Supplements may offer neuroprotection

Although clinical studies have not yet proven that nutritional supplements play a role in glaucoma, optometrists are increasingly interested in discovering alternative therapies for this disease. Supplements such as ginkgo biloba, resveratrol, fish oil and co-enzyme Q10 are among the most promising treatments, according to our sources.

When looking toward alternative and complementary therapies, Primary Care Optometry News Editorial Board Member Murray Fingeret, OD, said clinicians are trying to discover new treatment methods that protect the optic nerve, not just lower IOP.

“We know glaucoma is not due to having too much aqueous in the eye and yet we treat it by just lowering the IOP and releasing the aqueous,” he said in an interview. “When we talk about complementary or supplementary ways to deal with glaucoma, we are looking at ways to get to the core reason why glaucoma damage develops. We believe there are parallels in terms of why glaucoma and other neurodegenerative diseases develop, which is why ginkgo or resveratrol may be significant.”

Neurodegenerative disease

The parallels between glaucoma and diseases such as Alzheimer’s and macular degeneration have been noted in an unpublished paper by Robert Ritch, MD, FACS, FRCOphth, and Joseph R. Zelefsky, MD. In an interview, Dr. Ritch explained that these neurodegenerative disorders share similar attributes that he believes can be improved with supplementation.

“All of these diseases are characterized by a low grade inflammatory component, oxidative damage, mitochondrial dysfunction and glial-hyperactivity. So what’s good for one of these diseases should be good for all of them, outside of the specific things such as lowering IOP,” Dr. Ritch told PCON.

Glaucoma, which Dr. Ritch defines in his paper as a progressive optic neuropathy characterized by a specific pattern of optic nerve head and visual field damage, causes vision loss when the retinal ganglion cells are killed by apoptosis. The aim of neuroprotection in glaucoma, he writes, is to slow the progression by blocking the mechanisms that lead to apoptosis.

The argument for ginkgo

According to Dr. Ritch, ginkgo biloba extract appears to have many properties related to the treatment of pressure-independent risk factors for glaucomatous damage.

“Ginkgo provides everything you would want from a neuroprotectant for glaucoma,” he said. “It inhibits inducible nitric oxide synthase, glutamate-excito toxicity and lipid peroxidation of membranes. It preserves mitochondrial morphology from aging changes and preserves mitochondrial ATP production. It improves the blood supply to the periphery, the brain and the eye.”

While PCON Editorial Board member Alan M. Robin, MD, acknowledges benefits of ginkgo biloba, he feels more studies are needed in humans to prove the link to glaucoma.

“Ginkgo has never been proven in a masked study to be better than a placebo,” Dr. Robin told PCON “And, in many people, it can cause serious problems with blood clotting.”

PCON Editorial Board member J. James Thimons, OD, tells his glaucoma patients to maintain good nutrition and take supplements such as ginkgo biloba and co-enzyme Q10.

“Many good clinicians have worked hard to understand the role of ginkgo in glaucoma and recommend its use in patients who have glaucoma that is not necessarily related to IOP,” he said. “A patient with a normal-tension glaucoma diagnosis usually has something other than just a pressure-related concern; there’s usually an underlying vasculopathic process.

“They have Raynaud’s disease, they get severe migraines, they have extremely low blood pressure or they may have clotting dysfunction,” he continued, “so the use of an agent that increases blood flow by decreasing platelet stickiness actually makes a lot of sense from a purely mechanistic perspective.”

Resveratrol as antioxidant

Originally discovered as the component in red wine that contributed to the “French Paradox” – the theory that red wine consumption is responsible for the low incidence of heart disease in the French despite a rich diet – resveratrol is found in the skin of red grapes and has been widely studied for its antioxidant properties.

According to Brisdelli and colleagues, “Resveratrol is a naturally occurring polyphenol that shows pleiotropic health beneficial effects, including antioxidant, anti-inflammatory, anti-aging, cardioprotective and neuroprotective activities.”

These properties make it an effective alternate therapy for glaucoma, Dr. Ritch writes, because of its ability to activate sirtuins, a family of proteins that play an important role in chromosomal stability and longevity.

“A single infusion of resveratrol can elicit neuroprotective effects on cerebral ischemia-induced neuron damage through free radical scavenging and cerebral blood elevation due to nitric oxide release,” Dr. Ritch’s paper reads. “Its antiapoptotic activity has led to the suggestion that resveratrol may make a useful dietary supplement for minimizing oxidative injury in immune-perturbed states and human chronic degenerative diseases.”

Dr. Fingeret commented, “Resveratrol is fascinating. If you look at anti-aging and anti-oxidation, there’s a very strong case for it. However, I’m not aware of anything specifically that links it to being a glaucoma agent.”

Fish oil

A study by Nguyen and colleagues is one of the best arguments for fish oil, Dr. Fingeret said. The study found that rats fed omega-3 fatty acids had an improvement in ganglion cells, which play a pivotal role in the function and health of the optic nerve.

“The paper showed that taking fish oil actually lowered IOP,” Dr. Fingeret said. “However, you need more than an animal model to support telling a patient to take it; you need human studies.”

Dr. Thimons also hailed the anti-inflammatory properties of fish oil. “There’s good evidence to suggest that omega-3 fatty acids are a potential long-term mechanism to combat the inflammatory damage that produces glaucoma,” he said. “It makes sense because omega-3 is a natural, low-grade, constant source of inflammatory control in the human body.”

Co-enzyme Q10

According to Dr. Thimons, another drug that plays a significant role in metabolic function is co-enzyme Q10.

“Co-enzyme Q10 is a good drug for a variety of issues, and it promotes a much better metabolic function in all tissue levels, including neural tissue,” he said. “It’s been well established that it is useful to a patient’s overall metabolic health, particularly as it relates to the replacement of cells within the neuro complex.”

According to Dr. Ritch’s paper on natural compounds, co-enzyme Q10 “may be beneficial in glaucoma, as [it] has been shown to prevent apoptosis in retinal ganglion cells subjected to ischemia by limiting the release of glutamate.”

More studies needed

Despite optometrists’ increasing interest in this area, our sources agree that more research is needed.

“These are expensive studies to conduct, and drug companies don’t have an interest in this right now,” Dr. Fingeret said.

Dr. Robin said optometrists should carefully consider how alternative therapies might adversely affect a patient’s health. In addition, one brand of ginkgo may not contain the same formulation as another, resulting in different absorption rates, dose response curves and side effect profiles.

“You have to make sure these compounds are checked out with their primary care physician,” he said. “Just because it’s a natural supplement doesn’t mean it’s safe and effective. You have to make sure these therapies do not interact with other medications patients might be taking.”

For more information:

• Murray Fingeret, OD, is chief of the optometry section at the Department of Veterans’ Affairs Medical Center in Brooklyn and Saint Albans, N.Y., and a professor at SUNY College of Optometry. He is also a member of the Primary Care Optometry News Editorial Board. He may be contacted at St. Albans VA Hospital, Linden Blvd. and 179th St., St. Albans, NY 11425; (718) 298-8498; fax: (516) 569-3566; e-mail: murrayf@optonline.net.
• Robert Ritch, MD, FACS, FRCOphth, is the Shelley and Steven Einhorn Distinguished Chair in Ophthalmology and can be reached at the New York Eye and Ear Infirmary, 310 East 14th Street, New York, NY 10003; e-mail: ritchmd@earthlink.net.
• Alan M. Robin, MD, is an associate professor of ophthalmology and international health at Johns Hopkins University and a member of the PCON Editorial Board. He can be reached at 6115 Falls Rd., Ste. 333, Baltimore, MD 21209-2226; (410) 377-2422; fax: (410) 377-7960; e-mail: arobin@glaucomaexpert.com.
• J. James Thimons, OD, is a PCON Editorial Board member and chairman of the National Glaucoma Society. He can be reached at Ophthalmic Consultants of Connecticut, 75 Kings Highway Cutoff, Fairfield, CT 06430; (203) 257-7336; fax: (203) 330-4958; e-mail: jthimons@sbcglobal.net.

References:

• Brisdelli F, D’Andrea G, Bozzi A. Resveratrol: A natural polyphenol with multiple chemopreventive properties. Curr Drug Metab. 2009;10(6):530-546.
• Nguyen CTO, Vingrys AJ, Bui BV. Dietary omega-3 fatty acids and ganglion cell function. Inves Ophth Vis Sci. 2008;49:3586-3594.
• Zelefsky JR, Ritch R. Natural compounds: Evidence for a protective role in eye disease. Unpublished, 2009.