Continuous dose-response relationship of the LDL-cholesterol-lowering effect of phytosterol intake

Journal of Nutrition

Volumn 139, Issue 2, 2009, Pages 271-284

  Demonty, Isabelle ^a   Ras, Rouyanne T ^b   Van Der Knaap, Henk C M ^a   Duchateau, Guus S M J E ^a   Meijer, Linsie ^b   Zock, Peter L ^a   Geleijnse, Johanna M ^b   Trautwein, Elke A ^a  

^a UNILEVER RESEARCH VLAARDINGEN   (Netherlands)

^b WAGENINGEN UNIVERSITY   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

CHOLESTEROL; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; LOW DENSITY LIPOPROTEIN CHOLESTEROL; PHYTOSTEROL;

ARTICLE; CHOLESTEROL BLOOD LEVEL; CLINICAL TRIAL; DAIRY PRODUCT; FOOD COMPOSITION; FOOD INTAKE; HUMAN; META ANALYSIS; SYSTEMATIC REVIEW; ADULT; BLOOD; DOSE RESPONSE; REVIEW;

ADULT; CHOLESTEROL, LDL; DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS; PHYTOSTEROLS;

EID: 60249092628     PISSN: 00223166     EISSN: 15416100     Source Type: Journal    
DOI: 10.3945/jn.108.095125     Document Type: Article

References (114)

1. Pollak OJ. Reduction of blood cholesterol in man. Circulation. 1953; 7:702-6.
2. Law M. Plant sterol and stanol margarines and health. BMJ. 2000; 320:861-4.
3. 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;78:965-78.
4. National Cholesterol Education Program (NCEP) Expert Panel (Adult Treatment Panel III). 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. 2002;106:3143-421.
5. International Atherosclerosis Society. International Atherosclerosis Society harmonised clinical guidelines on prevention of atherosclerotic vascular disease. Full report [monograph on the Internet]. 2003 [cited 2003 Apr 30]. Available from: http://www.athero.org/guidelines.asp.
6. Lichtenstein AH, Appel LJ, Brands M, Carnethon M, Daniels S, Franch HA, Franklin B, Kris-Etherton P, Harris WS, et al. Summary of American Heart Association Diet and Lifestyle Recommendations revision 2006. Arterioscler Thromb Vase Biol. 2006;26:2186-91.
7. Poli A, Marangoni F, Paoletti R, Mannarino E, Lupattelli G, Notarbartolo A, Aureli P, Bernini F, Cicero A, et al. Non-pharmacological control of plasma cholesterol levels. Nutr Metab Cardiovasc Dis. 2008;18:Sl-16.
8. Trautwein EA, Duchateau GS, Lin YG, Mel'nikov SM, Molhuizen HOF, Ntanios FY. Proposed mechanisms of cholesterol-lowering action of plant sterols. Eur J Lipid Sci Technol. 2003;105:171-85.
9. Normén L, Frohlich JJ, Trautwein EA. Role of plant sterols in cholesterol lowering. In: Dutta PC, editor. Plant sterols: analytical, nutritional, and safety aspects as functional food. New York: Marcel Dekker; 2004:243-315.
10. Clifton PM, Noakes M, Sullivan D, Erichsen N, Ross D, Annison G, Fassoulakis A, Cehun M, Nestel P. Cholesterol-lowering effects of plant sterol esters differ in milk, yoghurt, bread and cereal. Eur J Clin Nutr. 2004;58:503-9.
11. 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;44:214-22.
12. Thomsen AB, Hansen HB, Christiansen C, Green H, Berger A. Effect of free plant sterols in low-fat milk on serum lipid profile in hypercholesterolemic subjects. Eur J Clin Nutr. 2004;58:860-70.
13. Hyun YJ, Kim OY, Kang JB, Lee JH, Jang Y, Liponkoski L, Salo P. Plant stanol esters in low-fat yoghurt reduces total and low-density lipoprotein cholesterol and low-density lipoprotein oxidation in normocholester-olemic and mildly hypercholesterolemic subjects. Nutr Res. 2005; 25:743-53.
14. Korpela R, Tuomilehto J, Hogstrom P, Seppo L, Piironen V, Salo-Vaananen P, Toivo J, Lamberg-Allardt C, Karkkainen M, et al. Safety aspects and cholesterol-lowering efficacy of low fat dairy products containing plant sterols. Eur J Clin Nutr. 2006;60:633-42.
15. Mensink RP, Ebbing S, Lindhout M, Plat J, van Heugten MM. Effects of plant stanol esters supplied in low-fat yoghurt on serum lipids and lipoproteins, non-cholesterol sterols and fat soluble antioxidant concentrations. Atherosclerosis. 2002;160:205-13.
16. Seppo L, Jauhiainen T, Nevala R, Poussa T, Korpela R. Plant stanol esters in low-fat milk products lower serum total and LDL cholesterol. EurJ Nutr. 2007;46:111-7.
17. Devaraj S, Jialal I, Vega-Lopez S. Plant sterol-fortified orange juice effectively lowers cholesterol levels in mildly hypercholesterolemic healthy individuals. Arterioscler Thromb Vase Biol. 2004;24:e25-8.
18. Devaraj S, Autret BC, Jialal I. Reduced-calorie orange juice beverage with plant sterols lowers C-reactive protein concentrations and improves the lipid profile in human volunteers. Am J Clin Nutr. 2006;84:756-61.
19. Hironaka T, Shroya N, Matsubara H, Matsuoka Y, Itakura H. Double-blind, placebo-controlled study of effects of plant sterol enriched vegetable juice on serum cholesterol concentrations in mildly hypercholesterolemic subjects and safety evaluation. J Oleo Sci. 2006;55: 593-606.
20. 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 hyper-cholesterolaemic subjects. Eur J Clin Nutr. 2006;60:325-33.
21. Algorta Pineda J, Chinchetru Ranedo MJ, Aguirre Anda J, Francisco Terreros S. Hypocholesteremic effectiveness of a yogurt containing plant stanol esters. Rev Clin Esp. 2005;205:63-6.
22. Salo P, Wester I. Low-fat formulations of plant stanols and sterols. Am J Cardiol. 2005;96:D51-4.
23. Plana N, Nicolle C, Ferre R, Camps J, Cos R, Villoria J, Masana L. Plant sterol-enriched fermented milk enhances the attainment of LDL-cholesterol goal in hypercholesterolemic subjects. Eur J Nutr. 2008; 47:32-9.
24. Hansel B, Nicolle C, Lalanne F, Tondu F, Lassel T, Donazzolo Y, Ferrieres J, Krempf M, Schlienger JL, et al. Effect of low-fat, fermented milk enriched with plant sterols on serum lipid profile and oxidative stress in moderate hypercholesterolemia. Am J Clin Nutr. 2007;86:790-6.
25. Thurnhofer H, Hauser H. Uptake of cholesterol by small intestinal brush border membrane is protein-mediated. Biochemistry. 1990;29:2142-8.
26. Lewington S, Whitlock G, Clarke R, Sherliker P, Emberson J, Halsey J, Qizilbash N, Peto R, Collins R. Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths. Lancet. 2007;370: 1829-39.
27. Neil HA, Meijer GW, Roe LS. Randomised controlled trial of use by hypercholesterolaemic patients of a vegetable oil sterol-enriched fat spread. Atherosclerosis. 2001;156:329-37.
28. Simons LA. Additive effect of plant sterol-ester margarine and cerivastatin in lowering low-density lipoprotein cholesterol in primary hypercholesterolemia. Am J Cardiol. 2002;90:737-40.
29. Jones PJ, Ntanios FY, Raeini-Sarjaz M, Vanstone CA. Cholesterol-lowering efficacy of a sitostanol-containing phytosterol mixture with a prudent diet in hyperlipidemic men. Am J Clin Nutr. 1999;69:1144-50.
30. 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;41:697-705.
31. Hallikainen MA, Uusitupa MI. Effects of 2 low-fat stanol ester-containing margarines on serum cholesterol concentrations as part of a low-fat diet in hypercholesterolemic subjects. Am J Clin Nutr. 1999;69: 403-10.
32. 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;57:170-6.
33. Harris WS. n-3 fatty acids and serum lipoproteins: human studies. Am J Clin Nutr. 1997;65:S1645-54.
34. Balk EM, Lichtenstein AH, Chung M, Kupelnick B, Chew P, Lau J. Effects of omega-3 fatty acids on serum markers of cardiovascular disease risk: a systematic review. Atherosclerosis. 2006;189:19-30.
35. Robinson JG, Stone NJ. Antiatherosclerotic and antithrombotic effects of omega-3 fatty acids. Am J Cardiol. 2006;98:i39-49.
36. Sierksma A, Weststrate JA, Meijer GW. Spreads enriched with plant sterols, either esterified 4,4-dimethylsterols or free 4-desmethylsterols, and plasma total- and LDL-cholesterol concentrations. Br J Nutr. 1999;82:273-82.
37. Vissers MN, Zock PL, Meijer GW, Katan MB. Effect of plant sterols from rice bran oil and triterpene alcohols from sheanut oil on serum lipoprotein concentrations in humans. Am J Clin Nutr. 2000;72:1510-5.
38. Verhagen AP, de Vet HC, de Bie RA, Kessels AG, Boers M, Bouter LM, Knipschild PG. The Delphi list: a criteria list for quality assessment of randomized clinical trials for conducting systematic reviews developed by Delphi consensus. J Clin Epidemiol. 1998;51:1235-41.
39. Chalmers TC, Smith H Jr, Blackburn B, Silverman B, Schroeder B, Reitman D, Ambroz A. A method for assessing the quality of a randomized control trial. Control Clin Trials. 1981;2:31-49.
40. Khan KS, ter Riet G, Popay J, Nixon J, Kleijnen J. Study quality assessment. In: Khan KS, ter Riet G, Glanville J, Sowden AJ, Kleijnen J, editors. Undertaking systematic reviews of research on effectiveness: CRD's guidance for carrying out or commissioning reviews. CRD Report 4. York: University of York; 2001.
41. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177-88.
42. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539-58.
43. Egger M, Davey SG, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629-34.
44. Vandeginste BGM, Massart DL, Buydens LMC, De Jong S, Lewi PJ, Smeyers-Verbeke J. Part B. Handbook of chemometrics and quali-metrics. Amsterdam: Elsevier; 1998.
45. Matsuoka R, Masuda Y, Takeuchi A, Marushima R, Hasegawa M, Sakamoto A, Hirata H, Kajimoto OA. Double-blind, placebo-controlled study on the effects of mayonnaise containing free plant sterol on serum cholesterol concentration; safety evaluation for normocholester-olemic and mildly hypercholesterolemic Japanese subjects. J Oleo Sci. 2004;53:79-88.
46. Naumann E, Plat J, Kester ADM, Mensink RP. The baseline serum lipoprotein profile is related to plant stanol induced changes in serum lipoprotein cholesterol and triacylglycerol concentrations. J Am Coll Nutr. 2008;27:117-26.
47. Richelle M, Enslen M, Hager C, Groux M, Tavazzi I, Godin JP, Berger A, Metairon S, Quaile S, et al. Both free and esterified plant sterols reduce cholesterol absorption and the bioavailability of beta-carotene and alpha-tocopherol in normocholesterolemic humans. Am J Clin Nutr. 2004;80:171-7.
48. Mattson FH, Grundy SM, Crouse JR. Optimizing the effect of plant sterols on cholesterol absorption in man. Am J Clin Nutr. 1982;35:697-700.
49. 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;52:334-43.
50. Hallikainen MA, Sarkkinen ES, Gylling H, Erkkila AT, Uusitupa MI. 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;54:715-25.
51. Noakes M, Clifton P, Ntanios F, Shrapnel W, Record I, Mclnerney 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.
52. De Jong A, Plat J, Lutjohann D, Mensink RP. Effects of long-term plant sterol or stanol ester consumption on lip id and lipoprotein metabolism in subjects on statin treatment. Br J Nutr. 2008;100:937-77.
53. Plat J, van Onselen EN, van Heugten MM, Mensink RP. 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;54:671-7.
54. Kassis AN, Vanstone CA, AbuMweis SS, Jones PJ. Efficacy of plant sterols is not influenced by dietary cholesterol intake in hypercholes-terolemic individuals. Metabolism. 2008;57:339-46.
55. Alhassan S, Reese KA, Mahurin J, Plaisance EP, Hilson BD, Garner JC, Wee SO, Grandjean PW. Blood lipid responses to plant stanol ester supplementation and aerobic exercise training. Metabolism. 2006;55: 541-9.
56. Andersson SW, Skinner J, Ellegard L, Welch AA, Bingham S, Mulligan A, Andersson H, Khaw KT. 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;58:1378-85.
57. 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;37:1127-38.
58. Beer MU, Pritchard H, Belsey EM, Davidson M. Effect of a milk drink enriched with increasing doses of free tall oil phytosterols on plasma lipid levels of mildly hypercholesteroleamic subjects. Document submitted by Altus Foods to FDA concerning the interim final rule for Vegetable oil sterol esters and coronary heart disease (Docket Nos. 00P-1275 and 00P-1276).
59. Blomqvist SM, Jauhiainen M, Vantol A, Hyvonen M, Torstila I, Vanhanen HT, Miettinen TA, Ehnholm C. Effect of sitostanol ester on composition and size distribution of low-density and high-density-lipoprotein. Nutr Metab Cardiovasc Dis. 1993;3:158-64.
60. 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;62:968-77.
61. Davidson MH, Maki KC, Umporowicz DM, Ingram KA, Dicklin MR, Schaefer E, Lane RW, McNamara JR, Ribaya Mercado JD, et al. 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;20:307-19.
62. De Graaf J, de Sauvage-Nolting PRW, van Dam M, Belsey EM, Kastelein JJP, Pritchard PH. Consumption of tall oil-derived phytosterols in a chocolate matrix significantly decrease plasma total and low-density lipoprotein cholesterol levels. Br J Nutr. 2002;88:479-88.
63. de Jong A, Plat J, Bast A, Godschalk RW, Basu S, Mensink RP. Effects of plant sterol and stanol ester consumption on lipid metabolism, antioxidant status and markers of oxidative stress, endothelial function and low-grade inflammation in patients on current statin treatment. Eur J Clin Nutr. 2008;62:263-73.
64. Earnest CP, Mikus CR, Lemieux I, Arsenault BJ, Church TS. Examination of encapsulated phytosterol ester supplementation on lipid indices associated with cardiovascular disease. Nutrition. 2007;23:625-33.
65. Goldberg AC, Ostlund RE, Bateman JH, Schimmoeller L, McPherson TB, Spilburg CA. Effect of plant stanol tablets on low-density lipoprotein cholesterol lowering in patients on statin drugs. Am J Cardiol. 2006;97:376-9.
66. Homma Y, Ikeda I, Ishikawa T, Tateno M, Sugano M, Nakamura H. 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. 2003;19:369-74.
67. Ishiwata K, Homma Y, Ishikawa T, Nakamura H, Handa S. Influence of apolipoprotein E phenotype on metabolism of lipids and apolipo-proteins after plant stanol ester ingestion in Japanese subjects. Nutrition. 2002;l 8:561-5.
68. Jauhiainen T, Salo P, Niittynen L, Poussa T, Korpela R. Effects of low-fat hard cheese enriched with plant stanol esters on serum lipids and apolipoprotein B in mildly hypercholesterolaemic subjects. Eur J Clin Nutr. 2006;60:1253-7.
69. Lagstrom H, Helenius H, Salo P. Serum cholesterol-lowering efficacy of stanol ester incorporated in gelatin capsules. Scand J Food Nutr. 2006; 50:124-130.
70. 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;42:111-7.
71. 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;98:978-83.
72. Maki KC, Davidson MH, Umporowicz DM, Schaefer EJ, Dicklin MR, Ingram KA, Chen S, McNamara JR, Gebhart BW, et al. Lipid responses to plant-sterol-enriched reduced-fat spreads incorporated into a National Cholesterol Education Program Step I diet. Am J Clin Nutr. 2001;74:33-43.
73. Matvienko OA, Lewis DS, Swanson M, Arndt B, Rainwater DL, Stewart J, Alekel DL. 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.
74. McPherson TB, Ostlund RE, Goldberg AC, Bateman JH, Schimmoeller L, Spilburg CA. Phytostanol tablets reduce human LDL-cholesterol. J Pharm Pharmacol. 2005;57:889-96.
75. Miettinen TA, Vanhanen H. Dietary sitostanol related to absorption, synthesis and serum level of cholesterol in different apolipoprotein E phenotypes. Atherosclerosis. 1994;105:217-26.
76. Miettinen TA, Puska P, Gylling H, Vanhanen H, Vartiainen E. Reduction of serum cholesterol with sitostanol-ester margarine in a mildly hypercholesterolemic population. N Engl J Med. 1995;333: 1308-12.
77. Niittynen LH, Jauhiainen TA, Poussa TA, Korpela R. Effects of yoghurt enriched with free plant sterols on the levels of serum lipids and plant sterols in moderately hypercholesterolaemic subjects on a high-fat diet. Int J Food Sci Nutr. 2007;18:1-ll.
78. Plat J, Mensink RP. Vegetable oil based versus wood based stanol ester mixtures: effects on serum lipids and hemostatic factors in non- hypercholesterolemic subjects. Atherosclerosis. 2000;148:101-12.
79. Quilez J, Rafecas M, Brufau G, Garcia-Lorda P, Megias I, Bullo M, Ruiz JA, Salas-Salvado J. Bakery products enriched with phytosterol esters, alpha-tocopherol and beta-carotene decrease plasma LDL-cholesterol and maintain plasma beta-carotene concentrations in normocholesterolemic men and women. J Nutr. 2003;133:3103-9.
80. Seki S, Hidaka I, Kojima K, Yoshino H, Aoyama T, Okazaki M, Kondo K. Effects of phytosterol ester-enriched vegetable oil on plasma lipoproteins in healthy men. Asia Pac J Clin Nutr. 2003;12:282-91.
81. Seki S, Abe T, Hidaka I, Kojima K, Yoshino H, Aoyama T, Okazaki M, Kondo K. Effects of phytosterol ester-enriched vegetable oil on serum cholesterol and assessment of safety in healthy men. J Oleo Sci. 2003; 52:205-13.
82. Spilburg CA, Goldberg AC, McGill JB, Stenson WF, Racette SB, Bateman J, McPherson TB, Ostlund REJ. Fat-free foods supplemented with soy stanol-lecithin powder reduce cholesterol absorption and LDL cholesterol. J Am Diet Assoc. 2003;103:577-81.
83. Taichi I. Effects of long-term intake of mayonnaise containing phytosterolester on blood cholesterol concentration in Japanese with borderline or mild cholesterolemia. J Clin Biochem Nutr. 2003;33:75-82.
84. Vanhanen HT, Kajander J, Lehtovirta H, Miettinen TA. Serum levels, absorption efficiency, faecal elimination and synthesis of cholesterol during increasing doses of dietary sitostanol esters in hypercholesterolaemic subjects. Clin Sci (Lond). 1994;87:61-7.
85. Vanhanen H. Cholesterol malabsorption caused by sitostanol ester feeding and neomycin in pravastatin-treated hypercholesterolaemic patients. Eur J Clin Pharmacol. 1994;47:169-76.
86. Varady KA, Ebine N, Vanstone CA, Parsons WE, Jones PJ. Plant sterols and endurance training combine to favorably alter plasma lipid profiles in previously sedentary hypercholesterolemic adults after 8 wk. Am J Clin Nutr. 2004;80:1159-66.
87. Woodgate D, Chan CHM, Conquer JA. Cholesterol-lowering ability of a phytostanol softgel supplement in adults with mild to moderate hypercholesterolemia. Lipids. 2006;41:127-32.
88. AbuMweis SS, Vanstone CA, Ebine N, Kassis A, Ausman LM, Jones PJ, 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;136:1012-6.
89. Cater NB, Garcia-Garcia AB, Vega GL, Grundy SM. Responsiveness of plasma lipids and lipoproteins to plant stanol esters. Am J Cardiol. 2005;96:D23-8.
90. 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; 98:563-70.
91. 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;17:561-9.
92. Geelen A, Zock PL, de Vries JH, Katan MB. Apolipoprotein E polymorphism and serum lipid response to plant sterols in humans. Eur J Clin Invest. 2002;32:738-42.
93. Gylling H, Miettinen TA. Serum cholesterol and cholesterol and lipoprotein metabolism in hypercholesterolaemic NIDDM patients before and during sitostanol ester-margarine treatment. Diabetologia. 1994;37:773-80.
94. Gylling H, Miettinen TA. Cholesterol reduction by different plant stanol mixtures and with variable fat intake. Metabolism. 1999;48: 575-80.
95. Gylling H, Radhakrishnan R, Miettinen TA. Reduction of serum cholesterol in postmenopausal women with previous myocardial infarction and cholesterol malabsorption induced by dietary sitostanol ester margarine: women and dietary sitostanol. Circulation. 1997;96:4226-31.
96. Hayes KC, Pronczuk A, Perlman D. Nonesterified phytosterols dissolved and recrystallized in oil reduce plasma cholesterol in gerbils and humans. J Nutr. 2004;134:1395-9.
97. Hendriks HF, Weststrate JA, van VT 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;53:319-27.
98. Jakulj L, Trip MD, Sudhop T, Bergman BK, Kastelein JJ, Vissers MN. Inhibition of cholesterol absorption by the combination of dietary plant sterols and ezetimibe: effects on plasma lipid levels. J Lipid Res. 2005;46:2692-8.
99. Jones PJH, Vanstone CA, Raeini-Sarjaz M, St-Onge MP. Phytosterols in low- and nonfat beverages as part of a controlled diet fail to lower plasma lipid levels. J Lipid Res. 2003;44:1713-9.
100. Judd JT, Baer DJ, Chen SC, Clevidence BA, Muesing RA, Kramer M, Meijer GW. Plant sterol esters lower plasma lipids and most carote-noids in mildly hypercholesterolemic adults. Lipids. 2002;37:33-42.
101. Kratz M, Kannenberg F, Gramenz E, Berning B, Trautwein E, 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;61:896-905.
102. Lau VW, Journoud M, Jones PJ. 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;81:1351-8.
103. Lottenberg AM, Nunes VS, Nakandakare ER, Neves M, Bernik M, Lagrost L, dos-Santos JE, Quintao E. The human cholesteryl ester transfer protein I405V polymorphism is associated with plasma cholesterol concentration and its reduction by dietary phytosterol esters. J Nutr. 2003;133:1800-5.
104. Madsen MB, Jensen AM, Schmidt EB. The effect of a combination of plant sterol-enriched foods in mildly hypercholesterolemic subjects. Clin Nutr. 2007;26:792-8.
105. 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;51:189-94.
106. Naumann E, Plat J, Mensink RP. Changes in serum concentrations of noncholesterol sterols and lipoproteins in healthy subjects do not depend on the ratio of plant sterols to stanols in the diet. J Nutr. 2003;133:2741-7.
107. Nestel P, Cehun M, Pomeroy S, Abbey M, Weldon G. Cholesterol-lowering effects of plant sterol esters and non-esterified stanols in margarine, butter and low-fat foods. Eur J Clin Nutr. 2001;55:1084-90.
108. 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;132:3650-5.
109. Pelletier X, Belbraouet S, Mirabel D, Mordret F, Perrin JL, Pages X, Debry G. A diet moderately enriched in phytosterols lowers plasma cholesterol concentrations in normocholesterolemic humans. Ann Nutr Metab. 1995;39:291-5.
110. Temme EH, Van Hoydonck PG, Schouten EG, Kesteloot H. Effects of a plant sterol-enriched spread on serum lipids and lipoproteins in mildly hypercholesterolaemic subjects. Acta Cardiol. 2002;57:111-5.
111. Vanstone CA, Raeini-Sarjaz M, Parsons WE, Jones PJ. Unesterified plant sterols and stanols lower LDL-cholesterol concentrations equiv-alently in hypercholesterolemic persons. Am J Clin Nutr. 2002;76: 1272-8.
112. Volpe R, Niittynen L, Korpela R, Sirtori C, Bucci A, Fraone N, Pazzucconi F. Effects of yoghurt enriched with plant sterols on serum lipids in patients with moderate hypercholesterolaemia. Br J Nutr. 2001;86:233-9.
113. Yoshida M, Vanstone CA, Parsons WD, Zawistowski J, Jones PJ. Effect of plant sterols and glucomannan on lipids in individuals with and without type II diabetes. Eur J Clin Nutr. 2006;60:529-37.
114. Blair SN, Capuzzi DM, Gottlieb SO, Nguyen T, Morgan JM, Cater NB. Incremental reduction of serum total cholesterol and low-density lipoprotein cholesterol with the addition of plant stanol ester-containing spread to statin therapy. Am J Cardiol. 2000;86:46-52.