Plant Stanol and Sterol Esters in the Control of Blood Cholesterol Levels: Mechanism and Safety Aspects

      Incorporation of plant stanol esters into margarine is among the first examples of a functional food with proven low-density lipoprotein (LDL) cholesterol-lowering effectiveness. Recently, there have been many studies on the effects of plant stanols/sterols on cholesterol metabolism. It has been found that the serum LDL cholesterol-lowering effect of plant stanols/sterols originates from reduced intestinal cholesterol absorption, a process in which changes in micellar composition are thought to play a major role. However, recent findings suggest that there is an additional process in which plant stanols/sterols actively influence cellular cholesterol metabolism within intestinal enterocytes. Furthermore, in response to the reduced supply of exogenous cholesterol, receptor-mediated lipoprotein cholesterol uptake is probably enhanced, as shown by increased LDL receptor expression. At recommended intakes of about 2 to 2.5 g/day, products enriched with plant stanol/sterol esters lower plasma LDL cholesterol levels by 10% to 14% without any reported side effects. Thus, plant stanols/sterols can be considered to be effective and safe cholesterol-lowering functional food ingredients.
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        • Fernandez-Britto J.E.
        • Wong R.
        • Contreras D.
        • Nordet P.
        • Sternby N.H.
        Pathomorphometrical characteristics of atherosclerosis in youth.
        Nutr Metab Cardiovasc Dis. 1999; 9: 210-219
        • Martin M.J.
        • Hulley S.B.
        • Browner W.S.
        • Kuller L.H.
        • Wentworth D.
        Serum cholesterol, blood pressure and mortality.
        Lancet. 1986; 11: 933-936
        • Grundy S.M.
        United States Cholesterol Guidelines 2001.
        Am J Cardiol. 2001; 88: 23J-27J
        • Normén L.
        • Dutta P.
        • Lia A.
        • Andersson H.
        Soy sterol esters and beta-sitostanol ester as inhibitors of cholesterol absorption in human small bowel.
        Am J Clin Nutr. 2000; 71: 908-913
        • Hallikainen M.A.
        • Sarkkinen E.S.
        • Gylling H.
        • Erkkila A.T.
        • Uusitupa M.I.J.
        Comparison of the effects of plant sterol ester and plant stanol ester-enriched margarines in lowering serum cholesterol concentrations in hypercholesterolaemic subjects on a low-fat diet.
        Eur J Clin Nutr. 2000; 54: 671-677
        • Mattson F.H.
        • Grundy S.M.
        • Crouse J.R.
        Optimizing the effect of plant sterols on cholesterol absorption in man.
        Am J Clin Nutr. 1982; 35: 697-700
        • Plat J.
        • van Onselen E.N.
        • van Heugten M.M.
        • Mensink R.P.
        Effects on serum lipids, lipoproteins and fat-soluble antioxidant concentrations of consumption frequency of margarines and shortenings enriched with plant stanol esters.
        Eur J Clin Nutr. 2000; 54: 671-677
        • Law M.
        Plant sterol and stanol margarines and health.
        BMJ. 2000; 320: 861-864
        • Matvienko O.A.
        • Lewis D.S.
        • Swanson M.
        • Arndt B.
        • Rainwater D.L.
        • Stewart J.
        • Alekel D.L.
        A single daily dose of soybean phytosterols in ground beef decreases serum total cholesterol and LDL cholesterol in young, mildly hypercholesterolemic men.
        Am J Clin Nutr. 2002; 76: 57-64
        • Igel M.
        • Giesa U.
        • Lutjohann D.
        • Von Bergman K.
        Comparison of the intestinal uptake of cholesterol, plant sterols, and stanols in mice.
        J Lipid Res. 2003; 44: 533-538
        • Field F.J.
        • Mathur S.N.
        β-sitosterol: esterification by intestinal acylcoenzyme A:cholesterol acyltransferase (ACAT) and its effect on cholesterol esterification.
        J Lipid Res. 1983; 24: 409-417
        • Plat J.
        • Mensink R.P.
        Increased intestinal ABC1 expression contributes to the decrease in cholesterol absorption after plant stanol consumption.
        FASEB J. 2002; 16: 1248-1253
        • Repa J.J.
        • Turley S.D.
        • Labaccaro J.M.A.
        • Medina J.
        • Li L.
        • Lustig K.
        • Shan B.
        • Heyman R.A.
        • Dietchy J.M.
        • Mangelsdorf D.J.
        Regulation of absorption and ABC1-mediated efflux of cholesterol by RXR heterodimers.
        Science. 2000; 289: 1524-1529
        • McNeish J.
        • Aiello R.J.
        • Guyot D.
        • Turi T.
        • Gabel C.
        • Aldinger C.
        • Hoppe K.L.
        • Roach M.L.
        • Royer L.J.
        • de Wet J.
        • et al.
        High density lipoprotein deficiency and foam cell accumulation in mice with targeted disruption of ATP-binding cassette transporter-1.
        Proc Natl Acad Sci U S A. 2000; 97: 4245-4250
        • Brown M.S.
        • Goldstein J.L.
        The SREBP pathway.
        Cell. 1997; 89: 331-340
        • Gylling H.
        • Miettinen T.A.
        Serum cholesterol and lipoprotein metabolism in hypercholesterolemic NIDDM patients before and during sitostanol ester-margarine treatment.
        Diabetologia. 1994; 37: 773-780
        • Miettinen T.A.
        • Tilvis R.S.
        • Kesäniemi Y.A.
        Serum plant sterols and cholesterol precursors reflect cholesterol absorption and synthesis in volunteers of a randomly selected male population.
        Am J Epidemiol. 1990; 131: 20-31
        • Kempen H.J.M.
        • Glatz J.F.C.
        • Gevers Leuven J.A.
        • van der Voort H.A.
        • Katan M.B.
        Serum lathosterol concentration is an indicator of whole- body cholesterol synthesis in humans.
        J Lipid Res. 1988; 29: 1149-1155
        • Blair S.
        • Capuzzi D.M.
        • Gottlieb S.O.
        • Nguyen T.
        • Morgan J.M.
        • Cater N.B.
        Incremental reduction of serum total cholesterol and low-density lipoprotein cholesterol with the addition of plant stanol ester containing spread to statin treatment.
        Am J Cardiol. 2000; 86: 46-52
        • Gylling H.
        • Miettinen T.A.
        Effects of inhibiting cholesterol absorption and synthesis on cholesterol and lipoprotein metabolism in hypercholesterolemic non-insulin-dependent diabetic men.
        J Lipid Res. 1996; 37: 1776-1785
        • Baker V.A.
        • Hepburn P.A.
        • Kennedy S.J.
        • Jones P.A.
        • Lea L.J.
        • Sumpter J.P.
        • Ashby J.
        Safety evaluation of phytosterol esters. Part 1. Assessment of oestrogenicity using a combination of in vivo and in vitro assays.
        Food Chem Toxicol. 1999; 37: 13-22
        • Thurnbull D.
        • Frankos V.H.
        • Leeman W.R.
        • Jonker D.
        Short-term tests of estrogenic potential of plant stanols and plant stanol esters.
        Regul Toxicol Pharmacol. 1999; 29: 211-215
        • Slesinsky R.S.
        • Turnbull D.
        • Frankos V.H.
        • Woterbeek A.P.M.
        • Waalkens-Berendsen D.H.
        Developmental toxicity study of vegetable oil-derived stanol fatty acid esters.
        Regul Toxicol Pharmacol. 1999; 29: 227-233
        • Waalkens-Berendsen D.H.
        • Wolterbeek A.P.M.
        • Wijnands M.V.W.
        • Richold M.
        • Hepburn P.A.
        Safety evaluation of phytosterol esters. Part 3. Two-generation reproduction study in rats with phytosterol esters: a novel functional food.
        Food Chem Toxicol. 1999; 37: 683-696
        • Whittaker M.H.
        • Frankos V.H.
        • Woterbeek A.P.M.
        • Waalkens-Berendsen D.H.
        Two-generation reproductive toxicity study of plant stanol esters in rats.
        Regul Toxicol Pharmacol. 1999; 29: 196-204
        • Thurnbull D.
        • Frankos V.H.
        • van Delft J.H.M.
        • DeVogel N.
        Genotoxicity evaluation of wood-derived and vegetable oil-derived stanol esters.
        Regul Toxicol Pharmacol. 1999; 29: 205-210
        • Moghadasian M.H.
        • McManus B.M.
        • Godin D.V.
        • Rodrigues B.
        • Frohlich J.J.
        Proatherogenic and antiatherogenic effects of probucol and phytosterols in apolipoprotein E-deficient mice.
        Circulation. 1999; 99: 1733-1739
        • Moghadasian M.H.
        • McManus B.M.
        • Pritchard P.H.
        • Frohlich J.J.
        Tall oil-derived phytosterols reduce atherosclerosis in apoE deficient mice.
        Arterioscler Thromb Vasc Biol. 1997; 17: 119-126
        • Volger O.L.
        • van der Boom J.
        • de Wit E.C.M.
        • van Duyvenvoorde W.
        • Hornstra G.
        • Plat J.
        • Havekes L.M.
        • Princen H.M.G.
        • Mensink R.P.
        Dietary vegetable-, wood-, or vegetable/wood derived stanol esters reduce atherosclerotic lesion size and severity in apoE*3-Leiden transgenic mice.
        Atherosclerosis. 2000; 151 ([abstract]): 77
        • Plat J.
        • Mensink R.P.
        Effects of diets enriched with two different plant stanol ester mixtures on plasma ubiquinol-10 and fat-soluble antioxidant concentrations.
        Metabolism. 2001; 50: 520-529
        • Plat J.
        • Kerckhoffs D.A.J.M.
        • Mensink R.P.
        Therapeutic potential of plant sterols and stanols.
        Curr Opin Lipidol. 2000; 11: 571-576
        • Noakes M.
        • Clifton P.
        • Ntanios F.
        • Shrapnel W.
        • Record I.
        • McInerney J.
        An increase in dietary carotenoids when consuming plant sterols or stanols is effective in maintaining plasma carotenoid concentrations.
        Am J Clin Nutr. 2002; 75: 79-86
        • Borel P.
        • Grolier P.
        • Armand M.
        • Partier A.
        • Lafont H.
        • Lairon D.
        • Azais-Braesco V.
        Carotenoids in biological emulsions.
        J Lipid Res. 1996; 37: 250-261
        • Miettinen T.A.
        • Strandberg T.E.
        • Gylling H.
        Noncholesterol sterols and cholesterol lowering by long-term simvastatin treatment in coronary patients.
        Arterioscler Thromb Vasc Biol. 2000; 20: 1340-1346
        • Miettinen T.A.
        • Gylling H.
        • Lindbohm N.
        • Miettinen T.E.
        • Rajaratnam R.A.
        • Relas H.
        • Finnish Treat-to-Target Study Investigators
        Serum noncholesterol sterols during inhibition of cholesterol synthesis by statins.
        J Lab Clin Med. 2003; 141: 131-137
        • Miettinen T.A.
        • Gylling H.
        • Strandberg T.
        • Sarna S.
        • Finnish 4S Investigators
        Baseline serum cholestanol as predictor of recurrent coronary events in subgroup of Scandinavian simvastatin survival trial.
        BMJ. 1998; 316: 1127-1130
        • Sudhop T.
        • Gottwald B.M.
        • Von Bergmann K.
        Serum plant sterols as a potential risk factor for coronary heart disease.
        Metabolism. 2002; 51: 1519-1521
        • Glueck C.J.
        • Speirs J.
        • Tracey T.
        • Streicher P.
        • Illig E.
        • Vandegrift J.
        Relationships of serum plant sterols (phytosterols) and cholesterol in 595 hypercholesterolemic subjects, and familial aggregation of phytosterols, cholesterol, and premature coronary heart disease in hypercholesterolemic probands and their first-degree relatives.
        Metabolism. 1991; 40: 842-848
        • Brown A.J.
        • Jessup W.
        Oxysterols and atherosclerosis.
        Atherosclerosis. 1999; 142: 1-28
        • Plat J.
        • Brzezinka H.
        • Lütjohann D.
        • Mensink R.P.
        • von Bergmann K.
        Oxidized plant sterols in human serum and lipid infusions as measured by combined gas-liquid chromatography-mass spectrometry.
        J Lipid Res. 2001; 42: 2030-2038
        • Grandgirard A.
        • Martine L.
        • Demaison L.
        • Cordelet C.
        • Joffre C.
        • Berdeaux O.
        • Semon E.
        Oxyphytosterols are present in plasma of healthy human subjects.
        Br J Nutr. 2004; 91: 101-106
        • Adcox C.
        • Boyd L.
        • Oehrl L.
        • Allen J.
        • Fenner G.
        Comparative effects of phytosterol oxides and cholesterol oxides in cultured macrophage-derived cell lines.
        J Agric Food Chem. 2001; 49: 2090-2095
        • Child P.
        • Kuksis A.
        Differential uptake of cholesterol and plant sterols by rat erythrocytes in vitro.
        Lipids. 1982; 17: 748-754
        • Ratnayake W.M.N.
        • L’Abbe M.R.
        • Mueller R.
        • Hayward S.
        • Plouffe L.
        • Hollywood R.
        • Trick K.
        Vegetable oils high in phytosterols make erythrocytes less deformable and shorten the life span of stroke-prone spontaneously hypertensive rats.
        J Nutr. 2000; 130: 1166-1178
      1. Ratnayake WMN, L’Abbe MR. Adverse health effects of plant sterols and stanols on SHRSP and diabetes-prone rats: the other side of the story [abstract]. Presented at the 92nd American Oil Chemists’ Society Meeting & Expo; May 13–16, 2001; Minneapolis, Minnesota.

        • de Jong A.
        • Plat J.
        • Mensink R.P.
        Plant sterol or stanol consumption does not change osmotic fragility of the enterocyte.
        Atherosclerosis. 2004; 5 ([abstract]): 115s