Article Date: 4/1/2006

nutrition
One Solution in the Battle Against Dry Eye: Nutrition
Nutritional supplements can provide relief for patients who suffer from DES.
BY JEFFREY ANSHEL, O.D.

Dry Eye Syndrome (DES) has become not only a significant quality-of-life issue but has shown itself to be a very real disease process. Whether it's called Dysfunctional Tear Syndrome, Chronic Dry Eye, or Dry Eye Disease, it's a condition whereby the anterior surface of the eye is not properly maintained and/or the patient is experiencing an uncomfortable feeling in his or her eyes.

For many years, the logical "treatment" for this condition has been to attempt to supplement the tear film with additional lubrication. The science of lubrication has come a long way and now we realize that it will require more than just "adding moisture" to resolve this problem. New methods of treatment include enhanced artificial tears, punctal plugs, lipid layer and tear quality enhancements and epithelial surface treatments. In the past few years a new approach to resolving this condition has included oral nutritional supplementation. Here we'll look at the facts and fiction surrounding the oral treatment of DE

Good fats for eye health

Essential Fatty Acids (EFAs) are involved in producing energy in our bodies from food substances, and moving that energy through our systems. They govern growth, vitality and mental state. They connect oxygen, electron transport and energy in the process of oxidation. EFAs are also important in oxygen transfer, hemoglobin production and control of nutrients through cell membranes. EFAs play a part in almost every function of our body. Humans do not produce fatty acids, so we must get them from our diet. The EFAs we will address are here Omega-6 and Omega-3.

Strike a balance

Omega-6 fatty acids are the most plentiful in the U.S. diet. They are in most everything we eat that contains fat, including meat, most seed oil, dairy products and eggs. Omega-3 fatty acids are available in many seed oils and almost all cold-water fish. A proper balance of these fatty acids is essential to good health. The Institute of Medicine (www.iom.edu) recommends a daily intake ratio of 4:1 � four times as many Omega-6 fatty acids as Omega-3. It's currently estimated that the average American diet maintains 25:1 ratio!

From fat to prostaglandins

The problem with trans fats

What are trans fatty acids and where do they come from? A fatty acid molecule consists of a chain of carbon atoms in carbon-carbon double bonds with hydrogen atoms attached. In nature, most unsaturated fatty acids are cis fatty acids. This means that the hydrogen atoms are on the same side of the double carbon bond. In trans fatty acids, the two hydrogen atoms are on opposite sides of the double bond, giving them a sharper, almost spiked, texture. Trans double bonds can occur in nature as the result of fermentation in grazing animals. People eat them in the form of meat and dairy products. Trans double bonds are also formed during the hydrogenation of either vegetable or fish oils. French fries, donuts, cookies, chips and other snack foods are high in trans fatty acids.

The purpose of hydrogenating oils is to harden them to improve their "spreadability," feel, baking qualities, and especially to extend shelf life. To hydrogenate oil, manufacturers use hydrogen gas under pressure in the presence of metal catalysts to heat it to a high temperature (248-410�F) for six to eight hours. However, since this process will likely destroy all of the double bonds of the fatty acids, it is stopped prematurely (thus creating a partially-hydrogenated product). The result is a complex mixture of compounds, including trans fatty acids. These trans fatty acids are linked to increased risk of cancer, increased inflammation, accelerated aging, obstruction of immunity and impaired healing.

Fatty acids are stored in every cell membrane of our body. They have two primary functions. First, they ensure cellular fluidity, acting as sentinel gatekeepers for every cell. They allow vital nutrients to enter the cell and force destructive free radical debris out. Second, nutrient co-factors like Vitamin C, Vitamin B6, zinc and magnesium help our bodies produce enzymes that convert dietary Omega-6 and Omega-3 fatty acids into three types of prostaglandins. The prosta-glandins (PGE1, PGE2 and PGE3) are site specific.

►PGE1 prostaglandins reduce inflammation and inhibit blood clotting. They are also capable of reducing pain, swelling and redness associated with inflammation, particularly in mucosal tissues, including the eyes. Only Omega-6 fatty acids can produce this particular prostaglandin.

►PGE2 prostaglandins can also only be produced by Omega-6 fatty acids. These pro-inflammatory prostaglandins constrict blood vessels, increase body temperature and encourage blood clotting. These events are lifesaving when the body suffers a wound or injury. Without PGE2s, a person could bleed to death from the slightest of cuts, or succumb to a viral or bacterial attack. However, in excess, this type of prostaglandin is harmful because it sets up a chronic inflammatory condition in the body.

►PGE3 prostaglandins are available from Omega-3 fatty acids. Omega-3s, particularly docosahexaenoic acid (DHA), keep brain cells healthy and also keep the rods and cones in our retinas supple and working properly. The Omega-3 fatty acid, eicosapentaenoic acid (EPA), also plays an important anti-inflammatory role. When necessary, it blocks the release of Omega-6 arachidonic acid, which is necessary for the production of pro-inflammatory PGE2.

Without sufficient Omega-3s in the diet, chronic inflammation can become a problem, one that's now linked to many degenerative diseases of the eye, including macular degeneration, glaucoma and diabetic retinopathy. As with all dietary intake, a proper balance of EFAs is the key to good health. Most scientists agree that a diet including cold-water fish two or three times a week, or EPA/DHA supplementation, helps maintain the proper balance of EFAs (Women of childbearing age and children should check local mercury warnings for fish).

Inflammation

Researchers suggest that Omega-6 fatty acids metabolize to the site-specific anti-inflammatory eicosanoid, prostaglandin E1 (PGE1). Literature suggests these particular prostaglandins reduce ocular surface inflammation, as well as the inflammatory process associated with meibomianitis and reduced lacrimal gland aqueous output.

It's true that the typical American diet is overloaded with Omega-6 linoleic acid (LA) from vegetable oils such as sunflower, safflower, corn, cottonseed and soybean oils, which are added to nearly all processed foods. Many pantries are far too full of processed crackers, chips and baked goods � and thus the Omega-6 oils that oxidize too quickly and become pro-inflammatories.

However, good health also depends on Omega-6 gamma linolenic acid (GLA), which is a downstream metabolite of Omega-6 linoleic acid. It's found in sources such as black currant seed oil, borage oil and evening primrose oil. This compound is necessary to metabolize Omega-6 fatty acid to the series one anti-inflammatory PGE1s, which are associated with healthy mucosal tissue and tear film. On the other hand, the human body cannot metabolize Omega-3 fatty acids to these specific anti-inflammatory prostaglandins.

Patient Education

Educating patients is a challenging task because many may not be aware of their nutritional balance. While a qualified nutritionist should make complete recommendations of nutritional supplements, you can offer them valuable information about treating chronic eye disease. Review the various companies that supply eye-related nutritional products and look at their rationale. Be sure their ingredients are backed by qualified research studies. Most likely you'll be making a "recommendation" for a nutritional supplement, rather than "prescribing" it, but the patients will value your opinion as an eyecare expert.

Success! When I encounter patients with a likely dry eye condition, I briefly discuss the anatomy of the tear layer and explain why they are experiencing their symptoms. I then discuss the product I am recommending and my rationale for doing so. I give them a brochure from the manufacturer and let them consider the process. I also let them know that it will likely be effective within 30 days but that they will need to continue to take the supplement as long as their symptoms persist. Many patients have called in within two weeks to say that they can already feel a difference! This is good for my practice, for my patients and for my bottom line.

Metabolization is the key

Most Omega-6 fatty acids are consumed in (polyunsaturated) vegetable oils as linoleic acid (LA). Excessive intake of LA is unhealthy, because it can promote inflammation if not properly metabolized. In contrast, Omega-6 fatty acids that are successfully metabolized or those that have the metabolic advantage of containing GLA, reduce inflammation after further metabolizing to dihomo-gamma-linolenic acid (DGLA). DGLA also blocks, when appropriate, the pro-inflammatory arachidonic acid (AA) conversion.

Sources of EFAs

Flaxseed oil does not include any GLA, so the body's ability to utilize it is totally dependent on the unpredictable delta 6 enzymatic conversion of its LA to GLA. As an Omega-3 fatty acid, flax does not contain EPA/DHA; therefore it's totally dependent on the enzymatic conversion of its high-content alpha-linolenic-acid (ALA) to EPA/DHA, which is required to produce the series three anti-inflammatory prostaglandins.

All fatty acids compete for the same metabolic desaturase, so for good health, we should consume fewer trans fat Omega-6s and more GLA Omega-6s and DHA/EPA Omega-3s.

Put supplements to work

The body requires all of the EFAs for optimal health. They are particularly important for dry eye patients because PGE1s from Omega-6 interrupt the inflammatory loop associated with chronic DES. The PGE1s also increase the anti-inflammatory immunosuppressive effects of cyclosporine. So if you choose to use a cyclosporine agent to treat DES, an oral supplement will serve to enhance this action.

A good nutritional supplement should address many of the underlying inflammatory processes associated with DES. Studies suggest oral administration of specific Omega-6 EFAs that contain sufficient amounts of GLA stimulate the natural production of PGE1.

►Black currant seed oil is an excellent source of Omega-6 GLA because it is more stable than either borage oil or evening primrose oil.

►Many anecdotal stories abound regarding the use of flax seed oil. However, it's the most unstable of the EFA oils and it does not contain GLA. Flax stability issues keep it from easily converting to GLA, which it must do to produce PGE1.

Taking It To the Streets

Here are some tips for applying this knowledge to your patients:

Who?
Not all patients will present with symptoms of dry eyes. Discuss dry eye with those who either mention dry eyes as one of their symptoms or who fit the likely demographic. This latter group consists of:

Patients who work in a dry environment (many offices, airplanes, air conditioning)

Women over 40 years of age

Patients who have had (or are considering) LASIK surgery

Those who have lid abnormalities that might disrupt the tear film

Patients who work on computers on a regular basis

Patients who are using systemic medications (antihistamines, psychotropics, HRT, beta-blockers, etc.)

Those who have chronic disease (Sjogrens, lupus, rheumatoid arthritis, diabetes)

Those contact lens wearers who can't wear lenses as long as they would like.

►Pharmaceutical-grade cold-water fish oil, as a source of Omega-3 EPA/DHA, is germane to a good formulation. It serves as a metabolic gateway boost to the downstream conversion of the Omega-3 to the anti-inflammatory PGE3. Peer reviewed literature suggests Vitamin E, specifically gamma tocopherols, that stabilizes EFAs and inhibits COX2 enzyme activity to prevent oxidation.

►Experts suggest curcumin to appropriately block Omega-6 and Omega-3 fatty acids from metabolizing to the pro-inflammatory PGE2 and IL1. Curcu-min is a natural COX2 in- hibitor with similar chemical properties to ibuprofens (NSAIDs). But curcumin doesn't inhibit production of the COX1 enzyme that's necessary to protect the stomach lining. The first sign of an adverse response can be severe gastric bleeding.

►Vitamin C, as ascorbic acid and fat-soluble ascorbyl palmitate, best modulates PGE1 synthesis due to the extended half- life of the fat-soluble vitamin C over water-soluble ascorbic acid. This vitamin C combination also enhances the production of IgE concentrates in tears, the first line of basophil and mast cell defense against invading pathogens and allergens that frequently cause dry eye symptoms.

►Studies also recommend lactoferrin to increase the level of iron-binding proteins to better inhibit viral and bacterial infections and to balance other tear lipocalins (the family of proteins that transport small hydrophobic molecules), which modulate the surface tension of the tear film and contact lens comfort. Neutrophils, the first line of defense against infection, located in the tear film, produce lactoferrin. Neutrophil apoptosis signals the macrophage to clean up debris from wounds, including surgically-induced wounds, such as in LASIK.

In looking for a tear-specific formula for oral administration, be sure to look for nutrient co-factors necessary to address DES by physiologic rather than pharmacological means. These ingredients are designed to work synergistically rather than individually, and effectively address the inflammatory process responsible for most DES, as well as enhance and restore function to the glands involved in all three layers of the tear film.

Find the lucky combination

Treating idiopathic dysfunctional tear film with oral nutritional supplements can be an effective method to resolve this frustrating and uncomfortable condition in our patients. While it's worthwhile to uncover the cause of the condition, using the right combination of ingredients can work regardless of the causative factors. And your patients will be glad you did.

Dr. Anshel offers on-site consultations and seminars on CVS to eyecare professionals through his company, Corporate Vision Consulting, He also has a private practice in Carlsbad, Calif. He can be reached at eyedoc@adnc.com.



Optometric Management, Issue: April 2006