Plasma concentrations of plant sterols: Physiology and relationship with coronary heart disease

Nutrition Reviews

Volumn 64, Issue 9, 2006, Pages 385-402

  Chan, Yen Ming ^a   Varady, Krista A ^a   Lin, Yuguang ^b   Trautwein, Elke ^b   Mensink, Ronald P ^c   Plat, Jogchum ^c   Jones, Peter J H ^a  

^a MCGILL UNIVERSITY   (Canada)

^b UNILEVER RESEARCH VLAARDINGEN   (Netherlands)

^c MAASTRICHT UNIVERSITY   (Netherlands)

Author keywords

Blood concentrations; Cholesterol; Coronary heart disease; Plant sterols

Indexed keywords

APOLIPOPROTEIN E; ATORVASTATIN; CAMPESTEROL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; PHYTOSTEROL; SIMVASTATIN; SITOSTEROL;

CARDIOVASCULAR RISK; DIETARY INTAKE; HUMAN; HYPERCHOLESTEROLEMIA; ISCHEMIC HEART DISEASE; LIPID BLOOD LEVEL; NONHUMAN; REVIEW;

ANIMALS; APOLIPOPROTEINS E; ATP-BINDING CASSETTE TRANSPORTERS; CORONARY DISEASE; FEMALE; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; LIPOPROTEINS; MALE; MICE; PHENOTYPE; PHYTOSTEROLS; RISK FACTORS; SEX FACTORS;

EID: 33749523918     PISSN: 00296643     EISSN: 00296643     Source Type: Journal    
DOI: 10.1301/nr.2006.sept.385-402     Document Type: Review

References (104)

1. Glueck CJ, Speirs J, Tracy T, et al. Relationships of serum plant sterols (phytosterols) and cholesterol in 595 hypercholesterolemic subjects, and familial aggregation of phytosterols, cholesterol, and premature coronary heart disease in hyperphytosterolemic probands and their first-degree relatives. Metabolism. 1991;40:842-848.
2. Rajaratnam RA, Gylling H, Miettinen TA. Independent association of serum squalene and noncholesterol sterols with coronary artery disease in postmenopausal women. J Am Coll Cardiol. 2000;35:1185-1191.
3. Sudhop T, Britta MG, Von Bergmann K. Serum plant sterols as a potential risk factor for coronary heart disease. Metabolism. 2002;51:1519-1521.
4. Assmann G, Cullen P, Erbey J, et al. Plasma sitosterol elevations are associated with an increased incidence of coronary events in men: results of a nested case-control analysis of the Prospective Cardiovascular Munster (PROCAM) Study. Nutr Metab Cardiovasc Dis. 2006;16:13-21.
5. Wilund KR, Yu L, Xu F, et al. No association between plasma levels of plant sterols and atherosclerosis in mice and men. Arterioscler Thromb Vasc Biol. 2004;24:2326-2332.
6. Smahelova A, Hyspler R, Haas T, et al. Effect of atorvastatin on non-cholesterol sterols in patients with type 2 diabetes mellitus and cardiovascular disease. Pharmacol Res. 2005;51:31-36.
7. Varady KA, Ebine N, Vanstone CA, et al. 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;80:1159-1166.
8. Clifton PM, Noakes M, Sullivan D, et al. Cholesterol-lowering effects of plant sterol esters differ in milk, yoghurt, bread and cereal. Eur J Clin Nutr. 2004;58:503-509.
9. Clifton PM, Noakes M, Ross D, et al. High dietary intake of phytosterol esters decreases carotenoids and increases plasma plant sterol levels with no additional cholesterol lowering. J Lipid Res. 2004;45:1493-1499.
10. Gylling H, Hallikainen M, Pihlajamaki J, et al. Polymorphisms in the ABCG5 and ABCG8 genes associate with cholesterol absorption and insulin sensitivity. J Lipid Res. 2004;45:1660-1665.
11. Pihlajamaki J, Gylling H, Miettinen TA, et al. Insulin resistance is associated with increased cholesterol synthesis and decreased cholesterol absorption in normoglycemic men. J Lipid Res. 2004;45:507-512.
12. Quilez J, Rafecas M, Brufau G, et al. Bakery products enriched with phytosterol esters, α-tocopherol and beta-carotene decrease plasma LDL-cholesterol and maintain plasma beta-carotene concentrations in normocholesterloemic men and women. J Nutr. 2003;133:3103-3109.
13. Muti P, Awad AB, Schunemann H, et al. A plant food-based diet modifies the serum beta-sitosterol concentration in hyperandrogenic postmenopausal women. J Nutr. 2003;133:4252-4255.
14. Ketomaki AM, Gylling H, Antikainen M, et al. Red cell and plasma plant sterols are related during consumption of plant stanol and sterol ester spreads in children with hypercholesterolemia. J Pediatr. 2003;142:524-531.
15. Ketomaki A, Gylling H, Martti AS, et al. Squalene and noncholesterol sterols in serum and lipoprotein of children with and without familial hypercholesterolemia. Pediatr Res. 2003;53:648-653.
16. Jones PJ, Vanstone CA, Raeini-Sarjaz M, et al. Phytosterols in low-and nonfat beverages as part of a controlled diet fail to lower plasma lipid levels. J Lipid Res. 2003;44:1713-1719.
17. Homma Y, Ikeda I, Ishikawa T, et al. 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;19:369-374.
18. 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;133:2741-2747.
19. Miettinen TA, Gylling H. Cholesterol synthesis and absorption in coronary patients with lipid triad and isolated high LDL cholesterol in a 4S subgroup. Atherosclerosis. 2003;168:343-349.
20. Chan DC, Watts GF, Barrett PH, et al. Relationships between cholesterol homoeostasis and triacylglycerol-rich lipoprotein remnant metabolism in the metabolic syndrome. Clin Sci (Lond). 2003;104:383-388.
21. Vanstone CA, Raeini-Sarjaz M, Parsons WE, et al. Unesterified plant sterols lower LDL-cholesterol concentrations equivalently in hypercholesterolemic persons. Am J Clin Nutr. 2002;76:1272-1278.
22. De Graaf J, De Sauvage-Nolting PRW, Van Dam M, et al. Consumption of tall oil-derived phytosterols in a chocolate matrix significantly decreases plasma total and low-density lipoprotein-cholesterol levels. Br J Nutr. 2002;88:479-488.
23. Mensink RP, Ebbing S, Lindhout M, et al. 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;160:205-213.
24. Mussner MJ, Parhofer KG, Von Bergmann K, et al. Effects of phytosterol ester-enriched margarine on plasma lipoproteins in mild to moderate hypercholesterolemia are related to basal cholesterol and fat intake. Metabolism. 2002;51:189-194.
25. Gylling H, Miettinen TA. Inheritance of cholesterol metabolism of probands with high or low cholesterol absorption. J Lipid Res. 2002;43:1472-1476.
26. Tammi A, Ronnemaa T, Miettinen TA, et al. 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;91:1155-1162.
27. Berge KE, von Bergmann K, Lutjohann D, et al. Heritability of plasma noncholesterol sterols and relationship to DNA sequence polymorphism in ABCG5 and ABCG8. J Lipid Res. 2002;43:486-494.
28. Nestel P, Cehun M, Pomeroy S, et al. Cholesterol-lowering effects of plant sterol esters and non-esterified stanols in margarine, butter and low-fat foods. Eur J Clin Nutr. 2001;55:1084-1090.
29. Christiansen LI, Lahteenmaki PL, Mannelin MR, et al. Cholesterol-lowering effect of spreads enriched with microcrystalline plant sterols in hypercholesterolemic subjects. Eur J Nutr. 2001;40:66-73.
30. Neil HA, Meijer GW, Roe LS. Randomised controlled trial of use by hypercholesterolaemic patients of a vegetable oil sterol-enriched fat spread. Atherosclerosis. 2001;156:329-337.
31. Plat J, Mensink RP. 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.
32. Davidson MH, Maki KC, Umporowicz DM, 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;20:307-319.
33. Maki KC, Davidson MH, Umporowicz DM, 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.
34. Tammi A, Ronnemaa T, Rask-Nissila L, et al. Apolipoprotein E phenotype regulates cholesterol absorption in healthy 13-month-old children - The STRIP Study. Pediatr Res. 2001;50:688-691.
35. Jones PJ, Raeini-Sarjaz M, Ntanios FY, et al. Modulation of plasma lipid levels and cholesterol kinetics by phytosterol versus phytostanol esters. J Lipid Res. 2000;41:697-705.
36. Hallikainen MA, Sarkkinen ES, Gylling H, et al. 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;54:715-725.
37. Hallikainen MA, Sarkkinen ES, Uusitupa MI. Plant stanol esters affect serum cholesterol concentrations of hypercholesterolemic men and women in a dose-dependent manner. J Nutr. 2000;130:767-776.
38. Simonen P, Gylling H, Howard AN, et al. Introducing a new component of the metabolic syndrome: low cholesterol absorption. Am J Clin Nutr 2000;72: 82-8.
39. Jones PJ, Ntanios FY, Raeini-Sarjaz M, et al. Cholesterol-lowering efficacy of a sitostanol-containing phytosterol mixture with a prudent diet in hyperlipidemic men. Am J Clin Nutr. 1999;69:1144-1150.
40. Gylling H, Puska P, Vartiainen E, et al. Serum sterols during stanol ester feeding in a mildly hypercholesterolemic population. J Lipid Res. 1999;40:593-600.
41. Sutherland WHF, Williams MJA, Nye ER, et al. Association of plasma noncholesterol sterol levels with severity of coronary artery disease. Nutr Metab Cardiovasc Dis. 1998;8:386-391.
42. Uusitupa MI, Miettinen TA, Sarkkinen ES, et al. Lathosterol and other non-cholesterol sterols during treatment of hypercholesterolaemia with beta-glucan-rich oat bran. Eur J Clin Nutr. 1997;51:607-611.
43. Gylling H, Miettinen TA. Cholesterol absorption, synthesis, and LDL metabolism in NIDDM. Diabetes Care. 1997;20:90-95.
44. Gylling H, Siimes MA, Miettinen TA, et al. Sitostanol ester margarine in dietary treatment of children with familial hypercholesterolemia. J Lipid Res. 1995;36:1807-1812.
45. Chisholm A, Sutherland W, Ball M. The effect of dietary fat content on plasma noncholesterol sterol concentrations in patients with familial hypercholesterolemia treated with simvastatin. Metabolism. 1994;43:310-314.
46. Sutherland WH, Robertson MC, Williamson SA, et al. Plasma noncholesterol sterols in male distance runners and sedentary men. Eur J Appl Physiol Occup Physiol. 1991;63:119-123.
47. Kempen HJ, de Knijff P, Boomsma DI, et al. Plasma levels of lathosterol and phytosterols in relation to age, sex, anthropometric parameters, plasma lipids, and apolipoprotein E phenotype, in 160 Dutch families. Metabolism. 1991;40:604-611.
48. Gylling H, Kuusi T, Vanhanen H, et al. Apolipoprotein E phenotype and cholesterol metabolism in familial hypercholesterolemia. Atherosclerosis. 1989;80:27-32.
49. Miettinen TA, Tilvis RS, Kesaniemi YA. 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.
50. Tilvis RS, Miettinen TA. Serum plant sterols and their relation to cholesterol absorption. Am J Clin Nutr. 1986;43:92-97.
51. Katan MB, Grundy SM, Jones P, et al.; Stresa Workshop Participants. Efficacy and safety of plant stanols and sterols in the management of blood cholesterol levels. Mayo Clin Proc. 2003;78:965-978.
52. Weihrauch JL, Gardner JM. Sterol content of foods of plant origin. J Am Diet Assoc. 1978;73:39-47.
53. Hirai K, Shimazu C, Takezoe R, et al. Cholesterol, phytosterol and polyunsaturated fatty acid levels in 1982 and 1957 in Japanese diets. J Nutr Sci Vitaminol. 1986;32:363-372.
54. Morton GM, Lee SM, Buss DH, et al. Intakes and major dietary sources of cholesterol and phytosterols in the British diet. J Human Nutr Diet. 1995;8:429-440.
55. Normen AL, Brants HA, Voorrips LE, et al. Plant sterol intakes and colorectal cancer risk in the Netherlands Cohort Study on Diet and Cancer. Am J Clin Nutr. 2001;74:141-148.
56. Vuoristo M, Miettinen TA. Absorption, metabolism, and serum concentrations of cholesterol in vegetarians: effects of cholesterol feeding. Am J Clin Nutr. 1994;59:1325-1331.
57. Andersson SW, Skinner J, Ellegard L, et al. 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;58:1378-1385.
58. Tammi A, Ronnemaa T, Valsta L, et al. Dietary plant sterols alter the serum plant sterol concentration but not the cholesterol precursor sterol concentrations I young children (STRIP Study). J Nutr. 2001;131:1942-1945.
59. Kesaniemi YA, Ehnholm C, Miettinen TA. Intestinal cholesterol absorption efficiency in men is related to apoprotein E phenotype. J Clin Invest. 1987;80:578-581.
60. Miettinen TA, Gylling H, Vanhanen H, et al. Cholesterol absorption, elimination, and synthesis related to LDL kinetics during varying fat intake in men with different apoprotein E phenotypes. Arterioscler Thromb. 1992;12:1044-1052.
61. Ehnholm C, Lukka M, Kuusi T, et al. Apolipoprotein E polymorphism in the Finnish population: gene frequencies and relation to lipoprotein concentrations. J Lipid Res. 1986;27:227-235.
62. Welty FK, Lichtenstein AH, Barrett PH, et al. Effects of ApoE genotype on ApoB-48 and ApoB-100 kinetics with stable isotopes in humans. Arterioscler Thromb Vasc Biol. 2000;20:1807-1810.
63. Igel M, Giesa U, Lutjohann D, et al. Comparison of the intestinal uptake of cholesterol, plant sterols, and stanols in mice. J Lipid Res. 2003;44:533-538.
64. Yu L, Hammer RE, Li-Hawkins J, et al. Disruption of Abcg5 and Abcg8 in mice reveals their crucial role in biliary cholesterol secretion. Proc Natl Acad Sci U S A. 2002;99:16237-16242.
65. Lee MH, Lu K, Patel SB. Genetic basis of sitosterolemia. Curr Opin Lipidol. 2001;12:141-149.
66. Berge KE, Tian H, Graf GA, Yu L, et al. Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science. 2000;290:1771-1775.
67. Sehayek E, Yu HJ, von Bergmann K, et al. Phytosterolemia on the island of Kosrae: founder effect for a novel ABCG8 mutation results in high carrier rate and increased plasma plant sterol levels. J Lipid Res. 2004;45:1608-1613.
68. Kwiterovich PO Jr, Chen SC, Virgil DG, et al. Response of obligate heterozygotes for phytosterolemia to a low-fat diet and to a plant sterol ester dietary challenge. J Lipid Res. 2003;44:1143-1155.
69. Stalenhoef AF, Hectors M, Demacker PN. Effect of plant sterol-enriched margarine on plasma lipids and sterols in subjects heterozygous for phytosterolaemia. J Intern Med. 2001;249:163-166.
70. 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;52:334-343.
71. Hubacek JA, Berge KE, Cohen JC, et al. Mutations in ATP-cassette binding proteins G5 (ABCG5) and G8 (ABCG8) causing sitosterolemia. Hum Mutat. 2001;18:359-360.
72. Plat J, Bragt MC, Mensink RP. Common sequence variations in ABCG8 are related to plant sterol metabolism in healthy volunteers. J Lipid Res. 2005;46:68-75.
73. Weggemans RM, Zock PL, Tai ES, et al. ATP binding cassette G5 C1950G polymorphism may affect blood cholesterol concentrations in humans. Clin Genet. 2002;62:226-229.
74. Miettinen TA, Strandberg TE, Gylling H. Noncholesterol sterols and cholesterol lowering by long-term simvastatin treatment in coronary patients: relation to basal serum cholestanol. Arterioscler Thromb Vasc Biol. 2000;20:1340-1346.
75. Kajinami K, Brousseau ME, Nartsupha C, et al. ATP binding cassette transporter G5 and G8 genotypes and plasma lipoprotein levels before and after treatment with atorvastatin. J Lipid Res. 2004;45:653-656.
76. Miettinen TA, Gylling H. Cholesterol absorption efficiency and sterol metabolism in obesity. Atherosclerosis. 2000;153:241-248.
77. van Waarde WM, Verkade HJ, Wolters H, et al. Differential effects of streptozotocin-induced diabetes on expression of hepatic ABC-transporters in rats. Gastroenterology. 2002;122:1842-1852.
78. Nguyen L, Salen G, Shefer S, et al. Unexpected failure of bile acid malabsorption to stimulate cholesterol synthesis in sitosterolemia with xanthomatosis. Comparison with lovastatin. Arteriosclerosis. 1990;10:289-297.
79. Nguyen LB, Shefer S, Salen G, et al. Regulation of 3-hydroxy-3- methylglutaryl-coenzyme A reductase activity in the rat ileum: effects of bile acids and lovastatin. Metabolism. 1994;43:1446-1450.
80. Miettinen TA, Gylling H. Synthesis and absorption markers of cholesterol in serum and lipoproteins during a large dose of statin treatment. Eur J Clin Invest. 2003;33:976-982.
81. Matthan NR, Giovanni A, Schaefer EJ, et al. Impact of simvastatin, niacin, and/or antioxidants on cholesterol metabolism in CAD patients with low HDL. J Lipid Res. 2003;44:800-806.
82. Miettinen TA, Gylling H, Lindbohm N, et al. Serum noncholesterol sterols during inhibition of cholesterol synthesis by statins. J Lab Clin Med. 2003;141:131-137.
83. Uusitupa MI, Miettinen TA, Happonen P, et al. Lathosterol and other noncholesterol sterols during treatment of hypercholesterolemia with lovastatin alone and with cholestyramine or guar gum. Arterioscler Thromb. 1992;12:807-813.
84. Vanhanen H, Kesaniemi YA, Miettinen TA. Pravastatin lowers serum cholesterol, cholesterol-precursor sterols, fecal steroids, and cholesterol absorption in man. Metabolism. 1992;41:588-595.
85. Kuriyama M, Tokimura Y, Fujiyama J, et al. Treatment of cerebrotendinous xanthomatosis: effects of chenodeoxycholic acid, pravastatin, and combined use. J Neurol Sci. 1994;125:22-28.
86. Hidaka H, Kojima H, Kawabata T, et al. Effects of an HMG-CoA reductase inhibitor, pravastatin, and bile sequestering resin, cholestyramine, on plasma plant sterol levels in hypercholesterolemic subjects. J Atheroscler Thromb. 1995;2:60-65.
87. Ntanios FY, Jones PJ, Frohlich JJ. Effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor on sterol absorption in hypercholesterolemic subjects. Metabolism. 1999;48:68-73.
88. Gylling H, Miettinen TA. LDL cholesterol lowering by bile acid malabsorption during inhibited synthesis and absorption of cholesterol in hypercholesterolemic coronary subjects. Nutr Metab Cardiovasc Dis. 2002;12:19-23.
89. Gylling H, Miettinen TA. Baseline intestinal absorption and synthesis of cholesterol regulate its response to hypolipidaemic treatments in coronary patients. Atherosclerosis. 2002;160:477-481.
90. Miettinen TA, Gylling H. Ineffective decrease of serum cholesterol by simvastatin in a subgroup of hypercholesterolemic coronary patients. Atherosclerosis. 2002;164:147-152.
91. Kuksis, A. Plasma non-cholesterol sterols. J Chromatogr. 2001;935:203-236.
92. Phillips KM, Ruggio DM, Bailey JA. Precise quantitative determination of phytosterols, stanols and cholesterol metabolites in human serum by capillary gas-liquid chromatography. J Chromatogr B Biomed Sci Appl. 1999;732:17-29.
93. Salen G, Shefer S, Nguyen L, et al. Sitosterolemia. J Lipid Res. 1992;33:945-955.
94. Vissers MN, Pinedo S, Boekholdt SM, et al. Plasma levels of plant sterols and the risk of future coronary artery disease in healthy men and women; the prospective epicnorfolk population study [abstract]. Atheroscler Suppl. 2006;7:318. Abstract# We-W36:6.
95. Windler E, Zyriax B-CHR, Kuipers F, et al. Lack of association of plasma phytosterols with risk of coronary heart disease in the cora-study [abstract]. Atheroscler Suppl. 2006;7:177. Abstract# Tu-W28:5.
96. Pollak OJ, Kritchevsky D. Sitosterol. Monogr Atheroscler. 1981;10:1-219.
97. Ikeda I, Kawasaki A, Samezima KM, et al. Antihypercholesterolemic activity of β-sitostanol in rabbits. J Nutr Sci Vitaminol. 1981;27:243-251.
98. Moghadasian MH, McManus BM, Pritchard PH, et al. Tall oil-derived phytosterols reduce atherosclerosis in apoE- deficient mice. Arterioscler Thromb Vasc Biol. 1997;17:119-126.
99. Moghadasian MH, McManus BM, Godin DV, et al. Proatherogenic and antiatherogenic effects of probucol and phytosterols in apolipoprotein E-deficient mice. Possible mechanisms of action. Circulation. 1999;99:1733-1739.
100. Ntanios FY, Jones PJ, Frohlich JJ. Dietary sitostanol reduces plaque formation but not lecithin cholesterol acyl transferase activity in rabbits. Atherosclerosis. 1998;138:101-110.
101. Volger OL, Mensink, Plat J, et al. Dietary vegetable oil and wood derived plant stanol esters reduce atherosclerotic lesion size and severity in apoE*3-Leiden transgenic mice. Atherosclerosis. 2001;157:375-381.
102. Ntanios FY, van de Kooij AJ, de Deckere EA, et al. 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;169:41-50.
103. Moghadasian MH, Godin DV, McManus BM, et al. Lack of regression of atherosclerotic lesions in phytosterol treated apoE deficient mice. Life Sciences. 1999;64:1029-1036.
104. Vaskonen T, Mervaala E, Krogerus L, et al. Supplementation of plant sterols and minerals benefits obese Zucker rats fed an atherogenic diet. J Nutr. 2002;132:231-237.