EPA and DHA
These fatty acids affect body systems differently.
KIMBERLY K. REED, O.D., F.A.A.O.
Recent studies reveal the total amount as well as relative amounts of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) appear to have a significant impact on the outcomes of different body systems.
Here, I discuss these studies and how you can use them to improve patient care.
A high dose of EPA+DHA significantly lowers triglycerides, a recent study shows. Specifically, a 3.4g/d dose of EPA+DHA vs. a 0.85g/d dose considerably decreased triglycerides in moderate hypertriglyceridemia (150mg/dL to 500mg/dL) patients.1 The placebo-controlled, double-blind, randomized, three-period crossover trial (eight weeks of treatment, six weeks of washout) was comprised of 23 men and three postmenopausal women who had moderate hypertriglyceridemia.
EPA, though not DHA, is effective in improving symptoms of depressive conditions, such as bipolar disorder, a recent meta-analysis study reveals. Specifically, symptoms were significantly decreased in 13 studies in which subjects took supplements containing greater than 50% EPA and in eight studies in which pure ethyl-EPA was taken.2 Meanwhile, depression symptoms weren’t significantly decreased in three of the pure DHA studies or in four studies in which subjects took supplements containing more than 50% DHA.2 The meta-analysis study was comprised of 28 randomized, placebo-controlled studies in which an omega-3 LC-PUFA preparation containing quantifiable amounts of DHA and EPA and sufficient statistics on scores of a recognizable measure of depressive symptoms was included.*
The study’s authors propose several theories for this finding, among them that EPA is more effective than DHA in lowering levels of pro-inflammatory mediators, like tumor necrosis factor-alpha (TNF-a).3,4 Since inflammation is a proposed factor in many mood-and-affect disorders, such as depression, Alzheimer’s disease and attention deficit hyperactivity disorder, this theory is certainly plausible.
Several studies underscore the importance of DHA on visual development. To start, one shows DHA-enriched (0.32%) formula-fed 12-month-old babies had better visual acuity (VA) vs. infants who drank the control formula.5 Specifically, the double-masked, randomized trial was comprised of 244 healthy, term, formula-fed infants randomly assigned to four formulas each containing equivalent nutrient amounts, except for long-chain polyunsaturated fatty acids. Researchers measured VA via visual evoked potentials. A follow-up study reveals the babies who drank the DHA-enriched formula had enhanced cognitive development at age 18 months, as measured by the Mental Development Index.6
DHA intake during gestation demonstrates beneficial effects on the visual system function of school-age children, a study shows.7 Specifically, after adjustment for confounders, cord plasma DHA level was found linked with shorter latencies of the N1 and P1 components of the color visual evoked potentials.
Also, full-field electroretinogram (ERG) amplitudes and ERG implicit times are affected by omega-3 types and amounts, a study reveals.8 Specifically, very-low-birth-weight infants who received a corn oil-based formula containing mainly linoleic acid (18:2 omega-6) and low in all omega-3 fatty acids had significantly greater rod thresholds than infants who received long-chain omega-3 nutrition (e.g. human milk, a formula supplemented with alpha linoleic acid/marine oils and intrauterine nutrition). Further, infants who received a formula that had ample alpha linolenic acid (18:3 omega-3) had intermediate thresholds that were significantly greater than those who received intrauterine nutrition. The study was comprised of 81 infants born at 30.4 weeks and within 10 days of birth were either enrolled to have their mother’s milk or randomized to receive an infant formula.
Finally, DHA supplementation was shown to provide a “positive and clear beneficial effect” on reading speed in dyslexic children, a study shows.9 Specifically, 13 of the 17 children enrolled in the open pilot study experienced a major improvement in a word test, reading speed improved by 60%, and motoric-perceptual velocity improved by 23%. All subjects took eight capsules per day of a long-chain polyunsaturated fatty acid supplement containing high-DHA fish oil and evening primrose oil for five months.
Using this information
Given the preponderance of evidence that the long-chain omega-3 fatty acids support cardiovascular, emotional and ocular health and function individually in the body, you must assess your patients current nutrition intake and lifestyle. This way, you can determine the best supplement to prescribe, if any. Provide patients with either an informal food frequency survey (e.g. “How often do you eat fish, what kind of fish is it and how is it prepared?”, etc.) or a more formal written assessment of your patients’ nutrient intake. (See www.permanente.net/homepage/kaiser/pdf/6116.pdf) Alternatively, you can refer patients for formal laboratory analysis of their omega-3 levels, which is identified through an arachidonic acid (AA)/EPA ratio. This ratio should be between 2:1 and 4:1, say most experts. Higher levels of AA, which is a pro-inflammatory derivative of the omega-6 pathway, indicates higher levels of inflammation. As a result, higher levels of omega-3 supplementation can help reduce this ratio. A caveat: Remember to always check with the patient’s primary care provider to rule out bleeding disorders or the concurrent use of blood thinners prior to supplement initiation. OM
Seek informal food frequency surveys for your patients.
* Keep in mind that when “no benefit” is found in a meta-analysis study, it’s essential to look critically at the study methods and outcomes. The reason: Often a benefit may have been found in the bulk of the studies included, but when all together, the results get diluted to lose statistical significance. When a clear benefit is found in these studies, however, it definitely adds power to the individual studies because in spite of study design differences, the same effect is seen across these different methodologies. Thus, the outcome is very likely the real effect.
1. Skulas-Ray AC, Kris-Etherton PM, Harris WS, et al. Dose-response effects of omega-3 fatty acids on triglycerides, inflammation, and endothelial function in healthy persons with moderate hypertriglyceridemia. Am J Clin Nutr 2011 Feb;93 (2):243-52.
2. Martins HG. EPA but not DHA appears to be responsible for the efficacy of omega-3 long chain polyunsaturated fatty acid supplementation in depression: evidence from a meta-analysis of randomized controlled trials. J Am Coll Nutr. 2009 Oct;28(5):525-42.
3. Thies F, Nebe-von-Carn G, Powell JR, et al. Dietary supplementation with eicosapentaenoic acid, but not with other long-chain n-3 or n-6 polyunsaturated fatty acids, decreases natural killer cell activity in healthy subjects aged >55y. Am J Clin Nutr 2001;73(3):539-48.
4. Sierra S, Lara-Villoslada F, Comalada M, et al. Dietary eicosapentaenoic acid and docosahexaenoic acid equally incorporate as docosahexaenoic acid but differ in inflammatory effects. Nutrition. 2008 Mar;24(3):245-54.
5. Birch EE, Carlson SE, Hoffman DR, et al. The DIAMOND (DHA Intake And Measurement Of Neural Development) Study: a double-masked, randomized controlled clinical trial of the maturation of infant visual acuity as a function of the dietary level of docosahexaenoic acid. Am J Clin Nutr. 2010 Apr;91(4):848-59.
6. Drover JR, Hoffman DR, Castaneda YS, et al. Cognitive function in 18-month-old term infants of the DIAMOND study: a randomized, controlled clinical trial with multiple dietary levels of docosahexaenoic acid. Early Hum Dev. 2011 Mar;87(3): 223-30.
7. Jacques C, Levy E, Muckle G, et al. Long-term effects of prenatal omega-3 fatty acid intake on visual function in school-age children. J Pediatr. 2011 Jan;158(1):83-90.
8. Birch DG, Birch EE, Hoffman DR, Uauy RD. Retinal development in very-low-birth-weight infants fed diets differing in omega-3 fatty acids. Invest Ophthalmol Vis Sci. 1992 Jul;33(8):2365-76.
9. Lindmark L, Clough P. A 5-month open study with long-chain polyunsaturated fatty acids in dyslexia. J Med Food. 2007 Dec;10(4):662-6.
DR. REED IS AN ASSOCIATE PROFESSOR AT THE NOVA SOUTHEASTERN UNIVERSITY COLLEGE OF OPTOMETRY IN FORT LAUDERDALE, FLA., A MEMBER OF THE OCULAR NUTRITION SOCIETY AND AUTHOR OF NUMEROUS ARTICLES ON OCULAR NUTRITION, DISEASE AND PHARMACOLOGY, SHE IS
ALSO A FREQUENT CONTINUING EDUCATION LECTURER. TO COMMENT ON THIS COLUMN, E-MAIL DR. REED AT KIM REED@NOVA.EDU.
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