Similar eicosapentaenoic acid and docosahexaenoic acid plasma levels achieved with fish oil or krill oil in a randomized double-blind four-week bioavailability study

Karin Yurko-Mauro, Jaroslav Kralovec, Eileen Bailey-Hall, Vanessa Smeberg, Jeffrey G Stark, Norman Salem Jr, Karin Yurko-Mauro, Jaroslav Kralovec, Eileen Bailey-Hall, Vanessa Smeberg, Jeffrey G Stark, Norman Salem Jr

Abstract

Background: Long-chain n-3 polyunsaturated fatty acids (LC n-3-PUFA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) provide multiple health benefits for heart, brain and eyes. However, consumption of fatty fish, the main source of LC n-3-PUFAs is low in Western countries. Intakes of LC n-3-PUFA can be increased by taking dietary supplements, such as fish oil, algal oil, or krill oil. Recently, conflicting information was published on the relative bioavailability of these omega-3 supplements. A few studies suggested that the phospholipid form (krill) is better absorbed than the fish oil ethyl ester (EE) or triglyceride (TG) forms. Yet studies did not match the doses administered nor the concentrations of DHA and EPA per supplement across such comparisons, leading to questionable conclusions. This study was designed to compare the oral bioavailability of the same dose of both EPA and DHA in fish oil-EE vs. fish oil-TG vs. krill oil in plasma at the end of a four-week supplementation.

Methods: Sixty-six healthy adults (n = 22/arm) were enrolled in a double blind, randomized, three-treatment, multi-dose, parallel study. Subjects were supplemented with a 1.3 g/d dose of EPA + DHA (approximately 816 mg/d EPA + 522 mg/d DHA, regardless of formulation) for 28 consecutive days, as either fish oil-EE, fish oil-TG or krill oil capsules (6 caps/day). Plasma and red blood cell (RBC) samples were collected at baseline (pre-dose on Day 1) and at 4, 8, 12, 48, 72, 336, and 672 h. Total plasma EPA + DHA levels at Week 4 (Hour 672) were measured as the primary endpoint.

Results: No significant differences in total plasma EPA + DHA at 672 h were observed between fish oil-EE (mean = 90.9 ± 41 ug/mL), fish oil-TG (mean = 108 ± 40 ug/mL), and krill oil (mean = 118.5 ± 48 ug/mL), p = 0.052 and bioavailability differed by < 24 % between the groups. Additionally, DHA + EPA levels were not significantly different in RBCs among the 3 formulations, p = 0.19, providing comparable omega-3 indexes.

Conclusions: Similar plasma and RBC levels of EPA + DHA were achieved across fish oil and krill oil products when matched for dose, EPA, and DHA concentrations in this four week study, indicating comparable oral bioavailability irrespective of formulation.

Trial registration: Clinicaltrials.gov identifier NCT02427373.

Figures

Fig. 1
Fig. 1
Disposition of subjects
Fig. 2
Fig. 2
Mean Plasma DHA + EPA Concentration-Time Profiles after Administration of fish oil-Ethyl Ester, fish oil-Triglyceride, and krill oil, on a Linear Scale, Week 4 ANCOVA, p = 0.052, showing comparable bioavailability
Fig. 3
Fig. 3
a Mean Plasma EPA Concentration-Time Profiles after Administration of fish oil-Ethyl Ester, fish oil-Triglyceride, and krill oil on a Linear Scale, Week 4 ANCOVA, p = 0.17, showing comparable bioavailability. b Mean Plasma DHA Concentration-Time Profiles after Administration of fish oil-Ethyl Ester, fish oil-Triglyceride, and krill oil on a Linear Scale. Week 4 ANCOVA, p = 0.013; a bioequivalence trend between fish oil-TG and krill oil is shown, GMR = 0.95 (0.79,1.13), p = 0.059
Fig. 4
Fig. 4
Mean Red Blood Cell DHA + EPA Concentration-Time Profiles after Administration of fish oil-Ethyl Ester, fish oil-Triglyceride, and krill oil on a Linear Scale, Week 4 ANCOVA, p = 0.19, showing comparable bioavailability

References

    1. Nestel P, Clifton P, Colquhoun D, Noakes M, Mori T, Sullivan D, et al. Indications for Omega-3 Long Chain 3 Polyunsaturated Fatty Acid in the Prevention and Treatment of Cardiovascular Disease. Heart Lung Circ. 2015
    1. Abu-Ouf N, Jan M. The Influence of Fish Oil on Neurological Development and Function. Can J Neurol Sci. 2014;41:13–18. doi: 10.1017/S031716710001619X.
    1. Yurko-Mauro K, Alexander D, van Elswyk M. Docosahexaenoic Acid and Adult Memory: A Systematic Review and Meta-Analysis. PLoS ONE. 2015;10(3):e0120391. doi: 10.1371/journal.pone.0120391.
    1. Dawczynski J, Jentsch S, Schweitzer D, Hammer M, Lang G, Strobel J. Long term effects of lutein, zeaxanthin and omega-3-LCPUFAs supplementation on optical density of macular pigment in AMD patients: the LUTEGA study. Graefes Arch Clin Exp Ophthalmol. 2013;251:2711–2723. doi: 10.1007/s00417-013-2376-6.
    1. U.S. Department of Agriculture, Agricultural Research Service . Nutrient Intakes from Food: Mean Amounts Consumed per Individual, by Gender and Age, What We Eat in America, NHANES 2009–2010. 2012.
    1. . Accessed 7/13/15.
    1. Ramprasath V, Eyal I, Zchut S, Jones PJH. Enhanced increase of omega-3 index in healthy individuals with response to 4-week fatty acid supplementation from Krill oil versus fish oil. Lipids Health Dis. 2013;12:178. doi: 10.1186/1476-511X-12-178.
    1. Ulven S, Kirkhus B, Lamglait A, Basu S, Elind E, Haider T, et al. Metabolic effects of Krill oil are essentially similar to those of Fish oil but at lower dose of EPA and DHA, in healthy volunteers. Lipids. 2011;46:37–46. doi: 10.1007/s11745-010-3490-4.
    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. doi: 10.1186/1476-511X-10-145.
    1. Maki KC, Reeves MS, Farmer M, Griinari M, Berge K, Vik H, et al. Krill oil supplementation increases plasma concentrations of eicosapentaenoic and docosahexaenoic acids in overweight and obese men and women. Nutr. Res. 2009;29:9,609–615. doi: 10.1016/j.nutres.2009.09.004.
    1. Salem N, Kuratko C. A reexamination of Krill bioavailability studies. Lipids Health Dis. 2014;13:137. doi: 10.1186/1476-511X-13-137.
    1. Arterburn L, Hall EB, Oken H. Distribution, interconversion, and dose response of n-3 fatty acids in humans. Am J Clin Nutr. 2006;83(suppl):1467S–1476S.
    1. Kuratko C. Food-frequency questionnaire for assessing long-chain u-3 fatty-acid intake, Re: Assessing long-chain ω-3polyunsaturated fatty acids: A tailored food-frequency questionnaire is better. Nutrition. 2013;29:807–808. doi: 10.1016/j.nut.2012.10.013.
    1. Bligh EG, Dyer WJ. A rapid method of total lipid extraction and purification. Can. J. Biochem. Physiol. 1959;37:911–917. doi: 10.1139/o59-099.
    1. Folch J, Lees M, Sloane S. A simple method for the isolation and purification of total lipids from animal tissue. J Biol Chem. 1957;226:497–509.
    1. Morrison WR, Smith LM. Preparation of fatty acid methyl esters and dimethylacetals from lipids with boron fluoride-methanol. J Lipid Res. 1964;5:600–8.
    1. Food US, Administration D. Guidance for Industry: Bioavailability and Bioequivalence Studies for Orally Administered Drug Products—General Considerations. Washington: US Department of Health and Human Services, Center for Drug Evaluation and Research; 2003.
    1. Kagan M, West A, Zante C, Calder P. Acute appearance of fatty acids in human plasma – a comparative study between polar-lipid rich oil from the microalgae Nannochloropsisoculata and Krill oil in healthy young males. Lipids Health Dis. 2013;12:102. doi: 10.1186/1476-511X-12-102.
    1. Kohler A, Sarkinnen E, Tapola N, Niskanen T, Bruheim I. Bioavailability of fatty acids from krill oil, krill meal and fish oil in healthy subjects: a randomized, single-dose, crossover trial. Lipids Health Dis. 2015;14:19. doi: 10.1186/s12944-015-0015-4.
    1. Harris WS. The Omega-3 Index as a risk factor for Coronary Heart Disease. Am J Clin Nutr. 2008;87(suppl):1997S–2002S.
    1. Schuchardt JP, Neubronner J, Kressel G, Merkel M, von Schacky C, Hahn A. Moderate doses of EPA and DHA from re-esterified triacylglycerols but not from ethyl-esters lower fasting serum triacylglycerols in statin-treated dyslipidemic subjects: Results from a six month randomized controlled trial. PLEFA. 2011;85:381–386.
    1. Dyerberg J, Madsen P, Møller JM, Aardestrup I, Schmidt EB. Bioavailability of marine n-3 fatty acid formulations. PLEFA. 2010;83:137–141.
    1. Laidlaw M, Cockerline C, Rowe W. 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. Lipids Health Dis. 2014;13:99. doi: 10.1186/1476-511X-13-99.
    1. Araujo P, Zhu H, Breivik JF, Hjelle JI, Zeng Y. Determination and structural elucidation of triacylglycerols in krill oil by chromatographic techniques. Lipids. 2014;49:163–172. doi: 10.1007/s11745-013-3855-6.

Source: PubMed

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