Cataract is the major cause of treatable
blindness worldwide, while age-related macular degeneration (AMD)
is the leading cause of non-treatable blindness among the elderly.
The costs associated with both conditions are enormous and will
continue to rise. Over the next few decades, the number of those
affected by cataracts and AMD here in the US is expected to increase
Results from the National Eye Institute's
Age-related Eye diseases study have already shown that antioxidants
can delay vision loss in moderate to advanced AMD for at risk
individuals. It's been estimated that delaying cataract by only
10 years would reduce the number of extractions by 50%. Modifying
dietary patterns and increasing intakes of specific nutrients
may very well be factors that can impact the onset or progression
of these age-related eye disorders.
For insight into the current state of nutrition,
cataract, and AMD research, we turn to Allen Taylor,
PhD, a distinguished scientist and recipient of multiple awards
for research excellence. Dr. Taylor's work on the influence of
nutrition and aging on vision has led to significant advances
in our understanding of eye diseases and has opened up new avenues
of research. Allen Taylor (AT) is interviewed by nutritionist Penelope Edwards, MPH, CNS (PE).
View biographies of the interview
Penelope Edwards - Dr. Taylor: you
and your collaborators, including epidemiologist Dr. Chung-Jung
Chiu, have led the field in investigating the effects of carbohydrate
intake on AMD and cataract. Several studies indicate that high
glycemic index diets (dGI) raise the risk for early AMD, or that
low dGI patterns might be protective for nuclear cataracts.
The glycemic index-a weighted measure of
how quickly carbohydrates raise blood glucose levels-speaks to
carbohydrate quality. Please tell us more about your research
in this area, and can you elaborate on how carbohydrates may be
harmful to eye tissues?
Allen Taylor - We were the first to
demonstrate that people who consume diets which are richer in
more readily available sugar from carbohydrates have higher risk
for all grades of AMD and prevalent types of cataract. We think
that the carbohydrate damages proteins which are directly needed
for the visual function of the lens and retina. The carbohydrate
also causes indirect damage by compromising the function of pathways
which usually serve to identify and remove the damaged proteins.
This leaves the cells with accumulations of dysfunctional and
cytotoxic proteins. Thus, the carbohydrates cause "double
PE - The data also suggest that carbohydrate
quantity rather quality is important for cortical cataracts. Does
that imply that nuclear and cortical cataracts form in different
AT - We are not sure why there are different relationships
with cortical cataract, or cataract in general, from the relationships
that are observed for AMD and dGI. It might be that there is far
lower blood supply and slower migration of sugars into the cortical
or nuclear areas of the lens as compared with the retina. We are
currently investigating this.
PE - Do you think it would it be
appropriate to begin labeling foods with dGI information to help
consumers plan a healthy diet?
AT - In my opinion, yes. I base my opinion on practical
considerations that include: 1) eating a lot of simple carbohydrate
is unnecessary and leads to many adverse health effects, including
obesity, metabolic syndrome and all of their complications, as
well as vision problems, 2) diminishing sugar intake is not difficult,
3) having excess sugars does damage the protein workhorses of
the cells of the body, and 4) consumption of simple sugars has
increased dramatically during the last 30 or so years.
PE - You've also investigated the
relationship between cataract and dietary fats which can affect
the composition and function of cellular membranes in the lens.
What have you found?
AT - Higher intake of alpha-linolenic acid was associated
with slightly higher risk for, and more rapid progress of early
nuclear cataracts. Because nuclear cataracts are often right in
the visual axis they disturb vision more than some cortical cataracts
and it is important to diminish risk for such cataract. In comparison,
higher intake of long-chain omega-3
fatty acid (eicosapentaenoic acid and docosahexaenoic acid)
and consumption of fish may modestly reduce the risk of cataract.
Higher intake of omega-3
fatty acids is associated with several health benefits.
PE - Realizing that people eat groups
of foods rather than single nutrients, you've analyzed the effects
of eating according to the food guide pyramid and by looking at
food groupings. Tell us what your findings indicate about eating
AT - Generally we found that people who consume lower
glycemic index diets and who consume larger proportions of fruits
and vegetables as well as dark-meat fish containing meals enjoy
better eye health, as measured by lower risk for AMD and cataract.
PE - You designed and directed the
Nutrition and Vision Project (NVP)-a long time collaboration between
your group, the Brigham and Women's Hospital, and the Nurses'
Health Study at Harvard. Please tell us a little about the NVP
and some of the project's key findings.
AT - The NVP was an outgrowth of the larger Nurses' Health
Study (NHS). Because the NHS was already obtaining state of the
art nutritional information and we were generously given access
to the cohort in the Boston area by Drs. Frank Speizer and Walter
Willett, we asked those nurses who live locally if they would
undergo a thorough eye examination at approximately 5 year intervals.
We also were able to collaborate with ophthalmologists like Dr.
Lahav at Tufts Medical Center and Dr. Chylack at Harvard, who
generously provided the eye examinations. Using a "reading"
center at Wisconsin and photo-grading at Harvard, we obtained
numerically graded images of the retinas and lenses at both visits.
Thus, we obtained photographs of different aspects of the lenses
and retinas of each nurse and we were also able to monitor the
change over 5 or so years by comparing images from the "baseline"
and the 5-year follow up. By collaborating we saved millions of
dollars in set up costs and we were able to complete analysis
at a fraction of the cost. Because we were also given access to
a wealth of additional data about the participants, we were able
to associate our new findings with prior information, thus, to
get added value to the work, and to provide a more mature perspective
to prior NVP investigations, such as relations between risk for
cataract extraction and fat intake or post-menopausal hormone
Since we now invest over $57 billion in eye care in the US, if
we can save a small proportion of the population from loss of
sight this would enhance their life quality immeasurably and the
small cost of these studies is an excellent investment of public
dollars. Our studies regarding carbohydrate indicate that we can
diminish risk significantly. In fact, we predict that we can save
about 200,000 people from advanced AMD in only 5 years just by
limiting simple carbohydrate intake. Thus, we are already repaying
the small investment.
PE - One finding from the NVP is
the observed link between vitamin
C supplement use for a decade or more and a decreased risk
of cortical or nuclear cataract in women. Will you fill us in
on how long term antioxidant intake dovetails with the process
AT - Many tissues of the body replace their constituents
often. For example, every few days you get new cells in your intestine.
Every 10 days you get new receptors for light in your retina.
In comparison, lens proteins last for decades and are damaged
by the light, oxygen, and sugars to which they are exposed. The
accumulation of such damage is causally related to onset and progress
of cataract. Stated a different way, if we are to protect the
lens, the protection should begin early and last a long time.
Thus, we rationalize our observations that prolonged intake of
adequate levels of antioxidants, such as vitamin
C, confers protection to lens proteins as compared to lens
proteins in persons who are poorly nourished.
PE - A large-scale prospective study
of women health professionals followed for 10 years just reported
in January that higher intakes of lutein, lutein and vitamin
E are associated with a reduced risk of cataract. A month
prior to that, the same research group found that giving women
600 IU natural-source vitamin
E every other day for nearly 10 years provides no benefit
for age-related cataract or subtypes. Your thoughts?
AT - Measuring and quantifying cataract is a highly specialized
field. My guess is that in the former case photograding of the
opacities was not possible, and this may have compromised their
ability to execute the study properly. But certainly there are
different opinions. There are several studies that failed to find
associations between vitamin
E intake and cataract, although we did find such a relationship.
One might hypothesize that the lens is primarily an aqueous environment
and thus rationalize stronger roles for vitamin
C, which is also aqueous soluble. vitamin
E is lipid soluble. But, the confusion is unsatisfactory.
Given the huge rewards and returns on maintaining sight among
the elderly, the returns are certainly worth the investment and
more intervention studies should be done.
PE - You've said that daily dietary
intake of about 250 mg vitamin
C, 90 mg vitamin
E, and 3 mg/day lutein – begun early in life –
should provide sufficient reserves to provide lens and macular
health benefits. These levels are considerably higher than the
current recommended daily intakes for C and E,
and higher than the average amount of lutein we consume. How "early in life" should a higher level
of intake begin in your estimation?
AT - I think that healthy eating should begin at birth
and be inculcated early and reinforced regularly. Our health would
be certainly be improved if by young adulthood we were already
consuming diets which are rich in fruits and vegetables and not
high in fats or simple carbohydrates.
PE - For older individuals participating
in the cataract portion of AREDS,
high dose C, E and beta-carotene had no apparent benefit. Yet a subsequent AREDS analysis found a reduced risk of nuclear cataract-and any cataract
- in those who elected
to take a simple multi-nutrient supplement throughout the trial.
Can you comment on these findings?
AT - I have several responses to this question. First,
it is important to remember that a large proportion of the AREDS subjects were already taking a multivitamin. Additional analyses
of the AREDS cohort implied some benefit to consuming multivitamins with respect
to risk for cataract. The benefit of taking the high dose supplement
with respect to nuclear cataract is consistent with several other
studies. It should be pointed out, however, that only high dose
supplements were used. It is also possible that the benefit could
be gained using lower levels. Clearly, more study is required.
PE - Can you tell us more about why
cataract and AMD form or occur?
AT - The lens and retina both have the job of "processing"
light. The lens receives it and transmits it to the retina where
it is received and converted to chemical and electrical impulses.
Just as a newspaper in the back of a car window gets brown from
the light of the day and the oxidation that the light energy causes
to the paper, so do our retinas and lenses get oxidized. The oxidation
of the proteins and sugars in these cells cause the proteins to
clump and precipitate. Such precipitation in the lens results
in opacification of the normally clear milieu.
In the retina the oxidation has many repercussions, including
accumulation of deposits, called drusen, which push cells away
from their blood supply, thus, resulting in their dysfunction
and loss. Such loss results in AMD-associated blindness. Moreover,
cells usually have protein quality control machinery that can
identify and destroy damaged proteins before they become cytotoxic.
This "machinery" is also damaged by oxidative or glycoxidative
stress. Thus, in the aged tissue, the cells are subject to multiple
insults and an inability to recover from those insults. For example,
one system for identifying damaged proteins involves the "ubiquitin
pathway". Discovery of this ubiquitous protein digesting
pathway was awarded the Nobel Prize in 2004 because it has so
many uses. Among them is the tagging of the damaged protein prior
to its degradation. We find that the function of the ubiquitin
pathway is itself compromised upon aging, hence the multiple jeopardy
of aged tissues. We hypothesize that similar compromises occur
in many tissues upon aging.
PE - Dr. Taylor, in your opinion
what are the biggest challenge(s) to reducing the prevalence of
cataract and AMD in our aging population?
AT - I think that identifying the optimal ways to protect
the eye and when protection needs to be started, is crucial. Also,
it is important to instill in children and youths the value of
good sight and good health in general. As it is said, "you
do not even think about it when you have sight, but when it is
gone it is invaluable". When we compare the expenditures
on health care or less rewarding investments vs. the costs of
research, given the repeating returns of the research it is clearly
well worth the investment. But, the time required for that research
may exceed political memories of a few months or a few years.
Thus, the public must demand that this research be given high
Given that we will all eventually have compromised vision, it
is essential to understand how the lens and retina are originally
assembled and maintained and to harness such capabilities to prolong
their function over time and in the face of stress.
Suggested further reading:
Interview with John D. Sheppard, MD
and Stephen C. Pflugfelder, MD:
New Developments in Dry Eye Treatment and Diagnosis
Dry eye is often said to be the most common
condition seen in ophthalmology practice. While it affects people
of all ages, this is a condition that increases with age. That
means clinicians will be seeing even more patients with dry eye
as a large portion of our population ages. What advances have
been made in understanding the etiology, diagnosis and treatment
of this condition, including the role of nutritional intervention?
For insight into the latest developments, we turn to John
D. Sheppard, MD (JDS) and Stephen C. Pflugfelder,
MD (SCP), interviewed by Penelope Edwards, MPH,
View biographies of the
to the audio version
Paul Bernstein, MD, PhD is an Associate
Professor of Ophthalmology and Visual Sciences in the Retina Division
at the Moran Eye Center, University of Utah School of Medicine.
Extensively published, 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 our current understanding of the
role lutein plays in eye health. Dr. Bernstein was interviewed
in December, 2005 by Penny Edwards, MPH, CNS, ScienceBased Health's
Science and Education Advisor.
MPH, CNS - Dr. Bernstein, you pioneered the use of Raman spectroscopy
to measure the levels of lutein, zeaxanthin and their metabolites
in the macula. Can you give a short explanation of how this technology
MD, PhD - 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 non-invasively 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.
PE - What
have you found out about lutein and macular health using the Raman
PB - Using
this technique, we have measured hundreds of subjects 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 three months after their
diagnosis of AMD had 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.
PE - Some research suggests
that 6-7 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
consider supplementation of these carotenoids?
PB - Yes, I think that greater
intake of lutein and/or zeaxanthin is probably beneficial for
macular health. Six milligrams 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 will 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 considerably higher than 6-10 mg probably do not provide
further enhancement because specific binding proteins in the macula
PE - Well, let's talk about
these specific binding proteins. You and your colleagues discovered
that the uptake of lutein
into the retina from the circulation is carried out via xanthophyll
binding proteins called XBP. Explain a little about lutein,
and meso-zeaxanthin - how they get into the macula, where they're
located in the retina and macula, and the importance of finding
these xanthophyll binding proteins.
PB - All lutein
in the human 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 carotenoids anywhere
in the human body. In the macula, there are approximately equal
amounts of three xanthophyll carotenoids: lutein,
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 xanthophyll binding protein (XBP) in any vertebrate
system. This XBP binds zeaxanthin
and meso-zeaxanthin and seems to enhance their antioxidant functions.
PE - Earlier this year you
published a paper describing an XBP that appears to be specific
Since most food sources like spinach contain far more lutein
is the body able to convert sufficient amounts of lutein
PB - The human
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.
PE - 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?
PB - 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 two compounds to determine if one is better than
PE - Some
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's 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's your
PB - 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.
PE - 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?
PB - 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. Since 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.
PE - 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?
PB - 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
a 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.
PE - 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?
PB - Although
there 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.
PE - If
you won some sort of research grant lottery and had unlimited
funding, what study would you conduct?
PB - 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.
PE - Thank You, Dr. Bernstein,
for shedding light on our current state of knowledge about these
important carotenoids, and your insights about future research
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