Phytosterols-health benefits and potential concerns: A review

Nutrition Research

Volumn 25, Issue 5, 2005, Pages 413-428

  Kritchevsky, David ^a   Chen, Shirley C ^b  

^a WISTAR INSTITUTE   (United States)

^b NONE

Author keywords

Atherosclerosis; Campesterol; Cholesterol; Phytosterols; Sitosterol

Indexed keywords

CAMPESTEROL; PHYTOSTEROL; SITOSTEROL;

ATHEROGENESIS; ATHEROSCLEROSIS; CARDIOVASCULAR RISK; CHOLESTEROL METABOLISM; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG EFFECT; DRUG EFFICACY; DRUG METABOLISM; DRUG SAFETY; HUMAN; HYPERCHOLESTEROLEMIA; ISCHEMIC HEART DISEASE; NONHUMAN; PRIORITY JOURNAL; REVIEW;

EID: 20444463926     PISSN: 02715317     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.nutres.2005.02.003     Document Type: Article

References (111)

1. G.A. Bean Phytosterols Adv Lipid Res 11 1973 193 218
2. R.A. Moreau, B.D. Whitaker, and K.B. Hicks Phytosterols, phytostanols, and their conjugates in foods: structural diversity, quantitative analysis and health-promoting uses Prog Lipid Res 41 2002 457 500
3. J.L. Weihrauch, and J.M. Gardner Sterol content of foods of plant origin J Am Diet Assoc 73 1978 39 47
4. T. Itoh, T. Tamura, and T. Matsumoto Sterol composition of 19 vegetable oils J Am Oil Chem Soc 50 1973 122 125
5. V. Piironen, D.G. Lindsay, and T.A. Miettinen Plant sterols: biosynthesis, biological function and their importance to human nutrition J Sci Food Agric 80 2000 939 966
6. G.W. Ellis, and J.A. Gardner The origin and destiny of cholesterol in the organism VIII. On the cholesterol content of the liver of rabbits under various diets and during inanition Proc R Soc Lond B84 1912 461 470
7. R. Schönheimer New contributions in sterol metabolism Science 74 1931 579 584
8. O.J. Pollak, and D. Kritchevsky Sitosterol 1981 S. Karger Basel
9. G. Salen, E.H. Ahrens Jr., and S.M. Grundy Metabolism of beta-sitosterol in man J Clin Invest 49 1949 952 967
10. R.E. Ostlund Jr., J.B. McGill, and C.-M. Zeng Gastrointestinal absorption and plasma kinetics of soy δ-5-phytosterols and phytostanols in humans Am J Physiol Endocrinol Metab 282 2002 E911 E916
11. 3H to fatty acids in tissue lipids in vivo Nature 207 1965 194 195
12. 24 bile acids in humans J Lipid Res 31 1990 1083 1088
13. D. Kritchevsky, L.M. Davidson, and E.M. Mosbach Identification of acidic steroids in feces of monkeys fed β-sitosterol Lipids 16 1981 77 78
14. K.M. Boberg, E. Lund, and J. Olund Formation of C21 bile acids from plant sterols in the rat J Biol Chem 265 1990 7967 7975
15. M.T.R. Subbiah, and A. Kuksis Differences in metabolism of cholesterol and sitosterol following intravenous injection in rats Biochim Biophys Acta 306 1973 95 105
16. D.W. Peterson Effect of soybean sterols in the diet on plasma and liver cholesterol in chicks Proc Soc Exp Biol Med 78 1951 143 147
17. D.W. Peterson, C.W. Nichols Jr., and E.A. Shneour Some relationships among dietary sterols, plasma and liver cholesterol levels, and atherosclerosis in chicks J Nutr 47 1952 57 65
18. D.W. Peterson, E.A. Shneour, and N.F. Peek Dietary constituents affecting plasma and liver cholesterol in cholesterol-fed chicks J Nutr 50 1953 191 201
19. O.J. Pollak Reduction of blood cholesterol in man Circulation 7 1953 702 706
20. E.H. Ahrens Jr., J. Hirsch, and W. Insull Jr. The influence of dietary fats on serum lipid levels in man Lancet i 1957 943 953
21. E.H. Ahrens Jr., J. Hirsch, and W. Insull Jr. Dietary control of serum lipids in relation to atherosclerosis JAMA 164 1957 1905 1911
22. H. Engelberg Studies of serum cholesterol and low density lipoproteins, previously lowered by a reduced fat intake, after the addition of corn oil to the diet J Chronic Dis 6 1957 229 233
23. J.M.R. Beveridge, W.F. Connell, and G.A. Mayer The effect of certain vegetable and animal fats on the plasma lipids of humans J Nutr 56 1955 311 320
24. J.M.R. Beveridge, W.F. Connell, and G.A. Mayer Dietary factors affecting the level of plasma cholesterol in humans: the role of fat Can J Biochem Physiol 34 1956 441 455
25. J.M.R. Beveridge, W.F. Connell, and G.A. Mayer Plant sterols, degree of unsaturation, and hypocholesterolemic action of certain fats Can J Biochem Physiol 36 1958 895 911
26. R.E. Ostlund Jr., S.B. Racette, and A. Okeke Phytosterols that are naturally present in commercial corn oil significantly reduce cholesterol absorption in humans Am J Clin Nutr 75 2002 1000 1004
27. T.J. Howell, D.E. MacDougall, and P.J.H. Jones Phytosterols partially explain differences in cholesterol metabolism caused by corn or olive oil feeding J Lipid Res 39 1998 892 900
28. D.W. Peterson, C.W. Nichols Jr., and N.F. Peek Depression of plasma cholesterol in human subjects consuming butter containing soy sterols Fed Proc 1956 65 69
29. T.A. Miettinen, P. Puska, and H. Gylling Reduction of serum cholesterol with sitostanol-ester margarine in a mildly hypercholesterolemic population N Engl J Med 333 1995 1308 1312
30. J.A. Weststrate, and G.W. Meijer Plant sterol enriched margarines and reduction of plasma total- and LDL-cholesterol concentrations in normocholesterolemic and mildly hypercholesterolemic subjects Eur J Clin Nutr 52 1998 334 343
31. J. Plat, and R.P. Mensink Vegetable oil based versus wood based stanol ester mixtures: effects on serum lipids and hemostatic factors in non-hypercholesterolemic subjects Atherosclerosis 148 2000 101 112
32. M.A. Hallikainen, E.S. Sarkkinen, and H. Gylling 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 54 2000 715 725
33. C.A. Vanstone, M. Raeini-Sarjaz, and W.E. Parsons Unesterified plant sterols and stanols lower LDL-cholesterol concentrations equivalently in hypercholesterolemic persons Am J Clin Nutr 76 2002 1271 1278
34. D.H. Duncan, and M.M. Best Comparative effects of free and esterified sitosterol on serum and liver cholesterol in rats J Clin Invest 35 1956 700 709
35. F.H. Mattson, S.M. Grundy, and J.R. Crouse Optimizing the effect of plant sterols on cholesterol absorption in man Am J Clin Nutr 35 1982 696 700
36. L. Normén, J. Frohlich, and E. Trautwein Role of plant sterols in cholesterol lowering P.C. Dutta Phytosterols as functional food components and nutraceuticals 2004 Marcel Dekker, Inc New York 243 315
37. M.B. Katan, S.M. Grundy, and P. Jones Efficacy and safety of plant stanols and sterols in the management of blood cholesterol levels Mayo Clin Proc 78 2003 965 978
38. O.J. Pollak Effect of plant sterols on serum lipids and atherosclerosis Pharmacol Ther 31 1985 177 208
39. R.E. Shipley, R.R. Pfieffer, and M.M. Marsh Sitosterol feeding: chronic animal and clinical toxicity and tissue analysis Circ Res 6 1958 373 382
40. V.A. Baker, P.A. Hepburn, and S.J. Kennedy Safety evaluation of sitosterol esters. Part 1. Assessment of oestrogenicity using a combination of in vivo and in vitro assays Food Chem Toxicol 37 1999 13 22
41. P.A. Hepburn, S.A. Horner, and M. Smith Safety evaluation of phytosterol esters. Part 2. Subchronic 90-day oral toxicity study on phytosterol esters-a novel functional food Food Chem Toxicol 37 1999 521 532
42. H.D. Waalkens-Berendsen, A.P.M. Wolterbeek, and M.V.W. Wijnands Safety evaluation of phytosterol esters. Part 3. Two-generation reproduction study in rats with phytosterol esters-a novel functional food Food Chem Toxicol 37 1999 683 696
43. J.A. Weststrate, R. Ayesh, and C. Bauer-Plank Safety evaluation of phytosterol esters. Part 4. Faecal concentrations of bile acids and neutral sterols in healthy normolipaedemic volunteers consuming a controlled diet either with or without a phytosterol ester-enriched margarine Food Chem Toxicol 37 1999 1063 1071
44. R. Ayesh, J.A. Weststrate, and P.N. Drewitt 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 normolipaedemic volunteers consuming a controlled diet either with or without a phytosterol ester-enriched margarine Food Chem Toxicol 37 1999 1127 1138
45. D.J. Sanders, H.J. Minter, and D. Hower The safety evaluation of phytosterol esterol. Part 6. The comparative absorption and tissue distribution of phytosterols in the rat Food Chem Toxicol 38 2000 485 491
46. A.M. Wolfreys, and P.A. Hepburn 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 40 2002 461 470
47. L.J. Lea, P.A. Hepburn, and A.M. Wolfreys Safety evaluation of phytosterol esters. Part 8. Lack of genotoxicity and subchronic toxicity with phytosterol oxides Food Chem Toxicol 42 2004 771 783
48. M.H. Whittaker, V.H. Frankos, and A.P.M. Wolterbeek Two-generation reproductive toxicity study of plant stanol esters in rats Regul Toxicol Pharmacol 29 1999 196 204
49. D. Turnbull, V.H. Frankos, and J.H.M. van Delft Genotoxicity evaluation of wood-derived and vegetable oil-derived stanol esters Regul Toxicol Pharmacol 29 1999 205 210
50. D. Turnbull, M.H. Whittaker, and V.H. Frankos 13-Week oral toxicity study with stanol esters in rats Regul Toxicol Pharmacol 29 1999 216 226
51. R.S. Slesinski, D. Turnbull, and V.H. Frankos Developmental toxicity study of vegetable oil-derived stanol fatty acid esters Regul Toxicol Pharmacol 29 1999 227 233
52. T. Malini, and G. Vanithakumari Rat toxicity studies with β sitosterol J Ethnopharmacol 28 1990 221 234
53. M. Richelle, M. Enslen, and C. Hager Both free and esterified plant sterols reduce cholesterol absorption and the bioavailability of β-carotene and β-tocopherol in normocholesterolemic humans Am J Clin Nutr 2004 171 177
54. M.A. Hallikainen, and M.I.J. Uusitupa Effects of 2 low-fat stanol-esterol containing margarines on serum cholesterol concentrations as part of a low fat diet in hypercholesterolemic subjects Am J Clin Nutr 1999 403 410
55. C. Maki, M.H. Davidson, and D.M. Umporowicz Lipid responses to plant-sterol-enriched reduced-fat spreads incorporated into a National Cholesterol Education Program Step 1 diet Am J Clin Nutr 74 2001 33 43
56. P. Nestel, M. Cehun, and S. Pomeroy Cholesterol-lowering effects of plant sterol esters and non-esterified stanols in margarine, butter and low fat foods Eur J Clin Nutr 55 2001 1084 1090
57. H.F.J. Hendricks, J.A. Weststrate, and T. van Vliet 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 53 1999 319 327
58. J.T. Judd, D.J. Baer, and S.C. Chen Plant sterol esters lower plasma lipids and most carotenoids in mildly hypercholesterolemic adults Lipids 37 2002 33 42
59. F. Ntanios, Y. Homma, and S. Ushiro 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 132 2002 3650 3655
60. A.L. Amundsen, L. Ose, and M.S. Nenseter Plant sterol ester-enriched spread lowers plasma total and LDL cholesterol in children with familial hypercholesterolemia Am J Clin Nutr 76 2002 338 344
61. M. Noakes, P. Clifton, and F. Ntanios An increase in dietary carotenoids when consuming plant sterols or stanols is effective in maintaining plasma carotenoid concentrations Am J Clin Nutr 75 2002 79 86
62. Lipid Research Clinics Program The Lipid Research Clinics Coronary Primary Prevention Trial results. I. Reduction in incidence of coronary heart disease JAMA 251 1984 351 364
63. A.K. Bhattacharyya, and W.E. Connor Beta sitosterolemia and xanthomatosis. A newly described lipid storage disease in two sisters J Clin Invest 53 1974 1033 1043
64. G. Salen, S. Shefer, and L. Nguygen Sitosterolemia J Lipid Res 33 1992 945 955
65. E. Sehayek Genetic regulation of cholesterol absorption and plasma plant sterol levels: commonalities and differences J Lipid Res 44 2003 2030 2034
66. G.M.B. Berger, R.J. Pegoraro, and S.A. Patel HMG-CoA reductase is not the site of the primary defect in phytosterolemia J Lipid Res 39 1998 1046 1054
67. M.H. Lee, K. Lu, and S.B. Patel Genetic basis of sitosterolemia Curr Opin Lipidol 12 2001 141 149
68. A.F.H. Stalenhoef, M. Hectors, and P.N.M. Demacker Effect of plant sterol-enriched margarine on plasma lipids and sterols in subjects heterozygous for phytosterolaemia J Int Med 249 2001 163 166
69. P.O. Kwiterovich Jr., S.C. Chen, and D.G. Virgil Response of obligate heterozygotes for phytosterolemia to a low-fat diet and to a plant sterol esterol dietary challenge J Lipid Res 44 2003 1143 1155
70. R.S. Lees, and A.M. Lees Effect of sitosterol therapy on plasma lipid and lipoprotein concentration H. Greten Lipoprotein metabolism 1976 Springer Verlag Berlin 119 124
71. A.M. Lees, H.Y.I. Mok, and R.S. Lees Plant sterols as cholesterol lowering agents: clinical trials in patients with hypercholesterolemia and studies of sterol balance Atherosclerosis 28 1977 325 338
72. C.J. Glueck, J. Speirs, and T. Tracy Relationship of serum plant sterols (phytosterol) and cholesterol in 595 hypercholesterolemic subjects, and familial aggregation of phytosterols, cholesterol, and premature coronary heart disease in hypercholesterolemic probands and their first degree relatives Metabolism 40 1991 842 848
73. C.J. Glueck, P. Streicher, and E. Illig Serum and dietary phytosterols, cholesterol and coronary heart disease in hypercholesterolemic probands Clin Biochem 25 1992 331 334
74. T. Heinemann, G. Axtmann, and K. von Bergmann Comparison of intestinal absorption of cholesterol with different plant sterols in man Eur J Clin Invest 23 1993 827 831
75. H.F.J. Hendricks, E.J. Brink, and G.W. Meijer Safety of long-term consumption of plant sterol esters-enriched spread Eur J Clin Nutr 57 2003 681 692
76. T. Sudhop, B.M. Gottwald, and K. von Bergmann Serum plant sterols as a potential risk factor for coronary heart disease Metabolism 51 2002 1519 1521
77. R.A. Rajaratnam, H. Gylling, and T.A. Miettinen Independent association of serum squalene and noncholesterol sterols with coronary artery disease in postmenopausal women J Am Coll Cardiol 35 2000 1185 1191
78. W.H.F. Sutherland, M.J.A. Williams, and E.R. Trye Association of plasma noncholesterol sterol levels with severity of CAD Nutr Metab Cardiovasc Dis 8 1998 386 391
79. E.S. Sarkkinen, M.I.J. Uusitupa, and H. Gylling Fat-modified diets influence serum concentrations of cholesterol precursors and plant sterols in hypercholesterolemic subjects Metabolism 47 1998 744 750
80. R.G. Dyer, M.W. Stewart, and F.L. Game Phytosterols and lipoprotein composition of patients with non-insulin dependent diabetes and patients with peripheral vascular disease Diabetes Nutr Metab 8 1995 234 24181
81. H.A.W. Neil, G.W. Meijer, and L.S. Roe Randomized control trial of use by hypercholesterolaemic patients of a vegetable oil sterol-enriched fat spread Atherosclerosis 156 2001 329 337
82. H.F.J. Hendriks, E.J. Brink, and G.W. Meijer Safety of long term consumption of plant sterol esters-enriched spread Eur J Clin Nutr 57 2003 681 692
83. P.J. Jones, M. Raeini-Sarjaz, and F. Ntanios Modulation of plasma lipid levels and cholesterol kinetics by phytosterol versus phytostanol esters J Lipid Res 41 2000 697 705
84. M.J. Mussner, K.G. Parhofer, and K. von Bergmann Effects of phytosterol ester-enriched margarine on plasma lipoproteins in mild to moderate hypocholesterolemia are related to both cholesterol and fat intakes Metabolism 51 2002 189 194
85. A.L. Amundsen, F. Ntanios, and N. van der Put 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 [Advanced online publication 16. June 2004]
86. J. de Graaf, P.R.W. de Sauvage-Nolting, and M. van Dam Consumption of tall oil-derived phytosterols in a chocolate matrix significantly decreases plasma total and low density lipoprotein levels Br J Nutr 88 2002 479 488
87. L.I. Christiansen, P.L.A. Laheetnmaki, and M.R. Mannelien Cholesterol-lowering effect of spreads enriched with microcrystalline plant sterols in hypercholesterolemic subjects Eur J Nutr 40 2001 66 73
88. C.J.W. Brooks, G. Steel, and J.D. Gilbert Lipids of human atheroma. Part 4. Characterization of a new group of polar sterol esters from human atherosclerotic plaques Atherosclerosis 13 1971 223 237
89. H.N. Hodes, D.W. Crawford, and A. Sevanian Cholesterol feeding increases plasma and aortic tissue cholesterol oxide levels in parallel: further evidence for the role of cholesterol oxidation in atherosclerosis Atherosclerosis 89 1991 117 126
90. J. Vaya, M. Aviram, and S. Mahmood Selective distribution of oxysterols in atherosclerotic lesions and human plasma lipoproteins Free Radic Res 34 2001 485 497
91. D. Kritchevsky, R. Fumagalli, and F. Cattabeni Effect of triparanol on sterol composition in normal and atherosclerotic rabbit aorta Riv Farmacol Ter 1 1970 455 463
92. D. Kritchevsky, S.A. Tepper, and S.K. Czarnecki Serum and aortic levels of phytosterols in rabbits fed sitosterol or sitostanol ester preparations Lipids 38 2003 1115 1118
93. M.H. Moghadasian, B.M. McManus, and P.H. Pritchard Tall oil-derived phytosterols reduce atherosclerosis in ApoE-deficient mice Arterioscler Thromb Vasc Biol 17 1997 119 126
94. M.H. Moghadasian, B.M. McManus, D.V. Godin, and B. Rodrigues Proatherogenic and antiatherogenic effects of probucol and phytosterols in apolipoprotein E-deficient mice. Possible mechanisms of action Circulation 99 1999 1733 1739
95. F.Y. Ntanios, P.J. Jones, and J.J. Frohlich Dietary sitostanol reduces plaque formation but not lecithin cholesterol acyl transferase activity in rabbits Atherosclerosis 138 1998 101 110
96. O.L. Volger, R.P. Mensink, and J. Plat Dietary vegetable oil and wood derived plant stanol esters reduce atherosclerotic lesion size and severity in apoE*3-Leiden transgenic mice Atherosclerosis 157 2001 375 381
97. F.Y. Ntanios, A.J. van de Kooij, and E.A.M. de Deckere 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 169 2003 41 50
98. J.H.M. de Vries, M. Jansen, and D. Kromhout The fatty acid and sterol content of food composites of middle-aged men in seven countries J Food Compos Anal 10 1997 115 141
99. A. Keys Coronary heart disease in seven countries Circulation 41 Suppl 1 1997 1 211
100. G. Salen, G. Xu, and G.S. Tint Hyperabsorption and retention of campestanol in a sitosterolemic homozygote: comparison with her mother and three control subjects J Lipid Res 41 2000 1883 1889
101. W.M.N. Ratnayake, L. Plouffe, and R. Hollywood Influence of sources of dietary oils on the life-span of stroke-prone spontaneously hypertensive rats Lipids 35 2000 409 420
102. A. Kagan, J.S. Poppler, and G.G. Rhodes Factors related to stroke incidence in Hawaiian Japanese men: the Honolulu Heart Study Stroke 13 1982 62 72
103. J.D. Neaton, H. Blackburn, and D. Jacobs Serum cholesterol level and mortality findings for men screened in the multiple risk factor intervention trial Arch Intern Med 152 1992 1490 1500
104. W.M.N. Ratnayake, M.R. L'Abbe, and R. Mueller Vegetable oils high in phytosterols make erythrocytes less deformable and shorten life in stroke-prone spontaneously hypertensive rats J Nutr 130 2000 1166 1178
105. W.M.N. Ratnayake, L. Plouffe, and M.R. L'Abbe Comparative health effects of margarines fortified with plant sterols and stanols on a rat model for hemorrhagic stroke Lipids 38 2003 1237 1247
106. I. Ikeda, N. Nakagiri, and M. Sugano Mechanisms of phytosterolemia in stroke-prone spontaneously hypertensive and WKY rats Metabolism 50 2001 1361 1368
107. K.A. Scoggan, H. Gruber, and K. Lariviere A missense mutation in the Abcg5 gene causes phytosterolemia in SHR, stroke-prone SHR, and WKY rats J Lipid Res 44 2003 911 916
108. D.J.A. Jenkins, and C.W.C. Kendall Plant sterols: health claims and strategies to reduce cardiovascular risk J Am Coll Nutr 18 1999 559 562
109. W.H. Ling, and P.J.H. Jones Dietary phytosterols: a review of metabolism, benefits and side effects Life Sci 57 1995 195 206
110. M.H. Moghadasian Pharmacological properties of plant sterols: in vivo and in vitro observations Life Sci 67 2000 605 615
111. K.R. Wilund, L. Yu, and F. Xu No association between plasma levels of plant sterols and atherosclerosis in mice and men Arterioscler Thromb Vasc Biol 24 2004 2322 2326