Lipids

, 40:807

Docosahexaenoic acid supplementation in vegetarians effectively increases omega-3 index: A randomized trial

  • Julia Geppert
  • Veronika Kraft
  • Hans Demmelmair
  • Berthold Koletzko
Articles

Abstract

Low red blood cell (RBC) membrane content of FPA+DHA (hereafter called omega-3 index) has recently been described as an indicator for increased risk of death from coronary heart disease. The relationship between plasma and RBC FA, focusing on omega-3 index, and the response to DHA supplementation were investigated in a double-blind, randomized, placebo-controlled, intervention study. Healthy vegetarians (87 f, 17 m) consumed daily a microalgae oil from Ulkenia sp. (0.94 g DHA/d) or olive oil (placebo) for 8 wk. DHA supplementation significantly increased DHA in RBC total lipids (7.9 vs. 4.4 wt%), in RBC PE (12.1 vs. 6.5 wt%), in RBC PC (3.8 vs. 1.4 wt%), and in plasma phospholipids (PL) (7.4 vs. 2.8 wt%), whereas EPA levels rose to a much lesser extent. Microalgae oil supplementation increased the omega-3 index from 4.8 to 8.4 wt%. After intervention, 69% of DHA-supplemented subjects (but no subject of the placebo group) reached an omega-3 index above the desirable value of 8 wt%. Omega-3 index and EPA+DHA levels in RBC PE, RBC PC, and plasma PL were closely correlated (r always >0.9). We conclude that an 8-wk supplementation with 0.94 g DHA/d from microalgae oil achieves a beneficial omega-3 index of ≥8% in most subjects with low basal EPA+DHA status. RBC total FA analyses can be used instead of RBC lipid fraction analyses for assessing essential FA status, e.g., in clinical studies.

Abbreviations

AA

arachidonic acid

ALA

α-linolenic acid

BMI

body mass index

CHD

coronary heart disease

DPA

docosapentaenoic acid

LA

linoleic acid

LCPUFA

long-chain polyunsaturated fatty acid

OA

oleic acid, 18∶1n−9

PA

palmitic acid, 16∶0

PL

phospholipids

RBC

red blood cells

SFA

saturated fatty acid

References

  1. 1.
    Bucher, H.C., Hengstler, P., Schindler, C., and Meier, G. (2002) n−3 Polyunsaturated Fatty Acids in Coronary Heart Disease: A Meta-Analysis of Randomized Controlled Trials, Am. J. Med. 112, 298–304.PubMedCrossRefGoogle Scholar
  2. 2.
    Kris-Etherton, P.M., Harris, W.S., and Appel, L.J. (2002) Fish Consumption, Fish Oil, Omega-3 Fatty Acids, and Cardiovascular Disease, Circulation 106, 2747–2757.PubMedCrossRefGoogle Scholar
  3. 3.
    Whelton, S.P., He, J., Whelton, P.K., and Muntner, P. (2004) Meta-analysis of Observational Studies on Fish Intake and Coronary Heart Disease, Am. J. Cardiol. 93, 1119–1123.PubMedCrossRefGoogle Scholar
  4. 4.
    Leaf, A., Kang, J.X., Xiao, Y., and Billman, G.E. (2003) Clinical Prevention of Sudden Cardiac Death by n−3 Polyunsaturated Fatty Acids and Mechanism of Prevention of Arrhythmias by n−3 Fish Oils, Circulation 107, 2646–2652.PubMedCrossRefGoogle Scholar
  5. 5.
    Harris, W.S., Sands, S.A., Windsor, S.L., Ali, H.A., Stevens, T.L., Magalski, A., Porter, C.B., and Borkon, A.M. (2004) Omega-3 Fatty Acids in Cardiac Biopsies from Heart Transplantation Patients: Correlation with Erythrocytes and Response to Supplementation, Circulation 110, 1645–1649.PubMedCrossRefGoogle Scholar
  6. 6.
    Harris, W.S., and von Schacky, C. (2004) The Omega-3 Index: A New Risk Factor for Death from Coronary Heart Disease? Prev. Med. 39, 212–220.PubMedCrossRefGoogle Scholar
  7. 7.
    Conquer, J.A., and Holub, B.J. (1997) Docosahexaenoic Acid (omega-3) and Vegetarian Nutrition, Veg. Nutr. Int. J. 1/2, 42–49.Google Scholar
  8. 8.
    Li, D., Sinclair, A.J., Wilson, A., Nakkote, S., Kelly, F., Abedin, L., Mann, N.J., and Turner, A. (1999) Effect of Dietary α-Linolenic Acid on Thrombotic Risk Factors in Vegetarian Men, Am. J. Clin. Nutr. 69, 872–882.PubMedGoogle Scholar
  9. 9.
    Burdge, G.C., and Wootton, S.A. (2002) Conversion of α-Linolenic Acid to Eicosapentaenoic, Docosapentaenoic and Docosahexaenoic Acids in Young Women, Br. J. Nutr. 88, 411–420.PubMedGoogle Scholar
  10. 10.
    Burdge, G.C., Jones, A.E., and Wootton, S.A. (2002) Eicosapentaenoic and Docosapentaenoic Acids Are the Principal Products of α-Linolenic Acid Metabolism in Young Men, Br. J. Nutr. 88, 355–363.PubMedCrossRefGoogle Scholar
  11. 11.
    Emken, E.A., Adlof, R.O., and Gulley, R.M. (1994) Dietary Linoleic Acid Influences Desaturation and Acylation of Deuterium-Labeled Linoleic and Linolenic Acids in Young Adult Males, Biochim. Biophys. Acta 1213, 277–288.PubMedGoogle Scholar
  12. 12.
    Hussein, N., Ah-Sing, E., Wilkinson, P., Leach, C., Griffin, B.A., and Millward, D.J. (2005) Long-Chain Conversion of [13C]Linoleic Acid and α-Linolenic Acid in Response to Marked Changes in Their Dietary Intake in Men, J. Lipid Res. 46, 269–280.PubMedCrossRefGoogle Scholar
  13. 13.
    Pawlosky, R.J., Hibbeln, J.R., Novotny, J.A., and Salem, N., Jr. (2001) Physiological Compartmental Analysis of α-Linolenic Acid Metabolism in Adult Humans, J. Lipid Res. 42, 1257–1265.PubMedGoogle Scholar
  14. 14.
    Pawlosky, R.J., Hibbeln, J.R., Lin, Y., Goodson, S., Riggs, P., Sebring, N., Brown, G.L., and Salem, N., Jr. (2003) Effects of Beef- and Fish-Based Diets on the Kinetics of n−3 Fatty Acid Metabolism in Human Subjects, Am. J. Clin. Nutr. 77, 565–572.PubMedGoogle Scholar
  15. 15.
    Burdge, G.C., Finnegan, Y.E., Minihane, A.M., Williams, C.M., and Wootton, S.A. (2003) Effect of Altered Dietary n−3 Fatty Acid Intake upon Plasma Lipid Fatty Acid Composition, Conversion of [13C]α-Linolenic Acid to Longer-Chain Fatty Acids and Partitioning Towards β-Oxidation in Older Men, Br. J. Nutr. 90, 311–321.PubMedCrossRefGoogle Scholar
  16. 16.
    Sanders, T.A.B., and Roshanai, F. (1992) Platelet Phospholipid Fatty Acid Composition and Function in Vegans Compared with Age- and Sex-Matched Omnivore Controls, Eur. J. Clin. Nutr. 46, 823–831.PubMedGoogle Scholar
  17. 17.
    Agren, J.J., Törmälä, M.L., Nenonen, M.T., and Hänninen, O.O. (1995) Fatty Acid Composition of Erythrocyte, Platelet, and Serum Lipids in Strict Vegans, Lipids 30, 365–369.PubMedCrossRefGoogle Scholar
  18. 18.
    Krajcovicova-Kudlackova, M., Simoncic, R., Bederova, A., and Klvanova, J. (1997) Plasma Fatty Acid Profile and Alternative Nutrition, Ann. Nutr. Metab. 41, 365–370.PubMedCrossRefGoogle Scholar
  19. 19.
    Li, D., Ball, M., Bartlett, M., and Sinclair, A.J. (1999) Lipoprotein(a), Essential Fatty Acid Status and Lipoprotein Lipids in Female Australian Vegetarians, Clin. Sci. 97, 175–181.PubMedCrossRefGoogle Scholar
  20. 20.
    Lee, H.Y., Woo, J., Chen, Z.Y., Leung, S.F., and Peng, X.H. (2000) Serum Fatty Acid, Lipid Profile and Dietary Intake of Hong Kong Chinese Omnivores and Vegetarians, Eur. J. Clin. Nutr. 54, 768–773.PubMedCrossRefGoogle Scholar
  21. 21.
    Manjari, V., Suresh, Y., Sailaja Devi, M.M., and Das, U.N. (2001) Oxidant Stress, Anti-oxidants and Essential Fatty Acids in South Indian Vegetarians and Non-vegetarians, Prostaglandins Leukotrienes Essent. Fatty Acids 64, 53–59.CrossRefGoogle Scholar
  22. 22.
    Carnielli, V.P., Pederzini, F., Vittorangeli, R., Luijendijk, I.H., Boomaars, W.E., Pedrotti, D., and Sauer, P.J. (1996) Plasma and Red Blood Cell Fatty Acid of Very Low Birth Weight Infants Fed Exclusively with Expressed Preterm Human Milk, Pediatr. Res. 39, 671–679.PubMedGoogle Scholar
  23. 23.
    Conquer, J.A., and Holub, B.J. (1996) Supplementation with an Algae Source of Docosahexaenoic Acid Increases (n−3) Fatty Acid Status and Alters Selected Risk Factors for Heart Disease in Vegetarian Subjects, J. Nutr. 126, 3032–3039.PubMedGoogle Scholar
  24. 24.
    Conquer, J.A., and Holub, B.J. (1997) Dietary Docosahexaenoic Acid as a Source of Eicosapentaenoic Acid in Vegetarians and Omnivores, Lipids 32, 341–345.PubMedCrossRefGoogle Scholar
  25. 25.
    Conquer, J.A., and Holub, B.J. (1998) 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. 39, 286–292.PubMedGoogle Scholar
  26. 26.
    Theobald, H.E., Chowienczyk, P.J., Whittall, R., Humphries, S.E., and Sanders, T.A.B. (2004) LDL Cholesterol-Raising Effect of Low-Dose Docosahexaenoic Acid in Middle-Aged Men and Women, Am. J. Clin. Nutr. 79, 558–563.PubMedGoogle Scholar
  27. 27.
    Stark, K.D., and Holub, B.J. (2004) Differential Eicosapentaenoic Acid Elevations and Altered Cardiovascular Disease Risk Factor Responses After Supplementation with Docosahexaenoic Acid in Postmenopausal Women Receiving and Not Receiving Hormone Replacement Therapy, Am. J. Clin. Nutr. 79, 765–773.PubMedGoogle Scholar
  28. 28.
    Buckley, R., Shewring, B., Turner, R., Yaqoob, P., and Minihane, A.M. (2004) Circulating Triacylglycerol and ApoE Levels in Response to EPA and Docosahexaenoic Acid Supplementation in Adult Human Subjects, Br. J. Nutr. 92, 477–483.PubMedCrossRefGoogle Scholar
  29. 29.
    Conquer, J.A., Cheryk, L.A., Chan, E., Gentry, P.A., and Holub, B.J. (1999) Effect of Supplementation with Dietary Seal Oil on Selected Cardiovascular Risk Factors and Hemostatic Variables in Healthy Male Subjects, Thromb. Res. 96, 239–250.PubMedCrossRefGoogle Scholar
  30. 30.
    Laidlaw, M., and Holub, B.J. (2003) Effects of Supplementation with Fish Oil-Derived n−3 Fatty Acids and γ-Linolenic Acid on Circulating Plasma Lipids and Fatty Acid Profiles in Women, Am. J. Clin. Nutr. 77, 37–42.PubMedGoogle Scholar
  31. 31.
    German Nutrition Society (2002) Reference Values for Nutrient Intake, 1st end., pp. 45–49, Umschau Braus GmbH, Frankfurt am Main, Germany.Google Scholar
  32. 32.
    Arab, L. (2003) Biomarkers of Fat and Fatty Acid Intake, J. Nutr. 133, 925S-993S.PubMedGoogle Scholar
  33. 33.
    Verkleij, A.J., Zwaal, R.F.A., Roelofsen, B., Comfurius, P., Kastelijn, D., and Van Deenen, L.L.M. (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.PubMedCrossRefGoogle Scholar
  34. 34.
    Renooij, W., and Van Golde, L.M.G. (1977) The Transposition of Molecular Classes of Phosphatidylcholine Across the Rat Erythrocyte Membrane and Their Exchange Between the Red Cell Membrane and Plasma Lipoproteins, Biochim. Biophys. Acta 470, 465–474.PubMedCrossRefGoogle Scholar
  35. 35.
    Renooij, W., Van Golde, L.M.G., Zwaal, R.F.A., Roelofsen, B., and Van Deenen, L.L.M. (1974) Preferential Incorporation of Fatty Acids at the Inside of Human Erythrocyte Membranes, Biochim. Biophys. Acta 363, 287–292.PubMedCrossRefGoogle Scholar
  36. 36.
    Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., and Walter, P. (1995) Molekularbiologie der Zelle, 3rd edn., pp. 675–685, Wiley-VCH, Weinheim.Google Scholar
  37. 37.
    Vlaardingerbroek, H., and Hornstra, G. (2004) Essential Fatty Acids in Erythrocyte Phospholipids During Pregnancy and at Delivery in Mothers and Their Neonates: Comparison with Plasma Phospholipids, Prostaglandins Leukotrienes Essent. Fatty Acids 71, 363–374.CrossRefGoogle Scholar
  38. 38.
    Leichsenring, M., Hardenack, M., and Laryea, M.D. (1992) Relationship Among the Fatty Acid Composition of Various Lipid Fractions in Normally Nourished German Adults, Int. J. Vitam. Nutr. Res. 62, 181–185.PubMedGoogle Scholar

Copyright information

© AOCS Press 2005

Authors and Affiliations

  • Julia Geppert
    • 1
  • Veronika Kraft
    • 1
  • Hans Demmelmair
    • 1
  • Berthold Koletzko
    • 1
  1. 1.Div. Metabolic Diseases and Nutrition, Dr. von Hauner Children’s HospitalLudwig Maximilians University of MunichMunichGermany

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