July 8, 2011
Blindness is scarier than heart disease, according to respondents of the Eye on Eyesight" survey, which was conducted by Surge Research for the nonprofit Choice Magazine Listening. While nearly twice the number of respondents aged 50 to 64 years said they feared losing their eyesight more than than they feared heart disease, 79 percent of adults said losing their eyesight is the third biggest fear after their own death and the death of a loved one.
Forgoing the connection between death and heart disease, the importance of eyesight to quality of life is apparent. Sight endows us with not just aesthetic rewards, but it also provides us valuable information and tools for our interactions with the world and other beings.
The National Federation of the Blind (NFB) estimated 1.75 million people in the United States are legally blindcentral visual acuity of 20/200 or less in the better eye with the best possible correction, or a visual field of 20 degrees or less. However, NFB further noted as many as 10 million Americans are blind or visually impairedincluding some 5.5 million seniorswith 75,000 additional people joining the ranks of blind or visually impaired each year. Given just 1 percent of Americans are born blind, the majority of blindness occurs later in life due to deterioration caused by diseases such as age-related macular degeneration (AMD), glaucoma and diabetes.
To see is to process light. The cornea layer of the eye focuses light through the pupil, lens and vitreous fluid to the retina. An ultra-sensitive layer of photoreceptor cells, the retina absorbs the incoming light and converts it to nerve signals. The optic nerve attached at the back of the eye carries these signals to the brain for further processing and use of the information.
Among the neuronal photoreceptor cells in the retina are the rods and cones. Found more on the periphery of the retina, the rods number in the hundreds of millions and are adept at black and white vision in dimmer environments. There are far fewer cones, about 7 million, which dominate the central retina and handle colors and brighter environments. High-resolution central vision, however, is handled by the macula, a yellow-pigmented area near the center of the retina. Its yellow color comes from its content of the xanthophyll carotenoids lutein and zeaxanthin, and is responsible for the maculas ability to filter blue and ultraviolet (UV) light.
Lutein and zeaxanthin are derived from the diet, found in abundance in dark, leafy greens such as spinach, kale and collards, and moderately plentiful in vegetables such as bell peppers, corn and broccoli. There is mounting evidence that increased consumption of lutein and zeaxanthin improves the macular pigment optical density (MPOD), indicating an important role in preserving vision and supporting retinal function.1 DSM researchers found the xanthophylls increased MPOD in different areas of the macula: lutein appears to be predominant in the fovea, while zeaxanthin covers a wider retinal area.2
Zeaxanthin (as OPTISHARP, from DSM Nutritional Products) has been shown to improve human color vision, visual acuity and vision in low-light conditions in healthy adults.3 Subjects took regular supplements of zeaxanthin, lutein, a combination of the two or placebo. Those who took lutein and zeaxanthin showed significant improvements in visual acuity and color vision.
These yellow carotenoids take a multifaceted approach to eye health, absorbing potentially harmful bands of spectral light, protecting against oxidative stress and damage, and helping to stymie inflammation.
Bill Hammond, Ph.D., professor and director of the graduate program on brain and behavior at University of Georgia, explained these xanthophylls are the best filters of scattered light in the retina and help the eye recover fast from photostress, in addition to increasing tolerance for photostress/glare. Hammond has put these theories to test in his universitys Vision Sciences Laboratory.
His 2007 report supported the theory that higher MPOD correlated to shortened recovery time from photostress and improved resistance to glare.4 A 2008 report followed, detailing how four to six months of supplementation with 12 mg/d of lutein and zeaxanthin (10 mg FloraGLO® brand lutein from Kemin Health and 2 mg OPTISHARP zeaxanthin) for six months significantly increased MPOD and improved visual performance in glare for most subjects in the trial.5 The researchers measured MPOD, glare disability and photostress recovery at baseline and then one, two, four and six months after starting supplementation.
MPOD increased in most subjects after one month of supplementation, with an average increase of 12 percent at two months, 24 percent at four months and 39 percent at six months, relative to baseline values. The increases were seen across the board, regardless of MPOD at the start of the trial. Hammond also noted a significant increase in veiling glare tolerance starting at the four-month mark, as well as a significant improvement in photostress recovery times (a decrease of 5 seconds after six months of supplementation).
Then in 2010, Hammond reported MPOD was linked to temporal visionthe temporal lobe processes high-level vision, including facial and spatial elements.6 He noted while lutein and zeaxanthin are concentrated in the central retinal macular pigment, 70 percent of total carotenoid concentration is in the brain, including the temporal lobe. He investigated the connection between MPOD and both critical flicker fusion threshold (CFF), an established method of studying temporal vision, and the more complete temporal contrast sensitivity function (TCSF). The results showed MPOD was positively linked to temporal function, based on the full TCSF in the center, but not at the parafoveal location; MPOD was also positively related to CFF.
The protections afforded by lutein and zeaxanthins mechanisms of action may help people stave off degenerative eye diseases. Cataract, the leading cause of blindness in the world, is characterized by the development of a cloudy or opaque lens due to damage caused by oxidative stress, exposure to UV light, genetics, aging and inflammation. The common types of age-related cataracts are nuclear (center of the lens) and cortical (in the lens periphery).
A major trial on antioxidant supplementation and lens opacities funded by the National Eye Institute (NEI), part of the National Institutes of Health (NIH), found no association between antioxidants and age-related cataracts.7 The Age-Related Eye Disease Study (AREDS) involved more than 4,700 older adults across the United States who received either antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; and beta carotene, 15 mg) or no antioxidants. Researchers concluded the intervention had no apparent effect on the seven-year risk of development or progression of age-related lens opacities or visual acuity loss.
Similar to AREDS, the Blue Mountain Eye Study conducted in Australia and published in 2002 featured 3,654 adults 49 years and older examined initially and 2,335 re-examined five years later for nutrient intakes and eye issues.8 in 2008, using lens photographs taken during these examinations, the research team conducted a specific investigation of cataract incidence and intakes of vitamin, mineral and carotenoid antioxidants.9 Higher antioxidant intakes had long-term protective associations against development of nuclear cataract, but not incident cortical or posterior subcapsular cataract.
London School of Hygiene and Tropical Medicine researchers also published results in 2008 on their investigation of blood antioxidant levels and cataracts in a North Indian Population, detailing inverse associations found between cataract and blood antioxidantsvitamin C, zeaxanthin, lutein, lycopene, alpha- and beta-carotene, and beta-cryptoxanthin, but not for alpha- or gamma-tocopherolin an antioxidant-depleted study sample.10
Rounding out the 2008 antioxidant cataract reports, researchers from the Nurses Health Study, Harvard Medical School, Boston, looked at more than 35,000 female health professionals without cataract and tracked their nutrient intakes and eye health over a period of 10 years.11 They found higher dietary intakes of vitamin E and lutein/zeaxanthin from food and dietary supplements were associated with significantly reduced risk of cataract
Harvard researchers have also focused specifically on cataract and carotenoids. Researchers from the Womens Health Initiative, Harvard, recruited 1,802 older women from the original cohort into the Carotenoids in Age-Related Eye Disease Study (CAREDS) and analyzed lutein and zeaxanthin intake with cataract development.12 They found those with the highest dietary intake of lutein and zeaxanthin had a 23-percent lower prevalence of nuclear cataract compared to placebo and a 32-percent lower prevalence compared to the lowest intake group. University of Melbourne, Australia, researchers reported finding similar results, highlighting an inverse association between high dietary lutein-zeaxanthin intake and prevalence of nuclear cataract.13
French researchers studied the associations of plasma lutein and zeaxanthin and other carotenoids with the risk of age-related maculopathy (ARM) and cataract in the population-based Pathologies Oculaires Liées à l'Age (POLA) Study, finding zeaxanthin alone was linked to reduced nuclear cataract and any cataract;14 beta-carotene was the only other carotenoid associated with reduced nuclear cataract.
Cataracts are often a consequence of diabetes, as is diabetic retinopathy (retinal damage), but both conditions have responded positively to carotenoid intervention in research. Australian researchers reported type 2 diabetics with retinopathy had significantly lower serum levels of lutein, zeaxanthin and lycopene compared to the non-retinopathy group.15 A combination of lutein and insulin showed the potential to prevent alterations in glutathione content linked to diabetic cataract onset and progression in an animal trial.16 Zeaxanthin supplementation also demonstrated an ability to inhibit diabetes-induced retinal oxidative damage and other abnormalities associated with pathogenesis of diabetic retinopathy in animal-based diabetes research.17
In other areas of eye health, genetic variations of the ABCA4 gene can lead to inherited eye diseases such as Stargardt disease and cone-rod dystrophy. Stargardts is a form of juvenile macular degeneration that triggers vision loss, which often progresses to legal blindness over time. Such patients are sensitive to glare and endure impaired central vision deterioration linked to a damaged macula. Similarly, cone-rod dystrophy is marked by deterioration of the rod and cone photoreceptor cells, often resulting in blindness.
Researchers from Scheie Eye Institute at the University of Pennsylvania, Philadelphia, investigated serum carotenoids, visual acuity, foveal sensitivity and retinal thickness in patients with either of these diseases as well as foveal fixation.18 They found this group of patients has reduced foveal MPOD and significantly lower than normal serum concentration of lutein and zeaxanthin. However, oral lutein supplementation for six months significantly increased serum lutein in 91 percent of patients and significantly augmented MPOD in 63 percent of patients. Despite these improvements, there was no improvement to central vision in these patients after six months of lutein supplementation; longer-term studies were recommended.
Age-related macular degeneration (AMD) is a much more common form of macular degeneration, as Prevent Blindness America reported 1.6 million U.S. adults have late-stage AMD. In AMD, irreversible degeneration of the retinal macula leads to progressive vision loss. The most common form is dry AMD, the slow breakdown of light-sensitive cells in the macula, leading to blurred vision. Common early symptoms include the presence of drusen, yellow deposits under the retina. Wet AMD is far less common and occurs when abnormal blood vessels behind the retina start to grow under the macula, raising the macula from its normal position and causing rapid damage.
The good news is the incidence of AMD may be declining, according to a recent collaborative analysis from University of Wisconsin School of Medicine and Public Health, Madison and the Centers for Disease Control and Prevention (CDC), Atlanta. Comparing data from the 2005 to 2008 National Health and Nutrition Examination Survey (NHANES) with data from the 1988 to 1994 NHANES, researchers found a 6.5-percent estimated prevalence of AMD and 0.8-percent prevalence of late-AMD in the general U.S. population, aged 40 years and older, for the years 2005 to 2008. These figures are significantly lower than the 9.5-percent AMD prevalence charted in the 1988 to 1994 NHANES cohort. The researchers noted the decline could be due in part to methodological differences, but the numbers are consistent with an observed trend in decreasing incidence of AMD.
The other good news is supplementation with lutein and zeaxanthin can provide some benefit to AMD patients.The Lutein Antioxidant Supplementation Trial (LAST), undertaken by the Department of Veterans Affairs, Chicago, looked at 90 patients with atrophic AMD who received 10 mg of purified lutein (as FloraGLO), purified lutein plus a broad spectrum antioxidant (as OcuPower, from Vitacost.com), or placebo for 12 months.19 Subjects in the lutein (10 mg) and lutein combination groups experienced improvements in visual parameters such as MPOD, visual acuity and contrast sensitivity, suggesting a potential role for lutein in treating AMD. Follow-up research showed lutein supplementation increased MPOD, which declined in those not taking supplements.20 Further, AMD patients who did respond to lutein supplementation (either 10 mg lutein alone or 10 mg lutein combined with vitamins, minerals and antioxidants) had continuing increases in MPOD, even at 12 months of supplementation; the researchers concluded such an intervention could effectively re-establish the beneficial macular barrier.
Optometrists at Singapore University compared macular response to lutein supplementation in both AMD and non-AMD subjects, finding the disease is not linked to intestinal malabsorption of the relevant macular carotenoids, and a diseased macula can accumulate and stabilize lutein and/or zeaxanthin.21 Both AMD and non-AMD subjects took 20 mg/d lutein ester (as XANGOLD®, from Cognis Nutrition & Health, now part of BASF, supplying the equivalent of 10 mg/day free lutein) for 18 to 20 weeks; MPOD and plasma lutein were measured. The results showed similarly significant plasma lutein and MPOD increases in both groups.
While the original AREDS and Blue Mountain Eye Study both failed to find associations between antioxidants and AMD, NEI decide to add other nutrients, such as lutein and zeaxanthin, to the original AREDS formula for use in the AREDS 2 trial, which is still underway. They recruited 4,000 AMD patients, who will receive one of four treatments10 mg/d of lutein (as FloraGLO) plus 2 mg/d of zeaxanthin; 1 g/d of omega-3 fatty acids; a combination of lutein, zeaxanthin and omega-3s; or a placebofor five years.
Omega-3s are included in AMD interventions due to a multi-mechanism benefit to eye health similar to lutein/zeaxanthin. In 2005, NEI researchers detailed the various roles played by docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in the eye: protecting against light- and oxygen-induced oxidative damage; bolstering the health of retinal photoreceptor cell membranes; fighting inflammation and endothelial cell dysfunction; and down-regulating genes associated with vascular instability.22
Tufts University, Boston, researchers examining the formula and patients from AREDS found combining a low-glycemic index (GI) diet with the AREDS nutrients (including both DHA and EPA) had the greatest reduction in risk for prevalent drusen and advanced AMD.23 Another analysis by the same team revealed a DHA-rich diet was associated with lower progression of early AMD, while combining a lower GI diet with increased DHA and EPA intake correlated with reduced progression of advanced AMD.24
Omega-3s may be protective in cases of glaucoma, the second leading cause of blindness in America. Glaucoma is a group of diseases marked by damage to the optic nerve and driven by increasing intraocular pressure. Six months of supplementation with a combination of omega-3 and omega-6 essential fatty acids (EFAs) appeared more effective than supplementation with individual essential fatty acids (EFAs) in a French trial that found a dietary combination of EPA, DHA and gamma-linolenic acid (GLA) prevented retinal cell structure and decreased glial cell activation induced by the elevation of intraocular pressure in rats.25 Additional research from the same French group (INRA) showed patients with primary open-angle glaucoma have lower levels of blood cells of phophatidylcholine (PC) carrying DHA, the levels of which were linearly correlated to visual field loss.26
Omega-3s may also help hamper dry eye syndrome, a lack of sufficient tears to lubricate and nourish the eye. A review from Mt. Sinai School of Medicine, New York, concluded various studies suggest a relationship between EFA supplementation and improvement in dry eye syndrome.27 Among these studies, the INRA group in France examined the efficacy of omega-3 and omega-6 PUFAs in a rat model of dry eye syndrome, finding a combination of EPA, DHA and GLA partially prevented the course of dry eye induced by scopolamine administration, impacting lipid homeostatis.28 Researchers from Louisiana State University, New Orleans, reported resolvins from EPA increase tear volume and decrease inflammation induced by dry eye, while topical application of DHA following corneal surgery was also shown in an animal trial to increase corneal epithelial cell proliferation.29 In subsequent research, the researchers found resolving E1 encourages tear production, corneal epithelial integrity, and a decrease in inflammatory inducible COX-2.30 Most recently, they noted while no firm recommendation for human use of DHA/EPA in dry eye syndrome can be made based only on the animal trials, the EFAs could prove useful in humans due to their apparent ability to resolve inflammation and the regenerate damaged corneal nerves.31
Antioxidant and anti-inflammatory mechanisms appear effective in various areas of eye health and are the mechanisms behind the use of various flavonoid-rich herbal products in protecting the eye and visual abilities, as well as improving eye function.
Anthocyanins have been specifically studied in eye health botanicals. A review from The Horticulture and Food Research Institute of New Zealand Ltd., Auckland, highlighted the antioxidant and anti-inflammatory benefits of anthocyanins in detailing their ability to preserve capillary integrity and improve vision.32
Containing more than 15 different antioxidant anthocyanins, black currant (Ribis nigrum) has demonstrated some potential benefits to the eyes. Researchers at Meiji Seika Kaisha Ltd., Saitama, Japan, investigated the ocular distribution of black currant anthocyanins in animals after oral, intravenous and intraperitoneal administration.33 They discovered intact forms of the anthocyanins could pass through the blood-aqueous barrier and blood-retinal barrier, and found these anthocyanins in the vitreous, lens and ocular tissues.34 In vitro research conducted by this team further demonstrated the ability of black currant anthocyanins to regenerate rhodopsin, a purple pigment in the retina that is responsible for the formation of photoreceptors.35
In clinical research on healthy adults, black currant anthocyanins administered at three dose levels (12.5 mg, 20 mg, 50 mg) significantly improved eye adaptation to darkness and subjective symptoms of visual fatigue in a dose-dependent manner.36 These flavanoids were also beneficial in the phototransduction transformation of rhodpsin in the eye upon and after light absorption in another clinical trial.37
In 2010, Japanese researchers published research showing administration of black currant extract (BCE) may curtail the development of myopia (nearsightedness).38 Researchers from Meiji Seika Kaisha Ltd. evaluated the effects of oral BCE on the enlargement of globe component dimensionsa step in myopia developmentin a negative lens-induced chick myopia model. The birds received BCE once daily for three days, and black currant anthocyanins intravenously once daily for three days. Results showed BCE significantly inhibited enlargement of vitreous-chamber depth, axial and ocular lengths in a dose-dependent manner, while the intravenous anthocyanins also inhibited elongation of vitreous-chamber depth and axial length.
Bilberry (Vaccinium myrtillus) is also rich in anthocyanins and has been studied for mechanisms in ocular disorders. According to a monograph in the Alternative Medicine Review, French researchers studying Royal Air Force pilots during World War II found consumption of bilberry improved nighttime visual acuity.39 However, more recent trials on this association have proven inconclusive. Two studies in young adult men found bilberry anthocyanosides at various dosages (24 mg, 48 mg, 160 mg) had no effect on night vision acuity or night contrast sensitivity.40,41 Additionally, a systematic review on trials about bilberry anthocyanosides for effects on night vision reported mixed results, but noted negative outcomes were associated with more rigorous methodology, lower dose levels and extracts from berries with more varied anthocyanoside content.42 The researchers suggested additional trials should investigate the effects of bilberry anthocyanosides and night vision.
More definitive benefits were generated in research on bilberry and protecting the retina from oxidation. Columbia University, New York, in vitro research revealed bilberry anthocyanins could protect retinal epithelial cells against photooxidation and membrane permeability.43 Additionally, bilberry anthocyanoside and its constituents (cyanidin, delphinidin and malvidin) were found to protect retinal ganglion cells from damage via antioxidant mechanisms, according to Japanese researchers.44 And oral administration of bilberry extract showed a dose-dependent decrease in oxidative stress and ocular inflammation in a Chinese animal study of endotoxin-induced uveitis (swelling of the middle layer of the eye due to inflammation).45
MirtoSelect®, from Indena, which is standardized to 36-percent anthocyanosides, has demonstrated specific eye benefits in recent research. Preliminary pharmacological studies found this extract increases capillary resistance, reduces abnormal vascular permeability and exerts antioxidant activity. In addition, the extract may promote resynthesis of retinal pigments, benefiting visual acuity.
Based on results from one clinical study, MirtoSelect may help recover reduced visual function caused by overuse of the eyes.46 Results show MirtoSelect improved subjective symptoms such as vision with sparks, dimming of eyesight and ocular fatigue in computer operators, office workers and students, compared to subjects treated with a placebo.
Intraocular inflammation, a significant risk factor in development of glaucoma, may be lessened by a combination of standardized bilberry extract and French maritime pine bark extract (as Mirtogenol®, containing 80 mg MirtoSelect and 40 mg Pycnogenol®, from Horphag Research).47 Italian researchers at the University of Chieti-Pescara in San Valentino, Italy, gave 38 individuals either Mirtogenol or placebo for six months and measured intraocular pressure. At the end of the trial, they found intraocular pressure decreased in 19 of the 20 Mirtogenol patients, compared to only one of the 18 patients in the control group.
Pycnogenol (supplied in the United States by Natural Health Science), which is manufactured for a variety of flavonoids and other phenolic compounds, has made its mark in diabetic retinopathy research. One review reported Pycnogenol increases capillary resistance and reduces leakages into the retina, thereby helping to partially recover visual acuity.48 Among results of animal research, Pycnogenol can increase retinal glutathione reductase activity and normalize elevated activity of superoxide dismutase (SOD) in the retina of diabetic rats.49 Further, Pycnogenol was shown to counter retinopathy and diabetic cataractogenesis in diabetic rats, with the greatest benefit resulting when combined with a low-glycemic diet.50
In subsequent clinical trials involving 24 patients with early diabetic retinopathy, Pycnogenol supplementation for three months improved vision in 18 patients, based on self-assessment, with results confirmed by testing of visual acuity at both baseline and studys end.51 The researchers noted Pycnogenol taken at an early stage of retinopathy may enhance retinal blood circulation and reduce edema, improving vision.
Ayurvedic botanical curcumin may suppress cataract onset and progression in animals, according to a 2010 study report from Alagappa University, India.52 Oral administration of curcumin affected expression of alpha-A- and alpha-B-crystallin and heat shock protein 70 (Hsp 70) during selenium-induced cataractogenesis. Another 2010 study investigated the potential therapeutic role of curcumin in eye-relapsing diseases such as anterior uveitis, as well as other eye inflammatory and degenerative conditions such as dry eye, maculopathy, glaucoma and diabetic retinopathy.53 Researchers administered an adjunctive-to-traditional treatment of curcumin-phosphatidylcholine complex (as Meriva®, from Indena) twice a day for 12 months in 106 patients with recurrent anterior uveitis of different etiologies. The results showed the curcumin-based intervention reduced eye discomfort symptoms and signs after a few weeks of treatment in more than 80 percent of patients.
Research on nutrients found in the eye and its important structures, including the retina, is increasingly indicating eye health benefits from greater intake of these compounds. The mechanisms appear to be antioxidative, anti-inflammatory and absorptive, offering protection from damage, stress and degeneration. Various eye diseases appear to improve with supplementation of such nutrients, and constituents of various botanicals can offer additional antioxidant and protective benefits to eye health.
References are on the next page...
References for Eye Health Preservation
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