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Study Demonstrates Essential Role of ZEAXANTHIN in Eye Health |
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Schepens/Harvard study provides direct proof of dietary nutrient's essential role in protecting the
retina from the damaging effects of light. Research performed at Schepens Eye Research Institute and Department of Ophthalmology, Harvard Medical School has established that the
dietary zeaxanthin (zee-uh-zan'-thin) plays an essential role in protecting the retina of the eye from the damaging effects of light.
From the many carotenoids in the
diet, the human retina selectively accumulates only two: zeaxanthin and lutein. Their concentration is so high in the macula, (the retinal region responsible for fine visual
activities) that the carotenoids are visible as a dark yellow spot called the macular pigment. Because these carotenoids absorb blue light, and because they are powerful
antioxidants, scientists have hypothesized that they protect the retina. Working with quail as an animal model, the Schepens project provided the first direct experimental evidence
that carotenoids do protect the retina.
Clinical Relevance of the New Findings Macular pigment has been implicated as a risk factor in age-related macular degeneration (AMD),
the most prevalent cause of vision loss in the elderly. Vision loss in AMD is due to the irreversible death of photoreceptors and/or the invasion of leaky, unwanted blood vessels into
the retina. At advanced stages of this progressive disease, everyday activities such as reading, driving, or even seeing the face of a loved one become impossible.
It is
estimated that more than 17 million Americans may have symptoms of AMD and that 2 million having functional blindness; 500,000 new cases are diagnosed each year. Some
clinical studies have found evidence that people with higher dietary or serum levels of zeaxanthin and lutein had reduced risk for advanced stages of age-related macular degeneration,
but others have found no association.
Significantly lower macular pigment levels have been found in people with factors known to increase risk for AMD (e.g. smoking), in eyes
with AMD, and in eyes at high risk for AMD. Epidemiologic studies have shown that people with higher dietary or plasma lutein/zeaxanthin have reduced risk for advanced stages of AMD.
It is not yet clear whether the reduced risk for AMD is due to lutein/zeaxanthin or due to some other nutrient in the plants containing carotenoids. The Schepens work has clearly
shown that the carotenoids protect the retina from light damage in animals. Some studies, but not all, have identified light damage as a risk factor in AMD.
To test this
hypothesized protection, the team selected Japanese quail because the retina resembles the human macula in having more cone photoreceptor s than rods and in highly selective
accumulation of zeaxanthin and lutein from their diet. Rodents were not studied because their retinas have very few cones and do not accumulate carotenoids. The studies examined the
effect of manipulating dietary carotenoids on light damage to retinas. C. Kathleen Dorey, principal investigator formerly with Schepens and now with R&D Consulting, and her
colleagues raised quail on diets that were normal, carotenoid-deficient, or carotenoid-deficient supplemented with high doses of zeaxanthin.
In the short-term study, reported
in the November 2002 issue of Investigative Ophthalmology and Visual Science (IOVS), the team divided the carotenoid-deficient quail into two groups, and for one week preceding light
damage, they fed one group zeaxanthin-supplemented diet. The study established that photoprotection was strongly correlated with the concentration of zeaxanthin in the retinas of the
quail. Retinas with low concentrations of zeaxanthin had suffered severe light damage, as evidenced by a very high number of apoptotic photoreceptor cells, while the group with high
zeaxanthin concentrations had minimal damage. Apoptosis is programmed cell death, the final common pathway for photoreceptor death in retinal degeneration.
In the
long-term study, reported in the November 2002 issue of Experimental Eye Research, groups of quail were raised for six months on carotenoid-deficient, normal or
zeaxanthin-supplemented diets before exposure to brighter light. The results showed extensive damage to the retina in the carotenoid-deficient animals, as evidenced by large
numbers of both dying photoreceptors and gaps or "ghosts" marking sites where photoreceptors had died. The group of quail with normal dietary levels of zeaxanthin
showed significantly less retinal damage than did the zeaxanthin-deprived group, while the quail group receiving high levels of zeaxanthin had few ghosts in their retinas.
These experiments by Dr. Dorey's team showed protection of both rod and cone photoreceptors. The research further demonstrated that retinas were protected by both zeaxanthin and
another antioxidant, vitamin E. Damage in these experiments was clearly reduced by zeaxanthin and tocopherol, but not lutein. Further experiments would be needed to
determine whether elevated lutein would offer protection.
These results are reminiscent of the early 20th century discovery of the role of vitamins. In those experiments,
extensive efforts were made to show that dietary deficiency of a compound caused health problems that were reversed by adding the substance back to the animal's diet.
The
results of the Schepens studies come on the heels of the Age Related Eye Disease Study (AREDS), sponsored by the National Eye Institute of the National Institutes of Health, which
concluded that daily consumption of a formula containing high doses of dietary antioxidants are effective in slowing the progression of AMD in patients with advanced stages of the
disease. It is noteworthy that zeaxanthin and lutein, two antioxidants selectively concentrated by the macula, were not commercially available when the AREDS began and were,
therefore, not able to be included in that study.
The Implications for Macular Degeneration Commenting on the implications of the Schepens studies, Dr. Dorey said: "AMD
is a multi-factorial disease clearly influenced by both genetic (family history) and environmental factors (diet, and possibly light history). The retina is constantly exposed
to oxidative injury, a leading candidate for initiating or accelerating retinal degeneration. Zeaxanthin is well suited to its role in maintaining retinal health, and may be an
important strategy to prevent or intervene in macular degeneration. It accumulates in the macula where it absorbs harmful blue wavelength light, and it accumulates in the RPE and the
most vulnerable portions of the photoreceptors where its potent anti-oxidant capacity can prevent oxidative damage, a problem that increases with aging.
"Our studies showed
that light damage was strongly influenced by the amount of zeaxanthin in the retina, and that significantly greater retinal protection was provided at dietary levels higher than those
normally occurring in the diet. Zeaxanthin has been extensively studied for safety and has been reviewed as a dietary ingredient by the FDA. We hope this work further stimulates
interest in clinical trials, and believe that zeaxanthin has a potential to eventually complement other strategies to improve the treatment of this vision-robbing disease."
# # #
The research team included: ** Lauren R. Thomson, M.D. Yoko Toyoda, M.D. Z-Y Wong, M.D., Francois C. Delori, Ph.D., and C. Kathleen Dorey, Ph.D. (now with R&D
Consulting) at Schepens Eye Research Institute. ** Kevin M. Garnett, BS, MBA at Applied Food Biotechnology, Inc. (O'Fallon, Mo.) ** Kimberly M. Cheng, Ph.D. and Cathleen R. Nichols at
Department of Animal Sciences, University of British Columbia (Vancouver) ** Neal E. Craft, Craft Technologies, Inc. (Wilson, N.C.) |
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Expert Commentary on Research Findings
"The two articles from Dr. Dorey's group use quail as a model because these birds concentrate the "macular pigments" (the
carotenoids, lutein and zeaxanthin) in their retinas, although in a manner different from humans. Some (but not all) epidemiologic studies on nutrition and eye diseases have shown
that these yellow compounds may help protect our eyes from developing age-related macular degeneration (AMD), a common and devastatin g disease of the retina. The researchers fed some
of their birds a diet rich in zeaxanthin for six months, and then observed the effect of very bright light on the Z-fed and on the control quail. Light of this intensity and duration
caused much more damage to the retinas of the control animals than to those of the Z-fed birds, who had accumulated lots of Z in their retinas.
"The importance of these
results is that they are the first direct, experimental evidence that Z can protect the retina, preventing photoreceptor cells (the rods and cones) from dying from an insult (in this
case, bright light). The thinking is that Z may also protect the retina from whatever insults, at present unknown, result in AMD. It is also important that dietary supplement ation
with Z resulted in higher concentrations of this compound in the quail retina. Zeaxanthin is found in some yellow, orange, and red fruits and vegetables; corn is a good source for
people. However, it would be easier to raise the level of Z in the retina through supplementation, in those people who have low levels of macular pigment. (This level can be measured
by a simple, non-invasive test.) Although lutein-containing supplements have been on the market for some time, this is not yet true for zeaxanthin." Alice Adler, Ph.D. Schepens
Eye Research Institute. "We first reported the beneficial effect of dietary zeaxanthin/lutein in reducing the risk of age-related macular degeneration in JAMA, 1994. Dr.
Dorey should be congratulated for her innovative research, which applied and expanded these clinical research findings to an experimental animal model. Her research supports our
findings and adds to the growing knowledge that the macular pigments play an important role in ocular health. The recently completed randomized trial component of the Age-Related Eye
Disease Study demonstrated that supplementation with antioxidant vitamins C, E and beta-carotene, as well the mineral zinc, reduces the rate of AMD progressio n by 25 percent over
five years. The growing evidence that the carotenoids -- zeaxanthin and lutein -- have beneficial effects requires more emphasis and a possible randomized trial to test their role in
the prevention of the serious visual consequences associated with the growing burden of macular degeneration among the elderly." Johanna M. Seddon, M.D., Sc.M. Director,
Epidemiology Unit for Macular Degeneration Research Massachusetts Eye and Ear Infirmary Harvard Medical School Harvard School of Public Health
"There is growing awareness
among both physicians and their patients that nutrition can play an important role in the prevention of visual loss from age-related macular degeneration (AMD), the leading cause of
irreversible blindness in the developed world. Two dietary micronutrients, zeaxanthin and lutein, are carotenoids derived from fruits and vegetables that are uniquely
concentrated in the macula of the human eye where they are likely to protect against blue light and oxidative damage. While there is compelling epidemiological data that high
levels of these two carotenoids in the diet, blood, and eye may protect against AMD, mechanistic evidence for their protective effect in living animals is notably lacking.
"In the recently published papers by Thomson et al., the authors begin to fill this void by demonstrating that zeaxanthin supplementation to Japanese quails affords partial
protection against acute light damage to the retina. This important research work provides further support for the clinical recommendation that individuals at risk for visual
loss from AMD should consider increasing their intakes of zeaxanthin and lutein through their diet or through nutritional supplementation." Paul S. Bernstein, MD, PhD Associate
Professor of Ophthalmology and Visual Sciences Moran Eye Center, University of Utah
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Contact Information for Expert Sources
Principle Investigator:
C. Kathleen Dorey, Ph.D. 781-646-8525 kdorey@earthlink.net
Ophthalmologists:
Johanna Seddon, M.D. Departments of Ophthalmology and Epidemiology Mass Eye and Ear
Infirmary 617-573-4010 johannna_seddon@meei.harvard.edu Background: Dr. Seddon was the first to report that higher levels of zeaxanthin /lutein in the diet or in the plasma were
associated with reduced the risk for advanced stages of AMD. Professor of both ophthalmology and epidemiology, Dr. Seddon is considered an expert in the dietary influence on the
progression of AMD. She has strong interest in the inherited, familial factors causing AMD. She showed that AMD was more likely to occur in both members of identical twins
than in both members of fraternal twins, strong evidence for a genetic component in the pathogenesis of AMD.
Paul S. Bernstein, M.D., Ph.D. Associate Professor of Ophthalmology
and Visual Sciences University of Utah, Moran Eye Center 801-581-6078 paul.bernstein@hsc.utah.edu Background: Dr. Bernstein is an ophthalmologist who has devoted his career to the
discovery of factors that contribute to AMD and other retinal degenerati ons. He has investigated whether abnormalities in genes causing recessive inherited macular degenerations
contribute to AMD, and has contributed to the advancement of understanding of macular pigments. Dr. Bernstein has conducted research on proteins that mediate the uptake of
carotenoids in the human macula, and recently developed new methods that permit measurement of macular pigment in patients with AMD. A statement from Dr. Bernstein is enclosed.
Macular Pigment Experts:
John T. Landrum, Ph.D. Chemistry Department Florida International University 305-348-3091 landrumj@fiu.edu Background: Dr. Landrum conducted
groundbreaking research that demonstrated donor eyes with AMD have lower concentrations lutein and zeaxanthin, the components of macular pigment. Dr. Landrum and his colleague,
Dr. Bone, also demonstrated that human subjects taking lutein or zeaxanthin have increased macular pigment. (Alert: since the same two subjects took lutein for several
months before they took the zeaxanthin, their conclusion that lutein raised macular pigment more is a controversial interpretation.)
Billy Hammond, Ph.D. University of
Georgia's Department of Psychology 706-542-4812 bhammond@egon.psy.uga.edu Background: Dr. Hammond is noted for his work showing that dietary supplementat ion results in elevated
macular pigment, and for work showing that macular pigment is lower in subjects who are smokers, female, older, obese, or have blue or green eyes. Numerous studies have shown
that advanced age and smoking dramatically increase risk for AMD. The other factors have been associated with risk for AMD in some studies, but not in others.
Experts in Carotenoid Protection:
Norman Krinsky, Ph.D Emeritus Department of Biochemistry, School of Medicine U.S. Department of Agriculture Human Nutrition Research Center on
Aging Tufts University School of Medicine 617-636-6861 norman.krinsky@tufts.edu Background: Dr. Krinsky has authored numerous articles, including a recent review article on biological
mechanisms for the protective action of xanthophyl ls (e.g. zeaxanthin) (J. Nutrition, 2002, 132:540-542). He is perhaps best known for his work on the anti-oxidant
characteristics of carotenoids, but he has numerous articles on the metabolism of carotenoids to retinoids and retinoic acids, (both molecules that play an important role in
development and normal tissue function). His recent work has focused on the role of cleavage products of b-carotene in inhibiting growth of breast cancer cells.
Alice
Adler, Ph.D. Carotenoid Biochemist: Macular Pigment & Carotenoid Binding Proteins Schepens Eye Research 617-912-7428 aadler@vision.eri.harvard.edu Background: Dr. Adler is a
biochemist who has worked on the transport of carotenoids in the eye, and their role in the eye. She was the first scientist to identify a protein that could bind Vitamin A and
transport it across the space between the photoreceptors that need it to make rhodopsin (the visual pigment) and the retinal pigment epithelial cells that store retinol and convert it
to a form that the photoreceptors can use. More recently, Dr. Adler identified xanthophyll-binding proteins in the human retina, and proposed that they bind to the same site on
microtubules that binds taxol, a compound used to treat breast cancer. |
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