A randomized clinical trial to determine the efficacy of manufacturers' recommended doses of omega-3 fatty acids from different sources in facilitating cardiovascular disease risk reduction

Maggie Laidlaw, Carla A Cockerline, William J Rowe, Maggie Laidlaw, Carla A Cockerline, William J Rowe

Abstract

Background: Omega-3 fatty acids confer beneficial health effects, but North Americans are lacking in their dietary omega-3-rich intake. Supplementation is an alternative to consumption of fish; however, not all omega-3 products are created equal. The trial objective was to compare the increases in blood levels of omega-3 fatty acids after consumption of four different omega-3 supplements, and to assess potential changes in cardiovascular disease risk following supplementation.

Methods: This was an open-label, randomized, cross-over study involving thirty-five healthy subjects. Supplements and daily doses (as recommended on product labels) were:Concentrated Triglyceride (rTG) fish oil: EPA of 650 mg, DHA of 450 mgEthyl Ester (EE) fish oil: EPA of 756 mg, DHA of 228 mgPhospholipid (PL) krill oil: EPA of 150 mg, DHA of 90 mgTriglyceride (TG) salmon oil: EPA of 180 mg, DHA of 220 mg.Subjects were randomly assigned to consume one of four products, in random order, for a 28-day period, followed by a 4-week washout period. Subsequent testing of the remaining three products, followed by 4-week washout periods, continued until each subject had consumed each of the products. Blood samples before and after supplementation were quantified for fatty acid analysis using gas chromatography, and statistically analysed using ANOVA for repeated measures.

Results: At the prescribed dosage, the statistical ranking of the four products in terms of increase in whole blood omega-3 fatty acid levels was concentrated rTG fish oil > EE fish oil > triglyceride TG salmon oil > PL krill oil. Whole blood EPA percentage increase in subjects consuming concentrated rTG fish oil was more than four times that of krill and salmon oil. Risk reduction in several elements of cardiovascular disease was achieved to a greater extent by the concentrated rTG fish oil than by any other supplement. Krill oil and (unconcentrated) triglyceride oil were relatively unsuccessful in this aspect of the study.

Conclusion: For the general population, the form and dose of omega-3 supplements may be immaterial. However, given these results, the form and dose may be important for those interested in reducing their risk of cardiovascular disease.

Trial registration: ClinicalTrials.gov: NCT01960660.

Figures

Figure 1
Figure 1
Mean levels of EPA + DHA for four supplement groups at Day 0 and Day 28.
Figure 2
Figure 2
Mean percentage change in EPA, DHA and EPA + DHA levels from Day 0 to Day 28, with statistical comparisons among the four comparator products.

References

    1. Schwalfenberg G. Omega-3 fatty acids: their beneficial role in cardiovascular health. Can Fam Physician. 2006;52:734–740.
    1. Wu JHY, Lemaitre RN, King IB, Song X, Sacks FM, Rimm EB, Heckbert SR, Siscovick DS, Mozaffarian D. Association of plasma phospholipid long-chain omega-3 fatty acids with incident atrial fibrillation in older adults: the cardiovascular health study. Circulation. 2012;125:1084–1093.
    1. Oh R. Practical applications of fish oil (ω-3 fatty acids) in primary care. J Am Board Fam Pract. 2005;18:28–36.
    1. Bucher HC, Hengstler P, Schindler C, Meier G. N-3 polyunsaturated fatty acids in coronary heart disease: a meta-analysis of randomized controlled trials. Am J Med. 2002;112:298–304.
    1. Lopez LB, Kritz-silverstein D, Barrett-Connor E. High dietary and plasma levels of the omega-three fatty acid docosahexaenoic acid are associated with decreased dementia risk: the Rancho Bernardo study. J Nutr Health Aging. 2011;15(1):25–31.
    1. Yurko-Mauro K, McCarthy D, Rom D, Nelson EB, Ryan AS, Blackwell A, Salem N Jr, Stedman M. on behalf of the MIDAS Investigators. Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline. Alzheimers Dement. 2010;6:456–464.
    1. Navqi AZ, Buettner C, Phillips RS, David RB, Mukamel KJ. n-3 fatty acids and periodontitis in US adults. J Am Diet Assoc. 2010;110:1669–1675.
    1. Lee YH, Bae SC, Song GG. Omega-3 polyunsaturated fatty acids and the treatment of rheumatoid arthritis: a meta-analysis. Arch Med Res. 2012;43(5):356–362.
    1. Dawczynski C, Hackermeier U, Viehweger M, Strange R, Springer M, Jahreis G. Incorporation of n-3 PUFA and γ-linolenic acid in blood lipids and red blood cell lipids together with their influence on disease activity in patients with chronic inflammatory arthritis–a randomized controlled human intervention trial. Lipids Health Dis. 2011;10:130–138.
    1. United States Department of Agriculture; Department of Health and Human Services. Dietary Guidelines for Americans, 2010. U.S Government printing office Washington, DC, USA, 2010.
    1. Kris-Etherton PM, Harris WS, Appel LJ, Committee FTN. Fish consumption, fish oil, omega-3 fatty acids, and cardio-vascular disease. Circulation. 2002;106:2747–2757.
    1. Harris WS, Mozaffarian D, Lefevre M, Toner CD, Columbo J, Cunnane SC, Holden JM, Klurfeld DM, Morris MC, Whelan J. Towards establishing dietary reference intakes for eicosapentaenoic and docosahexaenoic acids. J Nutr. 2009;139:804S–819S.
    1. Agricultural Research Service, United States Department of Agriculture (USDA) USDA National Nutrient Database for Standard Reference, Release 25. 2012. USDA Washington, DC, USA.
    1. Raatz SK, Silverstein JT, Jahns L, Picklo MJ. Issues of fish consumption for cardiovascular disease risk reduction. Nutrients. 2013;5(4):1081–1097.
    1. Sekikawa A, Steingrimdottir L, Ueshima H, Shin C, Curb JD, Evans RW, Hauksdottir AM, Kadota A, Choo J, Masaki K, Thorsson B, Launer LJ, Garcia ME, Maegawa H, Willcox BJ, Eiriksdottir G, Fujiyoshi A, Miura K, Harris TB, Kuller LH, Gudnason V. Serum levels of marine-derived n-3 fatty acids in Icelanders, Japanese, Koreans, and Americans – A descriptive epidemiologic study. Prostaglandins Leukot Essent Fatty Acids. 2012;87:11–16.
    1. Giraldi G, De Luca dÀlessandro E. Dietary habits in Italy: the importance of the Mediterranean diet. Ann Ig. 2012;24(4):311–317.
    1. Cardoso C, Lourenco H, Costa S, Goncalves S, Nunes ML. Survey into the seafood consumption preferences and patterns in the Portuguese population. Gender and regional variability. Appetite. 2013;54:20–31.
    1. Calderon-Garcia JF, Moran JM, Roncero-Martin R, Rey-Sanchez P, Rodriguez-Velasco FJ, Pedrera-Zamorano JD. Dietary habits, nutrients and bone mass in Spanish premenopausal women: the contribution of fish to better bone health. Nutrients. 2012;5(1):10–22.
    1. Guili C, Papa R, Mocchegiani M, Marcellini F. Dietary habits and ageing in a sample of Italian older people. J Nutr Health Aging. 2012;16(10):875–879.
    1. Council for Responsible Nutrition contact: Nancy Stewart. Consumer confidence in supplements remains at two year high: New Survey Results Confirm: Two-thirds of U.S. adults take supplements. Washington, D.C. September 20, 2013.
    1. Schulthess G, Lipka G, Compassi S, Boffelli D, Weber FE, Paltauf F, Hauser H. Absorption of monoacylglycerols by small intestinal brush border membrane. Biochemistry. 1994;33:4500–4508.
    1. Lawson L, Hughes B. Human absorption of fish oil fatty acids as triglycerides, free acids, or ethyl esters. Biochem Biophys Res Commun. 1988;152(1):328–335.
    1. el Boustani S, Colette C, Monnier L, Descomps B, Crastes de Paulet A, Mendy F. Eternal absorption in man of eicosapentaenoic acid in different chemical forms. Lipids. 1987;22(10):711–714.
    1. Beckermann B, Beneke M, Seitz I. Comparative bioavailability of eicosapentaenoic acid and docosahexaenoic acid from triglycerides, free fatty acids and ethyl esters in volunteers. Arzneimittelforschung. 1990;40(6):700–704.
    1. Wakil A, Mir M, Mellor DD, Mellor SF, Atkin SL. The bioavailability of eicosapentaenoic acid from reconstituted triglyceride fish oil is higher than that obtained from the triglyceride and monoglyceride forms. Asia Pac J Clin Nutr. 2010;19(4):499–505.
    1. Dyerberg J, Madsen P, Moller JM, Aardstrup I, Schmidt EB. Bioavailability of marine n-3 fatty acid formulations. Prostaglandins Leukot Essent Fatty Acids. 2010;83(3):137–141.
    1. Milte CM, Coates AM, Buckley JD, Hill AM, Howe PR. Dose-dependent effects of docosahexaenoic acid-rich fish oil on erythrocyte docosahexaenoic acid and blood lipid levels. Br J Nutr. 2008;99(5):1083–1088.
    1. Conquer JA, Holub BJ. Effect of supplementation with different doses of DHA on the levels of circulating DHA as non-esterified fatty acid in subjects of Asian Indian background. J Lipid Res. 1998;39(2):286–292.
    1. Mozaffarian D, Lemaitre RN, King IB, Song X, Huang H, Sacks FM, Rimm EB, Wang M, Siscovick DS. Plasma phospholipid long-chain omega-3 fatty acids and total and cause-specific mortality in older adults: the cardiovascular health study. Ann Int Med. 2013;158(7):515–525.
    1. Schuchardt JP, Schneider I, Meyer H, Neubronner J, von Schacky C, Hahn A. Incorporation of EPA and DHA into plasma phospholipids in response to different omega-3 fatty acid formulations – a comparative bioavailability study of fish oil vs. krill oil. Lipids Health Dis. 2011;10(145):1–7.
    1. Davidson MH, Johnson J, Rooney MW, Kyle ML, Kling DF. A novel omega-3 free fatty acid formulation has dramatically improved bioavailability during low-fat diet compared with omega-3-acid ethyl esters: The ECLIPSE (Epanova compared to Lovaza in a pharmacokinetic single-dose evaluation) study. J Clin Lipidol. 2012;6(6):573–584.
    1. Albert CM, Campos C, Stampfer MJ, Ridker PM, Manson JE, Willett WC, Ma J. Blood Levels of long-chain n–3 fatty acids and the risk of sudden death. N Engl J Med. 2002;346(15)):1113–1118.
    1. Simon JA, Hodgkins ML, Browner WS, Neuhaus JM, Bernert JT, Hulley SB. Serum fatty acids and the risk of coronary heart disease. Am J Epidemiol. 1995;142(5):469–476.
    1. Lemaitre RN, King IB, Mozaffarian D, Kuller LH, Tracy RP, Siscovick DS. N-3 Polyunsaturated fatty acids, fatal ischemic heart disease, and nonfatal myocardial infarction in older adults: the Cardiovascular Health Study. Am J Clin Nutr. 2003;77(2):319–325.
    1. Harris WS, von Schacky C. The Omega-3 Index: a new risk factor for death from coronary heart disease? Prev Med. 2004;39(1):212–220.
    1. Wallace J. Nutritional and botanical modulation of the inflammatory cascade – eicosanoids, cyclooxygenases, and lipooxygenases – as an adjunct in cancer therapy. Integr Cancer Ther. 2002;1(1):7–37.
    1. Wall R, Ross RP, Fitzgerald GF, Stanton C. Fatty acids form fish: the anti-inflammatory potential of long-chain omega-3 fatty acids. Nutr Rev. 2010;68(5):280–289.
    1. Dessi M, Noce A, Bertucci P, Manca di Villahermosa S, Zenobi R, Castagnola V, Addessi E, Daniele N. Atherosclerosis, dyslipidemia, and inflammation: the significant role of polyunsaturated fatty acids. ISRN Inflamm. 2013;12:191823.
    1. Cottin SC, Sanders TA, Hall WL. The differential effects of EPA and DHA on cardiovascular risk factors. Proc Nutr Soc. 2011;70(2):215–231.
    1. Serini S, Fasano E, Piccioni E, Cittadini AR, Calviello G. Differential anti-cancer effects of purified EPA and DHA and possible mechanisms involved. Curr Med Chem. 2011;18(26):4065–4075.
    1. Wei MY, Jacobson TA. Effects of eicosapentaenoic acid versus docosahexaenoic acid on serum lipids: a systematic review and meta-analysis. Curr Atheroscler Rep. 2011;13(6):474–483.
    1. Serini S, Bizzarro A, Piccioni E, Fasano E, Rossi C, Lauria A, Cittadini AR, Masullo C, Calviello G. EPA and DHA differentially affect in vitro inflammatory cytokine release by peripheral blood mononuclear cells from Alzheimer’s patients. Curr Alzheimer Res. 2012;9(8):913–923.
    1. Russell FD, Bürgin-Maunder CS. Distinguishing health benefits of eicosapentaenoic and docosahexaenoic acids. Mar Drugs. 2012;10(11):2535–2559.

Source: PubMed

Подписаться