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May 2002

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Influence of lutein supplementation on macular pigment, assessed with two objective techniques.

PURPOSE: Macular pigment (MP) may protect against age-related macular degeneration. This study was conducted to determine the extent of changes in the macular pigment density as a consequence of oral supplementation with lutein. A second purpose was to compare two objective measurement techniques. METHODS: In the first technique, reflectance maps were made with a scanning laser ophthalmoscope. Digital subtraction of log reflectance maps and comparison between the foveal area and a 14 degrees temporal site provided MP density estimates. In the second technique, spectral fundus reflectance of the fovea was measured with a fundus reflectometer and analyzed with a detailed optical model, to arrive at MP density values. Eight subjects participated in this study. They took 10 mg lutein per day for 12 weeks. Plasma lutein concentration was measured at 4-week intervals. RESULTS: After 4 weeks, mean blood level of lutein had increased from 0.18 to 0.90 microM. It stayed at this level throughout the intake period and declined to 0.28 microM 4 weeks after termination. Measurement of the density of MP showed a within-subject variation of 10% with MP maps and 17% with spectral reflectance analysis. MP density showed a mean linear 4-week increase of 5.3% (P: < 0.001) and 4.1% (P: = 0. 022), respectively. CONCLUSIONS: Supplementation with lutein significantly increased the density of the MP. Analyzing reflectance maps with a scanning laser ophthalmoscope provided very reliable estimates of MP.

Invest Ophthalmol Vis Sci 2000 Oct;41(11):3322-6

Lutein and zeaxanthin concentrations in rod outer segment membranes from perifoveal and peripheral human retina.

PURPOSE: In addition to acting as an optical filter, macular (carotenoid) pigment has been hypothesized to function as an antioxidant in the human retina by inhibiting the peroxidation of long-chain polyunsaturated fatty acids. However, at its location of highest density in the inner (prereceptoral) layers of the foveal retina, a specific requirement for antioxidant protection would not be predicted. The purpose of this study was to determine whether lutein and zeaxanthin, the major carotenoids comprising the macular pigment, are present in rod outer segment (ROS) membranes where the concentration of long-chain polyunsaturated fatty acids, and susceptibility to oxidation, is highest. METHODS: Retinas from human donor eyes were dissected to obtain two regions: an annular ring of 1.5- to 4-mm eccentricity representing the area centralis excluding the fovea (perifoveal retina) and the remaining retina outside this region (peripheral retina). ROS and residual (ROS-depleted) retinal membranes were isolated from these regions by differential centrifugation and their purity checked by polyacrylamide gel electrophoresis and fatty acid analysis. Lutein and zeaxanthin were analyzed by high-performance liquid chromatography and their concentrations expressed relative to membrane protein. Preparation of membranes and analysis of carotenoids were performed in parallel on bovine retinas for comparison to a nonprimate species. Carotenoid concentrations were also determined for retinal pigment epithelium harvested from human eyes. RESULTS: ROS membranes prepared from perifoveal and peripheral regions of human retina were found to be of high purity as indicated by the presence of a dense opsin band on protein gels. Fatty acid analysis of human ROS membranes showed a characteristic enrichment of docosahexaenoic acid relative to residual membranes. Membranes prepared from bovine retinas had protein profiles and fatty acid composition similar to those from human retinas. Carotenoid analysis showed that lutein and zeaxanthin were present in ROS and residual human retinal membranes. The combined concentration of lutein plus zeaxanthin was 70% higher in human ROS than in residual membranes. Lutein plus zeaxanthin in human ROS membranes was 2.7 times more concentrated in the perifoveal than the peripheral retinal region. Lutein and zeaxanthin were consistently detected in human retinal pigment epithelium at relatively low concentrations. CONCLUSIONS: The presence of lutein and zeaxanthin in human ROS membranes raises the possibility that they function as antioxidants in this cell compartment. The finding of a higher concentration of these carotenoids in ROS of the perifoveal retina lends support to their proposed protective role in age-related macular degeneration.

Invest Ophthalmol Vis Sci 2000 Apr;41(5):1200-9

The role of oxidative stress in the pathogenesis of age-related macular degeneration.

Age-related macular degeneration (AMD) is the leading cause of blind registration in the developed world, and yet its pathogenesis remains poorly understood. Oxidative stress, which refers to cellular damage caused by reactive oxygen intermediates (ROI), has been implicated in many disease processes, especially age-related disorders. ROIs include free radicals, hydrogen peroxide, and singlet oxygen, and they are often the byproducts of oxygen metabolism. The retina is particularly susceptible to oxidative stress because of its high consumption of oxygen, its high proportion of polyunsaturated fatty acids, and its exposure to visible light. In vitro studies have consistently shown that photochemical retinal injury is attributable to oxidative stress and that the antioxidant vitamins A, C, and E protect against this type of injury. Furthermore, there is strong evidence suggesting that lipofuscin is derived, at least in part, from oxidatively damaged photoreceptor outer segments and that it is itself a photoreactive substance. However, the relationships between dietary and serum levels of the antioxidant vitamins and age-related macular disease are less clear, although a protective effect of high plasma concentrations of alpha-tocopherol has been convincingly demonstrated. Macular pigment is also believed to limit retinal oxidative damage by absorbing incoming blue light and/or quenching ROIs. Many putative risk-factors for AMD have been linked to a lack of macular pigment, including female gender, lens density, tobacco use, light iris color and reduced visual sensitivity. Moreover, the Eye Disease Case-Control Study found that high plasma levels of lutein and zeaxanthin were associated with reduced risk of neovascular AMD. The concept that AMD can be attributed to cumulative oxidative stress is enticing, but remains unproven. With a view to reducing oxidative damage, the effect of nutritional antioxidant supplements on the onset and natural course of age-related macular disease is currently being evaluated.

Surv Ophthalmol 2000 Sep-Oct;45(2):115-34

Protein oxidation and loss of protease activity may lead to cataract formation in the aged lens.

Over 95% of the dry mass of the eye lens consists of specialized proteins called crystallins. Aged lenses are subject to cataract formation, in which damage, cross-linking, and precipitation of crystallins contribute to a loss of lens clarity. Cataract is one of the major causes of blindness, and it is estimated that over 50,000,000 people suffer from this disability. Damage to lens crystallins appears to be largely attributable to the effects of UV radiation and/or various active oxygen species (oxygen radicals, 1O2, H2O2, etc.). Photooxidative damage to lens crystallins is normally retarded by a series of antioxidant enzymes and compounds. Crystallins which experience mild oxidative damage are rapidly degraded by a system of lenticular proteases. However, extensive oxidation and cross-linking severely decrease proteolytic susceptibility of lens crystallins. Thus, in the young lens the combination of antioxidants and proteases serves to prevent crystallin damage and precipitation in cataract formation. The aged lens, however, exhibits diminished antioxidant capacity and decreased proteolytic capabilities. The loss of proteolytic activity may actually be partially attributable to oxidative damage which proteases (like any other protein) can sustain. We propose that the rate of crystallin damage increases as antioxidant capacity declines with age. The lower protease activity of aged lens cells may be insufficient to cope with such rates of crystallin damage, and denatured crystallins may begin to accumulate. As the concentration of oxidatively denatured crystallins rises, cross-linking reactions may produce insoluble aggregates which are refractive to protease digestion. Such a scheme could explain many events which are known to contribute to cataract formation, as well as several which have appeared to be unrelated.

Free Radic Biol Med 1987;3(6):371-7

Macular pigment optical density in a midwestern sample.

OBJECTIVE: To assess the distribution of the macular pigments (MPs) lutein (L) and zeaxanthin (Z) in a healthy sample more representative of the general population than past studies and to determine which dietary factors and personal characteristics might explain the large interindividual differences in the density of these MPs. DESIGN: Prevalence study in a self-selected population. PARTICIPANTS: Two hundred eighty healthy adult volunteers, consisting of 138 men and 142 women, between the ages of 18 and 50 years, recruited from the general population. METHODS: MP optical density was measured psychophysically at 460 nm by use of a 1 degrees test field. Serum was analyzed for carotenoid and vitamin E content with reversed-phase high-performance liquid chromatography. Usual intakes of nutrients over the past year were determined by means of a food frequency questionnaire. MAIN OUTCOME MEASURES: MP optical density. RESULTS: Mean MP optical density measured 0.211 +/- 0.13, which is approximately 40% lower than the average reported in smaller, less representative studies. MP density was 44% lower in the bottom versus the top quintile of serum L and Z concentrations. Similarly, MP density was 33% lower in the bottom compared with the top quintile of L and Z intake. MP density was 19% lower in blue-grey-eyed subjects than in subjects with brown-black irises. When all variables were considered together in a general linear model of determinants of MP, statistically significant (P < 0.05) relationships were found between MP density and serum L and Z, dietary L and Z intake, fiber intake, and iris color. CONCLUSIONS: These data suggest that MP values in this healthy adult population are lower than in smaller select samples. Moreover, these data indicate that MP is related to serum L and Z, dietary L and Z intake, fiber intake, and iris color.

Ophthalmology 2001 Apr;108(4):730-7

The potential role of dietary xanthophylls in cataract and age-related macular degeneration.

The carotenoid xanthophylls, lutein and zeaxanthin, accumulate in the eye lens and macular region of the retina. Lutein and zeaxanthin concentrations in the macula are greater than those found in plasma and other tissues. A relationship between macular pigment optical density, a marker of lutein and zeaxanthin concentration in the macula, and lens optical density, an antecedent of cataractous changes, has been suggested. The xanthophylls may act to protect the eye from ultraviolet phototoxicity via quenching reactive oxygen species and/or other mechanisms. Some observational studies have shown that generous intakes of lutein and zeaxanthin, particularly from certain xanthophyll-rich foods like spinach, broccoli and eggs, are associated with a significant reduction in the risk for cataract (up to 20%) and for age-related macular degeneration (up to 40%). While the pathophysiology of cataract and age-related macular degeneration is complex and contains both environmental and genetic components, research studies suggest dietary factors including antioxidant vitamins and xanthophylls may contribute to a reduction in the risk of these degenerative eye diseases. Further research is necessary to confirm these observations.

J Am Coll Nutr 2000 Oct;19(5 Suppl):522S-527S

Continued on Page 4 of 4

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