high metabolic rates found in the fovea (the center of the macula) require extra antioxidant protection.7
Macular degeneration pathology often starts at the edges of the macula, where macular pigment concentrations start to decrease. Analyses of cadaver eyes have shown this direct link by contrasting macular pigment concentrations at distances from the macula's center in eyes with macular degeneration with those in normal matched eyes.37 These experiments found a significant drop in pigment concentrations in eyes with macular degeneration compared to normal matched eyes, a difference corresponding to the relative concentrations of zeaxanthin in the eyes.
To summarize, the eye concentrates just three xanthophylls—dietary zeaxanthin, non-dietary meso-zeaxanthin, and lutein—in the macula and other ocular tissues. Of the 16-20 carotenoids in the blood serum, only two are selected for deposition and hyper-concentration in the eye. This highly selective process is the most specific distribution in the entire field of carotenoid biochemistry.18-21,38
How Many Xanthophylls Do We Need?
Determining a daily intake of lutein and zeaxanthin is problematic because food composition tables often do not analyze or report lutein and zeaxanthin separately, and comparisons of published data are often inconsistent. Despite the recommendation by many health agencies to eat at least five servings of fruits and vegetables per day, consumption varies widely.
Several major epidemiological studies have linked dietary carotenoid consumption with reduced risks of macular degeneration and cataract. The dietary gap between low-and high-risk individuals was equivalent to about 6 mg/day of lutein and zeaxanthin.22,25,29-32,39 The data suggest that a difference of 4-5 mg/day in consumption of xanthophylls could influence the risks of contracting eye disease and may be a basis for a maintenance or preventive dosage.
For low-risk individuals, perhaps 3-6 mg/day of zeaxanthin may be extrapolated as a preventive dosage for degenerative eye diseases, though a dose as low as 0.5 mg/day over an entire lifetime may be sufficient. A number of other clinical trials are using 20-30 mg/day of zeaxanthin.
Differences Between Zeaxanthin and Lutein
Zeaxanthin and its chemical cousin, lutein, differ in several important ways. Lutein's three-dimensional structure is asymmetrical and bent, a perfect fit for its role in harvesting and transferring light energy in the photoreaction center of the chloroplast of a plant cell. As noted previously, this means that the human diet contains 5-20 times more lutein than zeaxanthin. In human blood serum, lutein is 3-10 times more predominant than zeaxanthin.1,2,5,6,38 Zeaxanthin is a straight, symmetrical molecule that can perfectly transverse a biological membrane and influence and protect membrane-bound cellular functions more effectively than lutein, regardless of its orientation.42 This may account for the ocular preference of zeaxanthin over lutein. This selective preference has also been seen recently in human cadaver brain.43 This membrane spanning and greater antioxidant properties may also explain why the retina makes the unusual isomer meso-zeaxanthin (which is structurally closer) from the more abundant lutein. Most likely this is because the eye attempts to supplement the lower intake of preferred dietary zeaxanthin by converting lutein to meso-zeaxanthin, which is better than lutein but not as good as dietary zeaxanthin. This selective deposition and concentration of dietary antioxidants in the macula's center has also been demonstrated with vitamin E and selenium.7
A misconception among consumers is that they get enough dietary zeaxanthin from their lutein products. A second misconception, even among eye specialists, is that lutein is converted to zeaxanthin in the eye. In fact, lutein comes from marigold flowers and contains only a tiny amount of zeaxanthin compared to the 2:1 ratio seen in the section of the macula that seems to be protected. A second fact is that lutein is converted into a compromise structure, meso-zeaxanthin, in the eye.
Continued . . .
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