When my ophthalmologist introduced me to dry eye disease (DED), I was intrigued by the idea that itching, burning, grittiness, blurred vision, and increased need to blink might have different etiologies that all lead to ocular surface inflammation. A 2005 report showed a lower prevalence of DED among women who ate five to six servings of tuna per week (odds ratio, 0.32) compared with those who ate less than one serving per week.1 This opened the possibility that eating foods that increase the amounts of omega-3 (n-3) relative to omega-6 (n-6) essential fatty acids stored in our tissues might decrease the unwanted DED inflammation.
The validity of this idea was later examined in 13 clinical trials of supplements (reviewed in two 2014 meta-analyses) with no clear consensus on dose, composition, or length of treatment. By 2015, even the issue of whether n-3 or n-6 supplements were more effective remained unresolved. Since then, three clinical trials involving hundreds of patients have affirmed that oral omega-3 supplements significantly, but only modestly, improved the clinical status of DED patients.
N-3 AND N-6 DERIVATIVES DIFFER
The above history sets the stage for considering some detailed dry facts about n-3 and n-6 essential fatty acids. These facts may facilitate the design of more effective ways to treat and prevent unwanted ocular surface inflammation. Inflammation has a lot of moving parts, and its many signaling molecules have several positive feedback steps that amplify events and shift healthy physiology toward pathophysiology. Beneficial treatments with either steroidal or nonsteroidal anti-inflammatory drugs point to an important early step in inflammation: the release of 20- and 22-carbon highly unsaturated fatty acids (HUFAs) from tissue membrane phospholipids by an activated cytosolic phospholipase A2 (cPLA2).
The balance of n-3 and n-6 HUFAs is predictably related to the average balance of essential n-3 and n-6 nutrients in foods eaten, and it is a useful health risk assessment biomarker that associates with prevalence and severity of chronic inflammatory and cardiovascular conditions. A 1982 Nobel Prize recognized the importance of HUFA-based eicosanoids as potent mediators of physiology and pathophysiology. More vigorous action by n-6 than n-3 eicosanoids amplify inflammatory processes. The balance of n-3 and n-6 HUFAs from which eicosanoids are formed ranges from 25% n-6 in HUFAs to 80% n-6 in HUFAs for various ethnic food choices. Somehow, different groups of people unknowingly developed traditional food habits with very different impacts on health.
Food items can be described by a simple omega 3-6 balance score derived from the United States Department of Agriculture nutrient database values for the amounts (milligrams per kilocalorie) of 11 n-3 and n-6 nutrients in the item. Foods with positive scores increase the percentage of n-3 in HUFAs, and foods with negative scores increase the percentage of n-6 in HUFAs. Typical American food choices have an average score near -6 or -7, accompanying a resulting HUFA balance near 75% to 80% n-6 in HUFAs. The top 100 foods include 10 items with scores more negative than -20 and no item with a score more positive than +5 (spinach). Seafood is not among the top US foods but is more abundant in other ethnic lifestyles. Eating canned light tuna (+16) or solid white tuna (+46) can lower the percentage of n-6 in HUFAs (ie, raise the percentage of n-3 in HUFAs).
Very positive scores occur for wild sockeye salmon (+60) and fish oil supplements (cod liver oil, +140; menhaden oil, +200; salmon oil, +260). Concentrated forms of n-3 HUFAs are available to balance the negative scores of typical Western foods, such as soybean oil (-50), mayonnaise (-46), tub margarine (-39), microwave popcorn (-37), Italian salad dressing (-35), potato chips (-29), stick margarine (-28), vegetable shortening (-28), peanut butter (-24), and tortilla chips (-24). People need to consider whether any benefit comes from having such foods in their daily diet. They make the daily intake of n-6 nutrients exceed their narrow therapeutic window.
Eating 2,000 calories of a typical Western diet (average score, -6) might be “balanced” by 60 calories of an n-3 HUFA supplement (score, +200). Alternatively, 60 calories of the supplement could have an even greater effect if the daily foods had an average score of -4 (as in the traditional Mediterranean diet) or +1 (as in the traditional Japanese diet). A wide diversity of food choices can inform people about foods that could help them maintain a desired HUFA balance without need for a supplement. The most abundant omega nutrients, alpha-linolenic acid (18:3n-3) and linoleic acid (18:2n-6), continually compete with each other, as they are desaturated, elongated, and accumulated as n-3 and n-6 HUFA in tissue phospholipids. Their continual competitive impact has not been widely recognized in current clinical discussions of the efficacy of n-3 supplements.
Consuming expensive n-3 supplements while eating large amounts of competing n-6 nutrients is like test-driving a high-performance car with its hand brake on. Such action prevents performance from being optimal. Physicians and patients deserve better information on the dry facts about competing nutrients and inflammatory mediators that affect their efforts to build a balanced life.
1. Miljanovic B, Trivedi KA, Dana MR, Gilbard JP, Buring JE, Schaumberg DA. The relationship between dietary n-3 and n-6 fatty acids and clinically diagnosed dry eye syndrome in women. Am J Clin Nutr. 2005;82(4):887-893.