European Journal of Nutrition

, Volume 52, Issue 3, pp 895–904 | Cite as

A short-term n-3 DPA supplementation study in humans

  • Eliza Miller
  • Gunveen Kaur
  • Amy Larsen
  • Su Peng Loh
  • Kaisa Linderborg
  • Harrison S. Weisinger
  • Giovanni M. Turchini
  • David Cameron-Smith
  • Andrew J. SinclairEmail author
Original Contribution



Despite the detailed knowledge of the absorption and incorporation of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) into plasma lipids and red blood cells (RBC) in humans, very little is known about docosapentaenoic acid (DPA, 22:5 n-3). The aim of this study was to investigate the uptake and incorporation of pure DPA and EPA into human plasma and RBC lipids.


Ten female participants received 8 g of pure DPA or pure EPA in randomized crossover double-blinded manner over a 7-day period. The placebo treatment was olive oil. Blood samples were collected at days zero, four and seven, following which the plasma and RBC were separated and used for the analysis of fatty acids.


Supplementation with DPA significantly increased the proportions of DPA in the plasma phospholipids (PL) (by twofold) and triacylglycerol (TAG) fractions (by 2.3-fold, day 4). DPA supplementation also significantly increased the proportions of EPA in TAG (by 3.1-fold, day 4) and cholesterol ester (CE) fractions (by 2.0-fold, day 7) and of DHA in TAG fraction (by 3.1-fold, day 4). DPA proportions in RBC PL did not change following supplementation. Supplementation with EPA significantly increased the proportion of EPA in the plasma CE and PL fractions, (both by 2.7-fold, day 4 and day 7) and in the RBC PL (by 1.9-fold, day 4 and day 7). EPA supplementation did not alter the proportions of DPA or DHA in any lipid fraction. These results showed that within day 4 of supplementation, DPA and EPA demonstrated different and specific incorporation patterns.


The results of this short-term study suggest that DPA may act as a reservoir of the major long-chain n-3 fatty acids (LC n-3 PUFA) in humans.


n-3 Polyunsaturated fatty acids (PUFA) Docosapentaenoic acid (DPA) Eicosapentaenoic acid (EPA) Docosahexaenoic acid (DHA) Fatty acid metabolism 



Research support from Meat & Livestock Australia for financial support, Equateq Ltd (UK) for the generous provision of the pure supplements and Deakin University Strategic Research Centre for Molecular Medicine for financial support is gratefully acknowledged. EM, AL, DCS and AJS planned and designed the study; EM and AL recruited the participants and collected samples and dietary data; GK, EM and GT conducted the plasma analyses; GK, SPL and GT conducted the RBC analyses; GK conducted the statistical analysis; GK, AJS and DCS wrote the manuscript; GK, AJS, DCS, KL and HSW made significant contributions to the discussion.


  1. 1.
    Saravanan P, Davidson NC, Schmidt EB, Calder PC (2010) Cardiovascular effects of marine omega-3 fatty acids. Lancet 376(9740):540–550CrossRefGoogle Scholar
  2. 2.
    Calder PC, Yaqoob P (2010) Omega-3 (n-3) fatty acids, cardiovascular disease and stability of atherosclerotic plaques. Cell Mol Biol (Noisy-le-grand) 56(1):28–37Google Scholar
  3. 3.
    Mann NJ, Johnson LG, Warrick GE, Sinclair AJ (1995) The arachidonic acid content of the Australian diet is lower than previously estimated. J Nutr 125(10):2528–2535Google Scholar
  4. 4.
    Or-Rashid MM, Odongo NE, Wright TC, McBride BW (2009) Fatty acid profile of bovine milk naturally enhanced with docosahexaenoic acid. J Agric Food Chem 57(4):1366–1371CrossRefGoogle Scholar
  5. 5.
    Howe P, Meyer B, Record S, Baghurst K (2006) Dietary intake of long-chain omega-3 polyunsaturated fatty acids: contribution of meat sources. Nutrition 22(1):47–53CrossRefGoogle Scholar
  6. 6.
    Akiba S, Murata T, Kitatani K, Sato T (2000) Involvement of lipoxygenase pathway in docosapentaenoic acid-induced inhibition of platelet aggregation. Biological Pharmacol 23(11):1293–1297CrossRefGoogle Scholar
  7. 7.
    Kaur G, Sinclair AJ, Cameron-Smith D, Barr DP, Molero-Navajas JC, Konstantopoulos N (2011) Docosapentaenoic acid (22:5n–3) down-regulates the expression of genes involved in fat synthesis in liver cells. Prostaglandins Leukot Essent Fatty Acids 85(3–4):155–161CrossRefGoogle Scholar
  8. 8.
    Yoshida H, Mawatari M, Ikeda I, Imaizumi K, Seto A, Tsuji H (1999) Effect of dietary seal and fish oils on triacylglycerol metabolism in rats. J Nutr Sci Vitaminol 45(4):411–421CrossRefGoogle Scholar
  9. 9.
    Akiba S, Murata T, Kitatani K, Sato T (2000) Involvement of lipoxygenase pathway in docosapentaenoic acid-induced inhibition of platelet aggregation. Biol Pharm Bull 23(11):1293–1297CrossRefGoogle Scholar
  10. 10.
    Phang M, Garg ML, Sinclair AJ (2009) Inhibition of platelet aggregation by omega-3 polyunsaturated fatty acids is gender specific-redefining platelet response to fish oils. Prostaglandins Leukot Essent Fatty Acids 81(1):35–40CrossRefGoogle Scholar
  11. 11.
    Gotoh N, Nagao K, Onoda S, Shirouchi B, Furuya K, Nagai T et al (2009) Effects of three different highly purified n-3 series highly unsaturated fatty acids on lipid metabolism in C57BL/KsJ-db/db mice. J Agric Food Chem 57(22):11047–11054CrossRefGoogle Scholar
  12. 12.
    Pawar A, Jump DB (2003) Unsaturated fatty acid regulation of peroxisome proliferator-activated receptor alpha activity in rat primary hepatocytes. J Biol Chem 278(38):35931–35939CrossRefGoogle Scholar
  13. 13.
    Kishida E, Tajiri M, Masuzawa Y (2006) Docosahexaenoic acid enrichment can reduce L929 cell necrosis induced by tumour necrosis factor. Biochim Biophys Acta 1761(4):454–462CrossRefGoogle Scholar
  14. 14.
    Holub BJ, Swidinsky P, Park E (2011) Oral docosapentaenoic acid (22:5n–3) is differentially incorporated into phospholipid pools and differentially metabolized to eicosapentaenoic acid in tissues from young rats. Lipids [Research Support, Non-US Gov’t] 46(5):399–407Google Scholar
  15. 15.
    Kaur G, Begg DP, Barr D, Garg M, Cameron-Smith D, Sinclair AJ (2010) Short-term docosapentaenoic acid (22:5 n-3) supplementation increases tissue docosapentaenoic acid, DHA and EPA concentrations in rats. Br J Nutr [Research Support, Non-US Gov’t] 103(1):32–37CrossRefGoogle Scholar
  16. 16.
    Meyer B, Mann N (2009) Comparison of seal oil to tuna oil on plasma lipid levels and blood pressure in hypertriglyceridaemic subjects. Lipids 44(9):827–835CrossRefGoogle Scholar
  17. 17.
    Sullivan B, Brown J, Williams P, Meyer B (2008) Dietary validation of a new food frequency questionnaire that estimates long-chain omega-3 polyunsaturated fatty acids. Br J Nutr 99:660–666CrossRefGoogle Scholar
  18. 18.
    Sullivan B, Williams P, Meyer B (2006) Biomarker validation of a new food frequency questionnaire that estimates long-chain omega-3 polyunsaturated fatty acids. Lipids 41:845–850CrossRefGoogle Scholar
  19. 19.
    Swierk M, Williams P, Meyer B, Wilcox J, Russel K (2011) Validation of an Australian electronic food frequency questionnaire to measure polyunsaturated fatty acid intake. Nutrition 6:641–646CrossRefGoogle Scholar
  20. 20.
    Sinclair A, O’Dea K, Dunstan G, Ireland P, Niall M (1987) Effects on plasma lipids and fatty acid composition of very low fat diets enriched with fish or kangaroo meat. Lipids 22:523–529CrossRefGoogle Scholar
  21. 21.
    Ackman RG (2002) The gas chomatograph in practical analyses of common and uncommon fatty acids for the 21st century. Anal Chim Acta 465(1–2):175–192CrossRefGoogle Scholar
  22. 22.
    Folch J, Lees M, Sloane-Stanley GH (1957) Methods for the isolation and purification of total lipids from animal tissue. J Biol Chem 226:497–509Google Scholar
  23. 23.
    Armstrong JM, Metherel AH, Stark KD (2008) Direct microwave transesterification of fingertip prick blood samples for fatty acid determinations. Lipids 43(2):187–196CrossRefGoogle Scholar
  24. 24.
    Popovic T, Borozan S, Arsic A, Martacic JD, Vucic V, Trbovic A et al (2011) Fish oil supplementation improved liver phospholipids fatty acid composition and parameters of oxidative stress in male wistar rats. J Anim Physiol Anim Nutr. doi: 10.1111/j.1439-0396.2011.01216.x
  25. 25.
    Abeywardena MY, Patten GS (2011) Role of ω3 long-chain polyunsaturated fatty acids in reducing cardio-metabolic risk factors. Endocr Metab Immune Disord Drug Targets 11(3):232–246. ISSN: 2212–3873Google Scholar
  26. 26.
    Westphal S, Orth M, Ambrosch A, Osmundsen K, Luley C (2000) Postprandial chylomicrons and VLDLs in severe hypertriacylglycerolemia are lowered more effectively than are chylomicron remnants after treatment with n-3 fatty acids. Am J Clin Nutr 71(4):914–920Google Scholar
  27. 27.
    Roche HM, Gibney MJ (2000) Effect of long-chain n-3 polyunsaturated fatty acids on fasting and postprandial triacylglycerol metabolism. Am J Clin Nutr 71(1 Suppl):232S–237SGoogle Scholar
  28. 28.
    Fox JC, Hay RV (1992) Eicosapentaenoic acid inhibits cell growth and triacylglycerol secretion in McA-RH7777 rat hepatoma cultures. Biochem J 286(Pt 1):305–312Google Scholar
  29. 29.
    Benner KG, Sasaki A, Gowen DR, Weaver A, Connor WE (1990) The differential effect of eicosapentaenoic acid and oleic acid on lipid synthesis and VLDL secretion in rabbit hepatocytes. Lipids 25(9):534–540CrossRefGoogle Scholar
  30. 30.
    Chen HW, Lii CK, Ko JJ, Wang ST, Hsu JD (1996) Regulatory effects of dietary n-3 and n-6 lipids on plasma and hepatic lipid levels, liver cell number and microsomal protein content in spontaneously hypertensive rats. Prostaglandins Leukot Essent Fatty Acids 55(5):329–335CrossRefGoogle Scholar
  31. 31.
    Willumsen N, Skorve J, Hexeberg S, Rustan AC, Berge RK (1993) The hypotriglyceridemic effect of eicosapentaenoic acid in rats is reflected in increased mitochondrial fatty acid oxidation followed by diminished lipogenesis. Lipids 28(8):683–690CrossRefGoogle Scholar
  32. 32.
    Skulas-Ray AC, Kris-Etherton PM, Harris WS, vanden Heuvel JP, Wagner PR, West SG (2011) Dose-response effects of omega-3 fatty acids on triglycerides, inflammation, and endothelial function in healthy persons with moderate hypertriglyceridemia. Am J Clin Nutr 93(2):243–252CrossRefGoogle Scholar
  33. 33.
    Oya J, Nakagami T, Sasaki S, Jimba S, Murakami K, Kasahara T et al (2010) Intake of n-3 polyunsaturated fatty acids and non-alcoholic fatty liver disease: a cross-sectional study in Japanese men and women. Eur J Clin Nutr 64(10):1179–1185CrossRefGoogle Scholar
  34. 34.
    Hodge J, Sanders K, Sinclair AJ (1993) Differential utilization of eicosapentaenoic acid and docosahexaenoic acid in human plasma. Lipids 28(6):525–531CrossRefGoogle Scholar
  35. 35.
    Yep YL, Li D, Mann NJ, Bode O, Sinclair AJ (2002) Bread enriched with microencapsulated tuna oil increases plasma docosahexaenoic acid and total omega-3 fatty acids in humans. Asia Pac J Clin Nutr 11(4):285–291CrossRefGoogle Scholar
  36. 36.
    Conquer JA, Cheryk LA, Chan E, Gentry PA, Holub BJ (1999) Effect of supplementation with dietary seal oil on selected cardiovascular risk factors and hemostatic variables in healthy male subjects. Thromb Res 96(3):239–250CrossRefGoogle Scholar
  37. 37.
    Mori TA, Burke V, Puddey IB, Watts GF, O’Neal DN, Best JD et al (2000) Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men. Am J Clin Nutr 71(5):1085–1094Google Scholar
  38. 38.
    Cao J, Schwichtenberg KA, Hanson NQ, Tsai MY (2006) Incorporation and clearance of omega-3 fatty acids in erythrocyte membranes and plasma phospholipids. Clin Chem [Randomized Controlled Trial] 52(12):2265–2272CrossRefGoogle Scholar
  39. 39.
    Zuijdgeest-van Leeuwen SD, Dagnelie PC, Rietveld T, van den Berg JW, Wilson JH (1999) Incorporation and washout of orally administered n-3 fatty acid ethyl esters in different plasma lipid fractions. Br J Nutr 82(6):481–488Google Scholar
  40. 40.
    Christensen E, Woldseth B, Hagve TA, Poll-The BT, Wanders RJ, Sprecher H et al (1993) Peroxisomal beta-oxidation of polyunsaturated long chain fatty acids in human fibroblasts. The polyunsaturated and the saturated long chain fatty acids are retroconverted by the same acyl-CoA oxidase. Scand J Clin Lab Invest Suppl 215:61–74CrossRefGoogle Scholar
  41. 41.
    Stoffel W, Eker A, Assad H, Sprecher H (1970) Enzymatic studies on the mechanism of the retroconversion of C22-polyenoic fatty acids to their C20-homologues. Hoppe Seylers Z Physiol Chem 351(12):1545–1554CrossRefGoogle Scholar
  42. 42.
    Achard F, Benistant C, Lagarde M (1995) Interconversions and distinct metabolic fate of eicosapentaenoic, docosapentaenoic and docosahexaenoic acids in bovine aortic endothelial cells. Biochim Biophys Acta 1255(3):260–266CrossRefGoogle Scholar
  43. 43.
    Rosenthal MD, Garcia MC, Jones MR, Sprecher H (1991) Retroconversion and delta 4 desaturation of docosatetraenoate (22:4(n-6)) and docosapentaenoate (22:5(n-3)) by human cells in culture. Biochim Biophys Acta 1083(1):29–36CrossRefGoogle Scholar
  44. 44.
    Katan MB, Deslypere JP, van Birgelen AP, Penders M, Zegwaard M (1997) Kinetics of the incorporation of dietary fatty acids into serum cholesteryl esters, erythrocyte membranes, and adipose tissue: an 18-month controlled study. J Lipid Res 38(10):2012–2022Google Scholar
  45. 45.
    Krul ES, Lemke SL, Mukherjea R, Taylor ML, Goldstein DA, Su H et al (2012) Effects of duration of treatment and dosage of eicosapentaenoic acid and stearidonic acid on red blood cell eicosapentaenoic acid content. Prostaglandins Leukot Essent Fatty Acids 86(1–2):51–59CrossRefGoogle Scholar
  46. 46.
    Meyer BJ, Lane AE, Mann NJ (2009) Comparison of seal oil to tuna oil on plasma lipid levels and blood pressure in hypertriglyceridaemic subjects. Lipids 44(9):827–835CrossRefGoogle Scholar
  47. 47.
    Brown AJ, Pang E, Roberts DC (1991) Erythrocyte eicosapentaenoic acid versus docosahexaenoic acid as a marker for fish and fish oil consumption. Prostaglandins Leukot Essent Fatty Acids 44(2):103–106CrossRefGoogle Scholar
  48. 48.
    Brown AJ, Pang E, Roberts DC (1991) Persistent changes in the fatty acid composition of erythrocyte membranes after moderate intake of n-3 polyunsaturated fatty acids: study design implications. Am J Clin Nutr 54(4):668–673Google Scholar
  49. 49.
    Cartwright IJ, Pockley AG, Galloway JH, Greaves M, Preston FE (1985) The effects of dietary omega-3 polyunsaturated fatty acids on erythrocyte membrane phospholipids, erythrocyte deformability and blood viscosity in healthy volunteers. Atherosclerosis 55(3):267–281CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Eliza Miller
    • 1
  • Gunveen Kaur
    • 2
  • Amy Larsen
    • 1
  • Su Peng Loh
    • 3
  • Kaisa Linderborg
    • 4
  • Harrison S. Weisinger
    • 5
  • Giovanni M. Turchini
    • 6
  • David Cameron-Smith
    • 7
  • Andrew J. Sinclair
    • 5
    Email author
  1. 1.School of Exercise and Nutrition SciencesDeakin UniversityBurwoodAustralia
  2. 2.Institute of Sport, Exercise and Active Living (ISEAL)Victoria UniversityMelbourneAustralia
  3. 3.Department of Nutrition and DieteticsUniversiti Putra MalaysiaSelangorMalaysia
  4. 4.Department of Biochemistry and Food ChemistryUniversity of TurkuTurkuFinland
  5. 5.School of MedicineDeakin UniversityWaurn PondsAustralia
  6. 6.School of Life & Environmental SciencesDeakin UniversityWarrnamboolAustralia
  7. 7.Liggins InstituteThe University of AucklandAucklandNew Zealand

Personalised recommendations