Stanols/Sterols
• Phytostanols, Sitostanol, Campestanol, Stigmastanol, 5-Alpha-Stanols, Stanol esters, Sterols, Sterol esters, Phytosterols
Stanols are substances that occur naturally in various plants. Their cholesterol-lowering effects were first observed in animals in the 1950s. Since then, a substantial amount of research suggests that plant stanols (usually modified into stanol esters) can help to lower cholesterol in individuals with normal or mildly to moderately elevated levels. Stanols are available in margarine spreads, salad dressings, and dietary supplement tablets.
Related substances called sterols or phytosterols (such as beta-sitosterol) and sterol esters appear to lower cholesterol in much the same manner as stanols. 9,20,22,54,55,57-60
( Note : Use of beta-sitosterol for conditions other than high cholesterol is discussed in the beta-sitosterol article.)
Requirements/Sources
Sterols are found in most plant foods. Stanols occur naturally in wood pulp, tall oil (a by-product of paper manufacturing), and soybean oil, and can also be manufactured from the sterols found in many foods. Stanol and sterol esters are manufactured by processing stanols or sterols with fatty acids from vegetable oils. 3 Stanol/sterols and their esters are added to margarine spreads and salad dressings and are also available as dietary supplement tablets.
Therapeutic Dosages
Typical dosages of stanol/sterols and their esters to improve cholesterol profile range from 2.7 to 5.1 g per day. 4,74 One study suggests that using stanol products once a day may be as effective as dividing up your intake throughout the day. 5 It may take up to 3 months to show a substantial decrease in total cholesterol values. 6
Therapeutic Uses
Strong evidence tells us that stanol/sterols and their ester forms can significantly improve cholesterol profile 7-20,36,54-56,58-67,70,74,75
There are no other known medicinal uses of stanols or stanol esters. Phytosterols do offer additional potential benefits, but these are discussed in the Beta-sitosterol article.
What Is the Scientific Evidence for Stanols/Sterols?
Because they are structurally similar to cholesterol, stanols (and sterols) can displace cholesterol from the "packages" that deliver cholesterol for absorption from the intestines to the bloodstream. 22 This displaced cholesterol is then excreted from the body. This action not only interferes with the absorption of cholesterol from food, it has the additional (and probably more important) effect of removing cholesterol from substances made in the liver that are recycled through the digestive tract.
Numerous double-blind, placebo-controlled studies, ranging in length from 30 days to 12 months and involving a total of more than 1,000 people, have found that sterol/stanols and their esters are effective for improving cholesterol profile. 17,23-36,54-56,58-67,70,71,74-77 The combined results suggest that these substances can reduce total cholesterol and LDL ("bad") cholesterol by about 10% to 15%. They do not, however, have much of an effect on HDL (“good”) cholesterol, nor on triglycerides.
For example, in a double-blind, placebo-controlled study, 153 people with mildly elevated cholesterol were given sitostanol esters in margarine (at 1.8 or 2.6 g of sitostanol per day), or margarine without sitostanol ester, for a total of one year. 39 The results in the treated group receiving 2.6 g per day showed improvements in total cholesterol by 10.2% and LDL cholesterol by 14.1%—significantly better than the results in the control group. Neither triglycerides nor HDL cholesterol levels were affected.
Fish oil too has been shown to have a favorable effect on fats in the blood, in particular triglycerides. A study investigating the possible benefit of combining sterols with fish oil found that together they significantly lowered total cholesterol, LDL-cholesterol, and triglycerides, and raised HDL-cholesterol in subjects with undesirable cholesterol profiles. 78
Even people already taking standard medications to improve cholesterol profile (specifically, drugs in the statin family) appear to benefit when they additionally use stanols/sterols. 42,43,57,73,75 According to one study, if you are on statins and start taking sterol ester margarine as well, your cholesterol will improve to the same effect as if you doubled the statin dose. 57
Stanols or sterols also appear to be safe and effective for improving cholesterol profile in people with type 2 (adult-onset) diabetes . 40,41,62
Safety Issues
Sterols are presumed safe because they are found in many foods. Stanols are also considered safe, but for a different reason: they are not absorbed. 44,45,68 No adverse effects have been reported in any of the studies on lowering cholesterol, with the exception of one study that reported mild gastrointestinal complaints in a few preschool children. 46 In addition, no toxic signs were observed in rats given stanol esters for 13 weeks at levels comparable to or exceeding those recommended for lowering cholesterol. 47
Although concerns have been expressed that stanol esters might impair absorption of the fat-soluble vitamins A , D , and E , this does not seem to occur at the dosages required to lower cholesterol. 48 Stanol esters might interfere with absorption of alpha- and beta-carotene , 49,50,53 although some studies have found no such effect. 51,52 Evidence is also conflicting whether sterols or sterol esters impair nutrient absorption. 69,72 Until more is learned, it may be reasonable for people using stanol or sterol products to take a multivitamin/multimineral tablet .
References
1. Nguyen TT. The cholesterol-lowering action of plant stanol esters. J Nutr . 1999;129:2109-2112.
2. Gylling H, Miettinen TA. Cholesterol reduction by different plant stanol mixtures and with variable fat intake. Metabolism . 1999;48:575-580.
3. Blair SN, Capuzzi DM, Gottlieb SO, et al. 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 . 2000;86:46-52.
4. Blair SN, Capuzzi DM, Gottlieb SO, et al. 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 . 2000;86:46-52.
5. Plat J, van Onselen EN, van Heugten MM, et al. 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.
6. Miettinen TA, Puska P, Gylling H, et al. Reduction of serum cholesterol with sitostanol-ester margarine in a mildly hypercholesterolemic population. N Engl J Med . 1995;333:1308-1312.
7. 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.
8. Gylling H, Miettinen TA. Cholesterol reduction by different plant stanol mixtures and with variable fat intake. Metabolism . 1999;48:575-580.
9. Vanhanen HT, Blomqvist S, Ehnholm C, et al. 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.
10. Blair SN, Capuzzi DM, Gottlieb SO, et al. 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 . 2000;86:46-52.
11. Nguyen TT, Dale LV, von Bergmann K, et al. Cholesterol-lowering effect of stanol ester in a US population of mildly hypercholesterolemic men and women: a randomized controlled trial. Mayo Clin Proc . 1999;74:1198-2206.
12. Miettinen TA, Puska P, Gylling H, et al. Reduction of serum cholesterol with sitostanol-ester margarine in a mildly hypercholesterolemic population. N Engl J Med . 1995;333:1308-1312.
13. Hallikainen MA, Sarkkinen ES, Uusitupa MI. 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.
14. Gylling H, Siimes MA, Miettinen TA. Sitostanol ester margarine in dietary treatment of children with familial hypercholesterolemia. J Lipid Res . 1995;36:1807-1812.
15. Tammi A, Ronnemaa T, Gylling H, et al. Plant stanol ester margarine lowers serum total and low-density lipoprotein cholesterol concentrations of healthy children: the STRIP project. Special Turku Coronary Risk Factors Intervention Project. J Pediatr . 2000;136:503-510.
16. Gylling H, Miettinen TA. Effects of inhibiting cholesterol absorption and synthesis on cholesterol and lipoprotein metabolism in hypercholesterolemic non-insulin-dependent diabetic men. J Lipid Res . 1996;37:1776-1785.
17. Williams CL, Bollella MC, Strobino BA, et al. Plant stanol ester and bran fiber in childhood: effects on lipids, stool weight and stool frequency in preschool children. J Am Coll Nutr . 1999;18:572-581.
18. 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.
19. Heinemann T, Leiss O, von Bergmann K. Effect of low-dose sitostanol on serum cholesterol in patients with hypercholesterolemia. Atherosclerosis . 1986;61:219-223.
20. Neil HA, Meijer GW, Roe LS. Randomised controlled trial of use by hypercholesterolaemic patients of a vegetable oil sterol-enriched fat spread. Atherosclerosis . 2001;156:329-337.
21. Tammi A, Ronnemaa T, Gylling H, et al. Plant stanol ester margarine lowers serum total and low-density lipoprotein cholesterol concentrations of healthy children: the STRIP project. Special Turku Coronary Risk Factors Intervention Project. J Pediatr . 2000;136:503-510.
22. Law M. Plant sterol and stanol margarines and health. BMJ . 2000;320:861-864.
23. 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.
24. Gylling H, Miettinen TA. Cholesterol reduction by different plant stanol mixtures and with variable fat intake. Metabolism . 1999;48:575-580.
25. Vanhanen HT, Blomqvist S, Ehnholm C, et al. 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.
26. Blair SN, Capuzzi DM, Gottlieb SO, et al. 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 . 2000;86:46-52.
27. Nguyen TT, Dale LV, von Bergmann K, et al. Cholesterol-lowering effect of stanol ester in a US population of mildly hypercholesterolemic men and women: a randomized controlled trial. Mayo Clin Proc . 1999;74:1198-2206.
28. Miettinen TA, Puska P, Gylling H, et al. Reduction of serum cholesterol with sitostanol-ester margarine in a mildly hypercholesterolemic population. N Engl J Med . 1995;333:1308-1312.
29. Hallikainen MA, Sarkkinen ES, Uusitupa MI. 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.
30. Gylling H, Siimes MA, Miettinen TA. Sitostanol ester margarine in dietary treatment of children with familial hypercholesterolemia. J Lipid Res . 1995;36:1807-1812.
31. Tammi A, Ronnemaa T, Gylling H, et al. Plant stanol ester margarine lowers serum total and low-density lipoprotein cholesterol concentrations of healthy children: the STRIP project. Special Turku Coronary Risk Factors Intervention Project. J Pediatr . 2000;136:503-510.
32. Hallikainen MA, Uusitupa MI. 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.
33. Gylling H, Radhakrishnan R, Miettinen TA. 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 . 1997;96:4226-4231.
34. Jones PJ, Ntanios FY, Raeini-Sarjaz M, et al. Cholesterol-lowering efficacy of a sitostanol-containing phytosterol mixture with a prudent diet in hyperlipidemic men. Am J Clin Nutr . 1999;69:1144-1150.
35. Vanhanen HT, Kajander J, Lehtovirta H, et al. 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.
36. Neil HA, Meijer GW, Roe LS. Randomised controlled trial of use by hypercholesterolaemic patients of a vegetable oil sterol-enriched fat spread. Atherosclerosis . 2001;156:329-337.
37. Nguyen TT. The cholesterol-lowering action of plant stanol esters. J Nutr . 1999;129:2109-2112.
38. Maki KC, Davidson MH, Umporowicz DM, et al. 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.
39. Miettinen TA, Puska P, Gylling H, et al. Reduction of serum cholesterol with sitostanol-ester margarine in a mildly hypercholesterolemic population. N Engl J Med . 1995;333:1308-1312.
40. Gylling H, Miettinen TA. Effects of inhibiting cholesterol absorption and synthesis on cholesterol and lipoprotein metabolism in hypercholesterolemic non-insulin-dependent diabetic men. J Lipid Res . 1996;37:1776-1785.
41. 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.
42. Gylling H, Miettinen TA. Effects of inhibiting cholesterol absorption and synthesis on cholesterol and lipoprotein metabolism in hypercholesterolemic non-insulin-dependent diabetic men. J Lipid Res . 1996;37:1776-1785.
43. Blair SN, Capuzzi DM, Gottlieb SO, et al. 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. 2000;86:46-52.
44. Blair SN, Capuzzi DM, Gottlieb SO, et al. 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 . 2000;86:46-52.
45. Moghadasian MH, Frohlich JJ. Effects of dietary phytosterols on cholesterol metabolism and atherosclerosis: clinical and experimental evidence. Am J Med . 1999;107:588-594.
46. Williams CL, Bollella MC, Strobino BA, et al. Plant stanol ester and bran fiber in childhood: effects on lipids, stool weight and stool frequency in preschool children. J Am Coll Nutr . 1999;18:572-581.
47. Turnbull D, Whittaker MH, Frankos VH, et al. 13-week oral toxicity study with stanol esters in rats. Regul Toxicol Pharmacol . 1999;29:216-226.
48. Nguyen TT, Dale LV, von Bergmann K, et al. Cholesterol-lowering effect of stanol ester in a US population of mildly hypercholesterolemic men and women: a randomized controlled trial. Mayo Clin Proc . 1999;74:1198-2206.
49. Gylling H, Miettinen TA. Cholesterol reduction by different plant stanol mixtures and with variable fat intake. Metabolism . 1999;48:575-580.
50. Tammi A, Ronnemaa T, Gylling H, et al. Plant stanol ester margarine lowers serum total and low-density lipoprotein cholesterol concentrations of healthy children: the STRIP project. Special Turku Coronary Risk Factors Intervention Project. J Pediatr . 2000;136:503-510.
51. Hallikainen MA, Sarkkinen ES, Uusitupa MI. 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.
52. Miettinen TA, Puska P, Gylling H, et al. Reduction of serum cholesterol with sitostanol-ester margarine in a mildly hypercholesterolemic population. N Engl J Med. 1995;333:1308-1312.
53. Hallikainen MA, Sarkkinen ES, Uusitupa MI. 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.
54. Ostlund RE Jr, Racette SB, Okeke A, et al. Phytosterols that are naturally present in commercial corn oil significantly reduce cholesterol absorption in humans. Am J Clin Nutr. 2002;75:1000-1004.
55. Temme EH, Van Hoydonck PG, Schouten EG, et al. Effects of a plant sterol-enriched spread on serum lipids and lipoproteins in mildly hypercholesterolaemic subjects. Acta Cardiol . 2002;57:111-115.
56. Amundsen AL, Ose L, Nenseter MS, et al. Plant sterol ester-enriched spread lowers plasma total and LDL cholesterol in children with familial hypercholesterolemia. Am J Clin Nutr . 2002;76:338-344.
57. Simons L. Additive effect of plant sterol-ester margarine and cerivastatin in lowering low-density lipoprotein cholesterol in primary hypercholesterolemia. Am J Cardiol. 2002;90:737.
58. Vanstone CA, Raeini-Sarjaz M, Parsons WE, et al. Unesterified plant sterols and stanols lower LDL-cholesterol concentrations equivalently in hypercholesterolemic persons. Am J Clin Nutr . 2002;76:1272-1278.
59. Weststrate JA, Meijer GW. Plant sterol-enriched margarines and reduction of plasma total- and LDL-cholesterol concentrations in normocholesterolaemic and mildly hypercholesterolaemic subjects. Eur J Clin Nutr . 1998;52:334-343.
60. Jones PJ, Raeini-Sarjaz M, Ntanios FY, et al. Modulation of plasma lipid levels and cholesterol kinetics by phytosterol versus phytostanol esters. Lipid Res . 2000;41:697-705.
61. Cleghorn CL, Skeaff CM, Mann J, et al. Plant sterol-enriched spread enhances the cholesterol-lowering potential of a fat-reduced diet. Eur J Clin Nutr . 2003;57:170-176.
62. Lee YM, Haastert B, Scherbaum W, et al. A phytosterol-enriched spread improves the lipid profile of subjects with type 2 diabetes mellitus: a randomized controlled trial under free-living conditions. Eur J Nutr . 2003;42:111-117.
63. Richelle M, Enslen M, Hager C, et al. Both free and esterified plant sterols reduce cholesterol absorption and the bioavailability of beta-carotene and alpha-tocopherol in normocholesterolemic humans. Am J Clin Nutr . 2004;80:171-177.
64. Noakes M, Clifton PM, Doornbos AM, et al. Plant sterol ester-enriched milk and yoghurt effectively reduce serum cholesterol in modestly hypercholesterolemic subjects. Eur J Nutr . 2004 Aug 17. [Epub ahead of print]
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66. Seki S, Hidaka I, Kojima K, et al. Effects of phytosterol ester-enriched vegetable oil on plasma lipoproteins in healthy men. Asia Pac J Clin Nutr . 2003;12:282-291.
67. 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;78:965-980.
68. Hendriks HF, Brink EJ, Meijer GW, et al. Safety of long-term consumption of plant sterol esters-enriched spread. Eur J Clin Nutr . 2003;57:681-692.
69. Richelle M, Enslen M, Hager C, et al. Both free and esterified plant sterols reduce cholesterol absorption and the bioavailability of beta-carotene and alpha-tocopherol in normocholesterolemic humans. Am J Clin Nutr . 2004;80:171-177.
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72. Saito S, Tomonobu K, Kudo N, et al. Serum Retinol, alpha-Tocopherol, and beta-Carotene Levels Are Not Altered by Excess Ingestion of Diacylglycerol-Containing Plant Sterol Esters. Ann Nutr Metab. 2006 Jun 28 [Epub ahead of print].
73. Castro Cabezas M, de Vries JH, Van Oostrom AJ, et al. Effects of a stanol-enriched diet on plasma cholesterol and triglycerides in patients treated with statins. J Am Diet Assoc. 2006;106:1564-1569.
74. Woodgate D, Chan CH, Conquer JA. Cholesterol-lowering ability of a phytostanol softgel supplement in adults with mild to moderate hypercholesterolemia. Lipids. 2006;41:127-132.
75. Plana N, Nicolle C, Ferre R, et al. Plant sterol-enriched fermented milk enhances the attainment of LDL-cholesterol goal in hypercholesterolemic subjects. Eur J Nutr. 2008 Jan 14.
76. Vissers MN, Trip MD, Pritchard PH, et al. Efficacy and safety of disodium ascorbyl phytostanol phosphates in men with moderate dyslipidemia. Eur J Clin Pharmacol. 2008 Mar 5. [Epub ahead of print]
77. Allen RR, Carson L, Kwik-Uribe C, et al. Daily consumption of a dark chocolate containing flavanols and added sterol esters affects cardiovascular risk factors in a normotensive population with elevated cholesterol. J Nutr. 2008;138:725-731.
78. Micallef MA, Garg ML. The lipid-lowering effects of phytosterols and (n-3) polyunsaturated fatty acids are synergistic and complementary in hyperlipidemic men and women. J Nutr. 2008;138:1086-1090.
Last reviewed April 2009 by EBSCO CAM Review Board
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