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Alzheimer's disease (AD) is characterized by impaired insulin/insulin-like growth factor-1 signaling in the hippocampus. Zeaxanthin and lutein, known for their antioxidant and anti-inflammatory properties, have been reported to protect against brain damage and cognitive decline. However, their mechanisms related to insulin signaling in AD remain unclear. This study investigated the efficacy and mechanisms of zeaxanthin, lutein, and resveratrol in modulating an AD-like pathology in an amyloid-β rat model. Rats were administered hippocampal infusions of 3.6 nmol/day amyloid-β (Aβ)(25-35) for 14 days to induce AD-like memory deficits (AD-CON). Normal control rats received Aβ(35-25) (Normal-CON). All rats had a high-fat diet. Daily, AD rats consumed 200 mg/kg body weight of zeaxanthin (AD-ZXT), lutein (AD-LTN), and resveratrol (AD-RVT; positive-control) or resistant dextrin as a placebo (AD-CON) for eight weeks. The AD-CON rats exhibited a higher Aβ deposition, attenuated hippocampal insulin signaling (reduced phosphorylation of protein kinase B [pAkt] and glycogen synthase kinase-3β [pGSK-3β]), increased neuroinflammation, elevated acetylcholinesterase activity, and memory deficits compared to the Normal-CON group. They also showed systemic insulin resistance and high hepatic glucose output. Zeaxanthin and lutein prevented memory impairment more effectively than the positive-control resveratrol by suppressing acetylcholinesterase activity, lipid peroxidation, and pro-inflammatory cytokines ( TNF-α , IL-1β ). They also potentiated hippocampal insulin signaling and increased brain-derived neurotrophic factor ( BDNF ) and ciliary neurotrophic factor ( CTNF ) mRNA expression to levels comparable to the Normal-CON rats. Additionally, zeaxanthin and lutein improved glucose disposal, reduced hepatic glucose output, and normalized insulin secretion patterns. In conclusion, zeaxanthin and lutein supplementation at doses equivalent to 1.5-2.0 g daily in humans may have practical implications for preventing or slowing human AD progression by reducing neuroinflammation and maintaining systemic and central glucose homeostasis, showing promise even when compared to the established neuroprotective compound resveratrol. However, further clinical trials are needed to evaluate their efficacy and safety in human populations.

Lutein is a naturally occurring carotenoid synthesized by plants and algae that has a beneficial effect on several biological processes and associated ailments. Its immediate application is in ophthalmology, where it significantly lowers the incidences of age-related macular degeneration (AMD). It also has anti-inflammatory action, treatment of diabetic retinopathy, and cataracts, and enhancement of visual contrast. To critically assess lutein biosynthesis, therapeutic applicability, and market research literature. We have discussed its theoretical frameworks, experimental evidence, limitations, as well as clinical trial results, and future research prospects. The literature for this review article was mined and compiled by collecting and analyzing articles from several databases, including ScienceDirect, Google Scholar, PubMed, Wiley Online Library, Patentscope, and ClinicalTrials.gov published until March 30, 2022. Patent publications were identified using the search terms like IC:(C07C67/56) AND EN_AB:(lutein) OR EN_TI:(lutein) OR EN_AB:(extraction) OR EN_TI:(process). According to the literature, lutein is an essential nutrient given that it cannot be synthesized in the human body and acts as an antioxidant, affecting AMD, diabetic retinopathy, Rheumatic diseases, inflammation, and cancer. Due to inadequate production and laborious extraction, lutein is expensive despite its high demand and applicability. Market research predicts a 6.3% compound annual growth rate for lutein by 2032. Optimizing lutein extraction for high yield and purity is necessary. Lutein has proven applicability in various ailments as well as cosmetics that can be developed as a candidate drug for various diseases discussed in the review., (© 2024 John Wiley & Sons Ltd.)

Background and Aim: Vascular dementia (VD) is a common type of dementia. This study aimed to evaluate the effects of low and high doses of lutein administration in bilateral-carotid vessel occlusion (2VO) rats., Experimental Procedure: The rats were divided into the following groups: the control, sham-, vehicle (2VO+V) groups, and two groups after 2VO were treated with lutein 0.5 (2VO+LUT-o.5) and 5mg/kg (2VO+LUT-5). The passive-avoidance and Morris water maze were performed to examine fear and spatial memory. The field-potential recording was used to investigate the properties of basal synaptic transmission (BST), paired-pulse ratio (PPR), as an index for measurement of neurotransmitter release, and long-term potentiation (LTP). The hippocampus was removed to evaluate hippocampal cells, volume, and MDA level., Result: Treatment with low and high doses improves spatial memory and LTP impairment in VD rats, but only the high dose restores the fear memory, hippocampal cell loss, and volume and MDA level. Interestingly, low-dose, but not high-dose, increased PPR. However, BST recovered only in the high-dose treated group., Conclusions: Treatment with a low dose might affect neurotransmitter release probability, but a high dose affects postsynaptic processes. It seems likely that low and high doses improve memory and LTP through different mechanisms., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Asadi nejad et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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/2022/05/042364., (© 2024. The Author(s).)

Background: Gastric cancer is characterized by high invasiveness, heterogeneity, and late diagnosis, leading to high incidence and mortality rates. It is a significant public health concern globally. Early prevention is crucial in reducing the occurrence of gastric cancer, and dietary prevention, particularly focusing on carotenoids, has been considered a convenient and effective approach. However, the association between carotenoid intake and gastric cancer incidence remains controversial., Methods: A systematic search was conducted in PubMed, Ovid Embase, Web of Science, and Cochrane databases from inception to January 5, 2023. Two reviewers independently screened search results, extracted relevant data, and evaluated study quality. Statistical analysis was performed using the "metan" command in STATA 16 software. Random-effects or fixed-effects models were chosen based on the magnitude of heterogeneity among studies., Results: This study included a total of 35 publications, consisting of 23 case-control studies and 12 cohort studies. Meta-analysis of case-control studies showed that alpha-carotene (OR = 0.71, 95% CI: 0.55-0.92), beta-carotene (OR = 0.62, 95% CI: 0.53-0.72), and lutein (OR = 0.82, 95% CI: 0.69-0.97) significantly reduced the risk of gastric cancer, while beta-cryptoxanthin (OR = 0.88, 95% CI: 0.75-1.04) and lycopene (OR = 0.86, 95% CI: 0.73-1.00) showed no significant correlation. Meta-analysis of cohort studies indicated no significant associations between any of the five carotenoids and gastric cancer incidence (alpha-carotene: RR = 0.81, 95% CI: 0.54-1.23; beta-carotene: RR = 0.86, 95% CI: 0.64-1.16; beta-cryptoxanthin: RR = 0.86, 95% CI: 0.64-1.16; lutein: RR = 0.94, 95% CI: 0.69-1.29; lycopene: RR = 0.89, 95% CI: 0.69-1.14)., Conclusions: The relationship between carotenoids and gastric cancer incidence may vary depending on the type of study conducted. Considering that evidence from cohort studies is generally considered stronger than evidence from case-control studies, and high-quality randomized controlled trials show no significant association between carotenoids and gastric cancer incidence, current evidence does not support the supplementation of carotenoids for gastric cancer prevention. Further targeted research is needed to explore the association between the two., (© 2024. The Author(s).)

Fibromyalgia (FM) is a chronic disorder characterized by widespread musculoskeletal pain, fatigue, and cognitive impairment. Despite the availability of various treatment options, FM remains a challenging condition to manage. In the present study, we investigated the efficacy of formulated nanodispersions of lutein and beta-carotene in treating FM-related symptoms induced by reserpine in female Wistar rats. Several techniques have been implemented to assess this efficacy at various levels, including biochemical, bioelectrical, and behavioral. Namely, oxidative stress markers, monoamine levels, electrocorticography, pain threshold test, and open field test were conducted on control, FM-induced, and FM-treated groups of animals. Our results provided compelling evidence for the efficacy of carotenoid nanodispersions in treating FM-related symptoms. Specifically, we found that the dual action of the nanodispersion, as both antioxidant and antidepressant, accounted for their beneficial effects in treating FM. With further investigation, nano-carotenoids and particularly nano-lutein could potentially become an effective alternative treatment for patients with FM who do not respond to current treatment options., (© 2023. The Author(s).)

Oxidative stress and inflammation are crucial factors in the development of cardiovascular diseases. In previous research, the oxidative stress and inflammation models have frequently been explored independently. In the current study, we investigated the antioxidant and anti-inflammatory effects of tomato extract and its two main carotenoids (lutein and lycopene) with various concentrations using a rat cardiomyocyte model of co-existing oxidative stress and persistent chronic inflammation. It was discovered that the antioxidant effects of 0.5-5 μM lutein, 0.5-5 μM lycopene, and 50-200 μg/mL tomato extract increased in a dose-dependent manner. However, the pro-oxidation effects emerged by measuring the antioxidant-related indices, including the levels of ROS, SOD, and GPX in H9c2 cells as concentrations exceeded those mentioned above. The anti-inflammatory effects of lutein, lycopene, and tomato extract were simultaneously strengthened with higher concentrations, potentially due to the suppression of the NF-κB signaling pathway. Furthermore, high concentrations of lutein, lycopene, and tomato extract potentially regulated Nrf2/HO-1 and NF-κB signaling pathways dependent on TGF-1β and IL-10 to demonstrate high concentrations of pro-oxidation and anti-inflammation effects. Our findings indicate that the dose-effect regulatory mechanisms of antioxidant and anti-inflammatory properties among lutein, lycopene, and tomato extract will be advantageous in developing more effective therapeutic strategies to prevent cardiovascular diseases.

Lutein is a strong antioxidant with anti-inflammatory, anti-oxidative and cardioprotective effects and could be a promising candidate for the treatment of hypertensive heart disease (HHD), but is not clinically appealing because of its low oral bioavailability and main distribution in the eyes. To address this, a biomimetic drug delivery system-MMLNPs was established by coating macrophage membranes (MMs) onto lutein-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (LNPs). This study characterized the physical properties of biomimetic nanoparticles and examined the targeting capability, therapeutic effects and mechanism, and biosecurity of administering them for cardiac fibrosis therapy in the transverse aortic constriction (TAC) model and in vitro. Transmission electron microscope mapping and dynamic light scattering analysis proved that MMLNPs were spherical nanoparticles camouflaged by a layer of cell membrane and had negative zeta potential. Confocal laser scanning microscopy and flow cytometry analysis showed that MMs on the biomimetic nanoparticles hindered the phagocytosis of macrophages and facilitated the targeting of activated endothelial cells. Ex vivo fluorescence imaging experiments demonstrated the targeting of biomimetic nanoparticles to the injured heart. EdU assay indicated that MMLNPs have the same potential to inhibit angiotensin (Ang) II-induced cardiac fibroblast proliferation as free lutein. Furthermore, echocardiography showed that MMLNPs improved cardiac function and structure, and Masson staining and western blotting showed that MMLNPs ameliorated cardiac fibrosis. We found MMLNPs inhibited the interleukin (IL)-11/ERK signaling pathway which was up-regulated in the TAC model compared to the sham-operated mouse. Biochemical testing and hematoxylin and eosin staining proved that the long-term use of MMLNPs lacked biological toxicity. Collectively, MMLNPs might be a promising nanodrug delivery approach to attenuate pressure overload (PO)-induced cardiac fibrosis., Competing Interests: Declaration of Competing Interest All authors disclosed no relevant relationships., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

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 (OR 0.75, 95% CI 0.51 to 1.10; moderate-certainty evidence), and a lower risk of losing 3 or more lines of visual acuity (OR 0.77, 95% CI 0.62 to 0.96; moderate-certainty evidence). Low-certainty evidence from one study of 110 people suggested higher quality of life scores (measured with the Visual Function Questionnaire) in treated compared with non-treated people after 24 months (mean difference (MD) 12.30, 95% CI 4.24 to 20.36). In exploratory subgroup analyses in the follow-on study to AREDS (AREDS2), replacing beta-carotene with lutein/zeaxanthin gave hazard ratios (HR) of 0.82 (95% CI 0.69 to 0.96), 0.78 (95% CI 0.64 to 0.94), 0.94 (95% CI 0.70 to 1.26), and 0.88 (95% CI 0.75 to 1.03) for progression to late AMD, neovascular AMD, geographic atrophy, and vision loss, respectively. Six studies compared lutein (with or without zeaxanthin) with placebo and one study compared a multivitamin including lutein/zeaxanthin with multivitamin alone. The duration of supplementation and follow-up ranged from six months to five years. Most evidence came from the AREDS2 study in the USA; almost all participants in AREDS2 also took the original AREDS supplementation formula. People taking lutein/zeaxanthin may have similar or slightly reduced risk of progression to late AMD (RR 0.94, 95% CI 0.87 to 1.01), neovascular AMD (RR 0.92, 95% CI 0.84 to 1.02), and geographic atrophy (RR 0.92, 95% CI 0.80 to 1.05) compared with control (1 study, 4176 participants, 6891 eyes; low-certainty evidence). A similar risk of progression to visual loss of 15 or more letters was seen in the lutein/zeaxanthin and control groups (RR 0.98, 95% CI 0.91 to 1.05; 6656 eyes; low-certainty evidence). Quality of life (Visual Function Questionnaire) was similar between groups (MD 1.21, 95% CI -2.59 to 5.01; 2 studies, 308 participants; moderate-certainty evidence). One study in Australia randomised 1204 people to vitamin E or placebo with four years of follow-up; 19% of participants had AMD. The number of late AMD events was low (N = 7) and the estimate of effect was uncertain (RR 1.36, 95% CI 0.31 to 6.05; very low-certainty evidence). There was no evidence of any effect of treatment on visual loss (RR 1.04, 95% CI 0.74 to 1.47; low-certainty evidence). There were no data on neovascular AMD, geographic atrophy, or quality of life. Five studies compared zinc with placebo. Evidence largely drawn from the largest study (AREDS) found a lower progression to late AMD over six years (OR 0.83, 95% CI 0.70 to 0.98; 3 studies, 3790 participants; moderate-certainty evidence), neovascular AMD (OR 0.76, 95% CI 0.62 to 0.93; moderate-certainty evidence), geographic atrophy (OR 0.84, 95% CI 0.64 to 1.10; moderate-certainty evidence), or visual loss (OR 0.87, 95% CI 0.75 to 1.00; 2 studies, 3791 participants; moderate-certainty evidence). There were no data on quality of life. Gastrointestinal symptoms were the main reported adverse effect. In AREDS, zinc was associated with a higher risk of genitourinary problems in men, but no difference was seen between high- and low-dose zinc groups in AREDS2. Most studies were too small to detect rare adverse effects. Data from larger studies (AREDS/AREDS2) suggested there may be little or no effect on mortality with multivitamin (HR 0.87, 95% CI 0.60 to 1.25; low-certainty evidence) or lutein/zeaxanthin supplementation (HR 1.06, 95% CI 0.87 to 1.31; very low-certainty evidence), but confirmed the increased risk of lung cancer with beta-carotene, mostly in former smokers., Authors' Conclusions: Moderate-certainty evidence suggests that antioxidant vitamin and mineral supplementation (AREDS: vitamin C, E, beta-carotene, and zinc) probably slows down progression to late AMD. People with intermediate AMD have a higher chance of benefiting from antioxidant supplements because their risk of progression is higher than people with early AMD. Although low-certainty evidence suggested little effect with lutein/zeaxanthin alone compared with placebo, exploratory subgroup analyses from one large American study support the view that lutein/zeaxanthin may be a suitable replacement for the beta-carotene used in the original AREDS formula., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Lung cancer is the leading cause of cancer-related death. In particular, non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases. Due to tumor resistance and the toxicity of chemotherapeutic agents, it is increasingly critical to discover novel, potent antitumorigenic drugs for treating NSCLC. Lutein, a carotenoid, has been reported to exert toxic effects on cells in several tumor types. However, the detailed functions and underlying mechanisms of lutein in NSCLC remain elusive. The present study showed that lutein significantly and dose-dependently inhibited cell proliferation, arrested the cell cycle at the G0/G1 phase, and induced apoptosis in NSCLC cells. RNA-sequencing analysis revealed that the p53 signaling pathway was the most significantly upregulated in lutein-treated A549 cells. Mechanistically, lutein exerted antitumorigenic effects by inducing DNA damage and subsequently activating the ATR/Chk1/p53 signaling pathway in A549 cells. In vivo, lutein impeded tumor growth in mice and prolonged their survival. In conclusion, our findings demonstrate the antitumorigenic potential of lutein and reveal its molecular mechanism of action, suggesting that lutein is a promising candidate for clinical NSCLC treatment., (© 2022 The Authors. Phytotherapy Research published by John Wiley & Sons Ltd.)

Objective: To explore the effects of lutein on the adhesion, invasiveness and metastasis of human prostate cancer PC-3M cells and its action mechanism., Methods: We divided human prostate cancer PC-3M cells into a control, a low-dose lutein, a medium-dose lutein and a high-dose lutein group, and treated them with 0, 10, 20 and 40 μmol/L lutein, respectively. Then we examined the adhesion of the cells to matrix by cell adhesion assay and the changes in cell pseudopodia by Phalloidin staining, detected the expressions of paxillin, matrix metalloproteinase 2 (MMP-2), MMP-9, recombinant tissue inhibitors of metalloproteinase 1 (TIMP-1), E-cadherin, N-cadherin and vimentin by Western blot, determined the invasiveness and migration of the cells by scratch and Transwell assays, and observed their dynamic movement by high-intension imaging., Results: Compared with the control, the lutein intervention groups showed significant reduction in the number of the cells adhered to matrix, the number of cell pseudopodia, the expressions of paxillin, MMP-2, MMP-9, N-cadherin and vimentin, the rates of migration, invasion and metastasis, and the distances of displacement and movement of the cells. However, the expressions of TIMP-1 and epithelial-mesenchymal transition-related E-cadherin were upregulated significantly., Conclusion: Lutein can inhibit cell adhesion, reduce the expressions of MMPs, and suppress cell invasion and migration by inhibiting the process of epithelial-mesenchymal transition.

Aims: The relationship between circulating Lutein and zeaxanthin (L/Z) concentrations, and plasma lipoproteins has been indicated by observational studies. However, the beneficial impact of L/Z administration on dyslipidemia are unclear. This meta-analysis aimed to investigate the effect of oral intake of L/Z on circulating total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), as well as high-density lipoprotein-cholesterol (HDL-C) levels., Methods: We electronically assessed all eligible interventional studies through different electronic databases, including PubMed, Scopus, ISI -Web of Science, and Cochrane library until Jun 2021. After identifying the quality of each included randomized controlled trials, they were evaluated by assessing the risk-difference between treatment and control groups by pooling available data on net change of serum LDL-C, HDL-C, and Cholesterol., Results: L/Z supplementation has null effect on circulating levels of TC (WMD: -3.82 95% CI: -13.83, 6.18; I-square: 85.2%), and LDL-C (WMD: -4.54; 95% CI: -11.5, 2.48; I-square: 83.9%). In contrast, L/Z treatment could significantly increase HDL-C levels in older adults (WMD: 4.06; 95% CI: 0.64, 7.48; I-square: 50.7%)., Conclusion: L/Z administration could be an effective treatment for improving circulating HDL-C concentration in elderly adults., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Lutein and zeaxanthin (L + Z) are carotenoids that accumulate in neural tissue and potentially confer benefits to cognition. Whereas cross-sectional studies have revealed positive associations between macular carotenoids (MC) and cognition, no studies have investigated whether L + Z supplementation impacts MC and cognition in childhood. Accordingly, the Integrated Childhood Ocular Nutrition Study aims to investigate the impact of L + Z supplementation over 9-months on academic abilities, attentional control, memory, and MC among preadolescent children. Children 8-10 years (N = 288) will enroll in a 9-month double-blind, placebo-controlled, randomized trial. The study is registered and approved as a clinical trial on the U.S. National Library of Medicine http://ClinicalTrials.gov registry (NCT05177679). Participants will be randomized into an active (10 mg lutein+2 mg zeaxanthin) or waitlist placebo-controlled group. Primary outcomes include hippocampal-dependent memory, attentional inhibition, and academic achievement using a spatial reconstruction task, an Eriksen flanker task, and the Kaufman Test of Academic and Educational Achievement 3rd edition, respectively. Secondary outcomes include event-related brain potentials of attentional resource allocation and information processing speed (i.e., P3/P300 amplitude and latency) recorded during the flanker task. Macular pigment optical density (MPOD) will be assessed using heterochromatic flicker photometry. Cognitive assessments will be completed prior to and after completion of the supplementation period. MPOD will be quantified prior to, at the mid-point of (4-5 months), and after (9 months) the supplementation period. It is hypothesized that L + Z supplementation will improve cognition and academic achievement. Further, benefits for cognition and achievement are anticipated to be mediated by increases in MC among treatment group participants., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Oxidative stress is one of the common factors leading to age-related eye diseases in older adults. Factors such as high oxygen consumption, high concentration of polyunsaturated fatty acids, and cumulative exposure to high-energy visible light in the eyes, lead to excessive generation of reactive oxygen species, hence triggering apoptosis of ocular cells and giving rise to ophthalmic diseases. Dietary supplements such as carotenoids, anthocyanins, and vitamins have antioxidant properties which may be of benefit in retaining better vision or reversing vision impairment; thus, studies have been conducted to understand the role of dietary supplements in the treatment or prevention of ophthalmic diseases. While high concentration of carotenoids such as lutein and zeaxanthin decrease the risk of developing age-related macular disease, anthocyanins and vitamins play a role in the treatment and prevention of other ophthalmic diseases: saffron extract reduced intraocular pressure in glaucoma patients; bilberry extract prevented impairments in lenses and retina, as well as alleviate symptoms of dry eye disease; high concentration of beta-carotene may reduce the risk of developing cataract. Further studies with clinical measurements are required to investigate the effectiveness of antioxidants on visual function and ophthalmic diseases., Competing Interests: The authors report no conflict of interest., (Copyright © 2022 Priscilla Peixi Choo et al.)

Background and Objectives: The aim of this study was to investigate the impact of oral administration of the combination of astaxanthin (AXT), lutein, folic acid, vitamin D3, and bromelain with antioxidants on choroidal blood flow in patients with age-related intermediate macular degeneration (AMD). Materials and Methods: Patients affected by intermediate AMD and treated with daily oral nutritional supplement with AXT, bromelain, vitamin D3, folic acid, lutein, and antioxidants for a period of at least 6 months were included in this retrospective study. A control group homogenous for age and sex was also included in the analysis. All participants underwent a complete ophthalmologic examination, spectral domain optical coherence tomography (SD-OCT), and optical coherence tomography angiography (OCTA) evaluation. Outcome measures were choroidal thickness (CHT) and choriocapillary vessel density (CCVD) after six months of AXT assumption. Results: CCVD values showed statistically significant difference between cases and controls at baseline (p < 0.001) and in the cases during follow-up (p < 0.001). The CHT measurements showed statistically significant difference between cases and controls (p = 0.002) and in the cases during follow-up (p < 0.001). Conclusions: The combined use of structural OCT and OCTA allows for a detailed analysis in vivo of perfusion parameters of the choriocapillaris and choroid and evaluation of changes of choroidal blood flow after oral nutritional supplements that affect blood flow velocity.

Age-related macular degeneration (AMD) is a complex disease that mainly affects people over 50 years of age. Even though management of the vascularisation associated with the "wet" form of AMD is effective using anti-VEGF drugs, there is currently no treatment for the "dry" form of AMD. Given this, it is imperative to develop methods for disease prevention and treatment. For this review, we searched scientific articles via PubMed and Google Scholar, and considered the impact of nutrients, specific dietary patterns, and probiotics on the incidence and progression of AMD. Many studies revealed that regular consumption of foods that contain ω-3 fatty acids is associated with a lower risk for late AMD. Particular dietary patterns, such as the Mediterranean diet that contains ω-3 FAs-rich foods (nuts, olive oil, and fish), seem to be protective against AMD progression compared to Western diets that are rich in fats and carbohydrates. Furthermore, randomized controlled trials that investigated the role of nutrient supplementation in AMD have shown that treatment with antioxidants, such as lutein/zeaxanthin, zinc, and carotenoids, may be effective against AMD progression. More recent studies have investigated the association of the antioxidant properties of gut bacteria, such as Bacteroides and Eysipelotrichi, with lower AMD risk in individuals whose microbiota is enriched with them. These are promising fields of research that may yield the capacity to improve the quality of life for millions of people, allowing them to live with a clear vision for longer and avoiding the high cost of vision-saving surgery., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Carotenoids in food substances are believed to have health benefits by lowering the risk of diseases. Lutein, a carotenoid compound, is one of the essential nutrients available in green leafy vegetables (kale, broccoli, spinach, lettuce, and peas), along with other foods, such as eggs. As nutrition plays a pivotal role in maintaining human health, lutein, as a nutritional substance, confers promising benefits against numerous health issues, including neurological disorders, eye diseases, skin irritation, etc. This review describes the in-depth health beneficial effects of lutein. As yet, a minimal amount of literature has been undertaken to consider all its promising bioactivities. The step-by-step biosynthesis of lutein has also been taken into account in this review. Besides, this review demonstrates the drug interactions of lutein with β-carotene, as well as safety concerns and dosage. The potential benefits of lutein have been assessed against neurological disorders, eye diseases, cardiac complications, microbial infections, skin irritation, bone decay, etc. Additionally, recent studies ascertained the significance of lutein nanoformulations in the amelioration of eye disorders, which are also considered in this review. Moreover, a possible approach for the use of lutein in bioactive functional foods will be discussed., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Diabetic retinopathy, which was primarily regarded as a microvascular disease, is the leading cause of irreversible blindness worldwide. With obesity at epidemic proportions, diabetes-related ocular problems are exponentially increasing in the developed world. Oxidative stress due to hyperglycemic states and its associated inflammation is one of the pathological mechanisms which leads to depletion of endogenous antioxidants in retina in a diabetic patient. This contributes to a cascade of events that finally leads to retinal neurodegeneration and irreversible vision loss. The xanthophylls lutein and zeaxanthin are known to promote retinal health, improve visual function in retinal diseases such as age-related macular degeneration that has oxidative damage central in its etiopathogenesis. Thus, it can be hypothesized that dietary supplements with xanthophylls that are potent antioxidants may regenerate the compromised antioxidant capacity as a consequence of the diabetic state, therefore ultimately promoting retinal health and visual improvement. We performed a comprehensive literature review of the National Library of Medicine and Web of Science databases, resulting in 341 publications meeting search criteria, of which, 18 were found eligible for inclusion in this review. Lutein and zeaxanthin demonstrated significant protection against capillary cell degeneration and hyperglycemia-induced changes in retinal vasculature. Observational studies indicate that depletion of xanthophyll carotenoids in the macula may represent a novel feature of DR, specifically in patients with type 2 or poorly managed type 1 diabetes. Meanwhile, early interventional trials with dietary carotenoid supplementation show promise in improving their levels in serum and macular pigments concomitant with benefits in visual performance. These findings provide a strong molecular basis and a line of evidence that suggests carotenoid vitamin therapy may offer enhanced neuroprotective effects with therapeutic potential to function as an adjunct nutraceutical strategy for management of diabetic retinopathy.

Epilepsy is one of the most frequent neurological disorders characterized by an enduring predisposition to generate epileptic seizures. Oxidative stress is believed to directly participate in the pathways of neurodegenerations leading to epilepsy. Approximately, one-third of the epileptic patients who suffer from seizures do not receive effective medical treatment. Sodium valproate (SVP) is a commonly used antiepileptic drug (AED); however, it has toxic effects. Lutein (L), a carotenoid, has potent antioxidant and anti-inflammatory properties. The aim of this study was to determine the neuroprotective effect of sodium valproate (SVP) and lutein (L) in a rat model of pilocarpine- (PLC-) induced epilepsy. To achieve this aim, fifty rats were randomly divided into five groups. Group I: control, group II: received PLC (400 mg/kg intraperitoneally), group III: received PLC + SVP (500 mg/kg orally), group IV: received PLC + SVP + L (100 mg/kg orally), and group V: received (PLC + L). Racine Scale (RC) and latency period to onset seizure were calculated. After eight weeks, the hippocampus rotarod performance and histological investigations were performed. Oxidative stress was investigated in hippocampal homogenates. Results revealed that SVP and L, given alone or in combination, reduced the RC significantly, a significant delay in latency to PLC-kindling onset, and improved rotarod performance of rats compared with the PLC group. Moreover, L was associated with a reduction of oxidative stress in hippocampal homogenate, a significant decrease in serum tumor necrosis factor-alpha (TNF- α ) level, and inhibition of cerebral injury and displayed antiepileptic properties in the PLC-induced epileptic rat model. Data obtained from the current research elucidated the prominent neuroprotective, antioxidant, and anti-inflammatory activities of lutein in this model. In conclusion, lutein cotreatment with AEDs is likely to be a promising strategy to improve treatment efficacy in patients suffering from epilepsy., Competing Interests: The authors declare no competing interests., (Copyright © 2021 Aziza Rashed Al-Rafiah and Khlood Mohammed Mehdar.)

Objective: Vasospasm developing after subarachnoid hemorrhage (SAH) is an important cause of mortality and morbidity. Lutein is a carotenoid with antioxidant and anti-inflammatory properties. The aim of present study was to investigate effects of lutein on the basilar artery and nerve tissues., Methods: Wistar rats were randomly divided into 3 groups: control (group 1), SAH (group 2), and SAH treated with lutein (group 3). Lutein was administered for 3 days by means of orogastric gavage. Basilar artery lumen area, wall thickness, serum total antioxidant status, serum total oxidant status, and oxidative stress index were calculated. Histopathologic and immunohistochemical analyses were conducted., Results: No statistically significant difference was found between groups in terms of wall thickness; lumen area; and serum total antioxidant status, serum total oxidant status, and oxidative stress index values. A statistically significant difference was found between groups colored with terminal deoxynucleotidyl transferase dUTP nick end labeling (P < 0.005). Post hoc analysis was used to examine the results between groups. Results of group 1 and group 3 were equal (P = 1) and lower than group 2 (P = 0.04 and P = 0.006, respectively)., Conclusions: Lutein was found to have a positive effect on width of the basilar artery lumen area. Therefore, positive effects of lutein on vasospasm might be statistically significant if lutein is administered at higher doses. Lutein was found to be effective in preventing brain damage after SAH. To our knowledge, this study is the first in the literature to examine the effect of lutein on vasospasm and brain damage after SAH., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Loss of α-crystallin chaperone function results in the lens protein aggregation leading to cataract. In this study, we evaluated the efficacy of micellar lutein with different fatty acids in modulating α-crystallin chaperone function under selenite cataract conditions., Methods: Cataract was induced in rat pups by giving sodium selenite (25 μM/kg body weight) by IP. Lutein [(L), 1.3 μmol/kg body weight)] was given day before and five days after selenite injection as a micelle with 7.5 mM linoleic acid (LA), or 7.5 mM eicosapentaenoic acid (EPA)+docosahexaenoic acid (DHA) or 7.5 mM oleic acid (OA). Lens α-crystallins was purified, and its chaperone function and integrity was assessed. Cholesterol, calcium, calpain-2, procaspase-3, and expression of α-A and β-B1 crystallin in the lens of cataract and micellar lutein administered rats were evaluated., Results: Cataract induction significantly (p < 0.05) decreased lens α-crystallin chaperone function. Cataract rats had increased cholesterol and calcium level, increased the expression of calpain-2, and α-A and β-B1 crystallin, and reduced the pro-caspase-3 level in the lens. However, micellar lutein administration significantly (p < 0.05) protected client proteins from aggregation via the modulation of calcium-dependent calpain-2 protease activity. The chaperone function of lens α-crystallins in rats administered micellar lutein with EPA + DHA was found to be highest when compared to OA and LA., Conclusions: Micellar lutein with unsaturated fatty acids beneficially modulates α-crystallin chaperone function. Among the fatty acids tested, micellar lutein with EPA + DHA exhibited superior effects, thereby offering a promising strategy for cataract management., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Lutein is a carotenoid whose protective effects in the retina have been reported in various studies. The effect of lutein has not been reported in the retina of the Ins2 Akita/+ mouse, a well-characterized genetic model for diabetic retinopathy (DR) in which the etiology of diabetes is better defined than the chemically induced diabetes. The objective of the present study is to investigate the effect of long-term administration of lutein in early stages of DR using the Ins2 Akita/+ mouse., Research Design and Methods: Heterozygous male Ins2 Akita/+ and age-matched wild-type mice were used. Lutein was administered to the mice in drinking water starting 6 weeks old daily until analysis at 4.5, 6.5 or 9 months of age. Plain water served as non-treatment control. Microglia were immunostained with ionized calcium-binding adapter molecule 1 (Iba-1) and cluster of differentiation 68 (CD68) in retinal flat-mounts. Vascular endothelial growth factor (VEGF) level in the retina was assessed by enzyme-linked immunosorbent assay (ELISA). Vascular permeability was analyzed in retinal flat-mounts after fluorescein isothiocyanate (FITC)-dextran perfusion. Retinal occludin expression was assessed via Western blots. Retinal function was examined by electroretinography (ERG)., Results: Increased microglial reactivity was detected in the Ins2 Akita/+ mouse retina and was suppressed by lutein. Lutein administration also reduced the upregulation of VEGF in the Ins2 Akita/+ mouse retina. Increased vascular leakage and decreased occludin expression were observed in the Ins2 Akita/+ mouse retina, and these alterations were attenuated by lutein treatment. ERG recordings showed reduced a-wave and b-wave amplitudes in the Ins2 Akita/+ mice. With lutein treatment, the ERG deficits were significantly alleviated., Conclusions: We showed beneficial effects of long-term lutein administration in the Ins2 Akita/+ mouse retina, including suppression of retinal inflammation, protection of retinal vasculature and preservation of retinal function. These results point to lutein's potential as a long-term therapeutic intervention for prevention of inflammation and retinal degeneration in patients with early DR., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Currently, there is a high interest in 177 Lu targeted radionuclide therapies, which could be attributed to favorable results obtained from 177 Lu compounds targeting neuro-endocrine and prostate tumors. SPECT based dosimetry could be used for deriving dose values for individual voxels, as is the standard in external-beam radiation-therapy (EBRT). For this a time-activity-curve (TAC) at voxel resolution and also a voxel-wise modeling of radiation energy deposition are necessary. But a voxel-wise determination of TACs is problematic, since several confounding factors exist, such as e.g. poor count-statistics or registration inaccuracies, which add noise to the observed activity states. A particle filter (PF) is a class of methods which applies regularization based on a model of the temporal evolution of activity states. The aim of this study is to introduce the application of PFs for de-noising of per-voxel time-activity curves., Methods: We applied a PF for de-noising the TACs of 26 patients, who underwent 177 Lu-DOTATOC or -PSMA therapy. The TACs were obtained from fully-quantitative, serial SPECT(/CT) data, acquired at 4h, 24h, 48h, 72h p.i. The model used in the PF was a mono-exponential decay and its free parameters were determined based on objective criteria. The time-integrated activities (TIA) resulting from the PF (PFF) were compared to the results of a mono-exponential fit (SF) of individual voxels in several volumes of interest (kidneys, spleen, tumors). Additionally, an organ-averaged TIA was derived from whole-organ VOIs and subsequent curve-fitting. This whole-organ TIA was also compared to the whole-organ TIAs obtained from summation of the voxel-wise TIAs from PFF and SF., Results: The number of particles was set to 1000. Optimal values for noise of observations and noise of the model were 0.25 and 0.5, respectively. The deviation of whole-organ TIAs from conventional organ-based dosimetry and the summation of the voxel-wise TIAs was substantial for SF (kidneys -22.3%, spleen -49.6%, tumor -60.0%), as well as for PFF (kidneys -37.1%, spleen -57.9%, tumor -70.9%). The distribution of voxel-wise half-lives resulting from the PFF method was considerably closer to the organ-averaged value, and the number of implausibly long half-lives (>physical HL) was reduced., Conclusion: The PFF leads to voxel-wise half-lives, which are more plausible than those resulting from SF. However, one has to admit that voxel-wise fitting generally leads to considerable deviations from the organ-averaged TIA as obtained by conventional whole-organ evaluation. Unfortunately, we did not have ground-truth TIA of our patient data and proper ground-truth could even be impossible to obtain. Nevertheless, there are strong indicators that particle filtering can be used for reducing voxel-wise TAC noise., (Copyright © 2019. Published by Elsevier GmbH.)

Background: Fruits and vegetables are generally rich in antioxidants such as carotenoids. Consumption of carotenoids is expected to have benefits on cognitive functions in humans. However, previous randomized controlled trials (RCT) using carotenoids have reported inconsistent results. Therefore, this systematic review (SR) aimed to summarize the effect of carotenoid intake on cognitive functions in humans., Method: PubMed, Cochrane Library, Web of Science, and PsychoINFO were searched for research papers on carotenoid intake with the criteria that 1) oral carotenoid intake was evaluated using RCTs, 2) participants were healthy young, middle-aged, or older, and 3) cognitive functions were measured using RCTs., Results: Five studies using lutein and two studies using astaxanthin met the inclusion criteria. Consumption of lutein and its isomer showed consistent results in selective improvement of visual episodic memory in young and middle-aged adults while inhibition was observed in middle-aged and older adults. One of the two included astaxanthin studies reported a significant improvement of verbal episodic memory performance in middle-aged adults., Conclusion: This SR showed that the 10 mg lutein per day for twelve months can lead to improvement of cognitive functions. Due to the small number of studies, it is difficult to conclude whether astaxanthin would have a positive effect on cognitive functions., Competing Interests: This study was a corroborative study between Institute of Development, Aging, and Cancer (IDAC), Tohoku University and Lion Corporation. supported by Lion Corporation. R.N and R.K received research grants from Lion Corporation. T.S., E.K, H.T., M.M., A.U., and M.A are full-time employees of Lion Corporation. The company policy was not involved in the study design, collection, analysis, interpretation of data, or writing of the manuscript. The authors declare that they have no other competing interests.

Age-related macular degeneration (AMD) is the leading cause of severe vision loss in developed countries and is highly common among aging individuals. Considering the rate at which the global population is aging, the increasing prevalence of AMD and age-related eye disease is cause for concern. AMD is associated with the degeneration of the macula, the most central region of the retina, leading to a loss of central vision. A wide array of research has focused on the ability of lipid soluble nutrients to prevent and mitigate the harmful effects of AMD. These nutrients in question tend to be highly saturated within retinal tissues including the carotenoids lutein and zeaxanthin and the polyunsaturated fatty acid docosahexaenoic acid (DHA). Additionally, the unique presence of very long chain polyunsaturated fatty acids (VLCPUFAs, C24-C36) in the retina may be essential to prevent retinal degeneration as demonstrated by abnormal retinal functioning in the absence of these novel fatty acids. Existing literature has suggested that lutein, zeaxanthin and DHA consumption tend to enhance the health of the retina, protecting against the development of AMD. However, little improvement to the previously deteriorated retina is demonstrated and more research is required to understand the role of these nutrients in the retina and for the prevention of AMD. Considering the global impact of AMD and age-related eye disease, utilizing nutrients to prevent the formation of these debilitating diseases is a highly affordable and promising strategy., Competing Interests: Conflict of interest The authors declare no conflicts of interest., (© 2020 Elsevier Inc. All rights reserved.)

Context: Lutein (LU) is a major carotenoid with various pharmacological activities including anti-inflammatory, antioxidant and anti-apoptosis. Objective: The cardioprotective efficacy of LU was determined by evaluating the biochemical and histopathological changes in isoproterenol (ISO) induced myocardial infarction (MI) rat model. Materials and methods: Healthy male albino rats ( n  = 40) were segregated into 4 equal groups. Group I (control) rats were administered with olive oil, Group II (LU) rats were orally pre-treated with only 40 mg of LU for 28 days, Group III (MI induced) rats were injected (subcutaneously; s.c) with 85 mg/kg of ISO for 2 consecutive days, whereas Group IV (LU + ISO) rats were pre-treated with 40 mg of LU for 28 days before ISO induction. Results: ISO-induced group showed increased infarct size and cardiac/inflammatory/apoptotic markers. However, pre-treatment with LU (28 days) considerably reduced ( p  < 0.01) the infarct size (14%), lipid peroxidation product (MDA;42%), cardiac markers [(lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB), cardiac troponin T (cTn T)], inflammatory markers [IL-1β, IL-6, tumour necrosis factor alpha (TNF-α), nuclear factor kappa B p65 subunit (NF-κB p65)] and apoptotic markers (caspase-3 and -9). Also, LU significantly improved ( p  < 0.01) the antioxidants [catalase (CAT), superoxide dismutase (SOD)] as well as markedly upregulated ( p  < 0.01) the protein expression of HO-1 and Nrf2. Moreover, LU considerably reversed all the histopathological changes and thus exhibits its cardioprotective activity. Conclusion: LU exhibits potent cardioprotective activity against ISO-induced cardiotoxicity and might be recommended with standard cardioprotective agents for treating various MI-related complications.

Lutein is an essential carotenoid commonly consumed in the diet; however, its dietary intake does not usually reach the minimum recommended intake to decrease the incidence of chronic diseases. Experimental and epidemiological evidence suggests an anti-atherosclerotic effect for lutein-rich foods or lutein supplementation. This systematic review aimed to assess the mechanistic pathways of lutein in the prevention of atherosclerosis. Electronic databases, including PubMed, SCOPUS, ProQuest, Embase, and Google Scholar were searched to May 2019. Original studies published in English-language journals that investigated the effects of lutein on atherosclerosis and related risk factors, including lipid profile, hemodynamic, glycemic and inflammatory measurements, and endothelial function indices, were considered. Two reviewers independently extracted data on study characteristics, methods and outcomes. The review protocol has been registered at PROSPERO database of Systematic Reviews (registration number: CRD42019121381). A total of 5818 articles were found in the first phase of the search; from these, 19 met the inclusion criteria: 3 in vitro, 1 ex vivo, 11 animal, and 4 human studies. Nine of ten studies showed positive effects of lutein on endothelial function by reducing blood pressure, arterial thickness, monocyte migration, and vascular smooth muscle cell migration. Twelve studies examined the anti-inflammatory properties of lutein and found a significant decrease in proinflammatory cytokines. Although few studies investigated the anti-hyperlipidemic effects of lutein, three animal studies and one clinical trial found a beneficial effect of lutein on lipid profile. Evidence supports positive effects of lutein on atherosclerosis development and some common risk factors of atherosclerosis, including inflammation and endothelial dysfunction. Further studies focused on the effects of lutein on hyperglycemia, lipid profile, blood pressure and coagulation are required., (Copyright © 2019. Published by Elsevier Ltd.)

Aim: Ethambutol and isoniazid are two major effective first line agents in tuberculosis treatment having some visual adverse effects. We aimed to determine the protective effects of lutein on oxidative optic neuropathy induced by ethambutol and isoniazid in an experimental model., Material and Method: Totally 24 albino Wistar male rats were assigned into 4 groups, with 6 rats in each group as follows: healthy controls (HC group), 50 mg/kg ethambutol +50 mg/kg isoniazid administered group (EI), 0.5 mg/kg lutein +50 mg/kg ethambutol +50 mg/kg isoniazid administered group (LEI-05) and only Lutein (0.5 mg/kg) (LUT group) administered group. From the blood samples and tissues obtained from the rats, Malondialdehyde (MDA), total glutathione (GSH), interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) levels were studied. Histopathological evaluations were performed at the end of the study., Results: Serum and tissue IL-1β, TNF-α and MDA levels were the highest in EI group which were significantly lower in lutein administered group. On the other hand, serum and tissue total GSH levels were the lowest in EI group which were significantly higher in Lutein administered group. In histopathological evaluations, there were significant differences between EI group and all other three groups with edema and hemorrhage in connective tissue covering optic nerve, dilated and congested capillary, decrease in astrocytes and oligodendrocytes., Conclusion: Isoniazid and ethambutol induced toxic optic neuropathy although not common, may have some potential devastating effects on vision. Lutein is determined as an effective agent in prevention of isoniazid and ethambutol induced toxic optic neuropathy.

Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness worldwide, and the prevalence is projected to increase to 112 million worldwide by 2040. Intraocular pressure is currently the only proven modifiable risk factor to treat POAG, but recent evidence suggests a link between antioxidant levels and risk for prevalent glaucoma. Studies have found that antioxidant levels are lower in the serum and aqueous humor of glaucoma patients. In this review, we provide a brief overview of the evidence linking oxidative stress to glaucomatous pathology, followed by an in-depth discussion of epidemiological studies and clinical trials of antioxidant consumption and glaucomatous visual field loss. Lastly, we highlight a possible role for antioxidant carotenoids lutein and zeaxanthin, which accumulate in the retina to form macular pigment, as evidence has emerged supporting an association between macular pigment levels and age-related eye disease, including glaucoma. We conclude that the evidence base is inconsistent in showing causal links between dietary antioxidants and glaucoma risk, and that prospective studies are needed to further investigate the possible relationship between macular pigment levels and glaucoma risk specifically.

Purpose: To analyze the prevalence, incidence, and clinical characteristics of eyes with geographic atrophy (GA) in age-related macular degeneration (AMD), including clinical and genetic factors affecting enlargement., Design: Prospective cohort study within a controlled clinical trial., Participants: Age-Related Eye Disease Study 2 (AREDS2) participants, aged 50-85 years., Methods: Baseline and annual stereoscopic color fundus photographs were evaluated for GA presence and area. Analyses included GA prevalence and incidence rates, Kaplan-Meier rates, mixed-model regression, and multivariable analysis of the square root of GA, area adjusted for covariates, including clinical/imaging characteristics and genotype., Main Outcome Measures: (1) Presence or development of GA; (2) change in the square root of GA area over time., Results: At baseline, 517 eyes (6.2%) of 411 participants (9.8%) had pre-existing GA (without neovascular AMD), with the following characteristics: 33% central, 67% noncentral; and the following configurations: 36% small, 26% solid/unifocal, 24% multifocal, 9% horseshoe/ring, and 6% indeterminate. Of the remaining 6530 eyes at risk, 1099 eyes (17.3%) of 883 participants developed incident GA without prior neovascular disease during mean follow-up of 4.4 years. The Kaplan-Meier rate of incident GA was 19% of eyes at 5 years. In eyes with incident GA, 4-year risk of subsequent neovascular AMD was 29%. In eyes with incident noncentral GA, 4-year risk of central involvement was 57%. GA enlargement rate (following square root transformation) was similar in eyes with pre-existing GA (0.29 mm/year; 95% confidence interval 0.27-0.30) and incident GA (0.28 mm/year; 0.27-0.30). In the combined group, GA enlargement was significantly faster with noncentrality, multifocality, intermediate baseline size, and bilateral GA (P < 0.0001 for interaction in each case) but not with AREDS2 treatment assignment (P = 0.33) or smoking status (P = 0.05). Enlargement was significantly faster with ARMS2 risk (P < 0.0001), C3 non-risk (P = 0.0002), and APOE non-risk (P = 0.001) genotypes., Conclusions: Analyses of AREDS2 data on natural history of GA provide representative data on GA evolution and enlargement. GA enlargement, which was influenced by lesion features, was relentless, resulting in rapid central vision loss. The genetic variants associated with faster enlargement were partially distinct from those associated with risk of incident GA. These findings are relevant to further investigations of GA pathogenesis and clinical trial planning., (Published by Elsevier Inc.)

Background: Effects of lutein (L) and fatty acids [linoleic acid (LA), eicosapentaenoic acid (EPA)+docosahexaenoic acid (DHA) and oleic acid (OA)] on oxidative stress and inflammation in cataract were assessed., Methods: Cataract was induced in male Wistar rat pups (11 days old) by giving a single dose of sodium selenite (25 μM/kg body weight) by IP. Lutein (1.3 μmol/kg body weight) was given one day before and five days after selenite injection as a micelle with 7.5 mM LA, or 7.5 mM EPA + DHA or 7.5 mM OA. Serum and lens oxidative stress and inflammatory parameters having a bearing cataract were assessed., Results: Serum and lens nitric oxide, MDA and protein carbonyls were significantly (p < 0.05) increased in cataract compared to control and experimental groups. Catalase, SOD, glutathione peroxidase and glutathione transferase activity and glutathione level in serum and lens of cataract group were significantly (p < 0.05) decreased. Serum eicosanoids (PGE 2 , LTB 4 , and LTC 4 ) and cytokines (CRP, TNF-α, IL1-β, and MCP-1) were significantly (p < 0.05) increased in cataract. The activity of cPLA2 and Cox-2 in cataract lens was higher (p < 0.05) compared to other groups. EP-1, NOS-2 and NF-kB expression were higher (p < 0.05) in cataract. The ratio of water insoluble to water soluble protein was increased in cataract lens. Group administered with L + EPA + DHA exhibited highest cataract prevention compared to L + LA and L + OA. Pups given lutein with EPA + DHA had the highest amount of lutein in the lens., Conclusions: The anti-cataract activity of lutein was influenced by fatty acids and found to be highest with EPA + DHA compared to LA or OA., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Thermal injury may lead to multiple organ dysfunction through release of proinflammatory mediators and reactive oxygen radicals. This study investigated the effects of thermal injury on remote organs of rats and the possible protective effect of lutein. Thermal trauma was induced in the back of rats by exposing them to 90 °C bath for 10 s. Rats were sacrificed 48 h after burn, and blood samples were collected to monitor liver and kidney functions. Tissue samples from liver, kidneys, and lungs were taken for studying oxidative stress parameters, gene expressions of TNF-α and Casp-3, besides histopathological examination. Skin scald injury caused significant elevations of liver and kidney function biomarkers in the serum. In tissue samples, increments of MDA, GPx, and 8-OHdG were recorded while GSH level and the activities of CAT and SOD were suppressed. The expressions of TNF-α and caspase-3 mRNA were increased, and histopathological results revealed remote organ injury. Oral administration of lutein (250 mg/kg) resulted in amelioration of the biochemical and molecular changes induced by burn as well as the histopathological alterations. According to the findings of the present study, lutein possesses anti-oxidant, anti-inflammatory, and anti-apoptotic effects that protect against burn-induced damage in remote organs.

Purpose: Age-related macular degeneration (AMD), a multifactorial disease with variable phenotypic presentation, was associated with 52 single nucleotide polymorphisms (SNPs) at 34 loci in a genome-wide association study (GWAS). These genetic variants could modulate different biological pathways involved in AMD, contributing to phenotypic variability. To better understand the effects of these SNPs, we performed a deep phenotype association study (DeePAS) in the Age-Related Eye Disease Study 2 (AREDS2), followed by replication using AREDS participants, to identify genotype associations with AMD and non-AMD ocular and systemic phenotypes., Design: Cohort study., Participants: AREDS and AREDS2 participants., Methods: AREDS2 participants (discovery cohort) had detailed phenotyping for AMD; other eye conditions; cardiovascular, neurologic, gastrointestinal, and endocrine disease; cognitive function; serum nutrient levels; and others (total of 139 AMD and non-AMD phenotypes). Genotypes of the 52 GWAS SNPs were obtained. The DeePAS was performed by correlating the 52 SNPs to all phenotypes using logistic and linear regression models. Associations that reached Bonferroni-corrected statistical significance were replicated in AREDS., Main Outcome Measures: Genotype-phenotype associations., Results: A total of 1776 AREDS2 participants had 5 years follow-up; 1435 AREDS participants had 10 years. The DeePAS revealed a significant association of the rs3750846 SNP at the ARMS2/HTRA1 locus with subretinal/sub-retinal pigment epithelial (RPE) hemorrhage related to neovascular AMD (odds ratio 1.55 [95% confidence interval 1.31-1.84], P = 2.67 × 10 -7 ). This novel association remained significant after conditioning on participants with neovascular AMD (P = 2.42 × 10 -4 ). Carriers of rs3750846 had poorer visual acuity during follow-up (P = 6.82 × 10 -7 ) and were more likely to have a first-degree relative with AMD (P = 5.38 × 10 -6 ). Two SNPs at the CFH locus, rs10922109 and rs570618, were associated with the drusen area in the Early Treatment Diabetic Retinopathy Study Report (ETDRS) grid (P = 2.29 × 10 -11 and P = 3.20 × 10 -9 , respectively) and the center subfield (P = 1.24 × 10 -9 and P = 6.68 × 10 -8 , respectively). SNP rs570618 was additionally associated with the presence of calcified drusen (P = 5.38 × 10 -6 ). Except for positive family history of AMD with rs3750846, all genotype-phenotype associations were significantly replicated in AREDS. No pleiotropic associations were identified., Conclusions: The association of the SNP at the ARMS2/HTRA1 locus with subretinal/sub-RPE hemorrhage and poorer visual acuity and of SNPs at the CFH locus with drusen area may provide new insights in pathophysiological pathways underlying different stages of AMD., (Published by Elsevier Inc.)

Purpose: To evaluate the association of mortality with visual acuity (VA) impairment, age-related macular degeneration (AMD), and cataract surgery., Design: Cohort study., Participants: Participants with at least intermediate AMD enrolled in a randomized controlled clinical trial of lutein/zeaxanthin and/or omega-3 fatty acids, the Age-Related Eye Disease Study 2 (AREDS2), for treatment of AMD and cataract., Methods: Baseline and annual eye examinations included best-corrected visual acuity (BCVA) assessments, slit-lamp examinations, and stereoscopic fundus photographs that were centrally graded for development of late AMD (central geographic atrophy or neovascular AMD) or pseudophakia. Cause-specific mortality was determined on the basis of the International Classification of Diseases 9th or 10th Revision codes. Risk of all-cause and cause-specific mortality was assessed with Cox proportional hazards models adjusted for age, sex, AMD severity, VA, history of cataract surgery, and assigned AREDS2 study treatment. Analyses included baseline covariates: race, education, smoking status, diabetes, and cardiovascular disease., Results: During follow-up (median 5 years), 368 (9%) of the 4203 AREDS2 participants died. Participants with neovascular AMD in 1 eye at baseline had a statistically significant increased risk for mortality compared with participants with no or few drusen (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.21-2.01; P < 0.001). Poorer survival was associated with bilateral cataract surgery before enrollment compared with baseline bilateral phakia (HR, 1.63; 95% CI, 1.29-2.07; P < 0.001) and with BCVA of less than 20/40 compared with participants with 20/40 or better (HR, 1.56; 95% CI, 1.06-2.30; P = 0.024), adjusted for age, sex, and statistically significant covariates. Participants who received antivascular endothelial growth factor therapies for neovascular AMD had decreased mortality compared with those who did not (HR, 0.71; 95% CI, 0.57-0.88; P = 0.002). The association between all-cause mortality and AREDS2 treatment whether assessing the main or individual treatment effect was not significantly different (omega-3 fatty acids main effect HR, 1.18; 95% CI, 0.96-1.45; P = 0.12; lutein/zeaxanthin main effect HR, 1.04; 95% CI, 0.85-1.28; P = 0.71)., Conclusions: In AREDS2, the presence of late AMD, bilateral cataract surgery, and VA less than 20/40 was associated with decreased survival. However, oral supplementation with omega-3 fatty acids, lutein plus zeaxanthin, zinc, or beta-carotene had no statistically significant impact on mortality., (Published by Elsevier Inc.)

Antioxidants can decrease oxidative damage and prevent age-related ocular disease. Our previous investigation on human aqueous humor following intake of a lutein-containing antioxidant supplement reported an increase in the scavenging activity of superoxide in both genders and an increase in the amount of hydrogen peroxide (H 2 O 2 ) in females. Aquaporin 8 (AQP8) is a diffusion facilitator of H 2 O 2 and glutathione peroxidase (Gpx) is a H 2 O 2 scavenging enzyme. The correlation between AQP8 and Gpx may be the key to determining how oxidative stress in the aqueous humor affects the lens after intake of antioxidant supplements. In this study, 24 patients with the same grade of binocular cataract were included. Anterior capsule samples, including lens epithelial cells (LECs), were collected during cataract surgery before (as pre-intake samples) and after 6 weeks of oral intake of Ocuvite Lutein ® (as post-intake samples). The mRNA expression of APQ8 and Gpx was measured using real-time polymerase chain reaction. Among males, AQP8 expression decreased significantly after the supplementation (P = .03), while there was no statistical change among females. AQP8 expression was significantly correlated to that of Gpx in post-intake samples among females (R = 0.69, P = .02), while no correlation was evident among males. The results suggest antioxidant supplementation may work by different mechanisms on LECs between genders. After supplementation, a decrease in AQP8 in LECs may inhibit the influx of H 2 O 2 from the aqueous humor in males. In females however, the correlation between AQP8 and Gpx in LECs may indicate an increase in Gpx activity following the influx of H 2 O 2 from the aqueous humor and further scavenging of H 2 O 2 ., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cancer, the uncontrolled growth of cells, is a major disease that threatens the worldwide population. Among all cancer types, lung cancer has the highest morbidity rate, with a survival rate of less than 5%. Various studies have focused on discovering a potent anticancer drug that will increase the survival rate of lung cancer patients. Lutein (3,3'-dihydroxy-β, ε-carotene), a carotenoid present in fruits and vegetables, is one such compound that possesses excellent antioxidant properties. The present study was designed to determine the anticancer effect of lutein against A549, a non-small-cell lung cancer cell line. The cytotoxic effect of lutein against lung cancer cells (A549 and HCC827) and normal cells (BEAS-2B) was detected by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The Transwell assay was performed to detect the inhibitory potential of lutein against cell invasion and migration of A549 cells. The induction of apoptosis by lutein in A549 was analyzed by a double-staining technique using TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling) and DAPI (4',6-diamidino-2-phenylindole) staining assays to confirm the molecular mechanism exhibited by lutein to induce apoptosis through regulating the phosphoinositide 3-kinase (PI3K)/AKT signaling molecules that are often deregulated in cancerous condition. The results show that lutein inhibits the PI3K/AKT signaling pathway and induces apoptosis in A549, which may therefore be used as a potent natural anticancer drug with no side effects to treat lung cancer.

Retinitis pigmentosa (RP) encompasses a heterogeneous group of inherited retinal disorders characterized by progressive photoreceptor and/or retinal pigment epithelial (RPE) degenerations with a prevalence approximately 1 in 4000 in the general population. Over 70 causative genes have been defined in RP families, and a number of animal models have been identified so far. However there have been no widely recognized treatments able to recover or reverse the degenerating retina, to prevent the disease deterioration, ultimately to restore the remaining vision. Therapeutics advancements have been achieved including gene therapy, pharmacotherapy, cell replacement, neurotrophic factors, and retinal prosthesis. In this review, we focus on the pharmaceutical drugs for RP with emphases on the context of drug discovery, development, and clinical translation.

Many studies have reported that lutein may exert its biological activities, including anti‑inflammation, anti‑oxidase and anti‑apoptosis, through effects on reactive oxygen species (ROS). Thus, lutein may prevent the damaging activities of ROS in cells. The current study investigated the effect of lutein against severe traumatic brain injury (STBI) and examined the mechanism of this protective effect. Sprague‑Dawley rats were randomly divided into 5 groups: Control group, STBI model group, 40 mg/kg lutein‑treated group, 80 mg/kg lutein‑treated group and 160 mg/kg lutein‑treated group. In this study, lutein protects against STBI, suppressed, interleukin (IL)‑1β, IL‑6 and monocyte chemoattractant protein‑1 expression, reduced serum ROS levels, and reduced superoxide dismutase and glutathione peroxidase activities in STBI rats. Treatment with lutein effectively downregulated the expression of NF‑κB p65 and cyclooxygenase‑2, intercellular adhesion molecule (ICAM)‑1 protein, and upregulated nuclear factor erythroid 2 like 2 (Nrf‑2) and endothelin‑1 protein levels in STBI rats. These findings demonstrated that lutein protects against STBI, has anti‑inflammation and antioxidative effects and alters ICAM‑1/Nrf‑2 expression, which may be a novel therapeutic for STBI the clinic.

Purpose: The purpose of this study was to evaluate the impact of supplemental macular carotenoids (including versus not including meso-zeaxanthin) in combination with coantioxidants on visual function in patients with nonadvanced age-related macular degeneration., Methods: In this study, 121 participants were randomly assigned to group 1 (Age-Related Eye Disease Study 2 formulation with a low dose [25 mg] of zinc and an addition of 10 mg meso-zeaxanthin; n = 60) or group 2 (Age-Related Eye Disease Study 2 formulation with a low dose [25 mg] of zinc; n = 61). Visual function was assessed using best-corrected visual acuity, contrast sensitivity (CS), glare disability, retinal straylight, photostress recovery time, reading performance, and the National Eye Institute Visual Function Questionnaire-25. Macular pigment was measured using customized heterochromatic flicker photometry., Results: There was a statistically significant improvement in the primary outcome measure (letter CS at 6 cycles per degree [6 cpd]) over time (P = 0.013), and this observed improvement was statistically comparable between interventions (P = 0.881). Statistically significant improvements in several secondary outcome visual function measures (letter CS at 1.2 and 2.4 cpd; mesopic and photopic CS at all spatial frequencies; mesopic glare disability at 1.5, 3, and 6 cpd; photopic glare disability at 1.5, 3, 6, and 12 cpd; photostress recovery time; retinal straylight; mean and maximum reading speed) were also observed over time (P < 0.05, for all), and were statistically comparable between interventions (P > 0.05, for all). Statistically significant increases in macular pigment at all eccentricities were observed over time (P < 0.0005, for all), and the degree of augmentation was statistically comparable between interventions (P > 0.05)., Conclusions: Antioxidant supplementation in patients with nonadvanced age-related macular degeneration results in significant increases in macular pigment and improvements in CS and other measures of visual function. (Clinical trial, http://www.isrctn.com/ISRCTN13894787).

Behind blue eyes - the evidence for ocular nutritional supplements on the Swedish market Health claims for food are harmonized in the European Union by the European Food Safety Authority (EFSA). Nutritional supplements containing vitamin A or B, docosahexaenoic acid or zinc are allowed to state in their marketing that they preserve vision. This decision is based only on studies of cell metabolism and deficiency diseases and not on clinical interventions. A preventive effect on progression of age-related macular degeneration has however been proven with the AREDS-formula, with an absolute risk reduction for severe visual loss of 6% in certain groups. This treatment may however be associated with considerable side effects. Only 2 of the 25 nutritional supplements for preserved vision available on the Swedish market today follows the AREDS-formula. The present marking of ocular nutritional supplements might therefore be misleading for the customer.

This study targeted to test the potential protective role of lutein against lung and liver damage associated with cyclophosphamide (CP) administration. Lutein was given orally for 5days at two different doses both before and after CP injection. Results have shown that CP administration caused marked pulmonary and hepatic injurious effects in mice. Lung damage was evident through increased lung wet/dry ratio, elevated inflammatory cells infiltration into the pulmonary tissues, increased total protein content and lactate dehydrogenase (LDH) activity in the broncho-alveolar lavage fluid. Estimation of high levels of serum transaminases, alkaline phosphatase and LDH in serum revealed hepatic injury. Histopathological examination of both organs confirmed the biochemical analysis. Elevation of oxidative stress along with depressed anti-oxidant status of lung and liver were evident in CP-intoxicated animals. Furthermore, CP induced elevation of inflammatory cytokines (NOx, TNF-α, IL-6) contaminant with activation of nuclear factor kappa-B (NF-κB) and p38 mitogen activated protein kinase (p38-MAPK). On the other side, lutein treatment successfully protected the lung and the liver as indicated by improvement of the biochemical and histopathological parameters. These results suggest that lutein can ameliorate CP-induced pulmonary and hepatic oxidative injurious effects via inhibition of reactive oxygen species (ROS)/NF-κB/MAPK pathway., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

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-certainty evidence). In people with very early signs of AMD, who are at low risk of progression, this would mean that there would be approximately 4 fewer cases of progression to late AMD for every 1000 people taking vitamins (1 fewer to 6 fewer cases). In people at high risk of progression (i.e. people with moderate AMD) this would correspond to approximately 8 fewer cases of progression for every 100 people taking vitamins (3 fewer to 13 fewer). In one study of 1206 people, there was 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 (OR 0.75, 95% CI 0.51 to 1.10; moderate-certainty evidence) and a lower risk of losing 3 or more lines of visual acuity (OR 0.77, 95% CI 0.62 to 0.96; 1791 participants; moderate-certainty evidence). Low-certainty evidence from one study of 110 people suggested higher quality of life scores (National Eye Institute Visual Function Questionnaire) in treated compared with the non-treated people after 24 months (mean difference (MD) 12.30, 95% CI 4.24 to 20.36). Six studies compared lutein (with or without zeaxanthin) with placebo. The duration of supplementation and follow-up ranged from six months to five years. Most evidence came from the AREDS2 study in the USA. People taking lutein or zeaxanthin may have similar or slightly reduced risk of progression to late AMD (RR 0.94, 95% CI 0.87 to 1.01; 6891 eyes; low-certainty evidence), neovascular AMD (RR 0.92, 95% CI 0.84 to 1.02; 6891 eyes; low-certainty evidence), and geographic atrophy (RR 0.92, 95% CI 0.80 to 1.05; 6891 eyes; low-certainty evidence). A similar risk of progression to visual loss of 15 or more letters was seen in the lutein and control groups (RR 0.98, 95% CI 0.91 to 1.05; 6656 eyes; low-certainty evidence). Quality of life (measured with Visual Function Questionnaire) was similar between groups in one study of 108 participants (MD 1.48, 95% -5.53 to 8.49, moderate-certainty evidence). One study, conducted in Australia, compared vitamin E with placebo. This study randomised 1204 people to vitamin E or placebo, and followed up for four years. Participants were enrolled from the general population; 19% had AMD. The number of late AMD events was low (N = 7) and the estimate of effect was uncertain (RR 1.36, 95% CI 0.31 to 6.05, very low-certainty evidence). There were no data on neovascular AMD or geographic atrophy.There was no evidence of any effect of treatment on visual loss (RR 1.04, 95% CI 0.74 to 1.47, low-certainty evidence). There were no data on quality of life. Five studies compared zinc with placebo. The duration of supplementation and follow-up ranged from six months to seven years. People taking zinc supplements may be less likely to progress to late AMD (OR 0.83, 95% CI 0.70 to 0.98; 3790 participants; 3 RCTs; low-certainty evidence), neovascular AMD (OR 0.76, 95% CI 0.62 to 0.93; 2442 participants; 1 RCT; moderate-certainty evidence), geographic atrophy (OR 0.84, 95% CI 0.64 to 1.10; 2442 participants; 1 RCT; moderate-certainty evidence), or visual loss (OR 0.87, 95% CI 0.75 to 1.00; 3791 participants; 2 RCTs; moderate-certainty evidence). There were no data reported on quality of life.Very low-certainty evidence was available on adverse effects because the included studies were underpowered and adverse effects inconsistently reported., Authors' Conclusions: People with AMD may experience some delay in progression of the disease with multivitamin antioxidant vitamin and mineral supplementation. This finding was largely drawn from one large trial, conducted in a relatively well-nourished American population. We do not know the generalisability of these findings to other populations. Although generally regarded as safe, vitamin supplements may have harmful effects. A systematic review of the evidence on harms of vitamin supplements is needed. Supplements containing lutein and zeaxanthin are heavily marketed for people with age-related macular degeneration but our review shows they may have little or no effect on the progression of AMD.

Alzheimer's disease (AD) is a progressive, neurodegenerative disease, characterised by decline of memory, cognitive function and changes in behaviour. Generic markers of lipid peroxidation are increased in AD and reactive oxygen species have been suggested to be involved in the aetiology of cognitive decline. Carotenoids are depleted in AD serum, therefore we have compared serum lipid oxidation between AD and age-matched control subjects before and after carotenoid supplementation. The novel oxidised phospholipid biomarker 1-palmitoyl-2-(5'-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC) was analysed using electrospray ionisation tandem mass spectrometry (MS) with multiple reaction monitoring (MRM), 8-isoprostane (IsoP) was measured by ELISA and ferric reducing antioxidant potential (FRAP) was measured by a colorimetric assay. AD patients (n=21) and healthy age-matched control subjects (n=16) were supplemented with either Macushield™ (10mg meso-zeaxanthin, 10mg lutein, 2mg zeaxanthin) or placebo (sunflower oil) for six months. The MRM-MS method determined serum POVPC sensitively (from 10µl serum) and reproducibly (CV=7.9%). At baseline, AD subjects had higher serum POVPC compared to age-matched controls, (p=0.017) and cognitive function was correlated inversely with POVPC (r=-0.37; p=0.04). After six months of carotenoid intervention, serum POVPC was not different in AD patients compared to healthy controls. However, POVPC was significantly higher in control subjects after six months of carotenoid intervention compared to their baseline (p=0.03). Serum IsoP concentration was unrelated to disease or supplementation. Serum FRAP was significantly lower in AD than healthy controls but was unchanged by carotenoid intervention (p=0.003). In conclusion, serum POVPC is higher in AD patients compared to control subjects, is not reduced by carotenoid supplementation and correlates with cognitive function., (Copyright © 2017. Published by Elsevier Inc.)

Context: Carotenoids have been implicated in the regulation of adipocyte metabolism., Objective: To compare the effects of mixed-carotenoid supplementation (MCS) versus placebo on adipokines and the accrual of abdominal adiposity in children with obesity., Design and Setting: Randomized (1:1), double-blind, placebo-controlled intervention trial to evaluate the effects of MCS over 6 months in a subspecialty clinic., Participants: Twenty (6 male and 14 female) children with simple obesity [body mass index (BMI) > 90%], a mean age (± standard deviation) of 10.5 ± 0.4 years, and Tanner stage I to V were enrolled; 17 participants completed the trial., Intervention: MCS (which contains β-carotene, α-carotene, lutein, zeaxanthin, lycopene, astaxanthin, and γ-tocopherol) or placebo was administered daily., Main Outcome Measures: Primary outcomes were change in β-carotene, abdominal fat accrual (according to magnetic resonance imaging), and BMI z-score; secondary outcomes were adipokines and markers of insulin resistance., Results: Cross-sectional analysis of β-carotene showed inverse correlation with BMI z-score, waist-to-height ratio, visceral adipose tissue, and subcutaneous adipose tissue (SAT) at baseline. MCS increased β-carotene, total adiponectin, and high-molecular-weight adiponectin compared with placebo. MCS led to a greater reduction in BMI z-score, waist-to-height ratio, and SAT compared with placebo. The percentage change in β-carotene directly correlated with the percentage change in SAT., Conclusions: The decrease in BMI z-score, waist-to-height ratio, and SAT and the concomitant increase in the concentration of β-carotene and high-molecular-weight adiponectin by MCS suggest the putative beneficial role of MCS in children with obesity., (Copyright © 2017 Endocrine Society)

Diabetic retinopathy (DR) is one of the most important microvascular complications of diabetes and remains the leading cause of blindness in the working-age individuals. The exact aetiopathogenesis of DR remains elusive despite major advances in basic science and clinical research. Oxidative damage as one of the underlying causes for DR is increasingly being recognised. In humans, three hydroxycarotenoids, lutein (L), zeaxanthin (Z) and meso -zeaxanthin (MZ), accumulate at the central retina (to the exclusion of all other dietary carotenoids), where they are collectively known as macular pigment. These hydroxycarotenoids by nature of their biochemical structure and function help neutralise reactive oxygen species, and thereby, prevent oxidative damage to the retina (biological antioxidants). Apart from their key antioxidant function, evidence is emerging that these carotenoids may also exhibit neuroprotective and anti-inflammatory function in the retina. Since the preliminary identification of hydroxycarotenoid in the human macula by Wald in the 1940s, there has been astounding progress in our knowledge of the role of these carotenoids in promoting ocular health. While the Age-Related Eye Disease Study 2 has established a clinical benefit for L and Z supplements in patients with age-related macular degeneration, the role of these carotenoids in other retinal diseases potentially linked to oxidative damage remains unclear. In this article, we comprehensively review the literature germane to the putative protective role of two hydroxycarotenoids, L and Z, in the pathogenesis of DR., Competing Interests: Competing interestsNone declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Lutein, a member of the xanthophyll family of carotenoids, suppressed IL-1-induced osteoclast differentiation and bone resorption. The survival of mature osteoclasts was also suppressed by lutein in cultures. When lutein was added to the cultures of osteoblasts, lutein enhanced the formation of mineralized bone nodules by elevating BMP2 expression and inhibiting sclerostin expression. Lutein may be beneficial for bone health.

Objectives: Dietary carotenoids lutein (L) and zeaxanthin (Z) have been linked to improved visual and cognitive function. These effects are thought to be mediated by the presence of these pigments in critical regions of the retina and brain. There, it has been postulated that L and Z mediate improved performance by enhancing neural efficiency. The auditory system also relies on efficient segregating of signals and noise and LZ are also found in the auditory cortex. The purpose of the present study was to investigate the influence of LZ status (as assessed by the measuring levels in retina) on auditory thresholds in young non-smokers (N = 32, M = 20.72 ± 3.28 years)., Design: LZ status was determined by measuring macular pigment (MP) optical density using a standardized psychophysical technique (customized heterochromatic flicker photometry). Auditory thresholds were assessed with puretone thresholds and puretone auditory thresholds in white noise., Results: MP density was related to many, but not all, of the puretone thresholds we tested: 250 Hz (F(6,32) = 4.36, P < 0.01), 500 Hz (F(6,32) = 2.25, P < 0.05), 1000 Hz (F(6,32) = 3.22, P < 0.05), and 6000 Hz (F(6,32) = 2.56, P < 0.05)., Conclusion: The overall pattern of results is consistent with a role for L and Z in maintaining optimal auditory function.

Lutein is a member of the xanthophyll family of carotenoids, which are known to prevent hypoxia-induced cell damage in the eye by removing free radicals. However, its role in other tissues is controversial, and the effects of lutein on bone tissues are unknown. To identify a possible role of lutein in bone tissues, we examined the effects of lutein on bone formation and bone resorption and on femoral bone mass in mice. Lutein enhanced the formation of mineralized bone nodules in cultures of osteoblasts. On the other hand, lutein clearly suppressed 1α, 25-dihydroxyvitamin D 3 -induced bone resorption as measured by pit formation in organ culture of mouse calvaria. In co-cultures of bone marrow cells and osteoblasts, lutein suppressed 1α, 25-dihydroxyvitamin D 3 -induced osteoclast formation. In cultures of bone marrow macrophages, lutein suppressed soluble RANKL, the receptor activator of nuclear factor-kappaB (NF-κB) ligand, induced osteoclast formation. When five-week-old male mice were orally administered lutein for 4 weeks, the femoral bone mass was clearly enhanced in cortical bone, as measured by bone mineral density in dual X-ray absorptiometry and micro computed tomography (µCT) analyses. The present study indicates that lutein enhances bone mass in growing mice by suppressing bone resorption and stimulating bone formation. Lutein may be a natural agent that promotes bone turnover and may be beneficial for bone health in humans.

Several retinal degenerative diseases cause vision loss and retinal cell death. Currently, people face prolonged exposure to digital screens, rendering vision protection from light exposure a critical topic. In this study, we designed a complex lutein formula (CLF) by combining several natural compounds: Calendula officinalis, Lycium barbarum, Vaccinium myrtillus, Cassia obtusifolia, and Rhodiola rosea. In addition, we evaluated the protective effects of the formula on retinal functions in an animal model for light-induced retinal degeneration. We employed electroretinography to analyse retinal function, and conducted a histological examination of the morphological changes in the retina treated under various conditions. We revealed that the retinal function in animals exposed to light for 7 days decreased significantly; however, the retinal function of animals that had received the CLF exhibited superior performance, despite light exposure. In addition, a greater portion of the outer nuclear layer (ONL) (i.e. the nuclei of photoreceptors) in these animals was preserved compared with the animals that had not received the formula after 7 days of light exposure. These results revealed that our dietary CLF supplement attenuated retinal function loss resulting from long-term light exposure.