Lipid Disorders and Stanols/Sterols

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 cholesterol levels. The results are very promising.

Related substances called plant sterols appear to have equivalent effects,^173,189 and we will refer to sterols and stanols and their esters somewhat interchangeably.

The bottom-line from sterol/stanol research for lipid disorders is:

• When taken alone, stanols/sterols appear to lower LDL ("bad") cholesterol and probably have no significant effect on HDL ("good") cholesterol and triglycerides
• When taken in combination with fish oil, stanols/sterols probably help lower total cholesterol, LDL cholesterol, and triglycerides, while increasing HDL cholesterol
• Stanols/sterols enhance the effect of statins and cholesterol-lowering diets
• Stanols/sterols appear to be effective and safe for people with type 2 diabetes

Plant stanol esters reduce serum (blood) cholesterol levels by inhibiting cholesterol absorption.¹⁰ 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.¹ The displaced cholesterol is then excreted from the body. This 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.

Read more details about Stanols/Sterols.

Numerous double-blind, placebo-controlled studies, ranging in length from 30 days to 12 months, have found stanol esters and their chemical relatives effective for improving cholesterol profile levels.^{2-15,167-169,174,175,263,280} The combined results suggest that these substances can reduce total cholesterol and LDL ("bad") cholesterol by about 10%-15%.^16,278,279 However, stanols/sterols do not appear to have any significant effect on HDL ("good") cholesterol or triglycerides.

Fish oil has also 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.²⁸⁶

Individuals taking statin drugs may benefit from using stanols/sterols as well.^{20,21,170,241,278} According to one study, if you are on statins and start taking sterol ester margarine as well, your cholesterol will improve to the same extent as if you doubled the statin dose.¹⁷⁰ Stanols or sterols also appear to enhance the effects of cholesterol-lowering diets.^17,174

Stanols or sterols also appear to be safe and effective in helping to improve cholesterol profile in people with type 2 diabetes.^18,19,175

Typical dosages of stanol/sterols and their esters to improve cholesterol profile range from 2.7 to 5.1 g per day.^114,117 One study suggests that using stanol products once a day may be as effective as dividing up your intake throughout the day.¹¹⁵ It may take up to 3 months to show a substantial decrease in total cholesterol values.¹¹⁶

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.¹¹³ Stanol/sterols and their esters are added to margarine spreads and salad dressings and are also available as dietary supplement tablets.

• Integrative MD
• Naturopathic doctor
• Clinical nutritionist or registered dietitian

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. ¹ 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. ² 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. ³ 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. ⁴ Stanol esters might interfere with absorption of alpha- and beta-carotene , ⁵ although some studies have found no such effect. ⁶ Evidence is also conflicting whether sterols or sterol esters impair nutrient absorption. ⁷ Until more is learned, it may be reasonable for people using stanol or sterol products to take a multivitamin/multimineral tablet .

1. Blair SN, Capuzzi DM, Gottlieb SO, Nguyen T, Morgan JM, Cater NB. 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(1):46-52.
2. 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. 18(6):572-81.
3. Turnbull D, Whittaker MH, Frankos VH, Jonker D. 13-week oral toxicity study with stanol esters in rats. Regul Toxicol Pharmacol. 29(2 Pt 1):216-26.
4. 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.
5. Gylling H, Miettinen TA. Cholesterol reduction by different plant stanol mixtures and with variable fat intake. Metabolism. 48(5):575-80.
6. 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. 53(12):966-9.
7. Richelle M, Enslen M, Hager C, Groux M, Tavazzi I, Godin JP, Berger A, Métairon S, Quaile S, Piguet-Welsch C, Sagalowicz L, Green H, Fay LB. 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. 80(1):171-7.

1. Law M. Plant sterol and stanol margarines and health. BMJ. 2000;320:861-864.
2. 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.
3. Gylling H, Miettinen TA. Cholesterol reduction by different plant stanol mixtures and with variable fat intake. Metabolism. 1999;48:575-580.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. Gylling H, Siimes MA, Miettinen TA. Sitostanol ester margarine in dietary treatment of children with familial hypercholesterolemia. J Lipid Res. 1995;36:1807-1812.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. Nguyen TT. The cholesterol-lowering action of plant stanol esters. J Nutr. 1999;129:2109-2112.
17. 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.
18. 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.
19. 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.
20. 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.
21. 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.
111. Nguyen TT. The cholesterol-lowering action of plant stanol esters. J Nutr. 1999;129:2109-2112.
112. Gylling H, Miettinen TA. Cholesterol reduction by different plant stanol mixtures and with variable fat intake. Metabolism. 1999;48:575-580.

113. 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.
114. 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.
115. 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.
116. 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.
117. 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.
167. 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.
168. 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.
169. 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.
170. 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.
173. 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
174. 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.
175. 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.
189. 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.
241. 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.
263. 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.
278. 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.
279. 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]
280. 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.
286. 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.