Efficacy of Commercially Available Nutritional Supplements: Analysis of Serum Uptake, Macular Pigment Optical Density and Visual Functional Response.

Purpose: To compare the change in serum carotenoids, macular pigment optical density (MPOD) and visual function with the intake of two commercially available nutritional supplements. Methods: Participants were given a 24-week supply of a lipid-based micronized liquid medical food, Lumega-Z™ (LM), containing 28 mg of the macular carotenoids lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ), or given PreserVision™ AREDS 2 Formula (gel-caps; PV) containing 12 mg of the macular carotenoids L and Z, but no reported MZ. Serum levels of L, Z and MZ were obtained at baseline and after 12 weeks. Macular pigment optical densities (MPOD) and visual function were assessed at baseline and after 24 weeks. Results: Average blood serum concentrations of L, Z and MZ in the two groups at baseline were similar. The increases in L, Z and MZ were 0.434, 0.063 and 0.086 mol/L vs. 0.100, 0.043 and 0.001 mol/L, respectively, in the LM vs. PV group. From baseline to week 24, average MPOD in the LM-group increased by 0.064 from 0.418 to 0.482, whereas in the PV-group, it was essentially unchanged (0.461 to 0.459;). Although log-contrast sensitivity was improved in all groups under three conditions (photopic, mesopic and mesopic with glare), the change in log-contrast sensitivity was not statistically significant. Conclusion: Despite only a 2.3-fold higher carotenoid concentration than PV, LM supplementation provides approximately 3-4-fold higher absorption, which leads to a significant elevation of MPOD levels.

Efficacy of Diacetate Esters of Macular Carotenoids: Effect of Supplementation on Macular Pigment.

The accumulation of the carotenoids lutein, zeaxanthin, and mesozeaxanthin in the center of the human retina, and known as the macula lutea or macular pigment, is believed to protect the retina from age-related macular degeneration. Since the macular pigment is of dietary origin, supplements containing the relevant carotenoids are readily available. In this study, we compared the changes in macular pigment over a 24-week supplementation period for two groups of 24 subjects each assigned to either of two supplement formulations, 20 mg/day of lutein or 20 mg equivalent free carotenoids of a combination of diacetate esters of the macular carotenoids. The latter group responded with a larger increase (0.0666 ± 0.0481) in macular pigment optical density than the former group (0.0398 ± 0.0430), driven largely by the older subjects. The difference was statistically significant (p=0.0287). There was a general trend towards smaller increases in macular pigment for those subjects whose baseline value was high. However, the trend was only significant (p < 0.05) for subjects in the diacetate group. No differences in response could be attributed to the gender of the subjects. We also observed no indication that the use of statin drugs by a few of the older subjects influenced their responses.

Lens density measurements by two independent psychophysical techniques.

BACKGROUND: Cataract, a leading cause of vision impairment, is due to the lens becoming excessively optically dense. Change in the lens optical density (LOD) could be a useful indicator of incipient nuclear cataract and would necessitate the development of accurate measurement techniques. Mapcat sf™ is a heterochromatic flicker photometer for measuring macular pigment optical density (MPOD) under photopic conditions. In the process, it also measures LOD that is needed in the calculation of MPOD. LOD is then converted by the instrument to "lens equivalent age" (LEA). However, varying cone photoreceptor ratios among individuals could affect the LEA measurement. Scotopic vision is mediated by rod photoreceptors; therefore, LEA measurement under scotopic conditions potentially provides a reliable standard for assessing other methods. The study was conducted to test the level of agreement between the LEA data obtained under photopic and scotopic conditions for a sample population. We also comment on factors that might contribute to any disagreement. METHODS: LEAs were obtained by Mapcat sf for 25 subjects and compared with those obtained under absolute scotopic threshold conditions. RESULTS: The mean scotopic LEA for the subjects was 2.7 years higher than the mean photopic LEA, but this difference was not statistically significant. Measurements by the two methods were reasonably correlated (r(2) = 0.59, p < 0.0001). Significant individual differences in LEA by the two methods were found for six of the 25 subjects. Although our calculations included a standard long- to medium-wavelength-sensitive cone ratio, we found that different ratios could be found that rendered the differences in LEA insignificant for two of these six subjects. Variability in pupil diameter during scotopic measurements was considered another potential source of discrepancy between LEAs by the two methods. CONCLUSION: The absolute threshold technique, with long adaptation times, is probably impractical for routine lens density measurement, whereas Mapcat sf provided a rapid, straightforward test that may find its application in optometric/ophthalmic practice.

Innovative Troxler-free measurement of macular pigment and lens density with correction of the former for the aging lens.

Simplified measurement of macular pigment optical density (MPOD) is important because of the ocular health benefits that are attributed to these retinal carotenoids. Here, we describe a novel instrument designed for this purpose, based on heterochromatic flicker photometry (HFP), which removes a number of difficulties that subjects often experience with traditional HFP. The instrument generates 1.5- and 15-deg diameter, centrally viewed stimuli that alternate between blue and green colors generated by light emitting diodes (LED). The 15 deg stimulus replaces the small, eccentrically viewed stimulus used in traditional HFP. Subjects adjust the blue LED intensity until flicker is eliminated in the case of the 1.5 deg stimulus and eliminated around the periphery in the case of the 15 deg stimulus. A microprocessor computes the subject's MPOD, in addition to the lens OD, and uses the latter to correct the MPOD. Good repeatability was confirmed through test-retest measurements on 52 subjects. The overwhelming majority of them stated that they found the test easy. The importance of the lens correction on MPOD measurements was confirmed in a simulation study. The study showed that, without the correction, MPOD would show an apparent age-related decline in a population for whom there was no real age dependence.

Light distributions on the retina: relevance to macular pigment photoprotection.

Light exposure has been implicated in age-related macular degeneration (AMD). This study was designed to measure cumulative light distribution on the retina to determine whether it peaked in the macula. An eye-tracker recorded the subject's field of view and pupil size, and superimposed the gaze position. Fifteen naïve subjects formed a test group; 5 formed a control group. In phase 1, all subjects viewed a sequence of photographic images. In phase 2, the naïve subjects observed a video; in phase 3, they performed computer tasks; in phase 4, the subjects walked around freely. In phase 1, control subjects were instructed to gaze at bright features in the field of view and, in a second test, at dark features. Test group subjects were allowed to gaze freely for all phases. Using the subject's gaze coordinates, we calculated the cumulative light distribution on the retina. As expected for control subjects, cumulative retinal light distributions peaked and dipped in the fovea when they gazed at bright or dark features respectively in the field of view. The light distribution maps obtained from the test group showed a consistent tendency to peak in the macula in phase 3, a variable tendency in phase 4, but little tendency in phases 1 and 2. We conclude that a tendency for light to peak in the macula is a characteristic of some individuals and of certain tasks. In these situations, risk of AMD could be increased but, at the same time, mitigated by the presence of macular carotenoids.

Dose-dependent response of serum lutein and macular pigment optical density to supplementation with lutein esters.

We conducted a study to determine the effect of different doses of a lutein supplement on serum lutein concentration and macular pigment optical density (MPOD). Lutein is one of the major components of human macular pigment. Eighty-seven subjects received daily doses of 5, 10, or 20 mg of lutein, or a placebo, over a 140 day period. Serum lutein concentration was determined by HPLC and MPOD by heterochromatic flicker photometry (HFP). Serum lutein responded positively, except in the placebo group, reaching a plateau that, averaged for each dosage group, was linearly dependent on dose. Likewise MPOD, on average, increased at a rate that varied linearly with dose. For subjects deemed more proficient at HFP, approximately 29% of the variability in MPOD response could be attributed to a linear dependence on the fractional change in serum lutein concentration. We did not detect any significant influence of age on serum lutein uptake or MPOD response.

Optical anisotropy of the human cornea determined with a polarizing microscope.

We have investigated the optical anisotropy of the human cornea using a polarizing microscope normally used for optical mineralogy studies. The central part of the cornea was removed from 14 eyes (seven donors). With the sample placed on the microscope stage, we consistently observed hyperbolic isogyres characteristic of a negative biaxial material. The angle between the optic axes, generally similar in both eyes, ranged from 12 degrees to 40 degrees (mean+/-SD=31 degrees +/-8 degrees ). The optic axial plane always inclined downward in the nasal direction at 1 degrees -45 degrees below the horizontal (mean+/-SD=22+/-13 degrees ). The retardance produced by the corneas was estimated to be less than 200 nm. In conclusion, the human cornea possesses the anisotropy of a negative biaxial material. Both the angle between the optic axes and the retardance were fairly constant among the majority of samples, suggestive of uniformity in corneal structure.

Macular pigment, photopigments, and melanin: distributions in young subjects determined by four-wavelength reflectometry.

We have developed an objective procedure, using a modified retinal camera, to determine macular pigment (MP) optical density distributions in the human retina. Using two multi-band filters, reflectance maps of the retinas of young subjects (<25 years old) were obtained at 460, 528, 610 and 670 nm, without pupil dilation. The log-transformed maps were combined linearly to yield optical density maps of MP, cone and rod photopigments, and melanin. MP optical density and heterochromatic flicker photometry results for 22 subjects were in reasonable agreement. Cone photopigments, like MP, showed similar, well-defined peaks at the fovea, whereas rod photopigment showed a minimum. Melanin was more broadly distributed.

Macular pigment response to a supplement containing meso-zeaxanthin, lutein and zeaxanthin.

BACKGROUND: Age-related macular degeneration (AMD) is a disease with multiple risk factors, many of which appear to involve oxidative stress. Macular pigment, with its antioxidant and light-screening properties, is thought to be protective against AMD. A result has been the appearance of dietary supplements containing the macular carotenoids, lutein and zeaxanthin. More recently, a supplement has been marketed containing, in addition, the third major carotenoid of the macular pigment, meso-zeaxanthin. The purpose of the study was to determine the effectiveness of such a supplement in raising macular pigment density in human subjects. METHODS: A 120 day supplementation study was conducted in which 10 subjects were given gel-caps that provided 20 mg/day of predominantly meso-zeaxanthin, with smaller amounts of lutein and zeaxanthin. A second group of 9 subjects were given gel caps containing a placebo for the same 120 day period. Prior to and during the supplementation period, blood serum samples were analyzed by high performance liquid chromatography for carotenoid content. Similarly, macular pigment optical density was measured by heterochromatic flicker photometry. Differences in response between the supplementation and placebo groups were tested for significance using a student's t-test. RESULTS: During supplementation with the carotenoids, blood samples revealed the presence of all three carotenoids. Macular pigment optical density, measured at 460 nm, rose at an average rate of 0.59 +/- 0.79 milli-absorbance unit/day in the 10 supplemented subjects. This was significantly different from the placebo group (9 subjects) for whom the average rate was -0.17 +/- 0.42 milli-absorbance units/day. CONCLUSION: We have shown for the first time that meso-zeaxanthin is absorbed into the serum following ingestion. The data indicate that a supplement containing predominantly meso-zeaxanthin is generally effective at raising macular pigment density, and may turn out to be a useful addition to the defenses against AMD.

Dose-ranging study of lutein supplementation in persons aged 60 years or older.

PURPOSE: To examine the dose-response relationship between oral lutein supplementation and serum lutein concentrations in persons aged 60 years and older, with or without age-related macular degeneration (AMD). METHODS: Forty-five participants with no AMD, large drusen, or advanced AMD, were randomized to receive one of three doses (2.5, 5, or 10 mg) of lutein for 6 months and to be observed for 6 additional months after the cessation of lutein supplementation. RESULTS: The mean age of the participants (33 women) was 71 years (range: 60-91). The serum lutein concentrations of each dose group were similar before supplementation, increased at 1 month, and peaked by 3 months. Median serum concentrations of the 2.5-, 5-, and 10-mg groups from baseline to month 6 increased from 18.7 to 35.1 microg/dL (2-fold increase), from 17.8 to 59.2 microg/dL (2.9-fold increase), and from 15.1 to 66.8 microg/dL (4-fold increase), respectively (all P < 0.001). The increases in lutein serum concentrations did not vary with AMD disease severity (P = 0.98). No toxicity was observed with any dose of lutein. No significant changes were detected in visual acuity or visual field tests. CONCLUSIONS: Increasing doses of lutein supplements significantly increased the serum levels of lutein and zeaxanthin, and doses up to 10 mg were safely administered. A long-term large clinical trial is necessary to investigate the safety and efficacy of lutein in reducing the risk of the development of advanced AMD.

Macular pigment and the edge hypothesis of flicker photometry.

Heterochromatic flicker photometry is commonly used to measure macular pigment optical density (MPOD) in the human retina. It has been proposed, and accepted by many, that the MPOD so measured represents the value at a retinal location corresponding to the edge of the flickering, circular stimulus. We have investigated this proposal by using a series of annular stimuli to determine the MPOD distribution in the central 1.5 degrees of the retina for both eyes of 10 subjects. The MPOD obtained using a 1.5 degrees circular stimulus matched the MPOD distribution at a retinal eccentricity that was always less than the stimulus radius, and averaged, for the 10 subjects, 51% of the stimulus radius. Similar results were obtained using a 1 degrees stimulus. Thus the edge hypothesis is inconsistent with our data. We suggest that involuntary eye movements may be responsible for an apparent edge effect.

Heterochromatic flicker photometry.

Measurement of the macular pigment optical density (MPOD) by heterochromatic flicker photometry (HFP) is accomplished by viewing a small circular stimulus that alternates between a test wavelength that is absorbed by the MP (typically--blue, 460 nm) and a reference wavelength that is not absorbed (typically-green, 540 nm). Flicker observed by the subject is reduced to a null point by adjusting the intensity of the former while viewing the stimulus centrally, and then peripherally. A higher intensity, I, of the blue component of the stimulus is needed under central viewing conditions owing to attenuation by the MP. The MPOD at the test wavelength is given by log (Icentral/Iperipheral). Variation of the test wavelength has been used to measure the MPOD spectrum. This in vitro MPOD spectrum matches that of the carotenoids present in the macular region of the retina and demonstrates the validity and specificity of this methodology. The distribution of MPOD in the retina can be determined with HFP using a series of annular stimuli of different diameters.

Lutein and zeaxanthin dietary supplements raise macular pigment density and serum concentrations of these carotenoids in humans.

Age-related macular degeneration (AMD) is thought to be the result of a lifetime of oxidative insult that results in photoreceptor death within the macula. Increased risk of AMD may result from low levels of lutein and zeaxanthin (macular pigment) in the diet, serum or retina, and excessive exposure to blue light. Through its light-screening capacity and antioxidant activity, macular pigment may reduce photooxidation in the central retina. Lutein supplements, at 30 mg/d, were shown previously to increase serum lutein and macular pigment density in two subjects. In this study, we compared the effects of a range of lutein doses (2.4- 30 mg/d), as well as a high zeaxanthin dose (30 mg/d), on the serum and macular pigment in a series of experiments. Serum carotenoids were quantified by HPLC. Macular pigment densities were determined psychophysically. Serum lutein concentrations in each subject reached a plateau that was correlated with the dose (r = 0.82, P < 0.001). Plateau concentrations ranged from 2.8 x 10(-7) to 2.7 x 10(-6) mol/L. Zeaxanthin was less well absorbed than an equal lutein dose, resulting in plateaus of approximately 5 x 10(-7) mol/L. The rate of increase in macular pigment optical density was correlated with the plateau concentration of carotenoids in the serum (r = 0.58, P < 0.001), but not with the presupplementation optical density (r = 0.13, P = 0.21). The mean rate of increase was (3.42 +/- 0.80) x 10(5) mAU/d per unit concentration (mol/L) of carotenoids in the serum. It remains to be demonstrated whether lutein or zeaxanthin dietary supplements reduce the incidence of AMD.

Biologic mechanisms of the protective role of lutein and zeaxanthin in the eye.

The macular region of the primate retina is yellow in color due to the presence of the macular pigment, composed of two dietary xanthophylls, lutein and zeaxanthin, and another xanthophyll, meso-zeaxanthin. The latter is presumably formed from either lutein or zeaxanthin in the retina. By absorbing blue-light, the macular pigment protects the underlying photoreceptor cell layer from light damage, possibly initiated by the formation of reactive oxygen species during a photosensitized reaction. There is ample epidemiological evidence that the amount of macular pigment is inversely associated with the incidence of age-related macular degeneration, an irreversible process that is the major cause of blindness in the elderly. The macular pigment can be increased in primates by either increasing the intake of foods that are rich in lutein and zeaxanthin, such as dark-green leafy vegetables, or by supplementation with lutein or zeaxanthin. Although increasing the intake of lutein or zeaxanthin might prove to be protective against the development of age-related macular degeneration, a causative relationship has yet to be experimentally demonstrated.

A study of macular pigmentation in human eyes

The existence of the macular pigment in the living, human eye is at the present time fairly well established, but opinions on its role and effects on vision are still divided. To rectify this situation, several experiments were performed. In the main experiment, the optical density curve of the pigment was estimated for 49 European and West Indian subjects by comparing their foveal and extra-foveal spectral sensitivities measured by the flicker technique. No significant differences were observed related to race, normal environment, age, sex, colour of skin or colour of eyes, but red haired subjects had on average a significantly higher density of macular pigment. The extinction coefficient of the pigment, which appeared to be lutein, was the same for all subjects and differences in density were consistent with variations in pigment concentration and/or thickness of absorbing layer. In a subsidiary experiment, macular pigment density was assessed for a small sample of the 49 subjects by retinal photography. The combined results of this and the first experiment correlated well and led to the conclusion that visual performance is quite definitely affected by the presence in the fovea of a blue absorbing, non-photosensitive, pre-receptor pigment. The relatively low sensitivity of this region to blue light could not be explained satisfactorily in terms of differences associated with the receptors themselves. Spectral sensitivity measurements also revealed that West Indian subjects had more absorbent lenses than Europeans, equivalent to a difference in age of about 10 years. The dichroic ratio of the macular pigment layer was found to follow a similar spectral trend to the optical density spectrum. Some of the pigment molecules appeared to be arranged symmetrically about the fovea. It was shown that the number of such molecules was approximately the same for all subjects (AU)