Several years ago, Carol Boerner, MD, from Claremont, NH, suggested the use of flaxseed oil supplementation as an alternate therapy for dry eye.1 As with many alternatives to therapies in the mainstream, the approach initially encountered considerable skepticism. Now that doctors have begun to try the supplementation with their own patients and realize its potential benefit, flaxseed oil is joining the list of accepted current therapies. At a recent lecture, I polled the physician audience as to how many had heard of flaxseed oil as a treatment for dry eye; about two-thirds raised their hands. When I asked how many had actually been using flaxseed oil to treat dry eye, about half raised their hands.
I became interested in flaxseed oil and omega-3 essential fatty acids nearly 2 years ago and soon noticed that my patients suffering with chronic meibomitis, meibomian gland dysfunction, and dry eye benefited from supplementation. The effectiveness of pure flaxseed oil is about to be improved upon with better sources for supplementation.
FATTY ACID METABOLISM
Essential fatty acids are, as the name suggests, fats that the human body finds essential. The body must obtain them from food because it cannot produce them. The two most important types of essential fatty acids are omega-6s and omega-3s.
The majority of us consume an excess of omega-6 essential fatty acids by eating food such as milk, ice cream, butter, pizza, beef, hamburgers, steaks, fried items, cookies, crackers, and cake. In fact, the typical American receives 20 times too much omega-6 compared with omega-3 fatty acids in his diet. Unfortunately, omega-6 fatty acids are proinflammatory; they generate increased serum levels of proinflammatory arachodonic acid and its inflammatory metabolites (Table 1). These proinflammatory ecosanoids (eicosanoids are oxygenated fatty acids that act as local hormones near their site of synthesis) help promote posterior blepharitis and meibomitis in patients with a propensity for these conditions.
By contrast, omega-3 fatty acids are anti-inflammatory, and they counterbalance and suppress the effects of omega-6s. In addition, omega-3s are well known to be beneficial for cardiovascular health, because they lower both the ?bad? cholesterol and triglycerides while they raise the ?good? cholesterol. The problem is that most of us do not consume enough omega-3s. These fatty acids are found in flaxseed oil, salmon, sardines, mackerel, herring, and walnuts—foods not consumed often enough by the typical American.
So how does flaxseed oil help dry eye? Flaxseed oil contains an abundance of the omega-3 fatty acid called alpha-linolenic acid (ALA). ALA by itself is not directly anti-inflammatory, but it is converted by the body to an ecosanoid called ecosapentanoic acid (EPA) that is profoundly anti-inflammatory. Some individuals' metabolisms perform this conversion more readily than others; the more effectively someone generates EPA from ALA, the more effectively flaxseed oil suppresses inflammation. This disparity has resulted in some inconsistencies in the results seen with flaxseed oil supplementation alone. For this reason, I now supplement flaxseed oil with fish oils that provide a direct source of EPA.
EPA acts in five ways to decrease inflammation:
1. EPA is directly converted into two anti-inflammatory ecosanoids: prostaglandin E3 and leukotriene B5.
2. Through competitive inhibition, EPA blocks the creation of proinflammatory arachidonic acid.
3. EPA pushes the metabolism of omega-6 to produce more anti-inflammatory prostaglandin E1 (PGE1).
4. EPA blocks the formation of proinflammatory metabolites that are formed from arachidonic acid.
5. At the gene transcription level, EPA blocks the production of proinflammatory tissue necrosis factor alpha, interleukin 1-beta, interleukin 1-alpha, aggrecanases, and COX-2.
Fish oil supplements, rich in EPA, have such a potent anti-inflammatory effect that numerous peer-reviewed, prospective, controlled studies have found it to be effective in treating rheumatoid arthritis. Given the various ways in which EPA suppresses inflammation, we now understand why meibomitis patients treated with omega-3 supplementation have demonstrated a resolution of their ocular irritation.
In addition to suppressing inflammation, EPA has another remarkable effect based on its ability to increase the production of PGE1. PGE1 acts on both EP2 and EP4 receptors to activate adenylate cyclase and increase cyclic AMP. Gilbard and Dartt have previously shown that drugs that increase cyclic AMP stimulate tear secretion in dry eye patients.2,3 Others have shown in rabbits that PGE1, like the drugs tested in patients, stimulates tear secretion as well. Patients with dry eye who were treated with omega-3 fatty acids have been reported not only to feel better in the morning, but also throughout the day. The effect of EPA on PGE1 production may explain this dramatic effect.
So far, we have seen how omega-3s in general, and EPA in particular, decrease inflammation and stimulate tear secretion. There is one more benefit that omega-3s offer for the ocular surface: They improve the oil layer. The meibomian glands produce oil, and it would seem logical that this oil is produced from essential fatty acids. A recent study by Sullivan et al found that omega-3 fatty-acid intake in Sjögren's patients directly affected their meibomian gland lipid profiles.4 Omega-3 supplementation appears to improve the tear film oil layer by providing the ?building blocks? for meibum. Boerner has reported that the meibomian gland secretions of dry eye patients become thinner and clearer with omega-3 treatment. An improved oil layer would contribute to the greater comfort felt by dry eye patients throughout the day.
I believe we have developed a solid hypothesis as to why flaxseed oil supplementation has been observed to provide real benefits in the treatment of meibomitis, meibomian gland dysfunction, and dry eye. Based on this understanding, it would make sense to provide EPA from two sources: indirectly as a derivative from flaxseed oil and directly from fish oil, thus guaranteeing effective doses of EPA. Additionally, given the fact that long-term omega-3 supplementation depletes serum levels of vitamin E, should not this supplement be fortified with vitamin E? Indeed, this describes what I believe is the next generation of omega-3 supplements for dry eyes, TheraTears Nutrition for Dry Eyes (Advanced Vision Research, Woburn, MA). This supplement, which has just become available, is an EPA- and DHA-enriched flaxseed oil supplement in soft gel capsule form that is fortified with vitamin E. The starting dose is four soft gels per day, taken either at once or in divided doses. I recommend four capsules in the morning with breakfast, because that is when the body absorbs fats best. I make sure that all patients who have had their gall bladders removed are on simultaneous lipase supplementation.
Given the effectiveness of EPA in treating rheumatoid arthritis, many doctors are recommending omega-3 supplementation for Sjögren's patients. For these reasons, I double the Nutrition dose in patients with Sjögren's syndrome and ask them to take eight capsules per day in divided doses with meals. With this prescription, I aim to help both these patients' serious dry eyes and their rheumatoid arthritis. TheraTears Nutrition for Dry Eyes is becoming an essential adjunct in my practice for the treatment of dry eye and a broad range of ocular surface inflammatory disorders.
Terrence P. O'Brien, MD, serves as Associate Professor of Ophthalmology, Director of Refractive Surgery, and Director of Ocular Infectious Diseases at The Wilmer Ophthalmological Institute at Johns Hopkins University School of Medicine. Dr. O'Brien holds no financial interest in any of the products herein. He may be reached at (410) 583-2842; email@example.com.
1. Boerner CF. Flaxseed oil as a parenteral treatment for dry eye. Poster presented at the ASCRS meeting. Boston, MA. May 2000.
2. Gilbard JP, Rossi SR, Gray Heyda K, Dartt DA. Stimulation of tear secretion by topical agents that increase cyclic nucleotide levels. Invest Ophthalmol Vis SCI .1990;31:1381-1388.
3. Gilbard JP, Rossi SR, Gray Heyda K, Dartt DA. Stimulation of tear secretion and treatment of dry eye disease with 3-Isobutyl-1-methylxanthine. Arch Ophthalmol. 1991;109:672-676
4. BD Sullivan, et al. Correlations between nutrient intake and the polar lipid profiles of meibomian gland secretions in women with Sjogren's syndrome. In: Sullivan BD, ed. Lacrimal Gland, Tear Film and Dry Eye Syndromes. New York: Kluwer Academic Plenum Publishers. 2002:441-447.