Dry Eye and Diet: What Research Says About Essential Fatty Acids
By Eric Papas, PHD, MCOPTOM, DIPCL, FAAO
I well remember as a young optometrist being faced with problem contact lens patients struggling with dryness and discomfort and in need of some effective remedy to alleviate their problems. Around that time my attention was drawn to an article (Shreeve, 1982) suggesting that a combination of vitamins C and B6, taken together with the “Oil of the Evening Primrose Flower,” might be beneficial. Being a sucker for an attractive name, as well as desperate, I thought it ought to be worth a try and so I suggested the remedy to a couple of my most vocal symptomatic patients. After a few weeks, one returned to report that he was feeling better, but the other was grumpily unimpressed and blamed me for his having put on a few pounds!
About Essential Fatty Acids
Now I would be the first to admit that this wasn't the most definitive of clinical trials, but of course there was always more to this approach than just a pretty name. Evening primrose oil is a source of the essential fatty acid (EFA) gamma linolenic acid (GLA), and as such is a member of a family of substances that have received a lot of attention in recent years due to their potential to modulate inflammatory mechanisms in several parts of the body. This has led to proposals for their use to treat a wide variety of conditions including cardiovascular disease, cancer, asthma, eczema, mental illness, and, of course, dry eye.
EFAs are so named because they are critical to biological function. They are integral to the lipid bilayer structure of cell membranes throughout the body and play a key role in normal physiology. Unfortunately, humans lack the ability to synthesize these substances internally, so they must be regularly ingested for continued health. There are two types of EFAs, namely the omega-6 and the omega-3 groups, and though these are linked chemically, they maintain functional differences that make it important to actually eat both. Sources of omega-3s include cold water fish and flaxseed oil. Soybean, rapeseed, sunflower, and palm oils all contain omega-6s, as do nuts, cereals, and poultry. Once inside the liver, the relatively short EFA molecules undergo enzymatic alteration to form longer chain molecules of various types. Despite such changes, the downstream products that emerge remain recognizably within either the omega-6 or omega-3 categories, and it is these molecules that turn out to be influential in immune and inflammatory systems around the body. For example, both the omega-6 and omega-3 pathways can produce eicosanoids—a family of molecules including prostaglandins, prostacyclins, thromboxanes, and leukotrienes—which act locally to regulate a whole range of cellular functions. Broadly, the eicosanoids resulting from omega-3 metabolism are anti-inflammatory while those from omega-6 metabolism are pro-inflammatory.
While this view is an oversimplification, as there are many omega-6 pathways and not all result in “negative” outcomes, it is clear why there has been interest in the relative amounts of EFAs in the diet. Scrutiny of the types of foods common during the early development of humankind suggests that the omega-3 to omega-6 ratio at that time would have been around 1:1. This contrasts starkly with modern Western diets that produce ratios that may be closer to 1:20 (Simopoulos, 2011) and explains much of the desire to promote supplementation as a therapeutic strategy. The available epidemiological evidence tends to support this view, with data collected from the 32,470 participants in the Women's Health Study suggesting that those whose omega-3 to omega-6 ratio was in excess of 1:15 had roughly 2.5 times the dry eye risk of someone who had a ratio of 1:4. Women with higher omega- 3 intakes were also less likely to report a dry eye diagnosis (Miljanovic et al, 2005).
Does Supplementation Help?
Was my younger self on the right track in trying an oral EFA supplement for contact lens wearers? The GLA in evening primrose oil is certainly a source of omega-6s, but does it have a helpful therapeutic effect in this setting?
Rather surprisingly, there has been only one well-conducted clinical trial on which we can base an opinion (Kokke et al, 2008). This was a randomized, double-masked, controlled evaluation of evening primrose oil in a group of female contact lens wearers, all of whom were suffering from at least borderline dry eye or symptoms of contact lens-induced dry eye. One reason for choosing a single gender may have been because women seem to be more efficient metabolizers of some EFAs compared to men (Williams and Burdge, 2006). During the trial, half of the participants took six evening primrose oil capsules every day while the other half were given similar capsules containing just olive oil as a placebo. At the end of six months, the evening primrose oil group showed significant improvements in contact lens comfort, reduced symptoms of dryness, and increased tear meniscus heights, while there were no changes in the placebo users. This is an encouraging result, but there is clearly a need for more such studies to be conducted— not only to confirm the effect of omega-6s, but also to evaluate the value of omega-3 supplementation as well as how they function in combination.
The evidence in non-contact lens-related dry eye is only marginally better. Suffers of severe dry eye disease, i.e., Sjögren's syndrome, appear to benefit from omega-6 supplementation in terms of symptomatic improvement as well as in terms of reduced ocular surface disruption (Aragona et al, 2005; Barabino et al, 2003).
No one seems to have studied omega-3s for Sjögren's syndrome, but for individuals who have more moderate dry eye, omega-3 supplementation in the form of flaxseed oil has been found to reduce symptoms (Macsai, 2008), though the daily dose of 3.3 grams (six 1,000mg capsules) might be a challenge.
The remaining available work with mild-to-moderate dry eye amounts to only two studies, both of which used combination omega-3/omega-6 therapy. In the first, while there was a numerical improvement among the 71 participants in several ocular surface signs as well as in subjective symptoms, nothing quite reached statistical significance (Creuzot et al, 2006). Essentially the same result was achieved in a more recent study that enrolled roughly double the sample size (Brignole-Baudouin et al, 2011), despite the fact that assessment by impression cytology showed that the treatment actually lowered the expression of inflammatory markers in the conjunctiva.
We Need More to Go on
On the face of it, then, while there appears to be promise for contact lens wearers and for those who have very severe dry eye disease, the position for mild and moderate dry eye sufferers is a little disappointing. It should however be acknowledged that the number of studies conducted to date has really been very small, and so even this tentative conclusion is a “house of cards” that may be blown down at some point in the future.
Given the potential to manipulate variables such as formulation, dose, and treatment duration, it is clear that this field is a very long way from being exhaustively investigated. Particularly surprising is the minimal effort so far directed toward investigating the effects of omega-3 supplementation in isolation from omega-6. Much remains to be done to establish the true value of EFA supplementation as a means of improving the lot of dry eye sufferers. CLS
To obtain references for this article, please visit http://www.clspectrum.com/references.asp and click on document #196.
|Associate Professor Papas is executive director of Research & Development and director of Post Graduate Studies, Brien Holden Vision Institute and Vision Cooperative Research Centre, and senior visiting fellow, School of Optometry & Vision Science, University of New South Wales, Sydney, Australia. The Brien Holden Vision Institute and Vision Cooperative Research Centre have received research funds from B +L, AMO, and Allergan and have proprietary interest in products from Alcon, Cooper- Vision, and Carl Zeiss. You can reach him at firstname.lastname@example.org.|