Skip to main content

Plant Sterols and Stanols

  • Chapter
Book cover Atherosclerosis: Diet and Drugs

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 170))

Abstract

The expanding market of ‘functional foods’ containing plant sterols and stanols has focused interest on their cholesterol-lowering effects as well on possible adverse effects. Trials of cholesterol lowering demonstrate that intake of 2 g/day of plant sterols and stanols reduces serum low-density lipoprotein (LDL) cholesterol concentrations by approximately 10%. Safety concerns regarding elevations in serum plant sterol levels, or effects on fat-soluble vitamin absorption or hypothetical effects on serum sex hormone balance have received attention and been addressed in studies. Plant sterol (but not stanol) supplementation increased serum plant sterol concentrations but these levels remained much lower than those observed in homozygous sitosterolemia making an adverse health effect unlikely. Prolonged statin therapy also causes elevations in all cholesterol-adjusted plant sterol levels as well as small but significant elevations in serum unadjusted campesterol levels from baseline. This is probably caused by a statin-induced reduction in biliary cholesterol efflux resulting in a diminished intestinal cholesterol pool. The diminished competition with cholesterol molecules allows more plant sterol molecules to become incorporated in mixed micelles facilitating their uptake in enterocytes. With the exception of ß-carotene, reductions in serum concentrations of fat-soluble (pro)vitamins are usually abolished by adjustment for cholesterol suggesting that they reflect reductions in carrier lipoproteins, mainly LDL. The small reductions in serum ß-carotene are not regarded as a major concern, nor have any adverse effects on sex hormone metabolism been demonstrated apart from parenteral administration of large doses in experimental animals. However, as increasing consumer populations become exposed to a large variety of food products enriched with plant sterols and stanols the likelihood of rare adverse effects increases and surveillance is necessary.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 429.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 549.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 549.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Altmann SW, Davis HR Jr, Zhu L-J, Yao X, Hoos LM, Tetzloff G, Iyer SPN, Maguire M, Golonko A, Zeng M, Wang L, Murgolo N, Graziano MP (2004) Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption. Science 303:1201–1204

    Article  PubMed  Google Scholar 

  • Baker VA, Hepburn PA, Kennedy SJ, Jones PA, Lea LJ, Sumpter JP, Ashby J (1999) Safety evaluation of phytosterol esters. Part 1. Assessment of oestrogenicity using a combination of in vivo and in vitro assays. Food Chem Toxicol 37:13–22

    PubMed  Google Scholar 

  • Becker M, Staab D, von Bergmann K (1993) Treatment of severe familial hypercholesterolemia in childhood with sitosterol and sitostanol. J Pediatr 122:292–296

    PubMed  Google Scholar 

  • Berge KE, Tian H, Graf GA, Yu L, Grishin NV, Shultz J, Kwiterovich P, Shan B, Barnes R, Hobbs HH (2000) Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC tansporters. Science 290:1771–1775

    Article  PubMed  Google Scholar 

  • von Bergmann K, Salen G, Lütjohann D et al. (2002) Ezetimibe effectively reduces serum plant sterols in patients with sitosterolemia. Atherosclerosis 3(suppl):232

    Google Scholar 

  • Best MM, Duncan CH, Van Loon EJ, Wathen JD (1954) Lowering of serum cholesterol by administration of a plant sterol. Circulation 10:201–206

    PubMed  Google Scholar 

  • Best MM, Duncan CH, Van Loon EJ, Wathen JD (1955) The effects of sitosterol on serum lipids. Am J Med 19:61–70

    Article  PubMed  Google Scholar 

  • Bhattacharyya AK, Connor WE (1974) Beta-sitosterolemia and xanthomatosis. A newly described lipid starage disease in two sisters. J Clin Invest 53:1033–1043

    PubMed  Google Scholar 

  • Blair SN, Capuzzi DM, Gottlieb SO, Nguyen T, Morgan JM, Cater NB (2000) Incremental reduction of serum total cholesterol and low-density lipoprotein cholesterol with the addition of plant stanol ester-containing spread to statin therapy. Am J Cardiol 86:46–52

    Article  PubMed  Google Scholar 

  • Blomqvist SM, Jauhiainen M, Van Tol A, Hyvönen M, Torstila I, Vanhanen HT (1993) Effect of sitostanol ester on composition and size distribution of LDL and HDL. Nutr Metab Cardiovasc Dis 3:158–164

    Google Scholar 

  • Bosner MS, Lange LG, Stenson WF, Ostlund RE Jr. (1999) Percent cholesterol absorption in normal women and men quantified with dual stable isotopic tracers and negative ion mass spectrometry. J Lipid Res 40:302–308

    PubMed  Google Scholar 

  • Czubayko F, Beumers B, Lammsfuss S, Lütjohann D, von Bergmann K (1991) A simplified micro-method for quantification of fecal excretion of neutral and acidic sterols for outpatient studies in humans. J Lipid Res 32:1861–1867

    PubMed  Google Scholar 

  • Dietschy JM, Turley SD, Spady DK (1993) Role of liver in the maintenance of cholesterol and low density lipoprotein homeostasis in different animal apecies, including humans. J Lipid Res 34:1637–1659

    PubMed  Google Scholar 

  • Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) (2001) Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP). JAMA 285:2486–2497

    Google Scholar 

  • Farquhar JW, Smith RE, Dempsey ME (1956) The effect of beta sitosterol on the serum lipids of young men with arteriosclerotic heart disease. Circulation 14:77–82

    PubMed  Google Scholar 

  • Grundy SM, Mok HYI (1977) Determination of cholesterol absorption in man by intestinal perfusion. J Lipid Res 18:263–271

    PubMed  Google Scholar 

  • Gylling H, Miettinen TA (1994) Serum cholesterol and cholesterol and lipoprotein metabolism in hypercholesterolaemic NIDDM patients before and during sitostanol ester-margarine treatment. Diabetologia 37:773–780

    PubMed  Google Scholar 

  • Gylling H, Miettinen TA (1996) Effects of inhibiting cholesterol absorption and synthesis on cholesterol and lipoprotein metabolism in hypercholesterolemic non-insulin-dependent diabetic men. J Lipid Res 37:1776–1785

    PubMed  Google Scholar 

  • Gylling H, Radhakrishnan R, Miettinen TA (1997) Reduction of serum cholesterol in postmenopausal women with previous myocardial infarction and cholesterol malabsorption induced by dietary sitostanol ester margarine: women and dietary sitostanol. Circulation 96:4226–4231

    PubMed  Google Scholar 

  • Gylling H, Siimes MA, Miettinen TA (1995) Sitostanol ester margarine in dietary treatment of children with familial hypercholesterolemia. J Lipid Res 36:1807–1812

    PubMed  Google Scholar 

  • Hallikainen MA, Sarkkinen ES, Gylling H, Erkkilä AT, Uusitupa MI (2000) 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 54:715–725

    PubMed  Google Scholar 

  • Hallikainen MA, Sarkkinen ES, Uusitupa MI (2000) Plant stanol esters affect serum cholesterol concentrations of hypercholesterolemic men and women in a dose-dependent manner. J Nutr 130:767–776

    PubMed  Google Scholar 

  • Heinemann T, Leiss O, von Bergmann K (1986) Effect of low-dose sitostanol on serum cholesterol in patients with hypercholesterolemia. Atherosclerosis 61:219–223

    Article  PubMed  Google Scholar 

  • Heinemann T, Kullak-Ublick G-A, Pietruck B, von Bergmann K (1991) Mechanisms of action of plant sterols on inhibition of cholesterol absorption. Comparison of sitosterol and sitostanol. Eur J Clin Pharmacol 40:S59–S63

    Article  PubMed  Google Scholar 

  • Heinemann T, Axtmann G, von Bergmann K (1993) Comparison of intestinal absorption of cholesterol with different plant sterols in man. Eur J Clin Invest 23:827–831

    PubMed  Google Scholar 

  • Hendriks HF, Brink EJ, Meijer GW, Princen HM, Ntanios FY (2003) Safety of long-term consumption of plant sterol esters-enriched spread. Eur J Clin Nutr 57:681–692

    Article  PubMed  Google Scholar 

  • Hendriks HFJ, Weststrate JA, van Vliet T, Meijer GW (1999) 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 53:319–327

    Article  PubMed  Google Scholar 

  • Homan R, Krause BR (1997) Established and emerging strategies for inhibition of cholesterol absorption. Curr Pharm Design 3:29–44

    Google Scholar 

  • Ikeda I, Sugano M (1978) Comparison of absorption and metabolism of ß-sitosterol and ß-sitostanol in rats. Atherosclerosis 30:227–237

    Article  PubMed  Google Scholar 

  • Jones PJH, MacDougall DE, Ntanios F, Vanstone CA (1997) Dietary phytosterols as cholesterol-lowering agents in humans. Can J Physiol Pharmacol 75:217–227

    PubMed  Google Scholar 

  • Katan MB, Grundy SM, Jones P, Law M, Miettinen T, Paoletti R, for the Stresa Workshop participants (2003) Efficacy and safety of plant stanols and sterols in the management of blood cholesterol levels. Mayo Clin Proc 78:965–978

    PubMed  Google Scholar 

  • Lee M-H, Lu K, Patel SB (2001) Genetic basis of sitosterolemia. Curr Opin Lipidol 12:141–149

    Article  PubMed  Google Scholar 

  • Lee M-H, Lu K, Hazard S, Yu H, Shulenin S, Hidaka H, Kojima H, Allikmets R, Sakuma N, Pegoraro R, Srivasava AK, Salen G, Dean M, Patel SB (2001) Identification of a gene, ABCG5, important in the regulation of dietary cholesterol absorption. Nat Genet 27:79–83

    Article  PubMed  Google Scholar 

  • Lees RS, Lees AM (1976) Effects of sitosterol therapy on plasma lipid and lipoprotein concentrations. In: Greten H (ed) Lipoprotein metabolism. Springer-Verlag, New York, 119–124

    Google Scholar 

  • Lees AM, Mok HYI, Lees RS, McCluskey MA, Grundy SM (1977) Plant sterols as cholesterol-lowering agents: clinical trials in patients with hypercholesterolemia and studies of sterol balance. Atherosclerosis 28:325–338

    Article  PubMed  Google Scholar 

  • Ling WH, Jones PJH (1995) Dietary phytosterols: a review of metabolism, benefits and side effects. Life Sci 57:195–206

    PubMed  Google Scholar 

  • Lütjohann D, Björkhem I, Beil UF, von Bergmann K (1995) Sterol absorption and sterol balance in phytosterolemia evaluated by deuterium-labeled sterols: effect of sitostanol treatment. J Lipid Res 36:1763–1773

    PubMed  Google Scholar 

  • Malini T and Vanithakumari G (1991) Antifertility effects of ß-sitosterol in male albino rats. J Ethnopharmacol 35:149–153

    Article  PubMed  Google Scholar 

  • Mattson FH, Grundy SM, Crouse JR (1982) Optimizing the effect of plant sterols on cholesterol absorption in man. Am J Clin Nutr 35:697–700

    PubMed  Google Scholar 

  • Mellanen P, Petänen T, Lehtimäki J, Mäkelä S, Gylund G, Holmbom B, Mannila E, Oikari A, Santti R (1996) Wood-derived estrogens: studies in vitro with breast cancer cell lines and in vivo in trout. Toxicol Appl Pharmacol 136:381–388

    PubMed  Google Scholar 

  • Miettinen TA (1970) Detection of changes in human cholesterol metabolism. Ann Clin Res 2:300–320

    PubMed  Google Scholar 

  • Miettinen TA, Tilvis RS, Kesäniemi YA (1990) Serum plant sterols and cholesterol precursors reflect cholesterol absorption and synthesis in volunteers of a randomly selected male population. Am J Epidemiol 131:20–31

    PubMed  Google Scholar 

  • Miettinen TA, Puska P, Gylling H, Vanhanen H, Vartiainen E (1995) Reduction of serum cholesterol with sitostanol-ester margarine in a mildly hypercholesterolemic population. New Engl J Med 333:1308–1312

    Article  PubMed  Google Scholar 

  • Miettinen TA, Gylling H, Strandberg T, Sarna S, for the Finnish 4S investigators (1998) Baseline serum cholestanol as predictor of recurrent coronary events in subgroup of Scandinavian Simvastatin Survival Study. British Med J 316:1127–1130

    Google Scholar 

  • Miettinen TA, Strandberg TE, Gylling H for the Finnish 4S investigators (2000) Noncholesterol sterols and cholesterol lowering by long-term simvastatin treatment in coronary patients: relation to basal serum cholestanol. Arterioscl Thromb Vasc Biol 20:1340–1346

    PubMed  Google Scholar 

  • Miettinen TA (2001) Cholesterol absorption inhibition: A strategy for cholesterol-lowering therapy. Int J Pract 55:710–716

    Google Scholar 

  • Miettinen TA, and Gylling H (2002) Ineffective decrease of serum cholesterol by simvastatin in a subgroup of hypercholesterolemic coronary patients. Atherosclerosis 164:147–152

    PubMed  Google Scholar 

  • Miettinen TA, Gylling H (2003) Cholesterol synthesis and absorption in coronary patients with lipid triad and isolated high LDL cholesterol in a 4S subgroup. Atherosclerosis 168:343–349

    PubMed  Google Scholar 

  • Miettinen TA, Gylling H, Lindbohm N, Miettinen TE, Rajaratnam RA, Relas H (2003) Serum noncholesterol sterols during inhibition of cholesterol synthesis by statins. J Lab Clin Med 141:131–137

    Article  PubMed  Google Scholar 

  • Miettinen TA, Gylling H (2004) Plant stanol and sterol esters in prevention of cardiovascular diseases. Ann Med 36:126–134

    Article  PubMed  Google Scholar 

  • Nguyen TT, Dale LC, von Bergmann K, Croghan IT (1999) Cholesterol-lowering effect of stanol ester in a US population of mildly hypercholesterolemic men and women: a randomized controlled trial. Mayo Clin Proc 74:1198–1206

    PubMed  Google Scholar 

  • Nissinen M, Gylling H, Vuoristo M, and Miettinen TA (2002) Micellar distribution of cholesterol and phytosterols after duodenal plant stanol ester infusion. Am J Physiol 282:G1009–G1015

    Google Scholar 

  • Ostlund RE Jr, McGill JB, Zeng C-M, Covey DF, Stearns J, Stenson WF, Spilburg CA (2002) Gastrointestinal absorption and plasma kinetics of soyΔ5-phytosterols and phytostanols in humans. Am J Physiol Endocrinol Metab 282: E911–E916

    PubMed  Google Scholar 

  • Patel SB, Salen G, Hikada H, Kwiterovich Jr PO, Stalenhoef AFH, Miettinen TA, Grundy SM, Lee M-H, Rubenstein JS, Polymeropoulos MH, Brownstein MJ (1998) Mapping a gene involved in regulating dietary cholesterol absorption: the sitosterolemia locus is found at chromosome 2p21. J Clin Invest 102:1041–1044

    PubMed  Google Scholar 

  • Plat J, Mensink RP (2000) Vegetable oil based versus wood based stanol ester mixtures: effects on serum lipids and hemostatic factors in non-hypercholesterolemic subjects. Atherosclerosis 148:101–112

    Article  PubMed  Google Scholar 

  • Pollak OJ (1953) Reduction of blood cholesterol in man. Circulation 7:702–706

    PubMed  Google Scholar 

  • Pollak OJ (1985) Effect of plant sterols on serum lipids and atherosclerosis. Pharmacol Ther 31:177–208

    Article  PubMed  Google Scholar 

  • Salen G, Shefer S, Nguyen L, Ness GC, Tint GC, Shore V (1992) Sitosterolemia. J Lipid Res 33:945–955

    PubMed  Google Scholar 

  • Salen G, Shore V, Tint GS, Forte T, Shefer S, Horak I, Horak E, Dayal B, Nguyen L, Batta AK, Lindgren FT, Kwiterovich PO Jr. (1989) Increased sitosterol absorption, decreased removal, and expanded body pools compensate for reduced cholesterol synthesis in sitosterolemia with xanthomatosis. J Lipid Res 30:1319–1330

    PubMed  Google Scholar 

  • Sudhop T, Lütjohann D, Kodal A, Igel M, Tribble DL, Shah S (2002) Inhibition of intestinal cholesterol absorption by ezetimibe in humans. Circulation 106:1943–1948

    Article  PubMed  Google Scholar 

  • Sugano M, Kamo F, Ikeda I, Morioka H (1976) Lipid-lowering activity of phytostanols in rats. Atherosclerosis 24:301–109

    Article  PubMed  Google Scholar 

  • Sugano M, Morioka H, Ikeda I (1977) A comparison of hypocholesterolemic activity of ß-sitosterol and ß-sitostanol in rats. J Nutr 107:2011–2019

    PubMed  Google Scholar 

  • Tikkanen MJ, Höqström P, Tuomilehto J, Keinänen-Kiukaannjemi S, Sundvall J, Karppanen H (2001) Effects of a diet based on low-fat foods enriched with nonesterified plant sterols and mineral nutrients on serum cholesterol. Am J Cardiol 88:1157–1162

    PubMed  Google Scholar 

  • Tremblay L, Van Der Kraak G (1998) Use of a series of homologous in vitro and in vivo assays to evaluate the endocrine modulating actions of ß-sitosterol in rainbow trout. Aquatic Toxicol 43:149–162

    Article  Google Scholar 

  • Turley SD, Dietschy JM (2003) Sterol absorption by the small intestine Curr Opin Lipidol 14:233–240

    Article  PubMed  Google Scholar 

  • Vanhanen HT, Kajander J, Lehtovirta H, Miettinen TA (1994) Serum levels, absorption efficiency, faecal elimination, and synthesis of cholesterol during increasing doses of dietary sitostanol esters in hypercholesterolaemic subjects. Clin Sci 87:61–67

    PubMed  Google Scholar 

  • Vanhanen HT, Miettinen TA (1992) Effects on unsaturated and saturated dietary plant sterols on their serum contents. Clin Chim Acta 205:97–107

    PubMed  Google Scholar 

  • Vuorio AF, Gylling H, Turtola H, Kontula K, Ketonen P, Miettinen TA (2000) 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 20:500–506

    PubMed  Google Scholar 

  • Weststrate JA, Meijer GW (1998) Plant sterol-enriched margarines and reduction of plasma total-and LDL-cholesterol concentrations in normocholesterolaemic and mildly hypercholesterolaemic subjects. Eur J Clin Nutr 52:334–343

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Tikkanen, M. (2005). Plant Sterols and Stanols. In: von Eckardstein, A. (eds) Atherosclerosis: Diet and Drugs. Handbook of Experimental Pharmacology, vol 170. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-27661-0_7

Download citation

Publish with us

Policies and ethics