Nicole T. Stringham

Supplementation with macular carotenoids reduces psychological stress, serum cortisol, and sub-optimal symptoms of physical and emotional health in young adults

Purpose: Oxidative stress and systemic inflammation are the root cause of several deleterious effects of chronic psychological stress. We hypothesize that the antioxidant and anti-inflammatory capabilities of the macular carotenoids (MCs) lutein, zeaxanthin, and meso-zeaxanthin could, via daily supplementation, provide a dietary means of benefit. Methods: A total of 59 young healthy subjects participated in a 12-month, double-blind, placebo-controlled trial to evaluate the effects of MC supplementation on blood cortisol, psychological stress ratings, behavioural measures of mood, and symptoms of sub-optimal health. Subjects were randomly assigned to one of three groups: placebo, 13 mg, or 27 mg / day total MCs. All parameters were assessed at baseline, 6 months, and 12 months. Serum MCs were determined via HPLC, serum cortisol via ELISA, and macular pigment optical density (MPOD) via customized heterochromatic flicker photometry. Behavioural data were obtained via questionnaire. Results: Significant baseline correlations were found between MPOD and Beck anxiety scores (r = −0.28; P = 0.032), MPOD and Brief Symptom Inventory scores (r = 0.27; P = 0.037), and serum cortisol and psychological stress scores (r = 0.46; P < 0.001). Supplementation for 6 months improved psychological stress, serum cortisol, and measures of emotional and physical health (P < 0.05 for all), versus placebo. These outcomes were either maintained or improved further at 12 months. Conclusions: Supplementation with the MCs significantly reduces stress, cortisol, and symptoms of sub-optimal emotional and physical health. Determining the basis for these effects, whether systemic or a more central (i.e. brain) is a question that warrants further study.

Contrast Sensitivity and Lateral Inhibition Are Enhanced With Macular Carotenoid Supplementation

Purpose Once deposited in the retina, the so-called macular carotenoids lutein (L), zeaxanthin (Z), and mesozeaxanthin (MZ) have been shown to enhance visual performance. The purpose of our study was to investigate whether increasing macular pigment optical density (MPOD) could enhance lateral inhibitory processes, and thereby improve contrast sensitivity (CS). Methods A total of 59 young (18-25 years), healthy individuals participated in this 1-year, double-masked, placebo-controlled study. MPOD was assessed via heterochromatic flicker photometry. Lateral inhibition sensitivity (LIS) was determined with a computer-based, user-adjustable Hermann grid. CS (at 8 cycles/degree) was determined with a two-alternative, forced-choice procedure. Subjects received either the placebo (n = 10), 12 mg total macular carotenoids (n = 24), or 24 mg total macular carotenoids (n = 25). Results MPOD, LIS, and CS increased significantly in treatment groups between baseline and 6 months, and between 6 and 12 months (P < 0.05 for all) versus placebo. The relationships between changes in MPOD and both LIS and CS were significant at 6 and 12 months (P < 0.05 for both). Changes in CS and LIS over the 12-month study period were found to be significantly related (r = 0.41; P = 0.0014). Conclusions Increases in MPOD led to enhanced lateral inhibitory processes, which correspond to improved CS. Because optical filtering has the same net effect on dark versus light bars, it cannot explain these improvements. Improvement in CS with increases in MPOD therefore appears to involve enhancement of the fundamental physiological systems that give rise to edge detection.

Temporal Visual Mechanisms May Mediate Compensation for Macular Pigment

Macular pigment (MP) is a pre-receptoral filter that is diet derived and deposited in relatively high optical density in the foveal region of the retina. Due to its yellow coloration, MP absorbs light of relatively short wavelengths, ranging from 400 nm to 520 nm. Despite the spectral and spatial nonuniformity imposed upon the sensory retina by MP, perception appears to be relatively uniform across the central visual field. MP therefore offers an opportunity to determine experimentally potential mechanisms responsible for mediating this uniformity. After assessing, in 14 subjects, MP’s effects on the temporal sensitivity of both the short-wavelength- and middle-/long-wavelength-sensitive visual pathways, it appears that the visual system compensates for absorption of short-wavelength light by MP by slowing the sampling rate of short-wavelength cones and by increasing the processing speed of middle-/long-wavelength-sensitive cones. This mechanism could work via temporal summation or a temporal neural code, whereby slower response dynamics lead to amplification of relatively weak signals.

A potential mechanism for compensation in the blue—yellow visual channel

Due to their unique contribution to human vision, the short (S)-wavelength sensitive cones, their anatomical projections and, more recently, the cortical representation of their function, have motivated intense scientific interest. The principal study of the visual channel associated with S-cone projections has been conducted using psychophysical, neurophysiological, and ex vivo anatomical techniques, whereas more recent research on the pathway has employed functional magnetic resonance imaging (fMRI). The purpose of this manuscript is to present a perspective regarding the means by which color signals within this visual channel are processed in the brain, namely how differences in short-wavelength light transmission caused by intraocular, pre-receptoral filtration are compensated for. Recent results from fMRI and psychophysical studies indicate the existence of a frequency-dependent signal amplification mechanism, whereby lower frequencies result in an amplification of S-cone signals. This finding could motivate a future research direction for determining the localization of blue—yellow color processing and neural compensation in the blue–yellow visual channel.

Macular Carotenoid Supplementation Improves Visual Performance, Sleep Quality, and Adverse Physical Symptoms in Those with High Screen Time Exposure

The dramatic rise in the use of smartphones, tablets, and laptop computers over the past decade has raised concerns about potentially deleterious health effects of increased “screen time” (ST) and associated short-wavelength (blue) light exposure. We determined baseline associations and effects of 6 months’ supplementation with the macular carotenoids (MC) lutein, zeaxanthin, and mesozeaxanthin on the blue-absorbing macular pigment (MP) and measures of sleep quality, visual performance, and physical indicators of excessive ST. Forty-eight healthy young adults with at least 6 h of daily near-field ST exposure participated in this placebo-controlled trial. Visual performance measures included contrast sensitivity, critical flicker fusion, disability glare, and photostress recovery. Physical indicators of excessive screen time and sleep quality were assessed via questionnaire. MP optical density (MPOD) was assessed via heterochromatic flicker photometry. At baseline, MPOD was correlated significantly with all visual performance measures (p < 0.05 for all). MC supplementation (24 mg daily) yielded significant improvement in MPOD, overall sleep quality, headache frequency, eye strain, eye fatigue, and all visual performance measures, versus placebo (p < 0.05 for all). Increased MPOD significantly improves visual performance and, in turn, improves several undesirable physical outcomes associated with excessive ST. The improvement in sleep quality was not directly related to increases in MPOD, and may be due to systemic reduction in oxidative stress and inflammation.

Bioavailability of lutein/zeaxanthin isomers and macular pigment optical density response to macular carotenoid supplementation: A randomized double blind placebo controlled study

Purpose: To examine the bioavailability of Lutein (L) and Zeaxanthin isomers (Zi) concentrations in serum and changes in MPOD over 12 weeks macular carotenoids supplementation in healthy young subjects. Methods: In a randomized double blind placebo controlled study, twenty eight (N=28) healthy young male and female volunteers were randomized to receive one of three doses (6 mg L/1 mg Zi, 10 mg L/2 mg Zi or 20 mg L/4 mg Zi) for 12 weeks. Blood samples for serum L/Zi and macular pigment optical density (MPOD) were determined every two weeks over the 12 week study period. Serum lutein and zeaxanthin isomers concentration was determined by HPLC and MPOD by heterochromatic flicker photometry (HFP). The area under the curve (AUC) was calculated using the linear trapezoidal rule. Cmax and tmax was determined over 12 weeks of supplementation. Results: No significant difference in serum L/Zi concentrations of each dose group at baseline visit. Serum levels of L and Zi increased at 2 weeks, and peaked by 12 weeks. Median serum concentrations of 6 mg L, 10 mg L or 20 mg L groups from baseline to month 3 increased from 0.323 to 1.984 μg/dL (6-fold increase), from 0.353 to 2.234 μg/dL (7-fold increase), and from 0.372 to 3.163 (10-fold increase), respectively (all P<0.001). Median serum concentrations of 1 mg Zi, 2 mg Zi or 4 mg Zi groups from baseline to month 3 increased from 0.060 to 0.377 μg/dL (6-fold increase), from 0.096 to 0.350 μg/dL (4-fold increase), and from 0.117to 0.391 (3.3 fold increase), respectively (all P<0.001). Area under curve (AUC) for serum lutein increased (p<0.01) and AUC for serum Zi increased (p<0.03) with increased dose of L/Zi over placebo. AUCL increased in 6 mg of L & 1 mg Zi by 6 fold, 8 fold in 10 mgL and 2 mg, and 12 fold in 20 mg L and 4 mg Zi over placebo, respectively. AUCZi increased in all three treatments over placebo by 3 fold, 4 fold and 5 fold, respectively. MPOD increased significantly from baseline to month 3 increased for all L/Zi treatments over placebo. No adverse events were observed with any dose of lutein. Conclusion: Increasing doses of macular carotenoid supplementation significantly increased the serum AUC levels of lutein and zeaxanthin isomers, and doses up to 20 mg were safely administered. A long-term large clinical trial is necessary to investigate the safety and efficacy of macular carotenoids in health and disease. Introduction Lutein and zeaxanthin are 2 of the most abundant carotenoids present in the diet, and they are the pigments responsible for the bright colours of many fruits and vegetables. Lutein and zeaxanthin are isomers that differ by site of a single double bond [1,2]. Zeaxanthin exists as 3 stereoisomeric forms; (3R, 3’R)-zeaxanthin and (3R, 3’S)-zeaxanthin (also called meso-zeaxanthin) are the main forms present in the macula of the retina, while small amounts of (3S, 3’S)-zeaxanthin have also been detected [3,4]. Humans are unable to synthesize lutein and zeaxanthin isomers; thus, these nutrients are obtained from natural dietary sources or from supplementation. Circulating and tissue levels of xanthophylls increase with supplementation with lutein/zeaxanthin [5,6]. However, variability in their bioavailability has been reported [7-9], and has been related to factors such as the matrix of the formulation (e.g., presence of fat), the form in which they were administered (i.e., free versus esterified) and Correspondence to: Vijaya Juturu, Ph.D., F.A.C.N. Director (Global) Scientific and Clinical Affairs, OmniActive Health Technologies, 67 East Park Place, Suite 500, Morristown, NJ07950, USA, E-mail: v.juturu@omniactives.com

Macular carotenoid supplementation improves disability glare performance and dynamics of photostress recovery

BackgroundThe so-called macular carotenoids (MC) lutein (L), zeaxanthin (Z), and meso-zeaxanthin (MZ) comprise the diet-derived macular pigment (MP). The purpose of this study was to determine effects of MC supplementation on the optical density of MP (MPOD), repeated-exposure photostress recovery (PSR), and disability glare (DG) thresholds.MethodsThis was a double-blind, placebo-controlled trial. Fifty-nine young (mean age = 21.7), healthy volunteers participated in this study. Subjects supplemented their daily diet with either 10 mg L + 2 mg total Z (1 mg Z + 1 mg MZ; n = 24), 20 mg L + 4 mg total Z (2 mg Z + 2 mg MZ; n = 25), or placebo (n = 10) for 12 months. The primary outcome was a composite measure of visual performance in glare, defined by change in DG and PSR. Secondary outcomes included MPOD and visual fatigue. The primary endpoint for outcomes was 12 months. MPOD was assessed with customized heterochromatic flicker photometry. PSR times for an 8 cycle /degree, 15 % contrast Gabor patch target were determined after each of five successive exposures to intense LED lights. DG threshold was defined as the intensity of a ring of lights through which subjects were able to maintain visibility of the aforementioned target. Measures of all parameters were conducted at baseline, 6 months, and 12 months. Repeated-measures ANOVA, and Pearson product-moment correlations were used to determine statistically significant correlations, and changes within and between groups.ResultsMPOD for subjects in both supplementation groups increased significantly versus placebo at both 6- and 12-month visits (p < 0.001 for all). Additionally, PSR times and DG thresholds improved significantly from baseline compared to placebo at 6- and 12-month visits (p < 0.001 for all). At baseline, MPOD was significantly related to both DG thresholds (r = 0.444; p = 0.0021) and PSR times (r = -0.56; p < 0.001). As a function of MPOD, the repeated-exposure PSR curves became more asymptotic, as opposed to linear. The change in subjects’ DG thresholds were significantly related to changes in PSR times across the study period (r = -0.534; p < 0.001).ConclusionsIncreases in MPOD lead to significant improvements in PSR times and DG thresholds. The asymptotic shape of the repeated-exposure PSR curves suggests that increases in MPOD produce more consistent steady-state visual performance in bright light conditions. The mechanism for this effect may involve both the optical filtering and biochemical (antioxidant) properties of MP.Trial registrationISRCTN trial registration number: ISRCTN54990825. Data reported in this manuscript represent secondary outcome measures from the registered trial.

Nitric Oxide and Lutein: Function, Performance, and Protection of Neural Tissue.

The soluble gas neurotransmitter nitric oxide (NO) serves many important metabolic and neuroregulatory functions in the retina and brain. Although it is necessary for normal neural function, NO can play a significant role in neurotoxicity. This is often seen in disease states that involve oxidative stress and inflammation of neural tissues, such as age-related macular degeneration and Alzheimer’s disease. The dietary xanthophyll carotenoid lutein (L) is a potent antioxidant and anti-inflammatory agent that, if consumed in sufficient amounts, is deposited in neural tissues that require substantial metabolic demand. Some of these specific tissues, such as the central retina and frontal lobes of the brain, are impacted by age-related diseases such as those noted above. The conspicuous correspondence between metabolic demand, NO, and L is suggestive of a homeostatic relationship that serves to facilitate normal function, enhance performance, and protect vulnerable neural tissues. The purpose of this paper is to review the literature on these points.