Skip to main content
Log in

Changes of Molecular Glycerophospholipid Species in Plasma and Red Blood Cells During Docosahexaenoic Acid Supplementation

  • Original Article
  • Published:
Lipids

Abstract

Docosahexaenoic acid (DHA) status is related to health and disease risk. DHA status is mainly determined by dietary DHA intake, since endogenous synthesis of DHA is limited. We aimed to investigate the changes of different molecular glycerophospholipid species containing DHA in plasma and red blood cells (RBC) in response to increased DHA intake. Thirteen healthy adults had their diet supplemented with 510 mg DHA/day for 29 days. Fasted blood samples were taken at 11 time points and glycerophospholipid species were analyzed by liquid chromatography mass spectrometry. In plasma, percentages of glycerophospholipid species containing DHA increased significantly by 64–104 % relative to baseline values during supplementation, but the relative distribution between species was not markedly altered. In RBC, phosphatidylcholine (PtdCho) species containing DHA increased to a similar extent as in plasma, while phosphatidylethanolamine and phosphatidylserine species with DHA increased by only 12–25 %, respectively, which was significantly different compared to PtdCho species (p < 0.01). Despite the high increase, the contribution of DHA PtdCho species to total DHA remained minor (14 % after supplementation). In conclusion, DHA supplementation does not alter the relative distribution of DHA among glycerophospholipid species in plasma. A majority of PtdCho species are rapidly exchanged between plasma lipoproteins and RBC membrane lipids, while there is a minor exchange of phosphatidylethanolamine and phosphatidylserine species.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

CDP:

Cytidine diphosphate

DHA:

Docosahexaenoic acid

FA:

Fatty acid(s)

GPL:

Glycerophospholipid

LC:

Long chain

PtdCho:

Phosphatidylcholine

PtdEtn:

Phosphatidylethanolamine

PEMT:

Phosphatidylethanolamine N-methyltransferase

PtdSer:

Phosphatidylserine

RBC:

Red blood cell

References

  1. Kullenberg D, Taylor LA, Schneider M, Massing U (2012) Health effects of dietary phospholipids. Lipids Health Dis 11:3

    Article  PubMed  Google Scholar 

  2. Calder PC (2012) Mechanisms of action of (n-3) fatty acids. J Nutr 142:592S–599S

    Article  PubMed  CAS  Google Scholar 

  3. Harris WS, Von Schacky C (2004) The Omega-3 Index: a new risk factor for death from coronary heart disease? Prev Med 39:212–220

    Article  PubMed  CAS  Google Scholar 

  4. Brenna JT, Salem N Jr, Sinclair AJ, Cunnane SC (2009) alpha-Linolenic acid supplementation and conversion to n-3 long-chain polyunsaturated fatty acids in humans. Prostaglandins Leukot Essent Fatty Acids 80:85–91

    Article  PubMed  CAS  Google Scholar 

  5. Calder PC, Dangour AD, Diekman C, Eilander A, Koletzko B, Meijer GW, Mozaffarian D, Niinikoski H, Osendarp SJ, Pietinen P, Schuit J, Uauy R (2010) Essential fats for future health. In: Proceedings of the 9th Unilever Nutrition Symposium, 26–27 May 2010. Eur J Clin Nutr 64 Suppl 4: S1–S13

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

    PubMed  CAS  Google Scholar 

  7. Fekete K, Marosvolgyi T, Jakobik V, Decsi T (2009) Methods of assessment of n-3 long-chain polyunsaturated fatty acid status in humans: a systematic review. Am J Clin Nutr 89:2070S–2084S

    Article  PubMed  CAS  Google Scholar 

  8. 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 38:2012–2022

    PubMed  CAS  Google Scholar 

  9. Hodson L, Skeaff CM, Fielding BA (2008) Fatty acid composition of adipose tissue and blood in humans and its use as a biomarker of dietary intake. Prog Lipid Res 47:348–380

    Article  PubMed  CAS  Google Scholar 

  10. Leidl K, Liebisch G, Richter D, Schmitz G (2008) Mass spectrometric analysis of lipid species of human circulating blood cells. Biochim Biophys Acta 1781:655–664

    Article  PubMed  CAS  Google Scholar 

  11. Skeaff CM, Hodson L, McKenzie JE (2006) Dietary-induced changes in fatty acid composition of human plasma, platelet, and erythrocyte lipids follow a similar time course. J Nutr 136:565–569

    PubMed  CAS  Google Scholar 

  12. van den Boom MA, Wassink MG, Westerman J, de Fouw NJ, Roelofsen B, Op den Kamp JA, van Deenen LL (1994) In vivo turnover of phospholipids in rabbit erythrocytes. Biochim Biophys Acta 1215:314–320

    Article  PubMed  Google Scholar 

  13. Hermansson M, Hokynar K, Somerharju P (2011) Mechanisms of glycerophospholipid homeostasis in mammalian cells. Prog Lipid Res 50:240–257

    Article  PubMed  CAS  Google Scholar 

  14. Holub BJ (1978) Differential utilization of 1-palmitoyl and 1-stearoyl homologues of various unsaturated 1,2-diacyl-sn-glycerols for phosphatidylcholine and phosphatidylethanolamine synthesis in rat liver microsomes. J Biol Chem 253:691–696

    PubMed  CAS  Google Scholar 

  15. Bleijerveld OB, Brouwers JF, Vaandrager AB, Helms JB, Houweling M (2007) The CDP-ethanolamine pathway and phosphatidylserine decarboxylation generate different phosphatidylethanolamine molecular species. J Biol Chem 282:28362–28372

    Article  PubMed  CAS  Google Scholar 

  16. Pynn CJ, Henderson NG, Clark H, Koster G, Bernhard W, Postle AD (2011) Specificity and rate of human and mouse liver and plasma phosphatidylcholine synthesis analyzed in vivo. J Lipid Res 52:399–407

    Article  PubMed  CAS  Google Scholar 

  17. Kanoh H (1969) Biosynthesis of molecular species of phosphatidyl choline and phosphatidyl ethanolamine from radioactive precursors in rat liver slices. Biochim Biophys Acta 176:756–763

    Article  PubMed  CAS  Google Scholar 

  18. Uhl O, Glaser C, Demmelmair H, Koletzko B (2011) Reversed phase LC/MS/MS method for targeted quantification of glycerophospholipid molecular species in plasma. J Chromatogr B Anal Technol Biomed Life Sci 879:3556–3564

    Article  CAS  Google Scholar 

  19. Dayton S, Hashimoto S, Dixon W, Pearce ML (1966) Composition of lipids in human serum and adipose tissue during prolonged feeding of a diet high in unsaturated fat. J Lipid Res 7:103–111

    PubMed  CAS  Google Scholar 

  20. Klingler M, Klem S, Demmelmair H, Koletzko B (2012) Comparison of the incorporation of orally administered DHA into plasma, erythrocyte and cheek cell glycerophospholipids. Br J Nutr 109:962–968

    Article  PubMed  Google Scholar 

  21. Samborski RW, Ridgway ND, Vance DE (1990) Evidence that only newly made phosphatidylethanolamine is methylated to phosphatidylcholine and that phosphatidylethanolamine is not significantly deacylated–reacylated in rat hepatocytes. J Biol Chem 265:18322–18329

    PubMed  CAS  Google Scholar 

  22. da Costa KA, Sanders LM, Fischer LM, Zeisel SH (2011) Docosahexaenoic acid in plasma phosphatidylcholine may be a potential marker for in vivo phosphatidylethanolamine N-methyltransferase activity in humans. Am J Clin Nutr 93:968–974

    Article  PubMed  Google Scholar 

  23. da Costa KA, Kozyreva OG, Song J, Galanko JA, Fischer LM, Zeisel SH (2006) Common genetic polymorphisms affect the human requirement for the nutrient choline. FASEB J 20:1336–1344

    Article  PubMed  Google Scholar 

  24. Strunecka A, Folk P (1988) Phospholipid biosynthesis in mature human erythrocytes. Gen Physiol Biophys 7:205–216

    PubMed  CAS  Google Scholar 

  25. Lemaitre-Delaunay D, Pachiaudi C, Laville M, Pousin J, Armstrong M, Lagarde M (1999) Blood compartmental metabolism of docosahexaenoic acid (DHA) in humans after ingestion of a single dose of [(13)C]DHA in phosphatidylcholine. J Lipid Res 40:1867–1874

    PubMed  CAS  Google Scholar 

  26. Engelmann B, Wiedmann MK (2010) Cellular phospholipid uptake: flexible paths to coregulate the functions of intracellular lipids. Biochim Biophys Acta 1801:609–616

    Article  PubMed  CAS  Google Scholar 

  27. van Schravendijk MR, Handunnetti SM, Barnwell JW, Howard RJ (1992) Normal human erythrocytes express CD36, an adhesion molecule of monocytes, platelets, and endothelial cells. Blood 80:2105–2114

    PubMed  Google Scholar 

  28. Wustner D, Herrmann A, Muller P (2000) Head group-independent interaction of phospholipids with bile salts. A fluorescence and EPR study. J Lipid Res 41:395–404

    PubMed  CAS  Google Scholar 

  29. Donabedian RK, Karmen A (1967) Fatty acid transport and incorporation into human erythrocytes in vitro. J Clin Invest 46:1017–1027

    Article  PubMed  CAS  Google Scholar 

  30. Verkleij AJ, Zwaal RF, Roelofsen B, Comfurius P, Kastelijn D, van Deenen LL (1973) The asymmetric distribution of phospholipids in the human red cell membrane. A combined study using phospholipases and freeze-etch electron microscopy. Biochim Biophys Acta 323:178–193

    Article  PubMed  CAS  Google Scholar 

  31. Nagan N, Zoeller RA (2001) Plasmalogens: biosynthesis and functions. Prog Lipid Res 40:199–229

    Article  PubMed  CAS  Google Scholar 

  32. Vance DE (2013) Physiological roles of phosphatidylethanolamine N-methyltransferase. Biochim Biophys Acta 1831:626–632

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was financially supported in part by the German Ministry of Education and Research, Competence Network on Obesity, 01GI0826 and the PINGU project 0315680B. Additional financial support by the Commission of the European Communities, Project Early Nutrition (FP7-KBBE-2011-05) is grateful acknowledged. This manuscript does not necessarily reflect the views of the commission and in no way anticipates future policy in this area. The authors declare that they have no conflicts of interest. The present data are part of a Ph.D. thesis completed by Olaf Uhl at the Medical Faculty of the Ludwig-Maximilians-University of Munich.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Berthold Koletzko.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 625 kb)

About this article

Cite this article

Uhl, O., Demmelmair, H., Klingler, M. et al. Changes of Molecular Glycerophospholipid Species in Plasma and Red Blood Cells During Docosahexaenoic Acid Supplementation. Lipids 48, 1103–1113 (2013). https://doi.org/10.1007/s11745-013-3837-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11745-013-3837-8

Keywords

Navigation