Where Do Lutein and Zeaxanthin Fit?
A leading researcher discusses their roles
in the AMD treatment and prevention equation.
INTERVIEW WITH PAUL BERNSTEIN MD, PHD
Nutritionist Penelope Edwards, MPH, CNS, interviewed
Paul Bernstein, MD, PhD, for Retinal Physician recently about the evolving
role of carotenoids, specifically lutein and zeaxanthin. Dr. Bernstein is an associate
professor of Ophthalmology and Visual Sciences in the Retina Division at the Moran
Eye Center, University of Utah School of Medicine.
Dr. Bernstein has conducted research on the topic of macular
lutein and zeaxanthin concentrations and the relationship of these carotenoids to
AMD. His findings have contributed significantly to the current understanding of
the role lutein plays in ocular health.
Q. Dr. Bernstein, you pioneered the use of Raman spectroscopy
to measure the levels of lutein, zeaxanthin, and their metabolites in the macula.
Can you provide a short explanation of how this technology works?
While a number
of important epidemiological studies have found that high dietary intakes of foods
rich in lutein and zeaxanthin are associated with decreased risk of AMD, the critical
information on how much of these protective nutrients actually make it to the macula
is more challenging to obtain. We and other research groups have endeavored to develop
methods to measure macular carotenoid pigments noninvasively in living human subjects.
At the Moran Eye Center, we have found that resonance Raman spectroscopy
is a particularly useful method that is sensitive and specific for the macular carotenoids.
In this technique, we flash a low-power blue laser spot on the macula of the human
eye for less than a second, and we collect the light that is scattered back. A small
amount of this returning light is shifted to longer wavelengths owing to molecular
vibrations of the lutein and zeaxanthin in the macula.
It turns out that the concentration of the macular carotenoids
is so high and their Raman vibrations are so strong that we can readily detect their
signature Raman spectrum even in a complex biological system such as the eye. We
can then calculate the levels of lutein and zeaxanthin from the strength of the
collected Raman shifted light.
Q. What have you found out about lutein and macular health using
the Raman method?
We have measured hundreds of subjects both with and without AMD.
We have learned that macular carotenoid levels decline with age, reaching an especially
low level after age 60, just when the risk of AMD rises dramatically. We have also
found that macular pigment levels are significantly lower in AMD patients who were
not taking lutein supplements, relative to age-matched controls. Interestingly,
AMD patients who had been taking high dose lutein supplements for at least 3 months
after their diagnosis of AMD had macular carotenoid levels that were nearly the
same as the normal controls. These results are consistent with the hypothesis that
AMD is in part a disorder related to low macular levels of lutein and zeaxanthin,
and that supplementation can alter these levels in a potentially beneficial manner.
Q. Some research suggests that 6-10 mg of lutein/zeaxanthin represents
a reasonable level for supporting macular health, while the average dietary intake
is only 1-2 mg daily. Should people who are not consuming enough of these carotenoids
Yes, I think that greater intake of lutein and/or zeaxanthin
is probably beneficial for macular health, and 6 mg is a reasonable intake based
on our Raman results and on various epidemiological studies.
Increasing dietary intake of lutein and zeaxanthin is clearly
a healthy approach, but most Americans would have a hard time consuming that many
fruits and vegetables daily, so supplements would certainly play an important role
too. Ultimately, when noninvasive measurement of carotenoids is more widely available,
individuals who have unusually low levels could be identified and targeted for aggressive
nutritional intervention. For now, however, supplemental lutein doses considerable
higher than 6-10 mg probably do not provide further enhancement because specific
binding proteins in the macula become saturated.
Q. You and your colleagues discovered that the uptake of lutein
and zeaxanthin into the retina from the circulation is carried out via xanthophyll
binding proteins (XBP). Explain a little about lutein, zeaxanthin and meso-zeaxanthin:
how they get into the macula; where they are located in the retina and macula; and
the importance of XBP.
All lutein and zeaxanthin in the body must come from dietary
sources, usually fruits and vegetables or from supplements. The macula of the human
eye contains by far the highest concentrations of these carotenoids anywhere in
the human body. In the macula, there are approximately equal amounts of three xanthophyll
carotenoids: lutein, zeaxanthin and meso-zeaxanthin. Lutein's dietary source is
primarily dark green leafy vegetables. Zeaxanthin is less common in the human diet
coming from certain orange and yellow fruits and vegetables. Meso-zeaxanthin
is not found in the normal human diet, and is thought to originate from lutein.
The high concentrations and specific uptake of the macular carotenoids is mediated
by specific binding proteins that draw them into the tissue and stabilize them.
My laboratory has recently identified the first XBP in any vertebrate system. This
XBP binds zeaxanthin and meso-zeaxanthin and seems to enhance their antioxidant
Q. You recently published a paper describing an XBP that appears
to be specific for zeaxanthin. Since most food sources like spinach contain far
more lutein than zeaxanthin, is the body able to convert sufficient amounts of lutein
to zeaxanthin or meso-zeaxanthin?
The macula seems to want unusually high levels
of zeaxanthin, yet we get very little in the normal human diet. Lutein is much more
common in our diet, and it appears that some of our dietary lutein is converted
to meso-zeaxanthin in the macula, although the enzymes responsible for this conversion
have not yet been identified.
Q. Just what is our state of knowledge about the relative importance
of these two carotenoids? Do we need to be supplementing higher levels of zeaxanthin
as well as lutein?
The jury is still out on this question. There is much more
experience with lutein supplements, and there is some evidence that lutein can be
a precursor for macular meso-zeaxanthin, but it is also true that there is an exceptionally
large amount of zeaxanthin in the macula. Eventually, there will have to be head-to-head
studies of these 2 compounds to determine if one is better than the other.
Q. Some research papers have hinted at gender differences in handling
lutein. In one study, lutein supplements raised plasma levels of this carotenoid
equally well in both sexes, yet some women did not increase their macular pigment
density as well as the men. It has been suggested that some lutein may get diverted
away from the eye and stored in fat tissue instead more so in women than
in men. What are your thoughts?
I am not convinced there is a major difference between
women and men in this regard. At least in our Utah Raman studies, we do not see
a major difference between women and men.
Q. The antioxidant treatment arm of the age-related eye disease
study (AREDS) included beta-carotene, not lutein. The findings showed that zinc
and the antioxidant combination given in this trial was best at slowing AMD progression
and vision loss. Do you think that beta-carotene plays a role in protecting retinal
tissues, and if so, how?
In the AREDS study, it is impossible to sort out the effect
of beta-carotene independently from the effects of vitamin E and vitamin C. Very
little beta-carotene is actually present in the retina, so if it is having any effect,
it probably is due to its vitamin A precursor role. Because high doses of beta-carotene
are associated with increased risk of lung cancer in smokers, many people would
like to use lower doses and add lutein and/or zeaxanthin to the AREDS formula.
Q. The National Eye Institute (NEI) is planning a large-scale
trial examining the effects of lutein in AMD patients. Will they be utilizing the
Raman technology to measure carotenoid levels in the macula? Will you be involved
in this study?
As of December 2005, the NEI is evaluating applications for up to
60 sites for the AREDS II study which is expected to begin in 2006. A combination
of 10 mg of lutein and 2 mg of zeaxanthin will be tested against placebo. There
will also be an omega-3 fatty acid arm of the study. If we are selected as a site,
we would be interested in monitoring patient response to supplementation with our
ocular resonance Raman instruments.
Q. What do you see as the most important gaps in our knowledge
when it comes to the role of lutein and zeaxanthin in the macula?
is good epidemiologic and anecdotal evidence, we still don't have good prospective
results that lutein and zeaxanthin can decrease risk of developing AMD; hopefully,
AREDS II will give us some answers. From a basic science standpoint, there are still
many gaps in our knowledge of the uptake, metabolism, and function of lutein and
zeaxanthin that my laboratory hopes to solve.
Q. If you won some sort of research grant lottery and had unlimited
funding, what study would you conduct?
On the clinical side, I would like to see
a large-scale multiyear placebo-controlled head-to-head study of lutein and zeaxanthin
supplementation in high-risk patients for AMD using multiple methods to assess macular
response. On the basic science side, I would like to bring the state of knowledge
of carotenoid metabolism in humans to a level comparable to the intricate knowledge
we have of their roles in photosynthesis and photoprotection in plants.
Edwards is a science advisor to ScienceBased Health. Dr. Bernstein is a member of
the ScienceBased Health Scientific Advisory Board. He can be e-mailed at
Retinal Physician, Issue: January 2006