Biological effects of oxidized phytosterols: A review of the current knowledge

Progress in Lipid Research

Volumn 47, Issue 1, 2008, Pages 37-49

  Hovenkamp, Egbert ^a   Demonty, Isabelle ^a   Plat, Jogchum ^b   Lütjohann, Dieter ^c   Mensink, Ronald P ^b   Trautwein, Elke A ^a  

^a UNILEVER RESEARCH VLAARDINGEN   (Netherlands)

^b MAASTRICHT UNIVERSITY   (Netherlands)

^c UNIVERSITY OF BONN   (Germany)

Author keywords

Absorption; Modulation of cholesterol metabolism; Oxidized phytosterols; Oxyphytosterols; Phytosterol oxidation products; Plant sterol oxides

Indexed keywords

5 CAMPESTENONE; 7 KETOCAMPESTEROL; 7 KETOSITOSTEROL; 7 OXOCHOLESTEROL; 7ALPHA HYDROXYCAMPESTEROL; 7ALPHA HYDROXYCHOLESTEROL; 7ALPHA HYDROXYSITOSTEROL; 7BETA HYDROXYCAMPESTEROL; 7BETA HYDROXYCHOLESTEROL; 7BETA HYDROXYSITOSTEROL; ALPHA EPOXYCAMPESTEROL; ALPHA EPOXYCHOLESTEROL; ALPHA EPOXYSITOSTEROL; ALPHA EPOXYSTIGMASTEROL; BETA EPOXYCAMPESTEROL; BETA EPOXYCHOLESTEROL; BETA EPOXYSITOSTEROL; BRASSICASTEROL; CAMPESTANETRIOL; CAMPESTEROL; CHOLESTANETRIOL; CHOLESTEROL; CYTOCHROME P450; DELTA5 AVENASTEROL; LOW DENSITY LIPOPROTEIN CHOLESTEROL; PHYTOSTEROL; SITOSTANETRIOL; SITOSTEROL; STIGMASTEROL; UNCLASSIFIED DRUG; UNINDEXED DRUG;

CHOLESTEROL METABOLISM; DIETARY INTAKE; ESTROGEN ACTIVITY; FOOD COMPOSITION; FOOD QUALITY; HEALTH STATUS; HUMAN; IMMUNITY; IN VIVO STUDY; INFLAMMATION; NONHUMAN; OXIDATION; PRIORITY JOURNAL; QUANTITATIVE ANALYSIS; REVIEW;

ANDROGEN ANTAGONISTS; ANIMALS; ANTICHOLESTEREMIC AGENTS; CHOLESTEROL; CHOLESTEROL, DIETARY; HUMANS; HYPERCHOLESTEROLEMIA; IMMUNOSUPPRESSIVE AGENTS; LIVER; MEDICINE, TRADITIONAL; OXIDATION-REDUCTION; PHYTOSTEROLS;

EID: 36749086632     PISSN: 01637827     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.plipres.2007.10.001     Document Type: Review

References (89)

1. Moreau R.A., Whitaker B.D., and Hicks K.B. Phytosterols, phytostanols, and their conjugates in foods: structural diversity, quantitative analysis, and health-promoting uses. Prog Lipid Res 41 (2002) 457-500
2. Cleeman J.I., Grundy S.M., Becker D., Clark L.T., Cooper R.S., Denke M.A., et al. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA 285 (2001) 2486-2497
3. Katan M.B., Grundy S.M., Jones P., Law M., Miettinen T., and Paoletti R. Efficacy and safety of plant stanols and sterols in the management of blood cholesterol levels. Mayo Clin Proc 78 (2003) 965-978
4. Chan Y.M., Varady K.A., Lin Y., Trautwein E., Mensink R.P., Plat J., et al. Plasma concentrations of plant sterols: physiology and relationship with coronary heart disease. Nutr Rev 64 (2006) 385-402
5. Bjorkhem I., Meaney S., and Diczfalusy U. Oxysterols in human circulation: which role do they have?. Curr Opin Lipidol 13 (2002) 247-253
6. Grandgirard A. Biological effects of phytosterol oxidation products, future research areas and concluding remarks. In: Guardiola F., Dutta P.C., Codony R., and Savage G.P. (Eds). Cholesterol and phytosterol oxidation products, analysis, occurrence, and biological effects (2002), AOCS Press, Champaign (IL) 375-382
7. Guardiola F. Phytosterol oxidation products: state of the art. Reprod Nutr Dev 44 (2004) 597-598
8. Lutjohann D. Sterol autoxidation: from phytosterols to oxyphytosterols. Br J Nutr 91 (2004) 3-4
9. Oehrl L., and Boyd L. Biological effects and safety aspects of phytosterol oxides. In: Dutta P.C. (Ed). Phytosterols as functional food components and nutraceuticals (2004), Marcel Dekker Inc., New York 419-430
10. Smith L.L. Cholesterol autoxidation 1981-1986. Chem Phys Lipids 44 (1987) 87-125
11. Smith L.L. Mechanisms of formation of oxysterols: a general survey. In: Crastes de Paulet A., Douste-Blazy L., and Paoletti R. (Eds). Free radicals, lipoproteins and membrane lipids (1990), Plenum Press, New York 115-132
12. Smith L.L. Review of progress in sterol oxidations: 1987-1995. Lipids 31 (1996) 453-487
13. Morel E., and Guyot M. Immunosuppressive properties of new side chain sterol hydroperoxides and of the corresponding alcohols. Int J Immunopharmacol 9 (1987) 117-121
14. Björkhem I. Mechanism of degradation of the steroid side chain in the formation of bile acids. J Lipid Res 33 (1992) 455-471
15. Guardiola F., Bou R., Boatella J., and Codony R. Analysis of sterol oxidation products in foods. J AOAC Int 87 (2004) 441-466
16. Diczfalusy U. Analysis of cholesterol oxidation products in biological samples. J AOAC Int 87 (2004) 467-473
17. Plat J., Brzezinka H., Lütjohann D., Mensink R.P., and von Bergmann K. Oxidized plant sterols in human serum and lipid infusions as measured by combined gas-liquid chromatography-mass spectrometry. J Lipid Res 42 (2001) 2030-2038
18. Soupas L., Juntunen L., Lampi A.M., and Piironen V. Effects of sterol structure, temperature, and lipid medium on phytosterol oxidation. J Agric Food Chem 52 (2004) 6485-6491
19. Emanuel H.A., Hassel C.A., Addis P.B., Bergmann S.D., and Zavoral J.H. Plasma-cholesterol oxidation-products (oxysterols) in human-subjects fed a meal rich in oxysterols. J Food Sci 56 (1991) 843-847
20. Linseisen J., and Wolfram G. Absorption of cholesterol oxidation products from ordinary foodstuff in humans. Ann Nutr Metab 42 (1998) 221-230
21. Grandgirard A., Martine L., Joffre C., Juaneda P., and Berdeaux O. Gas chromatographic separation and mass spectrometric identification of mixtures of oxyphytosterol and oxycholesterol derivatives - application to a phytosterol-enriched food. J Chromatogr A 1040 (2004) 239-250
22. Johnsson L., and Dutta P.C. Determination of phytosterol oxides in some food products by using an optimized transesterification method. Food Chem 97 (2006) 606-613
23. Abramsson-Zetterberg L., Svensson M., and Johnsson L. No evidence of genotoxic effect in vivo of the phytosterol oxidation products triols and epoxides. Toxicol Lett 173 (2007) 132-139
24. van de Bovenkamp P., Kosmeijer-Schuil T.G., and Katan M.B. Quantification of oxysterols in Dutch foods: egg products and mixed diets. Lipids 23 (1988) 1079-1085
25. Lake R.J., and Scholes P. Consumption of cholesterol oxides from fast foods fried in beef fat in New Zealand. J Am Oil Chem Soc 74 (1997) 1069-1075
26. Krauss R.M., Eckel R.H., Howard B., Appel L.J., Daniels S.R., Deckelbaum R.J., et al. AHA dietary guidelines: revision 2000: a statement for healthcare professionals from the Nutrition Committee of the American Heart Association. Circulation 102 (2000) 2284-2299
27. Tonello A., and Poli G. Serum phytosterols not only from dietary intake. Br J Nutr 96 (2006) 791-792
28. Brooks C.J.W., McKenna R.M., Cole W.J., MacLachlan J., and Lawrie T.D.V. 'Profile' analysis of oxygenated sterols in plasma and serum. Biochem Soc Trans 11 (1983) 700-701
29. Grandgirard A., Bretillon L., Martine L., and Beaufrere B. Oxyphytosterols in human plasma. Chem Phys Lipids 101 (1999) 141-213 Abstract
30. Grandgirard A., Martine L., Demaison L., Cordelet C., Joffre C., Berdeaux O., et al. Oxyphytosterols are present in plasma of healthy human subjects. Br J Nutr 91 (2004) 101-106
31. Lutjohann D., Bjorkhem I., Beil U.F., and von Bergmann K. Sterol absorption and sterol balance in phytosterolemia evaluated by deuterium-labeled sterols: effect of sitostanol treatment. J Lipid Res 36 (1995) 1763-1773
32. Ostlund Jr. R.E., McGill J.B., Zeng C.M., Covey D.F., Stearns J., Stenson W.F., et al. Gastrointestinal absorption and plasma kinetics of soy Delta(5)-phytosterols and phytostanols in humans. Am J Physiol Endocrinol Metab 282 (2002) E911-E916
33. Bosner M.S., Lange L.G., Stenson W.F., and Ostlund Jr. R.E. Percent cholesterol absorption in normal women and men quantified with dual stable isotopic tracers and negative ion mass spectrometry. J Lipid Res 40 (1999) 302-308
34. Berge K.E., Tian H., Graf G.A., Yu L.Q., Grishin N.V., Schultz J., et al. Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science 290 (2000) 1771-1775
35. Grandgirard A., Sergiel J.P., Nour M., Demaison-Meloche J., and Ginies C. Lymphatic absorption of phytosterol oxides in rats. Lipids 34 (1999) 563-570
36. Tomoyori H., Kawata Y., Higuchi T., Ichi I., Sato H., Sato M., et al. Phytosterol oxidation products are absorbed in the intestinal lymphatics in rats but do not accelerate atherosclerosis in apolipoprotein E-deficient mice. J Nutr 134 (2004) 1690-1696
37. Grandgirard A., Demaison-Meloche J., Cordelet C., and Demaison L. Incorporation of oxyphytosterols in tissues of hamster. Reprod Nutr Dev 44 (2004) 599-608
38. Subbiah M.T., and Kuksis A. Oxidation of 4-14C-sitosterol by mitochondria of rat liver and testes. Fed Proc 28 2 (1969) 515 Abstract
39. Aringer L., and Eneroth P. Studies on the formation of C7-oxygenated cholesterol and beta-sitosterol metabolites in cell-free preparations of rat liver. J Lipid Res 14 (1973) 563-572
40. Aringer L. 7-Hydroxylation of 3-oxygenated C27-steroids, C28-steroids, and C29-steroids in rat-liver 18,000 G supernate. J Lipid Res 19 (1978) 933-944
41. Shefer S., Salen G., Nguyen L., Batta A.K., Packin V., Tint G.S., et al. Competitive-inhibition of bile-acid synthesis by endogenous cholestanol and sitosterol in sitosterolemia with xanthomatosis - effect on holesterol 7-alpha-hydroxylase. J Clin Invest 82 (1988) 1833-1839
42. Aringer L., and Eneroth P. Formation and metabolism invitro of 5,6-epoxides of cholesterol and beta-sitosterol. J Lipid Res 15 (1974) 389-398
43. Aringer L., Eneroth P., and Nordstrom L. Side-chain hydroxylation of cholesterol, campesterol, and beta-sitosterol in rat-liver mitochondria. J Lipid Res 17 (1976) 263-272
44. Aringer L., and Nordstrom L. Side-chain oxidation of monooxygenated C-27-steroids and C-29-steroids in rat-liver mitochondria and 18,000g supernatant. Biochim Biophys Acta 665 (1981) 13-21
45. Hwang K.K., and Kelsey M.I. Evidence of epoxide hydrase activity in human intestinal microflora. Cancer Biochem Biophys 3 (1978) 31-35
46. Fioriti J.A., Kanuk M.J., George M., and Sims R.J. Metabolic fate of epoxycholesterol in the rat. Lipids 5 (1970) 71-75
47. Coleman D.L., and Baumann C.A. Intestinal sterols. V. Reduction of sterols by intestinal microorganisms. Arch Biochem Biophys 72 (1957) 219-225
48. Bjorkhem I., and Gustafsson J.A. Mechanism of microbial transformation of cholesterol into coprostanol. Eur J Biochem 21 (1971) 428-432
49. Marsheck W.J., Kraychy S., and Muir R.D. Microbial degradation of sterols. Appl Microbiol 23 (1972) 72-77
50. Mahato S.B., Banerjee S., Mukherjee A., and Kumar R. Metabolism of sitosterol by a pseudomonas species. Biochem J 196 (1981) 629-631
51. Ambrus G., Ilkoy E., Jekkel A., Horvath G., and Bocskei Z. Microbial transformation of beta-sitosterol and stigmasterol into 26-oxygenated derivatives. Steroids 60 (1995) 621-625
52. Grandgirard A., Martine L., Juaneda P., and Cordelet C. Sitostanetriol is not formed in vivo from sitosterol in the rat. Reprod Nutr Dev 44 (2004) 609-616
53. Kakis G., Kuksis A., and Myher J.J. Injected 7-oxo cholesterol and plant sterol derivatives and hepatic cholesterogenesis. Adv Exp Med Biol 82 (1977) 297-299
54. Boberg K.M., Einarsson K., and Björkhem I. Apparent lack of conversion of sitosterol into C-24-bile acids in humans. J Lipid Res 31 (1990) 1083-1088
55. Boberg K.M., Lund E., Olund J., and Björkhem I. Formation of C21 bile-acids from plant sterols in the rat. J Biol Chem 265 (1990) 7967-7975
56. Kaneko E., Matsuda M., Yamada Y., Tachibana Y., Shimomura I., and Makishima M. Induction of intestinal ATP-binding cassette transporters by a phytosterol-derived liver X receptor agonist. J Biol Chem 278 (2003) 36091-36098
57. Oram J.F. ATP-binding cassette transporter A1 and cholesterol trafficking. Curr Opin Lipidol 13 (2002) 373-381
58. Engel R., Johannes C., Rubic T., Walz E., Lorenz R., Schubert H., et al. Pflanzliche Wirkstoffe im Kampf gegen hohe Cholesterolspiegel: Freie Phytosterole - Neue Wirkstoffe met hohen Anforderungen an die technische Formulierung. Chem Ingenieur Tech 77 (2005) 1184
59. Plat J., Nichols J.A., and Mensink R.P. Plant sterols and stanols: effects on mixed micellar composition and LXR (target gene) activation. J Lipid Res 46 (2005) 2468-2476
60. Janowski B.A., Willy P.J., Devi T.R., Falck J.R., and Mangelsdorf D.J. An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha. Nature 383 (1996) 728-731
61. Calpe-Berdiel L., Escola-Gil J.C., Ribas V., Navarro-Sastre A., Garces-Garces J., and Blanco-Vaca F. Changes in intestinal and liver global gene expression in response to a phytosterol-enriched diet. Atherosclerosis 181 (2005) 75-85
62. Plosch T., Kruit J.K., Bloks V.W., Huijkman N.C., Havinga R., Duchateau G.S., et al. Reduction of cholesterol absorption by dietary plant sterols and stanols in mice is independent of the Abcg5/8 transporter. J Nutr 136 (2006) 2135-2140
63. Field F.J., Born E., and Mathur S.N. LXR/RXR ligand activation enhances basolateral efflux of beta-sitosterol in CaCo-2 cells. J Lipid Res 45 (2004) 905-913
64. Ikeda I., Konno R., Shimizu T., Ide T., Takahashi N., Kawada T., et al. Campest-5-en-3-one, an oxidized derivative of campesterol, activates PPARalpha, promotes energy consumption and reduces visceral fat deposition in rats. Biochim Biophys Acta 1760 (2006) 800-807
65. Suzuki K., Tanaka M., Konno R., and Kaneko Y. Effects of 5-campestenone (24-methylcholest-5-en-3-one) on the type 2 diabetes mellitus model animal C57BL/KsJ-db/db mice. Horm Metab Res 34 (2002) 121-126
66. Konno R., Kaneko Y., Suzuki K., and Matsui Y. Effect of 5-campestenone (24-methylcholest-5-en-3-one) on Zucker diabetic fatty rats as a type 2 diabetes mellitus model. Horm Metab Res 37 (2005) 79-83
67. Suzuki K., Shimizu T., and Nakata T. The cholesterol metabolite cholest-4-en-3-one and its 3-oxo derivatives suppress body weight gain, body fat accumulation and serum lipid concentration in mice. Bioorg Med Chem Lett 8 (1998) 2133-2138
68. Naumann E, Plat J, Kester ADM, Mensink RP. The baseline serum lipoprotein profile is related to plant stanol induced changes in serum lipids and lipoproteins. J Am Coll Nutr, in press.
69. Plat J, Dallinga-Thie GM, Brufau G, Mensink RP. Plant stanol esters not only lower serum LDL cholesterol but also triacylglycerol concentrations in patients with the metabolic syndrome. In: European atherosclerosis society, 76th congress, 2007, Abstract.
70. Kimura Y., Yasukawa K., Takido M., Akihisa T., and Tamura T. Inhibitory effect of some oxygenated stigmastane-type sterols on 12-O-tetradecanoylphorbol-13-acetate-induced inflammation in mice. Biol Pharm Bull 18 (1995) 1617-1619
71. Sato H., Nishida S., Tomoyori H., Sato M., Ikeda I., and Imaizumi K. Oxysterol regulation of estrogen receptor alpha-mediated gene expression in a transcriptional activation assay system using HeLa cells. Biosci Biotechnol Biochem 68 (2004) 1790-1793
72. Muller C., Wagner J., Johannes C., Lorenz R.L., and Lehmann L. Oxidation products of the phytosterol stigmasterol interact with estrogen receptor-dependent processes in cultured human breast and endometrium cell lines. Naunyn Schmiedebergs Arch Pharmacol 375 (2007) 80
73. van den Heuvel M.R., Leusch F.D., Taylor S., Shannon N., and McKague A.B. Assessment of the reproductive-endocrine disrupting potential of chlorine dioxide oxidation products of plant sterols. Environ Sci Technol 40 (2006) 2594-2600
74. Baker V.A., Hepburn P.A., Kennedy S.J., Jones P.A., Lea L.J., Sumpter J.P., et al. Safety evaluation of phytosterol esters. Part 1. Assessment of oestrogenicity using a combination of in vivo and in vitro assays. Food Chem Toxicol 37 (1999) 13-22
75. Marshall W.J., and McLean A.E. A requirement for dietary lipids for induction of cytochrome P-450 by phenobarbitone in rat liver microsomal fraction. Biochem J 122 (1971) 569-573
76. Nagano H., Poyser J.P., Cheng K., Bang L., Ourisson G., and Beck J.P. Chemistry and biochemistry of Chinese drugs. Part II. Hydroxylated sterols, cytotoxic towards cancerous cells: synthesis and testing. J Chem Res Synop (1977) 218
77. Adcox C., Boyd L., Oehrl L., Allen J., and Fenner G. Comparative effects of phytosterol oxides and cholesterol oxides in cultured macrophage-derived cell lines. J Agric Food Chem 49 (2001) 2090-2095
78. Maguire L., Konoplyannikov M., Ford A., Maguire A.R., and O'Brien N.M. Comparison of the cytotoxic effects of beta-sitosterol oxides and a cholesterol oxide, 7-beta-hydroxycholesterol, in cultured mammalian cells. Br J Nutr 90 (2003) 767-775
79. Ryan E., Chopra J., McCarthy F., Maguire A.R., and O'Brien N.M. Qualitative and quantitative comparison of the cytotoxic and apoptotic potential of phytosterol oxidation products with their corresponding cholesterol oxidation products. Br J Nutr 94 (2005) 443-451
80. Roussi S., Winter A., Gosse F., Werner D., Zhang X., Marchioni E., et al. Different apoptotic mechanisms are involved in the antiproliferative effects of 7-beta-hydroxysitosterol and 7-beta-hydroxycholesterol in human colon cancer cells. Cell Death Differ 12 (2005) 128-135
81. Lea L.J., Hepburn P.A., Wolfreys A.M., and Baldrick P. Safety evaluation of phytosterol esters. Part 8. Lack of genotoxicity and subchronic toxicity with phytosterol oxides. Food Chem Toxicol 42 (2004) 771-783
82. Meyer W., Jungnickel H., Jandke M., Dettner K., and Spiteller G. On the cytotoxicity of oxidized phytosterols isolated from photoautotrophic cell cultures of Chenopodium rubrum tested on meal-worms Tenebrio molitor. Phytochemistry 47 (1998) 789-797
83. Pakrashi A., and Basak B. Abortifacient effect of steroids from Ananas comosus and their analogues on mice. J Reprod Fertil 46 (1976) 461-462
84. Pakrashi A., and Chakrabarty S. Antifertility effects of the steroid 5-alpha-stigmastane-3-beta, 5,6-beta-triol-3-monobenzoate on mice. Contraception 19 (1979) 145-150
85. Pakrashi A., and Chakrabarty S. Acute toxicity and teratological investigations of the steroid 5-alpha-stigmastane-3-beta, 5,6-beta-triol-3 monobenzoate. Indian J Exp Biol 18 (1980) 641-643
86. Pakrashi A., and Chakrabarty S. Biological profile of the steroid 5-alpha-stigmastane-3-beta, 5,6-beta-triol-3-monobenzoate. Contraception 23 (1981) 315-323
87. Carpenter K.L. Good COP, bad COP: an unsolved murder. Are dietary cholesterol oxidation products guilty of atherogenicity?. Br J Nutr 88 (2002) 335-338
88. Schroeder G., Rohmer M., Beck J.P., and Anton R. 7-Oxo-, 7[alpha]-hydroxy- and 7[beta]-hydroxysterols from Euphorbia fischeriana. Phytochemistry 19 (1980) 2213-2215
89. Chaurasia N., and Wichtl M. Sterols and steryl glycosides from Urtica dioica. J Nat Prod 50 (1987) 881-885