Abstract
Dietary enrichment with phytosterols (plant sterols similar to cholesterol) is able to reduce plasma cholesterol levels due to reduced intestinal absorption. The aim of this study was to investigate the effect of phytosterol-enriched yogurt consumption on the major serum lipid parameters, low density lipoprotein (LDL) receptor activity, LDL-receptor affinity, and CD36 expression in hypercholesterolemic subjects. Fifteen patients affected by polygenic hypercholesterolemia were evaluated in a single-blind randomized crossover study after a 4 weeks treatment with a phytosterol-enriched yogurt containing 1.6 g esterefied phytosterols (equivalent to 1.0 g free phytosterol). Lipid parameters were compared with a phytosterol-free placebo-controlled diet. The effect of the two treatments on each variable, measured as percentage change, was compared by paired samples t test and covariance analysis. The treatment induced a modest but significant decrease in LDL-cholesterol levels (4.3%, P = 0.03) and a significant increase in high density lipoprotein (HDL) 3-cholesterol (17.1%, P = 0.01). Phytosterol consumption had no effect on LDL-receptor activity whereas patient LDL-receptor affinity significantly increased (9.7%, P = 0.01) and CD36 expression showed a marked significant decrease (18.2%, P = 0.01) in the phytosterol-enriched yoghurt patients. Our data show that the oral administration of a phytosterol-enriched yogurt has modest but significant effects on commonly measured lipid parameters. The improvement of LDL-receptor affinity and the reduction in CD36 expression may reflect an important antiatherogenic effect.
Similar content being viewed by others
References
Moreaua RA, Whitakerb MB, Hicksa KB (2002) Phytosterols, phytostanols, and their conjugates in foods: structural diversity, quantitative analysis, and health-promoting uses. Prog Lipid Res 41:457–500. doi:10.1016/S0163-7827(02)00006-1
Best MM, Duncan CH, Van Loon EJ, Wathen JD (1954) Lowering of serum cholesterol by the administration of a plant sterol. Circulation 10:201–206
Heinemann T, Kullak-Ublick A, Pietruck B, von Bergman K (1991) Mechanism of action of plant sterols on inhibition of cholesterol absorption. Eur J Clin Pharmacol 40(suppl 1):59–63S
Plat J, Mensink RP (2005) Plant stanol and sterol esters in the control of blood cholesterol levels: mechanism and safety aspects. Am J Cardiol 96(suppl):15D–22D. doi:10.1016/j.amjcard.2005.03.015
AbuMweis SS, Vanstone CA, Ebine N, Kassis A, Ausman LM, Jones PJH et al (2006) Intake of a single morning dose of standard and novel plant sterol preparations for 4 weeks does not dramatically affect plasma lipid concentrations in humans. J Nutr 136:1012–1016
Katan MB, Grundy SM, Jones P, Law M, Miettinen T, Paoletti R (2003) for the Stresa Workshop participants. Efficacy and safety of plant stanols and sterols in the management of blood cholesterol levels. Mayo Clin Proc 78:965–978
Normen L, Frohlich J, Trautwein E et al (2004) Role of plant sterols in cholesterol lowering. In: Dutta PC (ed) Phytosterols as functional food components and nutraceuticals. Marcel-Dekker, Inc, New York, pp 243–315
National Cholesterol Education Program (NCEP) Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) (2002) Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 106:3143–3421
Shrestha S, Freake HC, McGrane MM, Volek JS, Fernandez ML (2007) A combination of psyllium and plant sterols alters lipoprotein metabolism in hypercholesterolemic subjects by modifying the intravascular processing of lipoproteins and increasing LDL uptake. J Nutr 137(5):1165–1170
Febbraio M, Silverstein RL (2007) CD36: Implications in cardiovascular disease. Int J Biochem Cell Biol 39:2012–2030. doi:10.1016/j.biocel.2007.03.012
Harris JA, Benedict FG (1919) A biometric study of basal metabolism in man. Carnegie Institute of Washington, Washington
Gidez LI, Miller GJ, Burstein M, Slagle S, Eder HA (1982) Separation and quantitation of subclasses of human plasma high density lipoproteins were performed by a simple precipitation procedure. J Lipid Res 23(8):1206–1223
Böyum A (1968) Isolation of mononuclear cells and granulocytes from human blood. Scand J Clin Lab Invest 97:77–89
Ruiu G, Pinach S, Gambino R, Uberti B, Alemanno N, Pagano G et al (2005) Influence of cyclosporine on low-density lipoprotein uptake in human lymphocytes. Metabolism 54:1620–1625. doi:10.1016/j.metabol.2005.06.010
Sawle A, Higgins MK, Olivant MP, Higgins JAA (2002) A rapid single-step centrifugation method for determination of HDL LDL, and VLDL cholesterol, and TG, and identification of predominant LDL subclass. J Lipid Res 43:335–343
Havel RJ, Eder HA, Bragdon JH (1955) The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest 34:1345–1353
Løhne K, Urdal P, Leren TP, Tonstad S, Ose L (1995) Standardization of a flow cytometric method for measurement of low density lipoprotein receptor activity on blood mononuclear cells. Cytometry 20:290–295
Innerarity TL, Pitas RE, Mahley RW (1986) Lipoprotein-receptor interactions. In: Albers JJ, Segrest JP (eds) Methods in enzymology, vol 129. Academic Press, Dublin, pp 542–565
Jones PJH, Vanstone CA, Raeini-Sarjaz M, St-Onge MP (2003) Phytosterols in low- and nonfat beverages as part of a controlled diet fail to lower plasma lipid levels. J Lipid Res 44:1713–1719
Seppo L, Jauhiainen T, Nevala R, Poussa T, Korpela R (2007) Plant stanol esters in low-fat milk products lower serum total and LDL cholesterol. Eur J Nutr 46:111–117
Vanhanen HT, Blomqvist S, Ehnholm C (1993) Serum cholesterol, cholesterol precursors, and plant sterols in hypercholesterolemic subjects with different apoE phenotypes during dietary sitostanol ester treatment. J Lipid Res 34:1535–1544
Barter P, Kastelein J, Nunn A, Hoobs R (2003) High density lipoproteins (HDLs) and atherosclerosis: the unanswered questions. Atherosclerosis 168:195–211. doi:10.1016/S0021-9150(03)00006-6
Goldstein JL, Brown MS (1976) Binding and degradation of low density lipoproteins by cultured human fibroblasts. Comparison of cells from a normal subject and from a patient with homozygous familial hypercholesterolemia. J Biol Chem 249:5153–5162
Terpstra V, van Amersfoot ES, van Velzen AG, Kuiper J, van Berkel TJC (2000) Hepatic and extrahepatic scavenger receptors: function in relation to disease. Arterioscler Thromb Vasc Biol 20:1860–1876
Duvillard L, Gambert P, Lizard G (2004) Etude du recepteur des lipoproteins de basse densite par cytometrie en flux: interest biologiques et cliniques. Ann Biol Clin 62:87–91
Plat J, Mensink RP (2002) Effects of plant stanol esters on LDL receptor protein expression and on LDL receptor and HMG-CoA reductase mRNA expression in mononuclear blood cells of healthy men and women. FASEB J 16:258–260
Berneis KK, Krauss RM (2002) Metabolic origins and clinical significance of LDL heterogeneity. J Lipid Res 43:1363–1379
Campos H, Arnold KS, Balestra ME, Innerarity TL, Krauss RM (1996) Differences in receptor binding of LDL subfractions. Arterioscler Thromb Vasc Biol 16:794–801
Han J, Hajjar DP, Febbraio M, Nicholson AC (1997) Native and modified low density lipoproteins increase the functional expression of the macrophage class B scavenger receptor, CD36. J Biol Chem 272:21654–21659
Viana M, Villacorta L, Bonet B, Indart A, Munteanu A, Sanchezvera I et al (2005) Effects of aldehydes on CD36 expression. Free Radic Res 39:973–977
van Bennekum A, Werder M, Thuahnai ST, Han CH, Duong P, Williams DL et al (2005) Class B scavenger receptor-mediated intestinal absorption of dietary β-carotene and cholesterol. Biochemistry 44:4517–4525
Hansel B, Nicolle C, Lalanne F, Tondu F, Lassel T, Donazzolo Y et al (2007) Effect of low-fat, fermented milk enriched with plant sterols on serum lipid profile and oxidative stress in moderate hypercholesterolemia. Am J Clin Nutr 86:790–796
Homma Y, Ikeda I, Ishikawa T, Tateno M, Sugano M, Nakamura H (2003) Decrease in plasma low-density lipoprotein cholesterol, apolipoprotein B, cholesteryl ester transfer protein, and oxidized low-density lipoprotein by plant stanol ester-containing spread: a randomized, placebo-controlled trial. Nutrition 19:369–374
Acknowledgments
We thank Franco De Michieli for helpful cooperation in the collection of data.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Ruiu, G., Pinach, S., Veglia, F. et al. Phytosterol-Enriched Yogurt Increases LDL Affinity and Reduces CD36 Expression in Polygenic Hypercholesterolemia. Lipids 44, 153–160 (2009). https://doi.org/10.1007/s11745-008-3259-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11745-008-3259-1