Essential Fatty Acids and Dry Eye Disease

To view Table 1 please refer to the print version of our September issue, page 64.

My colleagues and I became interested in determining whether any association existed between the risk of dry eye syndrome and the dietary intake of specific essential fatty acids in women. The study we conducted focused on the omega-3 and omega-6 fatty acids.1 We analyzed this relationship in a large cohort called the Women's Health Study. The Women's Health Study is an ongoing, randomized trial of the ability of aspirin and vitamin E to prevent cardiovascular disease and cancer. The study consists of 39,876 female health professionals, and each receives annual follow-up questionnaires. Our study population included 32,470 of the participants in the Women's Health Study who responded to the diet questionnaire, which was given to them at baseline and provided information on whether or not they had been diagnosed with dry eye syndrome.

ESSENTIAL FATTY ACIDS IN THE DIET
The highest concentrations of omega-3 fatty acids are found in species of dark, oily fish such as tuna, mackerel, and salmon (Table 1). Smaller amounts also exist in walnuts and flaxseeds (flaxseed oil has a precursor to EPA and DHA, which are the two omega-3 fatty acids found in fish oil). Omega-6 fatty acids are found in many foods in the typical American diet, including most of the vegetable oils that Americans use for cooking. Corn oil, which may be the most-consumed oil in the US, has high concentrations of omega-6 fatty acids. Significant amounts of omega-6 fatty acids are also found in margarine, which is often corn-oil based.

STUDY METHODS
We assessed dry eye in our patient population with a follow-up questionnaire approximately 4 years after giving the participants the original diet questionnaire. We then used logistic regression models to determine whether a relationship existed between the dietary intake of omega-3 fatty acids and dry eye syndrome. In summary, we found that women with a higher dietary intake of omega-3 fatty acids were at a significantly lower risk of dry eye syndrome.

My colleagues and I specifically examined the participants' consumption of tuna fish, because it is the major source of omega-3 fatty acids in the typical American diet. Other food sources of this fatty acid are less commonly consumed by the average American. When we looked at tuna fish consumption, we found a significant dose-response relationship between the amount of tuna fish these women ate and their risk of dry eye disease. Women who on average ate two to four 4-oz servings of tuna per week had an approximately 20% decrease in their risk of dry eye versus those who ate less than two 4-oz servings of the fish per week. Participants who ate five to six 4-oz servings of tuna per week had a 66% reduction in their risk of dry eye compared with women who ate less than two servings per week.

THE ROLE OF FATTY ACIDs RATIOs
We also discovered that the patients' risk of dry eye syndrome depended on the ratio of omega-3 to omega-6 fatty acids in their diet. Omega-3 fatty acids tend to have anti-inflammatory properties.2 An increase in omega-3 fatty acids in the diet tends to decrease the overall amount of inflammation in the body, particularly in specific tissues such as the eye. Omega-6 fatty acids, however, have proinflammatory effects, and eating significant amounts of them may negate the benefits of consuming omega-3 fatty acids.

Some research suggests3 that the ideal ratio of omega-6 to omega-3 fatty acids should be less than 4 to 1, so we used this ratio as a reference category. The average ratio in our population was 9 omega-6 fatty acids to 1 omega-3, which is fairly typical of Americans. When we compared women with a ratio of less than 4 to 1 with those with higher ratios, the latter group had a greater risk of dry eye. Those participants who had a ratio of 15 to 1 or more had a 2.5-fold increase in their risk of dry eye, compared with the women whose consumption ratios were less than 4 to 1.

SUMMARIZING THE DATA
This study produced three important findings: (1) a significant trend exists toward a decreased risk of dry eye with higher dietary intakes of omega-3 fatty acids; (2) there is a specific link between a reduced risk of dry eye syndrome and tuna fish, the major source of omega-3 fatty acids in the typical American diet, and (3) a higher dietary ratio of omega-6 versus omega-3 fatty acids increases the risk of dry eye in women.

FURTHER STUDY
My colleagues and I will continue to follow up with this cohort by assessing these participants' propensity for dry eye syndrome again, approximately 5 years after the first assessment. We also plan to examine the relationship between essential fatty acids and dry eye further, although not necessarily limited to this population and perhaps using other methodologies. We have already sent out the questionnaires for the follow-up study, and gathering that data will take approximately 3 years because of the size of the study.

Additional data on this topic are currently scarce. Some clinicians have anecdotally reported on treating dry eye patients with oral supplements of fish and/or flax seed oil. Although these clinicians report success, theirs are hypothesis-generating studies compared with this investigation, which is a hypothesis-testing study. Because ours is the only study of its kind thus far, making any public health recommendations based on its results would be premature. I believe, however, that the findings are interesting and deserve further study. They are certainly consistent with what we know about the biological mechanisms that may be involved in the pathogenesis of dry eye syndrome, as well as with those anecdotal clinical reports. I think our growing body of knowledge suggests that omega-3 fatty acids may play a causative role in the pathogenesis of dry eye syndrome instead of just being a chance finding in the data.

Debra A. Schaumberg, ScD, OD, MPH, is Assistant Professor of Medicine and Ophthalmology in the Division of Preventive Medicine at the Brigham and Women's Hospital, Harvard Medical School in Boston, Massachusetts. Dr. Schaumberg may be reached at (617) 278-0849; dschaumberg@rics.bwh.harvard.edu.
1. Trivedi KA, Dana MR, Gilbard JP, Buring JE, Schaumberg DA. Dietary omega-3 fatty acid intake and risk of clinically diagnosed dry eye syndrome in women [abstract]. Invest Ophthalmol Vis Sci. 2003;44:811.
2. Alexander JW. Immunonutrition: The role of omega-3 fatty acids. Nutrition. 1998; 14:627-633.
3. Simopoulos AP. The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomed Pharmacother. 2002;56:365-379.