Lutein + Zeaxanthin (AREDS2)

BACKGROUND: It has been proposed that antioxidants may prevent cellular damage in the retina by reacting with free radicals that are produced in the process of light absorption. Higher dietary levels of antioxidant vitamins and minerals may reduce the risk of progression of age-related macular degeneration (AMD). OBJECTIVES: The objective of this review was to assess the effects of antioxidant vitamin or mineral supplementation on the progression of AMD in people with AMD. SEARCH METHODS: We searched CENTRAL (2017, Issue 2), MEDLINE Ovid (1946 to March 2017), Embase Ovid (1947 to March 2017), AMED (1985 to March 2017), OpenGrey (System for Information on Grey Literature in Europe, the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 29 March 2017. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared antioxidant vitamin or mineral supplementation (alone or in combination) to placebo or no intervention, in people with AMD. DATA COLLECTION AND ANALYSIS: Both review authors independently assessed risk of bias in the included studies and extracted data. One author entered data into RevMan 5; the other author checked the data entry. We graded the certainty of the evidence using GRADE. MAIN RESULTS: We included 19 studies conducted in USA, Europe, China, and Australia. We judged the trials that contributed data to the review to be at low or unclear risk of bias.Nine studies compared multivitamins with placebo (7 studies) or no treatment (2 studies) in people with early and moderate AMD. The duration of supplementation and follow-up ranged from nine months to six years; one trial followed up beyond two years. Most evidence came from the Age-Related Eye Disease Study (AREDS) in the USA. People taking antioxidant vitamins were less likely to progress to late AMD (odds ratio (OR) 0.72, 95% confidence interval (CI) 0.58 to 0.90; 2445 participants; 3 RCTs; moderate-certai

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

IMPORTANCE: After the Age-Related Eye Disease Study 2 (AREDS2) study, the beta carotene component was replaced by lutein/zeaxanthin for the development of the revised AREDS supplement. However, it is unknown if the increased risk of lung cancer observed in those assigned beta carotene persists beyond the conclusion of the AREDS2 trial and if there is a benefit of adding lutein/zeaxanthin to the original AREDS supplement that can be observed with long-term follow-up. OBJECTIVE: To assess 10-year risk of developing lung cancer and late age-related macular degeneration (AMD). DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter epidemiologic follow-up study of the AREDS2 clinical trial, conducted from December 1, 2012, to December 31, 2018. Included in the analysis were participants with bilateral or unilateral intermediate AMD for an additional 5 years after clinical trial. Eyes/participants were censored at the time of late AMD development, death, or loss to follow-up. Data were analyzed from November 2019 to March 2022. INTERVENTIONS: During the clinical trial, participants were randomly assigned primarily to lutein/zeaxanthin and/or ω-3 fatty acids or placebo and secondarily to no beta carotene vs beta carotene and low vs high doses of zinc. In the epidemiologic follow-up study, all participants received AREDS2 supplements with lutein/zeaxanthin, vitamins C and E, and zinc plus copper. Outcomes were assessed at 6-month telephone calls. Analyses of AMD progression and lung cancer development were conducted using proportional hazards regression and logistic regression, respectively. MAIN OUTCOMES AND MEASURES: Self-reported lung cancer and late AMD validated with medical records. RESULTS: This study included 3882 participants (mean [SD] baseline age, 72.0 [7.7] years; 2240 women [57.7%]) and 6351 eyes. At 10 years, the odds ratio (OR) of having lung cancer was 1.82 (95% CI, 1.06-3.12; P = .02) for those randomly assigned to beta carotene and 1.15 (95% CI, 0.79-1.66; P = .46) for lutein/zeaxanthin. The hazard ratio (HR) for progression to late AMD comparing lutein/zeaxanthin with no lutein/zeaxanthin was 0.91 (95% CI, 0.84-0.99; P = .02) and comparing ω-3 fat

BACKGROUND: Age-related macular degeneration (AMD) is a degenerative condition of the back of the eye that occurs in people over the age of 50 years. Antioxidants may prevent cellular damage in the retina by reacting with free radicals that are produced in the process of light absorption. Higher dietary levels of antioxidant vitamins and minerals may reduce the risk of progression of AMD. This is the third update of the review. OBJECTIVES: To assess the effects of antioxidant vitamin and mineral supplements on the progression of AMD in people with AMD. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, one other database, and three trials registers, most recently on 29 November 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared antioxidant vitamin or mineral supplementation to placebo or no intervention, in people with AMD. DATA COLLECTION AND ANALYSIS: We used standard methods expected by Cochrane. MAIN RESULTS: We included 26 studies conducted in the USA, Europe, China, and Australia. These studies enroled 11,952 people aged 65 to 75 years and included slightly more women (on average 56% women). We judged the studies that contributed data to the review to be at low or unclear risk of bias. Thirteen studies compared multivitamins with control in people with early and intermediate AMD. Most evidence came from the Age-Related Eye Disease Study (AREDS) in the USA. People taking antioxidant vitamins were less likely to progress to late AMD (odds ratio (OR) 0.72, 95% confidence interval (CI) 0.58 to 0.90; 3 studies, 2445 participants; moderate-certainty evidence). In people with early AMD, who are at low risk of progression, this means there would be approximately four fewer cases of progression to late AMD for every 1000 people taking vitamins (one fewer to six fewer cases). In people with intermediate AMD at higher risk of progression, this corresponds to approximately 78 fewer cases of progression for every 1000 people taking vitamins (26 fewer to 126 fewer). AREDS also provided evidence of a lower risk of progression for both neovascular AMD (OR 0.62, 95% CI 0.47 to 0.82; moderate-certainty evidence) and geographic atrophy

INTRODUCTION: The macula is a pigmented area located at the centre of the retina, responsible for central, high-resolution colour vision. Previous research has demonstrated that oral carotenoid supplementation can enhance contrast sensitivity (CS) in European populations. This study aims to investigate whether carotenoid supplementation can also improve visual function in the Chinese population. METHODS AND ANALYSIS: The Contrast Sensitivity Vision (CSV) trial is a double-blind, randomised controlled trial conducted at the Zhongshan Ophthalmic Center in Guangzhou, China. 220 eligible Chinese adults will be randomised in a 1:1 ratio to receive either oral supplementation of 10 mg lutein, 10 mg meso-zeaxanthin and 2 mg zeaxanthin in a formula-based oil suspension (administered as one soft gel capsule) or a placebo oil soft gel capsule daily for 1 year. Participants in both groups will undergo ophthalmological study procedures including best-corrected visual acuity (BCVA), contrast sensitivity, optical coherence tomography, fundus photography and skin carotenoid examinations at baseline and at 3-month, 6-month and 12-month follow-up visits. Blood tests and a Dietary Carotenoid Screening Questionnaire will be administered at baseline and at the 12-month follow-up. Subjective visual function questionnaire interviews will be administered at baseline and at the 3-month, 6-month and 12-month follow-ups. The primary outcome will assess change in CS at 6 cycles per degree (cpd) over the 1-year study intervention. Secondary outcomes will examine CS at 6 cpd at the 3-month and 6-month follow-up, CS at other cpd, BCVA, subjective visual function and skin carotenoid levels as measured at baseline, 3-month, 6-month and 12-month follow-ups. ETHICS AND DISSEMINATION: The CSV trial was approved by the Ethics Committee of the Zhongshan Ophthalmic Center, Guangzhou, China (No. KYPJ141-4). Participants will have the opportunity to ask questions about the trial, and written informed consent will be obtained from all participants prior to their involvement in the study. Results will be disseminated through peer-reviewed publication and conference presentations. TRIAL REGISTRATION NUMB

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/OBJECTIVES: Nutritional supplementation has been proposed as a potential adjunct strategy in myopia prevention and control through antioxidative, anti-inflammatory, and extracellular matrix-regulating mechanisms. This systematic review aimed to evaluate randomized controlled trial (RCT) evidence on the effects of carotenoids, anthocyanins, polyunsaturated fatty acids, and combined nutraceutical formulations on refractive outcomes, axial length, macular pigment optical density (MPOD), visual function, and symptoms of visual fatigue. METHODS: The review was registered in PROSPERO (CRD420251149727) and conducted in accordance with PRISMA 2020 and AMSTAR-2 guidelines. PubMed, Web of Science, and Scopus were searched up to 5 August 2025. Eligible studies were RCTs involving individuals with myopia or at risk of myopia, comparing nutritional supplementation with placebo or active controls. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Cochrane RoB 2 tool. RESULTS: Nine RCTs were included. Carotenoids such as crocetin, lutein, zeaxanthin, and astaxanthin produced modest benefits, including improved MPOD, reduced visual fatigue, and-in one pediatric trial-slightly less axial elongation. Anthocyanin-rich extracts improved mesopic contrast sensitivity and subjective asthenopia. A combined carotenoid-polyphenol formulation enhanced accommodative facility. However, no consistent clinically meaningful reduction in myopia progression was observed. Trials were generally small, heterogeneous, and short in duration. CONCLUSIONS: Nutritional supplementation may improve visual function and retinal antioxidant status but lacks strong evidence for slowing myopia progression. Larger, long-term RCTs are needed before recommending supplementation for routine myopia management.

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.

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

Introduction Macular pigment (MP), consisting of lutein (L) and zeaxanthin (Z), is believed to provide retinal protection against photo-oxidative damage. The objective of the study was to evaluate the effect of lutein and zeaxanthin complex 5:1 (extracted from marigold flowers) supplementation on macular pigment optical density (MPOD), contrast sensitivity, and quality of sleep in healthy subjects who exposed themselves to an electronic gadget screen for a minimum of 8 hours every day. This study also aimed to assess the long-term safety of the supplement by administering it for 8 months in one of the groups. The study also assessed the retention effects of lutein and zeaxanthin on MPOD after discontinuation of supplementation. Methods The study was registered with the Clinical Trial Registry of India (CTRI/2022/12/048392). Subjects were screened as per the defined inclusion and exclusion criteria. Subjects aged 18-55 years with a screen time of at least 8 hours daily and MPOD values below 0.8 were recruited. The study, conducted at Narayana Nethralaya Super Specialty Eye Hospital, Bangalore, spanned from December 2022 to May 2024. This was a randomized, placebo-controlled, crossover study. Of the 96 volunteers screened for this study, 71 were recruited, and 60 completed the study. Subjects were divided into 3 groups, viz. A, B, and C. Group A received lutein 10mg and zeaxanthin 2mg twice daily for the first four months, had a wash-off period of 15 days, and continued with the same supplementation for the remaining four months. Group B received lutein 10mg and zeaxanthin 2mg twice daily for the first four months, had a wash-off period of 15 days, and then switched over to a placebo for the next four months. Group C received a Placebo for the first 4 months, had a wash-off period of 15 days, and then switched over to lutein 10mg and zeaxanthin 2mg for the next four months. All the subjects were given either, lutein and zeaxanthin complex-5:1 or placebo capsules as per the randomization chart prepared computationally. Subjects were analyzed for their MPOD values, contrast sensitivity scores, and quality of sleep. Intraocular pressure, retinal thickness, renal func

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: Age-related macular degeneration (AMD) is a leading cause of vision loss in older individuals, driven by a multifactorial etiology involving genetic, environmental, and dietary factors. Nutritional genomics, which studies gene-nutrient interactions, has emerged as a promising field for AMD prevention and management. Genetic predispositions, such as variants in CFH, C3, C2/CFB, APOE, and oxidative stress pathways, significantly affect the risk and progression of AMD. Methods: This narrative review synthesizes findings from randomized controlled trials and recent advances in nutritional genomics research. It examines the interplay between genetic predispositions and dietary interventions, exploring how personalized nutritional strategies can optimize AMD management. Results and Discussion: The AREDS and AREDS2 trials demonstrated that supplements, including vitamins C, E, zinc, copper, lutein, and zeaxanthin, can reduce the progression to advanced AMD. Nutritional interventions tailored to genetic profiles show promise: CFH risk alleles may enhance zinc supplementation's anti-inflammatory effects, while APOE variants influence the response to omega-3 fatty acids. Adjusting carotenoid intake, such as lutein and zeaxanthin, based on genetic susceptibility exemplifies emerging precision nutritional approaches. Ongoing research seeks to integrate nutrigenomic testing into clinical settings, enabling clinicians to tailor interventions to individual genetic profiles. Conclusions: Further studies are needed to assess the long-term effects of personalized interventions, investigate additional genetic variants, and develop tools for clinical implementation of nutrigenomics. Advancing these strategies holds the potential to improve patient outcomes, optimize AMD management, and pave the way for precision nutrition in ophthalmology.

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.

INTRODUCTION: Dry eye disease (DED) is multifactorial and characterized by a loss of tear film homeostasis that causes a cycle of tear film instability, tear hyperosmolarity, and inflammation. While artificial tears are the traditional mainstay of treatment, addressing the underlying pathophysiology could relieve symptoms and prevent progression. Increasing evidence indicates a role for oral nutritional supplementation in multiple ophthalmic diseases, including DED. Lutein, zeaxanthin, curcumin, and vitamin D3 have demonstrated protective and anti-inflammatory properties in ocular models. This prospective, randomized, double-blind, parallel, placebo-controlled study evaluated the efficacy and safety of a proprietary blend of lutein, zeaxanthin isomers, curcumin, and vitamin D3 (LCD) as a daily supplement in adult participants with DED. METHODS: Participants were randomized to receive one LCD supplement capsule (lutein 20 mg, zeaxanthin isomers 4 mg, curcumin 200 mg curcuminoids, and vitamin D3 600 IU) or placebo per day for 8 weeks (LCD, n=77; placebo, n=78). Primary outcomes were changes in tear volume (Schirmer's test) and ocular symptoms (Ocular Surface Disease Index [OSDI]). RESULTS: The study met its primary endpoints: the LCD group demonstrated significantly better Schirmer's test scores and improvement in overall OSDI score, versus placebo, at Day 56 (p<0.001 for both). Scores for total OSDI, and symptoms and vision domains, significantly improved by Day 14 for LCD versus placebo, (p<0.05 for all) and were maintained to Day 56 (p<0.001). In addition, the LCD group demonstrated significantly improved tear film break-up time (TBUT) and tear film osmolarity, versus placebo, by Day 56 (p<0.001), along with significant improvements in corneal and conjunctival staining (p<0.001 for both), and inflammation (matrix metalloproteinase-9; p<0.001 for each eye). Total Standard Patient Evaluation of Eye Dryness (SPEED) score, and scores for the frequency and severity domains, were significantly improved by Day 14 for LCD versus placebo (p<0.05 for all) and maintained to Day 56 (p<0.001). There was no difference between groups for artificial tear usage. The supplement

BACKGROUND AND AIMS: Systemic inflammation and oxidation are primary contributors to the development of atherosclerosis. Oxidation of low-density lipoprotein (LDL) particles within the vascular endothelium has been hypothesized to be an initial step in the formation of atherosclerotic plaques, with inflammatory cytokines serving as the signaling mechanism for concomitant macrophage activation. Supplementation with the antioxidative macular xanthophylls (lutein [L], zeaxanthin [Z], and meso-zeaxanthin [MZ]) has been shown to aid in the reduction of inflammatory physiologic responses; therefore, we hypothesized that in our study population, supplementation with these xanthophylls would facilitate a systemic reduction in markers of inflammation and cardiovascular lipid oxidation. METHODS AND RESULTS: In this double-blind placebo-controlled supplementation study, participants were randomly allocated to receive the active intervention containing L (10 mg) + MZ (10 mg) + Z (2 mg) or placebo (containing sunflower oil). Serum concentrations of carotenoids (assessed by HPLC), inflammatory cytokines (IL-6, IL-1β, TNF-α) and oxidized LDL (OxLDL; by solid-phase sandwich ELISA) were measured at baseline and at 6-months. Results showed that over the supplementation period, compared to placebo, the active group demonstrated statistically significant increases in serum concentrations of L, Z, & MZ (p < 0.05), reductions in inflammatory cytokines IL-1β (p < 0.001) and TNF-α (p = 0.003), as well as a corresponding reduction in serum OxLDL (p = 0.009). CONCLUSIONS: Our data show that L, Z, & MZ supplementation results in decreased serum IL-1β, TNF-α, and OxLDL. This suggests that these carotenoids are acting systemically to attenuate oxidative lipid products and inflammation, thus reducing their contribution to atherosclerotic plaque formation.

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

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.

INTRODUCTION: Supplementation with dietary neuro-pigments lutein (L) and zeaxanthin (Z) has been shown to improve many aspects of visual and cognitive function in adults. In this study, we tested whether a similar intervention could improve such outcomes in preadolescent children. METHODS: Sixty children (age range 5-12 years) were randomized in a 2:1 ratio in this double-blind, placebo-controlled clinical trial. Subjects were supplemented with gummies containing either a combination of 10 mg lutein and 2 mg zeaxanthin (LZ) or placebo for 180 days. Macular pigment optical density (MPOD) was the primary endpoint. The secondary endpoints included serum levels of L and Z, and brain-derived neurotrophic factor (BDNF), critical flicker fusion (CFF), eye strain and fatigue using visual analogue scales (VAS), Children's Sleep Habits Questionnaire-Abbreviated (CSHQ-A), and Creyos Health cognitive domains like attention, focus/concentration, episodic memory and learning, visuospatial working memory, and visuospatial processing speed. Safety was assessed throughout the study on the basis of physical examination, vital signs, clinical laboratory tests, and monitoring of adverse events. RESULTS: The LZ group showed significant increases in MPOD at all visits post-supplementation, with significant increases as early as day 42 compared to placebo. The LZ group showed significant increases in serum lutein levels, reduced eye strain and fatigue, and improved cognitive performance (focus, episodic memory and learning, visuospatial working memory) at days 90 and 180 compared to placebo. Further, the LZ group showed significant increases in processing speed (CFF), attention, visuospatial processing, and serum Z and BDNF levels on day 180 compared to placebo. No safety concerns were observed. CONCLUSIONS: Supplementing LZ resulted in increased MPOD levels, along with increased serum levels of L, Z, and BDNF. These changes were associated with improved visual and cognitive performances and reduction in eye strain and eye fatigue in the children receiving LZ gummies. The investigational product was safe and well tolerated. TRIAL REGISTRATION: http://ctri.nic.in/ Identifier CTRI/2022/