The Role of Nutrition in Macular DegenerationMay 2004
By Dennis L. Gierhard, PhD
|LE Magazine May 2004|
|The Role of Nutrition in Macular Degeneration |
By Dennis L. Gierhard, PhD
How Many Xanthophylls Do We Need?
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
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.
Zeaxanthin’s Protective Effects Against Eye Disease
With trials in Japanese quail and primates, the evidence from animal trials has recently become much stronger. In the early 1980s, researchers depleted primate diets of carotenoids and demonstrated retinal pathologies consistent with symptoms of macular degeneration. The studies were extended in the mid-1990s when Dr. C.K. Dorey and colleagues at Harvard Medical School and the Schepens Eye Institute established the Japanese quail as a model for studying degenerative eye disease and xanthophylls.16,44-46 Using aging and light-insult models, Dr. Dorey was the first to show directly that the photo-protective effects of zeaxanthin were related to the retinal levels of zeaxanthin that she controlled by feeding. This retinal protection extended to both rods and cones, and prevented the massive losses seen in late-stage dry macular degeneration. The team also went on to show that zeaxanthin:
Further results with primates have shown that zeaxanthin is more photo-protective (blue laser light insult) than lutein or meso-zeaxanthin.
Increasing the Macular Pigment’s Thickness
Doctors can now measure “macular pigment optical density” indirectly and noninvasively by at least six different techniques, though some of these techniques have been subject to criticism. The human trials that measured macular pigment optical density in response to lutein and zeaxanthin intake are summarized in the next column:
The association between macular pigment optical density and risk factors for macular degeneration and cataracts is compelling. Reduced macular pigment optical density in the target population has been related to smoking, obesity/high BMI, age, lens density and opacity, gender, light iris, and poor zeaxanthin intake.1,2,4,7,9,47-51
Zeaxanthin and Other Eye Diseases
The results to date are promising, but larger and longer clinical trials will be necessary to clarify the benefits for patients and eye-care professionals before zeaxanthin supplements will receive an unqualified recommendation. The FDA will need to see statistically relevant data, and the medical community will need to see these functional improvements along with reduced progression of symptoms like area of atrophy, drusen and lipofuscin progression, and reduced risk of neo-vascularization or its progression.
Major trials on intervention in all stages of macular degeneration are in various stages of planning and execution. The largest of these may be the AREDSII trial, with more than 5,000 patients in late-stage macular degeneration. The National Eye Institute and National Institutes of Health are scheduled to begin this trial using lutein and zeaxanthin later this year. Zeaxanthin and lutein were not commercially available for the first trial.
Finally, since zeaxanthin supplements were introduced, many patients who were hypersensitive to light (i.e., photophobic) are reporting dramatic decreases in this unpleasant phenomenon within months of initiating 20 mg/day doses of zeaxanthin. These observations are now being assessed objectively at two colleges of optometry.
Dual Mechanisms of Action
Both lutein and zeaxanthin are capable of quenching free-radical reactions that create reactive oxygen species. These reactive oxygen species then react with cell membranes and macromolecules to create pathogenesis leading to many human degenerative conditions. In the eye tissues, these oxidative processes can be further enhanced by the presence of light (which accelerates photo-oxidation), extremely high metabolic rates (in the retina), and the highly polyunsaturated lipids found in the retina and other neural tissues. Both singlet oxygen and peroxyl radicals are likely generated in eye tissues and quenched by the xanthophylls.
Light-driven photo-oxidation likely generates excited triplet-state species that also cause severe oxidative damage. As noted earlier, zeaxanthin is a better antioxidant and is more directly embedded in a manner to protect biological cell membranes than is lutein. Xanthophylls are particularly effective at lower oxygen tensions (concentrations) like the interior of a cell membrane or the center of lens tissue. The tocopherols are more effective at higher oxygen tensions. Thus it is highly likely the two lipophilic antioxidants are synergistic and complement ascorbates and the metal-containing enzyme-based antioxidant enzymes that are active in ocular tissues for protection against oxidative damage.
The very earliest steps in eye cells showing oxidative stress are the generation of lipoperoxides.56 In 2000, these very early oxidation markers were shown to directly induce the pathways of angiogenesis or neovasularization.57,58 This means that the earliest step of oxidation may be capable of increasing the risk of progressing to wet macular degeneration.
The second biologically plausible mechanism is UV and blue-light filtering or absorption. The xanthophylls are excellent light filters and absorb that part of the UV and blue-light spectrum thought to be most damaging to the eye. In the lens, the xanthophylls absorb the UV light thought to be the principal initiator of oxidative stress that results in cross-linking of the component crystalline that in turn reduces the clearness of the lens. The xanthophylls would also reduce the amount of blue light reaching the retina. The absorption of blue light in the lens and from reflection in the retina would reduce light scatter and chromatic aberrations. This would suggest a more direct role in reducing visual effects like glare and starburst effects seen in early stages of these diseases.7
This blue-light filtering may directly reduce the photo-oxidation in the susceptible axons and likely reduces photo-oxidative damage directly in the photoreceptors and posterior retinal pigmented epithelium cells that support and maintain the photoreceptors.
In the critically important retinal pigmented epithelium cells insulted with blue light, zeaxanthin has been shown to prevent oxidative damage, apoptosis, DNA damage, and cell death. In these cell culture experiments, zeaxanthin shows synergy with the other cellular protectants vitamins C and E, glutathione, and melanin.60
Theories of Aging Explain Degenerative Eye Disease
These two disparate and opposing functions are within an inch of each other inside the eye. Readers should also know that caloric restriction, the almost universal environmental anti-aging influence, has also been shown to slow degeneration or aging of the eye.
In addition to its role in the photo-oxidative mechanism of degenerative eye disease, it is likely that zeaxanthin also participates through other protective biological mechanisms. Because age-related eye degeneration is probably multi-etiological, it is likely zeaxanthin helps provide protection at multiple levels.1,4,7,35