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Fish oil fatty acid esters of phytosterols alter plasma lipids but not red blood cell fragility in hamsters

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Lipids

Abstract

In an attempt to combine the hypocholesterolemic properties of plant sterols with the hypotriglyceridemic action of fish oil FA, plant sterols have recently been esterified to fish oil n−3 PUFA. The objective of this study was to determine the effects of plant sterols esterified to n−3 PUFA on plasma lipid levels and erythrocyte fragility. For 5 wk, male Golden Syrian hamsters were fed diets varying in cholesterol and plant sterol content: (i) Noncholesterol (semipurified diet with no added cholesterol or plant sterols) (ii), Cholesterol (0.25% cholesterol) (iii), Sterols (0.25% cholesterol plus 1% nonesterified plant sterols), or (iv) Fish oil esters of plant sterols (0.25% cholesterol plus 1.76% EPA and DHA sterol esters, providing 1% plant sterols). The addition of fish oil esters of plant sterols to the cholesterol diet decreased (P=0.001) plasma total cholesterol levels by 20%, but nonesterified plant sterols did not have such a beneficial impact. In addition, non-HDL cholesterol concentrations were 29% lower in hamsters fed fish oil esters of plant sterols than in hamsters fed nonesterified plant sterols (P<0.0001). Despite higher (P<0.0001) plant sterol levels in whole erythrocytes of hamsters fed nonesterified plant sterols and fish oil esters of plant sterols compared with hamsters fed no plant sterols, no difference was observed in erythrocyte fragility. The present results show that EPA and DHA esters of plant sterols have a hypocholesterolemic effect in hamsters, and that these new esters of plant sterols exert no detrimental effect on erythrocyte fragility.

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Abbreviations

CVD:

cardiovascular disease

TMS:

trimethylchlorosilane

References

  1. Fruchart, J.-C., Nierman, M.C., Stroes, E.S.G., Kastelein, J.J.P., and Duriez, P. (2004) New Risk Factors for Atherosclerosis and Patient Risk Assessment, Circulation 109 (Suppl. III), III15-III19.

    PubMed  Google Scholar 

  2. Stone, N.J., and Van Horn, L. (2002) Therapeutic Lifestyle Change and Adult Treatment Panel III: Evidence Then and Now, Curr. Atheroscler. Rep. 4, 433–443.

    PubMed  Google Scholar 

  3. Katan, M.B., Grundy, S.M., Jones, P., Law, M., Miettinen, T., and Paoletti, R. (2003) Efficacy and Safety of Plant Stanols and Sterols in the Management of Blood Cholesterol Levels, Mayo Clin. Proc. 78, 965–978.

    Article  PubMed  CAS  Google Scholar 

  4. Ostlund, R.E. (2002) Phytosterols in Human Nutrition, Annu. Rev. Nutr. 22, 533–549.

    Article  PubMed  CAS  Google Scholar 

  5. Harris, W.S. (1997) n−3 Fatty Acids and Serum Lipoproteins: Human Studies, Am. J. Clin. Nutr. 65 (Suppl.), 1645S-1654S.

    PubMed  CAS  Google Scholar 

  6. Harris, W.S. (1997) n−3 Fatty Acids and Serum Lipoproteins: Animal Studies, Am. J. Clin. Nutr. 65 (Suppl.), 1611S-1616S.

    PubMed  CAS  Google Scholar 

  7. Moreau, R.A., Whitaker, B.D., and Hicks, K.B. (2002) Phytosterols, Phytostanols, and Their Conjugates in Foods: Structural Diversity, Quantitative Analysis, and Health-Promoting Uses, Prog. Lipid Res. 41, 457–500.

    Article  PubMed  CAS  Google Scholar 

  8. Ewart, S.H., Cole, L.K., Kralovec, J., Layton, H., Curtis, J.M., Wright, J.L.C., and Murphy, M.G. (2002) Fish Oil Containing Phytosterol Esters Alters Blood Lipid Profiles and Left Ventricle Generation of Thromboxane A2 in Adult Guinea Pigs, J. Nutr. 132, 1149–1152.

    PubMed  CAS  Google Scholar 

  9. Russell, J.C., Ewart, S.H., Kelly, S.E., Kralovec, J., Wright, J.L.C., and Dolphin, P.J. (2002) Improvement of Vascular Dysfunction and Blood Lipids of Insulin-Resistant Rats by a Marine Oil-Based Phytosterol Compound, Lipids 37, 147–152.

    Article  PubMed  CAS  Google Scholar 

  10. Ratnayake, W.M.N., L’Abbé, M.R., Mueller, R., Hayward S., Plouffe, L., Hollywood, R., and Trick, K. (2000) Vegetable Oils High in Phytosterols Make Erythrocytes Less Deformable and Shorten the Life Span of Stroke-Prone Spontaneously Hypertensive Rats, J. Nutr. 130, 1166–1178.

    PubMed  CAS  Google Scholar 

  11. Rabbani, P.I., Alam, H.Z., Chirtel, S.J., Duvall, R.E., Jackson, R.C., and Ruffin, G. (2001) Subchronic Toxicity of Fish Oil Concentrates in Male and Female Rats, J. Nutr. Sci. Vitaminol. (Tokyo) 47, 201–212.

    CAS  Google Scholar 

  12. Pöschl, J.M.B., Leray, C., Groscolas, R., Ruef, P., and Linderkamp, O. (1996) Dietary Docosahexaenoic Acid Improves Red Blood Cell Deformability in Rats, Thromb. Res. 81, 283–288.

    Article  PubMed  Google Scholar 

  13. Gans, R.O., Bilo, H.J., Weersink, E.G., Rauwerda, J.A., Fonk, T., Popp-Snidjers, C., and Donker, A.J. (1990) Fish Oil Supplementations in Patients with Stable Claudication, Am. J. Surg. 160, 490–495.

    Article  PubMed  CAS  Google Scholar 

  14. Cartwright, I.J., Pockley, A.G., Galloway, J.H., Greaves, M., and Preston, F.E. (1985) The Effects of Dietary Omega-3 Polyunsaturated Fatty Acids on Erythrocyte Membrane Phospholipids, Erythrocyte Deformability and Blood Viscosity in Healthy Volunteers, Atherosclerosis 55, 267–281.

    Article  PubMed  CAS  Google Scholar 

  15. Terano, T., Hirai, A., Hamazaki, T., Kobayashi, S., Fujita, T., Tanura, Y., and Kumagai, A. (1983) Effect of Oral Administration of Highly Purified Eicosapentaenoic Acid on Platelet Function, Blood Viscosity and Red Cell Deformability in Healthy Human Subjects, Atherosclerosis 46, 321–331.

    Article  PubMed  CAS  Google Scholar 

  16. Kris-Etherton, P.M., and Dietschy, J. (1997) Design Criteria for Studies Examining Individual Fatty Acid Effects on Cardiovascular Disease Risk Factors: Human and Animal Studies, Am. J. Clin. Nutr. 65, 1590S-1596S.

    PubMed  CAS  Google Scholar 

  17. Spady, D.K., Stange, E.F., Bilhartz, L.E., and Dietschy, J.M. (1986) Bile Acids Regulate Hepatic Low-Density Lipoprotein Receptor Activity in the Hamster by Altering Cholesterol Flux Across the Liver, Proc. Natl. Acad. Sci. USA 83, 1916–1920.

    Article  PubMed  CAS  Google Scholar 

  18. Spady, D.K., Turley, S.D., and Dietschy J.M. (1985) Rates of Low-Density Lipoprotein Uptake and Cholesterol Synthesis Are Regulated Independently in the Liver, J. Lipid Res. 26, 465–472.

    PubMed  CAS  Google Scholar 

  19. Burstein, M., Scholnick, H.R., and Morfin, R.V. (1970) Rapid Method for the Isolation of Lipoproteins from Human Serum, by Precipitation with Polyanions, J. Lipid Res. 11, 583–595.

    PubMed  CAS  Google Scholar 

  20. Friedewald, W.T., Levy, R.I., and Fredrickson, D.S. (1972) Estimation of the Concentration of Low-Density Lipoprotein Cholesterol in Plasma, Without Use of the Preparative Ultracentrifuge Clin. Chem. 18, 499–502.

    PubMed  CAS  Google Scholar 

  21. Kohlmeier, M. (1986) Direct Enzymic Measurement of Glycerides in Serum and in Lipoprotein Fractions, Clin. Chem. 32 (1, Pt. 1), 63–66.

    PubMed  CAS  Google Scholar 

  22. Ntanios, F.Y., and Jones, P.J.H. (1998) Effects of Variable Dietary Sitostanol Concentrations on Plasma Lipid Profile and Phytosterol Metabolism in Hamsters, Biochim. Biophys. Acta 1390, 237–244.

    PubMed  CAS  Google Scholar 

  23. Lütjohann, D., Meese, C.O., Crouse, J.R., III, and von Bergmann, K. (1993) Evaluation of Deuterated Cholesterol and Deuterated Sitostanol for Measurement of Cholesterol Absorption in Humans, J. Lipid Res. 34, 1039–1046.

    PubMed  Google Scholar 

  24. Naito, Y., Konishi, C., and Ohara, N. (2000) Blood Coagulation and Osmolar Tolerance of Erythrocytes in Stroke-Prone Spontaneously Hypertensive Rats Given Rapeseed Oil or Soybean Oil as the Only Dietary Fat, Toxicol. Lett. 117, 209–215.

    Article  Google Scholar 

  25. Jenkins, D.J.A., Kendall, C.W.C., Faulkner, D., Vidgen, E., Trautwein, E.A., Parker, T.L., Marchie, A., Koumbridis, G., Lapsley, K.G., Josse, R.G., et al. (2002) A Dietary Portfolio Approach to Cholesterol Reduction: Combined Effects of Plant Sterols, Vegetable Proteins, and Viscous Fibers in Hypercholesterolemia, Metabolism 51, 1596–1604.

    Article  PubMed  CAS  Google Scholar 

  26. Jenkins, D.J., Kendall, C.W., Marchie, A., Faulkner, D., Vidgen, E., Lapsley, K.G., Trautwein, E.A., Parker, T.L., Josse, R.G., Leiter, L.A., et al. (2003) The Effect of Combining Plant Sterols, Soy Protein, Viscous Fibers, and Almonds in Treating Hypercholesterolemia, Metabolism 52, 1478–1483.

    Article  PubMed  CAS  Google Scholar 

  27. Jones, P.J., Raeini-Sarjaz, M., Jenkins, D.J.A., Kendall, C.W., Vidgen, E., Trautwein, E.A., Lapsley, K.G., Marchie, A., Cunnane, S.C., and Connelly, P.W. (2005) Effects of a Diet High in Plant Sterols, Vegetable Proteins and Viscous Fibers (dietary protfolio) on Circulating Sterol Levels and Red Cell Fragility in Hypercholesterolemic Subjects, Lipids 40, 169–174.

    PubMed  CAS  Google Scholar 

  28. De Jong, A., Plat, J., and Mensink, R.P. (2003) Metabolic Effects of Plant Sterols and Stanols (review), J. Nutr. Biochem. 14, 362–369.

    Article  PubMed  CAS  Google Scholar 

  29. Plat, J., and Mensink, R.P. (2002) Increased Intestinal ABCA1 Expression Contributes to the Decrease in Cholesterol Absorption After Plant Stanol Consumption, FASEB J. 16, 1248–1253.

    Article  PubMed  CAS  Google Scholar 

  30. Dietschy, J.M., Turley, S.D., and Spady, D.K. (1993) Role of Liver in the Maintenance of Cholesterol and Low Density Lipoprotein Homeostasis in Different Animal Species, Including Humans, J. Lipid Res. 34, 1637–1659.

    PubMed  CAS  Google Scholar 

  31. Goulinet, S., and Chapman, M.J. (1993) Plasma Lipoproteins in the Golden Syrian Hamster (Mesocricetus auratus): Heterogeneity of ApoB- and ApoA-I-Containing Partcles, J. Lipid Res. 34, 943–959.

    PubMed  CAS  Google Scholar 

  32. Sicart, R., Sable-Amplis, R., and Guiro, A. (1984) Comparative Studies of the Circulating Lipoproteins in Hamster (Mesocricetus auratus) with a Normal or Spontaneous High Level of Cholesterol in the Plasma, Comp. Biochem. Physiol. 78A, 511–514.

    Article  CAS  Google Scholar 

  33. Ntanios, F.Y., MacDougall, D.E., and Jones, P.J.H. (1998) Gender Effects of Tall Oil Versus Soybean Phytosterols as Cholesterol-Lowering Agents in Hamsters, Can. J. Physiol. Pharmacol. 76, 780–787.

    Article  PubMed  CAS  Google Scholar 

  34. Meijer, G.W., Bressers, M.A., de Groot, W.A., and Rudrum, M. (2003) Effect of Structure and Form on the Ability of Plant Sterols to Inhibit Cholesterol Absorption in Hamsters, Lipids 38, 713–721.

    PubMed  CAS  Google Scholar 

  35. Trautwein, E.A., Schulz, C., Rieckhoff, D., Kunath-Rau, A., Erbersdobler, H.F., de Groot, W.A., and Meijer, G.W. (2002) Effect of Esterified 4-Desmethylsterols and-Stanols or 4′,4′-Dimethylsterols on Cholesterol and Bile Acid Metabolism in Hamsters, Br. J. Nutr. 87 227–237.

    Article  PubMed  CAS  Google Scholar 

  36. Wang, Y.W., Jones, P.J.H., Pischel, I., and Fairow, C. (2003) Effects of Policosanols and Phytosterols on Lipid Levels and Cholesterol Biosynthesis in Hamsters, Lipids 38, 165–170.

    Article  PubMed  CAS  Google Scholar 

  37. Ling, W.H., and Jones, P.J.H. (1995) Enhanced Efficacy of Sitostanol-Containing Versus Sitostanol-Free Phytosterol Mixtures in Altering Lipoprotein Cholesterol Levels and Synthesis in Rats, Atherosclerosis 118, 319–331.

    Article  PubMed  CAS  Google Scholar 

  38. Ntanios, F.Y., Jones, P.J.H., and Frohlich, J.J. (1998) Dietary Sitostanol Reduces Plaque Formation but Not Lecithin Cholesterol Acyl Transferase Activity in Rabbits, Atherosclerosis 138, 101–110.

    Article  PubMed  CAS  Google Scholar 

  39. Sessions, V.A., and Salter, A.M. (1994) The Effects of Different Dietary Fats and Cholesterol on Serum Lipoprotein Concentrations in Hamsters, Biochim. Biophys. Acta 1211, 207–214.

    PubMed  CAS  Google Scholar 

  40. de Silva, P.P., Agarwal-Mawal, A., Davis, P.J., and Cheema, S.K. (2005) The Levels of Plasma Low Density Lipoprotein Are Independent of Cholesterol Ester Transfer Protein in Fish-Oil Fed FIB Hamsters, Nutr. Metab. 2, 8.

    Article  CAS  Google Scholar 

  41. Lu, S.-C., Lin, M.-H., and Huang, P.-C. (1996) A High Cholesterol, (n−3) Polyunsaturated Fatty Acid Diet Induces Hypercholesterolemia More Than a High Cholesterol, (n−6) Polyunsaturated Fatty Acid Diet in Hamsters, J. Nutr. 126, 1759–1765.

    PubMed  CAS  Google Scholar 

  42. Spady, D.K., Horton, J.D., and Cuthbert, J.A. (1995) Regulatory Effects of n−3 Polyunsaturated Fatty Acids on Hepatic LDL Uptake in the Hamster and Rat, J. Lipid Res. 36, 1009–1020.

    PubMed  CAS  Google Scholar 

  43. Valeille, K., Gripois, D., Blouquit, M.-F., Souidi, M., Riottot, M., Bouthegourd, J.-C., Sérougne, C., and Marint, J.-C. (2004) Lipid Atherogenic Risk Markers Can Be More Favourably Influenced by the cis-9,trans-11-Octadecadienoate Isomer Than a Conjugated Linoleic Acid Mixture or Fish Oil in Hamsters, Br. J. Nutr. 91, 191–199.

    Article  PubMed  CAS  Google Scholar 

  44. Kubow, S., Goyette, N., Kermasha, S., Stewart-Phillip, J., and Koski, K.G. (1996) Vitamin E Inhibits Fish Oil-Induced Hyperlipidemia and Tissue Lipid Peroxidation in Hamsters, Lipids 31, 839–847.

    Article  PubMed  CAS  Google Scholar 

  45. Surette, M.E., Whelan, J., Broughton, K.S., and Kinsella, J.E. (1992) Evidence for Mechanisms of the Hypotriglyceridemic Effect of n−3 Polyunsaturated Fatty Acids, J. Lipid Res. 33, 263–271.

    PubMed  CAS  Google Scholar 

  46. Rivellese, A.A., Maffettone, A., Vessby, B., Uusitupa, M., Hermansen, K., Berglund, L., Louheranta, A., Meyer, B.J., and Riccardi, G. (2003) Effects of Dietary Saturated, Monounsaturated and n−3 Fatty Acids on Fasting Lipoproteins, LDL Size and Postprandial Lipid Metabolism in Healthy Subjects, Atherosclerosis 167, 149–158.

    Article  PubMed  CAS  Google Scholar 

  47. Harris, W.S. (1996) n−3 Fatty Acids and Lipoproteins: Comparisons of Results from Human and Animal Studies, Lipids 31, 243–252.

    PubMed  CAS  Google Scholar 

  48. Field, F.J., Born, E., and Mathur, S.N. (2003) Fatty Acid Flux Suppresses Fatty Acid Synthesis in Hamster Intestine Independently of SREBP-1 Expression, J. Lipid Res. 44, 1199–1208.

    Article  PubMed  CAS  Google Scholar 

  49. Berr, F., Goetz, A., Schreiber, E., and Paumgartner, G. (1993) Effect of Dietary n−3 Versus n−6 Polyunsaturated Fatty Acids on Hepatic Excretion of Cholesterol in the Hamster, J. Lipid Res. 34, 1275–1284.

    PubMed  CAS  Google Scholar 

  50. Surette, M.E., Whelan, J., Broughton, K.S., and Kinsella, J.E. (1992) Evidence for Mechanisms of the Hypotriglyceridemic Effect of n−3 Polyunsaturated Fatty Acids, Biochim. Biophys. Acta 1126, 199–205.

    PubMed  CAS  Google Scholar 

  51. Weststrate, J.A., and Meijer, G.W. (1998) Plant Sterol-Enriched Margarines and Reduction of Plasma Total- and LDL-Cholesterol Concentrations in Normocholesterolaemic and Mildly Hypercholesterolaemic Subjects, Eur. J. Clin. Nutr. 52, 334–343.

    Article  PubMed  CAS  Google Scholar 

  52. Hassan, A.S., and Rampone, A.J. (1979) Intestinal Absorption and Lymphatic Transport of Cholesterol and β-Sitostanol in the Rat, J. Lipid Res. 20, 646–653.

    PubMed  CAS  Google Scholar 

  53. Ntanios, F.Y., van de Kooij, A.J., de Deckere, E.A.M., Duchateau, G.S.M.J.E., and Trautwein, E.A. (2003) Effects of Various Amounts of Dietary Plant Sterol Esters on Plasma and Hepatic Sterol Concentration and Aortic Foam Cell Formation of Cholesterol-Fed Hamsters, Atherosclerosis 169, 41–50.

    Article  PubMed  CAS  Google Scholar 

  54. Hendriks, H.F.J., Brink, E.J., Meijer, G.W., Princen, H.M.G., and Ntanios, F.Y. (2003) Safety of Long-Term Consumption of Plant Sterol Esters-Enriched Spread, Eur. J. Clin. Nutr. 57, 681–692.

    Article  PubMed  CAS  Google Scholar 

  55. Heinemann, T., Axtmann, G., and von Bergmann, K. (1993) Comparison of Intestinal Absorption of Cholesterol with Different Plant Sterols in Man, Eur. J. Clin. Invest. 23, 827–831.

    Article  PubMed  CAS  Google Scholar 

  56. Pöschl, J.M.B., Paul, K., Leischsenring, M., Han, S.R., Pfisterer, M., Bremer, H.J., and Linderkamp, O. (1999) Effects of Dietary Supplementation of Saturated Fatty Acids and n−6 or n−3 Polyunsaturated Fatty Acids on Plasma and Red Blood Cell Membrane Phospholipids and Deformability in Weanling Guinea Pigs, Lipids 34, 467–473.

    Article  PubMed  Google Scholar 

  57. Blonk, M.C., Bilo, H.J., Nauta, J.J., Popp-Snijders, C., Mulder, C., and Donker, A.J. (1990) Dose-Response Effects of Fish-Oil Supplementation in Healthy Volunteers, Am. J. Clin. Nutr. 52, 120–127.

    PubMed  CAS  Google Scholar 

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Correspondence to Peter J. H. Jones.

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Demonty, I., Ebine, N., Jia, X. et al. Fish oil fatty acid esters of phytosterols alter plasma lipids but not red blood cell fragility in hamsters. Lipids 40, 695–702 (2005). https://doi.org/10.1007/s11745-005-1432-y

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