Cholesterol-lowering Sterols and Stanols

oPatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.

Sterols and stanols have a function in plants rather like cholesterol in humans. Stanols are saturated and sterols are not. A high intake of these substances impairs uptake of cholesterol from the gut. They reduce total and low-density lipoprotein (LDL) cholesterol and may beneficially influence other lipid variables such as apolipoprotein (apo) B/apo AI ratio and, in some studies, high-density lipoprotein (HDL) cholesterol and triglycerides (TG). Plant sterols/stanols may also affect inflammatory markers, coagulation parameters, as well as platelet and endothelial function.[1] Unfortunately, whilst the in vitro evidence for their beneficial effects on lipid profile is convincing, this does not translate with any compelling degree into prevention of primary cardiovascular events.

The National Institute for Health and Clinical Excellence (NICE) does not recommend routinely advising patients to use them until results of randomised controlled trials are known. [2]

Sterols and stanols are ubiquitous in the plant world. They are most effective when taken with food and are produced commercially to add to food.They are available under various trade names, eg Benecol® and Flora pro.activ®. They are usually sold in the form of margarine but can occur in other forms like yoghurt. Rich natural sources include rice bran, avocado oil, original wheat germ and extra virgin olive oil.

There does not seem to be any significance clinical differences between plant sterols and stanols in terms of their effects in total cholesterol, LDL cholesterol, HDL cholesterol, or TG levels.[3]

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The evidence shows that there is considerable variation between individuals in response to stanols and sterols.[4][5] They do tend to reduce LDL cholesterol and the effect is dose-related. In general terms, the reduction is between 10% and 20%. Two meta-analyses reported in Bandolier confirmed that 2 g per day of stanols and sterols reduce LDL cholesterol by about 10%, or 0.3 to 0.5 mmol/L. If such a reduction were directly translated into coronary heart disease (CHD) risk, such a risk should be lowered by about 25%.[6] As previously stated, however, further research is required.[2]

Such research will have to take into account the fact that stanols and sterols have to be esterified or in emulsion form to have their full effect and consistency of preparation will have to be addressed, so that like is compared with like. Interpretation of some of the early work is very difficult as different forms were used. Another variable is the background diet. Some of the early work used vegetarians and found no significant change but vegetarians have a higher level of sterols in their diet than omnivores.[7] Much of the early work was conducted on people with normal cholesterol. More recent work has found similar results in people with hypercholesterolaemia. In a recent study of 72 people with mildly raised cholesterol, taking 2 g a day of sterol in orange juice reduced LDL cholesterol by an average of 12.4% over 8 weeks.[8]

As mentioned in the NICE guidance, large randomised controlled trials need to be carried out over a two-year period to assess the effect of stanols and steroids on primary cardiovascular risk reduction.[2] There is however, considerable circumstantial evidence supporting the relationship between ingestion of sterols and stanols[9][10] and a reduction in cardiovascular risk and would seem to suggest the following conclusions:

  • The natural day-to-day variation in fasting lipids is up to 10% with significant variation for HDL cholesterol and triglycerides. A small decrease may thus be masked and yet offer very significant benefit.[11][12] A true reduction in LDL cholesterol of 10% is a very worthwhile achievement, reducing the risk of CHD by 50% at age 40, falling to 20% at age 70.
  • There are many sources of stanols and much variation in bioactivity in terms of ability to impair cholesterol absorption. Therefore, even studies that state the number of grams per day of sterols may be meaningless in terms of comparing like with like, particularly when one adds the variation in normal dietary intake to the equation.. Many studies, especially the early ones, used quite small numbers. Therefore, although meta-analysis may seem appropriate, the variation in source of stanols may make the results invalid.
  • Systematic reviews to date do seem to suggest a general trend that shows that stanols and sterols reduce LDL cholesterol in people with normal and moderately raised cholesterol and that this effect is related to dose. They are also effective in reducing LDL cholesterol in more severe cases as in familial hypercholesterolaemia, including homozygous individuals.[13]
  • The advent of powerful statins has led to neglect of dietary manipulation but sterols can be used in addition to statins to gain maximal effect.[14] Although the response is dose-dependent, the dictum of the more the better does not necessarily seem to apply. A diet containing over 1 g a day of free sterols in full esterified or emulsion form seems to be the threshold and a higher intake is probably not deleterious but offers little further benefit.[15] Any positive effect from sterols would be negated by patients who are also taking ezetimibe.
  • It is likely that the ideal dose is about 0.8-1.0 g a day of free sterol equivalent, in optimum form, taken with food but, at this level, not everyone will achieve a 5% reduction in LDL.[16]
  • One study suggests that plant sterols work best when taken 'little and often' rather than in one large daily dose.[17]

Sterols have been shown to have a beneficial effect in terms of prevention of cancer, especially carcinoma of colon, carcinoma of breast and carcinoma of prostate.[18] Not all studies have reported positive results and a number are based on samples of animals given carcinogens. Sterols appear to have antioxidant properties that would account for benefit with regard to both cancer and atheroma.

There is some evidence that sterols have beneficial effects on the inflammatory response in HIV, stress-induced immune suppression, rheumatoid arthritis and allergic rhinitis.[19] Much of the work has been based on animal studies.

There may be an antifungal effect.[20] Sterols may even protect against peptic ulcer disease, even in areas with a high prevalence of Helicobacter pylori.[21]

Although sterols are natural products ubiquitous in food, their safety cannot be assumed.

  • The ability to lower cholesterol is similar in both men and women but women seem to be much more susceptible to stanols causing impairment of the absorption of fat-soluble vitamins.
  • The greatest effect is on carotenoids but deficiency can be made up by increasing dietary intake.[22]
  • Sterols are not recommended for pregnant or lactating women or for children aged under 5. This is  because they have been shown to reduce the level of carotenoids, including vitamin A which is closely associated with fetal development[23]. Moreover, the developing brain needs cholesterol.
  • Sitosterolemia is a rare autosomal recessive inherited disorder which is known to be associated with high maternal absorption of plant sterol and cholesterol. It results in CHD at an early age.[24]

NICE recommends that patients should not routinely be advised to take plant sterols and stanols for the primary prevention of cardiovascular disease. This is based on the grounds that there are as yet no randomised controlled trials examining the effect of these substances on primary and secondary prevention with respect to cardiovascular outcomes. This recommendation may be subject to revision once the necessary data become available.

Further reading & references

  1. Derdemezis CS, Filippatos TD, Mikhailidis DP, et al; Review article: effects of plant sterols and stanols beyond low-density J Cardiovasc Pharmacol Ther. 2010 Jun;15(2):120-34. Epub 2010 Mar 3.
  2. Lipid modification - cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease; NICE Clinical Guideline (May 2008, amended May 2010)
  3. Talati R, Sobieraj DM, Makanji SS, et al; The comparative efficacy of plant sterols and stanols on serum lipids: a J Am Diet Assoc. 2010 May;110(5):719-26.
  4. Law M; Plant sterol and stanol margarines and health. BMJ. 2000 Mar 25;320(7238):861
  5. Katan MB, Grundy SM, Jones P, et al; Efficacy and safety of plant stanols and sterols in the management of blood cholesterol levels. Mayo Clin Proc. 2003 Aug;78(8):965
  6. Sterols, stanols and cholesterol, Bandolier
  7. Vanhanen HT, Miettinen TA; Effects of unsaturated and saturated dietary plant sterols on their serum contents. Clin Chim Acta. 1992 Jan 31;205(1
  8. Devaraj S, Jialal I, Vega; Plant sterol Arterioscler Thromb Vasc Biol. 2004 Mar;24(3):e25
  9. Strandberg TE, Gylling H, Tilvis RS, et al; Serum plant and other noncholesterol sterols, cholesterol metabolism and 22-year Atherosclerosis. 2010 May;210(1):282-7. Epub 2009 Nov 13.
  10. Silbernagel G, Fauler G, Hoffmann MM, et al; The associations of cholesterol metabolism and plasma plant sterols with J Lipid Res. 2010 Aug;51(8):2384-93. Epub 2010 Mar 14.
  11. Smith SJ, Cooper GR, Myers GL, et al; Biological variability in concentrations of serum lipids: sources of variation among results from published studies and composite predicted values. Clin Chem. 1993 Jun;39(6):1012
  12. 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 Feb 5;308(6925):367
  13. Ketomaki A, Gylling H, Miettinen TA; Effects of plant stanol and sterol esters on serum phytosterols in a family with familial hypercholesterolemia including a homozygous subject. J Lab Clin Med. 2004 Apr;143(4):255
  14. Grundy SM; Stanol esters as a component of maximal dietary therapy in the National Cholesterol Education Program Adult Treatment Panel III report. Am J Cardiol. 2005 Jul 4;96(1A):47D
  15. Hendriks HF, Weststrate JA, van Vliet T, et al; 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 Apr;53(4):319
  16. Sierksma A, Weststrate JA, Meijer GW; Spreads enriched with plant sterols, either esterified 4,4 Br J Nutr. 1999 Oct;82(4):273
  17. AbuMweis SS, Vanstone CA, Lichtenstein AH, et al; Plant sterol consumption frequency affects plasma lipid levels and cholesterol Eur J Clin Nutr. 2009 Jun;63(6):747-55. Epub 2008 Jun 4.
  18. Woyengo TA, Ramprasath VR, Jones PJ; Anticancer effects of phytosterols. Eur J Clin Nutr. 2009 Jul;63(7):813-20. Epub 2009 Jun 3.
  19. 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 Nov;4(6):471
  20. Smania EF, Delle Monache F, Smania A Jr, et al; Antifungal activity of sterols and triterpenes isolated from Ganoderma annulare. Fitoterapia. 2003 Jun;74(4):375
  21. Paul Jayaraj A, Tovey FI, Hobsley M; Duodenal ulcer prevalence: research into the nature of possible protective dietary lipids. Phytother Res. 2003 Apr;17(4):391
  22. Berger A, Jones PJ, Abumweis SS; Plant sterols: factors affecting their efficacy and safety as functional food ingredients. Lipids Health Dis. 2004 Apr 7;3:5.
  23. Vitamin A: a multifunctional tool for development. Semin Cell Dev Biol. 2011 Aug;22(6):603-10. Epub 2011 Jun 13.
  24. Sitosterolemia, Online Mendelian Inheritance in Man (OMIM)

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.

Original Author:
Dr Laurence Knott
Current Version:
Peer Reviewer:
Dr Hannah Gronow
Last Checked:
26/10/2010
Document ID:
445 (v5)
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