Eyeing Healthy Vision

Despite its physical protections, the sensitive human eye is prone to numerous degenerative conditions, many of which are the unfortunate consequences of aging. These maladies often result in decreased visual acuity, even blindness. The human eye is composed of intricate optical gadgetry, much of which depends upon various chemicals. Eye chemistry, in turn, is dependent upon various nutrients and related compounds, suggesting dietary supplements are essential to ensuring healthy vision.

To better understand how dietary ingredients can contribute to healthy vision, it is important to appreciate the eye’s physical attributes and how it produces vision. The eye is nothing without light. Light first enters through the cornea, the outermost optical part that is found in the tough sclera layer that keeps the eye’s shape. The sclera is also home to extraocular muscles that are responsible for eye movement, as well as aqueous humor, a watery fluid.

Next on light’s journey is the choroids layer, which contains the blood vessels that feed the eye, as well as the ciliary body, which controls the size and, thus, the focusing of the lens. Also found in this layer is the iris, an adjustable diaphragm around the pupil and the area of the eye’s color.The light passes through the pupil, an opening made larger or smaller to control the amount of light entering the inner eye, and into the bi-convex lens, which focuses the light through the jellylike vitreous humor and onto the retina.

The innermost layer of the eye, the retina is the light-sensing component and is comprised of rods, which “see” in low light, and cones, which sense color and detail. In the middle of the retina is the macula, in the center of which is the fovea centralis, the cone-rich segment responsible for fine detail. After processing by the retina, light is converted by a chemical called rhodopsin to electrical impulses for transmission to the brain via the optical nerve, the retinal fiber channel starting at the back of the eye, and the optical disk.

The eye has many protections within its structure and on the facial eye socket. Eyebrows curb the flow of liquids, such as sweat; eyelashes help prevent foreign particles from entering the eye; and eyelids help shield the eye and keep it moist by spreading antibacterial-laden tears.

When all the eye’s components are in tip-top shape and work well, clear vision is the result; but, any number of deficiencies and inefficiencies can cause visual impairment.

Visual impairment, especially blindness, costs the U.S. economy more than $68 billion in direct and indirect health care costs. More than 3.3 million Americans suffer from some level of vision loss, according to the National Eye Institute (NEI). Visual impairment is one of the top four causes of loss of independence. According to the Lewin Group’s Health Impact II Study, commissioned by the Dietary Supplement Education Alliance (DSEA), specialized dietary supplements could help prevent the transition to dependency related to vision loss, saving the health care system billions of dollars annually.

The most common eye diseases are age-related macular degeneration (AMD), which affects more than 35 percent of the elderly population, and cataracts, the leading cause of blindness in the world. AMD blurs sharp, central vision by affecting the macula region of the retina. Of wet and dry versions, dry AMD is by far the more common and occurs when the light-sensitive cells in the macula slowly break down, blurring central vision. Indicated by the presence of drusen, yellow deposits under the retina, dry AMD is marked by the increase in number and size of drusen. In wet AMD, abnormal blood vessels behind the retina start to grow under the macula, raising the macula from its normal position and causing rapid damage. Age, smoking and obesity are risk factors.

According to NEI, cataract is responsible for about 50 percent of all cases of low vision among all Americans, affecting an estimated 20 million Americans over age 40. Cataract surgery is the most frequently performed medical procedure in the United States, with more than 1.5 million cataract surgeries done annually. A cataract is an opacity (blurring) in the eye’s lens or its envelope, as a result of the denaturing of lens proteins. There are numerous possible causes, including chronic ultraviolet light exposure and diabetes.

Diabetes can also cause problems in the retina. Diabetic retinopathy, which affects more than 4 million Americans, involves damage to blood vessels that feed the retina, either breaking the vessels or contributing to the development of abnormal vessels. This disease is often marked by macular swelling (edema), which can impair vision.

Behind the macula and retina is where glaucoma haunts, damaging ganglion cells in the optic nerve causing visual field loss and blindness. A marker of glaucoma is intraocular pressure, which involves the production and draining of aqueous humor. NEI reports more than 2 million Americans over 40 suffer from glaucoma diseases, especially Hispanics. The resulting vision loss, which ispermanent, is often managed by surgery and drugs, but natural products have shown adjunctive benefits.

In fact, the diet has proven important to protecting against the development and progression of these diseases. The Nurses’ Health Study in Boston found a diet dominated by produce and whole grains was associated with a significantly reduced risk of developing cataract.¹ A study on 39,876 female health professionals revealed diets rich in fruits and vegetables showed a modest protective effect (a 10- to 15-percent reduction) against cataract development.² And the Age-Related Eye Disease Study (AREDS) found a diet overrun by high glycemic index foods correlated to a higher prevalence of all pure nuclear opacities and moderate nuclear opacities.³ Similarly, scientists from the Nurses’ Health Study found subjects whose average carbohydrate intake was between 200 and 268 g/d were 2.5 times more likely to get cortical cataracts than women whose intake was between 101 and 185 g/d—indicating carb quality, not quantity, is a prevailing risk factor.⁴

The eye appears particularly susceptible to oxidative damage, and antioxidant supplement ingredients have dominated eye disease research. The benefits from flavonoids in the human eye mimic those they confer to plants, including absorption of ultraviolet (UV) radiation, protection from pathogens, activation of growth and differentiation factors, and antioxidant protection. Among the flavonoids studied for antioxidant protection in eye health are tea catechins, berry anthocyanidins and various herbal phytochemicals.

Chinese researchers found tea polyphenols have the ability to prevent oxidative damage in human fetal lenses exposed to metallic oxidation.⁵ According to Indian researchers, administration of green tea extract to rats prior to selenite induction of cataract reduced incidence and severity of cataract, indicating a preservation of the antioxidant defenses in the eye.⁶ And, research on epigallocatechin-3-gallate (EGCG) from green tea suggested an ability to prevent rabbit lens cataract development.⁷

Pharmacological studies have shown a standardized extract of bilberry anthocyanosides (as MIRTOSELECT®, from Indena) increases capillary resistance, reduces abnormal vascular permeability and has antioxidant activity. In fact, the extract may promote resynthesis of retinal pigments, benefiting visual acuity. In a recent clinical trial, MIRTOSELECT promoted recovery of visual function caused by overused eyes.¹⁰ Researchers noted the extract improved subjective symptoms including vision with sparks, dimming of eyesight and ocular fatigue in computer operators, office workers and students compared to control subjects.

A bilberry extract, Catocyanic complex (as Diafrarel®, from Felux- Mediolanum), was studied extensively in the 1970s and ‘80s for benefits to various eye maladies, including optic capillary health, microangiopathy and myopia (nearsightedness). More recently, Chinese researchers reported school-aged children with mild myopia given oral bilberry anthocyanosides (as Diafrarel) for three months experienced improved visual acuity.¹¹

Anthocyanins are also abundant in black currant berries, which have been studied for impact on vision relative to specific eye parts. Japanese researchers found various anthocyanins from black currant stimulated regeneration of rhodopsin in frog photoreceptors, though the flavonoids had a minimal impact on oxidative activity in the lens.¹² And in a study at the University of Tsukuba, Tokyo, administration of black currant anthocyanosides to 12 healthy human subjects dosedependently lowered the dark adaptation threshold after work-induced visual fatigue.¹³

The anthocyanins from a combination extract of bilberry, blueberry, strawberry, cranberry, elderberry and raspberry (as OptiBerry®, from InterHealth Nutraceuticals) have demonstrated a range of positive properties for eye health, including protecting DNA integrity and supporting visual function¹⁴ The polyphenols in French maritime pine bark extract have been studied for the ability to strengthen capillaries and prevent diabetic retinopathy. A meta-analysis from Westfalische Wilhelms Universitat Munster, Germany, reviewed five early trials with a total of 1,289 patients using the extract (as Pycnogenol®, from Natural Health Science) for treatment and prevention of retinopathy.¹⁵ Researchers found Pycnogenol prevented progression of retinopathy, partially recovered visual acuity, improved capillary resistance and reduced leakages into the retina. Among more recent findings, Italian scientists reported two months of treatment with 150 mg/d Pycnogenol in patients suffering from diabetic, hypertensive and atherosclerotic retinopathy led to better retinal integrity and function.¹⁶ The herbal treatment significantly improved visual acuity and reduced capillary leakage compared to placebo treatment.

Additional herbal support for improved blood flow to the eye is provided by Ginkgo biloba, which has also been studied for benefits in diabetic retinopathy. A study at Taipei Medical University, Taiwan, examined the impact of the standardized ginkgo extract EGb761 (from Dr. Willmar Schwabe) on 25 Type II diabetics, finding significantly reduced blood viscosity and increased retinal capillary blood flow rates.¹⁷ Similarly, Polish researchers studying 15 children with Type II diabetes, who received ginkgo (as EGb 761) for three months, found the children performed better on the color vision test (a sensitive test of retinal function), and no diabetic retinopathy developed.¹⁸

Other tests have also revealed ginkgo’s ability to modulate the activity of antioxidant enzymes, prevent progression of cataract induction in vitro and protect cells and DNA from oxidative stress.¹⁹ And research reviews suggest ginkgo extract could also be beneficial in preventing and treating glaucoma, due to improved blood flow, reduced apoptosis and decreased serum viscosity.²⁰ In fact, Japanese researchers discovered early treatment with ginkgo extract (as EGb 761) in a rat model of glaucoma protected against neurotoxicity associated with increasing intraocular pressure.²¹

Still other phtyochemicals, including those from cruciferous botanicals, have produced positive results for eye health. Johns Hopkins University, Baltimore, scientists found sulforaphane protected human adult retinal pigment epithelial (RPE) cells from oxidation, and noted it significantly reduced the toxicity of the oxidants following supplementation—even several days after supplementation ceased.²2 The researchers suggested sulforaphane protects by inducing the Phase 2 enzyme response. Their subsequent study on human adult RPE cells to UV light revealed prior treatment with sulforaphane elevated levels of endogenous glutathione and other protective Phase 2 enzymes.²³

As protection from oxidation is crucial to the preservation of vision, research in eye health has more frequently focused on antioxidant nutrients, especially vitamins. Most recently, a Cochrane review found increased risk of AMD was inversely associated with intake of antioxidants, especially vitamins C and E, beta-carotene and zinc— based on tests of visual acuity among subjects.²⁴ An earlier review reporting similar results using AREDS data showed combination treatment with these antioxidants (500 mg vitamin C, 400 IU vitamin E, 15 mg beta-carotene and 80 mg zinc) reduced the risk of advanced AMD by 25 percent and the risk of central vision loss for 19 percent.²⁵

Further analysis of the AREDS results suggested antioxidant supplementation may also prevent the progression of age-related maculopathy (ARM) into AMD.²⁶ However, analysis of the Blue Mountains Eye Study failed to find a link between dietary antioxidant intake and progression of ARM to AMD.²⁷

The mineral zinc has a two-faced role in eye health relative to oxidation. Some tests suggest lower amounts of zinc protect retinal cells from oxidative stress, but higher amounts of zinc may work as a prooxidant.²⁸ In addition, darker colored eyes may be more susceptible to zinc absorption, according to a study showing 24 hours of zinc treatment did not increase zinc concentration in the blue eyes, while the brown eyes showed a 5.1-fold increase.²⁹

Zinc’s duality as an antioxidant in eye health has caused researchers to favor it in antioxidant combination, but its fellow nutrients have proven benefits on their own. Vitamin E has demonstrated efficacy against cataract progression. In one Swiss trial, pretreatment with vitamin E protected rats from development of UVBinduced cataract.³⁰ Meanwhile, pretreatment with vitamin E prevented sodium selenite-induced cataract in an Indian trial.³¹ Further, researchers at the University of Ankara, Turkey, found 10 mg/kg/d of vitamin E protected against radiation-induced cataract in rats, due to decreased oxidative stress.³²

Human trials on vitamin E and eye health have not quite produced the favorable results as have animal trials. The Vitamin E, Cataract and Age-Related Maculopathy Trial, involving 1,193 adults over age 55 with no cataract, reported 500 IU/d of vitamin E for four years produced no difference in the incidence or type of cataract development, nor in the rate of cataract extraction between patients taking vitamin E and those on placebo.³³ However, data from the Nurses’ Health Study reviewed for the impact of vitamin E on lens opacification concluded long-term use of vitamin E supplements, as well as increased intake of riboflavin, thiamin or both of these B vitamins, may thwart age-related lens opacification.³⁴

On the other side of vitamin C supplementation, a deficiency of this nutrient may immediately impact ocular oxidative stress. Researchers from Fujita Health University in Aichi, Japan, reported three weeks of vitamin C-deficiency in guinea pigs nearly doubled retinal lipid peroxidation, while levels of other antioxidants including glutathione and vitamin E were significantly reduced.³⁷ These findings confirmed the team’s earlier conclusions that a vitamin C-deficient diet induces serious retinal oxidative stress in both the short- and long-term.³⁸

Vitamin C has proven particularly effective against cataracts. British research on certain dietary antioxidants and the incidence of cataract in Spanish adults (older than 55) illustrated higher dietary intake and plasma levels of vitamin C significantly reduced incidence of cataract development.³⁹ Additional research involving 500 women from the Nurses Health Study found 10 years of vitamin C supplementation lowered the risk of cortical cataract by 60 percent.⁴⁰ In the study, women with the highest total vitamin C intake from food or dietary sources (greater than 362 mg/d) also exhibited a significantly reduced risk of cataract development, compared to women with the lowest intake (less than 140 mg/d).

Despite the benefits of certain vitamin, mineral and herbal antioxidants, the eye, namely the retina, has seemingly thrived on lipid-soluble compounds, including carotenoids. In 1940s, scientists hypothesized the yellow color of the macula lutea in the retina could be attributed to the presence of xanthophylls. These compounds cannot be synthesized in the human body, nor can they be converted from other carotenes.

The two most notable xanthophylls in eye health by far are lutein and zeaxanthin. These retinal carotenoids work to filter blue light and fight oxidative stress.

Johns Hopkins University, Baltimore, researchers concluded lutein and zeaxanthin should be considered conditionally essential nutrients, as low plasma levels of the carotenoids are associated with an increased risk of AMD, and dietary deprivation of the nutrients causes pathological changes in the macula.⁴¹

The scientific impact of these two xanthophylls on eye function has been charted by various researchers. Dutch scientists examining the impact of serum levels of various nutrients, including carotenoids, and macular pigment optical density (MPOD) found an inverse relationship between lens optical density and MPOD, suggesting lutein and zeaxanthin intake could retard lens aging.⁴² Then, researchers from the University of New Hampshire stated consumption of lutein and zeaxanthin may promote eye health by increasing MPOD.⁴³ Similar results were reported by Florida International University, Miami, researchers who charted an increase in MPOD with greater carotenoid supplementation, with lutein proving more bioavailable than zeaxanthin.⁴⁴

Researchers have drawn links between MPOD and body composition, suggesting obesity may increase the risk of AMD. Results from a Tufts University study explained obesity may promote AMD by increasing oxidative stress, changing the lipoprotein profile and increasing inflammation, possibly decreasing circulatory delivery of lutein and zeaxanthin from the macula.⁴⁵ And researchers from the Waterford Institute of Technology, Ireland, discovered a significant inverse relationship between percentage of body fat and MPOD in men and women, and a significant inverse relationship between serum zeaxanthin and percentage of body fat in women.⁴⁶ Then, University of Georgia, Athens, confirmed the obesity-AMD link, establishing an inverse relationship between MPOD and BMI, with obese subjects having lower retinal lutein and zeaxanthin levels.⁴⁷ They theorized the association could be due to either low xanthophyll intake or competition for uptake between the retina and adipose tissue.

Still other researchers have tested lutein against the possible inflammatory mechanisms of AMD. According to an animal lab study from Catholic University of Korea, Seoul, lutein (as FloraGLO®, from Kemin Foods LC) protected the macula from degeneration through anti-inflammatory actions, by dose-dependently inhibiting ischemiainduced cell death and expression levels of nNOS and COX- 2 in ischemic retinas.⁴⁸

Despite the preference for combining it with zeaxanthin, lutein has exhibited its own eye benefits in various trials on macular degeneration. In a human pilot study, 20 weeks of daily Vitamin A, also called retinol, is crucial to production of retinal, a part of the retinal compound rhodopsin and a fundamental factor in the transduction of light into visual signals in retinal photoreceptors. A deficiency of vitamin A results in low levels of lightsensitive molecules, possibly causing night blindness, a lack of sufficient light stimulation to produce vision. supplementation with 20 mg lutein ester (as XANGOLD®, from Cognis Nutrition & Health), supplying 10 mg/d free lutein, on seven early AMD sufferers and six age-matched controls significantly increased plasma lutein and mean MPOD.⁴⁹ They noted intestinal malabsorption of macular carotenoids likely has no role in AMD, and lutein supplementation could benefit even patients with established ARM. Researchers from the University of Manchester, England, conducted research showing eyes at risk of developing early-stage AMD exhibit lower macular pigment density than no-risk eyes, indicating a protective role for macular pigment.⁵⁰ Their subsequent study on senior patients with early-stage AMD showed 18 weeks of daily administration of lutein esters (as Xangold) helped maintain the density of macular pigment, at least in early AMD.^5l

Lutein has also shown promise against AMD in larger human trials.The 12-month Veterans Lutein Antioxidant Supplementation Trial (LAST)—in which 90 patients with atrophic AMD received either 10 mg of purified lutein (as FloraGLO), purified lutein plus a broad spectrum antioxidant (as OcuPower from Vitacost.com), or placebo—showed lutein alone and lutein plus other vitamins/minerals significantly improved MPOD, glare recovery, visual acuity and most measures of quality of vision, with the combination formula showing a broader effect.⁵² According to their conclusions, lutein supplementation may be beneficial at all stages of AMD.

Based on the eye health research, there has been an influx of lutein products hitting the market, raising issues of bioavailability between the different ingredient forms. A University of Illinois, Chicago, study compared an unesterified lutein formulation of 20 g/100 g lutein—as crystalline suspension in safflower oil—with 36.7 g/100 g lutein in esterified form, and found greater bioavailability from the esterified form.⁵³ The researchers hypothesized the bioavailability of lutein from supplements may depend on industrial formulation and processing. In another study, involving four lutein doses administered to 10 healthy men, luteinenriched egg showed the highest lutein bioavailability, while purified lutein, lutein esters and spinach were approximately equivalent in bioavailability.⁵⁴ The scientists theorized the difference between the dissolution and bioavailability in their research and findings in the University of Illinois study may be due to the use of the different formulations (crystalline lutein versus powder lutein esters). Meanwhile, an in vivo clinical study on the bioavailability of lutein esters (as Biolut™, from Blue California) versus free lutein is underway at the Florida International University of Florida, Miami, with results expected in September 2006.

Like lutein, zeaxanthin has also emerged from its successful combination to show promise on its own. Researchers from Harvard Medical School in Boston found zeaxanthin supplementation in carotenoid-deficient quail, which have similar retinal function and carotenoid uptake as humans, increased levels of the carotenoid in the serum, liver, fat and retina, and dose-dependently reduced lightinduced photoreceptor apoptosis upon exposure to UV light.⁵⁵ Seven In humans, a Swiss clinical trial conducted by Roche Vitamins, Basel, reported supplementation with 1 mg/d or 10 mg/d of zeaxanthin for 42 days in 20 healthy volunteers significantly increased serum levels of zeaxanthin in a dose-dependent manner.⁵⁶

Still other carotenoids have made individual inroads to eye health, including astaxanthin and lycopene. Japanese research has ascertained astaxanthin (as AstaREAL®, from Fuji Health Sciences) can improve retinal blood flow⁵⁷ and modulate parameters of asthenopia, an eye overuse condition marked by fatigue, red eyes, eye strain, pain in or around the eyes, blurred vision, headache and occasional double vision.^58,59 Specifically, astaxanthin (as astaREAL) improves eye fatigue in healthy subjects,⁶⁰ those suffering from visual display terminal fatigue,⁶¹ and those battling sports fatigue.⁶² Astaxanthin has also enhanced visual acuity in healthy subjects.⁶³

Astaxanthin has exhibited potential mechanisms against oxidative stress as well as eye stress from everyday activities. A Japanese study from Hokkaido University Graduate School of Medicine, Sapporo, determined astaxanthin could reduce ocular inflammation by blocking nitric oxide synthase (NOS) enzyme activity.⁶⁴ In animal studies, astaxanthin (as XANTHIN®, from Valensa) attenuated opacity formation, indicating the carotenoid has potent antioxidant effects in the eyes lens.^65,66

Lycopene may also impact cataract formation, as an in vitro study showed lycopene administered to rat lenses significantly reduced the incidence of selenite cataracts, with only 9 percent of the eyes in the test group developing dense nuclear opacities compared to 83 percent in the control group.⁶⁷ The University of Maryland, College Park, researchers concluded lycopene protected against experimental cataract through antioxidant properties, including restoring glutathione and malondialdehyde levels, and superoxide dismutase activity. Similarly, in vitro research from the All India Institute of Medical Sciences, New Delhi, revealed lycopene confers significant protection against galactose-induced morphological changes in and antioxidant status of human lens epithelial cells—both factors in diabetesrelated cataracts.⁶⁸

Beyond fat-soluble nutrients, dietary fats also impact healthy vision, via various mechanisms. An extensive review examining the role of long-chain polyunsaturated fatty acids (LC-PUFAs)— including the omega-3s eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)—determined LC-PUFAs may protect against oxidative-, inflammatory- and age-related pathology of the retina.⁶⁹ The reviewers noted LC-PUFAs modulate a number of metabolic processes linked to oxidative stress, inflammation and aging, and tissue status of LC-PUFAs is impacted by dietary intake. Essential fatty acids (EFAs) are critical to the structural and functional integrity of the retina.⁷⁰ As these dietary fats influence the expression of inflammatory cytokines, a higher intake of antiinflammatory omega-3 EFAs and reduced intake of pro-inflammatory omega-6 EFAs could beneficially influence intraocular pressure.⁷¹

Animal trials have shown omega-3-deficient diets can cause suboptimal neural signaling as well as reduced visual acuity.⁷² However, other research has reported diets high in omega-3 fatty acids can increase the level of DHA in the rod outer segment membranes, while also decreasing levels of the pro-inflammatory omega-6 EFAs.⁷³ A laboratory study at the University of Michigan, Ann Arbor, testing fish-oil derived LC-PUFAs on inhibition of AMD progression found retinal cells from monkeys fed fish oil EFAs exhibited significantly enhanced acid lipase activity, which reduced oxidative damage and possibly curbed development of AMD.⁷⁴

To the attentive eye, numerous dietary ingredients provide a broad spectrum of preventive and responsive solutions for improved ocular health. Research has shown vitamins, minerals, herbs and other nutrients can help preserve healthy vision by addressing potential malfunction in the retina and other key eye parts. Thus formulators seeking a bright future in the aging population, which is especially prone to vision loss, can envision numerous combinations of ingredients proven to benefit visual acuity and stave off degenerative eye diseases.

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