Skip to main content
SpringerLink
Log in

Phytosterol Therapy

  • Chapter
  • First Online:
Dyslipidemias

Part of the book series: Contemporary Endocrinology ((COE))

  • 2211 Accesses

Abstract

Phytosterols, the general name for plant sterols and plant stanols, are bioactive compounds present in different foods of plant origin. Phytosterols are normal components of plants, but they are not synthesized in the human body. The main food sources of phytosterols are vegetable oils, vegetable-fat spreads and margarines, cereals and cereal products (bread), and vegetables. Since the early 1950s, the hypolipidemic effect of large doses of phytosterols has interested scientists as a hypocholesterolemic nonpharmacological means. Phytosterols reduce serum total and low-density lipoprotein (LDL) cholesterol levels by partially blocking the intestinal cholesterol absorption. Fat-soluble plant stanol ester in food products was introduced to the research field in 1991 as part of a heart healthy diet, and other products followed later on so that at the moment several food products with added phytosterols are available worldwide. Recent large meta-analyses of randomized controlled studies including over 8000 subjects confirm that a daily intake of 2 g of phytosterols lowers LDL cholesterol by 9 % irrespective of age, gender, and cause of hypercholesterolemia. Phytosterols can be combined with cholesterol-lowering drugs, especially with statins, and the additional effect is larger than with doubling the statin dose. There is a convincing body of scientific evidence that phytosterol therapy is safe. Phytosterols have been implicated as hypocholesterolemic agents in health claims and dietary recommendations.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
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

References

  1. Klingberg S, Andersson H, Mulligan A, Bhaniani A, Welch A, Bingham S, et al. Food sources of plant sterols in the EPIC Norfolk population. Eur J Clin Nutr. 2008;62:695–703.

    Article  CAS  PubMed  Google Scholar 

  2. Valsta LM, Lemström A, Ovaskainen ML, Lampi AM, Toivo J, Korhonen T, Piironen V. Estimation of plant sterol and cholesterol intake in Finland: quality of new values and their effect on intake. Br J Nutr. 2004;92:671–8.

    Article  CAS  PubMed  Google Scholar 

  3. Ostlund RE Jr, McGill JB, Zeng C-M, Covey DF, Stearns J, Stenson WF, Spilburg CA. Gastrointestinal absorption and plasma kinetics of soy Δ 5-phytosterols and phytostanols in humans. Am J Physiol Endocrinol Metab. 2002;282:E911–6.

    Article  CAS  PubMed  Google Scholar 

  4. Miettinen TA, Railo M, Lepäntalo M, Gylling H. Plant sterols in serum and in atherosclerotic plaques of patients undergoing carotid endarterectomy. J Am Coll Cardiol. 2005;45:1792–1801.

    Article  Google Scholar 

  5. Miettinen TA, Nissinen M, Lepäntalo M, Albäck A, Railo M, Vikatmaa P, et al. Non-cholesterol sterols in serum and endarterectomized carotid arteries after a short-term plant stanol and sterol ester challenge. Nutr Metab Cardiovasc Dis. 2011;21:182–8.

    Article  CAS  PubMed  Google Scholar 

  6. Helske S, Miettinen T, Gylling H, Mäyränpää M, Lommi J, Turto H, et al. Accumulation of cholesterol precursors and plant sterols in human stenotic aortic valves. J Lipid Res. 2008;49:1511–8.

    Article  CAS  PubMed  Google Scholar 

  7. Weingärtner O, Lütjohann D, Ji S, Weisshoff N, List F, Sudhop T, et al. Vascular effects of diet supplementation of with plant sterols. J Am Coll Cardiol. 2008;51:1553–61.

    Article  PubMed  Google Scholar 

  8. Lin DS, Connor WE. Fecal steroids of the coprolite of a Greenland Eskimo mummy, AD 1475: a clue to dietary sterol intake. Am J Clin Nutr. 2001;74:44–9.

    CAS  PubMed  Google Scholar 

  9. Grundy SM, Ahrens Jr EH, Davignon J. The interaction of cholesterol absorption and cholesterol synthesis in man. J Lipid Res. 1969;10:304–15.

    CAS  PubMed  Google Scholar 

  10. Sugano M, Morioka H, Ikeda I. A comparison of hypocholesterolemic activity of β-sitosterol and β-sitostanol in rats. J Nutr. 1977;107:2011–9.

    CAS  PubMed  Google Scholar 

  11. Miettinen TA, Gylling H. Non-nutritive bioactive constituents of plants: phytosterols. Int J Vitam Nutr Res. 2003;73:127–34.

    Article  CAS  PubMed  Google Scholar 

  12. Klingberg S, Ellegård L, Johansson I, Hallmans G, Weinehall L, Andersson H, et al. Inverse relation between dietary intake of naturally occurring plant sterols and serum cholesterol in northern Sweden. Am J Clin Nutr. 2008;87:993–1001.

    CAS  PubMed  Google Scholar 

  13. 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. 2001;285:2486–97.

    Google Scholar 

  14. Wang DQ-H. Regulation of intestinal cholesterol absorption. Annu Rev Physiol. 2007;69:221–48.

    Article  CAS  PubMed  Google Scholar 

  15. Calpe-Berdiel L, Escola-Gil JC, Blanco-Vaca F. New insights into the molecular actions of plant sterols and stanols in cholesterol metabolism. Atherosclerosis. 2009;203:18–31.

    Google Scholar 

  16. Ostlund RE Jr. Phytosterols and cholesterol metabolism. Curr Opin Lipidol. 2004;15:37–41.

    Article  CAS  PubMed  Google Scholar 

  17. Ostlund RE Jr. Phytosterols, cholesterol absorption and healthy diets. Lipids. 2007;42:41–5.

    Article  CAS  PubMed  Google Scholar 

  18. Temel RE, Brown JM. Biliary and nonbiliary contributions to reverse cholesterol transport. Curr Opin Lipidol. 2012;23:85–90.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Salen G, Starc T, McCrary Sisk C, Patel SB. Intestinal cholesterol absorption inhibitor ezetimibe added to cholestyramine for sitosterolemia and xanthomatosis. Gastroenterology. 2006;130:1853–7.

    Article  PubMed  Google Scholar 

  20. Jesch ED, Carr TP. Sitosterol reduces micellar cholesterol solubility in model bile. Nutr Res. 2006;26:579–84.

    Article  CAS  Google Scholar 

  21. Nissinen M, Gylling H, Vuoristo M, Miettinen TA. Micellar distribution of cholesterol and phytosterols after duodenal plant stanol ester infusion. Am J Gastrointest Liver Physiol. 2002;282:G1009–15.

    Article  CAS  Google Scholar 

  22. Nissinen MJ, Vuoristo M, Gylling H, Miettinen TA. Respective hydrolysis and esterification of esterified and free plant stanols occur rapidly in human intestine after their duodenal infusion in triacyl- or diacylglycerol. Lipids. 2007;42:603–12.

    Article  CAS  PubMed  Google Scholar 

  23. Siperstein MD, Chaikoff IL, Reinhardt WO. C14-cholesterol. V. Obligatory function of bile in intestinal absorption of cholesterol. J Biol Chem. 1952;198:111–4.

    CAS  PubMed  Google Scholar 

  24. Williams CL, Bollella MC, Strobino BA, Boccia L, Campanaro L. Plant stanol ester and bran fiber in childhood: effects on lipids, stool weight and stool frequency in preschool children. J Am Coll Nutr. 1999;18:572–81.

    Article  CAS  PubMed  Google Scholar 

  25. Rideout T, Harding SV, Mackay DS. Metabolic and genetic factors modulating subject specific LDL-C responses to plant sterol therapy. Can J Physiol Pharmacol. 2012;90:509–14.

    Article  CAS  PubMed  Google Scholar 

  26. Lakoski SG, Xu F, Vega GL, Grundy SM, Chandalia M, Lam C, et al. Indices of cholesterol metabolism and relative responsiveness to ezetimibe and simvastatin. J Clin Endocrinol Metab. 2010;95:800–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Jakulj L, Vissers MN, Tanck MWT, Hutten BA, Stellaard F, Kastelein JJP, et al. ABCG5/G8 polymorphism and markers of cholesterol metabolism: systematic review and meta-analysis. J Lipid Res. 2010;51:3016–23.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Teupser D, Baber R, Ceglarek U, Scholz M, Illig T, Gieger C, et al. Genetic regulation of serum phytosterol levels and risk of coronary artery disease. Circ Cardiovasc Genet. 2010;3:331–9.

    Article  CAS  PubMed  Google Scholar 

  29. Gylling H, Hallikainen M, Raitakari OT, Laakso M, Vartiainen E, Salo P, et al. Long-term consumption of plant stanol and sterol esters, vascular function and genetic regulation. Br J Nutr. 2009;101:1688–95.

    Article  CAS  PubMed  Google Scholar 

  30. van der Velde AE, Vrins CLJ, van den Oever K, Kunne C, Oude Elferink RPJ, Kuipers F, Groen AK. Direct intestinal cholesterol secretion contributes significantly to total fecal neutral sterol excretion in mice. Gastroenterology. 2007;133:967–75.

    Article  PubMed  Google Scholar 

  31. Brufau G, Kuipers F, Lin Y, Trautwein EA, Groen AK. A reappraisal of the mechanism by which plant sterols promote neutral sterol loss in mice. PLoS ONE. 2011;6(6):e21576.

    Google Scholar 

  32. 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;333:1308–12.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  34. Demonty I, Ras RT, van der Knaap HCM, Duchateau GS, Meijer L, Zock PL, et al. Continuous dose-response relationship of the LDL-cholesterol-lowering effect of phytosterol intake. J Nutr. 2009;139:271–84.

    Google Scholar 

  35. Musa-Veloso K, Poon TH, Elliot JA, Chung C. A comparison of the LDL-cholesterol lowering efficacy of plant stanols and plant sterols over a continuous dose range: results of a meta-analysis of randomized, placebo-controlled trials. Prostaglandins Leukot Essent Fatty Acids. 2011;85:9–28.

    Article  CAS  Google Scholar 

  36. Plat J, Mackay D, Baumgartner S, Clifton PM, Gylling H, Jones PJH. Progress and prospective of plant sterol and plant stanol research: report of the Maastricht meeting. Atherosclerosis. 2012. http://dx.doi.org/10.1016/j.atherosclerosis. Accessed 18 Sept 2012.

    Google Scholar 

  37. Fransen HP, de Jong N, Wolfs M, Verhagen H, Verschuren WM, Lütjohann D, et al. Customary use of plant sterol and plant stanol enriched margarine is associated with changes in serum plant sterol and stanol concentrations in humans. J Nutr. 2007;137:1301–6.

    Google Scholar 

  38. Hallikainen M, Lyyra-Laitinen T, Laitinen T, Moilanen L, Miettinen TA, Gylling H. Effects of plant stanol esters on serum cholesterol concentrations, relative markers of cholesterol metabolism and endothelial function in type 1 diabetes. Atherosclerosis. 2008;199:432–9.

    Article  CAS  PubMed  Google Scholar 

  39. Hallikainen M, Kurl S, Laakso M, Miettinen TA, Gylling H. Plant stanol esters lower LDL cholesterol level in statin-treated subjects with type 1 diabetes by interfering the absorption and synthesis of cholesterol. Atherosclerosis. 2011;217:473–8.

    Article  CAS  PubMed  Google Scholar 

  40. 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;20:500–6.

    Article  CAS  PubMed  Google Scholar 

  41. Baker WL, Baker EL, Coleman CI. The effect of plant sterols or stanols on lipid parameters in patients with type 2 diabetes: a meta-analysis. Diabetes Res Clin Pract. 2009;84:e33–7.

    Google Scholar 

  42. Sutton D, Davey T, Venkatraman G, Hart K. Can a functional food exert a cholesterol lowering effect in renal transplant patients? J Ren Care. 2009;35:42–7.

    Article  PubMed  Google Scholar 

  43. Scholle JM, Baker WL, Talati R, Coleman CI. The effect of adding plant sterols or stanols to statin therapy in hypercholesterolemic patients: systematic review and meta-analysis. J Am Coll Nutr. 2009;28:517–24.

    Article  CAS  PubMed  Google Scholar 

  44. Jakulj L, Trip MD, Sudhop T, von Bergmann K, Kastelein JJP, Vissers MN. Inhibition of cholesterol absorption by the combination of dietary plant sterols and ezetimibe: effects on plasma lipid levels. J Lipid Res. 2005;46:2692–8.

    Article  CAS  PubMed  Google Scholar 

  45. Lin X, Racette SB, Lefevre M, Ma L, Spearie CA, Steger-May K, Ostlund Jr RE. Combined effects of ezetimibe and phytosterols on cholesterol metabolism. A randomized, controlled feeding study in humans. Circulation. 2011;124:596–601.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. Gylling H, Miettinen TA. LDL cholesterol lowering by bile acid malabsorption during inhibited synthesis and absorption of cholesterol in hypercholesterolemic coronary subjects. Nutr Metab Cardiovasc Dis. 2002;12:19–23.

    CAS  PubMed  Google Scholar 

  47. Linnebur SA, Capell WH, Saseen JJ, Wolfe P, Eckel RH. Plant sterols added to combination statin and colesevelam hydrochloride therapy failed to lower low-density lipoprotein cholesterol concentrations. J Clin Lipidol. 2007;1:626–33.

    Article  PubMed  Google Scholar 

  48. LaRosa JC. Low-density lipoprotein cholesterol reduction: the end is more important than the means. Am J Cardiol. 2007;100:240–2.

    Article  CAS  PubMed  Google Scholar 

  49. EFSA (European Food Safety Authority). Scientific opinion of the panel on dietetic products nutrition and allergies on a request from McNeil Nutritionals Ltd. related to the scientific substantiation of a health claim on plant stanol esters and lower/reduced blood cholesterol and reduced risk of (coronary) heart disease (EFSA-Q-2008-085). EFSA J. 2008;825:1–13.

    Google Scholar 

  50. de Jongh S Vissers MN Rol P Bakker HD Kastelein JJ Stroes ES. Plant sterols lower LDL cholesterol without improving endothelial function in prepubertal children with familial hypercholesterolemia. J Inherit Metab Dis. 2003;26:343–51.

    Google Scholar 

  51. Hallikainen M, Lyyra-Laitinen T, Laitinen T, Ågren JJ, Pihlajamäki J, Rauramaa R, et al. Endothelial function in hypercholesterolemic subjects: effects of plant stanol and sterol esters. Atherosclerosis. 2006;188:425–32.

    Article  CAS  PubMed  Google Scholar 

  52. Jakulj L, Vissers MN, Rodenburg J, Wiegman A, Trip MD, Kastelein JJ. Plant stanols do not restore endothelial function in pre-pubertal children with familial hypercholesterolemia despite reduction of low-density lipoprotein cholesterol levels. J Pediatr. 2006;148:495–500.

    Article  CAS  PubMed  Google Scholar 

  53. Raitakari OT, Salo P, Ahotupa M. Carotid artery compliance in users of plant stanol ester margarine. Eur J Clin Nutr. 2008;62:218–24.

    Article  CAS  PubMed  Google Scholar 

  54. Raitakari OT, Salo P, Gylling H, Miettinen TA. Plant stanol ester consumption and arterial elasticity and endothelial function. Br J Nutr. 2008;100:603–8.

    Article  CAS  PubMed  Google Scholar 

  55. Simonen P, Gylling H, Lindholm H, Konttinen J, Nissinen M, Hallikainen M. The effect of plant stanol ester on blood flow in adults. ESC Congress 2012, 25–29 August 2012 Munich, Germany.

    Google Scholar 

  56. Laitinen K, Gylling H. Dose-dependent LDL lowering effect by plant stanol ester consumption: clinical evidence. Lipids Health Dis. 2012;11:140. doi:10.1186/1476–511X-11–140.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  57. 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.

    CAS  PubMed  Google Scholar 

  58. Woollett LA, Wang Y, Buckley DD, Yao L, Chin S, Granholm N, et al. Micellar solubilisation of cholesterol is essential for absorption in humans. Gut. 2006;55:197–204.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Division of Internal Medicine, University of Helsinki, Biomedicum Helsinki, room C4 22, P.O. BOX 700, 00029 HUS, Helsinki, Finland

    Helena Gylling MD, PhD

  2. Department of Medicine, Division of Gastroenterology, Helsinki University Central Hospital/Peijas Hospital, Biomedicum Helsinki, room C4 22, P.O. BOX 700, 00029 HUS, Helsinki, Finland

    Markku J. Nissinen MD, PhD

Authors
  1. Helena Gylling MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Markku J. Nissinen MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Helena Gylling MD, PhD .

Editor information

Editors and Affiliations

  1. Professor of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA

    Abhimanyu Garg

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Humana Press

About this chapter

Cite this chapter

Gylling, H., Nissinen, M. (2015). Phytosterol Therapy. In: Garg, A. (eds) Dyslipidemias. Contemporary Endocrinology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-424-1_20

Download citation

  • DOI: https://doi.org/10.1007/978-1-60761-424-1_20

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60761-423-4

  • Online ISBN: 978-1-60761-424-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation