Lutein (20mg)

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.

BACKGROUND: Central serous chorioretinopathy (CSC) is characterized by a thickened and dysfunctional choroid which is accompanied by a serous detachment of the neural retina. The effects on the retina are usually self-limiting, although some people are left with irreversible vision loss due to progressive and permanent photoreceptor damage or atrophy of the retinal pigment epithelium (RPE). There has been a variety of interventions used in CSC, including, but not limited to, laser treatment, photodynamic therapy (PDT), and drug therapy with mineralocorticoid receptor antagonists or intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents. However, it is not known whether these treatments offer significant long-term advantages over observation or each other. At present, there is no evidence-based consensus on the management of CSC. OBJECTIVES: This is an update of a Cochrane review first published in 2015 where 25 studies with 1098 participants were included. Since then, many trials have been conducted and reports published. Our primary objective was to assess the comparative effectiveness of multiple interventions for CSC. The secondary objective was to provide the relative ranking of the interventions for CSC using network meta-analysis. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and three trial registries in 29 March 2024, together with reference checking. SELECTION CRITERIA: Randomized controlled trials (RCTs) that compared any intervention for CSC with any other intervention for CSC or control. DATA COLLECTION AND ANALYSIS: Two review authors (CL, LP) independently selected studies and extracted data. Our outcomes of interest were best corrected visual acuity (BCVA), recurrence of CSC, persistent CSC, contrast sensitivity, central retinal subfield thickness, quality of life, and adverse events. We used standard methodological procedures expected by Cochrane. We used Cochrane's statistical software, Review Manager, to perform pairwise analyses and Stata to perform network meta-analysis (NMA). For pairwise comparisons, we pooled data from studies using fixed or random-effects models if there were fewer or more than three

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

BACKGROUND: Dry Eye Disease (DED) significantly impacts global populations, causing discomfort and vision problems. This review explores the effects of lutein supplementation on DED symptoms and signs. METHODS: A systematic review was conducted following PRISMA guidelines, examining clinical trials from databases including PubMed, Web of Science, EMBASE, and the Cochrane Library. Six randomized controlled trials (RCTs) involving 584 subjects were included. Meta-analysis was not conducted due to heterogeneity in study designs, dosages, and outcome measures. RESULTS: Lutein dosages ranged from 3 mg/day to 20 mg/day, with treatment durations from 4 to 12 weeks. Improvements were observed in subjective symptoms, with significant reductions in Ocular Surface Disease Index (OSDI) scores in some studies. Objective measures also showed positive results: tear break-up time (TBUT) increased significantly in some trials. However, other studies reported no significant differences between treatment and control groups, reflecting heterogeneity in outcomes. Schirmer's test and corneal-conjunctival staining results varied, with some showing significant improvements and others not. CONCLUSIONS: Lutein supplementation may benefit DED patients by improving symptoms and tear film stability. However, due to study heterogeneity, larger, well-designed RCTs are needed to establish standardized dosing and confirm these findings. © 2024 The Author(s). Published by IMR Press.

Exposure to ultraviolet (UV) radiation is a significant risk factor for sunburn (solar erythema) and skin cancer. Current treatments focus primarily on symptom relief, making the need for new therapeutic approaches urgent. Xanthophylls, a class of natural pigments with antioxidant and anti-inflammatory properties, show promise in the management of UV burns. This review aimed to systematically analyze the potential of xanthophylls for the management of UV burns, evaluating their efficacy in clinical and experimental studies. A literature review was performed following the PRISMA guidelines. Searches were conducted in the PUBMED, Virtual Health Library and EMBASE databases for eligible articles, using combinations of keywords such as astaxanthin, lutein, fucoxanthin and their effects on burns. Three independent reviewers conducted the search and selection of studies with inclusion criteria that addressed the use of xanthophylls in the treatment of burns, their mechanisms of action, pathophysiology and therapeutic approaches. Systematic reviews, letters, conference abstracts and case reports were excluded, considering only articles published in English. The articles were pre-selected by reading titles and abstracts, and the pre-selected studies were read in full for the final selection. Xanthophylls with potential benefits were identified, highlighting lutein, astaxanthin and violaxanthin, which demonstrated antioxidant activity by reducing the generation of reactive oxygen species (ROS) and mitigating inflammatory responses in skin cells exposed to UV radiation. Furthermore, evidence suggests that these xanthophylls promote skin barrier function and accelerate healing, enhancing recovery from UV burns. In conclusion, this review suggests a promising role for xanthophylls in alleviating UV burn symptoms and promoting skin healing. However, further research, including in vivo studies and clinical trials, is needed to validate its therapeutic potential, determine the optimal dosage, and optimize its delivery for effective UV burn control.

Photoprotective effects of various nutritional components and supplements have been demonstrated in animal and in vitro studies. The objective of this systematic review is to assess the photoprotective effects of various dietary supplements. A systematic review of studies assessing dietary supplements on photoprotective outcomes was performed. Human studies were retrieved from PubMed, Embase, and Cochrane in February 2023. Supplement keywords included "dietary supplements," "vitamins," "minerals," "carotenoids," "lutein," "isoflavones," "polyphenols," "Polypodium leucotomos," "heliocare," "herbal medicine," "probiotics," "prebiotics," "astaxanthin," "rosmarinic acid," "botanical," and "herb," and outcome keywords included "photoprotection," "ultraviolet rays," UVA," "UVB," and "blue light." A total of 47 studies were included in the systematic review. Studied supplements included carotenoids, polyphenols, Polypodium leucotomos (PL), melon concentrate, vitamins, coenzyme Q, squalene, and omega-3 and omega-6 fatty acids. Some studies evaluated mixed supplementation and incorporated other active ingredients such as selenium and probiotics. The greatest evidence of photoprotection exists for polyphenols, carotenoid-based, and PL supplementation. While flavanol supplementation exhibited dose-dependency, dose-dependency could not be consistently demonstrated for polyphenol supplementation. The weakest evidence exists for photoprotective effects of isolated vitamin or coenzyme Q supplementation. Dietary supplements may promote enhanced photoprotection, although current evidence is limited by small sample size and short duration. Supplementation with photoprotective active ingredients may be especially favorable for individuals with predisposed ultraviolet sensitivity, such as those with polymorphic light eruption. Future research is necessary to determine optimal dosing and supplementation duration for intended photoprotective outcomes.

OBJECTIVES: Neurodegenerative diseases are defined by specific protein accumulation and anatomic vulnerability leading to neuronal loss. Some studies have shown that lutein may have an effect on neurodegenerative diseases. As most of the neurodegenerative diseases don't have certain cure and therapies focus on symptom control, Lutein may be a complementary treatment. Due to controversies in studies investigating lutein effect on neurodegenerative diseases, we decided to perform a systematic review on these studies. METHODS: A systematic search was carried out in the available databases. We used all MeSH terms and relevant keywords. Studies that reported relationship between lutein and any neurodegenerative disease were included. RESULTS: We found 278 studies. After removing duplicates, screening by titles and abstracts and excluding irrelevant papers, 17 articles were included in this study. Fourteen studies investigated Alzheimer's disease, 2 studies Parkinson's disease and 1 study Amyotrophic lateral sclerosis. 1/17 study found that high serum levels of lutein at baseline were associated with a lower risk of AD mortality and lutein effect on lipid profile have been investigated in 2/17 studies. Also, 1/17 study has been shown that high intake of lutein may reduce the risk of ALS progression. CONCLUSIONS: 4/17 studies confirm that lutein can improve cognitive function. 8/17 studies demonstrate a reduction in the progression of AD, and 2/17 studies indicate an improvement in lipid profiles. However, some studies did not find any significant associations. Additionally, there is a limited number of studies investigating the effects of lutein on other neurodegenerative diseases. © 2025 the author(s), published by De Gruyter, Berlin/Boston.

Background: due to the high incidence of liver disease and the severity of adverse outcomes, liver disease has become a serious public health problem, bringing a huge disease burden to individuals, families, and society. Most studies have shown significant differences in serum carotenoid content and dietary carotenoid intake between liver disease patients and non-liver disease patients, but some studies have reported contrary results. This paper aimed to systematically review and analyze all published epidemiological studies on carotenoids and liver disease to quantitatively assess the relationship between serum and dietary carotenoid concentrations and liver disease. Methods: by systematically searching PubMed, Web of Science, Scopus, Embase, and Cochrane databases according to pre-combined search terms from inception to July 23, 2024, 30 studies were found to meet the exclusion criteria. Finally, 3 RCT studies, 6 cohort studies, 11 case-control studies, 9 cross-sectional studies, and 1 RCT-combined cross-sectional study were included in the further analysis. Two reviewers independently scored the literature quality and extracted data, and the results were represented by the standard mean difference (SMD) with a 95% confidence interval. Cochran Q statistics and I2 statistics were used to evaluate statistical heterogeneity (defined as significant when P < 0.05 or I2 > 50%). When there was insignificant heterogeneity, a fixed effects model was selected; otherwise a random effects model was used. Publication bias was assessed by the Egger test. Results: pooled meta-analysis showed that serum α-carotene (SMD = -0.58, 95% CI (-0.83, -0.32), P < 0.001), β-carotene (SMD = -0.81, 95% CI (-1.13, -0.49), P < 0.001), and lycopene (SMD = -1.06, 95% CI (-1.74, -0.38), P < 0.001) were negatively correlated with the risk and severity of liver disease. However, no significant difference was observed between serum β-cryptoxanthin (SMD = 0.02, 95% CI (-0.41, 0.45), P = 0.92) and lutein/zeaxanthin (SMD = 0.62, 95% CI (-1.20, 2.45), P = 0.502). Dietary β-carotene intake (SMD = -0.22, 95% CI (-0.31, -0.13), P < 0.001) was negatively associated with the risk of liver disease. The Eg

PURPOSE: This systematic review studies the relationship between Macular Pigment Optical Density (MPOD) values and cognitive and visual function in childhood. METHODS: It included cross-sectional, observational studies or controlled clinical trials in humans between 0 and 18 years of age, analyzing MPOD values in 3 main databases: PubMed, Scopus and Web of Science. The study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations. RESULTS: Thirteen studies were included in this systematic review. The relationship of cognitive function, visual function and diverse variables with MPOD was analyzed in 4, 4 and 5 studies, respectively. The age of the participants ranged between premature infants to 12 years. Most of the studies used Heterochromatic Flicker Photometry (HFP) with macular densitometer to obtain MPOD values. MPOD values ranged between 0 (undetectable) to 0.66 ± 0.03 d.u. Only 4 articles studied the relationship between MPOD values and dietary intake of lutein and zeaxanthin using questionnaires about diet. CONCLUSIONS: Lutein and zeaxanthin accumulation plays an important role during the maturational stage and childhood development. Although cognitive function is more strongly correlated with MPOD values, the relationship with visual function remains unclear, and further studies are required to support this relationship.

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.

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

OBJECTIVES: Two infant formulas with unique combinations of 1,3-dioleoyl-2-palmitoyl-sn-glycerol sn2 palmitate, galactooligosaccharide, polydextrose, fructooligosaccharide, β-carotene, lutein, α-lactalbumin, osteopontin, and lactoferrin were evaluated for non-inferiority compared to a commercially available formula. METHODS: In a randomized, controlled, parallel-arm, double-blind, multicenter, non-inferiority study, eligible infants were enrolled to receive an experimental (BBN-001 [Part 1; N = 129], BBN-102 [Part 2; N = 117]) formula or commercial formula (Brand; N = 143) for 120 days (Clinical Trials.gov NCT03331276). Infants were considered eligible if they were healthy, term (≥ 37 and ≤ 42 weeks of gestation), singleton newborns, with a birth weight of at least 2,500 g, and no more than 14 postnatal days-of-age. Anthropometric growth, formula intake, gastrointestinal tolerance, and adverse events were measured throughout the study, and fecal soap fatty acids were measured at the end. The primary endpoint was weight gain at the end of the trial, with treatment groups to be considered non-inferior if their weight gain was > -3 g/d compared to the control group. RESULTS: Both experimental formulas were non-inferior to the Brand formula according to anthropometric outcomes. Formula intake, total adverse events, and stool frequency and consistency were similar to Brand formulas. Some measures of gassiness and fussiness improved in the experimental formulas (P < 0.05). Fecal calcium increased and fecal palmitic acid soaps decreased in both experimental formulas (all P ≤ 0.045), and total soap fatty acids were decreased in the BBN-102 group compared to the Brand group (P = 0.020). CONCLUSIONS: The experimental formulas were well tolerated and deemed non-inferior to those of a Brand formula. The experimental formulas improved some measures of gastrointestinal tolerance compared to standard commercially available infant formulas. TRIAL REGISTRATION: ClinicalTrials.gov NCT03331276. Copyright: © 2025 Fleming et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and r

PURPOSE: To assess the effect of a six-month lutein ester supplementation on children's choroidal thickness (CT). METHODS: This double-blind, randomized controlled trial recruited 180 children aged eight to twelve years in a school from April to May 2021. The follow-up was completed in November 2021. Participants were randomly assigned to the treatment group (n = 90, one sachet with 8 mg lutein ester) or the control group (n = 90, one placebo sachet). Each participant consumed one sachet daily orally for six months. Primary outcomes were between-group differences in changes in CT at six-month follow-up visits. RESULTS: The six-month mean subfoveal CT decrease was 1.16 (-3.32 to 5.63) µm for the treatment group and -8.92 (-13.43 to -4.41) µm for the control group, with a mean difference of 10.08 µm (95% confidence interval [CI], 3.68 to 16.47, P = 0.002, corrected P = 0.018). The six-month mean temporal 1 mm and temporal 1.5 mm CTs decrease were -2.83 (-9.63 to 3.96) µm and -1.24 (-9.64 to 7.15) µm for the treatment group and -16.76 (-24.20 to -9.33) µm and -15.77 (-22.67 to -8.88) µm for the control group, with mean differences of 13.93 µm (95% CI, 3.79-24.07, P = 0.007, corrected P = 0.030) and 14.53 µm (95% CI, 3.59-25.47, P = 0.010, corrected P = 0.030), respectively. The two groups were not significantly different in the other grids (all P > 0.05). CONCLUSIONS: Six-month lutein ester supplementation could effectively mitigate subfoveal and temporal choroidal thinning. TRANSLATIONAL RELEVANCE: Given lutein's favorable safety, affordability, and global availability, our study highlights its untapped potential as a promising, adjunctive nutritional strategy to support clinical efforts in myopia prevention and management.

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.

Central obesity poses a significant health threat. Lutein-rich fruits and vegetables may help manage obesity. Limited evidence suggests that lutein exerts health effects by inhibiting advanced glycation end products (AGEs), but data on its effects in centrally obese individuals are sparse. Thus, we aimed to investigate the effects of lutein supplementation in subjects with central obesity. A double-blind, randomized controlled trial was conducted involving patients with central obesity. Anthropometric indices, dietary intake, metabolic parameters, carotenoid and AGEs levels were compared between those receiving a 32-week intervention of 10 mg d-1 lutein and a placebo group. There were 117 patients randomly assigned in the analysis. Twenty-three patients were lost to follow-up. Both intention-to-treat analysis and the per-protocol analysis showed significant reductions in plasma total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, and malonaldehyde levels in the lutein supplementation group compared with the placebo group. Significant differences were also observed between the groups in plasma lutein, carboxyethyl lysine (CEL), carboxymethyl lysine (CML), methylglyoxal hydroimidazolone (MG-HI) levels and skin carotenoid index (all P < 0.05). The mean difference and 95% confidence interval were 0.12 [0.08 to 0.16] μg ml-1, -8.76 [-16.60 to -0.89] ng ml-1, -72.3 [-134.0 to -10.9] ng ml-1, -233.9 [-429.0 to -36.8] ng ml-1 and 0.94 [0.56 to 1.31] a.u., respectively. Furthermore, changes in plasma lutein concentration were positively correlated with changes in the skin carotenoid index (r = 0.41, P < 0.001), and negatively correlated with changes in plasma CEL (r = -0.24, P = 0.018), (CML) (r = -0.21, P = 0.051, and MG-H1) (r = -0.25, P = 0.017). In conclusion, regular lutein intake can improve metabolic health in adults with central obesity by increasing plasma lutein concentrations, reducing oxidative stress, lowering plasma TC, LDL-C, and ApoB levels, and downregulating AGEs.

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.

This review provides a comprehensive overview of the modulatory actions of plant-derived constituents on membrane ion channels in various cell types. Among their diverse bioactivities, ion channel regulation-governing membrane excitability, signal transduction, and cellular homeostasis-has emerged as a critical mechanistic basis for their pharmacological effects. Twenty-four representative phytoconstituents are discussed and classified into five major categories based on their structural features: alkaloids, terpenoids, lignans and acetogenins, polyphenols, and other aromatic and conjugated compounds. Across these categories, the reviewed compounds exhibit distinct and often highly specific effects on the amplitude and gating kinetics of multiple ionic currents, including voltage-gated Na+ currents (INa), delayed-rectifier K+ currents (IK(DR)), M-type K+ currents (IK(M)), hyperpolarization-activated cation currents (Ih), erg-mediated K+ currents (IK(erg)), inwardly rectifying K+ currents, and Ca2+-activated K+ currents (IK(Ca)). Alkaloids predominantly suppress voltage-gated K+ currents, with notable exceptions such as aconitine, which alters the properties of both INa and IK(DR), thereby contributing to its proarrhythmic toxicity. Terpenoids, including cannabidiol, croton diterpenoids, lutein, thymol, and triptolide, exert multifaceted effects on IK(M), Ih, inwardly rectifying K+ currents, and Ca2+-activated K+ channels. Lignans and acetogenins, such as gomisin A, honokiol, sesamin, and squamocin, primarily modulate INa, Ih, and IK(Ca), with several compounds demonstrating strong links between ion-channel modulation and anti-neoplastic or neuroprotective actions. Polyphenolic compounds, including curcumin, eugenol, resveratrol, gastrodigenin, gastrodin, and pterostilbene, display diverse ion-channel targeting profiles, influencing multiple Na+ and K+ channel subtypes. Other aromatic or conjugated compounds, such as isoplumbagin, plumbagin, and verteporfin, regulate IK(erg) and IK(Ca), potentially contributing to both therapeutic efficacy and adverse effects. Collectively, the compound-specific modulation of current amplitude and gating kinetics offers valuable

While global nutrient insufficiency remains a critical health challenge, eggs have emerged as a potential solution due to their profile as an accessible and nutrient-dense food source. To quantitatively assess this potential for mitigating nutrient insufficiencies and guide the production of nutrient-enriched eggs, the study proposes the concept of egg nutriomics, establishing a comprehensive evaluation system with 35 indicators across seven nutritional dimensions (fatty acids, amino acids, vitamins, trace elements, pigments, antioxidant capacity, and dietary restriction factors). Methodologically, the system normalizes raw analytical data into standardized scores (0-100) using indicator-specific functional models, with weights rationally allocated based on the essentiality of the nutrients. These quantitative metrics are subsequently translated into intuitive results using visualization tools such as heatmaps and radar charts. This study applied this system to evaluate six commercial egg varieties (pasteurized, lutein-enriched, ω-3 enriched, animal welfare, low-cholesterol, and conventional cage eggs), profiling multidimensional nutrition that allows for the intuitive visualization of performance scores across distinct dimensions. These profiles extend beyond comprehensive evaluation by revealing specific quantitative advantages-such as ω-3 enriched eggs scoring 79 in the fatty acid dimension compared to 49 for conventional eggs-thus providing a reference to guide precision modulation as illustrated by a dietary ω-3 enrichment case study involving 200 laying hens. Building upon this foundation, the strategy empowers a shift from the sole pursuit of high yields to precision nutritional modulation. This multi-dimensional strategy bridges nutritional analysis with production control, facilitating the development of nutrient-dense eggs as a potential application to mitigate human malnutrition.

Over 85% of young women in the United States do not meet fruit and vegetable intake recommendations, placing them at risk for low antioxidant nutrient intake. Social health programming (SHP) can improve dietary intake of fruits and vegetables, but it is not known how SHP impacts serum levels of specific antioxidant nutrients. This observational cohort study assessed the effect of participation in SHP through Girls Inc., Omaha, on serum carotenoid, retinol, and tocopherol levels for 12-29-year-old women. Serum nutrient levels were measured using high-performance liquid chromatography and nutrient intake from diet was measured using three 24 h dietary recalls (ASA24®). Pearson chi-squared tests, Mann-Whitney U tests, and linear regressions were used to compare differences in nutritional status between SHP participants and non-participants. After adjustment for age and race/ethnicity, SHP participation was associated with significantly higher serum concentrations of total lycopene, δ-tocopherol, β-carotene, β-cryptoxanthin, lutein + zeaxanthin, and α-carotene. There were no between-group differences in average daily intake of carotenoids, vitamin A, or vitamin E after adjustment for race/ethnicity and age. These findings suggest that SHP may be a successful intervention to improve antioxidant nutritional status.

PURPOSE: To quantify macular pigment optical density (MPOD) in eyes with lamellar macular holes (LMHs) diagnosed according to contemporary optical coherence tomography (OCT) criteria and to evaluate its relationship with structural and functional parameters. METHODS: This prospective observational study screened 66 patients with unilateral LMH. All participants underwent comprehensive ophthalmic examination, spectral-domain OCT, and MPOD assessment using heterochromatic flicker photometry. Central foveal thickness (CFT), best-corrected visual acuity (BCVA) and OCT features were recorded. Paired inter-eye comparisons and linear mixed-effects regression analyses were performed. RESULTS: Forty-eight patients (48 LMH eyes and 48 contralateral healthy fellow eyes) were included. CFT was significantly reduced in LMH eyes compared with fellow eyes (177.2 ± 13.6 µm vs. 251.9 ± 5.9 µm; P < 0.0001). MPOD was lower in LMH eyes than in fellow eyes (0.508 ± 0.096 vs. 0.583 ± 0.097; P < 0.0001), and BCVA was worse (P < 0.0001). In multivariable analysis restricted to LMH eyes, MPOD was independently associated with age (β = -0.010 per year; 95% CI, -0.018 to -0.003; P = 0.0085) and BCVA (β = -0.494 per logMAR; 95% CI, -0.910 to -0.079; P = 0.0207), but not with CFT (P = 0.1438). In eyes with marked foveal thinning (CFT < 180 µm; n = 26), MPOD was reduced (P = 0.0065). CONCLUSIONS: MPOD is reduced in eyes with OCT-defined LMH and is associated with BCVA. As MP is preferentially localized within the Müller cell cone, altered MPOD may reflect foveal remodeling or MP redistribution related to EP.

BACKGROUND: Twin molar pregnancy (TMP) represents one of the most complex and high-risk entities within the spectrum of gestational trophoblastic disease. Characterized by the coexistence of a potentially viable fetus and molar trophoblastic tissue, TMP poses significant diagnostic, obstetric, and oncologic challenges. OBJECTIVE: To provide a structured diagnostic and management framework for TMP, integrating clinical, biochemical, imaging, genetic, and pathological findings to support early recognition and informed clinical decision-making. METHODS: This narrative review synthesizes contemporary evidence from cohort studies and diagnostic guidelines, focusing on the clinical presentation, imaging characteristics, genetic evaluation, and outcomes associated with TMP. RESULTS: Early diagnosis is frequently hindered by overlapping features with partial hydatidiform mole and placental mesenchymal dysplasia, particularly as placental components merge with advancing gestation. Common clinical manifestations include vaginal bleeding, uterine enlargement disproportionate to gestational age, and systemic complications related to markedly elevated human chorionic gonadotropin levels, such as early-onset preeclampsia, hyperthyroidism, and theca lutein cysts. Ultrasonography remains the primary diagnostic modality, while magnetic resonance imaging provides additional value in complex cases. Genetic testing, including invasive fetal karyotyping and post-pregnancy molecular analysis, is essential for accurate classification and counseling. Management should be individualized, prioritizing maternal safety while recognizing the potential for favorable perinatal outcomes in selected cases. Current evidence suggests that continuation of pregnancy does not independently increase the risk of postmolar gestational trophoblastic neoplasia, which appears to be primarily driven by intrinsic trophoblastic biology. CONCLUSION: TMP remains a rare but clinically challenging condition requiring a high index of suspicion and a multidisciplinary approach. Early diagnosis, individualized management, and rigorous postmolar surveillance are essential to optimize maternal and perinatal outcomes.

PURPOSE: To quantify the effects of lutein-containing supplementation on structural and functional visual outcomes in patients with age-related macular degeneration (AMD), with particular focus on disease stage and treatment exposure. METHODS: A meta-analysis of randomized, placebo-controlled trials was conducted. Nine RCTs involving 860 participants were included. Eligible studies evaluated oral lutein alone or in combination with zeaxanthin or epilutein and reported pre- and post-treatment measurements of macular pigment optical density (MPOD) and best-corrected visual acuity (BCVA). Random-effects models were applied to calculate pooled effect sizes using Hedges' g. Subgroup and meta-regression analyses were performed to explore stage-specific responses and dose-duration associations. RESULTS: Across the 9 RCTs, lutein-containing supplementation significantly improved MPOD (Hedges' g = -0.589, p < 0.001) and BCVA (Hedges' g = -0.827, p = 0.001). Improvements were predominantly observed in early-stage AMD, whereas no statistically significant benefit was detected in late-stage disease. Lutein monotherapy demonstrated greater visual benefit than combination regimens. Meta-regression analyses revealed significant positive associations between treatment effect and both supplementation duration and total lutein exposure. Contrast sensitivity and serum lutein concentrations also improved significantly. CONCLUSION: Lutein-based supplementation is associated with measurable structural and functional visual benefits in early-stage AMD. Treatment effects appear dose- and duration-dependent, while evidence in late-stage AMD remains limited. These findings support early intervention strategies and warrant further investigation into long-term therapeutic impact.

Individuals with an ileostomy (ileostomists) face unique physiological and dietary challenges that may impact on the bioavailability of phytochemicals, including carotenoids and (poly)phenols. In this study, we aimed to investigate habitual intake of phytochemical-rich foods and circulating concentrations of lutein, zeaxanthin, and phenolic compounds in ileostomists. In a cohort of 57 adults with an ileostomy (mean age 52.1 ± 15.0 years), habitual intake of phytochemical-rich foods and circulating concentrations of key carotenoids and phenolic compounds were markedly low. Mean intakes of fruit and vegetables (181.8 g day-1), lutein (0.3 mg day-1) and total (poly)phenols (524.4 mg day-1) were substantially below population averages, which was reflected in low plasma concentrations of lutein (0.14 ± 0.11 µM), zeaxanthin (0.04 ± 0.04 µM) and phenolic metabolites (0.34 ± 0.15 µM). Associations between dietary intake and circulating biomarkers were generally weak, although lutein intake was moderately correlated with plasma lutein (r = 0.52, P < 0.001). Circulating phytochemicals remained consistently low irrespective of time since surgery, highlighting the combined effects of dietary restriction and loss of colonic metabolism. These findings underscore the need to explore dietary reintroduction strategies and targeted supplementation to support long-term health in ileostomists.

BACKGROUND: Nutrition has an influence on the condition of our retina and appears to play a role in the complex, multifactorial pathogenesis of age-related macular degeneration (AMD). OBJECTIVES: This article summarizes the current epidemiological evidence on nutrition and AMD and discusses the intake of specific nutrients as well as nutritional supplements and their potential role in prevention and disease modification. MATERIAL AND METHODS: A narrative literature review of epidemiological studies, clinical trials and experimental work on the role of individual micronutrients, supplements and dietary patterns in AMD was carried out. RESULTS: There is evidence of a protective effect for individual nutrients such as lutein, zeaxanthin, zinc and omega‑3 fatty acids. The AREDS studies in particular show a reduction in the progression of intermediate AMD to late stages through defined supplements. In addition, a Mediterranean diet correlates with a reduced risk of AMD. Nevertheless, the study results remain contradictory in some cases, which is due to methodological limitations and the complex pathogenesis of AMD. DISCUSSION: Nutrition can potentially influence and reduce the risk for and progression of AMD. The existing literature underlines the potential of nutrition-based approaches, which must be further investigated in the future. Publisher: ZUSAMMENFASSUNG: HINTERGRUND: Die Ernährung hat einen Einfluss auf den Zustand unserer Netzhaut und scheint eine Rolle in der komplexen, multifaktoriellen Pathogenese der altersabhängigen Makuladegeneration (AMD) zu spielen. ZIELE DER ARBEIT: Diese Arbeit fasst die aktuelle epidemiologische Evidenz zu Ernährung und AMD zusammen und diskutiert die Einnahme von spezifischen Nährstoffen sowie Nahrungsergänzungsmitteln und deren potenzielle Rolle in der Prävention und Krankheitsmodifikation. MATERIAL UND METHODEN: Es wurde eine narrative Literaturrecherche zu epidemiologischen Studien, klinischen Studien und experimentellen Arbeiten zur Rolle einzelner Mikronährstoffe, Supplemente und Ernährungsmuster bei AMD durchgeführt. ERGEBNISSE: Für einzelne Nährstoffe wie Lutein, Zeaxanthin, Zink und Omega-3-Fettsäuren zeigen sich Hinwe

Lutein, a natural pigment with diverse biological activities, exhibits low water solubility, stability, and bioavailability, necessitating encapsulation in suitable emulsions to enhance its utilization. In this study, enzymatic hydrolysates from Nannochloropsis oculata and soybean lecithin (SL) were utilized in grape seed oil emulsions to improve the delivery efficiency of lutein. The results indicated that enzymatic hydrolysates of N. oculata, derived from alkaline protease, papain, or a combination of both enzymes, exhibited emulsifying and antioxidant properties, which were further enhanced by complexation with SL. These complexes facilitated the formation of uniform emulsions characterized by reduced particle size and increased interfacial protein content, as evidenced by alterations in protein structure. Among the various formulations, the emulsion prepared with alkaline protease hydrolysate and its SL complex exhibited superior stability. Consequently, lutein-loaded grape seed oil emulsions were produced with particle sizes ranging from 281.44 to 321.86 nm, a polydispersity index of less than 0.3, and interfacial protein content between 4.95 and 5.16 mg. These SL-complex emulsions also demonstrated improved oxidative stability under accelerated testing conditions, as indicated by lower peroxide and malondialdehyde values. Following in vitro digestion, the bioavailability of lutein in SL-complex emulsion reached 25.35%-28.13%, surpassing that of non-emulsified oil-phase lutein, thereby underscoring the potential of this delivery system for enhancing lutein stability and absorption. The findings further emphasize the dual functionality of microalgal protein hydrolysates as natural emulsifiers and antioxidants, with their efficacy synergistically enhanced by phospholipid complexation. © 2026 Institute of Food Technologists.

Yellow silk cocoons of Bombyx mori provide two distinct bioactive classes: the carotenoid silk lutein (SL) and sericin-derived oligopeptides (SDOs). Their comparative efficacy and mechanisms in promoting cognitive health remain uncharacterized. This study compared the neuroprotective and cognitive-enhancing effects of SL and SDOs through chronic oral administration in two rodent models: an amyloid-beta (Aβ25-35)-induced amnesia model in mice and a natural aging model in rats. Cognitive function was assessed using the Morris Water Maze (MWM) and Novel Object Recognition (NOR) tests, and underlying mechanisms were investigated via in vivo hippocampal long-term potentiation (LTP) and immunohistochemical analysis for apoptosis markers. Both SL and SDOs significantly ameliorated Aβ-induced deficits in recognition and spatial memory. Both substances enhanced spatial memory and LTP in old male rats in the natural aging paradigm, with efficacy comparable to that of donepezil (Don). This LTP-enhancing effect was sex-specific, being prominent in males but absent in aged females, although both sexes showed improved recognition memory. Critically, cognitive impairments in the Aβ model were not associated with significant neuronal apoptosis, and the protective effects appeared independent of anti-apoptotic pathways. In conclusion, SL and SDOs are potent cognitive-enhancing agents that mitigate memory deficits in acute neurotoxicity and chronic aging models. Their primary mechanism appears to be a robust enhancement of hippocampal synaptic plasticity rather than apoptosis prevention, positioning them as powerful synaptoprotective agents. These findings validate the potential to upcycle this agro-industrial byproduct into high-value nutraceuticals for promoting healthy brain aging.