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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Use of Plant Sterol and Stanol Fortified Foods in Clinical Practice

Author(s): Montserrat Cofán* and Emilio Ros

Volume 26 , Issue 37 , 2019

Page: [6691 - 6703] Pages: 13

DOI: 10.2174/0929867325666180709114524

Price: $65


Plant sterols and stanols (PS) are natural, non-nutritive molecules that play a structural role in plant membranes similar to that of cholesterol in animal membranes and abound in seeds and derived oils. PS exert their physical effect of interference with micellar solubilization of cholesterol within the intestinal lumen and are marginally absorbed by enterocytes, with negiglible increases in circulating levels. The physiological role of PS in plants and their natural origin and non-systemic action, together with their cholesterol-lowering effect, make them an attractive option as non-pharmacological agents for the management of hypercholesterolemia. Recent meta-analyses have summarized the results of >100 controlled clinical trials and have firmly established that the consumption of PS-supplemented foods in different formats at doses of 2-3 g per day results in LDL-cholesterol reductions of 9-12%. PS are both effective and safe cholesterol-lowering agents and have many clinical applications: adjuncts to a healthy diet, treatment of common hypercholesterolemia, combination therapy with statins and other lipid-lowering drugs, and treatment of metabolic syndrome and diabetes. The cholesterol-lowering efficacy is similar in all clinical situations. PS are also useful agents for treatment of hypercholesterolemic children who are not yet candidates to statins or receive low-doses of these agents. In the setting of statin treatment, the average LDL-cholesterol reduction obtained with PS is equivalent to up- titrating twice the statin dose. However, information is still scarce on the efficacy of PS as an add-on therapy to ezetimibe, fibrates, omega- 3 fatty acids, or bile acid binding resins. The consistent scientific evidence on the cholesterollowering efficacy and safety of functional foods supplemented with PS has led several national and international scientific societies to endorse their use for the non-pharmacologic treatment of hypercholesterolemia as adjuncts to a healthy diet. There is, however, a lack of clinical trials of PS with outcomes on cardiovascular events.

Keywords: Plant sterols, plant stanols, blood cholesterol, cholesterol absorption, cardiovascular risk, LDLcholesterol reductions.

Valitova, J.N.; Sulkarnayeva, A.G.; Minibayeva, F.V. Plant sterols: diversity, biosynthesis, and physiological functions. Biochemistry (Mosc.), 2016, 81(8), 819-834.
[] [PMID: 27677551]
Moreau, R.A.; Nyström, L.; Whitaker, B.D.; Winkler-Moser, J.K.; Baer, D.J.; Gebauer, S.K.; Hicks, K.B. Phytosterols and their derivatives: Structural diversity, distribution, metabolism, analysis, and health-promoting uses. Prog. Lipid Res., 2018, 70, 35-61.
[] [PMID: 29627611]
Ros, E.; Hu, F.B. Consumption of plant seeds and cardiovascular health: epidemiological and clinical trial evidence. Circulation, 2013, 128(5), 553-565.
[] [PMID: 23897849]
Heinemann, T.; Axtmann, G.; von Bergmann, K. Comparison of intestinal absorption of cholesterol with different plant sterols in man. Eur. J. Clin. Invest., 1993, 23(12), 827-831.
[] [PMID: 8143759]
Ostlund, R.E., Jr; McGill, J.B.; Zeng, C-M.; Covey, D.F.; Stearns, J.; Stenson, W.F.; Spilburg, C.A. Gastrointestinal absorption and plasma kinetics of soy Delta(5)-phytosterols and phytostanols in humans. Am. J. Physiol. Endocrinol. Metab., 2002, 282(4), E911-E916.
[] [PMID: 11882512]
Bosner, M.S.; Lange, L.G.; Stenson, W.F.; Ostlund, R.E. Jr. Percent cholesterol absorption in normal women and men quantified with dual stable isotopic tracers and negative ion mass spectrometry. J. Lipid Res., 1999, 40(2), 302-308.
[PMID: 9925660]
Berge, K.E.; Tian, H.; Graf, G.A.; Yu, L.; Grishin, N.V.; Schultz, J.; Kwiterovich, P.; Shan, B.; Barnes, R.; Hobbs, H.H. Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science, 2000, 290(5497), 1771-1775.
[] [PMID: 11099417]
Gylling, H.; Simonen, P. Phytosterols, phytostanols, and lipoprotein metabolism. Nutrients, 2015, 7(9), 7965-7977.
[] [PMID: 26393644]
Ras, R.T.; Hiemstra, H.; Lin, Y.; Vermeer, M.A.; Duchateau, G.S.M.J.E.; Trautwein, E.A. Consumption of plant sterol-enriched foods and effects on plasma plant sterol concentrations--a meta-analysis of randomized controlled studies. Atherosclerosis, 2013, 230(2), 336-346.
[] [PMID: 24075766]
Brinton, E.A.; Hopkins, P.N.; Hegele, R.A.; Geller, A.S.; Polisecki, E.Y.; Diffenderfer, M.R.; Schaefer, E.J. The association between hypercholesterolemia and sitosterolemia, and report of a sitosterolemia kindred. J. Clin. Lipidol., 2018, 12(1), 152-161.
[] [PMID: 29169939]
Weingärtner, O.; Böhm, M.; Laufs, U. Controversial role of plant sterol esters in the management of hypercholesterolaemia. Eur. Heart J., 2009, 30(4), 404-409.
[] [PMID: 19158117]
Genser, B.; Silbernagel, G.; De Backer, G.; Bruckert, E.; Carmena, R.; Chapman, M.J.; Deanfield, J.; Descamps, O.S.; Rietzschel, E.R.; Dias, K.C.; März, W. Plant sterols and cardiovascular disease: a systematic review and meta-analysis. Eur. Heart J., 2012, 33(4), 444-451.
[] [PMID: 22334625]
Baumgartner, S.; Ras, R.T.; Trautwein, E.A.; Mensink, R.P.; Plat, J. Plasma fat-soluble vitamin and carotenoid concentrations after plant sterol and plant stanol consumption: a meta-analysis of randomized controlled trials. Eur. J. Nutr., 2017, 56(3), 909-923.
[] [PMID: 27591863]
Hunter, P.M.; Hegele, R.A. Functional foods and dietary supplements for the management of dyslipidaemia. Nat. Rev. Endocrinol., 2017, 13(5), 278-288.
[] [PMID: 28133369]
Demonty, I.; Ras, R.T.; van der Knaap, H.C.M.; Duchateau, G.S.M.J.E.; Meijer, L.; Zock, P.L.; Geleijnse, J.M.; Trautwein, E.A. Continuous dose-response relationship of the LDL-cholesterol-lowering effect of phytosterol intake. J. Nutr., 2009, 139(2), 271-284.
[] [PMID: 19091798]
Ras, R.T.; Geleijnse, J.M.; Trautwein, E.A. LDL-cholesterol-lowering effect of plant sterols and stanols across different dose ranges: a meta-analysis of randomised controlled studies. Br. J. Nutr., 2014, 112(2), 214-219.
[] [PMID: 24780090]
Ferguson, J.J.A.; Stojanovski, E.; MacDonald-Wicks, L.; Garg, M.L. Fat type in phytosterol products influence their cholesterol-lowering potential: A systematic review and meta-analysis of RCTs. Prog. Lipid Res., 2016, 64, 16-29.
[] [PMID: 27497855]
Ruiu, G.; Pinach, S.; Veglia, F.; Gambino, R.; Marena, S.; Uberti, B.; Alemanno, N.; Burt, D.; Pagano, G.; Cassader, M. Phytosterol-enriched yogurt increases LDL affinity and reduces CD36 expression in polygenic hypercholesterolemia. Lipids, 2009, 44(2), 153-160.
[] [PMID: 18998188]
Plana, N.; Nicolle, C.; Ferre, R.; Camps, J.; Cos, R.; Villoria, J.; Masana, L. DANACOL group. Plant sterol-enriched fermented milk enhances the attainment of LDL-cholesterol goal in hypercholesterolemic subjects. Eur. J. Nutr., 2008, 47(1), 32-39.
[] [PMID: 18193377]
Doornbos, A.M.; Meynen, E.M.; Duchateau, G.S.; van der Knaap, H.C.; Trautwein, E.A. Intake occasion affects the serum cholesterol lowering of a plant sterol-enriched single-dose yoghurt drink in mildly hypercholesterolaemic subjects. Eur. J. Clin. Nutr., 2006, 60(3), 325-333.
[] [PMID: 16234829]
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(9), 671-677.
[] [PMID: 11002377]
Escurriol, V.; Cofán, M.; Moreno-Iribas, C.; Larrañaga, N.; Martínez, C.; Navarro, C.; Rodríguez, L.; González, C.A.; Corella, D.; Ros, E. Phytosterol plasma concentrations and coronary heart disease in the prospective Spanish EPIC cohort. J. Lipid Res., 2010, 51(3), 618-624.
[] [PMID: 19786566]
Pelletier, X.; Belbraouet, S.; Mirabel, D.; Mordret, F.; Perrin, J.L.; Pages, X.; Debry, G. A diet moderately enriched in phytosterols lowers plasma cholesterol concentrations in normocholesterolemic humans. Ann. Nutr. Metab., 1995, 39(5), 291-295.
[] [PMID: 8585698]
Ostlund, R.E., Jr; Racette, S.B.; Okeke, A.; Stenson, W.F. Phytosterols that are naturally present in commercial corn oil significantly reduce cholesterol absorption in humans. Am. J. Clin. Nutr., 2002, 75(6), 1000-1004.
[] [PMID: 12036805]
Escurriol, V.; Cofán, M.; Serra, M.; Bulló, M.; Basora, J.; Salas-Salvadó, J.; Corella, D.; Zazpe, I.; Martínez-González, M.A.; Ruiz-Gutiérrez, V.; Estruch, R.; Ros, E. Serum sterol responses to increasing plant sterol intake from natural foods in the Mediterranean diet. Eur. J. Nutr., 2009, 48(6), 373-382.
[] [PMID: 19412676]
Lin, X.; Racette, S.B.; Lefevre, M.; Spearie, C.A.; Most, M.; Ma, L.; Ostlund, R.E., Jr The effects of phytosterols present in natural food matrices on cholesterol metabolism and LDL-cholesterol: a controlled feeding trial. Eur. J. Clin. Nutr., 2010, 64(12), 1481-1487.
[] [PMID: 20808333]
Racette, S.B.; Lin, X.; Lefevre, M.; Spearie, C.A.; Most, M.M.; Ma, L.; Ostlund, R.E. Jr. Dose effects of dietary phytosterols on cholesterol metabolism: a controlled feeding study. Am. J. Clin. Nutr., 2010, 91(1), 32-38.
[] [PMID: 19889819]
Andersson, S.W.; Skinner, J.; Ellegård, L.; Welch, A.A.; Bingham, S.; Mulligan, A.; Andersson, H.; Khaw, K-T. Intake of dietary plant sterols is inversely related to serum cholesterol concentration in men and women in the EPIC Norfolk population: a cross-sectional study. Eur. J. Clin. Nutr., 2004, 58(10), 1378-1385.
[] [PMID: 15054420]
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.; Leiter, L.A.; Connelly, P.W. A dietary portfolio approach to cholesterol reduction: combined effects of plant sterols, vegetable proteins, and viscous fibers in hypercholesterolemia. Metabolism, 2002, 51(12), 1596-1604.
[] [PMID: 12489074]
Jenkins, D.J.A.; Kendall, C.W.C.; Marchie, A.; Faulkner, D.; Vidgen, E.; Lapsley, K.G.; Trautwein, E.A.; Parker, T.L.; Josse, R.G.; Leiter, L.A.; Connelly, P.W. The effect of combining plant sterols, soy protein, viscous fibers, and almonds in treating hypercholesterolemia. Metabolism, 2003, 52(11), 1478-1483.
[] [PMID: 14624410]
Jenkins, D.J.A.; Kendall, C.W.C.; Nguyen, T.H.; Marchie, A.; Faulkner, D.A.; Ireland, C.; Josse, A.R.; Vidgen, E.; Trautwein, E.A.; Lapsley, K.G.; Holmes, C.; Josse, R.G.; Leiter, L.A.; Connelly, P.W.; Singer, W. Effect of plant sterols in combination with other cholesterol-lowering foods. Metabolism, 2008, 57(1), 130-139.
[] [PMID: 18078870]
Jenkins, D.J.A.; Kendall, C.W.C.; Marchie, A.; Faulkner, D.A.; Wong, J.M.W.; de Souza, R.; Emam, A.; Parker, T.L.; Vidgen, E.; Trautwein, E.A.; Lapsley, K.G.; Josse, R.G.; Leiter, L.A.; Singer, W.; Connelly, P.W. Direct comparison of a dietary portfolio of cholesterol-lowering foods with a statin in hypercholesterolemic participants. Am. J. Clin. Nutr., 2005, 81(2), 380-387.
[] [PMID: 15699225]
Naumann, E.; Plat, J.; Kester, A.D.M.; Mensink, R.P. The baseline serum lipoprotein profile is related to plant stanol induced changes in serum lipoprotein cholesterol and triacylglycerol concentrations. J. Am. Coll. Nutr., 2008, 27(1), 117-126.
[] [PMID: 18460490]
Demonty, I.; Ras, R.T.; van der Knaap, H.C.M.; Meijer, L.; Zock, P.L.; Geleijnse, J.M.; Trautwein, E.A. The effect of plant sterols on serum triglyceride concentrations is dependent on baseline concentrations: a pooled analysis of 12 randomised controlled trials. Eur. J. Nutr., 2013, 52(1), 153-160.
[] [PMID: 22252793]
Rocha, V.Z.; Ras, R.T.; Gagliardi, A.C.; Mangili, L.C.; Trautwein, E.A.; Santos, R.D. Effects of phytosterols on markers of inflammation: a systematic review and meta-analysis. Atherosclerosis, 2016, 248, 76-83.
[] [PMID: 26987068]
Robinson, J.G.; Smith, B.; Maheshwari, N.; Schrott, H. Pleiotropic effects of statins: benefit beyond cholesterol reduction? A meta-regression analysis. J. Am. Coll. Cardiol., 2005, 46(10), 1855-1862.
[] [PMID: 16286171]
Rudkowska, I.; AbuMweis, S.S.; Nicolle, C.; Jones, P.J.H. Association between non-responsiveness to plant sterol intervention and polymorphisms in cholesterol metabolism genes: a case-control study. Appl. Physiol. Nutr. Metab., 2008, 33(4), 728-734.
[] [PMID: 18641716]
Casas-Agustench, P.; Serra, M.; Pérez-Heras, A.; Cofán, M.; Pintó, X.; Trautwein, E.A.; Ros, E. Effects of plant sterol esters in skimmed milk and vegetable-fat-enriched milk on serum lipids and non-cholesterol sterols in hypercholesterolaemic subjects: a randomised, placebo-controlled, crossover study. Br. J. Nutr., 2012, 107(12), 1766-1775.
[] [PMID: 22018049]
Santosa, S.; Varady, K.A.; AbuMweis, S.; Jones, P.J.H. Physiological and therapeutic factors affecting cholesterol metabolism: Does a reciprocal relationship between cholesterol absorption and synthesis really exist? Life Sci., 2007, 80(6), 505-514.
[] [PMID: 17113605]
Scholle, J.M.; Baker, W.L.; Talati, R.; Coleman, C.I. The effect of adding plant sterols or stanols to statin therapy in hypercholesterolemic patients: systematic review and meta-analysis. J. Am. Coll. Nutr., 2009, 28(5), 517-524.
[] [PMID: 20439548]
Castro Cabezas, M.; de Vries, J.H.M.; Van Oostrom, A.J.H.H.M.; Iestra, J.; van Staveren, W.A. Effects of a stanol-enriched diet on plasma cholesterol and triglycerides in patients treated with statins. J. Am. Diet. Assoc., 2006, 106(10), 1564-1569.
[] [PMID: 17000189]
de Jong, A.; Plat, J.; Lütjohann, D.; Mensink, R.P. Effects of long-term plant sterol or stanol ester consumption on lipid and lipoprotein metabolism in subjects on statin treatment. Br. J. Nutr., 2008, 100(5), 937-941.
[] [PMID: 18846701]
Takeshita, M.; Katsuragi, Y.; Kusuhara, M.; Higashi, K.; Miyajima, E.; Mizuno, K.; Mori, K.; Obata, T.; Ohmori, R.; Ohsuzu, F.; Onodera, Y.; Sano, J.; Sawada, S.; Tabata, S.; Tokimitsu, I.; Tomonobu, K.; Yamashita, T.; Yasukawa, T.; Yonemura, A.; Nakamura, H. Phytosterols dissolved in diacylglycerol oil reinforce the cholesterol-lowering effect of low-dose pravastatin treatment. Nutr. Metab. Cardiovasc. Dis., 2008, 18(7), 483-491.
[] [PMID: 17964767]
Kelly, E.R.; Plat, J.; Mensink, R.P.; Berendschot, T.T.J.M. Effects of long term plant sterol and -stanol consumption on the retinal vasculature: a randomized controlled trial in statin users. Atherosclerosis, 2011, 214(1), 225-230.
[] [PMID: 21122856]
Hallikainen, M.; Kurl, S.; Laakso, M.; Miettinen, T.A.; Gylling, H. Plant stanol esters lower LDL cholesterol level in statin-treated subjects with type 1 diabetes by interfering the absorption and synthesis of cholesterol. Atherosclerosis, 2011, 217(2), 473-478.
[] [PMID: 21514589]
Thompson, G.R. Additive effects of plant sterol and stanol esters to statin therapy. Am. J. Cardiol., 2005, 96(1A), 37D-39D.
[] [PMID: 15992514]
Eussen, S.R.B.M.; Bouvy, M.L.; Rompelberg, C.J.M.; van der Elst, M.E.; Garssen, J.; Oosterveld, M.H.; de Boer, A.; de Gier, J.J.; van Kranen, H.J.; Klungel, O.H. Influence of the use of functional foods enriched with phytosterols/-stanols on adherence to statin therapy. Pharmacoepidemiol. Drug Saf., 2011, 20(8), 830-837.
[] [PMID: 21648012]
Garcia-Calvo, M.; Lisnock, J.; Bull, H.G.; Hawes, B.E.; Burnett, D.A.; Braun, M.P.; Crona, J.H.; Davis, H.R., Jr; Dean, D.C.; Detmers, P.A.; Graziano, M.P.; Hughes, M.; Macintyre, D.E.; Ogawa, A.; O’neill, K.A.; Iyer, S.P.; Shevell, D.E.; Smith, M.M.; Tang, Y.S.; Makarewicz, A.M.; Ujjainwalla, F.; Altmann, S.W.; Chapman, K.T.; Thornberry, N.A. The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1). Proc. Natl. Acad. Sci. USA, 2005, 102(23), 8132-8137.
[] [PMID: 15928087]
Jakulj, L.; Trip, M.D.; Sudhop, T.; von Bergmann, K.; Kastelein, J.J.P.; Vissers, M.N. Inhibition of cholesterol absorption by the combination of dietary plant sterols and ezetimibe: effects on plasma lipid levels. J. Lipid Res., 2005, 46(12), 2692-2698.
[] [PMID: 16162943]
Lin, X.; Racette, S.B.; Lefevre, M.; Ma, L.; Spearie, C.A.; Steger-May, K.; Ostlund, R.E. Jr. Combined effects of ezetimibe and phytosterols on cholesterol metabolism: a randomized, controlled feeding study in humans. Circulation, 2011, 124(5), 596-601.
[] [PMID: 21768544]
Gomes, G.B.; Zazula, A.D.; Shigueoka, L.S.; Fedato, R.A.; da Costa, A.B.B.A.; Guarita-Souza, L.C.; Baena, C.P.; Olandoski, M.; Faria-Neto, J.R. A randomized open-label trial to assess the effect of plant sterols associated with ezetimibe in low-density lipoprotein levels in patients with coronary artery disease on statin therapy. J. Med. Food, 2017, 20(1), 30-36.
[] [PMID: 28098515]
Cannon, C.P.; Blazing, M.A.; Braunwald, E. Ezetimibe plus a statin after acute coronary syndromes. N. Engl. J. Med., 2015, 373(15), 1476-1477.
[] [PMID: 26444734]
Ferri, N.; Corsini, A.; Sirtori, C.; Ruscica, M. PPAR-α agonists are still on the rise: an update on clinical and experimental findings. Expert Opin. Investig. Drugs, 2017, 26(5), 593-602.
[] [PMID: 28343425]
Maki, K.C.; Dicklin, M.R. Do triglyceride-lowering drugs decrease risk of cardiovascular disease? Curr. Opin. Lipidol., 2017, 28(4), 374-379.
[] [PMID: 28441155]
Becker, M.; Staab, D.; Von Bergman, K. Long-term treatment of severe familial hypercholesterolemia in children: effect of sitosterol and bezafibrate. Pediatrics, 1992, 89(1), 138-142.
[] [PMID: 1727999]
Nigon, F.; Serfaty-Lacrosnière, C.; Beucler, I.; Chauvois, D.; Neveu, C.; Giral, P.; Chapman, M.J.; Bruckert, E. Plant sterol-enriched margarine lowers plasma LDL in hyperlipidemic subjects with low cholesterol intake: effect of fibrate treatment. Clin. Chem. Lab. Med., 2001, 39(7), 634-640.
[] [PMID: 11522112]
Out, C.; Groen, A.K.; Brufau, G. Bile acid sequestrants: more than simple resins. Curr. Opin. Lipidol., 2012, 23(1), 43-55.
[] [PMID: 22186660]
Mazidi, M.; Rezaie, P.; Karimi, E.; Kengne, A.P. The effects of bile acid sequestrants on lipid profile and blood glucose concentrations: A systematic review and meta-analysis of randomized controlled trials. Int. J. Cardiol., 2017, 227, 850-857.
[] [PMID: 28029410]
Harris, W.S.; Miller, M.; Tighe, A.P.; Davidson, M.H.; Schaefer, E.J. Omega-3 fatty acids and coronary heart disease risk: clinical and mechanistic perspectives. Atherosclerosis, 2008, 197(1), 12-24.
[] [PMID: 18160071]
Sadovsky, R.; Kris-Etherton, P. Prescription omega-3-acid ethyl esters for the treatment of very high triglycerides. Postgrad. Med., 2009, 121(4), 145-153.
[] [PMID: 19641280]
Garaiova, I.; Muchová, J.; Nagyová, Z.; Mišľanová, C.; Oravec, S.; Dukát, A.; Wang, D.; Plummer, S.F.; Ďuračková, Z. Effect of a plant sterol, fish oil and B vitamin combination on cardiovascular risk factors in hypercholesterolemic children and adolescents: a pilot study. Nutr. J., 2013, 12(1), 7.
[] [PMID: 23297818]
Micallef, M.A.; Garg, M.L. The lipid-lowering effects of phytosterols and (n-3) polyunsaturated fatty acids are synergistic and complementary in hyperlipidemic men and women. J. Nutr., 2008, 138(6), 1086-1090.
[] [PMID: 18492838]
Khandelwal, S.; Demonty, I.; Jeemon, P.; Lakshmy, R.; Mukherjee, R.; Gupta, R.; Snehi, U.; Niveditha, D.; Singh, Y.; van der Knaap, H.C.M.; Passi, S.J.; Prabhakaran, D.; Reddy, K.S. Independent and interactive effects of plant sterols and fish oil n-3 long-chain polyunsaturated fatty acids on the plasma lipid profile of mildly hyperlipidaemic Indian adults. Br. J. Nutr., 2009, 102(5), 722-732.
[] [PMID: 19296875]
Normén, L.; Shaw, C.A.; Fink, C.S.; Awad, A.B. Combination of phytosterols and omega-3 fatty acids: a potential strategy to promote cardiovascular health. Curr. Med. Chem. Cardiovasc. Hematol. Agents, 2004, 2(1), 1-12.
[] [PMID: 15320801]
Demonty, I.; Chan, Y-M.; Pelled, D.; Jones, P.J.H. Fish-oil esters of plant sterols improve the lipid profile of dyslipidemic subjects more than do fish-oil or sunflower oil esters of plant sterols. Am. J. Clin. Nutr., 2006, 84(6), 1534-1542.
[] [PMID: 17158440]
Jacobs, D.M.; Mihaleva, V.V.; van Schalkwijk, D.B.; de Graaf, A.A.; Vervoort, J.; van Dorsten, F.A.; Ras, R.T.; Demonty, I.; Trautwein, E.A.; van Duynhoven, J. The effect of plant sterols and different low doses of omega-3 fatty acids from fish oil on lipoprotein subclasses. Mol. Nutr. Food Res., 2015, 59(9), 1745-1757.
[] [PMID: 26019023]
Hess, C.N.; Low Wang, C.C.; Hiatt, W.R. PCSK9 inhibitors: mechanisms of action, metabolic effects, and clinical outcomes. Annu. Rev. Med., 2017.
[] [PMID: 29095667]
Simonen, P.; Stenman, U-H.; Gylling, H. Serum proprotein convertase subtilisin/kexin type 9 concentration is not increased by plant stanol ester consumption in normo- to moderately hypercholesterolaemic non-obese subjects. The BLOOD FLOW intervention study. Clin. Sci. (Lond.), 2015, 129(5), 439-446.
[] [PMID: 25857271]
Williams, C.L.; Bollella, M.C.; Strobino, B.A.; Boccia, L.; Campanaro, L. Plant stanol ester and bran fiber in childhood: effects on lipids, stool weight and stool frequency in preschool children. J. Am. Coll. Nutr., 1999, 18(6), 572-581.
[] [PMID: 10613408]
Tammi, A.; Rönnemaa, T.; Miettinen, T.A.; Gylling, H.; Rask-Nissilä, L.; Viikari, J.; Tuominen, J.; Marniemi, J.; Simell, O. Effects of gender, apolipoprotein E phenotype and cholesterol-lowering by plant stanol esters in children: the STRIP study. Special turku coronary risk factor intervention project. Acta Paediatr., 2002, 91(11), 1155-1162.
[] [PMID: 12463311]
Moruisi, K.G.; Oosthuizen, W.; Opperman, A.M. Phytosterols/stanols lower cholesterol concentrations in familial hypercholesterolemic subjects: a systematic review with meta-analysis. J. Am. Coll. Nutr., 2006, 25(1), 41-48.
[] [PMID: 16522931]
Vuorio, A.F.; Gylling, H.; Turtola, H.; Kontula, K.; Ketonen, P.; Miettinen, T.A. Stanol ester margarine alone and with simvastatin lowers serum cholesterol in families with familial hypercholesterolemia caused by the FH-North Karelia mutation. Arterioscler. Thromb. Vasc. Biol., 2000, 20(2), 500-506.
[] [PMID: 10669649]
Ketomäki, A.M.; Gylling, H.; Antikainen, M.; Siimes, M.A.; Miettinen, T.A. Red cell and plasma plant sterols are related during consumption of plant stanol and sterol ester spreads in children with hypercholesterolemia. J. Pediatr., 2003, 142(5), 524-531.
[] [PMID: 12756385]
Jakulj, L.; Vissers, M.N.; Rodenburg, J.; Wiegman, A.; Trip, M.D.; Kastelein, J.J.P. Plant stanols do not restore endothelial function in pre-pubertal children with familial hypercholesterolemia despite reduction of low-density lipoprotein cholesterol levels. J. Pediatr., 2006, 148(4), 495-500.
[] [PMID: 16647412]
Guardamagna, O.; Abello, F.; Baracco, V.; Federici, G.; Bertucci, P.; Mozzi, A.; Mannucci, L.; Gnasso, A.; Cortese, C. Primary hyperlipidemias in children: effect of plant sterol supplementation on plasma lipids and markers of cholesterol synthesis and absorption. Acta Diabetol., 2011, 48(2), 127-133.
[] [PMID: 21057823]
Garoufi, A.; Vorre, S.; Soldatou, A.; Tsentidis, C.; Kossiva, L.; Drakatos, A.; Marmarinos, A.; Gourgiotis, D. Plant sterols-enriched diet decreases small, dense LDL-cholesterol levels in children with hypercholesterolemia: a prospective study. Ital. J. Pediatr., 2014, 40(1), 42.
[] [PMID: 24887013]
Ooi, E.M.M.; Watts, G.F.; Barrett, P.H.R.; Chan, D.C.; Clifton, P.M.; Ji, J.; Nestel, P.J. Dietary plant sterols supplementation does not alter lipoprotein kinetics in men with the metabolic syndrome. Asia Pac. J. Clin. Nutr., 2007, 16(4), 624-631.
[] [PMID: 18042521]
Hernández-Mijares, A.; Bañuls, C.; Jover, A.; Solá, E.; Bellod, L.; Martínez-Triguero, M.L.; Lagarda, M.J.; Víctor, V.M.; Rocha, M. Low intestinal cholesterol absorption is associated with a reduced efficacy of phytosterol esters as hypolipemic agents in patients with metabolic syndrome. Clin. Nutr., 2011, 30(5), 604-609.
[] [PMID: 21489663]
Sialvera, T.E.; Pounis, G.D.; Koutelidakis, A.E.; Richter, D.J.; Yfanti, G.; Kapsokefalou, M.; Goumas, G.; Chiotinis, N.; Diamantopoulos, E.; Zampelas, A. Phytosterols supplementation decreases plasma small and dense LDL levels in metabolic syndrome patients on a westernized type diet. Nutr. Metab. Cardiovasc. Dis., 2012, 22(10), 843-848.
[] [PMID: 21316934]
Baker, W.L.; Baker, E.L.; Coleman, C.I. The effect of plant sterols or stanols on lipid parameters in patients with type 2 diabetes: a meta-analysis. Diabetes Res. Clin. Pract., 2009, 84(2), e33-e37.
[] [PMID: 19243852]
Lee, Y-M.; Haastert, B.; Scherbaum, W.; Hauner, H. A phytosterol-enriched spread improves the lipid profile of subjects with type 2 diabetes mellitus--a randomized controlled trial under free-living conditions. Eur. J. Nutr., 2003, 42(2), 111-117.
[] [PMID: 12638032]
Lau, V.W.Y.; Journoud, M.; Jones, P.J.H. Plant sterols are efficacious in lowering plasma LDL and non-HDL cholesterol in hypercholesterolemic type 2 diabetic and nondiabetic persons. Am. J. Clin. Nutr., 2005, 81(6), 1351-1358.
[] [PMID: 15941886]
Plat, J.; Mackay, D.; Baumgartner, S.; Clifton, P.M.; Gylling, H.; Jones, P.J. Progress and prospective of plant sterol and plant stanol research: report of the Maastricht meeting. Atherosclerosis, 2012, 225(2), 521-533.
[] [PMID: 23083678]
Cofán, M.; Escurriol, V.; García-Otín, A.L.; Moreno-Iribas, C.; Larrañaga, N.; Sánchez, M.J.; Tormo, M.J.; Redondo, M.L.; González, C.A.; Corella, D.; Pocoví, M.; Civeira, F.; Ros, E. Association of plasma markers of cholesterol homeostasis with metabolic syndrome components. A cross-sectional study. Nutr. Metab. Cardiovasc. Dis., 2011, 21(9), 651-657.
[] [PMID: 20554170]
Zawistowski, J.; Jones, P. Regulatory aspects related to plant sterol and stanol supplemented foods. J. AOAC Int., 2015, 98(3), 750-756.
[] [PMID: 25942758]
European Union (EU). Commission Regulation (EU) No 686/2014 of 20 June 2014 amending Regulations (EC) No 983/2009 and (EU) No 384/2010 as regards the conditions of use of certain health claims related to the lowering effect of plant sterols and plant stanols on blood LDL-cholesterol Text with EEA relevance Retrieved March 19, 2018, from.
Food and Drug Administration (FDA). FDA talk paper. FDA letter regarding enforcement discretion with respect to expanded use of an interim health claim rule about plant sterol/stanol esters and reduced risk of coronary heart disease. FDA authorizes new coronary heart disease health claim for plant sterol and plant stanol esters. Retrieved March 19, 2018, from.
Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults. executive summary of the 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). JAMA, 2001, 285(19), 2486-2497.
[] [PMID: 11368702]
Gylling, H.; Plat, J.; Turley, S.; Ginsberg, H.N.; Ellegård, L.; Jessup, W.; Jones, P.J.; Lütjohann, D.; Maerz, W.; Masana, L.; Silbernagel, G.; Staels, B.; Borén, J.; Catapano, A.L.; De Backer, G.; Deanfield, J.; Descamps, O.S.; Kovanen, P.T.; Riccardi, G.; Tokgözoglu, L.; Chapman, M.J. Plant sterols and plant stanols in the management of dyslipidaemia and prevention of cardiovascular disease. Atherosclerosis, 2014, 232(2), 346-360.
[] [PMID: 24468148]
Stock, J. EAS Consensus Panel statement on homozygous FH. Atherosclerosis, 2015, 242(1), 323-326.
[] [PMID: 26247683]
Catapano, A.L.; Graham, I.; De Backer, G.; Wiklund, O.; Chapman, M.J.; Drexel, H.; Hoes, A.W.; Jennings, C.S.; Landmesser, U.; Pedersen, T.R.; Reiner, Ž.; Riccardi, G.; Taskinen, M.R.; Tokgozoglu, L.; Verschuren, W.M.M.; Vlachopoulos, C.; Wood, D.A.; Zamorano, J.L.; Cooney, M.T. ESC scientific document group. 2016 ESC/EAS guidelines for the management of dyslipidaemias. Eur. Heart J., 2016, 37(39), 2999-3058.
[] [PMID: 27567407]
Wiegman, A.; Gidding, S.S.; Watts, G.F.; Chapman, M.J.; Ginsberg, H.N.; Cuchel, M.; Ose, L.; Averna, M.; Boileau, C.; Borén, J.; Bruckert, E.; Catapano, A.L.; Defesche, J.C.; Descamps, O.S.; Hegele, R.A.; Hovingh, G.K.; Humphries, S.E.; Kovanen, P.T.; Kuivenhoven, J.A.; Masana, L.; Nordestgaard, B.G.; Pajukanta, P.; Parhofer, K.G.; Raal, F.J.; Ray, K.K.; Santos, R.D.; Stalenhoef, A.F.; Steinhagen-Thiessen, E.; Stroes, E.S.; Taskinen, M.R.; Tybjærg-Hansen, A.; Wiklund, O. Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment. Eur. Heart J., 2015, 36(36), 2425-2437.
[] [PMID: 26009596]
American Heart Association Nutrition Committee. A. H.; Lichtenstein, A. H.; Appel, L. J.; Brands, M.; Carnethon, M.; Daniels, S.; Franch, H. A.; Franklin, B.; Kris-Etherton, P.; Harris, W. S.; Howard, B.; Karanja, N.; Lefevre, M.; Rudel, L.; Sacks, F.; Van Horn, L.; Winston, M.; Wylie-Rosett, J. Diet and lifestyle recommendations revision 2006: a scientific statement from the American Heart Association Nutrition Committee. Circulation, 2006, 114(1), 82-96.
[] [PMID: 16785338]
Eckel, R.H.; Jakicic, J.M.; Ard, J.D.; de Jesus, J.M.; Houston Miller, N.; Hubbard, V.S.; Lee, I-M.; Lichtenstein, A.H.; Loria, C.M.; Millen, B.E.; Nonas, C.A.; Sacks, F.M.; Smith, S.C., Jr; Svetkey, L.P.; Wadden, T.A.; Yanovski, S.Z.; Kendall, K.A.; Morgan, L.C.; Trisolini, M.G.; Velasco, G.; Wnek, J.; Anderson, J.L.; Halperin, J.L.; Albert, N.M.; Bozkurt, B.; Brindis, R.G.; Curtis, L.H.; DeMets, D.; Hochman, J.S.; Kovacs, R.J.; Ohman, E.M.; Pressler, S.J.; Sellke, F.W.; Shen, W.K.; Smith, S.C., Jr; Tomaselli, G.F. 2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American college of cardiology/American heart association task force on practice guidelines. Circulation, 2014, 129(25)(Suppl. 2), S76-S99.
[] [PMID: 24222015]
Robinson, J.G.; Wang, S.; Smith, B.J.; Jacobson, T.A. Meta-analysis of the relationship between non-high-density lipoprotein cholesterol reduction and coronary heart disease risk. J. Am. Coll. Cardiol., 2009, 53(4), 316-322.
[] [PMID: 19161879]

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