Risk factors for age-related maculopathy are associated with a relative lack of macular pigment.
Macular pigment (MP) is composed of the two dietary carotenoids lutein (L) and zeaxanthin (Z), and is believed to protect against age-related maculopathy (ARM). This study was undertaken to investigate MP optical density with respect to risk factors for ARM, in 828 healthy subjects from an Irish population. MP optical density was measured psychophysically using heterochromatic flicker photometry, serum L and Z were quantified by HPLC, and dietary intake of L and Z was assessed using a validated food-frequency questionnaire. Clinical and personal details were also recorded, with particular attention directed towards risk factors for ARM. We report a statistically significant age-related decline in MP optical density (r2=0.082, p<0.01). Current and past smokers had lower average MP optical density than never smokers and this difference was statistically significant (p<0.01). Subjects with a confirmed family history of ARM had significantly lower levels of MP optical density than subjects with no known family history of disease (p<0.01). For each of these established risk factors, their statistically significant negative association with MP persisted after controlling for the other two, and also after controlling for other potentially confounding variables such as sex, cholesterol, dietary and serum L (p<0.01). In the absence of retinal pathology, and in advance of disease onset, the relative lack of MP seen in association with increasing age, tobacco use and family history of ARM supports the hypothesis that the enhanced risk that these variables represent for ARM may be attributable, at least in part, to a parallel deficiency of macular carotenoids.
Exp Eye Res. 2007 Jan;84(1):61-74
Plasma lutein and zeaxanthin and other carotenoids as modifiable risk factors for age-related maculopathy and cataract: the POLA Study.
PURPOSE: To assess the associations of plasma lutein and zeaxanthin and other carotenoids with the risk of age-related maculopathy (ARM) and cataract in the population-based Pathologies Oculaires Liées à l’Age (POLA) Study. METHODS: Retinal photographs were graded according to the international classification. ARM was defined by the presence of late ARM (neovascular ARM, geographic atrophy) and/or soft indistinct drusen (>125 microm) and/or soft distinct drusen (>125 microm) associated with pigmentary abnormalities. Cataract classification was based on a direct standardized lens examination at the slit lamp, according to Lens Opacities Classification System III. Plasma carotenoids were measured by high-performance liquid chromatography (HPLC), in 899 subjects of the cohort. RESULTS: After multivariate adjustment, the highest quintile of plasma zeaxanthin was significantly associated with reduced risk of ARM (OR=0.07; 95% CI: 0.01-0.58; P for trend=0.005), nuclear cataract (OR=0.23; 95% CI: 0.08-0.68; P for trend=0.003) and any cataract (OR=0.53; 95% CI: 0.31-0.89; P for trend=0.01). ARM was significantly associated with combined plasma lutein and zeaxanthin (OR=0.21; 95% CI: 0.05-0.79; P for trend=0.01), and tended to be associated with plasma lutein (OR=0.31; 95% CI: 0.09-1.07; P for trend=0.04), whereas cataract showed no such associations. Among other carotenoids, only beta-carotene showed a significant negative association with nuclear cataract, but not ARM. CONCLUSIONS: These results are strongly suggestive of a protective role of the xanthophylls, in particular zeaxanthin, for the protection against ARM and cataract.
Invest Ophthalmol Vis Sci. 2006 Jun;47(6):2329-35
Plasma carotenoids and prostate cancer: a population-based case-control study in Arkansas.
Carotenoids possess antioxidant properties and thus may protect against prostate cancer. Epidemiological studies of dietary carotenoids and this malignancy were inconsistent, partially due to dietary assessment error. In this study, we aimed to investigate the relation between plasma concentrations of carotenoids and the risk of prostate cancer in a population-based case-control study in Arkansas. Cases (n = 193) were men with prostate cancer diagnosed in 3 major hospitals, and controls (n = 197) were matched to cases by age, race, and county of residence. After adjustment for confounders, plasma levels of lycopene, lutein/zeaxanthin, and beta-cryptoxanthin were inversely associated with prostate cancer risk. Subjects in the highest quartile of plasma lycopene (513.7 microg/l) had a 55% lower risk of prostate cancer than those in the lowest quartile (140.5 microg/l; P trend = 0.042). No apparent association was observed for plasma alpha-carotene and beta-carotene. Further adjustment for the other 4 carotenoids did not materially alter the risk estimates for plasma lycopene, lutein/zeaxanthin, and beta-cryptoxanthin but appeared to result in an elevated risk with high levels of plasma alpha-carotene and beta-carotene. The results of all analyses did not vary substantially by age, race, and smoking status. This study added to the emerging evidence that high circulating levels of lycopene, lutein/zeaxanthin, and beta-cryptoxanthin are associated with a low risk of prostate cancer.
Nutr Cancer. 2007;59(1):46-53
Low plasma levels of oxygenated carotenoids in patients with coronary artery disease.
BACKGROUND AND AIMS: Low circulating levels of carotenoids have been associated with cardiovascular disease. The distribution of different carotenoids in blood may have an impact on the cardioprotective capacity. The aim of the present study was to determine the plasma levels of 6 major carotenoids in patients with coronary artery disease (CAD) and relate the findings to clinical, metabolic and immune parameters. METHODS AND RESULTS: Plasma levels of oxygenated carotenoids (lutein, zeaxanthin, beta-cryptoxanthin) and hydrocarbon carotenoids (alpha-carotene, beta-carotene, lycopene) were determined in 39 patients with acute coronary syndrome, 50 patients with stable CAD and 50 controls. Serological assays for inflammatory activity and flow cytometrical analysis of lymphocyte subsets were performed. Both patient groups had significantly lower plasma levels of oxygenated carotenoids, in particular lutein+zeaxanthin, compared to controls. Low levels of oxygenated carotenoids were associated with smoking, high body mass index (BMI), low high density lipoprotein (HDL) cholesterol and, to a minor degree, inflammatory activity. Plasma levels of lutein+zeaxanthin were independently associated with the proportions of natural killer (NK) cells, but not with other lymphocytes, in blood. CONCLUSION: Among carotenoids, lutein+zeaxanthin and beta-cryptoxanthin were significantly reduced in CAD patients independent of clinical setting. The levels were correlated to a number of established cardiovascular risk factors. In addition, the relationship between NK cells and lutein+zeaxanthin may indicate a particular role for certain carotenoids in the immunological scenario of CAD.
Nutr Metab Cardiovasc Dis. 2007 Jul;17(6):448-56
Plasma carotenoid levels and cognitive performance in an elderly population: results of the EVA Study.
BACKGROUND: The hypothesis of carotenoids having a preventive role in cognitive impairment is suggested by their antioxidant properties. METHODS: We examined, in a cross-sectional analysis, the relationship between cognitive performance (assessed by the Mini-Mental State Examination, Trail Making Test Part B, Digit Symbol Substitution, Finger Tapping Test, and Word Fluency Test) and different plasma carotenoids (lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, and trans-beta-carotene and cis-beta-carotene) in a healthy elderly population (the EVA,”Etude du Vieillissement Artériel,” study; n = 589, age = 73.5 +/- 3 years). RESULTS: Logistic regression showed that participants with the lowest cognitive functioning (<25th percentile) had a higher probability of having low levels of specific plasma carotenoids (<1st quartile): lycopene and zeaxanthin. For zeaxanthin, odds ratios (ORs) were as follows: OR(DSS) = 1.97 (95% confidence interval [CI] = 1.21-3.20), OR(FTT) = 1.70 (CI = 1.05-2.74), and OR(WFT) = 1.82 (CI = 1.08-3.07); for lycopene, OR(DSS) = 1.93 (CI = 1.20-3.12) and OR(TMTB) = 1.64 (CI = 1.04-2.59). CONCLUSION: Even if it is not possible to affirm if these low levels of carotenoids precede or are the consequence of cognitive impairment, our results suggest that low carotenoid levels could play a role in cognitive impairment. The biological significance of our findings needs further research.
J Gerontol A Biol Sci Med Sci. 2007 Mar;62(3):308-16
Immunopathological aspects of age-related macular degeneration.
Age-related macular degeneration (AMD) represents a leading cause of blindness worldwide. While the clinical and histopathological aspects of AMD are well characterized, its etiology and pathogenesis remain unclear. Recent findings suggest a role for immunologic processes in AMD pathogenesis, including the age-related generation of extracellular deposits inside the Brusch membrane and beneath the retinal pigment epithelium, recruitment of macrophages for clearance of these deposits, complement activation, recruitment of tissue-destructive macrophages, microglial activation and accumulation, and proinflammatory effects of chronic inflammation by Chlamydia pneumoniae. This review discusses the evidence for the role of inflammation in human AMD and in animal models of AMD.
Semin Immunopathol. 2008 Feb 26
Macular pigment: a review of current knowledge.
The existence of the macula lutea of the human retina has been known for more than 200 years. It is established that the xanthophylls lutein and zeaxanthin are responsible for the yellow color. The effect of macular photopigments on blue-light filtration and color perception is well established. It has been postulated that the pigment might serve to reduce chromatic aberration and to improve visual acuity. The antioxidant capabilities of these xanthophylls combined with their ability to trap short-wavelength light may serve to protect the outer retina, retinal pigment epithelium, and choriocapillaris from oxidative damage. Current ideas on the pathophysiology of age-related macular degeneration may be compatible with the proposed function of lutein and zeaxanthin. This review will summarize our knowledge about macular pigment regarding current efforts in research and the epidemiology of age-related eye disease.
Arch Ophthalmol. 2006 Jul;124(7):1038-45
Association between visual acuity and medical and non-medical costs in patients with wet age-related macular degeneration in France, Germany and Italy.
INTRODUCTION: Exudative (‘wet’) age-related macular degeneration (ARMD) is the major cause of blindness in Western developed countries. Treatments aimed at preserving vision are already available and new compounds are under development. Micro-economics information will be pivotal to justifying forthcoming investment. OBJECTIVE: This study sought to investigate the costs of exudative ARMD in patients who were actively treated at ophthalmology referral centres in three European countries: France, Germany and Italy. METHOD: This cross-sectional observational study was conducted in France, Germany and Italy in 2004. The following data were collected: ARMD description, visual acuity (VA), and the medical and non-medical resources used for ARMD in the preceding year. The economic perspective was that of society. ANOVA for cost variables estimated the impact of ARMD per eye, adjusted for sex and age. Both hospital and ambulatory eye centres were included. Patients with exudative ARMD were stratified into four levels of severity using VA thresholds of 20/200 for the worst eye (WE) and 20/40 for the best eye (BE). The main outcome measure was medical and non-medical costs. RESULTS: 360 patients were included (females 60%; mean age 77 years; mean interval since diagnosis 2.3 years). The two groups with the greatest difference in severity of VA loss consisted of BE >or= 20/40, WE >or= 20/200 (27.2% of patients) and BE <20/40, WE <20/200 (25.5% of patients). Total cost was two-thirds medical and one-third non-medical. Total costs increased with ARMD severity and were 1.1-2 times greater for severe disease compared with less severe disease. Average medical costs (2004 values) in France were euro 3714, compared with euro 1810 in Germany and euro 2020 in Italy, and showed slight increases with ARMD severity. Non-medical costs were significantly higher for patients with severe disease and highest in Germany. CONCLUSION:
The impact of ARMD on costs was considerable and a positive correlation was found between total costs and ARMD severity. Differences among countries were partly explained by differences in customary care delivery.
Drugs Aging. 2008;25(3):255-68
Nutritional supplementation to prevent cataract formation.
Age-related cataract (ARC) is the leading cause of blindness in the world, particularly in developing countries. In contrast, cataract surgery has become the most frequent surgical procedure in people aged 65 years or older in the Western world, causing a considerable financial burden to the health care system. The development of cataracts is mainly an age-related phenomenon, although socioeconomic and lifestyle factors appear to influence their development, e.g. smoking has been found to directly influence ARC. A key role in the pathomechanism of the crystalline lens alteration is played by glucose metabolism and associated effected redox potential, which may induce oxidative damages. Aldose reductase blockers were able to prevent the development of diabetic cataracts in experimental studies, however clinical trials were interrupted due to unclear side effects. Other drugs with radical scavenging properties were effective in in vitro and in vivo experiments, but could not be proven to be efficient and safe in preclinical human trials. A number of epidemiological studies showed an increased risk of nuclear or cortical cataract in people with low blood levels of vitamin E. It is also known that the measured levels of ascorbic acid decline with increasing age in the lens. Beta-Carotin and other non-polar carotenoids seem to be missing and may therefore only play a minor role. Polarized carotenoid lutein and zeaxanthin are available in low concentrations and may therefore have some direct effects. The results of the present interventional studies are still controversial. While the Linxian studies indicated that the prevalence for nuclear cataract was reduced by the supplementation with retinol/zinc or vitamin C/molybdenum, the AREDS trial showed no effect of the antioxidant formulation on the development or progression of ARC. Again, while the REACT study demonstrated a statistically significant positive treatment effect 2 years after treatment for the US patients and for both subgroups (US & UK) after 3 years, no effect was observed in UK patients alone. In another US study, the Physician Health Study, no positive or negative effect of Beta-carotin was observed. Taken together, these studies suggest that any effect of antioxidants on cataract development is likely to be very small and probably is of no clinical or public health significance, thus removing a major rationale for ‘anticataract’ vitamin supplementation among health-conscious individuals.
Dev Ophthalmol. 2005;38:103-19
Cataract surgery and quality of life implications.
Cataract surgery in the developed world has undergone a revolution over the last 20 years. An operation which used to require a stay in hospital and long visual rehabilitation is now a quick day-case procedure with immediate benefits. As with any surgery there is an associated morbidity, but there is now the potential to provide cataract surgery at an earlier stage of cataract maturation and save patients from a period of severe visual impairment. This article reviews the new techniques available to measure the impact that cataracts have not only on a patient’s visual acuity but also their general physical health, function, cognition, and emotional well-being. New research is described that takes into account these more holistic tests and how they can be used to judge the best time to refer and operate on a patient with cataracts.
Clin Interv Aging. 2007;2(1):105-8
Intake of vitamin A and carotenoids from the Italian population—results of an Italian total diet study.
The present study focused on vitamin A and carotenoids (alpha-and beta-carotene, lutein and zeaxanthin, beta-cryptoxanthin, lycopene) daily intake from the Italian total diet. The input of some food groups (cereals, vegetables, fruits, milk and dairy, meat and meat products, fish) most responsible for major and minor contributions to the daily intake of these molecules was evaluated. Furthermore the contribution to the dietary intake of beta-carotene and lutein of the most consumed vegetables in the market basket of the Italian total diet (beets, brassica vegetables, carrots, chicory, courgette (zucchini), green beans, lettuce, peas, pepper, spinach, tomatoes) was also investigated. Vitamin A daily intake was 855 mg/person/day. The vegetables food group made the greatest contribution (37%), followed by the meat and meat products food group (23%). The Italian total diet provided 14.3 mg/person/day of carotenoids; lycopene was the highest (7.4 mg/day), followed by lutein + zeaxanthin (4 mg/day), beta-carotene (2.6 mg/day), alpha-carotene (0.15 mg/day), and beta-cryptoxanthin (0.17 mg/day). Carrots and tomatoes were the main sources of beta-carotene in the diet, otherwise the daily consumption of leafy vegetables (spinach, beets, lettuce) made the main contribution to lutein + zeaxanthin daily intake.
Int J Vitam Nutr Res. 2006 May;76(3):103-9
Lutein and zeaxanthin and their potential roles in disease prevention.
Lutein and zeaxanthin are xanthophyll carotenoids found particularly in dark-green leafy vegetables and in egg yolks. They are widely distributed in tissues and are the principal carotenoids in the eye lens and macular region of the retina. Epidemiologic studies indicating an inverse relationship between xanthophyll intake or status and both cataract and age-related macular degeneration suggest these compounds can play a protective role in the eye. Some observational studies have also shown these xanthophylls may help reduce the risk of certain types of cancer, particularly those of the breast and lung. Emerging studies suggest as well a potential contribution of lutein and zeaxanthin to the prevention of heart disease and stroke. Even as the evidence for a role of lutein and zeaxanthin in disease prevention continues to evolve, particularly from human studies directed to their bioavailability, metabolism, and dose-response relationships with intermediary biomarkers and clinical outcomes, it is worth noting that recommendations to consume foods rich in xanthophylls are consistent with current dietary guidelines.
J Am Coll Nutr. 2004 Dec;23(6 Suppl):567S-587S
Application of nutrigenomics in eye health.
This paper reviews recent findings on the implication of nutritional and genetic factors in age-related eye diseases: age-related macular degeneration (AMD; a degenerative disease of the retina) and cataract (opacification of the lens). Because of direct exposure to light, the eye is particularly sensitive to oxidative stress. Antioxidants, such as vitamin E, C or zinc, clearly have a protective effect in AMD and probably in cataract. In addition, two carotenoids, lutein and zeaxanthin, may play a more specific role in the eye: they accumulate in the retina, where they form the macular pigment, and in the lens. Their role is probably to filter out phototoxic blue light and to quench singlet oxygen. Finally, docosahexaenoic acid (an omega-3 polyunsaturated fatty acid) is particularly important for the retina, where it exerts structural, functional and protective actions. Besides, these diseases are strongly influenced by genetics, as demonstrated by familial and twin studies. The apolipoprotein E4 allele is associated with a reduced risk of AMD, while an association of AMD with complement factor H polymorphism has recently been demonstrated. Nutrigenomics, by studying the interactions between genetic variability and nutritional factors, represents a new challenge in order to account for interindividual variations in disease susceptibility. Such potential interactions are presented.
Forum Nutr. 2007;60:168-75
Lutein and zeaxanthin dietary supplements raise macular pigment density and serum concentrations of these carotenoids in humans.
Age-related macular degeneration (AMD) is thought to be the result of a lifetime of oxidative insult that results in photoreceptor death within the macula. Increased risk of AMD may result from low levels of lutein and zeaxanthin (macular pigment) in the diet, serum or retina, and excessive exposure to blue light. Through its light-screening capacity and antioxidant activity, macular pigment may reduce photooxidation in the central retina. Lutein supplements, at 30 mg/d, were shown previously to increase serum lutein and macular pigment density in two subjects. In this study, we compared the effects of a range of lutein doses (2.4- 30 mg/d), as well as a high zeaxanthin dose (30 mg/d), on the serum and macular pigment in a series of experiments. Serum carotenoids were quantified by HPLC. Macular pigment densities were determined psychophysically. Serum lutein concentrations in each subject reached a plateau that was correlated with the dose (r = 0.82, P < 0.001). Plateau concentrations ranged from 2.8 x 10(-7) to 2.7 x 10(-6) mol/L. Zeaxanthin was less well absorbed than an equal lutein dose, resulting in plateaus of approximately 5 x 10(-7) mol/L. The rate of increase in macular pigment optical density was correlated with the plateau concentration of carotenoids in the serum (r = 0.58, P < 0.001), but not with the presupplementation optical density (r = 0.13, P = 0.21). The mean rate of increase was (3.42 +/- 0.80) x 10(5) mAU/d per unit concentration (mol/L) of carotenoids in the serum. It remains to be demonstrated whether lutein or zeaxanthin dietary supplements reduce the incidence of AMD.
J Nutr. 2003 Apr;133(4):992-8
Lycopene and beta-carotene decompose more rapidly than lutein and zeaxanthin upon exposure to various pro-oxidants in vitro.
Major carotenoids of human plasma and tissues were exposed to radical-initiated autoxidation conditions. The consumption of lutein and zeaxanthin, the only carotenoids in the retina, and lycopene and beta-carotene, the most effective quenchers of singlet oxygen in plasma, were compared. Under all conditions of free radical-initiated autoxidation of carotenoids which were investigated, the breakdown of lycopene and beta-carotene was much faster than that of lutein and zeaxanthin. Under the influence of UV light in presence of Rose Bengal, by far the highest breakdown rate was found for beta-carotene, followed by lycopene. Bleaching of carotenoid mixtures mediated by NaOCl, addition of azo-bis-isobutyronitril (AIBN), and the photoirradiation of carotenoid mixtures by natural sunlight lead to the following sequence of breakdown rates: lycopene > beta-carotene > zeaxanthin > lutein. The slow degradation of the xanthophylls zeaxanthin and lutein may be suggested to explain the majority of zeaxanthin and lutein in the retina of man and other species. In correspondence to that, the rapid degradation of beta-carotene and lycopene under the influence of natural sunlight and UV light is postulated to be the reason for the almost lack of those two carotenoids in the human retina. Nevertheless, a final proof of that theory is lacking.
The retinal carotenoids zeaxanthin and lutein scavenge superoxide and hydroxyl radicals: a chemiluminescence and ESR study.
PURPOSE: Carotenoids are present in many biological systems, often decreasing the formation of products of oxidative damage to biological molecules. In the macula their concentration is so high that it has been believed that the yellow color filters out damaging blue light. Recent reports that dietary lutein reduces the risk of cataract in the eye lens suggested that the antioxidant action of carotenoids, which has been inferred from decreased oxidative damage, warranted further direct investigation. METHODS: Superoxide and hydroxyl radical scavenging by lutein and zeaxanthin (retinal carotenoids), beta-carotene, lycopene, lutein esters (from marigolds), and a commercial mixture of soy carotenoids were compared to scavenging by ascorbate and ascorbyl palmitate. Radical scavenging was measured with a chemiluminescent assay (luminol) and by electron spin resonance, ESR. Inhibitory concentrations, IC(50), were determined with the luminescent assay. RESULTS: All of the carotenoids scavenged both superoxide (in ESR 30-50% at 16.7 microM) and hydroxyl radicals (in ESR 50-70% at 16.7 microM, in a luminescent assay 90-99%). CONCLUSIONS: While crocin may be unable to scavenge superoxide, some of the other carotenoids do so quite effectively. The mixtures of 15,15’-cis and all-trans-carotenoids studied by ESR and luminescent assay scavenge both superoxide and hydroxyl radicals. Lycopene and beta-carotene both scavenge superoxide more effectively than the xanthophylls of the retina, zeaxanthin and lutein. All of the carotenoids examined scavenged the hydroxyl radicals more effectively than superoxide radicals. The predominant carotenoid in the fovea of the retina, zeaxanthin, scavenged hydroxyl radicals more effectively than the other retinal carotenoid, lutein. Possible mechanisms of radical scavenging by the carotenoids are discussed.
Mol Vis. 2006 Sep 30;12:1127-35
The macular xanthophylls.
The macular pigments are predominantly composed of three carotenoids: lutein, zeaxanthin, and meso-zeaxanthin. These carotenoids are concentrated and distributed in a selective manner. The properties of these pigments are further explored along with their methods of uptake, stabilization, and storage. The dual nature of these pigments as filters and antioxidants are elaborated upon in relation to their protective effects upon the macula, specifically in age-related macular degeneration. Evidence suggests that increased levels of macular pigment are correlated with a decreased risk of age-related macular degeneration. Many have sought to exploit this therapeutic relation. Studies reveal that oral supplementation with lutein and zeaxanthin can increase the levels of macular pigments in the retina and plasma. The effects of such supplementation on actual ocular function have yet to be fully addressed. New and standardized methods of assessing macular pigment density are discussed and future areas of research to further our understanding of macular xanthophylls as they pertain to age-related macular degeneration are highlighted.
Surv Ophthalmol. 2005 Mar-Apr;50(2):183-93