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Abstracts

Zeaxanthin: 32 Research Abstracts

Macular degeneration/function

1. The role of oxidative stress in the pathogenesis of age-related macular degeneration. Beatty S, KohH, Phil M, Henson D, Boulton M. Academic Department of Ophthalmology, Manchester Royal Eye Hospital, Manchester, United Kingdom. Surv Ophthalmol 2000 Sep-Oct;45(2):115-34

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.

2. Lutein and zeaxanthin in the eyes, serum and diet of human subjects. Bone RA, Landrum JT, Dixon Z, Chen Y, Llerena CM. Department of Physics, Florida International University, Miami, FL 33199, USA. Exp Eye Res 2000 Sep;71(3):239-45

Inverse associations have been reported between the incidence of advanced, neovascular, age-related macular degeneration (AMD) and the combined lutein (L) and zeaxanthin (Z) intake in the diet, and L and Z concentration in the blood serum. We suggest that persons with high levels of L and Z in either the diet or serum would probably have, in addition, relatively high densities of these carotenoids in the macula, the so-called 'macular pigment'. Several lines of evidence point to a potential protective effect by the macular pigment against AMD. In this study we examined the relationship between dietary intake of L and Z using a food frequency questionnaire; concentration of L and Z in the serum, determined by high-performance liquid chromatography, and macular pigment optical density, obtained by flicker photometry. Nineteen subjects participated. We also analysed the serum and retinas, as autopsy samples, from 23 tissue donors in order to obtain the concentration of L and Z in these tissues. The results reveal positive, though weak, associations between dietary intake of L and Z and serum concentration of L and Z, and between serum concentration of L and Z and macular pigment density. We estimate that approximately half of the variability in the subjects' serum concentration of L and Z can be explained by their dietary intake of L and Z, and about one third of the variability in their macular pigment density can be attributed to their serum concentration of L and Z. These results, together with the reported associations between risk of AMD and dietary and serum L and Z, support the hypothesis that low concentrations of macular pigment may be associated with an increased risk of AMD.

3. Macular pigment in donor eyes with and without AMD: a case-control study. Bone RA, Landrum JT, Mayne ST, Gomez CM, Tibor SE, Twaroska EE. Department of Physics, Florida International University, Miami, Florida 33199, USA. bone@fiu.edu Invest Ophthalmol Vis Sci 2001 Jan;42(1):235-40

PURPOSE: To determine whether there is an association between the density of macular pigment in the human retina and the risk of age-related macular degeneration (AMD). METHODS: Retinas from 56 donors with AMD and 56 controls were cut into three concentric regions centered on the fovea. The inner, medial, and outer regions covered the visual angles 0 degrees to 5 degrees, 5 degrees to 19 degrees, and 19 degrees to 38 degrees, respectively. The amounts of lutein (L) and zeaxanthin (Z) extracted from each tissue sample were determined by high-performance liquid chromatography. RESULTS: L and Z levels in all three concentric regions were less, on average, for the AMD donors than for the controls. The differences decreased in magnitude from the inner to medial to outer regions. The lower levels found in the inner and medial regions for AMD donors may be attributable, in part, to the disease. Comparisons between AMD donors and controls using the outer (peripheral) region were considered more reliable. For this region, logistic regression analysis indicated that those in the highest quartile of L and Z level had an 82% lower risk for AMD compared with those in the lowest quartile (age- and sex-adjusted odds ratio = 0.18, 95% confidence interval = 0.05-0.64). CONCLUSIONS: The results are consistent with a theoretical model that proposes an inverse association between risk of AMD and the amounts of L and Z in the retina. The results are inconsistent with a model that attributes a loss of L and Z in the retina to the destructive effects of AMD.

4. Lutein, zeaxanthin, and the macular pigment. Landrum JT, Bone RA. Department of Chemistry, Florida International University, Miami 33199, USA. landrumj@fiu.edu Arch Biochem Biophys 2001 Jan 1;385(1):28-40

The predominant carotenoids of the macular pigment are lutein, zeaxanthin, and meso-zeaxanthin. The regular distribution pattern of these carotenoids within the human macula indicates that their deposition is actively controlled in this tissue. The chemical, structural, and optical characteristics of these carotenoids are described. Evidence for the presence of minor carotenoids in the retina is cited. Studies of the dietary intake and serum levels of the xanthophylls are discussed. Increased macular carotenoid levels result from supplementation of humans with lutein and zeaxanthin. A functional role for the macular pigment in protection against light-induced retinal damage and age-related macular degeneration is discussed. Prospects for future research in the study of macular pigment require new initiatives that will probe more accurately into the localization of these carotenoids in the retina, identify possible transport proteins and mechanisms, and prove the veracity of the photoprotection hypothesis for the macular pigments.

5. Lutein and zeaxanthin concentrations in rod outer segment membranes from perifoveal and peripheral human retina. Rapp LM, Maple SS, Choi JH. Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas 77030, USA. lrapp@bcm.tmc.edu Invest Ophthalmol Vis Sci 2000 Apr;41(5):1200-9

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. 6. Am J Clin Nutr. 2001 Dec;74(6):796-802.

6. Relation between dietary intake, serum concentrations, and retinal concentrations of lutein and zeaxanthin in adults in a Midwest population. Curran-Celentano J, Hammond BR Jr, Ciulla TA, Cooper DA, Pratt LM, Danis RB. Department of Animal and Nutritional Sciences, University of New Hampshire, Durham, NH 03824, USA. joannec@christa.unh.edu

BACKGROUND: Information on concentrations of retinal carotenoids (macular pigment, or MP) is of particular interest because MP protects against age-related macular degeneration, the leading cause of irreversible blindness in the United States. OBJECTIVE: This study was designed to evaluate the relation between dietary intake, blood concentrations, and retinal concentrations of carotenoids in a large group of volunteers. DESIGN: Two hundred eighty volunteers in the Indianapolis area completed health and diet questionnaires, donated a blood sample, and participated in MP density assessment to determine retinal carotenoid status. Dietary intake was assessed by food-frequency questionnaire. Serum concentrations of lutein, zeaxanthin, and beta-carotene were measured by HPLC. MP optical density (MPOD) was determined psychophysically with a 460-nm, 1 degrees test stimulus. RESULTS: Average MPOD was 0.21 +/- 0.13. Average intakes of lutein + zeaxanthin and beta-carotene were 1101 +/- 838 and 2935 +/- 2698 microg/d, respectively. Although several key dietary intake variables (eg, lutein + zeaxanthin and beta-carotene) differed by sex, no significant sex differences were found in either serum concentrations of lutein and zeaxanthin or MPOD. Serum beta-carotene concentrations were significantly higher in women than in men. Serum lutein + zeaxanthin and dietary intake of lutein + zeaxanthin were significantly correlated and significantly related to variations in MPOD (r = 0.21, P < 0.001, and r = 0.25, P < 0.001, respectively). CONCLUSIONS: Retinal carotenoids can be measured in epidemiologic studies. In this study, MPOD was associated with lutein + zeaxanthin in the diet and the serum. Retinal concentrations, however, were influenced by other factors as well. To understand the effect of dietary lutein + zeaxanthin intake on the retina and risk of age-related eye disease, future studies should include measures of macular concentrations of these pigments.

7. EXS. 1992;62:280-98.

Carotenoids in the retina--a review of their possible role in preventing or limiting damage caused by light and oxygen.

Schalch W.

Vitamins & Fine Chemical Division, F. Hoffmann - La Roche, Basel, Switzerland.

Two of the circa 600 naturally occurring carotenoids, zeaxanthin and lutein, the major carotenoids of maize and melon respectively, are the constituents of the macula lutea, the yellow spot in the macula, the central part of the retina in primates and humans. Of the circa ten carotenoids found in the blood these two are specifically concentrated in this area, which is responsible for sharp and detailed vision. This paper reviews the ideas that this concentration of dietary carotenoids in the macula is not accidental, but that their presence may prevent or limit damage due to their physicochemical properties and their capability to quench oxygen free radicals and singlet oxygen, which are generated in the retina as a consequence of the simultaneous presence of light and oxygen. Additionally, in vitro and in vivo animal experiments are reviewed as well as observational and epidemiological data in humans. These show that there is enough circumstantial evidence for a protective role of carotenoids in the retina to justify further research. Some emphasis will be put on age-related macular degeneration (AMD), a multifactorial degenerative retinal disease for which the exposure to light and thus photochemical damage has been suggested as one of the etiological factors. Recent attempts at nutritional intervention in this condition will also be reviewed.

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

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

Moeller SM, Jacques PF, Blumberg JB.

Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts 02111, USA.

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.

9. Lutein and zeaxanthin status and risk of age-related macular degeneration.

Gale CR, Hall NF, Phillips DI, Martyn CN.

Medical Research Council Environmental Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, United Kingdom. crg@mrc.soton.ac.uk

PURPOSE: To investigate the relation between plasma concentrations of lutein and zeaxanthin and age-related macular degeneration in a group of elderly men and women. METHODS: The Wisconsin Age-Related Maculopathy Grading System was used to grade features of early and late macular degeneration in 380 men and women, aged 66 to 75 years, from Sheffield, United Kingdom. Fasting blood samples were taken to assess plasma concentrations of lutein and zeaxanthin. RESULTS: Risk of age-related macular degeneration (early or late) was significantly higher in people with lower plasma concentrations of zeaxanthin. Compared with those whose plasma concentrations of zeaxanthin were in the highest third of the distribution, people whose plasma concentration was in the lowest third had an odds ratio for risk of age-related macular degeneration of 2.0 (95% confidence interval [CI] 1.0-4.1), after adjustment for age and other risk factors. Risk of age-related macular degeneration was increased in people with the lowest plasma concentrations of lutein plus zeaxanthin (odds ratio [OR] 1.9, 95% CI 0.9-3.5) and in those with the lowest concentrations of lutein (OR 1.7, 95% CI 0.9-3.3), but neither of these relations was statistically significant. CONCLUSIONS: These findings provide support for the view that zeaxanthin may protect against age-related macular degeneration.

10. Curr Eye Res. 1999 Dec;19(6):491-5.

Lutein and zeaxanthin are associated with photoreceptors in the human retina.

Sommerburg OG, Siems WG, Hurst JS, Lewis JW, Kliger DS, van Kuijk FJ.

University of Texas Medical Branch, Department of Ophthalmology & Visual Sciences TX, Galveston 77555-1067, USA.

PURPOSE. Previous studies showed that lutein and zeaxanthin, the major human retinal carotenoids, are concentrated in the macula. In this study, the carotenoids in human macular and peripheral retina and the retinal pigment epithelium (RPE) were analyzed. They were also determined in the rod outer segments (ROS) before and after removal of extrinsic membrane proteins. METHODS. Carotenoids were extracted from the macular and peripheral sections of human retina and RPE with hexane in dim light and analyzed by high performance liquid chromatography (HPLC). ROS samples equivalent to the amount in a single retina were also analyzed. RESULTS. Retinal carotenoid amounts were similar to previous reports, but only low levels were detected in the RPE. Regional ratios of lutein:zeaxanthin were similar in the retina and RPE. Approximately 25% of the total retinal carotenoids were found in the ROS, indicating that a substantial portion of peripheral retinal carotenoids are present in the ROS. However, after removal of the extrinsic membrane proteins and subsequent analysis, carotenoids were not detected. CONCLUSIONS: Most of the carotenoids in the human peripheral retina are present in the ROS. These ROS carotenoids are associated with soluble or salt-dependently bound proteins.

11. Fruits and vegetables that are sources for lutein and zeaxanthin: the macular pigment in human eyes.

Sommerburg O, Keunen JE, Bird AC, van Kuijk FJ.

Department of Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston 77555-1067, USA.

BACKGROUND: It has been suggested that eating green leafy vegetables, which are rich in lutein and zeaxanthin, may decrease the risk for age related macular degeneration. The goal of this study was to analyse various fruits and vegetables to establish which ones contain lutein and/or zeaxanthin and can serve as possible dietary supplements for these carotenoids. METHODS: Homogenates of 33 fruits and vegetables, two fruit juices, and egg yolk were used for extraction of the carotenoids with hexane. Measurement of the different carotenoids and their isomers was carried out by high performance liquid chromatography using a single column with an isocratic run, and a diode array detector. RESULTS: Egg yolk and maize (corn) contained the highest mole percentage (% of total) of lutein and zeaxanthin (more than 85% of the total carotenoids). Maize was the vegetable with the highest quantity of lutein (60% of total) and orange pepper was the vegetable with the highest amount of zeaxanthin (37% of total). Substantial amounts of lutein and zeaxanthin (30-50%) were also present in kiwi fruit, grapes, spinach, orange juice, zucchini (or vegetable marrow), and different kinds of squash. The results show that there are fruits and vegetables of various colours with a relatively high content of lutein and zeaxanthin. CONCLUSIONS: Most of the dark green leafy vegetables, previously recommended for a higher intake of lutein and zeaxanthin, have 15-47% of lutein, but a very low content (0-3%) of zeaxanthin. Our study shows that fruits and vegetables of various colours can be consumed to increase dietary intake of lutein and zeaxanthin.

12. Optom Vis Sci. 1997 Jul;74(7):499-504.

Density of the human crystalline lens is related to the macular pigment carotenoids, lutein and zeaxanthin.

Hammond BR Jr, Wooten BR, Snodderly DM.

Vision Sciences Laboratory, College of Arts & Sciences, Arizona State University, Phoenix, USA. BHammond@asuvm.inre.asu.edu

PURPOSE: Although oxidative stress may play an important role in the development of age-related cataract, the degree of protection reported for antioxidant vitamins and carotenoids has been inconsistent across studies. These varied results may be due in part to the lack of good biomarkers for measuring the long-term nutritional status of the eye. The present experiments investigated the relationship between retinal carotenoids (i.e., macular pigment), used as a long-term measure of tissue carotenoids, and lens optical density, used as an indicator of lens health. METHODS: Macular pigment (460 nm) and lens (440, 500, and 550 nm) optical density were measured psychophysically in the same individuals. Groups of younger subjects--7 females (ages 24 to 36 years), and 5 males (ages 24 to 31 years)--were compared with older subjects--23 older females (ages 55 to 78 years), and 16 older males (ages 48 to 82 years). RESULTS: Lens density (440 nm) increased as a function of age (r = 0.65, p < 0.001), as expected. For the oldest group, a significant inverse relationship (y = 1.53-0.83x, r = -0.47, p < 0.001) was found between macular pigment density (440 nm) and lens density (440 nm). No relationship was found for the youngest group (p < 0.42). CONCLUSIONS: The main finding of this study was an age-dependent, inverse relationship between macular pigment density and lens density. Macular pigment is composed of lutein and zeaxanthin, the only two carotenoids that have been identified in the human lens. Thus, an inverse relationship between these two variables suggests that lutein and zeaxanthin, or other dietary factors with which they are correlated, may retard age-related increases in lens density.

13. Invest Ophthalmol Vis Sci. 2001 Feb;42(2):439-46.

Macular pigment and risk for age-related macular degeneration in subjects from a Northern European population.

Beatty S, Murray IJ, Henson DB, Carden D, Koh H, Boulton ME.

University Department of Ophthalmology, Manchester Royal Eye Hospital, Manchester, UK. stephen@stiofanbetagh.demon.co.uk

PURPOSE: Age and advanced disease in the fellow eye are the two most important risk factors for age-related macular degeneration (AMD). In this study, the authors investigated the relationship between these variables and the optical density of macular pigment (MP) in a group of subjects from a northern European population. METHODS: The optical density of MP was measured psychophysically in 46 subjects ranging in age from 21 to 81 years with healthy maculae and in 9 healthy eyes known to be at high-risk of AMD because of advanced disease in the fellow eye. Each eye in the latter group was matched with a control eye on the basis of variables believed to be associated with the optical density of MP (iris color, gender, smoking habits, age, and lens density). RESULTS: There was an age-related decline in the optical density of macular pigment among volunteers with no ocular disease (right eye: r(2) = 0.29, P = 0.0006; left eye: r(2) = 0.29, P < 0.0001). Healthy eyes predisposed to AMD had significantly less MP than healthy eyes at no such risk (Wilcoxon's signed rank test: P = 0.015). CONCLUSIONS: The two most important risk factors for AMD are associated with a relative absence of MP. These findings are consistent with the hypothesis that supplemental lutein and zeaxanthin may delay, avert, or modify the course of this disease.

14. J Opt Soc Am A Opt Image Sci Vis. 2002 Jun;19(6):1172-86.

In vivo resonant Raman measurement of macular carotenoid pigments in the young and the aging human retina.

Gellermann W, Ermakov IV, Ermakova MR, McClane RW, Zhao DY, Bernstein PS.

Department of Physics and Dixon Laser Institute, University of Utah, Salt Lake City 84112, USA. werner@physics.utah.edu

We have used resonant Raman scattering spectroscopy as a novel, noninvasive, in vivo optical technique to measure the concentration of the macular carotenoid pigments lutein and zeaxanthin in the living human retina of young and elderly adults. Using a backscattering geometry and resonant molecular excitation in the visible wavelength range, we measure the Raman signals originating from the single- and double-bond stretch vibrations of the pi-conjugated molecule's carbon backbone. The Raman signals scale linearly with carotenoid content, and the required laser excitation is well below safety limits for macular exposure. Furthermore, the signals decline significantly with increasing age in normal eyes. The Raman technique is objective and quantitative and may lead to a new method for rapid screening of carotenoid pigment levels in large populations at risk for vision loss from age-related macular degeneration, the leading cause of blindness in the elderly in the United States.

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

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

Beatty S, Koh H, Phil M, Henson D, Boulton M.

Academic Department of Ophthalmology, Manchester Royal Eye Hospital, Manchester, United Kingdom.

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.

Cataracts

16. Curr Eye Res. 1999 Dec;19(6):502-5.

Fat-soluble nutrient concentrations in different layers of human cataractous lens.

Yeum KJ, Shang FM, Schalch WM, Russell RM, Taylor A.

Tufts University, Jean Mayer United States Department ofAgriculture Human Nutrition Research Center onAging at Tufts University, Boston, M A 0211, USA.

PURPOSE. Recent epidemiologic studies suggest that differential risk for cataract in different areas of the lens may be related to intake of carotenoids, retinol, and tocopherol. Nevertheless, there is little information about differential localization of these nutrients in the lens. To determine the spatial distribution of fat-soluble nutrients within the lens, we determined levels of these nutrients in the epithelium/ outer cortex vs. inner cortex/nucleus. METHODS. Concentrations of carotenoids, retinol, and tocopherol were determined in the epithelial/cortical (younger, more metabolically active tissue) and nuclear (older, less metabolically active) layers of human cataractous lenses (n = 7, 64-75 yr) by reverse-phase high-performance liquid chromatography (HPLC). RESULTS. Lutein/zeaxanthin was the only carotenoid, which was detected, in human lens. Consistent with prior reports, no beta-carotene or lycopene were detected. Concentrations of lutein/zeaxanthin, tocopherol, and retinol in epithelium/cortex tissue were approximately 3-, 1.8-, and 1.3-fold higher than in the older lens tissue. Specifically, the epithelial/cortical lens layer, comprising about half of the tissue, contains 74% of lutein/zeaxanthin (44 ng/g wet wt), 65% of alpha-tocopherol (2227 ng/g wet wt), and 60% of retinol (30 ng/g wet wt). CONCLUSIONS. The data suggest that upon development and aging, there is differential localization of these nutrients. The data are also consistent with a protective role of these nutrients against oxidative damage in the epithelium and cortex of the human lens.

17. Arch Ophthalmol. 2002 Dec;120(12):1732-7.

Lens aging in relation to nutritional determinants and possible risk factors for age-related cataract.

Berendschot TT, Broekmans WM, Klopping-Ketelaars IA, Kardinaal AF, Van Poppel G, Van Norren D.

Department of Ophthalmology, Universitair Medisch Centrum Utrecht, AZU E03.136, Heidelberglaan 100, PO Box 85500, NL-3508 GA Utrecht, the Netherlands. tosb@isi.uu.nl

OBJECTIVE: To investigate whether nutritional factors and possible risk factors for cataract influence the lens optical density (LOD). DESIGN: Three hundred seventy-six subjects, aged 18 to 75 years, were recruited. In a cross-sectional design, serum was analyzed for lutein, zeaxanthin, vitamin C, alpha-tocopherol, and cholesterol levels. Adipose tissue (n = 187) was analyzed for lutein level. The LOD and the macular pigment optical density (MPOD) were measured by spectral fundus reflectance. RESULTS: The mean +/- SD LOD at 420 nm was 0.52 +/- 0.17. It showed a significant association with age (beta =.008, P<001) and MPOD (beta = -.096, P =.02). For subjects 50 years and younger (mean +/- SD LOD, 0.45 +/- 0.11), we found only a single significant beta coefficient, for age (beta =.006, P<.001). For subjects older than 50 years (mean +/- SD LOD, 0.68 +/- 0.16), we found significant beta coefficients for age (beta =.011, P<.001) and MPOD (beta = -.240, P =.005). Controlling for age, we found no associations between LOD and other possible risk factors for age-related cataract or serum or adipose tissue concentrations of carotenoids, vitamin C, and alpha-tocopherol. CONCLUSIONS: Macular pigment is composed of lutein and zeaxanthin, the only carotenoids found in human lenses. The inverse relationship between LOD and MPOD suggests that lutein and zeaxanthin may retard aging of the lens.

18. J Nutr. 2002 Mar;132(3):518S-524S.

The body of evidence to support a protective role for lutein and zeaxanthin in delaying chronic disease. Overview.

Mares-Perlman JA, Millen AE, Ficek TL, Hankinson SE.

Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison Medical School, Madison, WI 53705-2397, USA. jmaresp@facstaff.wisc.edu

Recent evidence introduces the possibility that lutein and zeaxanthin may protect against the development of the two common eye diseases of aging, cataract and macular degeneration. This potential and the lack of other effective means to slow the progression of macular degeneration have fueled high public interest in the health benefits of lutein and zeaxanthin and the proliferation of supplements containing them on pharmacy shelves. An understanding of the biologic consequences of limiting or supplementing with these carotenoids is only beginning to emerge. Some epidemiologic evidence supports a role in eye disease and, to a lesser extent, cancer and cardiovascular disease. However, the overall body of evidence is insufficient to conclude that increasing levels of lutein and zeaxanthin, specifically, will confer an important health benefit. Future advances in scientific research are required to gain a better understanding of the biologic mechanisms of their possible role in preventing disease. Additional research is also required to understand the effect of their consumption, independent of other nutrients in fruits and vegetables, on human health. The newly advanced ability to measure levels of lutein and zeaxanthin in the retina in vivo creates a unique opportunity to contribute some of this needed evidence.

Function

19. Exp Eye Res. 2001 Mar;72(3):215-23.

Identification and quantitation of carotenoids and their metabolites in the tissues of the human eye.

Bernstein PS, Khachik F, Carvalho LS, Muir GJ, Zhao DY, Katz NB.

Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah School of Medicine, Salt Lake City, UT 84132, USA. paul.bernstein@hsc.utah.edu

There is increasing evidence that the macular pigment carotenoids, lutein and zeaxanthin, may play an important role in the prevention of age-related macular degeneration, cataract, and other blinding disorders. Although it is well known that the retina and lens are enriched in these carotenoids, relatively little is known about carotenoid levels in the uveal tract and in other ocular tissues. Also, the oxidative metabolism and physiological functions of the ocular carotenoids are not fully understood. Thus, we have set out to identify and quantify the complete spectrum of dietary carotenoids and their oxidative metabolites in a systematic manner in all tissues of the human eye in order to gain better insight into their ocular physiology.Human donor eyes were dissected, and carotenoid extracts from ocular tissues [retinal pigment epithelium/choroid (RPE/choroid), macula, peripheral retina, ciliary body, iris, lens, vitreous, cornea, and sclera] were analysed by high-performance liquid chromatography (HPLC). Carotenoids were identified and quantified by comparing their chromatographic and spectral profiles with those of authentic standards.Nearly all ocular structures examined with the exception of vitreous, cornea, and sclera had quantifiable levels of dietary (3R,3'R,6'R)-lutein, zeaxanthin, their geometrical (E / Z) isomers, as well as their metabolites, (3R,3'S,6'R)-lutein (3'-epilutein) and 3-hydroxy-beta,epsilon-caroten-3'-one. In addition, human ciliary body revealed the presence of monohydroxycarotenoids and hydrocarbon carotenoids, while only the latter group was detected in human RPE/choroid. Uveal structures (iris, ciliary body, and RPE/choroid) account for approximately 50% of the eye's total carotenoids and approximately 30% of the lutein and zeaxanthin. In the iris, these pigments are likely to play a role in filtering out phototoxic short-wavelength visible light, while they are more likely to act as antioxidants in the ciliary body. Both mechanisms, light screening and antioxidant, may be operative in the RPE/choroid in addition to a possible function of this tissue in the transport of dihydroxycarotenoids from the circulating blood to the retina. This report lends further support for the critical role of lutein, zeaxanthin, and other ocular carotenoids in protecting the eye from light-induced oxidative damage and aging. Copyright 2001 Academic Press.

Lung cancer

20. Cancer Causes Control. 2003 Feb;14(1):85-96.

Dietary carotenoids, vegetables, and lung cancer risk in women: the Missouri women's health study (United States).

Wright ME, Mayne ST, Swanson CA, Sinha R, Alavanja MC.

Department of Epidemiology, and Public Health, Yale University School of Medicine, New Haven, CT 05620-8034, USA

OBJECTIVE: To examine the effect of specific dietary carotenoids and their primary plant food sources on lung cancer risk in a population-based case-control study of women. METHODS: Data were available for 587 incident primary lung cancer cases and 624 controls frequency matched to cases based on age. A modified version of the 100-item NCI-Block food-frequency questionnaire was used to obtain information concerning usual diet 2-3 years prior to interview. RESULTS: In models adjusted for age, total calorie intake, pack-years of smoking, and education, beta-carotene, beta-cryptoxanthin, lutein + zeaxanthin, and total carotenoid intake were each associated with a significantly lower risk of lung cancer. Several vegetable groups were predictive of lower lung cancer risk, particularly the frequency of total vegetable intake. Individual and total carotenoids were no longer significantly associated with lower lung cancer risk in models adjusted for total vegetable intake. However, total vegetable intake remained significantly inversely associated with risk in models adjusted for total carotenoids. CONCLUSIONS: These results indicate that consumption of a wide variety of vegetables has a greater bearing on lung cancer risk in a population of smoking and nonsmoking women than intake of any specific carotenoid or total carotenoids.

Chronic disease

21. Int J Epidemiol. 2001 Feb;30(1):136-43.

Comment in: Int J Epidemiol. 2001 Feb;30(1):143-4.

Serum carotenoids, alpha-tocopherol and mortality risk in a prospective study among Dutch elderly.

De Waart FG, Schouten EG, Stalenhoef AF, Kok FJ.

The Division of Human Nutrition and Epidemiology, Wageningen University and Research Center, Wageningen, The Netherlands. frouwkje.hans@consunet.nl

BACKGROUND: Although beta-carotene has shown inverse associations with chronic diseases involving free radical damage in observational epidemiological studies less attention has been paid to five other major carotenoids also showing antioxidant activity in vitro. METHODS: We studied the associations between 7.2-year mortality and serum levels of six carotenoids, and alpha-tocopherol, measured in stored serum, sampled in 1991/1992 during a health survey among 638 independently living elderly subjects aged 65-85 years. Proportional hazards regression was used to estimate hazard ratios of all-cause mortality for the lowest tertiles of serum vitamins with the highest tertiles, adjusting for possible confounding effects. RESULTS: During a follow-up period of 7.2 years 171 elderly died. The adjusted hazard ratios for all-cause mortality for the lowest tertiles of vitamins compared with the highest tertiles were between 1.02 and 1.73. The strongest increase in mortality risk was seen for beta-cryptoxanthin (1.52, 95% CI : 1.00, 2.32), lutein (1.56, 95% CI : 1.05, 2.31) and zeaxanthin (1.32, 95% CI : 0.89, 1.97) and their sum (oxygenated carotenoids: 1.73, 95% CI : 1.12, 2.67). Tests for trend were significant (P < 0.05) for all-cause mortality risk and serum levels of total carotenoids, oxygenated carotenoids and beta-cryptoxanthin. CONCLUSIONS: Our findings suggest that serum levels of individual carotenoids, particularly the oxygenated species are inversely associated with all-cause mortality and should be considered as candidates for further investigations.

Anticarcinogenic

22. Int J Vitam Nutr Res. 1993;63(2):93-121.

Anticarcinogenic effect of common carotenoids.

Gerster H.

Vitamin Research Department, VFEH, F. Hoffmann-La Roche, Basel, Switzerland.

Of the common carotenoids present in food, beta carotene, alpha carotene, lycopene, lutein, zeaxanthin as well as canthaxanthin can be considered potential prophylactic agents against carcinogenesis. They are absorbed by the human organism in reasonable amounts, and they have antioxidant properties, immunomodulating effects and may possibly influence gene expression enhancing gap junction communication. Recent suggestions that beta carotene may be metabolized directly to retinoic acid in retinoic acid target tissue and the discovery of retinoic acid nuclear receptors open up new perspectives for research. The best established chain of evidence for a protective effect of carotenoids against cancer development is available for beta carotene. Positive effects were observed in cell culture and experimental animal studies as well as in dietary and blood level studies in humans. More conclusive evidence will be provided by double-blind intervention trials in humans that are in progress. Beta carotene appears to be active in the promotion phase of carcinogenesis stabilizing initiated cells. Canthaxanthin, which has often been included in animal experiments for comparative purposes having little or no provitamin A activity, also exhibits strong protective effects. Of the other carotenoids only limited data are available. Depending on the experimental model used, lycopene, lutein or alpha carotene was particularly active. In preliminary human blood level studies, lycopene was inversely associated with cancers of the pancreas and cervix. Much work remains to be done. Of particular interest is the question of organ specificity of individual carotenoids.

HIV

23. J Acquir Immune Defic Syndr. 2000 Apr 1;23(4):321-6.

Improved antioxidant status among HIV-infected injecting drug users on potent antiretroviral therapy.

Tang AM, Smit E, Semba RD, Shah N, Lyles CM, Li D, Vlahov D.

Department of Epidemiology, School of Hygiene and Public Health, Johns Hopkins University', Baltimore, Maryland, USA.

Low serum antioxidant levels in HIV-infected people have been attributed to altered metabolism associated with excess oxidative stress. We conducted a study to examine serum antioxidant levels in 175 HIV-positive and 210 HIV-negative injecting drug users (IDUs) in Baltimore, Maryland. At the time of data collection, 30 of the HIV-positive IDUs were receiving antiretroviral therapies (ART) including a protease inhibitor (PI), 43 ART without a PI, 22 monotherapies, and 80 not on any ART. Serum antioxidants examined included retinol, alpha-tocopherol and gamma-tocopherol, alpha-carotene and beta-carotene, lycopene, lutein/zeaxanthin, and beta-cryptoxanthin. Mean serum levels of lycopene and lutein/zeaxanthin were significantly lower in HIV-positive IDUs than HIV-negative IDUs. Contrary to the findings in other studies, however, levels of the remaining antioxidants in HIV-positive study subjects were not lower than in HIV-negative study subjects. In fact, serum alpha-tocopherol levels were significantly higher in HIV-positive IDUs than HIV-negative IDUs (medians = 744 microg/dl and 718 microg/dl, respectively; p = .04). Among HIV-positive study subjects, there were significant differences in antioxidant levels by ART regimen. In multivariate models adjusting for injecting drug use, dietary intake, supplement intake, gender, and alcohol intake, significant overall differences by ART regimen were observed for alpha-tocopherol, beta-carotene, and beta-cryptoxanthin. Serum levels of these three antioxidants were significantly higher in the PI group than in the other three ART groups combined (p = .0008, 0.02, and 0.02, respectively). These data provide indirect evidence of the effectiveness of PIs in lowering oxidative stress levels in HIV-positive IDUs.

24. Nutrition. 2001 Jul-Aug;17(7-8):567-72.

Relation of vitamin A and carotenoid status to growth failure and mortality among Ugandan infants with human immunodeficiency virus.

Melikian G, Mmiro F, Ndugwa C, Perry R, Jackson JB, Garrett E, Tielsch J, Semba RD.

Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Although growth failure is common during pediatric infection with human immunodeficiency virus (HIV) and associated with increased mortality, the relation of specific nutrition factors with growth and mortality has not been well characterized. A longitudinal study was conducted with 194 HIV-infected infants in Kampala, Uganda. Plasma vitamin A, carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, and lutein/zeaxanthin), and vitamin E were measured at age 14 wk, and weight and height were followed up to age 12 mo. Vitamin A and low plasma carotenoid concentrations were predictive of decreased weight and height velocity. Between ages 14 wk and 12 mo, 32% of infants died. Underweight, stunting, and low concentrations of plasma carotenoids were associated with increased risk of death in univariate analyses. Plasma vitamin A concentrations were not associated with risk of death. In a final multivariate model adjusting for weight-for-age, plasma beta-carotene was significantly associated with increased mortality (odds ratio: 3.16, 95% confidence interval: 1.38 to 7.21, P < 0.006). These data suggest that low concentrations of plasma carotenoids are associated with increased risk of death during HIV infection among infants in Uganda.

Cardiovascular

25. Free Radic Biol Med. 2002 Jan 15;32(2):148-52.

Plasma lipophilic antioxidants and malondialdehyde in congestive heart failure patients: relationship to disease severity.

Polidori MC, Savino K, Alunni G, Freddio M, Senin U, Sies H, Stahl W, Mecocci P.

Institute of Physiological Chemistry I, Heinrich-Heine University, Dusseldorf, Germany. polidori@uni-duesseldorf.de

Plasma levels of malondialdehyde (MDA), vitamin A, and of antioxidant micronutrients including vitamin E, lutein, zeaxanthin, beta-cryptoxanthin, lycopene, and alpha- and beta-carotene were measured in 30 patients with class II and III congestive heart failure (CHF) according to the New York Heart Association (NYHA) classification and in 55 controls. Ejection fraction was evaluated by echocardiography in all patients as a measure of the emptying capacity of the heart. Plasma levels of all measured compounds were significantly lower and MDA significantly higher in patients compared to controls (p <.001). Class II NYHA patients showed significantly lower MDA levels and significantly higher levels of vitamin A, vitamin E, lutein, and lycopene than class III patients. Ejection fraction was inversely correlated with MDA levels and directly correlated with vitamin A, vitamin E, lutein, and lycopene levels in patients. The present study supports the concept that an increased consumption of vitamin-rich fruits and vegetables might help in achieving cardiovascular health.

26. Nutrition. 2002 Jan;18(1):26-31.

Plasma status of retinol, alpha- and gamma-tocopherols, and main carotenoids to first myocardial infarction: case control and follow-up study.

Ruiz Rejon F, Martin-Pena G, Granado F, Ruiz-Galiana J, Blanco I, Olmedilla B.

Servicio de Cardiologia, Servicio de Medicina Interna, Hospital de Mostoles, Madrid, Spain. ferruiz@inicia.es

OBJECTIVE: Epidemiologic studies have suggested that dietary intake and plasma concentrations of antioxidants have an inverse relation with coronary heart disease. To test whether fat-soluble antioxidants can play a role against the occurrence of myocardial infarction (MI), we measured plasma levels of retinol, tocopherols, and individual carotenoids in MI patients. METHODS: A case-control and follow-up study of patients in the Mostoles area (Madrid, Spain). One hundred six patients (62 after 1 y) and 104 control subjects participated in the study. Blood samples were collected after overnight fast or during the first 24 h of MI onset for biochemical profiles of retinol, alpha- and gamma-tocopherols, and carotenoid by means of a quality-controlled high-performance liquid chromatography. RESULTS: During the acute phase after MI onset, plasma levels of retinol, gamma-tocopherol, and xanthophylls (lutein/zeaxanthin and beta-cryptoxanthin) decreased, whereas alpha-tocopherol, alpha-carotene, beta-carotene, and lycopene showed levels similar to those of control subjects. Logistic regression analysis showed low concentrations of gamma-tocopherol (and retinol) in plasma as the only statistically significant factor associated with MI, after adjusting for traditional risk factors. However, 1 y later, the MI patients showed a general improvement in plasma lipids and fat-soluble antioxidant status, and none of the analytes was associated with MI. CONCLUSIONS: The decreased plasma status of retinol, gamma-tocopherol, and xanthophylls during the acute phase of MI normalized the year after the MI event, suggesting that most subjects had followed an overall healthier lifestyle and dietary pattern. The results also raise concerns on the usefulness of these plasma compounds as specific, relevant, and predictive markers in relation to coronary heart disease.

27. Am J Clin Nutr. 2001 Oct;74(4):442-8.

Improvements in circulating cholesterol, antioxidants, and homocysteine after dietary intervention in an Australian Aboriginal community.

Rowley KG, Su Q, Cincotta M, Skinner M, Skinner K, Pindan B, White GA, O'Dea K.

University of Melbourne, Department of Medicine, St Vincent's Hospital, Fitzroy, VIC, Australia. kevinr@medstv.unimelb.edu.au

BACKGROUND: Poor nutrition contributes to high rates of coronary heart disease among Australian Aboriginal populations. Since late 1993, the Aboriginal community described here has operated a healthy lifestyle program aimed at reducing the risk of chronic disease. OBJECTIVE: We evaluated the effectiveness of a community-directed intervention program to reduce coronary heart disease risk through dietary modification. DESIGN: Intervention processes included store management policy changes, health promotion activities, and nutrition education aimed at high-risk individuals. Dietary advice was focused on decreasing saturated fat and sugar intake and increasing fruit and vegetable intake. Evaluation of the program included conducting sequential, cross-sectional risk factor surveys at 2-y intervals; measuring fasting cholesterol, lipid-soluble antioxidants, and homocysteine concentrations; and assessing smoking status. Nutrient intakes were estimated from analysis of food turnover in the single community store. RESULTS: There was a significant reduction in the prevalence of hypercholesterolemia (age-adjusted prevalences were 31%, 21%, and 15% at baseline, 2 y, and 4 y, respectively; P < 0.001). There were significant increases in plasma concentrations of alpha-tocopherol, lutein and zeaxanthin, cryptoxanthin, and beta-carotene across the population. Retinol and lycopene concentrations did not change significantly. Mean plasma homocysteine concentrations decreased by 3 micromol/L. There was no significant change in smoking prevalence between the 2 follow-up surveys. There was an increase in the density of fresh fruit and vegetables and carotenoids in the food supply at the community store. CONCLUSION: This community-directed dietary intervention program reduced the prevalence of coronary heart disease risk factors related to diet.

28. Am J Epidemiol. 2000 Dec 1;152(11):1065-71.

Serum carotenoids and markers of inflammation in nonsmokers.

Kritchevsky SB, Bush AJ, Pahor M, Gross MD.

Department of Preventive Medicine, University of Tennessee, Memphis 38105, USA. skritchevsky@utmem.edu

One explanation for discrepant results between epidemiologic studies and randomized trials of beta-carotene and cardiovascular disease may be a failure to consider inflammation as a confounder. To evaluate the potential for such confounding, the authors relate the serum concentrations of five carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, and lutein/zeaxanthin) to levels of three inflammatory markers (C-reactive protein, fibrinogen, and white blood cell count) measured during the Third National Health and Nutrition Survey, 1988-1994. The analysis included 4,557 nonsmoking participants aged 25-55 years. Adjusted concentrations of all five carotenoids were significantly lower in those with C-reactive protein levels above 0.88 mg/dl (p = 0.001). There was a trend toward lower adjusted beta-cryptoxanthin concentrations with increasing level of fibrinogen (p value test for trend = 0.01), but other carotenoids were not related. Many of the carotenoid concentrations were lower among participants with high white blood cell counts. After log transformation, only adjusted mean beta-carotene levels were significantly lower in those with white blood cell counts above 7.85 x 10(9)/liter (p < 0.01). These cross-sectional data do not clarify the biologic relation between carotenoids and C-reactive protein but, to the extent that the carotenoids are associated with C-reactive protein levels, a carotenoid-heart disease association may be, in part, an inflammation-heart disease association.

Concentrations among people

29. Ethn Dis. 2000 Spring-Summer;10(2):208-17.

Variations in serum carotenoid concentrations among United States adults by ethnicity and sex.

Ford ES.

Division of Nutrition and Physical Activity, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA 30341, USA. esf2@cdc.gov

Increased fruit and vegetable intake is associated with a lower risk of heart disease and cancer. Carotenoids, which occur primarily in fruits and vegetables, have been associated with reduced risk of some chronic diseases. To examine the distribution of serum carotenoid concentrations among US adults by ethnicity and sex, the author used data from the Third National Health and Nutrition Examination Survey, conducted from 1988 to 1994. After exclusions, 14,914 participants aged > or =20 years who attended the medical examination clinic had their serum carotenoid concentrations determined. Mexican-American men had higher total concentrations than European Americans and African Americans. In general, European-American participants were characterized by high lycopene but low beta-cryptoxanthin and lutein/zeaxanthin concentrations; African Americans by high lutein/zeaxanthin and low alpha-carotene and beta-cryptoxanthin concentrations; and Mexican Americans by high alpha-carotene, beta-cryptoxanthin, and lutein/zeaxanthin concentrations. The implications of these different carotenoid concentration patterns for future risk of disease within the ethnic and sex groups remain to be clarified.

30. Int J Vitam Nutr Res. 2001 Mar;71(2):97-102.

Plasma carotenoids in relation to food consumption in Granada (southern Spain) and Malmo (southern Sweden).

van Kappel AL, Martinez-Garcia C, Elmstahl S, Steghens JP, Chajes V, Bianchini F, Kaaks R, Riboli E.

Unit of Nutrition and Cancer, International Agency for Research on Cancer, 150 cours Albert-Thomas, 69372 Lyon, France.

We conducted a cross-sectional pilot study on healthy pre-menopausal women (aged 45-50 years) living in Granada, in the south of Spain (n = 39) and Malmo, in the south of Sweden (n = 38) in order to compare their plasma carotenoid levels and to investigate the relationship between the differences in food consumption. Plasma concentrations of six carotenoids were measured using high performance liquid chromatography, habitual diet (at individual level) was estimated by food frequency questionnaires and 24-hour diet recalls were used for standardised measurement of diet at group-level. We found that women in Granada consumed more fruit and vegetables than women in Malmo. Plasma concentrations of beta-cryptoxanthin, lycopene, zeaxanthin, total carotenoids and alpha-tocopherol were higher in Granada than in Malmo, although plasma concentrations of alpha-carotene and retinol were higher in Malmo. Both within and between study centres, consumption of fruit and vegetables correlated positively with plasma concentrations of different carotenoids. The study showed that differences in consumption of fruit and vegetables between the two European centres were reflected in plasma carotenoid concentrations.

Antioxidant

31. Arch Neurol. 2002 May;59(5):794-8.

Lymphocyte oxidative DNA damage and plasma antioxidants in Alzheimer disease.

Mecocci P, Polidori MC, Cherubini A, Ingegni T, Mattioli P, Catani M, Rinaldi P, Cecchetti R, Stahl W, Senin U, Beal MF.

Institute of Gerontology and Geriatrics, University of Perugia, Via Eugubina 42, 06122 Perugia, Italy. mecocci@unipg.it

CONTEXT: A large body of experimental evidence suggests that in Alzheimer disease (AD) pathogenesis an important role is played by oxidative stress, but there is still a lack of data on in vivo markers of free radical-induced damage. OBJECTIVES: To evaluate levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative damage to DNA, in peripheral lymphocytes; to measure plasma concentrations of several nonenzymatic antioxidants; and to assess the relationships between any observed changes in lymphocyte DNA 8-OHdG content and plasma antioxidant levels in patients with AD and healthy aged control subjects. SUBJECTS: Forty elderly outpatients with AD and 39 healthy age- and sex-matched controls were studied. MAIN OUTCOME MEASURES: The level of 8-OHdG was determined in DNA extracted from lymphocytes and plasma levels of vitamin C, vitamin A, vitamin E, and carotenoids (zeaxanthin, beta-cryptoxanthin, lycopene, lutein, and alpha- and beta-carotene) were measured by high-performance liquid chromatography. RESULTS: Lymphocyte DNA 8-OHdG content was significantly higher and plasma levels of antioxidants (with the exception of lutein) were significantly lower in patients with AD compared with controls. In patients with AD, a significant inverse relationship between lymphocyte DNA 8-OHdG content and plasma levels of lycopene, lutein, alpha-carotene, and beta-carotene, respectively, was observed. CONCLUSIONS: Markers of oxidative damage are increased in AD and correlate with decreased levels of plasma antioxidants. These findings suggest that lymphocyte DNA 8-OHdG content in patients with AD reflects a condition of increased oxidative stress related to a poor antioxidant status.

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

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

Beatty S, Koh H, Phil M, Henson D, Boulton M.

Academic Department of Ophthalmology, Manchester Royal Eye Hospital, Manchester, United Kingdom.

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.