May 2015 Issue

Omegas: Dissecting the Science on Omega-3 Supplements
By Mardi A. Parelman, PhD
Today's Dietitian
Vol. 17 No. 5 P. 14

A review of the various oils and their health benefits, plus recommendations for RDs.

Americans spend approximately $6 billion per year on omega-3 fatty acid supplements and fortified foods.1 The main omega-3 fatty acids in the diet are alpha-linolenic acid (ALA, C18:3n-3), EPA (C20:5n-3), and DHA (C22:6n-3). Many over-the-counter supplements contain oils from fish, krill, algae, flaxseed, and hempseed. However, all of these omega-3 supplement choices may leave clients and patients with questions: Which supplements should I choose? Is one better than the other? Are omega-3 supplements as effective as eating fish?

Health Benefits of Omega-3 PUFAs
EPA and DHA are the most biologically active omega-3 polyunsaturated fatty acids (PUFAs) and can be found in fatty fish such as trout, salmon, and albacore tuna. ALA is the omega-3 fatty acid found in a variety of plant foods such as flaxseeds, walnuts, kale, canola oil, Brussels sprouts, and spinach. In plant foods, less than 1% and up to 15% of ALA is enzymatically converted to EPA or DHA.2 Because of the low level of conversion of ALA, more of it is needed, particularly for individuals who don't eat fish. In the United States, the adequate intake for ALA is 1.1 to 1.6 g/day.2,3

Although there isn't a dietary reference intake for EPA and DHA in the United States, Americans are encouraged to increase omega-3 fatty acid intake by eating fish at least twice per week. EPA and DHA are precursors to molecules that impact inflammation. There are some omega-3 mediators that induce moderate inflammatory responses when they're needed and others that resolve existing inflammation, and still others that reduce the expression and activity of inflammatory omega-6 arachidonic acid-derived molecules.4,5 The typical American diet is low in omega-3 fatty acids and provides nearly 10 times more dietary omega-6 fatty acids.3,6

The anti-inflammatory functions of omega-3 PUFAs make them desirable targets of inflammatory disease research. Many epidemiologic and observational studies show an association between higher fish consumption and lower risk of heart disease.3-6 However, other studies have found that omega-3 intake has no impact on heart disease risk.7,8 The conflicting data are a result of differences in study design, populations, outcomes measures, and confounding factors such as lifestyle, saturated fat, fiber, and phytochemical intake.6 Still, omega-3 PUFAs are an essential part of a healthful diet, even though it remains unclear how increased intake of supplements may reduce heart disease risk.

Increased intake of omega-3s also has been shown to positively impact rheumatoid arthritis (RA). According to a recent study, three months of omega-3 fish oil supplementation (EPA + DHA) provided symptom relief for patients but didn't slow or stop the progression of RA.9 This suggests that omega-3 fish oil supplements (EPA + DHA) may be an alternative pain relief option to NSAIDs for some RA patients; however, more research is needed before nutrition and health care professionals can make any recommendations.

Additional research also is needed regarding the association between omega-3 supplementation and cognitive health. Research shows that inflammation may contribute to the development of dementia and Alzheimer's disease. There have been mixed results regarding the ability of omega-3 PUFAs to treat or prevent all-cause dementia.10-12 Emerging research suggests that low DHA levels may play a role in the development and progression of Alzheimer's disease, but no omega-3 PUFA recommendations have been established for the treatment of dementia or Alzheimer's.11 DHA is present in phospholipids of neural cells, synapses, and gray matter in the brain.11 According to authors of a meta-analysis published in the Journal of Clinical Psychiatry, patients with predementia had lower blood levels of EPA but not DHA, whereas patients diagnosed with dementia had decreased EPA, DHA, and total omega-3 PUFAs.11 Researchers involved with the Framingham Heart Study examined the relationship between DHA, all-cause dementia, and Alzheimer's disease in men and women. They found participants with the highest levels of DHA had a 47% lower risk of developing any type of dementia.12 Further clinical trials are needed to determine whether EPA or DHA levels predict the risk of dementia or Alzheimer's disease, if and when to initiate interventions, and if EPA + DHA supplementation effectively reduces the risk of all-cause dementia.

A diet that's high in ALA may reduce the risk of cardiovascular disease, increase HDL cholesterol, improve blood pressure, and reduce inflammation.2,9,13,14 Consuming between 2.6 g to 8 g/day reduced blood pressure in healthy and moderately hypertensive individuals.14 At doses greater than 4.5 g/day, women had lower blood levels of C-reactive protein, interleukin-6, and E-selectin.14 More research is needed to determine whether the benefits derived from ALA-rich foods come from ALA itself, other components such as fiber, protein, vitamins, minerals, and phytochemicals, or an interaction between ALA and other nutrients.

Differences in Omega-3 Supplements
Grocery store shelves are lined with supplements containing a variety of omega-3, EPA and DHA-rich oils such as fish, krill, and algal. Fish oil supplements typically are made from anchovies, herring, menhaden, and salmon.9 Some manufacturers add antioxidants such as tocopherols (vitamin E) to fish oil supplements to prevent fatty acid oxidation. Krill are crustaceans that look like tiny shrimp. As the consumption and use of other fish and seafood has increased, krill oil has emerged as an alternative source of EPA and DHA. As with other fish, the EPA and DHA concentration varies by species and season.7,10 Algal oil, rich with DHA extracted from algae, such as seaweed, provides an attractive vegetarian alternative for individuals who want to increase their EPA and DHA intake.15-17

EPA, DHA, and Health
Despite research that shows a protective association between increased dietary fish intake and reduced risk of coronary heart disease, it remains unclear whether DHA and EPA supplements have the same effect.2-5 According to a review published in the February 2014 issue of Current Atherosclerosis Reports, consuming at least 250 mg/day of EPA + DHA lowered the risk of sudden cardiac death among adult men.5 Another study found that 12 weeks of fish oil supplementation resulted in higher EPA and DHA levels in adult men and women, but didn't affect inflammatory markers.13 Moreover, in other research, regular intakes of high levels of supplemental EPA + DHA is recommended for patients with high triglycerides.18 A meta-analysis published in the Journal of the American Medical Association showed that omega-3 supplements didn't reduce the risk of all-cause mortality, myocardial infarction, or stroke in patients with a history of heart disease.7 Further research is needed to understand the efficacy of omega-3 supplements and differences between dietary and supplemental sources of omega-3 fatty acids.

Algal oil supplements are emerging as a viable alternative to fish oil. Study participants who took algal oil for 14 days obtained the same level of DHA and EPA in their plasma phospholipids and red blood cells as subjects who ate cooked salmon.17 In other research, postmenopausal vegetarian women who took algal oil supplements for 42 days showed increased DHA and EPA in their plasma LDL and had reduced cholesterol.15 These results suggest that omega-3 PUFAs from algal oil are bioavailable, usable, and increase DHA.

Little is known, however, about the bioavailability and efficacy of krill oil supplements. According to a 2014 obesity mouse model published in Nutrition & Metabolism, EPA and DHA from krill oil was more bioavailable than fish oil.19 While both krill and fish oil altered the expression of genes involved in fatty acid metabolism, mice didn't need as much krill as fish oil, which suggested krill oil was more bioavailable. Researchers found that Krill oil affected different genes than fish oil, and that both oils may protect against obesity-associated dyslipidemia, although they do it differently. Additional research is needed to determine if these results can be replicated in human clinical trials.

Fatty Acid Composition of ALA in Supplements
Flaxseed and hempseed oils are supplemental sources of ALA. More than 50% of flaxseed oil is comprised of ALA, which makes it a rich source of omega-3 PUFAs.9 Not much research has been done on the fatty acid composition of hempseed oil. One fatty acid analysis of the Finola variety of hempseed oil showed that it contains 22% ALA, 2% stearidonic acid, 56% linoleic acid, and 4% gamma linoleic acid.20 However, the composition of hempseed may differ by strain.

Conversion of Supplemental ALA
The conversion of ALA to EPA or DHA involves desaturase and elongase enzymes. The conversion rate is low and influenced by gender, genetics, and diet.2,21,22 Empirical evidence found that men convert between 0.3% to 8% of ALA to EPA and less than 4% of ALA to DHA, and women convert up to 21% of ALA to EPA and up to 9% of ALA to DHA.16,21,22 The authors attribute the difference to the female hormone estrogen.

Genetic variations of elongase and desaturase enzymes influence the rate and efficiency of conversion of ALA to EPA and DHA and linoleic acid to arachidonic acid. ALA and linoleic acid use the same elongase and desaturase enzymes to make longer-chain PUFAs. Delta-6 desaturase, the rate-limiting enzyme in long-chain PUFA synthesis, has greater affinity for ALA than for linoleic acid, but more linoleic acid is present in the diet—a typical American diet contains 10 times more linoleic acid than omega-3 fatty acids.2 High levels of linoleic acid outcompetes with ALA for delta-6 desaturase activity, resulting in reduced conversion of ALA to EPA or DHA.5,23 An optimal ratio of omega-6 to omega-3 fatty acids hasn't been established.3

ALA, Flaxseed Oil, Hempseed Oil, and Health
Dietary and supplemental flaxseed oil increases plasma ALA and EPA but doesn't increase DHA. This implies that the health benefits of flaxseed oil are separate from the conversion of ALA to long-chain omega-3 PUFAs.9,13 Research shows that supplementing with flaxseed oil at doses ranging between 2.4 g/day up to 9 g/day leads to increased blood levels of ALA and EPA, lowered blood pressure, and modestly improved lipid profiles.2,9,13,14 At higher doses (≥14 g/day), flaxseed oil supplements may reduce platelet aggregation and systemic markers of inflammation.2,9 If a patient's goal is to increase her DHA level, fish, krill, and algal oil (vegetarian options) may be more suitable choices because they directly provide DHA and EPA.

The health benefits of ALA from hempseed oil aren't well studied. When researchers compared flaxseed oil with hempseed oil, they found higher levels of ALA in serum cholesterol and triglycerides after supplementation with flaxseed oil but not hempseed oil.24 Hempseed oil lowered total- to HDL-cholesterol ratios, a finding with minimal clinical relevance. Currently, limited research is available about the efficacy of hempseed oil as an omega-3 supplement.24

Are Omega-3 Supplements Worth It?
Evidence suggests that supplements provide a bioavailable alternative source of omega-3 PUFAs. The effectiveness of supplements remains unclear and varies by the source of the fat and the composition of the fatty acids. Omega-3 supplements are well tolerated, although algal, krill, and fish oil supplements may cause eructation. In one study, an intake of 2.4 g/day of flaxseed oil supplements were well tolerated and increased plasma ALA.13 In another, 1 g to 3 g/day of krill oil supplements resulted in increased EPA, DHA, and improved lipid profiles.9 The dosages of fish oil supplements vary and range from 1 g to 9 g/day with varying concentrations of EPA + DHA.9 The American Heart Association recommends supervised use of 2 g to 4 g/day of EPA + DHA supplements for patients with elevated triglycerides.18 Up to 3 g/day of EPA + DHA has been designated as Generally Recognized as Safe.3 The 2015 Dietary Guidelines for Americans are expected to expand on recommendations to substitute saturated fat for PUFAs, further encourage fish and seafood intake so people can aim for 8 oz per week, and urge more nuts, seeds, and soy consumption as part of a balanced diet.25 These efforts will help guide Americans to increase EPA, DHA, and ALA through foods. Variety, balance, and moderation characterize a healthful eating plan. Maybe similar principles should apply to omega-3 supplements.

— Mardi A. Parelman, PhD, is a freelance writer living in San Diego, California.

1. Herper M. Fish oil or snake oil? Study questions omega-3 benefits. Forbes. June 11, 2012. Accessed February 27, 2015.

2. Vannice G, Rasmussen H. Position of the Academy of Nutrition and Dietetics: dietary fatty acids for healthy adults. J Acad Nutr Diet.114(1):136-153.

3. Omega-3 fatty acids and health: fact sheet for health professionals. National Institute of Health, Office of Dietary Supplements website. Updated October 28, 2005. Accessed February 13, 2015.

4. Flock MR, Harris WS, Kris-Etherton PM. Long-chain omega-3 fatty acids: time to establish a dietary reference intake. Nutr Rev. 2013;71(10):692-707.

5. Fares H, Lavie CJ, DiNicolantonio JJ, O'Keefe JH, Milani RV. Omega-3 fatty acids: a growing ocean of choices. Curr Atheroscler Rep. 2014;16(2):389.

6. Kris-Etherton PM, Harris WS, Appel LJ; American Heart Association. Nutrition Committee. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation. 2002;106(21):2747-2757.

7. Rizos EC, Ntzani EE, Bika E, Kostapanos MS, Elisaf MS. Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: a systematic review and meta-analysis. JAMA. 2012;308(10):1024-1033.

8. Hooper L, Thompson RL, Harrison RA, et al. Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review. BMJ. 2006;332(7544):752-760.

9. Tur JA, Bibiloni MM, Sureda A, Pons A. Dietary sources of omega-3 fatty acids: public health risks and benefits. Br J Nutr. 2012;107(Suppl 2):S23-S52.

10. Deckelbaum RJ, Torrejon C. The omega-3 fatty acid nutritional landscape: health benefits and sources. J Nutr. 2012;142(3):587S-591S.

11. Lin PY, Chiu CC, Huang SY, Su KP. A meta-analytic review of polyunsaturated fatty acid compositions in dementia. J Clin Psychiatry. 2012;73(9):1245-1254.

12. Schaefer EJ, Bongard V, Beiser AS, et al. Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and alzheimer disease: the Framingham Heart Study. Arch Neurol. 2006;63(11):1545-1550.

13. Barceló-Coblijn G, Murphy EJ, Othman R, Moghadasian MH, Kashour T, Friel JK. Flaxseed oil and fish-oil capsule consumption alters human red blood cell n-3 fatty acid composition: a multiple-dosing trial comparing 2 sources of n-3 fatty acid. Am J Clin Nutr. 2008;88(3):801-809.

14. Rajaram S. Health benefits of plant-derived alpha-linolenic acid. Am J Clin Nutr. 2014;100(Suppl 1):443S-448S.

15. Wu WH, Lu SC, Wang TF, Jou HJ, Wang TA. Effects of docosahexaenoic acid supplementation on blood lipids, estrogen metabolism, and in vivo oxidative stress in postmenopausal vegetarian women. Eur J Clin Nutr. 2006;60(3):386-392.

16. Arterburn LM, Hall EB, Oken H. Distribution, interconversion, and dose response of n-3 fatty acids in humans. Am J Clin Nutr. 2006;83(6 Suppl):1467S-1476S.

17. Arterburn LM, Oken HA, Bailey Hall E, Hamersley J, Kuratko CN, Hoffman JP. Algal-oil capsules and cooked salmon: nutritionally equivalent sources of docosahexaenoic acid. J Am Diet Assoc. 2008;108(7):1204-1209.

18. Fish 101. American Heart Association website. Updated January 23, 2015. Accessed February 20, 2015.

19. Tillander V, Bjørndal B, Burri L, et al. Fish oil and krill oil supplementations differentially regulate lipid catabolic and synthetic pathways in mice. Nutr Metab (Lond). 2014;11:20.

20. Callaway JC. Hempseed as a nutritional resource: an overview. Euphytica. 2004;140(1-2):65-72.

21. Burdge GC, Jones AE, Wootton SA. Eicosapentaenoic and docosapentaenoic acids are the principal products of alpha-linolenic acid metabolism in young men. Br J Nutr. 2002;88(4):355-363.

22. Burdge GC, Wootton SA. Conversion of alpha-linolenic acid to eicosapentaenoic, docosapentaenoic and docosahexaenoic acids in young women. Br J Nutr. 2002;88(4):411-420.

23. Gibson RA, Neumann MA, Lien EL, Boyd KA, Tu WC. Docosahexaenoic acid synthesis from alpha-linolenic acid is inhibited by diets high in polyunsaturated fatty acids. Prostaglandins Leukot Essent Fatty Acids. 2013;88(1):139-146.

24. Schwab US, Callaway JC, Erkkilä AT, Gynther J, Uusitupa MI, Järvinen T. Effects of hempseed and flaxseed oils on the profile of serum lipids, serum total and lipoprotein lipid concentrations and haemostatic factors. Eur J Nutr. 2006;45(8):470-477.

25. Scientific Report of the 2015 Dietary Guidelines Advisory Committee. Office of Disease Prevention and Health Promotion website. Accessed March 19, 2015.