Zeaxanthin

BACKGROUND: Lutein and zeaxanthin are nutrients with antioxidant properties found in the macula of the eye and brain tissue. They have been reported to play a role in reducing oxidative damage, especially in the eyes and possibly in other organ systems. Oxygen free radicals are one of the agents postulated to cause tissue damage in preterm infants, which leads to morbidities such as retinopathy of prematurity (ROP), intraventricular haemorrhage (IVH), and necrotising enterocolitis (NEC). Supplementation with lutein and zeaxanthin may reduce oxidative damage, hence reducing morbidity and mortality in preterm infants. OBJECTIVES: To assess the effectiveness of lutein and zeaxanthin supplementation in reducing morbidity and mortality in preterm infants. SEARCH METHODS: We conducted searches up to 17 December 2024 in CENTRAL, MEDLINE, Embase, and two trial registries. We also searched the reference lists of included studies, and related reviews and studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs), cluster-RCT, cross-over trials, and quasi-RCTs that compared lutein and zeaxanthin supplementation against placebo or no supplementation for preterm infants less than 37 completed weeks' postmenstrual age. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were the incidence of any stage of ROP, incidence of ROP stage 3 and above, incidence of visual impairment, and mortality assessed throughout the neonatal intensive care unit (NICU) stay. Secondary outcomes included the incidence of IVH, incidence of NEC, and any reported adverse effects. We used GRADE to assess the certainty of the evidence. MAIN RESULTS: We included five studies (666 preterm infants) that compared lutein and zeaxanthin supplementation versus control (placebo or no supplementation). All five studies were conducted in high-income countries (Italy and the USA). We did not find any studies comparing lutein or zeaxanthin separately versus placebo or no supplementation. Most of the studies had a low risk of bias in most key domains, such as allocation concealment and blinding. The evidence suggests that lutein and zeaxanthin supplementation proba

Antioxidants are bioactive molecules that function to scavenge free radicals and balance oxidative stress. Although all antioxidants can act as reactive oxygen species scavengers, their efficacy on eye health may vary. Moreover, the comparative effectiveness and potential additive effect between groups of antioxidants, hitherto, have not been systematically studied. A systematic review and network meta-analysis were conducted to investigate the comparative or additive effect of dietary antioxidant supplements on eye health. Four databases (PubMed, Embase, CINAHL, and Cochrane) were searched, and relevant randomized controlled trials were identified. Out of 60 articles selected for systematic review, 38 were included in the network meta-analysis, categorized into 8 distinct antioxidant-supplemented groups and placebo. All groups significantly increased macular pigment optical density and contrast sensitivity at low spatial frequency, whereas only the antioxidant mixture + lutein (L) + fatty acid combination exhibited significant improvements in visual acuity (hazard ratio = -0.15; 95% confidence interval: -0.28, -0.02) and L + zeaxanthin combination for photostress recovery time (hazard ratio = -5.75; 95% confidence interval: -8.80, -1.70). Especially, the L + zeaxanthin + fatty acid combination was ranked best for macular pigment optical density (surface under the cumulative ranking: 99.3%) and second best for contrast sensitivity at low spatial frequency (67.7%). However, these findings should be interpreted with caution due to low quality of evidence, primarily influenced by indirectness and potential publication bias. Overall, antioxidant supplementation was estimated to improve eye health parameters, whereas different combinations of antioxidants may also have varying effects on improving visual health from multiple perspectives. This study was registered at PROSPERO as CRD42022369250.

AIMS: The relationship between circulating Lutein and zeaxanthin (L/Z) concentrations, and plasma lipoproteins has been indicated by observational studies. However, the beneficial impact of L/Z administration on dyslipidemia are unclear. This meta-analysis aimed to investigate the effect of oral intake of L/Z on circulating total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), as well as high-density lipoprotein-cholesterol (HDL-C) levels. METHODS: We electronically assessed all eligible interventional studies through different electronic databases, including PubMed, Scopus, ISI -Web of Science, and Cochrane library until Jun 2021. After identifying the quality of each included randomized controlled trials, they were evaluated by assessing the risk-difference between treatment and control groups by pooling available data on net change of serum LDL-C, HDL-C, and Cholesterol. RESULTS: L/Z supplementation has null effect on circulating levels of TC (WMD: -3.82 95% CI: -13.83, 6.18; I-square: 85.2%), and LDL-C (WMD: -4.54; 95% CI: -11.5, 2.48; I-square: 83.9%). In contrast, L/Z treatment could significantly increase HDL-C levels in older adults (WMD: 4.06; 95% CI: 0.64, 7.48; I-square: 50.7%). CONCLUSION: L/Z administration could be an effective treatment for improving circulating HDL-C concentration in elderly adults.

Purpose: Age-related macular degeneration (AMD) is a neurodegenerative ophthalmic disease. The purpose of this systematic review (SR) and meta-analysis was to evaluate if dietary supplementation alone or in combinations might delay the progression of any of the stages of AMD. Methods: A SR and meta-analysis identifying cohort studies and randomized controlled trials (RCTs) evaluating the effect of supplements in patients diagnosed with AMD. PubMed, Scopus, Web of Science, CINAHL, and Cochrane were searched through 8th October 2021. Results: Twenty studies, examining 5634 participants ranging from 55 to 80 years, were included in the SR. Eight studies were selected for meta-analysis (414 and 216 subjects in the intervention and control groups). Lutein and zeaxanthin plus n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) supplementation showed significant improvements in best-corrected visual acuity (BCVA) (SMD: -1.99, 95% CI: -3.33, -0.65) compared to the control group. Multifocal electroretinogram results (mfERG) were significantly improved overall (SMD: 4.59, 95% CI: 1.75, 7.43) after lutein plus zeaxanthin supplementation. Conclusions: Combinations of lutein and zeaxanthin with n-3 LC-PUFA might be beneficial in preventing AMD progression and deterioration of visual function. Our results encourage initiating further studies with combinations of n-3 LC-PUFA, lutein, and zeaxanthin especially in early AMD patients.

AIM: Age-related macular degeneration (AMD) has become a predominant global health concern. The visual function of individuals with AMD seems to improve with dietary antioxidants. We assessed the efficacy of different antioxidants (carotenoids, zinc, vitamin E, and multivitamin) on visual function and the incidence of developing late AMD. METHODS: We searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials for related published studies. We considered randomized controlled trials (RCTs) comparing different nutrients. The main outcomes measurements included changes in visual acuity (VA), and the rate of developing late AMD. The network meta-analysis was registered on PROSPERO (CRD42020171288). RESULTS: We identified 13 studies, including 85321 individuals randomly assigned to different nutrients or placebo groups. In the network meta-analysis, we found that there was more risk of progression to late AMD in the multivitamin group than carotenoids and vitamin E groups (RR 0.45, 95% CI 0.32 to 0.65; RR 0.56, 95% CI 0.40 to 0.79; RR 0.42, 95% CI 0.26 to 0.67). The nutrients of zinc and carotenoids (Lutein/Zeaxanthin) ranked first and second and showed better improvement in VA. The efficacy of carotenoids (β-carotene) ranked first for delaying the progress of AMD among all of the four treatments. CONCLUSION: Taking multivitamin supplementation may not prevent the development of late AMD. The nutrient of zinc and carotenoids (lutein/zeaxanthin) supplementation were associated with better improvement in VA. Carotenoids (β-carotene) were the most likely to prevent the progression of late AMD.

Lutein, zeaxanthin, and meso-zeaxanthin are the only carotenoids found in the human macula and may have a role in visual function. These carotenoids are reported to protect the retina, and thus vision, as antioxidants and by acting as a blue light filter. Our objective was to determine a minimum concentration of lutein/zeaxanthin intake that is associated with a statistically significant and/or clinically important change in macular pigment optical density (MPOD) among adults with healthy eyes. We searched Ovid MEDLINE, CENTRAL, and the Commonwealth of Agriculture Bureau for English-language studies through to July 2020. Two reviewers screened results to identify studies that evaluated supplements or dietary sources of lutein/zeaxanthin on MPOD among adults with healthy eyes. One reviewer extracted data and assessed strength of evidence, which was confirmed by a second reviewer. Two independent reviewers assessed the risk of bias. Meta-analyses were stratified by total lutein/zeaxanthin dose. We included 46 studies (N = 3189 participants; mean age = 43 y; 42% male). There was no statistically significant change in MPOD among studies evaluating <5 mg/d of total lutein/zeaxanthin intake which primarily assessed dietary interventions for 3-6 mo (pooled mean difference, 0.02; 95% CI: -0.01 to 0.05). The pooled mean increase in MPOD was 0.04 units (95% CI: 0.02 to 0.07) among studies evaluating 5 to <20 mg/d of lutein/zeaxanthin and was 0.11 units (95% CI: 0.06 to 0.16) among studies evaluating ≥20 mg/d of lutein/zeaxanthin for 3-12 mo. MPOD increased with lutein/zeaxanthin intake, particularly at higher doses, among adults with healthy eyes. The effects of lutein/zeaxanthin intake at doses <5 mg/d or from dietary sources is less clear. Increased lutein/zeaxanthin intake can help with maintaining ocular health. Future research is needed to determine the minimum dose and duration of lutein/zeaxanthin intake that is associated with a clinically important change in MPOD or visual function. © The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.

The aim of this study was to perform a systematic review and meta-analysis on randomized controlled trials investigating the effects of carotenoids on selected inflammatory parameters. PubMed, SCOPUS, and Web of science were searched from inception until April 2021. The random-effect model was used to analyze data and the overall effect size was computed as weighted mean difference (WMD) and corresponding 95% of confidence interval (CI). A total of 26 trials with 35 effect sizes were included in this meta-analysis. The results indicated significant effects of carotenoids on C-reactive protein (CRP) (WMD: ‒0.54 mg/L, 95% CI: ‒0.71, ‒0.37, P < 0.001), and interleukin-6 (IL-6) (WMD: ‒0.54 pg/mL, 95% CI: ‒1.01, ‒0.06, P = 0.025), however the effect on tumor necrosis factor-alpha (TNF-α) was not significant (WMD: ‒0.97 pg/ml, 95% CI: ‒1.98, 0.03, P = 0.0.059). For the individual carotenoids, astaxanthin, (WMD: ‒0.30 mg/L, 95% CI: ‒0.51, ‒0.09, P = 0.005), lutein/zeaxanthin (WMD: ‒0.30 mg/L, 95% CI: ‒0.45, ‒0.15, P < 0.001), and β-cryptoxanthin (WMD: ‒0.35 mg/L, 95% CI: ‒0.54, ‒0.15, P < 0.001) significantly decreased CRP level. Also, only lycopene (WMD: ‒1.08 pg/ml, 95%CI: ‒2.03, ‒0.12, P = 0.027) led to a significant decrease in IL-6. The overall results supported possible protective effects of carotenoids on inflammatory biomarkers.

OBJECTIVE: Carotenoids (including zeaxanthin and lycopene) and phytosterols reportedly confer beneficial effects on metabolic profile and function, which is of clinical importance. Thus, we sought to review the saffron effects on waist circumstance (WC), fasting plasma glucose (FPG), and HA1C concentrations reported in Randomized Control Trials (RCTs). METHOD: A comprehensive systematic electronic search was performed in PubMed/MEDLINE, Embase, Google Scholar, Cochrane, Web of sciences, and SCOPUS to identify RCTs up to February 2019 without any language restrictions. The pooled weighted mean difference (WMD) calculated with DerSimonian-Laird random. PRISMA guidelines adhered to for this meta-analysis. RESULT: Nine articles with 12 arms containing 595 participants were included in this study. Our study found WC was significantly reduced (WMD: -2.18 cm, 95 % CI: -4.05, -0.32) and FPG (WMD: -6.54 mg/dl, 95 % CI: -10.22, -2.85) following saffron intervention. Subgroup analysis highlighted that FPG levels (WMD: -10.24 mg/dl, 95 % CI: -15.76, -4.72) reduced significantly when intervention duration was longer than twelve weeks. There was no significant effect on HA1C levels (WMD: -0.13 mg/dl, 95 % CI: -0.31, 0.04) following saffron intervention. CONCLUSION: In conclusion, the present study indicates beneficial effects on WC and FPG, following saffron supplementation.

BACKGROUND: Retinopathy of prematurity (ROP) is a multifactorial retinal disorder characterized by an abnormal vascular development of the retina of the preterm infants. Carotenoids are natural pigments that are synthesized by all plants and some microorganisms where they play a role in photoprotection and coloration. Lutein and zeaxanthin (L/Z) are two carotenoids identified as the major components of the macular pigment. Recently it has been suggested that lutein and its isomer zeaxanthin may act as antioxidant agents and that they may prevent ROP. OBJECTIVE: The primary objective of this study is to assess the safety and effectiveness of oral lutein in the prevention of retinopathy of prematurity in preterm neonates. STUDY DESIGN: We conducted a systematic search for randomized or quasi-randomized controlled trials without any language or publication year restriction. The studies have to recruit preterm neonates ≤32 completed weeks of gestation and to compare the administration of oral L/Z at any dosage or duration, versus placebo in order to prevent ROP. RESULT: Data from three RCT with a total of 406 participants failed to show any reduction in ROP incidence nor the risk of BPD, sepsis, NEC and mortality. It may reduce the number of transfusions but this result has to be assessed in a separate ad hoc trial.

BACKGROUND: Existing studies suggest that dietary vitamins and carotenoids might be associated with a reduced risk of age-related cataract (ARC), although a quantitative summary of these associations is lacking. OBJECTIVES: The aim of this study was to conduct a meta-analysis of randomized controlled trials (RCTs) and cohort studies of dietary vitamin and carotenoid intake and ARC risk. METHODS: The MEDLINE, EMBASE, ISI Web of Science, and Cochrane Library databases were searched from inception to June 2018. The adjusted RRs and corresponding 95% CIs for the associations of interest in each study were extracted to calculate pooled estimates. Dose-response relations were assessed with the use of generalized least-squares trend estimation. RESULTS: We included 8 RCTs and 12 cohort studies in the meta-analysis. Most vitamins and carotenoids were significantly associated with reduced risk of ARC in the cohort studies, including vitamin A (RR: 0.81; 95% CI: 0.71, 0.92; P = 0.001), vitamin C (RR: 0.80; 95% CI: 0.72, 0.88; P < 0.001), vitamin E (RR: 0.90; 95% CI: 0.80, 1.00; P = 0.049), β-carotene (RR: 0.90; 95% CI: 0.83, 0.99; P = 0.023), and lutein or zeaxanthin (RR: 0.81; 95% CI: 0.75, 0.89; P < 0.001). In RCTs, vitamin E (RR: 0.97; 95% CI: 0.91, 1.03; P = 0.262) or β-carotene (RR: 0.99; 95% CI: 0.92, 1.07; P = 0.820) intervention did not reduce the risk of ARC significantly compared with the placebo group. Further dose-response analysis indicated that in cohort studies the risk of ARC significantly decreased by 26% for every 10-mg/d increase in lutein or zeaxanthin intake (RR: 0.74; 95% CI: 0.67, 0.80; P < 0.001), by 18% for each 500-mg/d increase in vitamin C intake (RR: 0.82; 95% CI: 0.74, 0.91; P < 0.001), by 8% for each 5-mg/d increase in β-carotene intake (RR: 0.92; 95% CI: 0.88, 0.96; P < 0.001), and by 6% for every 5 mg/d increase in vitamin A intake (RR: 0.94; 95% CI: 0.90, 0.98; P < 0.001). CONCLUSIONS: Higher consumption of certain vitamins and carotenoids was associated with a significant decreased risk of ARC in cohort studies, but evidence from RCTs is less clear.

BACKGROUND: Adequate intake of carotenoids and vitamin E supports healthy aging, yet evidence is limited on whether multivitamin-multimineral (MVM) supplementation changes serum concentrations over time. OBJECTIVE: The aim of this investigation was to evaluate the effect of daily MVM supplementation among older adults on serum carotenoid and vitamin E concentrations over a 2-year period. DESIGN: The COcoa Supplement and Multivitamin Outcomes Study is a large-scale, randomized, placebo-controlled, 2 × 2 factorial trial, designed to test the effects of daily MVM and cocoa extract supplementation for chronic disease prevention. Participants completed semiannual questionnaires and provided optional biospecimen samples at baseline, 1-year, and 2-year follow-up. PARTICIPANTS AND SETTING: Between 2015 and 2020, US adults (women aged 65 years and older, men aged 60 years and older) without major cardiovascular disease or recent cancer were enrolled in the COcoa Supplement and Multivitamin Outcomes Study. This analysis included biospecimen substudy participants with blood samples provided at baseline and ≥1 follow-up timepoint (n = 400; 1 excluded due to unusable sample; final N = 399). INTERVENTION: Participants were randomized to receive daily MVM supplementation or a placebo, with or without cocoa extract. MAIN OUTCOME MEASURES: Changes in serum carotenoids and α-tocopherol concentrations were evaluated over the 2-year follow-up. STATISTICAL ANALYSES: Multivariable linear mixed models estimated changes in serum biomarker concentrations, comparing MVM with placebo, adjusting for covariates (age, sex, and cocoa extract intervention). RESULTS: Increases in serum carotenoids and α-tocopherol levels with MVM supplementation emerged at year 1 and persisted through year 2. MVM supplementation led to significantly higher serum concentrations of total carotenoids (percent change: 15.5%; 95% CI, 8.72 to 22.70), lutein (percent change: 17.17%; 95% CI, 7.53 to 27.66), beta carotene (percent change: 46.96%; 95% CI, 35.10 to 59.85), and α-tocopherol (percent change: 29.50%; 95% CI, 22.88 to 36.47) over 2 years compared with placebo. No significant differences were observed for lyco

BACKGROUND: Alzheimer disease (AD) prevention is a public health priority, yet the impact of dietary carotenoids on cognitive decline, particularly in apolipoprotein E (APOE) ε4 carriers, remains unclear. OBJECTIVES: The objective of this study was to examine whether the APOE ε4 genotype modifies the relationship between blood carotenoid concentrations and global cognition. METHODS: This study was conducted within the Mediterranean-Dietary Approaches to Stop Hypertension intervention for neurodegenerative delay trial, a 3-y randomized controlled trial comparing the effects of the Mediterranean-Dietary Approaches to Stop Hypertension intervention for neurodegenerative delay diet with the usual diet on global cognition in older adults. Eligible participants were ≥65 y, had a body mass index (in kg/m2) >25, a family history of AD, suboptimal diets, and a Montreal cognitive assessment score ≥22. The primary outcome was 3-y change in global cognitive function, assessed using a validated composite cognitive score converted to standardized units (SUs). Baseline plasma carotenoid concentrations were measured in a subgroup of participants (n = 442). Mixed-effects models were used to test the interaction between APOE ε4 status and baseline carotenoid concentrations on cognitive trajectories. RESULTS: The mean age was 70.0 y for noncarriers (n = 308) and 69.4 y for APOE ε4 carriers (n = 134). Among APOE ε4 carriers, a 1-unit increment in plasma total carotenoids at baseline was associated with higher global cognitive scores [β = 0.17 SU; 95% confidence interval (CI): 0.06, 0.28 SU; P = 0.009]. Similar associations were observed for β-carotene (β = 0.13 SU; 95% CI: 0.05, 0.21 SU; P = 0.001), α-carotene (β = 0.09 SU; 95% CI: 0.02, 0.15 SU; P = 0.008), lutein plus zeaxanthin (β = 0.14 SU; 95% CI: 0.04, 0.25 SU; P = 0.008), lycopene (β = 0.17 SU; 95% CI: 0.07, 0.28 SU; P = 0.005), and β-cryptoxanthin (β = 0.13 SU; 95% CI: 0.05, 0.21 SU; P = 0.03). Associations in noncarriers were weaker or nonsignificant. CONCLUSIONS: Higher plasma carotenoid concentrations were associated with slower cognitive decline in APOE ε4 carriers, potentially mitigating genetic risk. This trial was re

This study was conducted to evaluate and verify the improved bioavailability, as determined by the plasma concentrations of lutein and zeaxanthin, of the test supplement, XanMax® 2002 plus LuZeAbility™, as compared to the reference supplement, XanMax® 2002. For this purpose, this study was designed as a randomized, double-blind, two-group, two-period cross-over clinical trial research. A total of 24 male subjects participated in the clinical trial. They were randomized 1:1 into group 1 or 2 to consume two types of supplements in two separate periods. This study aimed to propose and demonstrate that the bioavailability and the plasma concentrations of lutein and zeaxanthin in the test supplement were significantly higher (110-132.8%) than in the reference supplement in all consecutive periods, such as 12 to 72 h after intake and at the time of maximum concentration. These results are expected to strengthen macular pigment optical density levels, ultimately providing a safe and effective intervention for comprehensively promoting eye health. Therefore, the findings of this study have significant pharmacokinetic implications and offer valid theoretical and practical insights for both academic research and the industrial development in the supplement market.

Neuroprotective nutrients including omega 3 fatty acid docosahexaenoic acid (DHA), choline, and carotenoids play an important role in infant brain structure and function; however, the effects of maternal nutrition on the infant brain are understudied. We leveraged data from our large randomized clinical trial among pregnant women to determine whether maternal nutrients including DHA, choline, lutein/zeaxanthin (L/Z) and egg intake (a food source of these nutrients) were related to infant brain function. Data from n = 241 maternal and infant dyads were included in this secondary analysis. Food frequency questionnaires (Diet History Questionnaire II) at 32 weeks' gestation were used to assess choline and carotenoid intake and a brief survey on egg consumption (# eggs consumed per week) was used to assess egg intake. Maternal red blood cell DHA status was measured at 32 weeks' gestation. Infant brain function was measured using high density electroencephalogram (EEG) to auditory (1 month of age) and visual (6 months of age) event-related potentials (ERP). At 1 month of age, maternal DHA status was associated with greater delta-band spectral power to the novel tone during the ERP. Choline, choline∗L/Z, L/Z∗DHA, and choline∗L/Z∗DHA were each related to power to the frequent tone during the ERP. At 6 months, choline, DHA status, and choline∗DHA were related to shorter latency to the novel visual stimulus. Choline∗L/Z and choline∗L/Z∗DHA were related to greater amplitude to the novel stimulus. Overall, maternal neuroprotective nutrients were related to several markers of infant brain function.

BACKGROUND/OBJECTIVES: Dry eye disease (DED) significantly impairs quality of life, affecting physical, social, and psychological well-being, as well as reducing workplace productivity. While lutein and zeaxanthin supplements have been shown to improve ocular health, existing research often overlooks the efficacy of lower dosages and shorter durations of supplementation. This study investigated the effects of combined supplementation with lutein, zeaxanthin, and elderberries in 110 voluntary participants through a randomized controlled trial. METHODS: Participants took 6 mg of lutein and 1 mg of zeaxanthin, along with 100 mg elderberry extract once daily for a duration of 20 days. Ocular health was assessed using the Ocular Surface Disease Index (OSDI), while immune status was evaluated with the Immune Status Questionnaire (ISQ). RESULTS: Results showed that combined supplementation significantly (p < 0.05) reduced the OSDI scores in the intervention group from 38.15 ± 11.14 to 18.26 ± 5.57, reflecting a 52.2% reduction. A similar trend was observed with the Visual Analog Scale (VAS), indicating significant (p < 0.05) improvement from 5.31 ± 1.62 to 6.73 ± 1.74, equivalent to a 26.7% improvement. Although the intervention group showed a 15.9% improvement in ISQ scores by the study's end, this was not significantly different from the placebo group, suggesting that higher dosages or longer durations may be needed to observe a meaningful effect. Additionally, findings from the Food Frequency Questionnaire revealed that the average dietary intake of lutein and zeaxanthin among participants was only 663.49 µg, equating to just 5.5% of the suggested optimal daily intake. This low consumption is concerning, as it is inversely correlated with the risk of ocular diseases. CONCLUSIONS: Collectively, these findings support the use of combined supplementation as an adjuvant approach to improving ocular health.

Background/Objectives: Age-related macular degeneration (AMD) is a leading cause of visual impairment in the elderly and is characterized by a multifactorial etiology. Emerging evidence points to the potential involvement of the gut-retina axis in AMD pathogenesis, prompting exploration into novel therapeutic strategies. This study aims to investigate the effects of some micronutrients (such as lutein and zeaxanthin) and saffron (as a supplement)-known for their anti-inflammatory properties-on ophthalmological and microbial parameters in neovascular AMD (nAMD) patients. Methods: Thirty naive nAMD patients were randomized to receive daily micronutrient supplementation alongside anti-VEGF (vascular endothelial growth factor) therapy, or anti-VEGF treatment alone, over a 6-month period, with comparisons made to a healthy control (HC) group (N = 15). Ophthalmological assessments, biochemical measurements, and stool samples were obtained before and after treatment. Gut microbiota (GM) characterization was performed using 16S rRNA sequencing, while short-chain fatty acids (SCFAs), medium-chain fatty acids (MCFAs), and long-chain fatty acids (LCFAs) were analyzed with a gas chromatography-mass spectrometry protocol. Results: Compared to HC, nAMD patients exhibited reduced GM alpha diversity, altered taxonomic composition, and decreased total SCFA levels, in addition to elevated levels of proinflammatory octanoic and nonanoic acids. Micronutrient supplementation was associated with improved visual acuity relative to the group treated with anti-VEGF alone, along with a decrease in the total amount of MCFAs, which are metabolites known to have adverse ocular effects. Conclusions: In conclusion, despite certain limitations-such as the limited sample size and the low taxonomic resolution of 16S rRNA sequencing-this study highlights compositional and functional imbalances in the GM of nAMD patients and demonstrates that micronutrient supplementation may help restore the gut-retina axis. These findings suggest the therapeutic potential of micronutrients in enhancing ocular outcomes for nAMD patients, underscoring the complex interaction between GM and ocular health.

BACKGROUND: Pistachios are a bioavailable source of the xanthophyll lutein. Along with zeaxanthin, these plant pigments are major components of macular pigment (MP) in the human retina. MP can be non-invasively measured and is referred to as MP optical density (MPOD). MPOD is modifiable with dietary interventions that include lutein and zeaxanthin (L/Z). Higher MPOD protects the eye from light damage and is positively associated with eye health. OBJECTIVES: This dietary intervention study aimed to evaluate the effect of pistachio consumption on MPOD. METHODS: This single-blinded, randomized controlled trial compared a 12-week pistachio intervention (2 oz/d) with usual diet (UD) on MPOD and serum L/Z in middle-aged to older healthy adults (n = 36) in a 1:1 randomization scheme. Participants were selected for habitually low L/Z intake and low baseline MPOD. MPOD was measured using heterochromatic flicker photometry at 4 retinal eccentricities during baseline, week 6, and week 12 study visits. Serum L/Z was analyzed using high-performance liquid chromatography. Primary statistical analysis was conducted on an intent-to-treat basis using repeated-measure analysis of variance. RESULTS: Compared with UD, MPOD of the participants in the pistachio intervention group (PIS) had significantly increased (P < 0.001) at all eccentricities over the initial 6-wk period. This increase was maintained at week 12. MPOD in the UD participants did not change during the 12-week period. Serum lutein concentration followed a similar pattern to MPOD; serum cis-lutein and zeaxanthin did not change in either group over the 12-wk intervention. CONCLUSIONS: The results of our study demonstrate that a dietary intervention with pistachios is efficacious in increasing MPOD in healthy adults selected for habitually low intake of L/Z and low baseline MPOD. This suggests that pistachio consumption could be an effective dietary strategy for preserving eye health. Future studies need to evaluate the generalizability of our findings to other populations. This trial was registered at clinicaltrials.gov as NCT05283941.

PURPOSE: To determine whether oral micronutrient supplementation slows geographic atrophy (GA) progression in age-related macular degeneration (AMD). DESIGN: Post hoc analysis of Age-Related Eye Disease Study (AREDS) and AREDS2, multicenter randomized placebo-controlled trials of oral micronutrient supplementation, each with 2 × 2 factorial design. PARTICIPANTS: A total of 392 eyes (318 participants) with GA in AREDS and 1210 eyes (891 participants) with GA in AREDS2. METHODS: The AREDS participants were randomly assigned to oral antioxidants (500 mg vitamin C, 400 IU vitamin E, 15 mg β-carotene), 80 mg zinc, combination, or placebo. The AREDS2 participants were randomly assigned to 10 mg lutein/2 mg zeaxanthin, 350 mg docosahexaenoic acid/650 mg eicosapentaenoic acid, combination, or placebo. Consenting AREDS2 participants were also randomly assigned to alternative AREDS formulations: original; no beta-carotene; 25 mg zinc instead of 80 mg; both. MAIN OUTCOME MEASURES: (1) Change in GA proximity to central macula over time and (2) change in square root GA area over time, each measured from color fundus photographs at annual visits and analyzed by mixed-model regression according to randomized assignments. RESULTS: In AREDS eyes with noncentral GA (n = 208), proximity-based progression toward the central macula was significantly slower with randomization to antioxidants versus none, at 50.7 μm/year (95% confidence interval [CI], 38.0-63.4 μm/year) versus 72.9 μm/year (95% CI, 61.3-84.5 μm/year; P = 0.012), respectively. In AREDS2 eyes with noncentral GA, in participants assigned to AREDS antioxidants without β-carotene (n = 325 eyes), proximity-based progression was significantly slower with randomization to lutein/zeaxanthin versus none, at 80.1 μm/year (95% CI, 60.9-99.3 μm/year) versus 114.4 μm/year (95% CI, 96.2-132.7 μm/year; P = 0.011), respectively. In AREDS eyes with any GA (n = 392), area-based progression was not significantly different with randomization to antioxidants versus none (P = 0.63). In AREDS2 eyes with any GA, in participants assigned to AREDS antioxidants without β-carotene (n = 505 eyes), area-based progression was not significantly diffe

43. Nutr Metab Cardiovasc Dis. 2024 Aug;34(8):1976-1983. doi: 10.1016/j.numecd.2024.05.009. Epub 2024 May 14. Lutein, zeaxanthin, and meso-zeaxanthin supplementation attenuates inflammatory cytokines and markers of oxidative cardiovascular processes in humans. Stringham NT(1), Green M(2), Roche

Lutein (Lut) and zeaxanthin (Zeax) are found in the blood and are deposited in the retina (macular pigment). Both are found in the diet in free form and esterified with fatty acids. A high intake and/or status is associated with a lower risk of chronic diseases, especially eye diseases. There is a large global demand for Lut in the dietary supplement market, with marigold flowers being the main source, mainly as lutein esters. As the bioavailability of Lut from free or ester forms is controversial, our aim was to assess the bioavailability of Lut (free vs. ester) and visual contrast threshold (CT). Twenty-four healthy subjects (twelve women, twelve men), aged 20-35 and 50-65 years, were enrolled in a cross-sectional study to consume 6 mg lutein/day from marigold extract (free vs. ester) for two months. Blood samples were taken at baseline and after 15, 40, and 60 days in each period. Serum Lut and Zeax were analysed using HPLC, and dietary intake was determined with a 7-day food record at the beginning of each period. CT, with and without glare, was at 0 and 60 days at three levels of visual angle. Lut + Zeax intake at baseline was 1.9 mg/day, and serum lutein was 0.36 µmol/L. Serum lutein increased 2.4-fold on day 15 (up to 0.81 and 0.90 µmol/L with free and ester lutein, respectively) and was maintained until the end of the study. Serum Zeax increased 1.7-fold. There were no differences in serum Lut responses to free or ester lutein at any time point. CT responses to lutein supplementation (free vs. ester) were not different at any time point. CT correlated with Lut under glare conditions, and better correlations were obtained at low frequencies in the whole group due to the older group. The highest correlations occurred between CT at high frequency and with glare with serum Lut and Lut + Zeax. Only in the older group were inverse correlations found at baseline at a high frequency with L + Z and with Lut/cholesterol and at a low frequency with Lut/cholesterol. In conclusion, daily supplementation with Lut for 15 days significantly increases serum Lut in normolipemic adults to levels associated with a reduced risk of age-related eye disease regardless of the ch

Prevention of neurodegeneration during aging, and support of optimal brain function throughout the lifespan, requires protection of membrane structure and function. We review the synergistic action of different classes of dietary micronutrients, as well as further synergistic contributions from exercise and stress reduction, in supporting membrane structure and function. We address membrane-associated inflammation involving reactive oxygen species (ROS) that produce immune regulators from polyunsaturated fatty acids (PUFAs) of membrane phospholipids. The potential of dietary micronutrients to maintain membrane fluidity and prevent chronic inflammation is examined with a focus on synergistically acting membrane-soluble components (zeaxanthin, lutein, vitamin E, and omega-3 PUFAs) and water-soluble components (vitamin C and various phenolics). These different classes of micronutrients apparently operate in a series of intertwined oxidation-reduction cycles to protect membrane function and prevent chronic inflammation. At this time, it appears that combinations of a balanced diet with regular moderate exercise and stress-reduction practices are particularly beneficial. Effective whole-food-based diets include the Mediterranean and the MIND diet (Mediterranean-DASH Intervention for Neurodegenerative Delay diet, where DASH stands for Dietary Approaches to Stop Hypertension).

In this work, the cytotoxicity of Beauvericin (BEA), lutein (LUT), zeaxanthin (ZEAX) and goji berries extract (GBE) rich in carotenoids, was investigated, as well as cytoprotective effects of these carotenoids against BEA induced-cytotoxicity on Caco-2 cells. Cytotoxicity was carried out using MTT and protein content (PC) assays during 24 and 48 h of exposure. Only BEA showed cytotoxic effect obtaining a reduction in cell proliferation range from 6.5 to 92.8%. Simultaneous combination of LUT and ZEAX with BEA slightly increased cell proliferation compared to BEA tested alone. LUT, ZEAX and GBE showed cytoprotective effects against cytotoxicity induced by BEA on Caco-2 cells. Pre-treatment assays showed the highest cytoprotection effect at the highest dose of BEA assayed (2.5 μM) in 29%, 31% and 35% for LUT, ZEAX and LUT + ZEAX, respectively; GBE showed a cytoprotection of 20%, for the same dose of BEA. The interaction between LUT, ZEAX and BEA studied by means of CI-isobologram method showed a synergism and antagaonism effect for all the combinations tested. These findings highlight that food containing high level of carotenoids, as goji berries, could contribute to reduce the toxicological risk that natural contaminant as BEA mycotoxin in diet can produce to the humans.

Despite the widespread use of the five major xanthophylls astaxanthin, β-cryptoxanthin, canthaxanthin, lutein, and zeaxanthin as dietary supplements, there have been no studies regarding their inhibitory effects on hepatic UDP-glucuronosyltransferases (UGTs). Here, we evaluated the inhibitory potential of these xanthophylls on the seven major human hepatic UGTs (UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, UGT2B7 and UGT2B15) in vitro by LC-MS/MS using specific marker reactions in human liver microsomes (except UGT2B15) or recombinant supersomes (UGT2B15). We also predicted potential dietary supplement-drug interactions for β-cryptoxanthin via UGT1A1 inhibition. We demonstrated that astaxanthin and zeaxanthin showed no apparent inhibition, while the remaining xanthophylls showed only weak inhibitory effects on the seven UGTs. β-Cryptoxanthin mildly inhibited UGT1A1, UGT1A3, and UGT1A4, with IC50 values of 18.8 ± 2.07, 28.3 ± 4.40 and 34.9 ± 5.98 μM, respectively. Canthaxanthin weakly inhibited UGT1A1 and UGT1A3, with IC50 values of 38.5 ± 4.65 and 41.2 ± 3.14 μM, respectively; and lutein inhibited UGT1A1 and UGT1A4, with IC50 values of 45.5 ± 4.01 and 28.7 ± 3.79 μM, respectively. Among the tested xanthophyll-UGT pairs, β-cryptoxanthin showed the strongest competitive inhibition of UGT1A1 (Ki, 12.2 ± 0.985 μM). In addition, we predicted the risk of UGT1A1 inhibition in vivo using the reported maximum plasma concentration after oral administration of β-cryptoxanthin in humans. Our data suggests that these xanthophylls are unlikely to cause dietary supplement-drug interactions mediated by inhibition of the hepatic UGTs. These findings provide useful information for the safe clinical use of the tested xanthophylls.

Lutein and its isomer zeaxanthin have gained considerable interest as possible nutritional ingredient in the prevention of age-related macular degeneration (AMD) in humans. Egg yolk is a rich source of these carotenoids. As an oxidative sensitive component, antioxidants such as α-tocopherol (T) might contribute to an improved accumulation in egg yolk. To test this, chickens were fed lutein esters (LE) with and without α-tocopherol as an antioxidant. After depletion on a wheat-soya bean-based lutein-poor diet for 21 days, laying hens (n = 42) were equally divided into three groups and fed the following diets for 21 days: control (basal diet), a LE group (40 mg LE/kg feed) and LE + T group (40 mg LE plus 100 mg T/kg feed). Eggs and blood were collected periodically. Carotenoids and α-tocopherol in yolk and blood plasma were determined by HPLC. Egg yolk was also analysed for total carotenoids using a one-step spectrophotometric method (iCheck((™)) ). Lutein, zeaxanthin, α-tocopherol and total carotenoids in egg yolk were highest after 14 days of feeding and decreased slightly afterwards. At the end of the trial, eggs of LE + T group contained higher amount of lutein (13.72), zeaxanthin (0.65), α-tocopherol (297.40) and total carotenoids (21.6) compared to the LE group (10.96, 0.55, 205.20 and 18.0 mg/kg, respectively, p < 0.05). Blood plasma values of LE + T group contain higher lutein (1.3), zeaxanthin (0.06) and tocopherol (20.1) compared to LE group (1.02, 0.04 and 14.90 mg/l, respectively, p < 0.05). In conclusion, dietary α-tocopherol enhances bioavailability of lutein reflecting higher content in egg yolk and blood plasma. Improved bioavailability might be due to increased absorption of lutein in the presence of tocopherol and/or a greater stability of lutein/zeaxanthin due to the presence of α-tocopherol as an antioxidant. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

Astaxanthin, β-cryptoxanthin, canthaxanthin, lutein and zeaxanthin, the major xanthophylls, are widely used in food, medicine, and health care products. To date, no studies regarding the inhibitory effects of these xanthophylls on the nine CYPs isozymes have been reported. This study investigated the reversible and time-dependent inhibitory potentials of five xanthophylls on CYPs activities in vitro. The reversible inhibition results showed that the five compounds had only a weak inhibitory effect on the nine CYPs. Lutein did not inhibit the nine CYPs activities. Astaxanthin weakly inhibited CYP2C19, with an IC₅₀ of 16.2 μM; and β-cryptoxanthin weakly inhibited CYP2C8, with an IC₅₀ of 13.8 μM. In addition, canthaxanthin weakly inhibited CYP2C19 and CYP3A4/5, with IC₅₀ values of 10.9 and 13.9 μM, respectively. Zeaxanthin weakly inhibited CYP3A4/5, with an IC₅₀ of 15.5 μM. However, these IC₅₀ values were markedly greater than the Cmax values reported in humans. No significant IC₅₀ shift was observed in the time-dependent inhibition screening. Based on these observations, it is unlikely that these five xanthophylls from the diet or nutritional supplements alter the pharmacokinetics of drugs metabolized by CYPs. These findings provide some useful information for the safe use of these five xanthophylls in clinical practice.

Aim of this study was to elucidate lutein oxidation products mediated through peroxyl radical inducer 2,2'-Azobis (2-methylpropionamidine) dihydrochloride (AAPH) and to study antioxidant and cytotoxic effects of oxidized lutein using liposome and HeLa cells. Lutein (20 μmol) with AAPH (5 mM) in liposome's was incubated at 37 °C in dark for 3 h, oxidized lutein products were characterized by LC-MS (APCI(+)) and studied for their free radical scavenging activity and cytotoxic effects in terms of cell viability, cellular glutathione, and malondialdehyde levels. AAPH mediated lutein fragmented ions were identified as 551 (M(+)+H(+)-H(2)O), 391 (M(+)+H(+)+O(2)-C(22)H(32)O) and 276 (M(+)+H(+)+O(2)-C(12)H(20)O) and its isomers as 13-Z lutein, 13-Z zeaxanthin, 13'-Z zeaxanthin and all-E zeaxanthin. Free radical scavenging activity of oxidized lutein was higher by 32.7% (IC(50), 2.64 μg) than lutein (IC(50), 5.28 μg). Oxidized lutein lowered the lipid peroxidation (21%), HeLa cells viability (22%) and glutathione levels (32%) than lutein. To conclude, the oxidized lutein may be highly reactive, since oxidation by AAPH results in peroxyl radical ions, which can react with conjugated polyene chain of lutein that could lead to higher antioxidant and cytotoxic effects on HeLa cells.

BACKGROUND: Dietary supplements are a product group of foods, which are meant to supplement the general nutrition with micronutrients and other substances. They are widely used in Germany. We evaluated the frequency of their use and of information requirements concerning dietary supplements in patients who contacted the independent drug information service at TU Dresden. PATIENTS AND METHODS: All inquiries from 2008 to 2010 were evaluated regarding information requirement about dietary supplements, the kind of products used and characteristics of patients using supplements. Sociodemographic characteristics, kind and number of drugs and dietary supplements as well as underlying diseases were recorded from the inquiring patients. RESULTS: 23.3 % of persons looking for advice used dietary supplements. The most frequently used product groups included vitamins and minerals (52.5 %) as well as plant extracts (14.0 %). Information requirements were especially high for plant extracts and for products containing glucosamine/chondroitin and lutein/zeaxanthin. Users of dietary supplements were exposed to a higher number of different products than non-users. CONCLUSIONS: Information requirements were primarily detected for products without clearly proven benefits or for supplements which are advertised to relieve certain diseases or symptoms although the product characteristics do not support such utilization. The frequency of use of dietary supplements among patients which already receive multiple medications substantiates the necessity to include dietary supplements in assessments of drug interactions and to scrutinize indications for supplement use. © Georg Thieme Verlag KG Stuttgart · New York.

PURPOSE: Although the exact pathogenesis of age-related macular degeneration (AMD) is not clear, most studies indicate a role for retinal pigment epithelial (RPE) cell damage and death caused by oxidative stress. The purpose of this study was to examine the potential protective effects of lutein, zeaxanthin, meclofenamic acid, and resveratrol on the acrolein-induced oxidative stress in human RPE cells. METHODS: Cultured human RPE R-50 cells were treated with acrolein at different concentrations and treatment times. The protective effects of lutein (100 microM), zeaxanthin (100 microM), meclofenamic acid (30 microM), and resveratrol (10 microM) were investigated by pretreatment with the above agents before toxicant exposure in acute toxicity models and cotreatment with the toxicant in chronic toxicity models. The synergistic effects of acrolein and hydrogen peroxide exposure were also studied. Fluorescent latex beads were used to assess the phagocytic function of the cells. RESULTS: Acrolein inhibited the phagocytic function of human RPE R-50 cells, and the inhibitory effects were time dependent. Pretreatment with lutein, zeaxanthin, meclofenamic acid, or resveratrol alleviated the inhibition of phagocytosis in the acute acrolein and combined acrolein/hydrogen peroxide toxicity models. Synergistic effects were seen between zeaxanthin and resveratrol or meclofenamic acid. Cotreatment with lutein, zeaxanthin, meclofenamic acid, or resveratrol showed a protective effect against the damage caused by 7-day acrolein exposure followed by hydrogen peroxide treatment. CONCLUSIONS: Our results indicated an inhibitory effect of compounds found in cigarette smoke on human RPE phagocytosis, and lutein, zeaxanthin, meclofenamic acid, and resveratrol each offered protection against this inhibition. Therefore, red wine polyphenol, resveratrol, might ameliorate acrolein-induced or age-related RPE degeneration, such as AMD.

The herbicide mesotrione inhibits a critical enzyme, phytoene desaturase, in plant carotenoid biosynthesis. Mesotrione is currently labeled for selective weed control in sweet corn ( Zea mays var. rugosa). Mesotrione applied alone, or in mixtures with the photosystem II inhibitor atrazine, acted to increase concentrations of kernel antheraxanthin, lutein, and zeaxanthin carotenoids in several sweet corn genotypes. Kernel lutein and zeaxanthin levels significantly increased 15.6% after mesotrione + atrazine early postemergence applications, as compared to the control treatment. It appears that mesotrione applications resulted in greater pools of kernel carotenoids once the sweet corn genotypes expressing moderate injury overcame the initial herbicidal photo-oxidative stress. This is the first report of herbicides directly up-regulating the carotenoid biosynthetic pathway in corn kernels, which is associated with the nutritional quality of sweet corn. Enhanced accumulation of lutein and zeaxanthin is important because dietary carotenoids function in suppressing aging eye diseases such as macular degeneration, now affecting 1.75 million older Americans.

The absorption of some carotenoids has been reported to be decreased by coingestion of relatively high concentrations of other carotenoids. It is unclear if such interactions occur among carotenoids during the digestion of plant foods. Current varieties of maize contain limited amounts of the pro-vitamin A (pro-VA) carotenoids beta-carotene (BC) and beta-cryptoxanthin (BCX) and relatively higher levels of their oxygenated metabolites lutein (LUT) and zeaxanthin (ZEA). Here, we examined if LUT and ZEA attenuate the bioaccessibility of pro-VA carotenoids at amounts and ratios present in maize. BC incorporation into bile salt mixed micelles during chemical preparation and during simulated small intestinal digestion of carotenoid-enriched oil was slightly increased when the concentration of LUT was sixfold or more greater than BC. Likewise, the efficiency of BC micellarization was slightly increased during simulated small intestinal digestion of white maize porridge supplemented with oil containing ninefold molar excess of LUT to BC. Mean efficiencies of micellarization of BC, BCX, LUT, and ZEA were 16.7, 27.7, 30.3, and 27.9%, respectively, and independent of the ratio of LUT plus ZEA to pro-VA carotenoids during simulated digestion of maize porridge prepared from flours containing 0.4-11.3 microg/g endogenous pro-VA carotenoids. LUT attenuated uptake of BC by differentiated cultures of Caco-2 human cells from medium-containing micelles in a dose-dependent manner with inhibition reaching 35% when the molar ratio of LUT to BC was 13. Taken together, these results suggest that the bioaccessibility of pro-VA carotenoids in maize is likely to be minimally affected by the relative levels of xanthophylls lacking pro-VA activity present in cultivars of maize.