Lutein, zeaxanthin, and meso-zeaxanthin supplementation attenuates inflammatory cytokines and markers of oxidative cardiovascular processes in humans.

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

Association between dietary carotenoid intake and breast cancer risk: a case-control study among Korean women.

The association between dietary carotenoids and breast cancer (BC) risks were inconsistent. Therefore, this study investigated the association between dietary carotenoid and BC risks among Korean women. We recruited participants from the National Cancer Centre of Korea. Odds ratios and 95% confidence intervals were calculated with a logistic regression model. There was an inverse association between dietary carotenoid subclasses and BC risks; in particular, a higher intake of ß-carotene and lutein/zeaxanthin was associated with reduced BC risks. After subgroup analysis with estrogen receptor (ER)/progesterone receptor (PR) status, there was similar trend among ER-/PR- women. We further investigated which foods contribute to the carotenoid intake. A higher intake of radish leaves, kale, and bracken was associated with lowered BC risks. Accordingly, dietary carotenoid, particularly ß-carotene and lutein/zeaxanthin, appears to be associated with a lower risk of BC among Korean women.

Bioavailability of Lutein from Marigold Flowers (Free vs. Ester Forms): A Randomised Cross-Over Study to Assess Serum Response and Visual Contrast Threshold in Adults.

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

Effect of Antioxidant Supplementation on Macular Pigment Optical Density and Visual Functions: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

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

Dietary patterns and carotenoid intake: Comparisons of MIND, Mediterranean, DASH, and Healthy Eating Index.

The Mediterranean-Dietary Approaches to Stop Hypertension (DASH) Intervention for Neurodegenerative Delay (MIND) dietary pattern is associated with reduced cognitive decline and dementia risk. However, the nutrient features that distinguish the MIND from other patterns are unknown. We investigated the relationship between accordance to the MIND pattern and carotenoid intake (phytonutrients hypothesized to confer neuroprotection) relative to the Mediterranean, DASH, and Healthy Eating Index (HEI-2020). We hypothesized that MIND diet accordance would be a stronger predictor of carotenoid intake relative to other diet indices. A total of 396 adults (aged 19-82 years) completed the Dietary History Questionnaire to assess carotenoid intake and adherence to each diet index. Stepwise regressions with adjustment for covariates followed by the Meng's Z-test were used to compare correlation strength between each diet pattern and carotenoid. All diet patterns were positively associated with lutein and zeaxanthin, ß-carotene, α-carotene, and ß-cryptoxanthin (all ßs ≥0.38, Ps <.01). Effect size comparisons revealed that MIND accordance predicted a greater proportion of variance in lutein and zeaxanthin (all Zs ≥ 3.3, Ps < .001) and ß-carotene (all Zs ≥ 2.6, Ps < .01) relative to the Mediterranean, DASH, and HEI-2020. MIND accordance explained a greater proportion of variance in α-carotene (Z = 3.8, P < .001) and ß-cryptoxanthin (Z = 3.6, P < .001) relative to the HEI-2020. MIND diet accordance was disproportionately related to carotenoid intake, indicating the MIND index places greater emphasis on carotenoid-rich foods, particularly those containing lutein, zeaxanthin, and ß-carotene, relative to other diet indices. Future research is needed to define the role of these carotenoids in nutritional interventions for cognitive health.

Carotenoid pattern intake and relation to metabolic status, risk and syndrome, and its components - divergent findings from the ORISCAV-LUX-2 survey.

Carotenoids are generally associated with health-beneficial effects; however, their intake patterns related to the metabolic syndrome (MetS) and its components remain controversial. This cross-sectional study investigated associations between dietary intakes of individual carotenoids, fruits and vegetables, and the MetS and its components. Dietary intakes of 1346 participants of the Observation des Risques et de la Santé Cardio-Vasculaire au Luxembourg (ORISCAV-LUX-2) study were investigated by a 174-item FFQ, and carotenoid intake was determined by linking findings using mainly the USDA food databases. Components of MetS and complementary variables, including anthropometric (BMI, waist circumferences and waist:hip ratio) and biological parameters (TAG, HDL-cholesterol, fasting blood glucose and blood pressure), were measured. Logistic (for MetS) and linear multivariable regression models (including assessing MetS as scores) adjusted for various confounders were created. α-and ß-Carotene, as well as lutein + zeaxanthin, were inversely associated with MetS (also when it was measured on a continuous scale), reducing the odds for MetS by up to 48 %. However, lycopene, phytoene and phytofluene were rather positively associated with MetS scores and its components, though these adverse effects disappeared, at least for lycopene, when controlling for intakes of tomato-based convenience foods, in line with indicating a rather unhealthy/westernised diet. All these associations remained significant when including fruits and vegetables as confounders, suggesting that carotenoids were related to MetS independently from effects within fruits and vegetables. Thus, a high intake of carotenoids was bidirectionally associated with MetS, its severity, risk and its components, depending on the type of carotenoid. Future investigations are warranted to explore the inverse role that tomato-based carotenoids appear to suggest in relation to the MetS.

Omega-3 fatty acid, carotenoid and vitamin E supplementation improves working memory in older adults: A randomised clinical trial.

BACKGROUND & AIMS: Accumulating evidence suggests that omega-3 fatty acids (ω-3FAs), carotenoids and vitamin E can improve cognitive performance. However, their collective impact on cognition has not yet been investigated in healthy individuals. This study investigated the combined effect of ω-3FA, carotenoid and vitamin E supplementation on the cognitive performance of older adults. METHODS: Cognitively healthy individuals aged ≥65 years consumed daily 1 g fish oil (of which 430 mg docosahexaenoic acid, 90 mg eicosapentaenoic acid), 22 mg carotenoids (10 mg lutein, 10 mg meso-zeaxanthin, 2 mg zeaxanthin) and 15 mg vitamin E or placebo for 24 months in a double-blind, placebo-controlled, randomised clinical trial. RESULTS: Following 24-month supplementation, individuals in the active group (n = 30; aged 69.03 ± 4.41 years; 56.7% female) recorded significantly fewer errors in working memory tasks than individuals receiving placebo (n = 30; aged 69.77 ± 3.74 years; 70% female) (point estimate effect sizes ranged 0.090-0.105). Interestingly, as the cognitive load of the working memory tasks increased, the active group outperformed the placebo group. Statistically significant improvements in tissue carotenoid concentrations, serum xanthophyll carotenoid concentrations and plasma ω-3FA concentrations were also observed in the active group versus placebo (point estimate effect sizes ranged 0.078-0.589). Moreover, the magnitude of change of carotenoid concentrations in tissue, and ω-3FA and carotenoid concentrations in blood were related to the magnitude of change in working memory performance. CONCLUSION: These results support a biologically plausible rationale whereby these nutrients work synergistically, and in a dose-dependent manner, to improve working memory in cognitively healthy older adults. Increasing nutritional intake of carotenoids and ω-3FAs may prove beneficial in reducing cognitive decline and dementia risk in later life. STUDY ID NUMBER: ISRCTN10431469; https://doi.org/10.1186/ISRCTN10431469.

Carotenoids in the Management of Glaucoma: A Systematic Review of the Evidence.

Primary open-angle glaucoma (POAG) remains a leading cause of irreversible blindness globally. Recent evidence further substantiates sustained oxidative stress, and compromised antioxidant defenses are key drivers in the onset of glaucomatous neurodegeneration. Overwhelming oxidative injury is likely attributed to compounding mitochondrial dysfunction that worsens with age-related processes, causing aberrant formation of free radical species. Thus, a compromised systemic antioxidant capacity exacerbates further oxidative insult in glaucoma, leading to apoptosis, neuroinflammation, and subsequent tissue injury. The purpose of this systematic review is to investigate the neuroprotective benefits of the macular carotenoids lutein, zeaxanthin, and meso-zeaxanthin on glaucomatous neurodegeneration for the purpose of adjunctive nutraceutical treatment in glaucoma. A comprehensive literature search was conducted in three databases (PubMed, Cochrane Library, and Web of Science) and 20 records were identified for screening. Lutein demonstrated enhanced neuroprotection on retinal ganglion cell survival and preserved synaptic activity. In clinical studies, a protective trend was seen with greater dietary consumption of carotenoids and risk of glaucoma, while greater carotenoid levels in macular pigment were largely associated with improved visual performance in glaucomatous eyes. The data suggest that carotenoid vitamin therapy exerts synergic neuroprotective benefits and has the capacity to serve adjunctive therapy in the management of glaucoma.

[Involvement of egg antioxidant components in macular protection and vision improvement]. / Implicación de los componentes antioxidantes del huevo en la protección macular y la mejora de la visión.

INTRODUCTION: Age-related macular degeneration (AMD) is an ocular pathology that occurs with excess free radicals, which damages the photoreceptors of the retina producing a disability in the pigment epithelium, which leads, in the most advanced cases, to severe and irreversible vision loss. Lutein and zeaxanthin (L & Z) intake, which are abundant pigments in the macula and have antioxidant and anti-inflammatory action, as well as a role as blue light filter, seem to have a positive effect on the prevention of AMD. These carotenoids cannot be synthesized in the body and must be ingested with the diet. Green leafy vegetables and eggs are the main sources. The former have a higher L & Z content than the latter, but their bioavailability is lower, due to the lipid matrix of the egg yolk, which improves absorption. In relation to the consumption of eggs and AMD prevention, short-term consumption has been associated with an increase in serum concentrations of L & Z, long-term consumption with an increase in the density of macular pigment, and very long- term consumption with a decrease in the risk of developing advanced and neovascular AMD. These facts highlight the advantages of consuming eggs, which should be incorporated into the usual diet in order to minimize the progression of this ocular disease.

INTRODUCCIÓN: La degeneración macular asociada a la edad (DMAE) es una patología ocular que cursa con exceso de radicales libres y que daña los fotorreceptores de la retina, produciendo incapacidad en el epitelio pigmentario, lo que lleva, en los casos más avanzados, a una pérdida de visión severa e irreversible. La ingesta de luteína y zeaxantina (L y Z), que son pigmentos muy abundantes en la mácula y presentan acción antioxidante y antiinflamatoria, así como de filtro de luz azul, parece presentar un efecto positivo en la prevención de la DMAE. Estos carotenoides no pueden ser sintetizados por el organismo y hay que ingerirlos con la dieta, siendo los vegetales de hoja verde y los huevos sus principales fuentes. Los primeros presentan un mayor contenido de L y Z que los segundos, pero su biodisponibilidad es menor debido a la matriz lipídica de la yema del huevo, que hace mejorar su absorción. Con respecto al consumo de huevo y el padecimiento de DMAE, a corto plazo se ha relacionado con un aumento de las concentraciones séricas de L y Z, a largo plazo con un aumento de la densidad del pigmento macular y a muy largo plazo con una disminución del riesgo de desarrollar DMAE avanzada y neovascular, lo que pone de manifiesto las ventajas de consumir este alimento y su recomendación para incorporarlo a la dieta habitual con el fin de minimizar la progresión de esta enfermedad ocular.

Protective Effect of Lutein/Zeaxanthin Isomers in Traumatic Brain Injury in Mice.

Previous studies revealed that oxidative stress and inflammation are the main contributors to secondary injury after traumatic brain injury (TBI). In an earlier study, we reported that lutein/zeaxanthin isomers (L/Zi) exert antioxidative and anti-inflammatory effects by activating the nuclear factor-kappa B (NF-κB) and nuclear factor-erythroid 2-related factor 2 (Nrf2) pathways. However, its precise role and underlying mechanisms were largely unknown after TBI. This study was conducted to investigate the potential mechanism of L/Zi isomers in a TBI model induced by a cold injury model in mice. To investigate the effects of L/Zi, male C57BL/6j mice-induced brain injury using the cold trauma model was allocated into two groups (n = 7): (i) TBI + vehicle group and (ii) TBI + L/Zi group (20 mg/kg BW). Brain samples were collected 24 h later for analyses. L/Zi given immediately after the injury decreased infarct volume and blood-brain barrier (BBB) permeability; L/Zi treatment also significantly reduced proinflammatory cytokines, including interleukin1 beta (IL-1ß), interleukin 6 (IL-6), and NF-κB levels and increased growth-associated protein 43 (GAP-43), neural cell adhesion molecule (NCAM), brain-derived neurotrophic factor (BDNF), and Nrf2 levels compared with vehicle control. These data suggest that L/Zi improves mitochondrial function in TBI models, possibly decreasing inflammation and activating the Nrf2 pathway.