Relationship of Lutein and Zeaxanthin Levels to Neurocognitive Functioning: An fMRI Study of Older Adults.

OBJECTIVES: It is well known that the carotenoids lutein (L) and zeaxanthin (Z) improve eye health and an accumulating evidence base suggests cognitive benefits as well. The present study investigated underlying neural mechanisms using functional magnetic resonance imaging (fMRI). It was hypothesized that lower L and Z concentrations would be associated with neurobiological inefficiency (i.e., increased activation) during cognitive performance. METHODS: Forty-three community-dwelling older adults (mean age=72 years; 58% female; 100% Caucasian) were asked to learn and recall pairs of unrelated words in an fMRI-adapted paradigm. L and Z levels were measured in retina (macular pigment optical density) and serum using validated procedures. RESULTS: Following first-level contrasts of encoding and retrieval trials minus control trials (p<.05, family-wise error corrected, minimum voxel cluster=8), L and Z were found to significantly and negatively relate to blood-oxygen-level-dependent signal in central and parietal operculum cortex, inferior frontal gyrus, supramarginal gyrus, planum polare, frontal and middle temporal gyrus, superior parietal lobule, postcentral gyrus, precentral gyrus, occipital cortex bilaterally, and cerebellar regions. CONCLUSIONS: To the authors' knowledge, the present study represents the first attempt to investigate neural mechanisms underlying the relation of L and Z to cognition using fMRI. The observed results suggest that L and Z promote cognitive functioning in old age by enhancing neural efficiency. (JINS, 2017, 23, 11-22).

Macular pigment optical density at four retinal loci during 120 days of lutein supplementation.

BACKGROUND: Increased consumption of lutein and zeaxanthin has been shown to increase macular pigment optical density (MPOD) in some individuals. Most interventions either obtained infrequent measures of MPOD or measured MPOD at a single retinal locus. PURPOSE: The aim of this study was to measure acute changes in MPOD at four retinal loci during lutein intervention. METHODS: For 120 days, three subjects consumed 30 mg of lutein and 2.7 mg of zeaxanthin supplement per day. MPOD was measured with heterochromatic flicker photometry at 20', 30', 60' and 120' eccentricity three or four times per week. High-performance liquid chromatography was used to measure serum carotenoid concentrations in blood samples collected at baseline and at 30-day intervals. RESULTS: At the two most central loci, MPOD significantly increased in all three subjects with a mean change of approximately 0.09 log units at 20' eccentricity and 0.08 log units at 30' eccentricity. MPOD significantly increased in two subjects at 60' eccentricity, and in one subject at 120' eccentricity. The increases in MPOD appeared to be linear and continued after treatment was ended. In all three subjects, log sensitivity at the reference locus decreased linearly. Serum lutein and serum zeaxanthin increased from baseline, reaching peak concentrations after 30 days of supplementation. CONCLUSION: The changes in MPOD suggest that carotenoid deposition occurs linearly and may be biased towards the central retina. Further, carotenoid deposition may occur outside the central fovea in interventions with pharmacological doses of carotenoid, resulting in underestimations of psychophysical measures of MPOD.

Bilberry (Vaccinium myrtillus) anthocyanins modulate heme oxygenase-1 and glutathione S-transferase-pi expression in ARPE-19 cells.

PURPOSE: To determine whether anthocyanin-enriched bilberry extracts modulate pre- or posttranslational levels of oxidative stress defense enzymes heme-oxygenase (HO)-1 and glutathione S-transferase-pi (GST-pi) in cultured human retinal pigment epithelial (RPE) cells. METHODS: Confluent ARPE-19 cells were preincubated with anthocyanin and nonanthocyanin phenolic fractions of a 25% enriched extract of bilberry (10(-6)-1.0 mg/mL) and, after phenolic removal, cells were oxidatively challenged with H(2)O(2). The concentration of intracellular glutathione was measured by HPLC and free radical production determined by the dichlorofluorescin diacetate assay. HO-1 and GST-pi protein and mRNA levels were determined by Western blot and RT-PCR, respectively. RESULTS: Preincubation with bilberry extract ameliorated the intracellular increase of H(2)O(2)-induced free radicals in RPE, though H(2)O(2) cytotoxicity was not affected. By 4 hours, the extract had upregulated HO-1 and GST-pi protein by 2.8- and 2.5-fold, respectively, and mRNA by 5.5- and 7.1-fold, respectively, in a dose-dependent manner. Anthocyanin and nonanthocyanin phenolic fractions contributed similarly to mRNA upregulation. CONCLUSIONS: Anthocyanins and other phenolics from bilberry upregulate the oxidative stress defense enzymes HO-1 and GST-pi in RPE, suggesting that they stimulate signal transduction pathways influencing genes controlled by the antioxidant response element.

Macular pigment optical density and photophobia light threshold.

Light absorption by macular pigment may attenuate visual discomfort, or photophobia, for targets composed of short-wavelength light. Macular pigment optical density (MPOD) and photophobia light thresholds were measured psychophysically in 10 subjects. The energy necessary to induce photophobia for a short-wavelength target relative to a long-wavelength target was linearly related to MPOD, as well as estimates of peak MPOD and integrated macular pigment. In four subjects who consumed lutein supplements, increases in MPOD corresponded to increases in photophobia light thresholds. Light absorption by macular pigment appears to influence the amount of short-wavelength light necessary to elicit photophobia.

Spinach cultigen variation for tissue carotenoid concentrations influences human serum carotenoid levels and macular pigment optical density following a 12-week dietary intervention.

Increasing intakes of carotenoid-rich plant foods can increase serum carotenoid concentrations and macular pigment optical density (MPOD) in most, but not all, individuals. Research objectives for this study were to (1) characterize tissue lutein (L) and beta-carotene (BC) concentrations in carotenoid-rich spinach (Spinacia oleracea L.) cultigens and (2) determine serum carotenoid and MPOD responses in human subjects consuming spinach cultigens differing in tissue L and BC concentrations. Thirteen spinach cultigens were evaluated for carotenoid accumulations over two consecutive growing seasons. "Springer" (8.4 and 6.5 mg/100 g of fresh mass for L and BC, respectively) and "Spinner" (12.1 and 9.2 mg/100 g of fresh mass for L and BC, respectively) spinach cultigens were selected for a dietary intervention study and represented low- and high-L concentrations. The high-L ("Spinner") and low-L ("Springer" ) spinach treatment groups consisted of 10 subject volunteers ingesting five 50-g spinach servings/week during a 12-week intervention. Average serum L concentrations increased by 22% (P = 0.07) from baseline (0.233 micromol/L) to 12 weeks (0.297 micromol/L) for subjects consuming low-L spinach. Subjects consuming high-L spinach showed increases of 33% (P = 0.04) in serum L from baseline (0.202 micromol/L) to 12 weeks (0.300 micromol/L). Average MPOD did not change for the low-L treatment group; however, subjects in the high-L group demonstrated increases (P = 0.02) in MPOD at the 30' eccentricity between baseline (0.343) and 12 weeks (0.374). This study demonstrates that serum carotenoid and MPOD are determined by L concentrations present in the spinach matrix. Results emphasize the role of cultigen selection among vegetable crops in determining phytochemical effects on human health.

A 12-wk egg intervention increases serum zeaxanthin and macular pigment optical density in women.

Two carotenoids found in egg yolk, lutein and zeaxanthin, accumulate in the macular retina where they may reduce photostress. Increases in serum lutein and zeaxanthin were observed in previous egg interventions, but no study measured macular carotenoids. The objective of this project was to determine whether increased consumption of eggs would increase retinal lutein and zeaxanthin, or macular pigment. Twenty-four females, between 24 and 59 y, were assigned to a pill treatment (PILL) or 1 of 2 egg treatments for 12 wk. Individuals in the PILL treatment consumed 1 sugar-filled capsule/d. Individuals in the egg treatments consumed 6 eggs/wk, containing either 331 microg (EGG 1) or 964 microg (EGG 2) of lutein and zeaxanthin/yolk. Serum cholesterol, serum carotenoids, and macular pigment OD (MPOD) were measured at baseline and after 4, 8, and 12 wk of intervention. Serum cholesterol concentrations did not change in either egg treatment group, but total cholesterol (P = 0.04) and triglycerides (P = 0.02) increased in the PILL group. Serum zeaxanthin, but not serum lutein, increased in both the EGG 1 (P = 0.04) and EGG 2 (P = 0.01) groups. Likewise, MPOD increased in both the EGG 1 (P = 0.001) and EGG 2 (P = 0.049) groups. Although the aggregate concentration of carotenoid in 1 egg yolk may be modest relative to other sources, such as spinach, their bioavailability to the retina appears to be high. Increasing egg consumption to 6 eggs/wk may be an effective method to increase MPOD.

Diet and serum carotenoid concentrations affect macular pigment optical density in adults 45 years and older.

The dietary carotenoids lutein (L) and zeaxanthin (Z) are the principal components of macular pigment (MP). Protection of the central retina by MP is suggested, but data are limited. Dietary practices and serum carotenoid concentrations were investigated in 98 adults, 45-73 y old, in relation to MP. Macular pigment optical density (MPOD) was measured at 4 loci: 10 min (10', 30 min (30'), 60 min (60'), and 120 min (120') retinal eccentricity. Serum L + Z concentrations in fasting subjects were correlated with MPOD: 10' (r = 0.29, P = 0.008), 30' (r = 0.342, P = 0.0006), and 60' (r = 0.73, P = 0.001) eccentricity. Dietary L + Z was positively correlated with MPOD: 10' (r = 0.24, P = 0.02), 30' (r = 0.237, P = 0.02), 60' (r = 0.27, P = 0.009), and 120' (r = 0.25, P = 0.02) eccentricity. The lowest fruit and vegetable consumers had lower MPOD at 30' (P = 0.01), 60' (P = 0.03), and 120' (P = 0.006) eccentricity compared with the highest consumers. Based on age quartiles (45-49 y), (50-55 y), (56-61 y), and (62-74 y), the youngest and oldest had higher MPOD than those 56-61 y at 60' (P < 0.05). Compared with those with a BMI (kg/m(2)) >/= 27, those with a BMI < 27 had higher serum concentrations of beta-carotene (P = 0.002), and higher MPOD at 60' (P = 0.04) and 120' (P = 0.01). These findings suggest that carotenoid-rich diets and serum carotenoids positively contribute to MP status.

Kale carotenoids remain stable while flavor compounds respond to changes in sulfur fertility.

Dietary intake of certain carotenoids has been associated with a reduced risk of disease. Kale (Brassica oleracea L. Acephala Group) has the highest levels of carotenoids lutein and beta-carotene, and is an excellent source of minerals among the green leafy vegetable crops. However, Brassica vegetables contain glucosinolate (GS) and S-methylcysteine sulfoxide (MCSO). While these sulfur compounds have medicinal value, they are also responsible for the bitter, acrid flavors that are often regarded as objectionable by consumers. Therefore, the objectives of this study were to investigate the influence of increased S fertility levels on (1) elemental accumulation, (2) GS and MCSO production, and (3) the accumulation patterns of carotenoid pigments in the leaves of three kale cultivars. Winterbor, Redbor, and Toscano kale were greenhouse-grown using nutrient solution culture with S treatment concentrations of 4, 8, 16, 32, and 64 mg of S/L. Decreasing S fertility decreased S leaf content, but increased the levels of Mg and Ca accumulation, two important minerals for human health. Levels of GS and MSCO decreased in response to a decreasing S level in nutrient solution. However, accumulation of lutein and beta-carotene was unaffected by S treatment. Lowering the S fertility in the production of kale should decrease the levels of negative flavors associated with high levels of GS and MCSO without affecting carotenoid pigment levels. Understanding the combined impact of fertility on flavor compounds and carotenoid pigments may help improve consumer acceptance of phytonutritionally enhanced vegetable crops.

In vivo assessment of retinal carotenoids: macular pigment detection techniques and their impact on monitoring pigment status.

Of the many carotenoids found within human tissue, only the carotenoids within the human retina can be assessed noninvasively at present. Such assessment should eventually provide a more complete understanding of the functional role of retinal lutein (L) and zeaxanthin (Z) (termed macular pigment, MP) in human vision. The emerging data allow for some initial observations. For example, there appears to be wide variation (>factor of 10) in the concentration of MP. Although MP levels have been recorded from nondetectable to 1.20 OD (optical density), the "average" levels, relative to what is possible, appear low. This may be due in part to the low average dietary intake of L and Z in the typical U.S. diet. Nonetheless, individual differences in MP may also be influenced by nondietary factors such as genetics, demographics and lifestyle characteristics. Some evidence indicates that the MP carotenoids may protect the retina and lens, and could improve vision through some optical mechanisms. Consequently, efforts to determine typical MP levels and the factors that influence individual differences in MP density should be continued.