Life Extension Magazine February 2002
Focus on eye health
While there is still much speculation about what causes various age-related eye diseases, many possible contributing factors have been examined by scientists. The usual suspect, as with most age-related diseases, is oxidative damage. For example, the lens of the eye, which acts as a light filter for the retina, is under chronic photo-oxidative stress. The retina, meanwhile, is particularly susceptible to the destructive effects of reactive oxygen species (ROS), which are produced in the retina as a result of photochemical reaction, cellular metabolism and high levels of polyunsaturated fatty acids that reactive oxygen species readily oxidize.
Some research suggests that aging processes of the eye may be the result of the breakdown of enzymes that usually metabolize and detoxify hydrogen peroxide and other free radicals found in eye fluids. Free radicals reside in the aqueous fluid and bathe the lens of the eye, destroying enzymes that produce energy and maintain cellular metabolism. Free radicals also break down fatty molecules in membranes and lens fibers, generating more free radicals and creating a cross-linking (denaturing or breakdown) of the laminated-like structural proteins inside the lens capsule. The lens capsule has the ability to swell or dehydrate. In doing so, the increase and/or decrease in pressure can cause breaks in the lens fiber membranes, resulting in microscopic spaces in the eye in which water and debris can reside.
In addition, blood flow within the eye decreases with age, basically depriving it of essential nutrients for proper function and antioxidant activity. An Indiana University study showed that vascular changes occur in the aging eyes of both men and women, which resemble the changes seen in patients with glaucoma or age-related macular degeneration. So such changes as occur typically during normal aging may contribute to the increased risk of these diseases. Meanwhile, German researchers showed that retinal and central retinal artery blood flow significantly decreases with age at approximately 6% to 11% per decade.
Looking at prevention
While the exact role of individual nutrients and optimum means of delivery (i.e. oral vs. topical) haven’t been solidified yet, some useful findings are surfacing about the benefits of antioxidants for eye health. Some research from the USDA Human Nutrition Research Center on Aging has demonstrated that antioxidants such as ascorbate, carotenoids and tocopherol, may protect against cataract formation. A five-year study of over 3000 Wisconsin residents, aged 43 to 86, showed that the five-year risk for cataract was 60% lower among people who reported taking multivitamins or any supplement containing vitamin C or E on a long-term basis (more than 10 years) compared to non-users.15 Similarly, a survey-based Harvard study of nearly 40,000 men aged 45 to 75 established, at eight-year follow-up, a 19% lower risk of cataract among men in the highest fifth of lutein and zeaxanthin intake compared to men in the lowest quintile.
It’s believed that lutein and zeanxanthin, the primary carotenoids concentrated in the macula, counter the free-radical forming action of light and oxygen.2 The macula is the central part of the retina that’s responsible for visual sharpness and detail. It’s been suggested that macular pigment protects the retina via a dual role that includes scavenging for free radicals and filtering out blue light, which can cause photochemical damage. Some studies have also suggested a link between dietary carotenoid intake and macular pigment density. In fact, eyes with age related maculopathy (ARM) have revealed significantly lower carotenoid levels in the macula and retina than healthy eyes.
And while a paucity of US-based clinical trials to demonstrate the effectiveness of specific neuroprotective compounds for glaucoma may limit their current therapeutic use, there is evidence slowly mounting to support their effectiveness. A Russian study of 64 patients with primary open-angle glaucoma found that a combined regimen of hyperbaric oxygen and antioxidants over a five-year period stabilized visual function in 80% of patients.
Other studies have been examining how antioxidant status relates to the risk of age-related macular degeneration. The Baltimore Longitudinal Study of Aging, for instance, found that tocopherol, and an antioxidant combination of tocopherol, carotene and ascorbate were protective. Researchers have also been looking at the potentially therapeutic role of individual compounds. For example, a study from Sete, France of 2584 inhabitants showed that higher plasma levels of alpha-tocopherol were inversely related to AMD development and progression.
Another study looked at the topical use of N-acetylcarnosine (NC) for treating cataracts. Carnosine is an endogenous free-radical scavenger and anti-glycating agent. In this six-month study, 49 volunteers (average age 65.3) with cataracts were treated with a 1% solution of NC (2 drops, twice daily), given a placebo composition, or were untreated. Results showed that, compared to baseline measurements, 41.5% of the eyes treated with NC showed a significant improvement in lens clarity at six months, 90% showed gradual improvement in visual acuity, and 88.9% improved in glare sensitivity. Results pointed to NC as a suitable and physiologically acceptable non-surgical treatment for cataracts.
The fact that the macula pigment is heavily comprised of lutein and zeaxanthin, that ascorbic acid (vitamin C) is found in both the aqueous humor and corneal epithelium, that glutathione is highly concentrated in the lens of the eye, and that there is a high content of zinc in the retinal pigment epithelium (RPE-the tissue behind the retina that feeds the rods and cones), there is compelling evidence for the essential need of these antioxidant and anti-glycating agents for maintaining optimal eye function. The question of how to get a sufficient daily intake of these vital eye nutrients is currently under investigation.
A recent study sought to measure dietary amounts of lutein and zeaxanthin by testing 33 various fruits and vegetables, two fruit juices and egg yolk. Surprisingly, results showed that although dark green, leafy vegetables are reputed to contain the highest amounts, lutein and zeaxanthin are also abundantly present in other food choices. Egg yolk and maize had the highest content (more than 85% of total carotenoid content), maize having the highest lutein content (60%) and orange peppers having the highest zeaxanthin content (37%). Substantial amounts were also found in kiwi, grapes, spinach, orange juice, zucchini and various types of squash (30% to 50%). Comparatively, green leafy vegetables actually had 15% to 47% of lutein content but only 0% to 3% of zeaxanthin content. Earlier studies had shown that eating dark leafy vegetables was associated with a 43% lower risk of AMD. Now it seems that some benefit can be derived from other food choices.
One of the current debates about antioxidant intake and eye health is that oral ingestion seems to effectively raise and correlate to blood plasma levels of nutrients, but the intake does not correlate as directly in eye tissues or get reflected in eye health. For example, one study showed that, while oral antioxidant therapy normalized blood levels of antioxidant activity even in advanced cases of glaucoma, it did not help lacrimal antioxidant activity, which argues for locally administered antioxidants perhaps being preferable in glaucoma patients. Another study that tested oral zinc supplementation in 112 subjects with AMD over a two-year treatment period discovered that serum levels of the nutrient were much higher in the supplementation group than controls, but disease progression was similar in both treated and untreated patients.
A recent study carried out by the National Eye Institute, however, had more positive results to report with regards to oral supplementation. The large, multicenter study explored the use of zinc and antioxidant oral supplements containing above the recommended daily requirements to prevent advanced AMD. It examined 3,640 persons aged 55 to 80, who had a high risk of developing advanced AMD, already had it, or had been blinded in one eye by the condition. These participants were randomly assigned to four oral regimen groups and followed up for over a six-year period. Group 1 received daily tablets containing antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; and beta carotene, 15 mg). Group 2 received a zinc supplement, 80 mg, as zinc oxide and copper, 2 mg, as cupric oxide. Group 3 received both the antioxidants and zinc. And group 4 received a placebo. Results showed that those with intermediate disease taking antioxidants plus zinc had a 25% lower risk of developing advanced AMD than those taking a placebo. The vitamin plus mineral regimen also reduced the risk of vision loss by about 19%. The authors, however, were careful not to generalize their findings to suggest an equal benefit of supplementation in everyone, since the supplements showed no effect in people with early-stage AMD.
Scientists are considering the value of topically administered antioxidants as a reasonable option to weigh. Some studies have already shown the success of this direct route of administration, but future evidence will hopefully point to the appropriateness of local and targeted delivery of helpful agents to the eye.
1. Taylor A. EXS 1992;62:266-279.