The putative role of lutein and zeaxanthin as protective agents against age-related macular degeneration: promise of molecular genetics for guiding mechanistic and translational research in the field.
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SUBMITTER: SanGiovanni JP
PROVIDER: S-EPMC3471204 | biostudies-literature | 2012 Nov
REPOSITORIES: biostudies-literature
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The putative role of lutein and zeaxanthin as protective agents against age-related macular degeneration: promise of molecular genetics for guiding mechanistic and translational research in the field.
SanGiovanni John Paul JP Neuringer Martha M
The American journal of clinical nutrition 20121010 5
Age-related macular degeneration (AMD) is the primary cause of vision loss in elderly people of western European ancestry. Genetic, dietary, and environmental factors affect tissue concentrations of macular xanthophylls (MXs) within retinal cell types manifesting AMD pathology. In this article we review the history and state of science on the putative role of the MXs (lutein, zeaxanthin, and meso-zeaxanthin) in AMD and report findings on AMD-associated genes encoding enzymes, transporters, ligan ...[more]
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Project description:Lutein and zeaxanthin (L/Z) are the predominant carotenoids which accumulate in the retina of the eye. The impact of L/Z intake on the risk and progression of age-related macular degeneration (AMD), a leading cause of blindness in the developed world, has been investigated in cohort studies and clinical trials. The aims of this review were to critically examine the literature and evaluate the current evidence relating to L/Z intake and AMD, and describe important food sources and factors that increase the bioavailability of L/Z, to inform dietary models. Cohort studies generally assessed L/Z from dietary sources, while clinical trials focused on providing L/Z as a supplement. Important considerations to take into account in relation to dietary L/Z include: nutrient-rich sources of L/Z, cooking methods, diet variety and the use of healthy fats. Dietary models include examples of how suggested effective levels of L/Z can be achieved through diet alone, with values of 5 mg and 10 mg per day described. These diet models depict a variety of food sources, not only from dark green leafy vegetables, but also include pistachio nuts and other highly bioavailable sources of L/Z such as eggs. This review and the diet models outlined provide information about the importance of diet variety among people at high risk of AMD or with early signs and symptoms of AMD.
| S-EPMC5331551 | biostudies-literature
Project description:IMPORTANCE:The Age-Related Eye Disease Study (AREDS) formulation for the treatment of age-related macular degeneration (AMD) contains vitamin C, vitamin E, beta carotene, and zinc with copper. The Age-Related Eye Disease Study 2 (AREDS2) assessed the value of substituting lutein/zeaxanthin in the AREDS formulation because of the demonstrated risk for lung cancer from beta carotene in smokers and former smokers and because lutein and zeaxanthin are important components in the retina. OBJECTIVE:To further examine the effect of lutein/zeaxanthin supplementation on progression to late AMD. DESIGN, SETTING, PARTICIPANTS:The Age-Related Eye Disease Study 2 is a multicenter, double-masked randomized trial of 4203 participants, aged 50 to 85 years, at risk for developing late AMD; 66% of patients had bilateral large drusen and 34% had large drusen and late AMD in 1 eye. INTERVENTIONS:In addition to taking the original or a variation of the AREDS supplement, participants were randomly assigned in a factorial design to 1 of the following 4 groups: placebo; lutein/zeaxanthin, 10 mg/2 mg; omega-3 long-chain polyunsaturated fatty 3 acids, 1.0 g; or the combination. MAIN OUTCOMES AND MEASURE:S Documented development of late AMD by central, masked grading of annual retinal photographs or by treatment history. RESULTS In exploratory analysis of lutein/zeaxanthin vs no lutein/zeaxanthin, the hazard ratio of the development of late AMD was 0.90 (95% CI, 0.82-0.99; P =?.04). Exploratory analyses of direct comparison of lutein/zeaxanthin vs beta carotene showed hazard ratios of 0.82 (95% CI, 0.69-0.96; P =?.02) for development of late AMD, 0.78 (95% CI, 0.64-0.94; P =?.01) for development of neovascular AMD, and 0.94 (95% CI, 0.70-1.26; P =?.67) for development of central geographic atrophy. In analyses restricted to eyes with bilateral large drusen at baseline, the direct comparison of lutein/zeaxanthin vs beta carotene showed hazard ratios of 0.76 (95% CI, 0.61-0.96; P =?.02) for progression to late AMD, 0.65 (95% CI, 0.49-0.85; P =?.002) for neovascular AMD, and 0.98 (95% CI, 0.69-1.39; P?=?.91) for central geographic atrophy. CONCLUSION AND RELEVANCE:The totality of evidence on beneficial and adverse effects from AREDS2 and other studies suggests that lutein/zeaxanthin could be more appropriate than beta carotene in the AREDS-type supplements. TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT00345176.
| S-EPMC4636082 | biostudies-literature
Project description:BackgroundSeveral genes implicated in high-density lipoprotein (HDL) metabolism have been reported to be associated with age-related macular degeneration (AMD). Furthermore, HDL transport the two carotenoids, lutein and zeaxanthin, which are highly suspected to play a key-role in the protection against AMD. The objective is to confirm the associations of HDL-related loci with AMD and to assess their associations with plasma lutein and zeaxanthin concentrations.MethodsAlienor study is a prospective population-based study on nutrition and age-related eye diseases performed in 963 elderly residents of Bordeaux, France. AMD was graded according to the international classification, from non-mydriatic colour retinal photographs. Plasma lutein and zeaxanthin were determined by normal-phase high-performance liquid chromatography. The following polymorphisms were studied: rs493258 and rs10468017 (LIPC), rs3764261 (CETP), rs12678919 (LPL) and rs1883025 (ABCA1).ResultsAfter multivariate adjustment, the TT genotype of the LIPC rs493258 variant was significantly associated with a reduced risk for early and late AMD (OR=0.64, 95%CI: 0.41-0.99; p=0.049 and OR=0.26, 95%CI: 0.08-0.85; p=0.03, respectively), and with higher plasma zeaxanthin concentrations (p=0.03), while plasma lipids were not significantly different according to this SNP. Besides, the LPL variant was associated with early AMD (OR=0.67, 95%CI: 0.45-1.00; p=0.05) and both with plasma lipids and plasma lutein (p=0.047). Associations of LIPC rs10468017, CETP and ABCA1 polymorphisms with AMD did not reach statistical significance.ConclusionThese findings suggest that LIPC and LPL genes could both modify the risk for AMD and the metabolism of lutein and zeaxanthin.
| S-EPMC3819249 | biostudies-literature
Project description:Supplementation with carotenoids is proposed to protect against age-related macular degeneration. There is, however, considerable variability in retinal macular pigment response, which may be due to underlying genetic variation. The purpose of this study was to determine whether genetic factors, which have been previously associated with cross-sectional macular pigment levels in the retina or serum lutein, also influence response to supplementation. To this end we conducted an association study in 310 subjects from the TwinsUK cohort between variants in 8 candidate genes and serum lutein and retinal macular pigment optical density (MPOD) levels before and after supplementation. Four variants were associated with MPOD response to supplementation (p < 0.05): rs11057841 (SCARB1), rs4926339 (RPE65), rs1929841 (ABCA1) and rs174534 (FADS1). We also confirmed previous associations between rs6564851 near BMCO1 (p < 0.001) and rs11057841 within SCARB1 (p = 0.01) and baseline measures of serum lutein; while the latter was also associated with MPOD response, none of the BMCO1 variants were. Finally, there was evidence for association between variants near RPE65 and ELOVL2 and changes in lutein concentration after supplementation. This study is the first to show association between genetic variants and response to carotenoids supplementation. Our findings suggest an important link between MP response and the biological processes of carotenoids transport and fatty acid metabolism.
| S-EPMC3819993 | biostudies-literature
Project description:Despite strong biological plausibility, evidence from epidemiologic studies and clinical trials on the relations between intakes of lutein and zeaxanthin and age-related macular degeneration (AMD) has been inconsistent. The roles of other carotenoids are less thoroughly investigated.To investigate the associations between intakes of carotenoids and AMD.Prospective cohort study, with cohorts from the Nurses' Health Study and the Health Professionals Follow-up Study in the United States. A total of 63,443 women and 38,603 men were followed up, from 1984 until May 31, 2010, in the Nurses' Health Study and from 1986 until January 31, 2010, in the Health Professionals Follow-up Study. All participants were aged 50 years or older and were free of diagnosed AMD, diabetes mellitus, cardiovascular disease, and cancer at baseline.Predicted plasma carotenoid scores were computed directly from food intake, assessed by repeated food frequency questionnaires at baseline and follow-up, using validated regression models to account for bioavailability and reporting validity of different foods, and associations between predicted plasma carotenoid scores and AMD were determined.We confirmed 1361 incident intermediate and 1118 advanced AMD cases (primarily neovascular AMD) with a visual acuity of 20/30 or worse by medical record review. Comparing extreme quintiles of predicted plasma lutein/zeaxanthin score, we found a risk reduction for advanced AMD of about 40% in both women and men (pooled relative risk comparing extreme quintiles?=?0.59; 95% CI, 0.48-0.73; P for trend?<?.001). Predicted plasma carotenoid scores for other carotenoids, including ?-cryptoxanthin, ?-carotene, and ?-carotene, were associated with a 25% to 35% lower risk of advanced AMD when comparing extreme quintiles. The relative risk comparing extreme quintiles for the predicted plasma total carotenoid index was 0.65 (95% CI, 0.53-0.80; P for trend?<?.001). We did not identify any associations of carotenoids, either as predicted plasma score or calculated intake, with intermediate AMD.Higher intake of bioavailable lutein/zeaxanthin is associated with a long-term reduced risk of advanced AMD. Given that some other carotenoids are also associated with a lower risk, a public health strategy aimed at increasing dietary consumption of a wide variety of fruits and vegetables rich in carotenoids may reduce the incidence of advanced AMD.
| S-EPMC5119484 | biostudies-literature
Project description:PurposeTo examine the association between xanthophyll intake and prevalent early age-related macular degeneration (AMD) using data from the Atherosclerosis Risk in Communities Study (n = 10,295). Potential effect modification by genetic polymorphisms and biomarkers of high-density lipoprotein (HDL) metabolism was explored.MethodsXanthophyll intake was assessed at visit 1 (1987-1989) using food frequency questionnaires. Prevalent early AMD was assessed at visit 3 (1993-1995) via retinal photographs. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for AMD by quintiles of xanthophyll intake, adjusted for age, sex, race, field center, and pack-years of smoking. To evaluate effect modification, the association between tertiles (T) of xanthophyll intake and AMD was stratified by complement factor H (CFH) rs1061170 and age-related maculopathy susceptibility 2 (ARMS2) rs10490924 genotypes, as well as by median cutpoints of HDL biomarkers.ResultsXanthophyll intake was not associated with AMD in the overall sample, Caucasians (n = 8257), or African-Americans (n = 2038). Exploratory analyses observed that the association between xanthophyll intake and AMD varied statistically significantly by CFH rs1061170 genotype among Caucasians (p for interaction = 0.045) but not African Americans. No interactions were observed between xanthophyll intake and ARMS2 rs10490924. Moreover, higher xanthophyll intake was associated with decreased odds of AMD among participants with lower HDL (OR = 0.79, 95% CI 0.57-1.09) but not higher HDL (p for interaction = 0.048).ConclusionXanthophyll intake was not associated with early AMD. Further studies to investigate this association by genetic susceptibility or variations in HDL metabolism are needed.
| S-EPMC6025894 | biostudies-literature
Project description:PurposeTo evaluate macular pigment response to carotenoid supplementation in glaucomatous eyes.DesignDouble-masked, randomized, placebo-controlled clinical trial, the European Nutrition in Glaucoma Management Study (ClinicalTrials.gov identifier, NCT04460365).ParticipantsSixty-two participants (38 men, 24 women) with a diagnosis of open-angle glaucoma were enrolled. Forty-two were randomized to receive the active supplement, 20 participants were allocated to placebo.MethodsMacular pigment optical density (MPOD) was measured by autofluorescence using the Heidelberg Spectralis scanning laser ophthalmoscope. Macular pigment optical density volume within the central 6° of retinal eccentricity as well as MPOD at 0.23°, 0.51°, 0.74°, and 1.02° were recorded at baseline and at 6-month intervals over 18 months. Visual function was assessed using visual acuity, mesopic and photopic contrast sensitivity under glare conditions, photo stress recovery time, microperimetry, and Glaucoma Activities Limitation 9 questionnaire. Advanced glaucoma module scans of retinal nerve fiber layer thickness and ganglion cell complex thickness over the central 6° of retinal eccentricity also were completed at each study visit.Main outcome measuresChange in MPOD after supplementation with 10 mg lutein, 2 mg zeaxanthin, and 10 mg meso-zeaxanthin or placebo over 18 months.ResultsA mixed-model repeated measures analysis of variance revealed a statistically significant increase in MPOD volume (significant time effect: F(3,111) = 89.31, mean square error (MSE) = 1656.9; P < 0.01). Post hoc t tests revealed a significant difference in MPOD volume at each study visit for the treatment group (P < 0.01 for all), but no change in the placebo group (P > 0.05 for all). A statistically significant increase in mesopic contrast sensitivity under glare conditions was noted at 18 months in the treatment group, but not placebo. No other structural or functional changes were observed. No serious adverse events were noted during the trial.ConclusionsMacular pigment can be augmented in glaucomatous eyes by supplementation with a formulation containing the carotenoids lutein, zeaxanthin, and meso-zeaxanthin. The greatest relative benefit was observed in those with the lowest baseline levels, but increases were noted across all participants and each retinal eccentricity. The potential benefits of MP augmentation for macular health in glaucoma merit further long-term evaluation.
| S-EPMC9562333 | biostudies-literature
Project description:PurposeA review of the role of the carotenoids, lutein and zeaxanthin, and their function in altering the pathogenesis of age-related macular degeneration (AMD).MethodsMedline and Embase search.ResultsRecent evidence introduces the possibility that lutein and zeaxanthin, carotenoids found in a variety of fruits and vegetables may protect against the common eye disease of macular degeneration. This potential and the lack to slow the progression of macular degeneration, has fueled high public interest in the health benefits of these carotenoids and prompted their inclusion in various supplements. The body of evidence supporting a role in this disease ranges from basic studies in experimental animals to various other clinical and epidemiological studies. Whilst some epidemiological studies suggest a beneficial role for carotenoids in the prevention of AMD, others are found to be unrelated to it. Results of some clinical studies indicate that the risk for AMD is reduced when levels of the carotenoids are elevated in the serum or diet, but this correlation is not observed in other studies. Published data concerning the toxicity of the carotenoids or the optimum dosage of these supplements is lacking.ConclusionAn intake of dietary supplied nutrients rich in the carotenoids, lutein and zeaxanthin, appears to be beneficial in protecting retinal tissues, but this is not proven. Until scientifically sound knowledge is available we recommend for patients judged to be at risk for AMD to: alter their diet to more dark green leafy vegetables, wear UV protective lenses and a hat when outdoors. Future investigations on the role of nutrition, light exposure, genetics, and combinations of photodynamic therapy with intravitreal steroid (triamcinolone-acetonide) injections hold potential for future treatment possibilities.
| S-EPMC305368 | biostudies-literature
Project description:Carotenoids are natural lipid-soluble antioxidants abundantly found as colorful pigments in fruits and vegetables. At least 600 carotenoids occur naturally, although about 20 of them, including β-carotene, α-carotene, lycopene, lutein, zeaxanthin, meso-zeaxanthin, and cryptoxanthin, are detectable in the human blood. They have distinct physiological and pathophysiological functions ranging from fetal development to adult homeostasis. β-carotene is a precursor of vitamin A that essentially functions in many biological processes including vision. The human macula lutea and eye lens are rich in lutein, zeaxanthin, and meso-zeaxanthin, collectively known as macular xanthophylls, which help maintain eye health and prevent ophthalmic diseases. Ocular carotenoids absorb light from the visible region (400-500 nm wavelength), enabling them to protect the retina and lens from potential photochemical damage induced by light exposure. These natural antioxidants also aid in quenching free radicals produced by complex physiological reactions and, consequently, protect the eye from oxidative stress, apoptosis, mitochondrial dysfunction, and inflammation. This review discusses the protective mechanisms of macular xanthophylls in preventing eye diseases such as cataract, age-related macular degeneration, and diabetic retinopathy. Moreover, some preclinical animal studies and some clinical trials are discussed briefly to understand carotenoid safety and efficacy.
| S-EPMC7692753 | biostudies-literature
Project description:The purpose of this meta-analysis was to evaluate the effects of lutein supplementation on macular pigment optical density (MPOD) in randomized controlled trials involving patients with age-related macular degeneration (AMD). A comprehensive search of the literature was performed in PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and Wan Fang database through December 2018. Nine randomized controlled trials involving 920 eyes (855 with AMD) were included. Meta-analysis suggested that lutein supplementation (10 or 20 mg per day) was associated with an increase in MPOD (mean difference (MD) 0.07; 95% confidence interval (CI) 0.03 to 0.10), visual acuity (MD 0.28; 95%CI 0.06 to 0.50) and contrast sensitivity (MD 0.26; 95%CI 0.22 to 0.30). Stratified analyses showed the increase in MPOD to be faster and greater with higher dose and longer treatment. The available evidence suggests that dietary lutein may be beneficial to AMD patients and the higher dose could make MPOD increase in a shorter time.
| S-EPMC6936877 | biostudies-literature