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ProActiv Key References

ProActiv Key References

This list includes publications of studies that investigated the cholesterol-lowering efficacy of plant sterols, as well as publications of studies on effects beyond cholesterol-lowering, safety studies, mechanism-of-action studies and reviews. All of these studies were commissioned/initiated/sponsored by Unilever or used plant sterol-enriched test products which were provided by Unilever. Also publications of meta-analyses (including Unilever sponsored studies) are included in this reference list. This list is organized chronologically.

Cholesterol-lowering efficacy studies with plant sterols

Weststrate JA, Meijer GW. Plant sterol-enriched margarines and reduction of plasma total and LDL-cholesterol concentrations in normocholesterolaemic and mildly hypercholesterolaemic subjects. Eur J Clin Nutr 1998; 52(5): 334-343.

Hendriks HF, Weststrate JA, van Vliet T, Meijer GW. Spreads enriched with three different levels of vegetable oil sterols and the degree of cholesterol lowering in normocholesterolaemic and mildly hypercholesterolaemic subjects. Eur J Clin Nutr 1999; 53(4): 319-327.

Jones PJ, Raeini-Sarjaz M, Ntanios FY, Vanstone CA, Feng JY, Parsons WE. Modulation of plasma lipid levels and cholesterol kinetics by phytosterol versus phytostanol esters. J Lipid Res 2000; 4(5): 697-705.

Davidson MH, Maki KC, Umporowicz DM, Ingram KA, Dicklin MR, Schaefer E, Lane RW, McNamara JR, Ribaya-Mercado JD, Perrone G, Robins SJ, Franke WC. Safety and tolerability of esterified phytosterols administered in reduced-fat spread and salad dressing to healthy adult men and women. J Am Coll Nutr 2001; 20(4): 307-319.

Maki KC, Davidson MH, Umporowicz DM, Schaefer EJ, Dicklin MR, Ingram KA, Chen S, McNamara JR, Gebhart BW, Ribaya-Mercado JD, Perrone G, Robins SJ, Franke WC. Lipid responses to plant-sterol-enriched reduced-fat spreads incorporated into a National Cholesterol Education Program Step I diet. Am J Clin Nutr 2001; 74(1): 33-43.

Neil HAW, Meijer GW, Roe LS. Randomised controlled trial of use by hypercholesterolaemic patients of a vegetable oil sterol-enriched fat spread. Atherosclerosis 2001; 156(2): 329-337.

Nigon F, Serfaty-Lacrosniere C, Beucler I, Chauvois D, Neveu C, Giral P, Chapman MJ, 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.

Stalenhoef AFH, Hectors M, Demacker PNM. Effect of plant sterol-enriched margarine on plasma lipids and sterols in subjects heterozygous for phytosterolaemia. J Int Med 2001; 249(2): 163-166.

Tijburg LBM, Meijer GW, Ntanios F, Rudrum M. Plant sterol-esters in a low fat spread are efficacious in lowering blood cholesterol levels in normal cholesterolemic subjects. FASEB J 2001; published abstract only.

Amundsen AL, Ose L, Nenseter MS, Ntanios FY. Plant sterol ester-enriched spread lowers plasma total and LDL cholesterol in children with familial hypercholesterolemia. Am J Clin Nutr 2002; 76(2): 338-344.

Geelen A, Zock PL, de Vries JHM, Katan MB. Apolipoprotein E polymorphism and serum lipid response to plant sterols in humans. Eur J Clin Invest 2002; 32(10): 738-742.

Judd JT, Baer DJ, Chen SC, Clevidence BA, Muesing RA, Kramer M, Meijer GW. Plant sterol esters lower plasma lipids and most carotenoids in mildly hypercholesterolemic adults. Lipids 2002; 37(1): 33-42.

Lottenberg AM, Nunes VS, Nakandakare ER, Neves M, Bernik M, dos Santos JE, Quintao EC. Food phytosterol ester efficiency on the plasma lipid reduction in moderate hypercholesterolemic subjects. Arq Bras Cardiol 2002; 79(2): 139-142.

Mussner MJ, Parhofer KG, Von Bergmann K, Schwandt P, Broedl U, Otto C. Effects of phytosterol ester-enriched margarine on plasma lipoproteins in mild to moderate hypercholesterolemia are related to basal cholesterol and fat intake. Metabolism 2002; 51(2): 189-194.

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(1): 79-86.

Ntanios FY, Homma Y, Ushiro S. A spread enriched with plant sterol-esters lowers blood cholesterol and lipoproteins without affecting vitamins A and E in normal and hypercholesterolemic Japanese men and women. J Nutr 2002; 132(12): 3650-3655.

Simons LA. Additive effect of plant sterol-ester margarine and cerivastatin in lowering low-density lipoprotein cholesterol in primary hypercholesterolemia. Am J Cardiol 2002; 90(7): 737-740.

Temme EHM, van Hoydonck PGA, Schouten EG, Kesteloot H. Effects of a plant sterol-enriched spread on serum lipids and lipoproteins in mildly hypercholesterolaemic subjects. Acta Cardiologica 2002; 57(2): 111-115.

Cleghorn CL, Skeaff CM, Mann J, Chisholm A. Plant sterol-enriched spread enhances the cholesterol-lowering potential of a fat-reduced diet. Eur J Clin Nutr 2003; 57(1): 170-176.

Jongh de S, Vissers MN, Rol P, Bakker HD, Kastelein JJP, Stroes ESG. Plant sterols lower LDL cholesterol without improving endothelial function in prepubertal children with familial hypercholesterolaemia. J Inh Metab Dis 2003; 26(4): 343-351.

Hendriks HFJ, Brink EJ, Meijer GW, Princen HMG, Ntanios FY. Safety of long-term consumption of plant sterol esters-enriched spread. Eur J Clin Nutr 2003; 57(5): 681-692.

Kozlowska-Wojciechowska M, Jastrzebska M, Naruszewicz M, Foltynska A. Impact of margarine enriched with plant sterols on blood lipids, platelet function, and fibrinogen level in young men. Metabolism 2003; 52(11): 1373-1378.

Kwiterovich PO, Chen SC, Virgil DG, Schweitzer A, Arnold DR, Kratz LE. Response of obligate heterozygotes for phytosterolemia to a low-fat diet and to a plant sterol ester dietary challenge. J Lipid Res 2003; 44(6): 1143-1155.

Lee YM, 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.

Lottenberg AM, Nunes VS, Nakandakare ER, Neves M, Bernik M, Lagrost L, dos Santos JE, Quintao EC. The human cholesteryl ester transfer protein I405V polymorphism is associated with plasma cholesterol concentration and its reduction by dietary phytosterol esters. J Nutr 2003; 133(6): 1800-1805.

Amundsen AL, Ntanios F, Put Nvd, Ose L. Long-term compliance and changes in plasma lipids, plant sterols and carotenoids in children and parents with FH consuming plant sterol ester-enriched spread. Eur J Clin Nutr 2004; 58(12): 1612-1620.

Colgan HA, Floyd S, Noone EJ, Gibney MJ, Roche HM. Increased intake of fruit and vegetables and a low-fat diet, with and without low-fat plant sterol-enriched spread consumption: effects on plasma lipoprotein and carotenoid metabolism. J Hum Nutr Diet 2004; 17(6): 561-569.

Vogt A, Thomas H, Schulze S, Steinhagen-Thiessen E, Kassner U. Effect of phytosterol ester-enriched margarine and diet compared to diet on plasma lipids in hypercholesterolemic subjects. Atherosclerosis Suppl 2004; published abstract only.

Jakulj L, Trip MD, Sudhop T, Von Bergmann K, Kastelein JJP, Vissers MN. Inhibition of cholesterol absorption by the combination of dietary plant sterols and ezetimibe: effects on plasma lipid levels. J Lip Res 2005; 46: 2692-2698.

Noakes M, Clifton PM, Doornbos AM, Trautwein EA. Plant sterol ester-enriched milk and yoghurt effectively reduce serum cholesterol in modestly hypercholesterolemic subjects. Eur J Nutr 2005; 44(4): 214-222.

Skeaff CM, Thoma C, Mann J, Chisholm A, Williams S, Richmond K. Isocaloric substitution of plant sterol-enriched fat spread for carbohydrate-rich foods in a low-fat, fibre-rich diet decreases plasma low-density lipoprotein cholesterol and increases high-density lipoprotein concentrations. Nutr Metab Cardiovasc Dis 2005; 15(5): 337-344.

AbuMweis SS, Vanstone CA, Ebine N, Kassis A, Ausman LM, Jones PJH, Lichtenstein AH. 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 2006; 136(4): 1012-1016.

Demonty I, Chan YM, Pelled D, Jones PJ. 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.

Doornbos AM, Meynen EM, Duchateau GS, van der Knaap HC, Trautwein EA. 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.

Chan YM, Demonty I, Pelled D, Jones PJ. Olive oil containing olive oil fatty acid esters of plant sterols and dietary diacylglycerol reduces low-density lipoprotein cholesterol and decreases the tendency for peroxidation in hypercholesterolaemic subjects. Br J Nutr 2007; 98(3): 563-570.

Demonty I, Haddeman E, van der Put N, Duchateau G, Steenbergen H, Diks R, Trautwein EA. Spreads fortified with a brassicasterol-rich phytosterol mixture from rapeseed oil lower total and LDL-cholesterol concentrations in mildly hypercholesterolemic subjects. FASEB J 2007; published abstract only.

Kratz M, Kannenberg F, Gramenz E, Berning B, Trautwein EA, Assmann G, Rust S. Similar serum plant sterol responses of human subjects heterozygous for a mutation causing sitosterolemia and controls to diets enriched in plant sterols or stanols. Eur J Clin Nutr 2007; 61(7): 896-905.

Li NY, Li K, Qi Z, Demonty I, Gordon M, Francis L, Molhuizen HO, Neal BC. Plant sterol-enriched milk tea decreases blood cholesterol concentrations in Chinese adults: a randomised controlled trial. Br J Nutr 2007; 98(5): 978-983.

Madsen MB, Jensen AM, Schmidt EB. The effect of a combination of plant sterol-enriched foods in mildly hypercholesterolemic subjects. Clin Nutr 2007; 26(6): 792-798.

Clifton PM, Mano M, Duchateau GS, van der Knaap HC, Trautwein EA. Dose-response effects of different plant sterol sources in fat spreads on serum lipids and C-reactive protein and on the kinetic behavior of serum plant sterols. Eur J Clin Nutr 2008; 62(8): 968-977.

Jong de A, Plat J, Lütjohann D, Mensink RP. 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.

Fuentes F, López-Miranda J, García A, Pérez-Martínez P, Moreno J, Cofan M, Caballero J, Panagua JA, Ros E, Pérez-Jiménez F. Basal plasma concentrations of plant sterols can predict LDL-C response to sitosterol in patients with familial hypercholesterolemia. Eur J Clin Nutr 2008; 60: 495-501.

Jenkins DJ, Kendall CW, Nguyen TH, Marchie A, Faulkner DA, Ireland C, Josse AR, Vidgen E, Trautwein EA, Lapsley KG, Holmes C, Josse RG, Leiter LA, Connelly PW, Singer W. Effect of plant sterols in combination with other cholesterol-lowering foods. Metab Clin Exp 2008; 57(1): 130-139.

AbuMweis SS, Vanstone CA, Lichtenstein AH, Jones PJ. Plant sterol consumption frequency affects plasma lipid levels and cholesterol kinetics in humans. Eur J Clin Nutr 2009; 63(6): 747-755.

Chen SC, Judd JT, Kramer M, Meijer GW, Clevidence BA, Baer DJ. Phytosterol intake and dietary fat reduction are independent and additive in their ability to reduce plasma LDL cholesterol. Lipids; 2009; 44(3): 273-281.

Houweling AH, Vanstone CA, Trautwein EA, Duchateau GS, Jones PJ. Baseline plasma plant sterol concentrations do not predict changes in serum lipids, C-reactive protein (CRP) and plasma plant sterols following intake of a plant sterol-enriched food. Eur J Clin Nutr 2009; 63(4): 543-551.

Khandelwal S, Demonty I, Jeemon P, Lakshmy R, Mukherjee R, Gupta R, Snehi U, Niveditha D, Singh Y, van der Knaap HC, Passi SJ, Prabhakaran D, Reddy KS. 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.

Bañuls C, Martínez-Triguero ML, López-Ruiz A, Morillas C, Lacomba R, Víctor VM, Rocha M, Hernández-Mijares A. Evaluation of cardiovascular risk and oxidative stress parameters in hypercholesterolemic subjects on a standard healthy diet including low-fat milk enriched with plant sterols. J Nutr Biochem 2010; 21(9): 881-886.

Gagliardi AC, Maranhão RC, de Sousa HP, Schaefer EJ and Santos RD. Effects of margarines and butter consumption on lipid profiles, inflammation markers and lipid transfer to HDL particles in free-living subjects with the metabolic syndrome Eur J Clin Nutr 2010; 64(10): 1141-1149.

Hernández-Mijares A, Bañuls C, Rocha M, Morillas C, Martínez-Triguero ML, Víctor VM, Lacomba R, Alegría A, Barberá R, Farré R and Lagarda MJ. Effects of phytosterol ester-enriched low-fat milk on serum lipoprotein profile in mildly hypercholsterolaemic patients are not related to dietary cholesterol or saturated fat intake. Br J Nutr 2010; 104(7): 1018-1025.

Bañuls C, Martínez-Triguero ML, Lopez-Ruiz A, Morillas C, Jarabo MM, Bellod L, Víctor VM, Rocha M, Hernández-Mijares A. Serum lipid responses to phytosterol-enriched milk in a moderate hypercholesterolemic population is not affected by apolipoprotein E polymorphism or diameter of low-density lipoprotein particles. Eur J Clin Nutr 2011; 65(2): 255-261.

Eady S, Wallace A, Willis J, Scott R, Frampton C. Consumption of a plant sterol-based spread derived from rice bran oil is effective at reducing plasma lipid levels in mildly hypercholesterolaemic individuals. Br J Nutr 2011; 105(12): 1808-1818.

Hernández-Mijares A, Bañuls C, Jover A, Sola E, Bellod L, Martínez-Triguero ML, Lagarda MJ, Víctor VM, 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.

Casas-Agustench P, Serra M, Pérez-Heras A, Cofán M, Pintó X, Trautwein EA, 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.

Sialvera TE, Pounis GD, Koutelidakis AE, Richter DJ, 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.

Turpeinen AM, Ikonen M, Kivimaki AS, Kautianen H, Vapaatalo H, Korpela R. A spread containing bioactive milk peptides Ile-Pro-Pro and Val-Pro-Pro, and plant sterols has antihypertensive and cholesterol-lowering effects. Food Funct 2012; 3(6): 621-627.

Khandelwal S, Shidhaye R, Demonty I, Lakshmy R, Gupta R, Prabhakaran D, Reddy S. Impact of omega-3 fatty acids and/or plant sterol supplementation on non-HDL cholesterol levels of dyslipidemic Indian adults. J Functional Foods 2013; 5: 36-43.

Ras RT, Demonty I, Zebregs YEMP, Quadt JFA, Olsson J, Trautwein EA. Low doses of eicosapentaenoic acid and docosahexaenoic acid from fish oil dose-dependently decrease serum triglyceride concentrations in the presence of plant sterols in hypercholesterolemic men and women. J Nutr 2014; 144(10): 1564-1570.

Ras RT, Fuchs D, Koppenol WP, Garczarek U, Greyling A, Keicher C, Verhoeven C, Bouzamondo H, Wagner F, Trautwein EA. The effect of a low-fat spread with added plant sterols on vascular function markers: results of the Investigating Vascular Function Effects of Plant Sterols (INVEST) study. Am J Clin Nutr 2015; 101(4): 733-741.

Jacobs DM, Mihaleva VV, van Schalkwijk DB, de Graaf AA, Vervoort J, van Dorsten FA, Ras RT, Demonty I, Trautwein EA, 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; doi: 10.1002/mnfr.201500152.

Studies investigating the cholesterol-lowering efficacy of plant sterols as part of a dietary approach

Jenkins DJ, Kendall CW, Faulkner D, Vidgen E, Trautwein EA, Parker TL, Marchie A, Koumbridis G, Lapsley KG, Josse RG, Leiter LA, Connelly PW. 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.

Jenkins DJ, Kendall CW, Marchie A, Faulkner DA, Wong JM, de Souza R, Emam A, Parker TL, Vidgen E, Lapsley KG, Trautwein EA, Josse RG, Leiter LA, Connelly PW. Effects of a dietary portfolio of cholesterol-lowering foods vs lovastatin on serum lipids and C-reactive protein. JAMA 2003; 290(4): 502-510.

Jenkins DJ, Kendall CW, Marchie A, Faulkner DA, Vidgen E, Lapsley KG, Trautwein EA, Parker TL, Josse RG, Leiter LA, Connelly PW. The effect of combining plant sterols, soy protein, viscous fibers, and almonds in treating hypercholesterolemia. Metabolism 2003; 52(11): 1478-1483.

Lamarche B, Desroches S, Jenkins DJ, Kendall CW, Marchie A, Faulkner D, Vidgen E, Lapsley KG, Trautwein EA, Parker TL, Josse RG, Leiter LA, Connelly PW. Combined effects of a dietary portfolio of plant sterols, vegetable protein, viscous fibre and almonds on LDL particle size. Br J Nutr 2004; 92(4): 657-663.

Jenkins DJ, Kendall CW, Marchie A, Faulkner DA, Wong JM, de Souza R, Emam A, Parker TL, Vidgen E, Trautwein EA, Lapsley KG, Josse RG, Leiter LA, Singer W, Connelly PW. 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.

Jones PJ, Raeini-Sarjaz M, Jenkins DJ, Kendall CW, Vidgen E, Trautwein EA, Lapsley KG, Marchie A, Cunnane SC, Connelly PW. Effects of a diet high in plant sterols, vegetable proteins, and viscous fibers (dietary portfolio) on circulating sterol levels and red cell fragility in hypercholesterolemic subjects. Lipids 2005; 40(2): 169-174.

Jenkins DJ, Kendall CW, Faulkner DA, Nguyen T, Kemp T, Marchie A, Wong JM, de Souza R, Emam A, Vidgen E, Trautwein EA, Lapsley KG, Holmes C, Josse RG, Leiter LA, Connelly PW, Singer W. Assessment of the longer-term effects of a dietary portfolio of cholesterol-lowering foods in hypercholesterolemia. Am J Clin Nutr 2006; 83(3): 582-591.

Gigleux I, Jenkins DJ, Kendall CW, Marchie A, Faulkner DA, Wong JM, de Souza R, Emam A, Parker TL, Trautwein EA, Lapsley KG, Connelly PW, Lamarche B. Comparison of a dietary portfolio diet of cholesterol-lowering foods and a statin on LDL particle size phenotype in hypercholesterolaemic participants. Br J Nutr 2007; 98(6): 1229-1236.

Jenkins DJ, Kendall CW, Nguyen TH, Teitel J, Marchie A, Chiu M, Taha AY, Faulkner DA, Kemp T, Wong JM, de Souza R, Emam A, Trautwein EA, Lapsley KG, Holmes C, Josse RG, Leiter LA. Effect on hematologic risk factors for coronary heart disease of a cholesterol reducing diet. Eur J Clin Nutr 2007; 61(4): 483-492.

Jenkins DJ, Kendall CW, Faulkner DA, Kemp T, Marchie A, Nguyen TH, Wong JM, de Souza R, Emam A, Vidgen E, Trautwein EA, Lapsley KG, Josse RG, Leiter LA, Singer W. Long-term effects of a plant-based dietary portfolio of cholesterol-lowering foods on blood pressure. Eur J Clin Nutr 2008; 62(6): 781-788.

Jenkins DAJ, Peter JH, Jones PJH, Benoit Lamarche B, Kendall CWC, Faulker D, et al. Effect of a dietary portfolio of cholesterol-lowering foods given at 2 levels of intensity of dietary advice on serum lipids in hyperlipidemia. A randomized controlled trial. JAMA 2011; 306(8): 831-839

Ramprasath VR, Jenkins DJ, Lamarchem B, Kendall CW, Faulkner D, Cermakova L, Couture P, Ireland C, Abdulnour S, Patel D, Bashyamm B, Srichaikul K, de Souza RJ, Vidgen E, Josse RG, Leiter LA, Connelly PW, Frohlich J, Jones PJ. Consumption of a dietary portfolio of cholesterol lowering foods improves blood lipids without affecting concentrations of fat soluble compounds. Nutr J 2014; 13(1): 101.

Studies investigating efficacy of plant sterols beyond cholesterol-lowering

Jones PJ, Demonty I, Chan YM, Herzog Y, Pelled D. Fish-oil esters of plant sterols differ from vegetable-oil sterol esters in triglycerides lowering, carotenoid bioavailability and impact on plasminogen activator inhibitor-1 (PAI-1) concentrations in hypercholesterolemic subjects. Lipids Health Dis 2007; 6(1): 28-37.

Berendschot TTJM, Plat J, Jong A de, Mensink RP. Long-term plant stanol and sterol ester-enriched functional food consumption, serum lutein/zeaxanthin concentration and macular pigment optical density. Br J Nutr 2009; 101: 1607-1610.

Kelly ER, Plat J, Mensink RP, Berendschot TT. 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.

Sialvera TE, Koutelidakis AE, Richter DJ, Yfanti G, Kapsokefalou M, Micha R, Goumas G, Diamantopoulos E, Zampelas A. Phytosterol supplementation does not affect plasma antioxidant capacity in patients with metabolic syndrome. Int J Food Sci Nutr 2013; 64(1): 21-27.

Ras RT, van der Schouw YT, Trautwein EA, Sioen I, Dalmeijer GW, Zock PL, Beulens JW. Intake of phytosterols from natural sources and risk of cardiovascular disease in the European Prospective Investigation into Cancer and Nutrition-the Netherlands (EPIC-NL) population. Eur J Prev Cardiol 2014; doi:10.1177/2047487314554864.

Plant sterol safety studies

Baker VA, Hepburn PA, Kennedy SJ, Jones PA, Lea LJ, Sumpter JP, 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(1): 13-22.

Hepburn PA, Horner SA, Smith M. Safety evaluation of phytosterol esters. Part 2. Subchronic 90-day oral toxicity study on phytosterol esters-a novel functional food. Food Chem Toxicol 1999; 37(5): 521-532.

Waalkens-Berendsen DH, Wolterbeek APM, Wijnands MVW, Richold M, Hepburn PA. 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(7): 683-696.

Weststrate JA, Ayesh R, Bauer-Plank C, Drewitt PN. Safety evaluation of phytosterol esters. Part 4. Faecal concentrations of bile acids and neutral sterols in healthy normolipidaemic volunteers consuming a controlled diet either with or without a phytosterol ester-enriched margarine. Food Chem Toxicol 1999; 37(11): 1063-1071.

Ayesh R, Weststrate JA, Drewitt PN, Hepburn PA. Safety evaluation of phytosterol esters. Part 5. Faecal short-chain fatty acid and microflora content, faecal bacterial enzyme activity and serum female sex hormones in healthy normolipidaemic volunteers consuming a controlled diet either with or without a phytosterol ester-enriched margarine. Food Chem Toxicol 1999; 37(12): 1127-1138.

Sanders DJ, Minter HJ, Howes D, Hepburn PA. The safety evaluation of phytosterol esters. Part 6. The comparative absorption and tissue distribution of phytosterols in the rat. Food Chem Toxicol 2000; 38(6): 485-491.

Raeini-Sarjaz M, Ntanios FY, Vanstone CA, Jones PJ. No changes in serum fat-soluble vitamin and carotenoid concentrations with the intake of plant sterol/stanol esters in the context of a controlled diet. Metabolism 2002; 51(5): 652-656.

Wolfreys AM, Hepburn PA. Safety evaluation of phytosterol esters. Part 7. Assessment of mutagenic activity of phytosterols, phytosterol esters and the cholesterol derivative, 4-cholesten-3-one. Food Chem Toxicol 2002; 40(4): 461-470.

Lea LJ, Hepburn PA, Wolfreys AM, Baldrick P. Safety evaluation of phytosterol esters. Part 8. Lack of genotoxicity and subchronic toxicity with phytosterol oxides. Food Chem Toxicol 2004; 42(5): 771-783.

Lea LJ, Hepburn PA. Safety evaluation of phytosterol-esters. Part 9: Results of a European post-launch monitoring programme. Food Chem Toxicol 2006; 44(8): 1213-1222.

Willems JI, Blommaert MA, Trautwein EA. Results from a post-launch monitoring survey on consumer purchases of foods with added phytosterols in five European countries. Food Chem Toxicol 2013; 62: 48-53.

Plant sterol mechanism-of-action studies

Trautwein EA, Schulz C, Rieckhoff D, Kunath-Rau A, Erbersdobler HF, de Groot WA, Meijer GW. Effect of esterified 4-desmethylsterols and -stanols or 4,4 '-dimethylsterols on cholesterol and bile acid metabolism in hamsters. Br J Nutr 2002; 87(3): 227-237.

Meijer GW, Bressers MAJJ, de Groot WA, Rudrum M. Effect of structure and form on the ability of plant sterols to inhibit cholesterol absorption in hamsters. Lipids 2003; 38(7): 713-721.

Ntanios FY, van de Kooij AJ, de Deckere EAM, Duchateau GSMJ, Trautwein EA. 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 2003; 169(1): 41-50.

Lin YG, Meijer GW, Vermeer MA, Trautwein EA. Soy protein enhances the cholesterol-lowering effect of plant sterol esters in cholesterol-fed hamsters. J Nutr 2004; 134(1): 143-148.

Mel'nikov SM, ten Hoorn JWMS, Eijkelenboom APAM. Effect of phytosterols and phytostanols on the solubilization of cholesterol by dietary mixed micelles: an in vitro study. Chemistry and Physics of Lipids 2004; 127(2): 121-141.

Mel'nikov SM, ten Hoorn JWMS, Bertrand B. Can cholesterol absorption be reduced by phytosterols and phytostanols via a cocrystallization mechanism? Chemistry and Physics of Lipids 2004; 127(1): 15-33.

Normén L, Ellegard L, Janssen HG, Steenbergen H, Trautwein E, Andersson H. Phytosterol and phytostanol esters are effectively hydrolysed in the gut and do not affect fat digestion in ileostomy subjects. Eur J Nutr 2006; 45(3): 165-170.

Plosch T, Kruit JK, Bloks VW, Huijkman NCA, Havinga R, Duchateau GSMJ, Lin YG, Kuipers F. Reduction of cholesterol absorption by dietary plant sterols and stanols in mice is independent of the ABCG5/8 transporter. J Nutr 2006; 136(8): 2135-2140.

Hovenkamp E, Lourbakos A, Duchateau GS, Tareilus EW, Trautwein EA. Preferential efflux of phytosterols over cholesterol from macrophages. Lipids 2007; 42(12): 1125-1132.

Zhao HL, Houweling AH, Vanstone CA, Jew S, Trautwein EA, Duchateau GS, Jones PJ. Genetic variation in ABC G5/G8 and NPC1L1 impact cholesterol response to plant sterols in hypercholesterolemic men. Lipids 2008; 43(12); 1155-1164.

Amiot MJ, Knol D, Cardinault N, Nowicki M, Bott R, Antona C, Borel P, Bernard JP, Duchateau G, Lairon D. Phytosterol ester processing in the small intestine: impact on cholesterol availability for absorption and chylomicron cholesterol incorporation in healthy humans. J Lipid Res 2011; 52(6): 1256-1264.

Brufau G, Kuipers F, Lin Y, Trautwein EA, Groen AK. A reappraisal of the mechanism by which plant sterols promote neutral sterol loss in mice. Plos One 2011; 6(6): e21576.

Zhao HL, Houweling AH, Vanstone CA, Jew S, Trautwein EA, Duchateau GS, Jones PJ. Action of plant sterol intervention on sterol kinetics in hypercholesterolemic men with high versus low basal circulatory plant sterol concentrations. J Am Coll Nutr 2011; 30(2): 155-165.

Szymanska E, van Dorsten FA, Troost J, Paliukhovich I, van Velzen EJ, Hendriks MM, Trautwein EA, van Duynhoven JP, Vreeken RJ, Smilde AK. A lipidomic analysis approach to evaluate the response to cholesterol-lowering food intake. Metabolomics 2012; 8(5): 894-906.

Amiot MJ, Knol D, Cardinault N, Nowicki M, Bott R, Antona C, Borel P, Bernard JP, Duchateau G, Lairon D. Comparable reduction in cholesterol absorption after two different ways of phytosterol administration in humans. Eur J Nutr 2013; 52(3): 1215-1222.

Keszthelyi D, Knol D, Troost FJ, van Avezaat M, Foltz M, Masclee AA. Time of ingestion relative to meal intake determines gastrointestinal responses to a plant sterol-containing yoghurt drink. Eur J Nutr 2013; 52(4): 1417-1420.

Plant sterol meta-analyses

Law M. Plant sterol and stanol margarines and health. BMJ 2000; 320(7238): 861-864.

Katan MB, Grundy SM, Jones P, Law M, Miettinen T, Paoletti R. Efficacy and safety of plant stanols and sterols in the management of blood cholesterol levels. Mayo Clin Proc 2003; 78(8): 965-978.

Castro IA, Barroso LP, Sinnecker P. Functional foods for coronary heart disease risk reduction: a meta-analysis using a multivariate approach. Am J Clin Nutr 2005: 82(1): 32-40.

Chen JT, Wesley R, Shamburek RD, Pucino F, Csako G. Meta-analysis of natural therapies for hyperlipidemia: plant sterols and stanols versus policosanol. Pharmacotherapy 2005; 25(2): 171-183.

Moruisi KG, Oosthuizen W, Opperman AM. Phytosterols/stanols lower cholesterol concentrations in familial hypercholesterolemic subjects: a systematic review with meta-analysis. J Am Coll Nutr 2006; 25(1): 41-48.

AbuMweis SS, Barake R, Jones PJH. Plant sterols/stanols as cholesterol lowering agents: A meta-analysis of randomized controlled trials. Food Nutr Res 2008; 52: doi:10.3402/fnrv52i0.1811.

Baker WL, Baker EL, Coleman CI. 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-d37.

Demonty I, Ras RT, van der Knaap HC, Duchateau GS, Meijer L, Zock PL, Geleijnse JM, Trautwein EA. Continuous dose-response relationship of the LDL-cholesterol-lowering effect of phytosterol intake. J Nutr 2009; 139(2): 271-284.

Scholle JM, Baker WL, Talati R, Coleman CI. 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.

Wu T, Fu J, Yang Y, Zhang L, Han J. The effects of phytosterols/stanols on blood lipid profiles: a systematic review with meta-analysis. Asia Pac J Clin Nutr 2009; 18(2): 179-186.

Shafiq N, Singh M, Kaur S, Khosla P, Malhotra S. Dietary treatment for familial hypercholesterolaemia. Cochrane Database Syst Rev 2010: 20(1): CD001918.

Talati R, Sobieraj DM, Makanji SS, Phung OJ, Coleman CI. The comparative efficacy of plant sterols and stanols on serum lipids: a systematic review and meta-analysis. J Am Diet Assoc 2010; 110(5): 719-726.

Musa-Veloso K, Poon TH, Elliot JA, Chung C. A comparison of the LDL-cholesterol lowering efficacy of plant stanols and plant sterols over a continuous dose range: Results of a meta-analysis of randomized, placebo-controlled trials. Prostaglandins Leukot Essent Fatty Acids 2011; 85(1): 9-28.

Demonty I, Ras RT, van der Knaap HC, Meijer L, Zock PL, Geleijnse JM, Trautwein EA. 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.

Ras RT, Hiemstra H, Lin Y, Vermeer MA, Duchateau GS, Trautwein EA. 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.

Malhotra A, Shafiq N, Arora A, Singh M, Kumar R, Malhotra S. Dietary interventions (plant sterols, stanols, omega-3 fatty acids, soy protein and dietary fibers) for familial hypercholesterolaemia. Cochrane Database Syst Rev 2014; 6.

Ras RT, Geleijnse JM, Trautwein EA. 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.

Plant sterol reviews

Meijer GW. Blood-cholesterol lowering plant sterols: types, doses and forms. Lipid Technol 1999; 11: 129-132.

Ntanios FY, Meijer GW, Hepburn P. Comments on the Review by Nguyen et al. 1999. J Nutr 2000; 130(9): 2390.

Ntanios F. Plant sterol-ester-enriched spreads as an example of a new functional food. Eur J Lipid Sci Technol 2001; 103(2): 102-106.

Ntanios FY, Duchateau GSMJ. A healthy diet rich in carotenoids is effective in maintaining normal blood carotenoid levels during the daily use of plant sterol-enriched spreads. Int J Vitam Nutrition Res 2002; 72(1): 32-39.

Trautwein EA, Duchateau GSMJ, Lin YG, Mel'nikov SM, Molhuizen HOF, Ntanios FY. Proposed mechanisms of cholesterol-lowering action of plant sterols. Eur J Lipid Sci Technol 2003; 105(3-4): 171-185.

Chan YM, Varady KA, Lin YG, Trautwein EA, Mensink RP, Plat J, Jones PJH. Plasma concentrations of plant sterols: Physiology and relationship with coronary heart disease. Nutr Rev 2006; 64(9): 385-402.

Gerber A, Evers T, Haverkamp H, Lauterbach KW. Cost-benefit analysis of a plant sterol containing low-fat margarine for cholesterol reduction. Eur J Health Econ 2006; 7(4): 247-254.

Hovenkamp E, Demonty I, Plat J, Lutjohann D, Mensink RP, Trautwein EA. Biological effects of oxidized phytosterols: a review of the current knowledge. Prog Lipid Res 2008; 47(1): 37-49.

Trautwein EA, Demonty I. Phytosterols: natural compounds with established and emerging health benefits. OCE 2008; 14: 259-266.

Trautwein EA, Demonty I, Ras RT. Plant sterols - A dietary approach for effective blood lipid lowering as part of a heart healthy diet. Curr Topics Nutraceutical Res 2010; 8(4): 137-148.

Plat J, Mackay D, Baumgartner S, Clifton PM, Gylling H, Jones PJ. Progress and prospective of plant sterol and plant stanol research: report of the Maastricht meeting. Atheroscelosis 2012; 225(2): 521-533.

Gylling H, Plat J, Turley S, Ginsberg HN, Ellegard L, Jessup W, Jones PJ, Lutjohann D, Maerz W, Masana L, Silbernagel G, Staels B, Boren J, Catapano AL, de Backer G, Deanfield J, Descamps OS, Kovanen PT, Riccardi G, Tokgozoglu L, Chapman MJ. Plant sterols and plant stanols in the management of dyslipidaemia and prevention of cardiovascular disease. Atherosclerosis 2014; 232(2): 346-360.

Silbernagel G, Baumgartner I, Wanner C, Marz W. Toward individualized cholesterol-lowering treatment in end-stage renal disease. J Ren Nutr 2014; 24(2): 65-71.

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