Schepens/Harvard study provides direct proof of dietary nutrient's essential role in protecting the retina from the damaging effects of light.
BOSTON -- (Nov. 11, 2002) -- 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.
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 have 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 photoreceptors 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. 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.
UPDATE: Press release dated June 9, 2003
A recent human study from the Medical Research Council Environmental Epidemiology Unit, University of Southampton, U.K. provides scientific evidence that a key nutrient and a strong antioxidant member of the carotenoid family, called zeaxanthin (zee-ah-ZAN'-thin,) may be far more important in preventing or stabilizing macular degeneration than previously realized. Macular pigment, which is primarily composed of lutein and zeaxanthin, is thought to protect the retina from damage due to light exposure and oxidative stress. Additionally, it has been shown that a high macular pigment density helps to retain visual sensitivity as we age and evidence indicates that raising the intake of dietary zeaxanthin can increase macular pigment. The macular pigment acts like "sunglasses" by protecting the critically important central sight from damaging light waves. The distribution of lutein and zeaxanthin in the eye may indicate they have different functions. Zeaxanthin is the dominant component in the center of the macula, while lutein dominates at the outer edges. The eye is selective and preferentially places dietary zeaxanthin in the very center of the macula, the most critical area for central vision with the greatest need for protection. This selective uptake of zeaxanthin occurs even though lutein is more available in the diet by a 20:1 ratio. Previous investigations may have obscured evidence of zeaxanthin's greater protective role by looking at the two carotenoids together, rather than separately. Although both of these carotenoids protect the retina, zeaxanthin has been shown to be a better photoprotector and a recent animal study supports the photoprotective activity of zeaxanthin. Additionally, zeaxanthin's chemical structure makes it a much more effective antioxidant than lutein. The human study concluded that decreased blood plasma zeaxanthin, but not blood plasma lutein, is significantly associated with the risk of age-related macular degeneration. This correlation strongly indicates that a high level of dietary zeaxanthin intake may directly affect the risk of developing macular degeneration. Increasing intake through diet or supplementation may help to slow down or stop vision loss with those who have been diagnosed with AMD.
The research team included Catharine R. Gale, Nigel F. Hall, David I.W. Phillips and Christopher N. Martyn.
|From a discussion between people from MDList and Malcolm Grover, representative of ZeaVision, LLC.|
1. What are specific sources of zeaxanthin?
Most lutein supplements come from a marigold flower extraction.
Are lutein and zeaxanthin always found in coexistence in dietary sources?
Lutein and zeaxanthin are not always found together. In nature, however, the answer is generally yes.
What are ranges of ratios of lutein and zeaxanthin in dietary sources?
The range is from nearly all zeaxanthin in some orange fruits and vegetables to nearly 40:1 lutein to zeaxanthin in some dark leafy greens. In a "normal" American diet, the ratio is probably 5-10:1 lutein to zeaxanthin. Blood serum levels would be 3-10:1 lutein to zeaxanthin. Most lutein supplements come from a marigold flower extraction and have a lutein to zeaxanthin ratio of 20-30:1. In the center of the macula the ratio shifts to a higher level of zeaxanthin, close to 1:1 which indicates a potential preferential uptake or use of zeaxanthin. This is an intriguing aspect to scientists and subject to hot debate.
What are lutein and zeaxanthin metabolisms? How does it get to the macula?
There are a number of oxidative metabolites of lutein and zeaxanthin found in the macula. Scientists have speculated that this is evidence for their role as antioxidants. The third most prevalent carotenoid in the macula is meso-zeaxanthin. This compound is not in our diet and is only found in the macula. The prevailing theory is that it is made from lutein in the macula and several laboratories are trying to prove this. Two other theories are that this compound occurs as part of an end product of a photoprotective reaction or that the eye is trying to convert the more prevalent lutein into the more preferred compound zeaxanthin, since meso-zeaxanthinıs structure is in between lutein and zeaxanthin. Dietary zeaxanthin is a right-handed isomer.
Little is known about how lutein and zeaxanthin get into the macula, although they are both carried predominantly on the ³good² cholesterol molecules (HDL) in the blood. Several research groups are looking for ³carrier or binding proteins² that may be important to a humanıs ability to respond to increases in their dietary consumption of those pigments. Most known risk factors have now been linked to reduced macular pigment levels. This year, animal and human research results have pointed towards competition between individualsı fat or adipose tissue and their retinal content of these pigments.
What available supplements contain zeaxanthin?
All lutein supplements contain trace amounts of ³natural² or dietary zeaxanthin. Some manufacturers label the zeaxanthin and some do not. Pure zeaxanthin became available only in 2002. Currently, only ZeaVision, LLC is selling pure zeaxanthin capsules in high potency.
How much zeaxanthin is believed necessary?
Unfortunately, no one knows the answer to this question. From epidemiology studies that showed positive benefits from dietary consumption of lutein and zeaxanthin, it appears as though 6 mg/ day of both compounds may be necessary to detect any beneficial effect. It is difficult to predict from this data, what the ratio or level should be for prevention or intervention. The National Eye Institute (NEI) is preparing for clinical studies by doing pre-clinical dosing experiments to determine the appropriate intake level of these nutrients. The use of supplements, however, should not be substituted for eating 4-7 servings of fruits and vegetables each day.
Is zeaxanthin from ZeaVision standardized? To me that is very important. It appears to me that taking two ICaps and eating a bit of the right foods is all that we need.
If the question is: "Are we standardized by an independent laboratory?" The answer is "no" we are not. Our raw product, however, comes from Roche, a respected leader in the pharmaceutical and fine chemicals business. Additonally, to the best of my knowledge, Alcon has not standardized ICaps.
Eating the right foods is terrific! So, many people just do not eat the right foods. The question that needs to be asked: "Is the quantity being consumed, providing enough of the nutrients?" This is where taking supplements ensures that the proper amount of nutients are being ingested. Continue to eat healthy foods and do not use supplements in lieu of eating the right foods.
ICaps indicate they contain zeaxanthin. That is true, however, what they are referring to is what is found with lutein during the process of extraction. If the lutein comes from marigolds (by far the most common source of lutein) then the ratio is 20:1 lutein to zeaxanthin. Therefore, if ICaps contains 4mg of lutein/zeaxanthin, then the amount of zeaxanthin is approximately .2mg.
A recommended amount of zeaxanthin is 10mg daily for anyone diagnosed with macular degeneration and 3mg for those taking it as a preventative measure. I believe if you check the food charts for zeaxanthin, it would be difficult to consume the quantities of the right foods to provide that level of zeaxanthin.
This web site has a very good explanation of lutein and zeaxanthin: www.rochenutrafacts.com/supplements/nutsci/LuteinSciReview.jsp#Introduction
What foods are highest in zeaxanthin content?
Here are the foods which are known to be high in zeaxanthin, listed in order from highest to least (>100mcg/100g serving), according to the Lutein and Zeaxanthin Scientific Review:
Pepper, orange, raw...1608
Corn, sweet, yellow, canned...528
Persimmons, Japanese, raw...488
Corn, frozen, cooked...375
Turnip greens, cooked...267
Collard greens, cooked...266
Lettuce. cos or romaine, raw...187
For additional information about zeaxanthin, see Lutein And Zeaxanthin May Offer Protection Against MD.
For information on how to obtain zeaxanthin as part of a balanced daily nutritional program, see Zeavision L.L.C. or call (888) 875-3937.