Supplementation With Carotenoids, Omega-3 Fatty Acids, and Vitamin E Has a Positive Effect on the Symptoms and Progression of Alzheimer's Disease.

BACKGROUND: Preliminary work by our center has reported behavior and functional benefits in patients with Alzheimer's disease (AD) following targeted micronutritional supplementation. OBJECTIVE: To build on the existing exploratory research and investigate the impact of these micronutrients on the natural progression of AD in a randomized controlled trial. METHODS: Patients with mild-moderate AD consumed daily 1 g fish oil (of which 500 mg DHA, 150 mg EPA), 22 mg carotenoids (10 mg lutein, 10 mg meso-zeaxanthin, 2 mg zeaxanthin), and 15 mg vitamin E or placebo for 12 months in a double-blind, placebo-controlled, randomized clinical trial. Carotenoids, ω-3FAs, and vitamin E were quantified in blood. Carotenoids were also measured in skin. AD severity was measured using the mini-mental state examination and dementia severity rating scale tools. Behavior, mood, and memory were measured using an informant-based questionnaire. RESULTS: Following 12 months of supplementation, the active group (n = 50) compared to the placebo group (n = 27), demonstrated statistically significant improvements in skin carotenoid measurements, blood carotenoids, ω-3FAs, and vitamin E concentrations (p < 0.05, for all). The active group also performed better in objective measures of AD severity (i.e., memory and mood), with a statistically significant difference reported in the clinical collateral for memory (p < 0.001). CONCLUSION: Exponential increases in the prevalence of AD and its relentless progressive nature is driving the need for interventions that help to ameliorate symptoms and improve quality of life in AD patients. Given the positive outcomes demonstrated in this trial, this combined micronutrient dietary supplement should be considered in the overall management of AD.

Comment on Richer et al. Night Vision and Carotenoids (NVC): A Randomized Placebo Controlled Clinical Trial on Effects of Carotenoid Supplementation on Night Vision in Older Adults. Nutrients 2021, 13, 3191.

Richer and colleagues [...].

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.

Dietary Intervention With a Targeted Micronutrient Formulation Reduces the Visual Discomfort Associated With Vitreous Degeneration.

Purpose: To investigate the impact of supplementation with a targeted micronutrient formulation on the visual discomfort associated with vitreous degeneration. Methods: In this clinical trial, 61 patients with symptomatic vitreous floaters were randomized to consume daily, the active supplement consisting of 125 mg L-lysine, 40 mg vitamin C, 26.3 mg Vitis vinifera extract, 5 mg zinc, and 100 mg Citrus aurantium or placebo for 6 months. Change in visual discomfort from floaters, assessed with the Floater Disturbance Questionnaire, was the primary outcome measure. Secondary outcome measures included best-corrected visual acuity, letter contrast sensitivity, photopic functional contrast sensitivity with positive and negative contrast polarity, and quantitative vitreous opacity areas. Results: After supplementation, the active group reported a significant decrease in their visual discomfort from floaters (P < 0.001), whereas the placebo group had no significant change in their visual discomfort (P = 0.416). At 6 months, there was a significant decrease in vitreous opacity areas in the active group (P < 0.001) and an insignificant increase in vitreous opacity areas in the placebo group (P = 0.081). Also, there was a significant improvement in photopic functional contrast sensitivity with positive contrast polarity in the active group after supplementation (P = 0.047). Conclusions: The findings of this study indicate improvements in vision-related quality of life and visual function of patients suffering from vitreous floaters after supplementation with a formulation of antioxidative and antiglycation micronutrients. Notably, these improvements were confirmed by the decrease in vitreous opacity areas in the active group. Translational Relevance: This targeted dietary intervention should be considered to support patients with symptomatic vitreous degeneration.

Omega-3 nutraceuticals, climate change and threats to the environment: The cases of Antarctic krill and Calanus finmarchicus.

The nutraceutical market for EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) is promoting fishing for Euphasia superba (Antarctic krill) in the Southern Ocean and Calanus finmarchicus in Norwegian waters. This industry argues that these species are underexploited, but they are essential in their ecosystems, and climate change is altering their geographical distribution. In this perspective, we advocate the cessation of fishing for these species to produce nutraceuticals with EPA and DHA. We argue that this is possible because, contrary to what this industry promotes, the benefits of these fatty acids only seem significant to specific population groups, and not for the general population. Next, we explain that this is desirable because there is evidence that these fisheries may interact with the impact of climate change. Greener sources of EPA and DHA are already available on the market, and their reasonable use would ease pressure on the Arctic and Antarctic ecosystems.

Targeted Nutritional Intervention for Patients with Mild Cognitive Impairment: The Cognitive impAiRmEnt Study (CARES) Trial 1.

Omega-3 fatty acids (ω-3FAs), carotenoids, and vitamin E are important constituents of a healthy diet. While they are present in brain tissue, studies have shown that these key nutrients are depleted in individuals with mild cognitive impairment (MCI) in comparison to cognitively healthy individuals. Therefore, it is likely that these individuals will benefit from targeted nutritional intervention, given that poor nutrition is one of the many modifiable risk factors for MCI. Evidence to date suggests that these nutritional compounds can work independently to optimize the neurocognitive environment, primarily due to their antioxidant and anti-inflammatory properties. To date, however, no interventional studies have examined the potential synergistic effects of a combination of ω-3FAs, carotenoids and vitamin E on the cognitive function of patients with MCI. Individuals with clinically confirmed MCI consumed an ω-3FA plus carotenoid plus vitamin E formulation or placebo for 12 months. Cognitive performance was determined from tasks that assessed global cognition and episodic memory. Ω-3FAs, carotenoids, and vitamin E were measured in blood. Carotenoid concentrations were also measured in tissue (skin and retina). Individuals consuming the active intervention (n = 6; median [IQR] age 73.5 [69.5-80.5] years; 50% female) exhibited statistically significant improvements (p < 0.05, for all) in tissue carotenoid concentrations, and carotenoid and ω-3FA concentrations in blood. Trends in improvements in episodic memory and global cognition were also observed in this group. In contrast, the placebo group (n = 7; median [IQR] 72 (69.5-75.5) years; 89% female) remained unchanged or worsened for all measurements (p > 0.05). Despite a small sample size, this exploratory study is the first of its kind to identify trends in improved cognitive performance in individuals with MCI following supplementation with ω-3FAs, carotenoids, and vitamin E.

Circulating Micronutrient Biomarkers Are Associated With 3 Measures of Frailty: Evidence From the Irish Longitudinal Study on Ageing.

OBJECTIVES: To examine the associations between 3 frailty instruments and circulating micronutrients in a large representative sample of older adults. DESIGN: Cross-sectional data from a nationally representative cohort study conducted between October 2009 and July 2011. PARTICIPANTS AND SETTING: Adults age ≥50 years (n = 4068) living in the community in Ireland. MEASUREMENTS: Circulating micronutrients (lutein, zeaxanthin, folate, vitamin B-12, and vitamin D) were measured, transformed, and standardized. Frailty was assessed using the Frailty Phenotype, the Frailty Index, and the FRAIL Scale (fatigue, resistance, ambulation, illnesses, and loss of weight), instruments. Multinomial logistic regression determined associations between micronutrients and prefrailty or frailty. Models were adjusted for sociodemographic, lifestyle, health, and seasonal factors. RESULTS: Adjusting for age, sex, and educational attainment, all 3 measures of frailty were associated with lower levels of lutein [relative risk ratios (RRRs): 0.43‒0.63], zeaxanthin (RRRs: 0.49‒0.63), and vitamin D (RRRs: 0.51‒0.75), and with the accumulation of micronutrient insufficiencies (RRRs: 1.42‒1.90). Attenuated but significant associations were also observed with all measures of prefrailty for lutein, vitamin D, and number of micronutrient insufficiencies. The associations with frailty persisted following additional adjustment for social, lifestyle, and health and seasonal factors, and following multiple test correction. CONCLUSIONS AND IMPLICATIONS: We have presented the most consistent evidence in the largest study to date that micronutrient concentrations are associated with prefrailty and frailty in older adults. Our data suggest that low micronutrient status has potential as an easily modifiable marker and intervention target for frailty and supports further investigation into micronutrient supplementation and fortification to prevent frailty and disability among older adults.

The Role of Nutrition for the Aging Population: Implications for Cognition and Alzheimer's Disease.

Improved life expectancy worldwide has resulted in a significant increase in age-related diseases. Dementia is one of the fastest growing age-related diseases, with 75 million adults globally projected to develop the condition by 2030. Alzheimer's disease (AD) is the most common form of dementia and represents the most significant stage of cognitive decline. With no cure identified to date for AD, focus is being placed on preventative strategies to slow progression, minimize the burden of neurological disease, and promote healthy aging. Accumulating evidence suggests that nutrition (e.g., via fruit, vegetables, fish) is important for optimizing cognition and reducing risk of AD. This review examines the role of nutrition on cognition and AD, with specific emphasis on the Mediterranean diet (MeDi) and key nutritional components of the MeDi, namely xanthophyll carotenoids and omega-3 fatty acids. Given their selective presence in the brain and their ability to attenuate proposed mechanisms involved in AD pathogenesis (namely oxidative damage and inflammation), these nutritional compounds offer potential for optimizing cognition and reducing the risk of AD.

Nutritional Intervention to Prevent Alzheimer's Disease: Potential Benefits of Xanthophyll Carotenoids and Omega-3 Fatty Acids Combined.

BACKGROUND: A growing body of scientific evidence suggests that enrichment of certain nutritional compounds in the brain may reduce the risk of Alzheimer's disease (AD). OBJECTIVE: To investigate the impact of supplemental xanthophyll carotenoids plus omega-3 fatty acids on disease progression in patients with AD. METHODS: Three trial experiments were performed. In Trials 1 and 2 (performed on patients with AD over an 18-month period), 12 patients (AD status at baseline: 4 mild and 8 moderate) were supplemented with a xanthophyll carotenoid only formulation (Formulation 1; lutein:meso-zeaxanthin:zeaxanthin 10:10:2 mg/day) and 13 patients (AD status at baseline: 2 mild, 10 moderate, and 1 severe) were supplemented with a xanthophyll carotenoid and fish oil combination (Formulation 2; lutein:meso-zeaxanthin:zeaxanthin 10:10:2 mg/day plus 1 g/day of fish oil containing 430 mg docohexaenoic acid [DHA] and 90 mg eicopentaenoic acid [EPA]), respectively. In Trial 3, 15 subjects free of AD (the control group) were supplemented for 6 months with Formulation 1. Blood xanthophyll carotenoid response was measured in all trials by HPLC. Omega-3 fatty acids were profiled by direct infusion mass spectrometry. RESULTS: Xanthophyll carotenoid concentration increases were significantly greater for Formulation 2 compared to Formulation 1 (p < 0.05), and progression of AD was less for this group (p = 0.003), with carers reporting functional benefits in memory, sight, and mood. CONCLUSION: This preliminary report suggests positive outcomes for patients with AD who consumed a combination of xanthophyll carotenoids plus fish oil, but further study is required to confirm this important observation.

Analysis of Lutein, Zeaxanthin, and Meso-Zeaxanthin in the Organs of Carotenoid-Supplemented Chickens.

The macular carotenoids (i.e., lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ)) exhibit anti-inflammatory, antioxidant and optical properties that are believed to support human health and function. Studying the accumulation and distribution of these nutrients in tissues and organs, in addition to the eye, is an important step in understanding how these nutrients might support global human function and health (e.g., heart and brain). Chicken is an appropriate animal model with which to study the accumulation of these carotenoids in organs, as the relevant transport molecules and carotenoid binding proteins for L, Z and MZ are present in both humans and chickens. In this experiment, a sample of 3 chickens that were supplemented with L and MZ diacetate (active group) and a sample of 3 chickens that received a standard diet (control group) were analysed. Both groups were analysed for L, Z and MZ concentrations in the brain, eyes, heart, lung, duodenum/pancreas, jejunum/ileum, kidney and breast tissue. L, Z and MZ were identified in all the organs/tissues analysed from the active group. L and Z were identified in all of the organs/tissues analysed from the control group; while, MZ was identified in the eyes of these animals only. The discovery that MZ is accumulated in the tissues and organs of chickens supplemented with this carotenoid is important, given that it is known that a combination of L, Z and MZ exhibits superior antioxidant capacity when compared to any of these carotenoids in isolation.

Supplemental Retinal Carotenoids Enhance Memory in Healthy Individuals with Low Levels of Macular Pigment in A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

BACKGROUND: There is a biologically plausible rationale whereby the dietary carotenoids lutein (L), zeaxanthin (Z), and meso-zeaxanthin (MZ), which are collectively referred to as macular pigment (MP) in the central retina (macula), support the maintenance of cognition via their antioxidant and anti-inflammatory properties. OBJECTIVE: To investigate the impact of supplemental L, Z, and MZ on memory, executive function, and verbal fluency among healthy individuals with low MP levels. METHODS: In this double-blind, placebo-controlled, randomized clinical trial, subjects (n = 91; mean±SD age = 45.42±12.40; % male = 51.6) consumed a daily formulation of 10 mg L, 10 mg MZ, and 2 mg Z (n = 45) or placebo (n = 46) for 12 months. Cognitive domains assessed included verbal and visual learning, immediate and delayed memory, executive function, and verbal fluency. MP and serum carotenoid concentrations of L, Z, and MZ were also measured. RESULTS: Following 12-month supplementation, individuals in the active group exhibited statistically significant improvements in memory when compared to the placebo group (paired associated learning [PAL] memory score [rANOVA, p = 0.009]; PAL errors [rANOVA, p = 0.017]). Furthermore, the observed reduction in the number of errors made in the PAL task among those in the intervention group was positively and significantly related to observed increases in MP volume (p = 0.005) and observed increases in serum concentrations of L (p = 0.009). CONCLUSION: This randomized, double-blind, placebo-controlled clinical trial demonstrates a memory-enhancing effect of daily supplementation with L, Z, and MZ in healthy subjects with low MP at baseline. The implications of these findings for intellectual performance throughout life, and for risk of cognitive decline in later life, warrant further study.

The Relationship Between Plasma Concentrations of Lutein and Zeaxanthin with Self-Reported and Actual Prevalence of AMD in an Irish Population-Based Sample.

PURPOSE: To investigate plasma lutein (L) and zeaxanthin (Z) concentrations with grading-confirmed and self-reported prevalence of age-related macular degeneration (AMD). MATERIAL AND METHODS: Data collected from a nationally representative prospective cohort study of community-dwelling adults aged 50 years and over in the Republic of Ireland. Participants underwent a computer-assisted personal interview and a center-based health assessment. Plasma concentrations of L and total Z (Z and meso-zeaxanthin [MZ]) were measured by high performance liquid chromatography, and retinal photographs were graded using a version of the AMD International Classification and Grading System. Consumption of supplements containing L and/or Z and/or MZ was recorded as supplement use. Four groups were identified: Group 1 (n = 24): AMD-afflicted and correctly aware; Group 2 (n = 264): AMD-afflicted but unaware; Group 3 (n = 41): AMD-free and incorrectly believed that they were afflicted with the condition; Group 4 (n = 4094): AMD-free and correctly self-reported absence of AMD. RESULTS: Of 4,423 participants with plasma concentrations of L and Z and gradable retinal photographs, 288 (6.5%) were afflicted with AMD, and 65 (1.5%) self-reported AMD. Controlling for family history and age, the relationship between grading-confirmed AMD and plasma L was positive and significant (p < 0.001). Mean plasma concentrations of L in Group 2 (mean = 0.2162 ± 0.132 µmol) and Group 4 (mean = 0.2040 ± 0.121 µmol/L) were significantly lower than Group 1 (mean = 0.4691 ± 0.0.372 µmol/L) and Group 3 (mean = 0.3176 ± 0.0.235 µmol/L). Supplement use was reported by 41.7% and 17.1% of participants in Groups 1 and 3, respectively, but only 2.7% and 1.9% of participants in Groups 2 and 4, respectively. CONCLUSION: A belief that one suffers from AMD, whether justified or not, is associated with supplement use and with higher plasma concentrations of L.

The Impact of Supplemental Antioxidants on Visual Function in Nonadvanced Age-Related Macular Degeneration: A Head-to-Head Randomized Clinical Trial.

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).

Stability of Commercially Available Macular Carotenoid Supplements in Oil and Powder Formulations.

We previously identified that the concentration of zeaxanthin in some commercially available carotenoid supplements did not agree with the product's label claim. The conclusion of this previous work was that more quality assurance was needed to guarantee concordance between actual and declared concentrations of these nutrients i.e., lutein (L) zeaxanthin (Z) and meso-zeaxanthin (MZ) in commercially available supplements. Since this publication, we performed further analyses using different commercially available macular carotenoid supplements. Three capsules from one batch of eight products were analysed at two different time points. The results have been alarming. All of the powder filled products (n = 3) analysed failed to comply with their label claim (L: 19-74%; Z: 57-73%; MZ: 83-97%); however, the oil filled soft gel products (n = 5) met or were above their label claim (L: 98-122%; Z: 117-162%; MZ: 97-319%). We also identified that the carotenoid content of the oil filled capsules were stable over time (e.g., L average percentage change: -1.7%), but the powder filled supplements degraded over time (e.g., L average percentage change: -17.2%). These data are consistent with our previous work, and emphasize the importance of using carotenoid interventions in oil based formulas rather than powder filled formulas.

Serum and macular response to carotenoid-enriched egg supplementation in human subjects: the Egg Xanthophyll Intervention clinical Trial (EXIT).

The macular carotenoids lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ) accumulate at the macula, where they are collectively referred to as macular pigment (MP). Augmentation of this pigment, typically achieved through diet and supplementation, enhances visual function and protects against progression of age-related macular degeneration. However, it is known that eggs are a rich dietary source of L and Z, in a highly bioavailable matrix. In this single-blind placebo-controlled study, L- and MZ-enriched eggs and control non-enriched eggs were fed to human subjects (mean age 41 and 35 years, respectively) over an 8-week period, and outcome measures included MP, visual function and serum concentrations of carotenoids and cholesterol. Serum carotenoid concentrations increased significantly in control and enriched egg groups, but to a significantly greater extent in the enriched egg group (P<0·001 for L, Z and MZ). There was no significant increase in MP in either study group post intervention, and we saw no significant improvement in visual performance in either group. Total cholesterol increased significantly in each group, but it did not exceed the upper limit of the normative range (6·5 mmol/l). Therefore, carotenoid-enriched eggs may represent an effective dietary source of L, Z and MZ, reflected in significantly raised serum concentrations of these carotenoids, and consequentially improved bioavailability for capture by target tissues. However, benefits in terms of MP augmentation and /or improved visual performance were not realised over the 8-week study period, and a study of greater duration will be required to address these questions.

Enrichment of Macular Pigment Enhances Contrast Sensitivity in Subjects Free of Retinal Disease: Central Retinal Enrichment Supplementation Trials - Report 1.

PURPOSE: The high-performance visual function associated with central vision is mediated by the macula (the central retina), which accumulates three diet-derived pigments (the carotenoids lutein [L], zeaxanthin [Z], and meso-zeaxanthin [MZ]). Our study sought to investigate the impact on visual function, including contrast sensitivity (CS), of supplementation with these naturally occurring carotenoids, in individuals with low retinal concentrations. METHODS: Subjects consumed daily a formulation containing 10 mg L, 2 mg Z, and 10 mg MZ (active group; n = 53) or placebo (n = 52) for a period of 12 months. Study visits were at baseline, 3, 6, and 12 months. Contrast sensitivity at 6 cycles per degree (cpd) was the primary outcome measure (POM). Secondary outcome measures included CS at other spatial frequencies, best-corrected visual acuity (BCVA), glare disability, photostress recovery, and light scatter. Macular pigment optical density (MPOD) was measured using dual-wavelength autofluorescence, and serum carotenoid concentrations were analyzed using high performance liquid chromatography (HPLC). RESULTS: Compared to placebo, statistically significant improvements from baseline CS were detected at 6 (P = 0.002) and 1.2 (P = 0.004) cpd in the active group. Additionally, improvements in CS were commensurate with the observed increases in retinal concentrations of these carotenoids (r = 0.342, P = 0.002 at 6 cpd). CONCLUSIONS: These results indicate that dietary fortification with the macular carotenoids can have meaningful effects on visual function.

Assessment of lutein, zeaxanthin and meso-zeaxanthin concentrations in dietary supplements by chiral high-performance liquid chromatography.

We investigated the concordance between actual and declared content of the three macular carotenoids in commercially available supplements aimed at eye health. Three batches of nine products were tested for content of lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ) by chiral HPLC-DAD. In every product tested, actual L concentration was close to target, but Z concentration varied greatly (47-248 % of declared concentration), and the L:Z ratio within some supplements was adversely affected in consequence. In six of seven products not declaring MZ, we found this carotenoid, and four of them, using the same L source, contained a concentration of MZ that correlated positively and significantly with measured concentrations of L (r2 = 0.86; P < 0.001). More transparency is needed in terms of concordance between actual and declared concentrations of Z in commercially available formulations, and MZ should be declared in those formulations where it is present.

Lutein, zeaxanthin and meso-zeaxanthin content of eggs laid by hens supplemented with free and esterified xanthophylls.

The xanthophyll carotenoids lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ) are found at the macula, the central part of the retina, where they are referred to as macular pigment (MP). MP is studied in human subjects because of its proven role in enhancing visual function and its putative role in protecting against age-related macular degeneration. These benefits are probably due to the antioxidant and short-wavelength filtering properties of MP. It is known that eggs are a dietary source of L and Z. This experiment was designed to measure the egg yolk carotenoid response to hen supplementation with L, Z and MZ. A total of forty hens were used in the trial and were divided into eight groups of five hens. Each group was supplemented (with about 140 mg active xanthophylls/kg feed) with one of the following oil-based carotenoid formulations for 6 weeks: unesterified L (group 1); L diacetate (group 2); unesterified Z (group 3); Z diacetate (group 4); unesterified MZ (group 5); MZ diacetate (group 6); L-MZ (1:1) diacetate mixture (group 7); L-MZ diacetate (1:3) mixture (group 8). Yolk carotenoid content was analysed weekly (in four randomly selected eggs) by HPLC. We found that hens supplemented with Z diacetate and MZ diacetate produced eggs with significantly greater carotenoid concentrations than their free form counterparts. This finding potentially represents the development of a novel food, suitable to increase MP and its constituent carotenoids in serum.

Lutein, zeaxanthin, and meso-zeaxanthin: The basic and clinical science underlying carotenoid-based nutritional interventions against ocular disease.

The human macula uniquely concentrates three carotenoids: lutein, zeaxanthin, and meso-zeaxanthin. Lutein and zeaxanthin must be obtained from dietary sources such as green leafy vegetables and orange and yellow fruits and vegetables, while meso-zeaxanthin is rarely found in diet and is believed to be formed at the macula by metabolic transformations of ingested carotenoids. Epidemiological studies and large-scale clinical trials such as AREDS2 have brought attention to the potential ocular health and functional benefits of these three xanthophyll carotenoids consumed through the diet or supplements, but the basic science and clinical research underlying recommendations for nutritional interventions against age-related macular degeneration and other eye diseases are underappreciated by clinicians and vision researchers alike. In this review article, we first examine the chemistry, biochemistry, biophysics, and physiology of these yellow pigments that are specifically concentrated in the macula lutea through the means of high-affinity binding proteins and specialized transport and metabolic proteins where they play important roles as short-wavelength (blue) light-absorbers and localized, efficient antioxidants in a region at high risk for light-induced oxidative stress. Next, we turn to clinical evidence supporting functional benefits of these carotenoids in normal eyes and for their potential protective actions against ocular disease from infancy to old age.

Concordance of Macular Pigment Measurement Using Customized Heterochromatic Flicker Photometry and Fundus Autofluorescence in Age-Related Macular Degeneration.

PURPOSE: We compared macular pigment (MP) measurements using customized heterochromatic flicker photometry (Macular Metrics Densitometer) and dual-wavelength fundus autofluorescence (Heidelberg Spectralis HRA + OCT MultiColor) in subjects with early age-related macular degeneration (AMD). METHODS: Macular pigment was measured in 117 subjects with early AMD (age, 44-88 years) using the Densitometer and Spectralis, as part of the Central Retinal Enrichment Supplementation Trial (CREST; ISRCTN13894787). Baseline and 6-month study visits data were used for the analyses. Agreement was investigated at four different retinal eccentricities, graphically and using indices of agreement, including Pearson correlation coefficient (precision), accuracy coefficient, and concordance correlation coefficient (ccc). RESULTS: Agreement was poor between the Densitometer and Spectralis at all eccentricities, at baseline (e.g., at 0.25° eccentricity, accuracy = 0.63, precision = 0.35, ccc = 0.22) and at 6 months (e.g., at 0.25° eccentricity, accuracy = 0.52, precision = 0.43, ccc = 0.22). Agreement between the two devices was significantly greater for males at 0.5° and 1.0° of eccentricity. At all eccentricities, agreement was unaffected by cataract grade. CONCLUSIONS: In subjects with early AMD, MP measurements obtained using the Densitometer and Spectralis are not statistically comparable and should not be used interchangeably in either the clinical or research setting. Despite this lack of agreement, statistically significant increases in MP, following 6 months of supplementation with macular carotenoids, were detected with each device, confirming that these devices are capable of measuring change in MP within subjects over time. (http://www.controlled-trials.com number, ISRCTN13894787.).