Eye Health Ingredients: Nutrition off the Charts

Long before we learn to drive, we understand that green light means “go” and red light means “stop.” But what about blue light?

Blue light means “watch out.” It means “take steps to protect your eyes.” Failure to do so could threaten your ability to see green lights, red lights, or anything else.

“For years now, professionals in the fields of light energy and vision have known about the hazards ultraviolet (UV) light presents to ocular health,” explains Elaine Kitchel, M.Ed., on the website of eye-health advocacy group Council of Citizens with Low Vision International. Unfortunately, she says, in today’s environment, we gradually experience longer and more-intense exposure to blue light. For instance, many workplaces as well as homes are lit with cool, white fluorescent tubes-the kind that emit light in the blue and ultraviolet ranges. And, she adds, “No one doubts more people are spending time in front of video display terminals (VDTs), which produce blue light.” (VDTs include computers, smartphones, video games, and their like.)

“Scientists only now are beginning to investigate [blue light’s] long-term effects and offer some solutions for maintaining ocular health in the presence of blue light,” she says.

In the face of these and other vision challenges, manufacturers and ingredient suppliers of eye-health supplements believe they have solutions that can help.

And don't forget to read about the new results from the National Eye Institute's AREDS2 study.

Internal Sunglasses

At Alhambra, CA–based GB Biotech Inc., an affiliate of Shanghai-based Cactus Botanics, general manager Carol Cheow lists major vision-support ingredients as zeaxanthin and lutein from the marigold flower (Tagetes erecta) and anthocyanins from bilberries (Vaccinium myrtillus).

“Lutein and zeaxanthin can filter the high-energy blue wavelengths of light that [are responsible for] the biggest damage on the retina. Anthocyanins can stop the free radicals that harm biofilm,” says Cheow.            

A similar message comes from DSM Nutritional Products (Parsippany, NJ). The company touts its Optisharp brand of zeaxanthin for functioning like “internal sunglasses.” Together with lutein, zeaxanthin absorbs blue light, helping to reduce photochemical damage caused by short-wavelength visible light, the company’s website explains. “Taking lutein and zeaxanthin-through green leafy vegetables or dietary supplements-increases macular pigment optical density (MPOD) in human eyes, which in turn reduces the risk of age-related macular degeneration (AMD).”

Beyond this, DSM states, lutein and zeaxanthin together also play a role in visual performance, especially when eyes are challenged by intense light such as glare from the sun, a camera flash, or blinding headlights at night. Together, DSM says, the two ingredients form a filter (macula pigment) over the part of the retina responsible for detailed vision. This filter blocks out blue light and haze from strong light, which in turn increases the eyes’ tolerance for bright lights.

On its website, Des Moines, IA–based Kemin Industries promotes FloraGLO, sourced from marigold flowers, as the leading, patented lutein brand associated with healthy eyes and skin. The company says research suggests that people need to get 10 mg of lutein every day “to keep eyes healthy and protect them as they age.” (In 2008, Kemin and DSM joined forces over FloraGLO. Kemin supplies FloraGLO brand lutein exclusively through DSM, and DSM globally commercializes FloraGLO products through distributors and directly to customers.)

Since October 2012, the two companies have jointly publicized a randomized, double-blind, crossover study that appeared online in the European Journal of Nutrition. This study, conducted under lead author Malkananthi Evans, suggested that not all sources of lutein are equivalent. Evans and his team compared the bioavailability of FloraGLO lutein when delivered in a starch matrix to lutein delivered in an alginate matrix. After 14 hours, total plasma lutein increased by 126% with the starch matrix, compared to only 7% with the alginate matrix. After 672 hours, the area under the curve for total lutein was 1.3-fold higher for the starch-matrix lutein.

Leading eye health ingredients from OmniActive Health Technologies (Morristown, NJ) include: Lutemax free lutein and lutein esters; Lutemax 2020, which “provides optimal amounts of lutein with enhanced levels of zeaxanthin isomers;” and OmniXan, a recently launched natural zeaxanthin from paprika. (Recently, the firm initiated a new eye-health educational campaign-Lutein for Every Age-which seeks to raise awareness of the importance of early and consistent lutein supplementation for maintaining eye health. To spread awareness, the company has enlisted the help of Jeffrey Anshel, OD, FAAO, president of the Ocular Nutrition Society, of which OmniActive is a platinum sponsor.)

The three yellow carotenoids found in the eye are lutein and zeaxanthin isomers RR-zeaxanthin and meso-zeaxanthin, explains Abhijit Bhattacharya, OmniActive’s COO. Collectively known as xanthophylls, they form a yellow spot on the retina at the very center of vision. These xanthophylls are potent antioxidants that can neutralize most free radicals-including singlet oxygen, superoxide, hydroxyl, and peroxynitrite radicals. They also activate antioxidant enzymes.

All three carotenoids neutralize blue light. (Lutein and the zeaxanthin isomers also span the entire membrane bilayer, which helps stabilize cell membranes, Bhattacharya says.) Lutein is more abundant throughout the rest of the retina, while the two zeaxanthin isomers are more concentrated at the very center of the eye, since they are the ultimate deterrents to solar damage and can protect during prolonged UV exposure, Bhattacharya explains.

“Because zeaxanthin is the primary pigment found at the focal point of the eye (macula fovea) and cannot be produced by the body, we must obtain this nutrient from our diet and supplementation. Zeaxanthin shows superior antioxidant properties as a direct result of its symmetrical structure,” he explains.

Furthermore, he posits, zeaxanthin’s structure allows for a broader wavelength of absorbency of blue light as compared to other carotenoids-which in turn amounts to its photoprotective activity. He says zeaxanthin is more effective than all antioxidants-including vitamin E-at inhibiting lipofuscin, which accumulates in the retina with age and is associated with vision loss.

Blue California (Rancho Santa Margarita, CA) is the exclusive global distributor for Biolut lutein esters, which are derived from the petals of marigold flowers.

Executive vice president Cecilia McCollum says Biolut contains 90% lutein esters. Disputing the position taken by some formulators that only free lutein is bioavailable, she cites a study conducted by John T. Landrum, PhD, from Florida International University in Miami. According to McCollum, Landrum’s research showed that even in very small amounts-3 to 6 mg per day-Biolut proved to be highly biovailable.

Increasingly, scientists and researchers are being called upon to legitimize the value of supplements in the struggle to preserve eye health. In fact, eye-health supplements manufacturer ZeaVision LLC has created a speakers’ bureau in order to have knowledgeable people available to tell the story of ingredients like lutein and zeaxanthin.

Recently, Jeffry Gerson and Joseph Pizzimenti, two optometrists associated with this bureau, presented remarks on a study conducted by a 14-person team at Peking University in China. The researchers asserted that lutein and zeaxanthin supplementation may improve early functional abnormalities of the central retina in early-AMD patients due to elevations in MPOD.

“This study is notable for its high-level design and relatively high doses of macular pigments, including 10 mg of dietary zeaxanthin,” Gerson and Pizzimenti commented. “Of further importance is the finding of retinal function improvement in early AMD patients as documented by an objective test of multifocal electroretinography (MfERG).” They also pointed out-echoing the study’s authors-that more, larger studies are needed to assess the long-term effects of lutein and zeaxanthin on reducing AMD progression.

Carotenoids specialist LycoRed, too, has invested in eye health science. “We have an ongoing scientific program in the eye health segment,” reports Golan Raz, business manager of the Orange, NJ–based company.

Golan says the company’s new product line, called Lyc-O-Vision, comprises three proprietary formulations whose ingredients act synergistically-and thus, he says, require a lower dosage while providing higher efficacy.

“For example,” he says, “our proprietary Lutein Complex is active in preventing inflammation way beyond what is possible with lutein by itself. We have demonstrated synergy between our proprietary Lutein Complex, EPA, and DHA. This synergy may allow the use of a lower dosage of EPA/DHA and a reduction from four capsules per day to only two capsules per day.”

Finally, some companies boast that the zeaxanthin that they sell is sourced from paprika and the lutein from marigold flowers. Ecuadorian Rainforest LLC comes to market from a different starting point. According to Steve Siegel, vice president of the Belleville, NJ–based company, Ecuadorian Rainforest kale powder and spinach powder are two products rich in lutein and zeaxanthin. In addition, he says, “We offer Ecuadorian Rainforest wheat germ powder, wheat germ 4:1 powdered extract, and sweet potato powder for their vitamin E value.”

Beyond Lutein and Zeaxanthin

Yet, as important as lutein and zeaxanthin are in contributing to eye health, they are not the whole story, as Ecuadorian Rainforest exemplifies. Other ingredients may make a difference, including bilberry, astaxanthin, and vitamins A and E.

At Seattle, WA–based Indena S.p.A., the top vision care ingredients are Mirtoselect, Mirtogenol, and Meriva. Christian Artaria, marketing director and head of functional food development, describes Mirtoselect as a bilberry extract made from Vaccinium myrtillus L. fresh berries standardized to contain 36% anthocyanins by HPLC.

“The product’s properties for eye health have been clinically validated in different studies, showing promotion of contrast sensitivity in retinal health and attenuation of free radical damage...in schoolchildren,” says Artaria.

In one recent multicenter study involving 88 subjects, Mirtoselect was administered to patients with non-proliferative diabetic retinopathy. After one year, the researchers reported a beneficial effect on contrast sensitivity, while visual acuity and macular edema were maintained at initial conditions.

The company’s other ingredient, Mirtogenol, is a trademark of Indena S.p.A. and Horphag Research Ltd. According to Artaria, it is a proprietary combination of the standardized bilberry extract Mirtoselect and French maritime pine bark extract Pycnogenol.

The Indena executive says, “This combination favors the maintenance of high intraocular pressure (IOP), which significantly reduces the likelihood of developing glaucoma and capitalizes on the synergy between polyphenolics belonging to distinct structural classes-namely, anthocyanidins and procyanidins.”

The third Indena ingredient, Meriva, is a bioavailable formulation of curcumin (Curcuma longa). Artaria cites three studies. In one, Meriva was given to 106 patients suffering from recurrent uveitis, an inflammatory condition of the inner part of the eye bulb, and it appeared to help a significant number maintain healthy status. In the second, similar beneficial effects were observed in a study on central serous chorioretinopathy. And finally, in a recent pilot study, the daily use of 1 g/day of Meriva was shown to ameliorate retinal function in patients with glucose impairment.

AstaReal Inc. (Burlington, NJ), the U.S. subsidiary of Fuji Chemical Industry Company, Ltd., offers natural astaxanthin in 2% powder and 10% oil extract forms. Extracted from freshwater algae, the company’s product is said to have “significantly demonstrated the beneficial effect of reducing eye fatigue, improving accommodation and enhancing visual acuity.”

Joe Kuncewitch, the company’s national sales manager, says that despite similarities to its carotenoid cousins lutein and zeaxanthin, “Astaxanthin functions on a different level and in a different area of the eye. It concentrates in the iris-ciliary muscle of the eye, which may contribute to improvement of ciliary body function via increased blood flow to this area and reduced muscular fatigue.”

He cites 10 human clinical studies suggesting that the use of astaxanthin may help relieve eye fatigue brought on by repetitive use of video display terminals.

Another ingredient that may prove highly useful is carnosic acid.

Ecuadorian Rainforest’s Siegel cites a study that was conducted by Stuart A. Lipton, MD, PhD, at Sanford-Burnham Medical Research Institute and published in the journal Investigative Ophthalmology & Visual Science. As Siegel tells it, Lipton discovered that carnosic acid may have clinical applications for diseases affecting the outer retina, including AMD. “Research like this is important in proving that natural ingredients may be beneficial in the ability to ward off eye disease and promote ocular health,” he says.

Similarly, Blue California’s McCollum points to resveratrol as a possibly effective agent in helping to prevent loss of vision-and in some cases of wet macular degeneration-actually effecting improvement in vision.

The study she cites was conducted by Stuart Richer, OD, PhD, director of the Ocular Preventative Medicine-Eye Clinic at the James A. Lovell Federal Health Care Center in North Chicago, IL. Using Longevinex, a blend of nutraceuticals, including resveratrol, Richer was able to successfully treat 16 out of 17 cases in patients for whom all other therapies had been tried and failed, McCollum says.

Three of the cases were presented in May 2012 at the annual Association for Research in Vision & Ophthalmology meeting in Ft. Lauderdale, FL.

One involved an 88-year-old woman for whom “all hope was gone,” according to retinal specialists. After just four days on the nutraceutical regimen, she is reported to have regained enough vision to see faces, read a menu, and visualize her handwriting.

In another case, a 75-year-old man with failing vision experienced recovery in five days and was able to renew his driver’s license after taking just seven capsules.

Of course, these may not be typical results seen in other study populations.

And as exciting as these results sound, they don’t represent what many consider to be the most important role for eye health supplement ingredients. Most would agree that the ideal time for taking care of one’s eyes is before, not after, one has already suffered considerable loss of vision-hence, OmniActive’s new Lutein for Every Age educational campaign.

Bhattacharya puts it this way: “There is a new world of thought emerging from the scientific community supporting the notion that the key to eye health is maintenance through a lifetime.”

Sidebar: Genetic Risk Factors Associated with AMD

An international group of researchers say they have discovered seven genetic risk factors connected to age-related macular degeneration (AMD), a leading cause of blindness. The AMD Gene Consortium, composed of investigators representing 18 research groups, also confirmed 12 human genome loci identified in previous studies.

Findings of the research, which was supported by the National Eye Institute (NEI), a part of the National Institutes of Health, appeared online March 3 in the journal Nature Genetics.

NEI Director Paul A. Sieving, MD, PhD, praised the scientists for their “compelling analysis,” and added, “Combining data from multiple studies, this international effort provides insight into the molecular basis of AMD, which will help researchers search for causes of the disease and will inform future development of new diagnostic and treatment strategies.”

“Like a map that identifies neighborhoods where the electricity has been knocked out by a storm, the AMD Gene Consortium’s study effectively tagged regions within the genome where researchers are most likely to find short circuits in DNA that cause AMD,” said Anand Swaroop, PhD, chief of the NEI Laboratory of Neurobiology and Neurodegeneration and Repair, and one of the group leaders of this consortium effort.

“Once you are in the right neighborhood, going block to block or house to house to look for downed power lines goes much faster. Likewise, by limiting their search to the 19 genomic regions identified by the AMD Gene Consortium, scientists can more efficiently search for specific genes and causative changes that play a role in AMD,” Swaroop explained.

Sidebar: Pour a Glass of Eye Health

While some people drink until they’re cockeyed, others more recently have been sipping to see better.

OJO, invented by Long Island, NY–based ophthalmologist Jodi Luchs, MD, is being promoted as “the world’s first beverage that provides the therapeutic benefits of the Age-Related Eye Disease Study (AREDS) vitamins, but without the pill-related side effects and issues that present obstacles for many patients.”
According to Luchs, these pill-related issues include stomach irritation, difficulty swallowing large pills, as well as the challenge many people face just remembering to take the recommended two-to-four supplements daily.

By contrast, he describes OJO as “a great tasting, all natural, 50%-juice beverage alternative” that contains vitamin C, vitamin E, and zinc-all recommended in the AREDS research-as well as lutein, zeaxanthin, omega-3 fatty acids, and superfruits such as bilberry extract, blueberry extract, black currant extract, and grapeseed extract.

Luchs says all of these are powerful anthocyanin-containing antioxidants, which have been shown to help protect the retina against damage from free radicals.

Sidebar: Zeaxanthin: Natural vs. Synthetic

When the European Commission (EC) ruled on January 22 that synthetic zeaxanthin is safe for human consumption at 2 mg daily, it reignited old arguments about the relative merits of natural versus synthetic nutritional ingredients.

Favoring the former, some of the suppliers interviewed in this article proudly note that their zeaxanthin is sourced from paprika (or, in one instance, from kale and spinach powder).

Meanwhile, the push to approve synthetic material came from a company that has long experience in the natural products industry-DSM Nutritional Products (Parsippany, NJ). DSM started the process in June 2004 when it petitioned New Zealand officials for synthetic zeaxanthin to be granted novel ingredient status with a maximum daily human intake of 20 mg daily.

The New Zealanders in turn brought the matter before the European Commission, and in April 2008 the European Food Safety Authority (EFSA) rejected the proposal, stating that the ingredient’s safety at this maximum level “has not been established.”

In January 2012, DSM came back, choked up on the bat a bit, offered new safety data, and asked for just 2 mg daily. This time, EFSA granted the request, and to mix metaphors, the nose of the camel is now inside the tent.

Trying to see both sides of the issue, Carol Cheow, general manager of GB Biotech Inc. (Alhambra, CA), acknowledges that natural resources are sometimes stretched thin in attempting to satisfy supplement makers’ needs. Nevertheless, she says, addressing synthetic ingredients in general-not zeaxanthin specifically-residues from the synthesizing process can sometimes still be present in the finished product and may do “new harm” or add an extra burden to metabolization. Cheow says she expects U.S. regulators to look at this matter closely to find a balance that is good for both consumers and the industry.

Standing on principle, Chris Oesterheld, assistant vice president of Parsippany, NJ–based Jiaherb Inc., says, “I personally feel that [the EFSA ruling] impacts the integrity of natural products in the market. Unfortunately, many consumers do not know whether they are ingesting natural material or synthetic.”

Taking a different stance, Christian Artaria, Indena’s marketing director and head of functional food development, declares, “We are happy about this positive outcome taking into consideration the efforts being made for this application. As a general comment, I am not expecting that this decision is going to make any change in the U.S. market. I believe, at least in the medium term, the EU and the United States will follow two different approaches.”

Sidebar: United for a Bright Future

With “platinum supporters” like Bausch & Lomb, Biosyntrx, MacuHealth, OmniActive, and ZeaVision, it is obvious that the Ocular Nutrition Society (ONS), now in its fifth year, has established its credibility with a number of large and prestigious firms specializing in eye care.

Dedicated to promoting “excellence in the care of patients through nutritional support for eye diseases and disorders through professional education and scientific investigation,” the Encinitas, CA–based organization serves its members with a “Doctor Locator,” a selection of online consumer education articles, a brochure, and a fellowship program to assist health professionals in learning more about the role nutrition plays in preserving eye health.

ONS president Jeffrey Anshel, OD, FAAO, says the organization has become “the default source for accurate and scientific data on nutrition in the eye care field. New research continues to emerge which supports the role of nutrition in maintaining eye health, and the ONS scientific committee is actively involved.”

Anshel adds, “While we don’t maintain a ‘development team,’ the scientific committee actively investigates and is involved with emerging research on the role of nutrition in the eye health and eye disease resolution. We offer our members access to this data so that they can make informed decisions with their patients’ welfare first and foremost in the treatment plan.”