Lutein and zeaxanthin supplementation improves visual performance

A report on DSM R&D Colloquium by Wolfgang Schalch, Research Department, DSM Nutritional Products, Kaiseraugst, Switzerland

Lutein and zeaxanthin are specifically accumulated in the human and primate retina where they form the yellow pigment of the macula lutea, the area in the center of the retina with the highest visual acuity (Figures 1 and 2) (Schalch 1999,2000,2003). Consistent with their yellow color, lutein and zeaxanthin absorb short wavelength (blue) light, the highest energy photons over the visual spectrum to reach the retina. Damage to the retina could be limited by lutein and zeaxanthin filtering out blue light.

Furthermore, lutein and zeaxanthin have antioxidant properties and can intercept and quench reactive oxygen species generated in the retina, which is characterised by the simultaneous presence of light and oxygen (Schalcht al.1992). These two properties of lutein and zeaxanthin, the absorption of blue light and their antioxidant potential, form the scientific basis for their possible contribution to reducing the risk of age-related macular degeneration, the most frequent irreversible blinding disease in Western countries.

Though research has been going on since 1980’s but efficacy of lutein was revealed only in 2004. However, the traditionally perceived “classical” role of the macular pigment in vision, namely its effects on visual acuity and contrast sensitivity (Nussbaum 1981) received only little attention. These effects are also thought to be mediated through filtering out the heavily scattered blue light before it impairs the image formed on the retina. Whilst this can be read in many textbooks (eg Oyster 1999), no study has systematically investigated these putative effects to date.

DSM is interested in these effects because their validation would demonstrate that, in addition to the ability of lutein and zeaxan, thin supplementation to reduce the risk of age-related macular disease, these molecules could confer benefits on healthy people as well.

In a recent DSM-initiated R&D Colloquium, Prof John L Barbur, Director of the Applied Vision Research Center at City University in London, reported on the results recently conducted clinical study with lutein and zeaxanthin, the results of which is presented as posters at two congresses in the USA (Schalch etal.2004a, Schalch et al 2004b).

The subjects Prof Barbur studied comprise a small sub-population of DSM’s LUXEA supplementation trial. In the course of this trial, 102 healthy young subjects were divided into four groups to receive daily amounts of 10 mg lutein, 10 mg zeaxanthin,10 mg lutein +10 mg zeaxanthin, or placebo. The duration of supplementation was six to 12 months.

The hypothesis At the center of Prof.Barbur’s interests regarding visual performance is vision in twilight, also called “mesopic ” vision (Figure 3).

In terms of illumination, mesopic vision is characterized by the intermediate light levels that prevail between complete darkness and brightness (the twilight zone).The retina has two light sensitive photoreceptor elements, rods and cones. In full brightness only cones are active, whilst at very low light levels only rods are sensitive enough to respond to light. In the twilight zone, however, both rods and cones are functional. The response of the densely packed cones is fast and precise but their required activation energy is relatively high.

Rods, on the other hand, require only little energy to generate signals that can contribute to a visual response. However, rod signals are sluggish and precise, not adding much to the details of the image formed (Rodieck 1998). The relative spectral sensitivity functions of rods and cones are represented in Figure 4.When the rod sensitivity function is compared with the absorption spectrum of the macular yellow pigment, it becomes evident that the two functions over lap to a large extent. This means that yellow macular pigment at tenuates light that stimulates the rods; in other words, macular pigment could reduce the effectiveness of rods to generate light-induced signals. This would have the consequence that in a small region of the retina the excellent characteristics of cone-mediate division are retained well into the mesopic range by minimising the detrimental effects of spatially summed and relatively sluggish rod signals.

Measurement of visual performance

Two of the main determinants of visual performance are visual acuity and contrast sensitivity. Visual acuity is usually expressed as the smallest letter-size someone can read under defined conditions and it is this parameter that is measured by the optician with vision charts. Contrast sensitivity can also be assessed using charts. These charts present letters of decreasing contrast and the subject ’s task is to find the letter with the lowest contrast he or she can just read. This determines his or her contrast sensitivity.

While these techniques are relatively imprecise and can only ensure gross changes, John Barbur has developed more sophisticated methods that allow small changes in the contrast threshold to be detected with high precision. He has been evaluating visual performance using different novel techniques for a range of parameters that are considered to be functionally important. One of these techniques, called “contrast acuity assessment ” (CAA).

CAA was originally designed to assess the vision of commercial airlines pilots (Chisholm 2003). The technique measures “contrast acuity thresholds” functionally useful measures that combine visual acuity and contrast sensitivity. To make the CAA technique even more sensitive for the detection of small changes, Prof Barbur has adapted it to be used with visual displays such as computer monitors. This setup makes it possible to conduct the measurements in different light-level situations in this case at low light levels. During the measurements, the task of the subjects is to locate the gap in a Landolt ring (Figure 5). The orientation of the stimulus is changed randomly and the contrast is adjusted to determine the threshold contrast for correct discrimination of gap location. The lower the threshold contrast measured, the better the visual performance of the subject.

Measurement of the macular pigment optical density profile

The profile of macular pigment optical density (MPOD) is measured by a new technique also developed by Prof. Barbur. This technique can record spatial profiles of the density of the yellow macular pigment across the retina. On a visual display, subjects view a target that alternates between two spectrally different components. One component, the blue light, is absorbed by the macular pigment, whilst the other component, which appears orange to the eye, is not absorbed by the macular pigment. This differential absorption causes an imbalance between the luminances of these two components and in turn causes the test stimulus to appear to be flickering.

Flicker can be eliminated by increasing the luminance of the blue component to compensate for the absorption by the macular pigment, and the lowest luminance just required for this condition is a quantitative measure of MPOD. This is an adaptation of the well-known principle of hetero chromatic flicker photometry (Delori 2001). For the construction of MPOD profiles these measurements are done with the test tar get presented at different points across the retina.

Results

Figure 6 shows the MPOD profiles of five subjects supplemented for six months with a combination of lutein and zeaxanthin (each 10 mg per day) and the equivalent profiles of six subjects from the placebo group. For the supplemented subjects an increase in total (integrated)MPOD of 44 percent as compared to the placebo group is evident and statistically significant (p=0.005). After supplementation had been discontinued for four months this difference had decreased to 20 percent, indicating that the prior supplementation was indeed the reason for the observed macular pigment density increase.

CAA thresholds were measured in a larger sub-population. In each of the three supplemented groups (lutein alone, zeaxanthin alone, lutein and zeaxanthin combined) as compared to placebo the data reveal a robust trend towards lower CAA thresholds, equivalent to improved visual performance. The improvement of about 24 percent which was found in the group supplemented with lutein alone was statistically significant. Other parameters were evaluated in addition to the effect of supplementation on CAA and the MPOD profile. These included retinal image quality, color vision, and light scattered in the eye.

The results obtained, although not statistically significant, exhibited the same trends as the CAA results, again indicating improvement in each of the supplemented groups. One explanation of this finding could be that supplementation can “correct ” higher-order aberrations of the eye. These higher order aberrations cannot normally be corrected by glasses but could in principle be corrected using customized, wavefront guided, corneal refractive laser surgery.

Conclusion

In his talk, Prof Barbur presented the results of a study that is probably the first systematic evaluation of the classical role of the macular pigment – its effect on vision to improve contrast sensitivity by specific absorption of blue light. In his exploratory study he has obtained preliminary results that are highly interesting and promising, and indicate that lutein and zeaxanthin supplementation could improve visual performance in healthy people, particularly in situations of low light intensity.

While the initial hypothesis of specific attenuation of rod activity in mesopic conditions could not yet be proven, the results indicate that lutein and zeaxanthin may have additional effects that are independent of macular pigment density. They therefore suggest that lutein and zeaxanthin supplementation may be beneficial for the vision of healthy young people.

These results warrant confirmation in a trial specifically designed for this approach. If the effects could indeed be confirmed, this would mean that macular pigment is not only important in reducing the risk of age-related macular degeneration, the most frequent irreversible blinding disease in Western countries, but could also improve the vision of healthy people, particularly in situations with low ambient light, such as driving at night.