Metabolism of fatty acids and vitamins can help quell the inflammation behind ocular surface disease.

We know now that there are myriad causes of dry eye disease, all with a common denominator of underlying inflammation.[1,2] However, we now have more diagnostic tests and more treatment tools at our disposal, including nutritional input. A look at the science behind this approach to treating dry eye can offer us a complete picture of dry eye from an alternative perspective.

Numerous studies have shown that omega-3 fatty acids (fish oil) are effective at treating dry eye disease.[3-9] However, they are not the only nutrient that addresses dry eye disease.

There are two essential (needed in our diet) fatty acids: alpha-linolenic acid (ALA), an omega-3, and linoleic acid (LA), an omega-6. Internal enzymes inside our bodies act upon these acids, producing functional molecules, including molecules that have pro- or anti-inflammatory reactions. Once metabolized, ALA and LA become prostaglandins E3 and E2 respectively. However, the progressive enzyme action is affected by many factors. For example, the delta-6 desaturase enzyme action on both omega molecules is reduced by aging, alcohol, nutrient deficiencies, trans fat, and elevated cholesterol. Thus, the metabolism of these molecules may not be as efficient as it appears.

One of the most important aspects of this metabolism is the balance between the two omegas. Because omega-3 progresses to an anti-inflammatory prostaglandin, we might think our bodies need more of that one. However, we also need the pro-inflammatory prostaglandins to fight off infections, diseases and a whole host of conditions.

The ideal ratio of omega-6 to omega-3 should be about four to one (yes, more omega-6).[10] However, the standard American diet maintains a ratio closer to 25 to one, which means that the pro-inflammatory pathway is pushed to the chronic inflammatory state.[11] However, if the omega-3 balance is maintained, the omega-3 molecules of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) will block off the conversion to arachidonic acid (AA). This will allow the omega-6 molecules gamma-linolenic acid (GLA) and dihomo-gamma-linolenic acid (DGLA) to convert to a mucus-specific anti-inflammatory prostaglandin E1. This reduces inflammation in all mucous membranes in the body, including those in the tear film.

So, should individuals increase the amount of omega-3 EFAs in the diet to balance out the ratio of omega-6 to omega-3 fatty acids? Not necessarily. Given the amount of omega-6 we currently consume, the additional amount of omega-3 required could lead to not-so-beneficial effects. For example, fish oil is a blood thinner, so ingesting excessive amounts could lead to easy bruising and other blood-thinning effects. A better approach is to reduce the amount of omega-6 fatty acids in our diet while moderately increasing the omega-3 fats in our diet.

DHA and EPA are formed when fish eat algae and are found in the triglyceride form.[12,13] A triglyceride consists of a three-carbon glycerol “backbone” with each carbon linked to a fatty acid molecule. Thus, each triglyceride molecule contains three fatty acids. In normally produced fish oil, about 20% to 30% of the fatty acids are EPA and DHA, while highly concentrated oils can contain 60% to 85% EPA and DHA. This is why it is important to check the label for the actual EPA/DHA concentrations in any particular formula.

Besides omega-3s and omega-6s, other nutrients also support the anterior segment of the eye, namely:

• vitamin A, which is vital for the health of the corneal and conjunctival epithelial cells of the cornea and conjunctiva, as well as the function of the immune system.[14-16] It is also necessary for goblet cell and lacrimal gland production of the large variety of mucins now associated with the base layer of the tear film.

• vitamin B6, which is one of the nutrient co-factors required to push the metabolic pathway conversion of GLA to DGLA.[17,18] It is also required for the neuronal blink response.[19]

• vitamin C, which as ascorbyl palmitate (fat-soluble form) modulates PGE1 synthesis. This vitamin C form also enhances the production of immunoglobulin E concentrates in tears, the first line of basophil and mast cell defense against invading pathogens and allergens that frequently cause dry eye symptoms.[20]

• vitamin E, which should be included in all fatty acid-based formulations to help prevent or slow lipid oxidation. This particularly includes any formulation that includes flaxseed oil or any type of fish oil.[21]

• vitamin D, which improves tear hyperosmolarity and should be included in all formulations that include vitamin A due to an increased risk of fractures in older patients taking large amounts of supplemental vitamin A.[22,23]

Black currant seed oil is an excellent source of GLA due to its four-to-one balance of omegas and should be included in a full-spectrum dry eye formula.[24-27] Lactoferrin is one of the proteins that transfer iron to the cells and control the level of free iron in the blood. Adequate levels of tear lactoferrin, naturally produced by the lacrimal gland and neutrophils, are particularly important for eye surgery and contact lens patients, who are disposed to a risk of infection.

Quality dry eye products also contain minerals, mucin enhancers, antioxidants and natural anti-inflammatory ingredients. Making recommendations based on solid science will assure that your patients receive products that can make a significant as well as rapid resolution to their dry eye concerns.

Jeffrey Anshel, OD, FAAO, is founding president of the Ocular Nutrition Society and is in private practice in Encinitas, CA.

Available Dry Eye Supplements
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Retaine Flax Omega 3, 6 Supplement
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EyePromise EZ Tears

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2. Stern ME, Beuerman RW, Fox RI, Gao J, Mircheff AK, Pflugfelder SC. The pathology of dry eye: the interaction between the ocular surface and lacrimal glands. Cornea. 1998 Nov;17(6):584-9.

3. Wojtowicz JC, Butovich I, Uchiyama E, et al.. Pilot, prospective, randomized, double-masked, placebo-controlled clinical trial of an omega-3 supplement for dry eye. Cornea. 2011 Mar;30(3):308-14.

4. Sheppard JD Jr, Singh R, McClellan AJ, et al. Long-term supplementation with n-6 and n-3 PUFAs improves moderate-to-severe keratoconjunctivitis sicca: a randomized double-blind clinical trial. Cornea. 2013 Oct;32(10):1297-304.

5. Viau S, Maire MA, Pasquis B, et al. Efficacy of a 2-month dietary supplementation with polyunsaturated fatty acids in dry eye induced by scopolamine in a rat model. Graefes Arch Clin Exp Ophthalmol. 2009 Aug;247(8):1039-50.

6. Kangari H, Eftekhari MH, Sardari S, et al. Short-term consumption of oral omega-3 and dry eye syndrome. Ophthalmology. 2013 Nov;120(11):2191-6.

7. Bhargava R, Kumar P, Kumar M, et al. A randomized controlled trial of omega-3 fatty acids in dry eye syndrome. Int J Ophthalmol. 2013 Dec 18;6(6):811-6.

8. Rosenberg ES, Asbell PA. Essential fatty acids in the treatment of dry eye. Ocul Surf. 2010 Jan;8(1):18-28.

9. Walter SD, Gronert K, McClellan AL, et al. ω-3 Tear Film Lipids Correlate With Clinical Measures of Dry Eye. Invest Ophthalmol Vis Sci. 2016 May 1;57(6):2472-8.

10. Miljanović B, Trivedi KA, Dana MR, et al. Relation between dietary n-3 and n-6 fatty acids and clinically diagnosed dry eye syndrome in women. Am J Clin Nutr. 2005 Oct;82(4):887-93.

11. Enos RT, Velázquez KT, McClellan JL, et al. Reducing the dietary omega-6:omega-3 utilizing α-linolenic acid; not a sufficient therapy for attenuating high-fat-diet-induced obesity development nor related detrimental metabolic and adipose tissue inflammatory outcomes. PLoS One. 2014 Apr 14;9(4):e94897.

12. Visioli F, Risé P, Barassi MC, et al. Dietary intake of fish vs. formulations leads to higher plasma concentrations of n-3 fatty acids. Lipids. 2003 Apr;38(4):415-8.

13. Dyerberg J, Madsen P, Møller JM, et al. Bioavailability of marine n-3 fatty acid formulations. Prostaglandins Leukot Essent Fatty Acids. 2010 Sep;83(3):137-41.

14. Odaka A, Toshida H, Ohta T, et al. Efficacy of retinol palmitate eye drops for dry eye in rabbits with lacrimal gland resection. Clin Ophthalmol. 2012;6:1585-93.

15. Ubels JL, Dennis MH, Rigatti BW, et al. Nuclear retinoic acid receptors in the lacrimal gland. Curr Eye Res. 1995 Nov;14(11):1055-62.

16. Ubels JL, MacRae SM. Vitamin A is present as retinol in the tears of humans and rabbits. Curr Eye Res. 1984 Jun;3(6):815-22.

17. Horrobin DF. Essential fatty acid and prostaglandin metabolism in Sjögren’s syndrome, systemic sclerosis and rheumatoid arthritis. Scand J Rheumatol Suppl. 1986;61:242-5.

18. Bordoni A, Hrelia S, Lorenzini A, et al. Dual influence of aging and vitamin B6 deficiency on delta-6-desaturation of essential fatty acids in rat liver microsomes. Prostaglandins Leukot Essent Fatty Acids. 1998 Jun;58(6):417-20.

19. Berman BD, Horovitz SG, Morel B, Hallett M. Neural correlates of blink suppression and the buildup of a natural bodily urge. Neuroimage. 2012 Jan 16;59(2):1441-50.

20. Horrobin DF, Campbell A. Sjögren’s syndrome and the sicca syndrome: the role of prostaglandin E1 deficiency. Treatment with essential fatty acids and vitamin C. Med Hypotheses. 1980 Mar;6(3):225-32.

21. Jiang Q, Elson-Schwab I, Courtemanche C, Ames BN. gamma-tocopherol and its major metabolite, in contrast to alpha-tocopherol, inhibit cyclooxygenase activity in macrophages and epithelial cells. Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11494-9.

22. Bosetti M, Sabbatini M, Calarco A, et al. Effect of retinoic acid and vitamin D3 on osteoblast differentiation and activity in aging. J Bone Miner Metab. 2016 Jan;34(1):65-78.

23. Kizilgul M, Kan S, Ozcelik O, et al. Vitamin D replacement improves tear osmolarity in patients with vitamin D deficiency. Semin Ophthalmol. 2018;33(5):589-594.

24. Barabino S, Rolando M, Camicione P, et al. Systemic linoleic and gamma-linolenic acid therapy in dry eye syndrome with an inflammatory component. Cornea. 2003 Mar;22(2):97-101.

25. Wu D, Meydani M, Leka LS, et al. Effect of dietary supplementation with black currant seed oil on the immune response of healthy elderly subjects. Am J Clin Nutr. 1999 Oct;70(4):536-43.

26. Tzen J, Cao Y, Laurent P, et al. Lipids, proteins, and structure of seed oil bodies from diverse species. Plant Physiol. 1993 Jan;101(1):267-276.

27. Flores G, Ruiz del Castillo ML. Enhancement of nutritionally significant constituents of black currant seeds by chemical elicitor application. Food Chem. 2016 Mar 1;194:1260-5.


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