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.
Similar content being viewed by others
Abbreviations
- CVD:
-
cardiovascular disease
- TMS:
-
trimethylchlorosilane
References
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.
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.
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.
Ostlund, R.E. (2002) Phytosterols in Human Nutrition, Annu. Rev. Nutr. 22, 533–549.
Harris, W.S. (1997) n−3 Fatty Acids and Serum Lipoproteins: Human Studies, Am. J. Clin. Nutr. 65 (Suppl.), 1645S-1654S.
Harris, W.S. (1997) n−3 Fatty Acids and Serum Lipoproteins: Animal Studies, Am. J. Clin. Nutr. 65 (Suppl.), 1611S-1616S.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Kohlmeier, M. (1986) Direct Enzymic Measurement of Glycerides in Serum and in Lipoprotein Fractions, Clin. Chem. 32 (1, Pt. 1), 63–66.
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.
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.
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.
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.
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.
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.
De Jong, A., Plat, J., and Mensink, R.P. (2003) Metabolic Effects of Plant Sterols and Stanols (review), J. Nutr. Biochem. 14, 362–369.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Harris, W.S. (1996) n−3 Fatty Acids and Lipoproteins: Comparisons of Results from Human and Animal Studies, Lipids 31, 243–252.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s11745-005-1432-y