Studies still weighing supplements for tear dysfunction

September 15, 2008

Supplementation with omega-3 fatty acids, omega-6 fatty acids, and fish oils in patients with dry eye probably will decrease the overall inflammatory state of the eye based on subjective evidence, but objective placebo-controlled trials should be conducted to validate this recommendation.

Key Points

While this news seems encouraging, she tempered this with the observation that no objective trials have been performed to support the use of nutritional supplements in patients with tear deficiency. Dr. Macsai presented the current thinking on why this may be a promising avenue of therapy to pursue for patients with dry eye.

Dry eye disease has an underlying inflammatory component that results in decreased aqueous tear production and increased evaporative tear loss. Fatty acid metabolism is a hot topic in this regard because omega-3 fatty acids metabolize into anti-inflammatory eicosanoids and thrombolytic agents, and omega-6 fatty acid metabolism is key in the production of arachidonic acid and other inflammatory mediators and platelet aggregators. Insulin, Dr. Macsai pointed out, produces desaturase enzymes that shunt the enzymatic processing of omega-3 fatty acids toward the omega-6 pathway.

Sjögren's disease is characterized by decreased saliva and tear formation because the lacrimal and salivary gland nerve function is shut down by tumor necrosis factor alpha (TNF-a), interleukin (IL)-1, and IL-2. Eicosapentaenoic acid blocks gene expression of TNF-a and the interleukins.

"The omega-6 fatty acids block linoleic acid metabolism to gamma linolenic acid and fish oil blocks the conversion of dihomo-gamma-linoleic acid to arachidonic acid.

Nutritional supplements

Flaxseed oil, which is composed of 55% alpha-linolenic acid, 15% omega-6 fatty acids, and 19% omega-9 fatty acids, is an omega-3 fatty acid that is thought to decrease inflammation by inhibiting TNF-a and IL-1 beta. One cautionary note is that one study associated alpha-linolenic acid with prostate cancer, although these results have not been reproduced. Other side effects are flatulence and increased bleeding time, according to Dr. Macsai.

Olive oil contains 1% omega-3, 10% omega-6, and 85% omega-9 fatty acids.

Fish oil contains both docosahexaenoic acid and eicosapentaenoic acid and is found in salmon and swordfish. A drawback is the high concentration of mercury in unfiltered supplements that can accumulate in the body, she noted. "Salmon has by far the most omega-3 fatty acids. Milk and yogurt contain very little omega-3 fatty acids," Dr. Macsai said.

Vitamin E levels have been shown to be decreased in dry eye and after fish oil supplementation. Bilberry up-regulates the oxidative stress defense enzymes and has been beneficial in animals in the prevention of macular degeneration and cataracts, but no role in dry eye has been reported. Evening primrose oil did not exhibit substantial improvements in ocular or oral tissue compared with placebo in patients with Sjögren's syndrome.

Published research on nutritional supplements has relied primarily on the nutritional diaries of the study participants. No studies have prospectively measured the effects of the supplements.

"In the Women's Health Study, the risk of dry eye decreased by about 30% per additional gram of omega-3 fatty acids consumed per day," she said; the study included 32,470 female health professionals who completed a validated food frequency questionnaire. In addition, omega-3 fatty acid supplementation also has been found to have a positive effect on asthma, cardiovascular disease, arthritis, depression, and adult-onset diabetes.