Plant sterols: factors affecting their efficacy and safety as functional food ingredients

Alvin Berger, Peter J H Jones, Suhad S Abumweis, Alvin Berger, Peter J H Jones, Suhad S Abumweis

Abstract

Plant sterols are naturally occurring molecules that humanity has evolved with. Herein, we have critically evaluated recent literature pertaining to the myriad of factors affecting efficacy and safety of plant sterols in free and esterified forms. We conclude that properly solubilized 4-desmetyl plant sterols, in ester or free form, in reasonable doses (0.8-1.0 g of equivalents per day) and in various vehicles including natural sources, and as part of a healthy diet and lifestyle, are important dietary components for lowering low density lipoprotein (LDL) cholesterol and maintaining good heart health. In addition to their cholesterol lowering properties, plant sterols possess anti-cancer, anti-inflammatory, anti-atherogenicity, and anti-oxidation activities, and should thus be of clinical importance, even for those individuals without elevated LDL cholesterol. The carotenoid lowering effect of plant sterols should be corrected by increasing intake of food that is rich in carotenoids. In pregnant and lactating women and children, further study is needed to verify the dose required to decrease blood cholesterol without affecting fat-soluble vitamins and carotenoid status.

References

    1. Piironen V, Lindsay DG, Miettinen TA, Toivo J, Lampi A-M. Plant sterols: biosynthesis, biological function and their importance to human nutrition. J Sci Food Agric. 2000;80:939–966. doi: 10.1002/(SICI)1097-0010(20000515)80:7<939::AID-JSFA644>;2-3.
    1. Moreau R, Whitaker B, Hicks K. Phytosterols, phytostanols, and their conjugates in foods: structural diversity, quantitative analysis, and health-promoting uses. Prog Lipid Res. 2002;41:457. doi: 10.1016/S0163-7827(02)00006-1.
    1. Ahrens EH Jr, Boucher CA. The composition of a simulated American diet. J Am Diet Assoc. 1978;73:613–620.
    1. Cerqueira MT, Fry MM, Connor WE. The food and nutrient intakes of the Tarahumara Indians of Mexico. Am J Clin Nutr. 1979;32:905–915.
    1. Nair PP, Turjman N, Kessie G, Calkins B, Goodman GT, Davidovitz H, Nimmagadda G. Diet, nutrition intake, and metabolism in populations at high and low risk for colon cancer. Dietary cholesterol, beta-sitosterol, and stigmasterol. Am J Clin Nutr. 1984;40:927–930.
    1. Hirai K, Shimazu C, Takezoe R, Ozeki Y. Cholesterol, phytosterol and polyunsaturated fatty acid levels in 1982 and 1957 Japanese diets. J Nutr Sci Vitaminol (Tokyo) 1986;32:363–372.
    1. Miettinen TA, Tilvis RS, Kesaniemi YA. Serum cholestanol and plant sterol levels in relation to cholesterol metabolism in middle-aged men . Metabolism. 1989;38:136–140. doi: 10.1016/0026-0495(89)90252-7.
    1. Morton GM, Lee SM, Buss DH, Lawrance P. Intakes and major dietary sources of cholesterol and phytosterols in the British diet. J Hum Nutr Diet. 1995;8:429–440.
    1. de Vries JHM, Jansen A, Kromhout D, van de Bovenkamp P, van Staveren WA, Mensink RP, Katan MB. The fatty acid and sterol content of food composites of middle-aged men in seven countries. J Food Comp Anal. 1997;10:115–141. doi: 10.1006/jfca.1997.0525.
    1. Jenkins DJ, Kendall CW, Marchie A, Jenkins AL, Connelly PW, Jones PJ, Vuksan V. The Garden of Eden--plant based diets, the genetic drive to conserve cholesterol and its implications for heart disease in the 21st century. Comp Biochem Physiol A Mol Integr Physiol. 2003;136:141–151. doi: 10.1016/S1095-6433(02)00345-8.
    1. Ostlund R E, Jr, McGill JB, Zeng CM, Covey DF, Stearns J, Stenson WF, Spilburg CA. Gastrointestinal absorption and plasma kinetics of soy Delta(5)-phytosterols and phytostanols in humans. Am J Physiol Endocrinol Metab. 2002;282:E911–E916.
    1. Bosner MS, Lange LG, Stenson WF, Ostlund Jr RE. Percent cholesterol absorption in normal women and men quantified with dual stable isotopic tracers and negative ion mass spectrometry. J Lipid Res. 1999;40:302–308.
    1. 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.
    1. Awad AB, Roy R, Fink CS. Beta-sitosterol, a plant sterol, induces apoptosis and activates key caspases in MDA-MB-231 human breast cancer cells. Oncol Rep. 2003;10:497–500.
    1. Moghadasian MH, McManus BM, Pritchard PH, Frohlich JJ. "Tall oil"-derived phytosterols reduce atherosclerosis in ApoE-deficient mice. Arterioscler Thromb Vasc Biol. 1997;17:119–126.
    1. Moghadasian MH, McManus BM, Godin DV, Rodrigues B, Frohlich JJ. Proatherogenic and antiatherogenic effects of probucol and phytosterols in apolipoprotein E-deficient mice: possible mechanisms of action. Circulation. 1999;99:1733–1739.
    1. Bouic PJ. The role of phytosterols and phytosterolins in immune modulation: a review of the past 10 years. Curr Opin Clin Nutr Metab Care. 2001;4:471–475. doi: 10.1097/00075197-200111000-00001.
    1. van Rensburg SJ, Daniels WM, van Zyl JM, Taljaard JJ. A comparative study of the effects of cholesterol, beta-sitosterol, beta-sitosterol glucoside, dehydroepiandrosterone sulphate and melatonin on in vitro lipid peroxidation. Metab Brain Dis. 2000;15:257–265. doi: 10.1023/A:1011167023695.
    1. 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;53:319–327. doi: 10.1038/sj.ejcn.1600728.
    1. Sierksma A, Weststate 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;82:273–282.
    1. Denke MA. Lack of efficacy of low-dose sitostanol therapy as an adjunct to a cholesterol-lowering diet in men with moderate hypercholesterolemia. Am J Clin Nutr. 1995;61:392–396.
    1. Ostlund RE, Spilburg CA, Stenson WF. Sitostanol administered in lecithin micelles potently reduces cholesterol absorption in humans. Am J Clin Nutr. 1999;70:826–831.
    1. Ikeda I, Nakashima-Yoshida K, Sugano M. Effects of cycloartenol on absorption and serum levels of cholesterol in rats. J Nutr Sci Vitaminol. 1985;31:375–384.
    1. Kritchevsky D, Tepper SA, Czarnecki SK, Kyle DJ. Effects of 4-methylsterols from algae and of b sitosterol on cholesterol metabolism in rats. Nutr Res. 1999;19:1649–1654. doi: 10.1016/S0271-5317(99)00120-7.
    1. Westrate JA, Meijer GW. Plant sterol-enriched margarines and reduction of plasma total and LDL-cholesterol concentrations in normocholesterolaemic and midly hypercholesterolaemic subjects. Eur J Clin Nutr. 1998;52:334–343. doi: 10.1038/sj.ejcn.1600559.
    1. 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;72:1510–1515.
    1. Vanhanen HT, Miettinen TA. Effects of unsaturated and saturated dietary plant sterols on their serum contents . Clin Chim Acta. 1992;205:97–107.
    1. Miettinen TA, Vanhanen H. Dietary sitostanol related to absorption, synthesis and serum level of cholesterol in different apolipoprotein E phenotypes. Atherosclerosis. 1994;105:217–226.
    1. Tilvis RS, Miettinen TA. Serum plant sterols and their relation to cholesterol absorption. Am J Clin Nutr. 1986;43:92–97.
    1. Miettinen TA, Kesaniemi YA. Cholesterol absorption: regulation of cholesterol synthesis and elimination and within-population variations of serum cholesterol levels . Am J Clin Nutr. 1989;49:629–635.
    1. Pouteau E, Piguet-Welsch C, Berger A, Fay LB. Determination of cholesterol absorption in humans: from radiolabel to stable isotope studies. Isotopes Environ Health Stud. 2003;39:247–257. doi: 10.1080/10256010310001621155.
    1. 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. 1994;87:61–67.
    1. 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;39:291–295.
    1. Smith SJ, Cooper GR, Myers GL, Sampson EJ. Biological variability in concentrations of serum lipids: sources of variation among results from published studies and composite predicted values . Clin Chem. 1993;39:1012–1022.
    1. Law MR, Wald NJ, Thompson SG. By how much and how quickly does reduction in serum cholesterol concentration lower risk of ischaemic heart disease? BMJ. 1994;308:367–372.
    1. Stampfer MJ, Sacks FM, Salvini S, Willett WC, Hennekens CH. A prospective study of cholesterol, apolipoproteins, and the risk of myocardial infarction . N Engl J Med. 1991;325:373–381.
    1. 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.
    1. 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;74:33–43.
    1. Christiansen LI, Lähteenmäki PLA, Mannelin MR, Seppänen-Laakso TE, Hiltunen RVK, Yliruusi JK. Cholesterol-lowering effect of spreads enriched with microcrystalline plant sterols in hypercholesterolemic subjects. Eur J Nutr. 2001;40:66–73. doi: 10.1007/s003940170017.
    1. 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;86:233–239.
    1. Nguyen TT, Dale LC, von Bergmann K, Croghan IT. Cholesterol-lowering effect of stanol ester in a US population of mildly hypercholesterolemic men and women: a randomized controlled trial. Mayo Clin Proc. 1999;74:1198–2006.
    1. 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.
    1. Schwab US, Vogel S, Lammi-Keefe CJ, Ordovas JM, Schaefer EJ, Li ZG, Ausman LM, Gualtieri L, Goldin BR, Furr HC, Lichtenstein AH. Varying dietary fat type of reduced-fat diets has little effect on the susceptibility of LDL to oxidative modification in moderately hypercholesterolemic subjects. J Nutr. 1998;128:1703–1709.
    1. Pouteau E, Monnard I, Piguet-Welsch C, Groux MJA, Sagalowicz L, Berger A. Non-esterified plant sterols solubilized in low fat milks inhibit cholesterol absorption: a stable isotope double-blind crossover study. Eur J Nutr. 2003;42:154–164.
    1. Devaraj S, Jialal I, Vega S. Plant sterol-fortified orange juice effectively lowers cholesterol levels in mildly hypercholesterolemic healthy individuals. Arterioscler Thromb Vasc Biol. 2004;24:e25. doi: 10.1161/01.ATV.0000120784.08823.99.
    1. Howard BV, Gidding SS, Liu K. Association of apolipoprotein E phenotype with plasma lipoproteins in African-American and white young adults. The CARDIA Study. Coronary Artery Risk Development in Young Adults. Am J Epidemiol. 1998;148:859–868.
    1. Pedersen A, Baumstark MW, Marckmann P, Gylling H, Sandstrom B. An olive oil-rich diet results in higher concentrations of LDL cholesterol and a higher number of LDL subfraction particles than rapeseed oil and sunflower oil diets. J Lipid Res. 2000;41:1901–1911.
    1. Wagner KH, Tomasch R, Elmadfa I. Impact of diets containing corn oil or olive/sunflower oil mixture on the human plasma and lipoprotein lipid metabolism. Eur J Nutr. 2001;40:161–167. doi: 10.1007/s003940170004.
    1. Ostlund RE, Jr, Racette SB, Okeke A, Stenson WF. Phytosterols that are naturally present in commercial corn oil significantly reduce cholesterol absorption in humans. Am J Clin Nutr. 2002;75:1000–1004.
    1. Berger A, Gremaud G, Baumgartner M, Rein D, Monnard I, Kratky E, Geiger W, Burri J, Dionisi F, Allan M, Lambelet P. Cholesterol-lowering properties of amaranth grain and oil in hamsters. Int J Vitam Nutr Res. 2003;73:39–47.
    1. Berger A, Monnard I, Dionisi F, Gumy D, Lambelet P, Hayes KC. Preparation of amaranth flakes, crude oils, and refined oils for evaluation of cholesterol-lowering properties in hamster. Food Chem. 2003;81:119–124. doi: 10.1016/S0308-8146(02)00387-4.
    1. 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;87:227–238. doi: 10.1079/BJNBJN2001509.
    1. Kritchevsky D, Tepper SA, Wright S, Czarnecki SK, Wilson TA, Nicolosi RJ. Cholesterol vehicle in experimental atherosclerosis 24: avocado oil. J Am Coll Nutr. 2003;22:52–55.
    1. Perona JS, Canizares J, Montero E, Sanchez-Dominguez JM, Ruiz-Gutierrez V. Plasma lipid modifications in elderly people after administration of two virgin olive oils of the same variety (Olea europaea var. hojiblanca) with different triacylglycerol composition. Br J Nutr. 2003;89:819–826. doi: 10.1079/BJN2003852.
    1. Garg ML, Blake RJ, Wills RB. Macadamia nut consumption lowers plasma total and LDL cholesterol levels in hypercholesterolemic men. J Nutr. 2003;133:1060–1063.
    1. Khallouki F, Younos C, Soulimani R, Oster T, Charrouf Z, Spiegelhalder B, Bartsch H, Owen RW. Consumption of argan oil (Morocco) with its unique profile of fatty acids, tocopherols, squalene, sterols and phenolic compounds should confer valuable cancer chemopreventive effects. Eur J Cancer Prev. 2003;12:67–75. doi: 10.1097/00008469-200302000-00011.
    1. Ostlund R E, Jr, Racette SB, Stenson WF. Inhibition of cholesterol absorption by phytosterol-replete wheat germ compared with phytosterol-depleted wheat germ. Am J Clin Nutr. 2003;77:1385–1389.
    1. Maki KC, Davidson MH, Umporowicz DM, Schaefer EJ, Diklin MR, Ingram KA, Chen S, McNamara Jr W, Gebhart B, Ribaya-Mercado JD, Perrone G, Robins SJ, Franke WC. Lipid responses to plant sterol-enriched reduced-fat spreads incorporated into a National Cholesterol Education step 1 diet. Am J Clin Nutr. 2001;74:33–43.
    1. 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.
    1. Law M. Plant sterol and stanol margarines and health. Br Med J. 2000;320:861–864. doi: 10.1136/bmj.320.7238.861.
    1. 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;78:965–978.
    1. Hallikainen MA, Uusitupa MIJ. 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;69:403–410.
    1. Jones PJH, Ntamios FY, Mahmoud Raeini-Sarjaz C. Cholesterol-lowering efficacy of sitostanol-containing phytosterol mixture with a prudent diet in hyperlipidemic men. Am J Clin Nutr. 1999;69:1144–1150.
    1. van Heyningen C. Cholesterol lowering margarine may not be useful in healthy fat modified diet. Brit Med J. 1999;319:186.
    1. 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;51:189–194. doi: 10.1053/meta.2002.29988.
    1. Maki KC, Shinnick F, Seeley MA, Veith PE, Quinn LC, Hallissey PJ, Temer A, Davidson MH. Food products containing free tall oil-based phytosterols and oat beta-glucan lower serum total and LDL cholesterol in hypercholesterolemic adults. J Nutr. 2003;133:808–813.
    1. Judd JT, Baer DJ, Clevidence BA, Muesing RA, Chen SC, Meijer GW. Dietary fat and fatty acids and plasma lipid modifying effects of sterol esters. FASEB J. 2001;15:A639.
    1. Gremaud G, Piguet C, Baumgartner M, Pouteau E, Decarli B, Berger A, Fay LB. Simultaneous assessment of cholesterol absorption and synthesis in humans using on-line gas chromatography/combustion and gas chromatography/pyrolysis/isotope-ratio mass spectrometry. Rapid Commun Mass Spectrom. 2001;15:1207–1213. doi: 10.1002/rcm.365.
    1. Gremaud G, Dalan E, Piguet C, Baumgartner M, Ballabeni P, Decarli B, Leser ME, Berger A, Fay LB. Effects of non-esterified stanols in a liquid emulsion on cholesterol absorption and synthesis in hypercholesterolemic men. Eur J Nutr. 2002;41:54–60. doi: 10.1007/s003940200008.
    1. Mensink RP, Ebbing S, Lindhout M, Plat J, van Heugten MMA. 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. doi: 10.1016/S0021-9150(01)00562-7.
    1. Richelle M, Enslen M, Hager C, Groux M, Tavazzi I, Godin JP, Berger A, Métairon S, Quaile S, Piguet C, Sagalowicz L, Green H, Fay LB. Both free and esterified plant sterols decrease the bioavailability of β-carotene and β-tocopherol, in normocholesterolemic humans. Am J Clin Nutr. 2004. p. (In press).
    1. 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;55:1084–1090. doi: 10.1038/sj.ejcn.1601264.
    1. 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.
    1. Carr TP, Cornelison RM, Illston BJ, Stuefer-Powell CL, Gallaher DD. Plant sterols alter bile acid metabolism and reduce cholesterol absorption in hamsters fed a beef-based diet . Nutr Res. 2002;22:745–754. doi: 10.1016/S0271-5317(02)00389-5.
    1. Spilburg CA, Goldberg AC, McGill JB, Stenson WF, Racette SB, Bateman J, McPherson TB, Ostlund R E, Jr. Fat-free foods supplemented with soy stanol-lecithin powder reduce cholesterol absorption and LDL cholesterol. J Am Diet Assoc. 2003;103:577–581. doi: 10.1053/jada.2003.50110.
    1. Hallikainen MA, Sarkkinen ES, Gylling H, Erkkilä AT, Uusitupa MIJ. 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. doi: 10.1038/sj.ejcn.1601083.
    1. Jones PJ, Raeini-Sarjaz M, Ntanios FY, Vanstone CA, Feng J, Parsons WE. Modulation of plasma lipid levels and cholesterol kinetics by phytosterol versus phytostanol esters. J Lipid Res. 2000;41:697–705.
    1. Neil HAW, Meijer GW, Roe LS. Randomised controlled trial of use by hypercholesterolaemic patients of a vegetable oil sterol-enriched fat spread. Atherosclerrosis. 2001;156:329–337. doi: 10.1016/S0021-9150(00)00653-5.
    1. 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;132:3650–3655.
    1. 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;57:170–176. doi: 10.1038/sj.ejcn.1601531.
    1. Hendriks HF, Brink EJ, Meijer GW, Princen HM, Ntanios FY. Safety of long-term consumption of plant sterol esters-enriched spread. Eur J Clin Nutr. 2003;57:681–692. doi: 10.1038/sj.ejcn.1601598.
    1. Homma Y, Ikeda I, Ishikawa T, Tateno M, Sugano M, Nakamura H. A randomized, placebo-controlled trial: Decrease in plasma low-density lipoprotein cholesterol, apolipoprotein B, cholesteryl ester transfer protein, and oxidized low-density lipoprotein by plant stanol ester-containing spread. Nutrition. 2003;19::369–374. doi: 10.1016/S0899-9007(02)00926-7.
    1. Jones PJH, Vanstone CA, Raieni-Sarjaz M, St-Onge M-P. Phytosterols in low-and non-fat beverages as part of a controlled diet fail to lower plasma lipid levels. J Lipid Res. 2003;44:1713–1719. doi: 10.1194/jlr.M300089-JLR200.
    1. Groux MJA, Leser M, Berger A. Milk product comprising unesterified sterol. Nestle SA; 2003. iPatent WO03009708.
    1. von Bonsdorff-Nikander A, Karjalainen M, Rantanen J, Christiansen L, Yliruusi J. Physical stability of a microcrystalline beta-sitosterol suspension in oil. Eur J Pharm Sci. 2003;19:173–179. doi: 10.1016/S0928-0987(03)00067-8.
    1. Jenkins DJ, Kendall CW, Marchie A, Faulkner D, 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;52:1478–1483. doi: 10.1016/S0026-0495(03)00260-9.
    1. Tikkanen MJ, Hogstrom P, Tuomilehto J, Keinanen-Kiukaanniemi S, Sundvall J, Karppanen H. Effect of a diet based on low-fat foods enriched with nonesterified plant sterols and mineral nutrients on serum cholesterol. Am J Cardiol. 2001;88:1157–1162. doi: 10.1016/S0002-9149(01)02053-7.
    1. Vaskonen T, Mervaala E, Krogerus L, Karppanen H. Supplementation of plant sterols and minerals benefits obese zucker rats fed an atherogenic diet. J Nutr. 2002;132:231–237.
    1. Vaskonen T, al. et. Effects of calcium and plant sterols on serum lipids in obese Zucker rats on a low-fat diet. Br J Nutr. 2002;87:239–246. doi: 10.1079/BJNBJN2001508.
    1. Manhas A, Farmer JA. Hypolipidemic therapy and cholesterol absorption. Curr Atheroscler Rep. 2004;6:89–93.
    1. Smart EJ, De Rose RA, Farber SA. Annexin 2-caveolin 1 complex is a target of ezetimibe and regulates intestinal cholesterol transport. Proc Natl Acad Sci U S A. 2004;101:3450–3455. doi: 10.1073/pnas.0400441101.
    1. Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, Joyal SV, Hill KA, Pfeffer MA, Skene AM. Comparison of Intensive and Moderate Lipid Lowering with Statins after Acute Coronary Syndromes. N Engl J Med. 2004;350:15. doi: 10.1056/NEJMoa040583.
    1. Topol EJ. Intensive Statin Therapy -- A Sea Change in Cardiovascular Prevention. N Engl J Med. 2004;350:15. doi: 10.1056/NEJMe048061.
    1. FDA Food labeling: health claims; plant sterol/stanol esters and coronary heart disease. Food and Drug Admin Fed Reg. 2000;65:54686–54739.
    1. Australia New Zealand Food Authority ANZFA Phytosterol esters derived from vegetable oils: Final Risk Analysis Report Application A410, 30/5/01. 2001.
    1. Plat J, Van Onselen ENM, Van Heugten MMA, 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;54:671–677. doi: 10.1038/sj.ejcn.1601071.
    1. 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;69:1144–1150.
    1. Homma Y, Ishikawa T, Tateno M, Mitaniyama A, Sugano M. Cholesterol and apolipoprotein-lowering effect of plant stanol ester in healthy Japanese men and women. J Jpn Soc Nutr Food Sci. 2000;53:155–162.
    1. 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;148:101–112. doi: 10.1016/S0021-9150(99)00261-0.
    1. Vanstone CA, Raeini-Sarjaz M, Parsons WE, Jones PJ. Unesterified plant sterols and stanols lower LDL-cholesterol concentrations equivalently in hypercholesterolemic persons. Am J Clin Nutr. 2002;76:1272–1278.
    1. Williams CL, Bollella MC, Strobino BA, Boccia L, Campanaro L. Plant stanol ester and bran fiber in chilhood : effects on lipids, stool weight and stool frequency in preschool children. J Am Coll Nutr. 1999;18:572–581.
    1. 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;333:1308–1312. doi: 10.1056/NEJM199511163332002.
    1. Jones PJ, Howell T, MacDougall DE, Feng JY, Parsons W. Short-term administration of tall oil phytosterols improves plasma lipid profiles in subjects with different cholesterol levels. Metabolism. 1998;47:751–756.
    1. Hallikainen MA, Sarkkinen ES, Uusitupa MIJ. Effects of low-fat stanol ester enriched margarines on concentrations of serum carotenoids in subjects with elevated serum cholesterol concentrations. Eur J Clin Nutr. 1999;53:966–969. doi: 10.1038/sj.ejcn.1600882.
    1. De Graaf J, De Sauvage Nolting PR, Van Dam M, Belsey EM, Kastelein JJ, Pritchard PH, Stalenhoef AF. 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. doi: 10.1079/BJN2002690.
    1. 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;75:79–86.
    1. Gylling H, Miettinen TA. Serum cholesterol and cholesterol and lipoprotein metabolism in hypercholesterolaemic NIDDM patients before and during sitostanol ester-margarine treatment. Diabetologia. 1994;37:773–780. doi: 10.1007/s001250050178.
    1. Gylling H, Miettinen TA. The effects of inhibiting cholesterol absorption and synthesis on cholesterol and lipoprotein metabolism in hypercholesterolemic non-insulin dependent men. J Lipid Res. 1996;37:1776–1785.
    1. Igel M, Giesa U, Lutjohann D, von Bergmann K. Comparison of the intestinal uptake of cholesterol, plant sterols, and stanols in mice. J Lipid Res. 2003;44:533–538. doi: 10.1194/jlr.M200393-JLR200.
    1. Turley SD, Dietschy JM. Sterol absorption by the small intestine. Curr Opin Lipidol. 2003;14:233–240. doi: 10.1097/00041433-200306000-00002.
    1. Field FJ, Born E, Mathur SN. LXR/RXR ligand activation enhances the basolateral efflux of {beta}-sitosterol in CaCo-2 cells. J Lipid Res. 2004;45:905–913. doi: 10.1194/jlr.M300473-JLR200.
    1. Mutch DM, Anderle P, Fiaux M, Mansourian R, Vidal K, Wahli W, Williamson G, Roberts MA. Regional variations in ABC transporter expression along the mouse intestinal tract. Physiol Genomics. 2004;17:11–20. doi: 10.1152/physiolgenomics.00150.2003.
    1. Scoggan KA, Gruber H, Lariviere K. A missense mutation in the Abcg5 gene causes phytosterolemia in SHR, stroke-prone SHR, and WKY rats. J Lipid Res. 2003;44:911–916. doi: 10.1194/jlr.M200438-JLR200.
    1. Plat J, Mensink RP. Increased intestinal ABCA1 expression contributes to the decrease in cholesterol absorption after plant stanol consumption. FASEB J. 2002;16:1248–1253. doi: 10.1096/fj.01-0718hyp.
    1. Kaneko E, Matsuda M, Yamada Y, Tachibana Y, Shimomura I, Makishima M. Induction of intestinal ATP-binding cassette transporters by a phytosterol-derived liver X receptor agonist. J Biol Chem. 2003;278:36091–36098. doi: 10.1074/jbc.M304153200.
    1. Yu L, von Bergmann K, Lutjohann D, Hobbs HH, Cohen JC. Selective sterol accumulation in ABCG5/ABCG8 deficient mice. J Lipid Res. 2004;45:301–307. doi: 10.1194/jlr.M300377-JLR200.
    1. Weggemans RM, Zock PL, Tai ES, Ordovas JM, Molhuizen HO, Katan MB. ATP binding cassette G5 C1950G polymorphism may affect blood cholesterol concentrations in humans. Clin Genet. 2002;62:226–229. doi: 10.1034/j.1399-0004.2002.620307.x.
    1. Berge KE, von Bergmann K, Lutjohann D, Guerra R, Grundy SM, Hobbs HH, Cohen JC. Heritability of plasma noncholesterol sterols and relationship to DNA sequence polymorphism in ABCG5 and ABCG8. J Lipid Res. 2002;43:486–494.
    1. Kesäniemi YA, Ehnholm C, Miettinen TA. Intestinal cholesterol absorption efficiency in man is related to apoprotein E phenotype. J Clin Invest. 1987;80:578–581.
    1. Vanhanen HT, Blomqvist S, Ehnholm C, Hyvonen M, Jauhiainen M, Torstila I, Miettinen TA. Serum cholesterol, cholesterol precursors, and plant sterols in hypercholesterolemic subjects with different apoE phenotypes during dietary sitostanol ester treatment. J Lipid Res. 1993;34:1535–1544.
    1. Kramer W, Girbig F, Corsiero D, Burger K, Fahrenholz F, Jung C, Muller G. Intestinal cholesterol absorption: identification of different binding proteins for cholesterol and cholesterol absorption inhibitors in the enterocyte brush border membrane. Biochim Biophys Acta. 2003;1633:13–26. doi: 10.1016/S1388-1981(03)00068-4.
    1. Harris M, Davis W, Brown WV. Ezetimibe. Drugs Today (Barc) 2003;39:229–247.
    1. Cruz ML, Wong WW, Mimouni F, Hachey DL, Setchell KD, Klein PD, Tsang RC. Effects of infant nutrition on cholesterol synthesis rates. Pediatr Res. 1994;35:135–140.
    1. Alasmi M, Thorkelson T, Krug-Wispe S, Bayley TM, Jones PJH, Tsang RC. Cholesterol supplementation effect on cholesterol synthesis rates (FSR) in infants. Pediatr Res. 1996;39:116A.
    1. Bayley TM, Alasmi M, Thorkelson T, Krugwispe S, Jones PJH, Bulani JL, Tsang RC. Influence of formula versus breast milk on cholesterol synthesis rates in four-month-old infants. Pediatr Res. 1998;44:60–67.
    1. Huisman M, van Beusekom CM, Lanting CI, Nijeboer HJ, Muskiet FA, Boersma ER. Triglycerides, fatty acids, sterols, mono- and disaccharides and sugar alcohols in human milk and current types of infant formula milk . Eur J Clin Nutr. 1996;50:255–260.
    1. Fall CH, Barker DJ, Osmond C, Winter PD, Clark PM, Hales CN. Relation of infant feeding to adult serum cholesterol concentration and death from ischaemic heart disease. Brit Med J. 1992;304:801–805.
    1. Kolacek S, Kapetanovic T, Zimolo A, Luzar V. Early determinants of cardiovascular risk factors in adults. A. Plasma lipids. Acta Paediatr. 1993;82:699–704.
    1. Palinski W, Napoli C. The fetal origins of atherosclerosis: maternal hypercholesterolemia, and cholesterol-lowering or antioxidant treatment during pregnancy influence in utero programming and postnatal susceptibility to atherogenesis. FASEB J. 2002;16:1348–1360. doi: 10.1096/fj.02-0226rev.
    1. Joki P, Suomalainen H, Jarvinen KM, Juntunen-Backman K, Gylling H, Miettinen TA, Antikainen M. Cholesterol precursors and plant sterols in children with food allergy. Am J Clin Nutr. 2003;77:51–55.
    1. Schlierf G, Vogel G, Heuck CC, Oster P, Raetzer H, Schellenberg B. [Dietary management of familial Hypercholesterolemia in Children and adolescents -- a feasibility study (author's transl)] Monatsschr Kinderheilkd. 1977;125:770–773.
    1. Becker M, Staab D, Von Bergman K. Long-term treatment of severe familial hypercholesterolemia in children: effect of sitosterol and bezafibrate. Pediatrics. 1992;89:138–142.
    1. Gylling H, Siimes MA, Miettinen TA. Sitostanol ester margarine in dietary treatment of children with familial hypercholesterolemia. J Lipid Res. 1995;36:1807–1812.
    1. Vuorio AF, Gylling H, Turtola H, Kontula K, Ketonen P, Miettinen TA. Stanol ester margarine alone and with simvastatin lowers serum cholesterol in families with familial hypercholesterolemia caused by the FH-North Karelia mutation. Arterioscler Thromb Vasc Biol. 2000;20:500–506.
    1. Schlierf G, Oster P, Heuck CC, Raetzer H, Schellenberg B. Sitosterol in juvenile type II hyperlipoproteinemia . Atherosclerosis. 1978;30:245–248.
    1. Amundsen ÅL, 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;76:338–344.
    1. Tammi A, Rönnemaa T, Gylling H, Rask-Nissilä L, Viikari J, Tuominen J, Pulkki K, Simell O. Plant stanol ester margarine lowers serum total and low-density lipoprotein cholesterol concentrations of healthy children: The STRIP project. J Pediatr. 2000;136:503–510.
    1. Tammi A, Rönnemaa T, Valsta L, Seppänen R, Rask-Nissilä L, Miettinen TA, Gylling H, Viikari J, Anttolainen M, Simell O. Dietary plant sterols alter the serum plant sterol concentration but not the cholesterol precursor sterol concentrations in young children (the STRIP Study). Special Turku Coronary Risk Factor Intervention Project. J Nutr. 2001;131:1942–1945.
    1. Mellies M, Glueck CJ, Sweeney C, Fallat RW, Tsang RC, Ishikawa TT. Plasma and dietary phytosterols in children . Pediatrics. 1976;57:60–67.
    1. Kempen HJ, de-Knijff P, Boomsma DI, Van der,V, Gevers Leuven JA, Havekes L. 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. doi: 10.1016/0026-0495(91)90102-3.
    1. Tammi A, Ronnemaa T, Miettinen TA, Gylling H, Rask-Nissila L, Viikari J, Tuominen J, Marniemi J, Simell O. 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. doi: 10.1080/080352502320777379.
    1. Miettinen TA. Phytosterolaemia, xanthomatosis and premature atherosclerotic arterial disease: a case with high plant sterol absorption, impaired sterol elimination and low cholesterol synthesis. Eur J Clin Invest. 1980;10:27–35.
    1. Miettinen HE, Gylling H, Miettinen TA, Viikari J, Paulin L, Kontula K. Apolipoprotein A-IFin. Dominantly inherited hypoalphalipoproteinemia due to a single base substitution in the apolipoprotein A-I gene. Arterioscler Thromb Vasc Biol. 1997;17:83–90.
    1. Patel SB, Salen G, Hidaka H, Kwiterovich PO, Stalenhoef AF, Miettinen TA, Grundy SM, Lee MH, Rubenstein JS, Polymeropoulos. Mh. Brownstein MJ. Mapping a gene involved in regulating dietary cholesterol absorption. The sitosterolemia locus is found at chromosome 2p21. J Clin Invest. 1998;102:1041–1044.
    1. Patel SB, Honda A, Salen G. Sitosterolemia: exclusion of genes involved in reduced cholesterol biosynthesis. J Lipid Res. 1998;39:1055–1061.
    1. 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. doi: 10.1046/j.1365-2796.2001.00788.x.
    1. Kwiterovich P O, Jr, 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;44:1143–1155. doi: 10.1194/jlr.M200455-JLR200.
    1. Awad AB, Smith AJ, Fink CS. Plant sterols regulate rat vascular smooth muscle cell growth and prostacyclin release in culture. Prostaglandins Leukot Essent Fatty Acids. 2001;64:323–330. doi: 10.1054/plef.2001.0273.
    1. 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. doi: 10.1016/S0021-9150(98)00008-2.
    1. Ntanios FY, van de Kooij AJ, de Deckere EA, Duchateau GS, 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;169:41–50. doi: 10.1016/S0021-9150(03)00132-1.
    1. Awad AB, Fink CS. Phytosterols as anticancer dietary components: evidence and mechanism of action . J Nutr. 2000;130:2127–2130.
    1. Awad AB, von Holtz RL, Cone JP, Fink CS, Chen YC. beta-sitosterol inhibits growth of Ht-29 human colon cancer cells by activating the sphingomyelin cycle. Anticancer Res. 1998;18:471–473.
    1. Awad AB, Gan Y, Fink CS. Effect of b-sitosterol, a plant sterol, on growth, protein phosphatase 2A, and phospholipase D in LNCaP cells. Nutr Cancer. 2000;36:74–78. doi: 10.1207/S15327914NC3601_11.
    1. Awad AB, Downie A, Fink CS, Kim U. Dietary phytosterol inhibits the growth and metastasis of MDA-MB-231 human breast cancer cells grown in SCID mice. Anticancer Res. 2000;20:821–824.
    1. Wilt T, Ishani A, MacDonald R, Stark G, Mulrow C, Lau J. Beta-sitosterols for benign prostatic hyperplasia. Cochrane Database Syst. Rev 2000; CD001043 Review.
    1. Normén AL, Brants HA, Voorrips LE, Andersson HA, van den Brandt PA, Goldbohm RA. Plant sterol intakes and colorectal cancer risk in the Netherlands Cohort Study on Diet and Cancer. Am J Clin Nutr. 2001;74:141–148.
    1. Quilliot D, Boman F, Creton C, Pelletier X, Floquet J, Debry G. Phytosterols have an unfavourable effect on bacterial activity and no evident protective effect on colon carcinogenesis. Eur J Cancer Prev. 2001;10:237–243. doi: 10.1097/00008469-200106000-00006.
    1. Mendilaharsu M, De Stefani E, Deneo-Pellegrini H, Carzoglio J, Ronco A. Phytosterols and risk of lung cancer: a case-control study in Uruguay. Lung Cancer. 1998;21:37–45. doi: 10.1016/S0169-5002(98)00044-0.
    1. Ronco A, De Stefani E, Boffetta P, Deneo-Pellegrini H, Mendilaharsu M, Leborgne F. Vegetables, fruits, and related nutrients and risk of breast cancer: a case-control study in Uruguay. Nutr Cancer. 1999;35:111–119. doi: 10.1207/S15327914NC352_3.
    1. De Stefani E, Boffetta P, Ronco AL, Brennan P, Deneo-Pellegrini H, Carzoglio JC, Mendilaharsu M. Plant sterols and risk of stomach cancer: a case-control study in Uruguay. Nutr Cancer. 2000;37:140–144. doi: 10.1207/S15327914NC372_4.
    1. De Stefani E, Brennan P, Boffetta P, Ronco AL, Mendilaharsu M, Deneo-Pellegrini H. Vegetables, fruits, related dietary antioxidants, and risk of squamous cell carcinoma of the esophagus: a case-control study in Uruguay. Nutr Cancer. 2000;38:23–29. doi: 10.1207/S15327914NC381_4.
    1. McCann SE, Freudenheim JL, Marshall JR, Brasure JR, Swanson MK, Graham S. Diet in the epidemiology of endometrial cancer in western New York (United States) Cancer Causes Control. 2000;11:965–974. doi: 10.1023/A:1026551309873.
    1. McCann SE, Freudenheim JL, Marshall JR, Graham S. Risk of human ovarian cancer is related to dietary intake of selected nutrients, phytochemicals and food groups. J Nutr. 2003;133:1937–1942.
    1. Bouic PJ, Clark A, Brittle W, Lamprecht JH, Freestone M, Liebenberg RW. Plant sterol/sterolin supplement use in a cohort of South African HIV-infected patients--effects on immunological and virological surrogate markers. S Afr Med J. 2001;91:848–850.
    1. Wang T, Hicks KB, Moreau R. Antioxidant activity of phytosterols, oryzanol, and other phytosterol conjugates. J Am Oil Chem Soc. 2002;79:1201–1206.
    1. Loscalzo J. Oxidant stress: a key determinant of atherothrombosis. Biochem Soc Trans. 2003;31:1059–1061.
    1. Quong J, Eppenberger-Castori S, Moore D, 3rd, Scott GK, Birrer MJ, Kueng W, Eppenberger U, Benz CC. Age-dependent changes in breast cancer hormone receptors and oxidant stress markers. Breast Cancer Res Treat. 2002;76:221–236. doi: 10.1023/A:1020886801674.
    1. Paul Jayaraj A, Tovey FI, Hobsley M. Duodenal ulcer prevalence: research into the nature of possible protective dietary lipids. Phytother Res. 2003;17:391–398. doi: 10.1002/ptr.1310.
    1. Smania EF, Delle Monache F, Smania A, Jr, Yunes RA, Cuneo RS. Antifungal activity of sterols and triterpenes isolated from Ganoderma annulare. Fitoterapia. 2003;74:375–377. doi: 10.1016/S0367-326X(03)00064-9.
    1. 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;20:307–319.
    1. Plat J, Mensink RP. Effects of plant stanol esters on LDL receptor protein expression and on LDL receptor and HMG-CoA reductase mRNA expression in mononuclear blood cells of healthy men and women. FASEB J. 2002;16:258–260. doi: 10.1096/fj.01-0718hyp.
    1. Ntanios FY, Duchateau GS. 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 Nutr Res. 2002;72:32–39.
    1. 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;51:652–656. doi: 10.1053/meta.2002.32021.
    1. Nissinen M, Gylling H, Vuoristo M, Miettinen TA. Micellar distribution of cholesterol and phytosterols after duodenal plant stanol ester infusion. Am J Physiol Gastrointest Liver Physiol. 2002;282:G1009–10015.
    1. Miettinen TA, Gylling H, Lindbohm N, Miettinen TE, Rajaratnam RA, Relas H. Serum noncholesterol sterols during inhibition of cholesterol synthesis by statins. J Lab Clin Med. 2003;141:131–137. doi: 10.1067/mlc.2003.9.
    1. Heinemann T, Leiss O, von Bergmann K. Effect of low-dose sitostanol on serum cholesterol in patients with hypercholesterolemia. Atherosclerosis. 1986;61:219–223.
    1. Howell TJ, MacDougall DE, Jones PJ. Phytosterols partially explain differences in cholesterol metabolism caused by corn or olive oil feeding. J Lipid Res. 1998;39:892–900.
    1. Gylling H, Miettinen TA. Cholesterol reduction by different plant stanol mixtures and with variable fat intake. Metabolism. 1999;48:575–580.
    1. Normen L, Dutta P, Lia A, Andersson H. Soy sterol esters and β-sitostanol ester as inhibitors of cholesterol absorbtion in human small bowel. Am J Clin Nutr. 2000;71:908–913.
    1. 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;19:369–374. doi: 10.1016/S0899-9007(02)00926-7.
    1. Gylling H, Puska P, Vartiainen E, Miettinen TA. Retinol, vitamin D, carotenes and alpha-tocopherol in serum of a moderately hypercholesterolemic population consuming sitostanol ester margarine. Atherosclerosis. 1999;145:279–285. doi: 10.1016/S0021-9150(99)00078-7.

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever