DLM: Plant Stanols and Sterols 2011
Click here to see the explanation of recommendation ratings (Strong, Fair, Weak, Consensus, Insufficient Evidence) and labels (Imperative or Conditional). To see more detail on the evidence from which the following recommendations were drawn, use the hyperlinks in the Supporting Evidence Section below.
DLM: Plant Stanols and Sterols
If consistent with patient preference and not contraindicated by risks or harms, the Registered Dietitian (RD) should consider incorporating plant sterol and stanol ester-enriched foods into a cardioprotective diet, to be consumed two or three times per day, for a total consumption of two to three grams per day. These doses further lower total cholesterol (TC) by 4% to 11% and low-density lipoprotein cholesterol (LDL-C) by 7% to 15%. Doses beyond three grams do not provide additional benefit. To prevent weight gain, isocalorically substitute stanol- and sterol-enriched foods for other foods. Plant stanols and plant sterols are also effective in people taking statin drugs.
DLM: Plant Stanols and Sterols and Adverse Effects
The Registered Dietitian (RD) should be aware that research to date has not documented adverse effects, including reduced absorption of carotenoids, retinol and tocopherols. Plant stanols and sterols may be included in a patient's nutrition prescription (e.g., two or three grams per day) to lower cholesterol.
Research from 17 randomized controlled trials (RCTs) indicates effective serum cholesterol-lowering benefits without any reported adverse effects, including no significant effect on plasma fat soluble vitamin status. Two observational studies reported an association between plasma levels and aortic tissue concentration of stanols and sterols in a small number of individuals who consumed foods supplemented with plant sterol and stanol esters. The clinical significance of the association has not been documented.
Risks/Harms of Implementing This Recommendation
- Plant sterol and stanol products should not be used in individuals with the rare genetic disorder of sitosterolemia (Patel, 2008)
- Spreads and other food sources of plant sterols and stanols can contain considerable calories. Caloric content should be considered while recommending appropriate weight control/loss strategies.
- Cost considerations should be discussed with patients to enable them to make appropriate substitutions within their food budget
- For more information, see Evaluating Safety: Data to Determine Risk.
Conditions of Application
- Patient preference and acceptability.
- Label advisory on product use.
Potential Costs Associated with Application
There will be an increased cost for fortified food sources of plant stanols and sterols.
Plant Stanols and Sterols
A total of twenty studies provide evidence for the following:
- Five positive quality randomized controlled trials (RCTs) of normocholesterolemic individuals (Hendricks et al, 2003; Quilez et al, 2003; Homma et al, 2003; Ntanios et al, 2002; Davidson et al, 2001) and seven positive quality RCTs (Christiansen et al, 2001; Miettinen et al, 1995, Devaraj et al, 2004; Tikkanen et al, 2001; Nestel et al, 2001; Hallikainen et al, 2000; Vanstone et al, 2002) of hypercholesterolemic individuals found sterol and stanol ester-enriched products lowered TC and LDL-C. Both sterols and stanols and the esterified and nonesterified forms were effective.
- Many studies provided sterols or stanols in foods other than margarines, such as low-fat yogurt, bakery products, and salad dressings, and beneficial effects still persisted
- Beneficial effects were seen when phytosterols were given as part of a low-fat, low cholesterol diet in three positive quality RCTs (Maki et al, 2001; Noakes et al, 2002; Volpe et al, 2001)
- One study (Hallikainen et al, 2000) gave varying doses of plant stanols and found a dose response at lower levels, but increasing the dose from 2.4g to 3.2g per day did not provide further benefit
- Two positive quality RCTs (Gylling et al, 1997; Blair et al, 2000) found that plant stanols are effective even when given with statin drugs
- Studies included 16 positive quality RCTs (Blair et al, 2000; Christiansen et al, 2001; Devaraj et al, 2004; Gylling et al, 1997; Hendriks et al, 2003; Homma et al, 2003; Maki et al, 2001; Mensink et al, 2002; Miettinen et al, 1995; Nestel et al, 2001; Noakes et al, 2002; Ntanios et al, 2002; Quilez et al, 2003; Tikkanen et al, 2001; Vanstone et al, 2002; Volpe et al, 2001), two neutral quality RCTs (Davidson et al, 2001; Hallikainen et al, 2000), one negative quality consensus statement (Lichtenstein et al, 2001), one neutral quality meta-analysis (Mensink et al, 2003).
Adverse Effects of Plant Stanols and Sterols
- Twenty-eight studies provide evidence that consumption of plant stanols and sterols was not associated with adverse effects. Seventeen RCTs demonstrated effective serum cholesterol-lowering benefits without any reported adverse effects, including NS effect on fat soluble vitamin status (assessed by plasma levels). Very limited data suggest otherwise. Two other positive quality studies (Amundsen et al, 2004; Mensink et al, 2002) reported lowering of carotenoid levels. Although two positive quality observational studies (Silbernagel et al, 2009, Weingärtner et al, 2008) report a possible association between plasma or tissue sterol levels and increased risk of coronary heart disease (CHD), the short-term RCTs do not indicate negative effects on vascular function.
- Six positive quality RCTs (Colgan H et al, 2004; De Jong et al, 2008; Korpela et al, 2006; Noakes et al 2002; Quilez et al, 2003; Tuomilehto J et al, 2009) and one positive quality non-randomized follow-up study of an RCT (Amundsen et al, 2004) found consuming foods rich in hydrocarbon carotenoids, a- or ß-carotenoids and a-, ß- or total tocopherol with phytosterols maintained plasma levels
- One RCT (Davidson et al, 2001) gave up to 9g per day for eight weeks and found no evidence of adverse effects. This was confirmed by three other studies (Christiansen et al, 2001, Gylling et al, 2009, Hendriks et al, 2003) that gave lower does of plant sterols and stanols, but for longer periods of time.
- Studies included 19 RCTs (Christiansen et al, 2001; Colgan H et al, 2004; Davidson MH et al, 2001; De Jong et al, 2008; Gylling et al, 2009; Hendriks et al, 2003; Homma et al, 2003; Korpela et al, 2006; Maki et al, 2001; Mensink et al, 2002; Nestel et al, 2001; Noakes M, Clifton P et al, 2002; Ntanios et al, 2002; O'Neill et al, 2005; Quilez et al, 2003; Raitakari et al, 2008; Schiepers OJ et al, 2009; Tuomilehto J et al, 2009; Volpe et al, 2001), one non-randomized follow-up study of an RCT (Amundsen et al, 2004), three case-control studies (Helske et al, 2008; Rajaratnam et al, 2000; Windler et al, 2009), and five correlation studies (Fassbender et al, 2008; Lea et al, 2006; Silbernagel G et al, 2009; Weingärtner et al, 2008; Wilund et al, 2009)
Recommendation Strength Rationale
- Consistency of results among multiple positive quality RCTs
- Although the ethnicity of study participants was not identified in all studies, few studies did report this information and studies included many populations such as Caucasians, blacks, Hispanics, and Asians; and men and women
- A biological plausibility for mechanisms of action of plant stanol and sterol esters-containing foods exists
- A dose-response relationship exists
- Conclusions statements are as follows:
- Grade I: 1) Stanol/Sterol Effects on Cholesterol-lowering as Part of Cholesterol-lowering Diet; Effects on TC and LDL; 2) Further Reduction in TC and LDL in Patients Taking Statins
- Grade II: 1) Comparison of Sterols/Stanols in Terms of Cholesterol-lowering; 2) Safety of Plant Stanols/Sterols
- Grade III: 1) Comparison of Esterified and Nonesterified Forms in Terms of Cholesterol-lowering Effect; 2) Consumption of Carotenoid-rich Foods With Plant Stanols/Sterols
- Above conclusion statements are based on 16 positive quality RCTs, two neutral quality RCTs, one negative quality consensus statement, and one neutral quality meta-analysis
- Grade II: Adverse Effects of Plant Stanols and Sterols, based on 17 positive quality RCTs, one neutral quality RCT, one positive quality non-randomized follow-up study of an RCT, two positive quality case-control studies, one neutral quality case-control study, five positive quality correlation studies and one neutral quality correlation study
Area of uncertainty: To date, no clinical outcome studies have evaluated the effects of stanols and sterols on CHD events.
- Risks/Harms of Implementing This Recommendation
The recommendations were created from the evidence analysis on the following questions. To see detail of the evidence analysis, click the blue hyperlinks below (recommendations rated consensus will not have supporting evidence linked).
(2010) In adults, are there any adverse effects when consuming plant stanols and sterols?
(2006) How do sterols and stanols compare in terms of their efficacy in lowering cholesterol?
(2005) How are the effects of stanols and sterols on cholesterol levels altered when eaten as part of a cholesterol lowering diet?
(2005) What effect does the intake of plant sterols and stanols have on total cholesterol and LDL cholesterol?
(2005) How do esterified and nonesterified forms of stanols and sterols compare in terms of their cholesterol lowering ability?
(2005) Can plant stanols further reduce LDL cholesterol and total cholesterol even for people receiving statin therapy?
(2005) Can statin dose be reduced through the use of stanols and sterols?
Amundsen AL, Ntanios F, Put N, Ose L. Long-term compliance and changes in plasma lipids, plant sterols and carotenoids in children and parents with FH consuming plant sterol ester-enriched spread. Eur J Clin Nutr. 2004; 58: 1,612-1,620.
Christiansen LI, Lahteenmaki PLA, Mannelin MR, Seppanen-Laakso TE, Hiltunen RVK, Yliruusi JK. Cholesterol-lowering effect of spreads enriched with microcrystalline plant sterols in hypercholesterolemic subjects. Eur J Nutrition 2001 Apr; 40 (2): 66-73.
Colgan HA, Floyd S, Noone EJ, Gibney MJ, Roche HM. Increased intake of fruit and vegetables and a low-fat diet, with and without low-fat plant sterol-enriched spread consumption: effects on plasma lipoprotein and carotenoid metabolism. J Hum Nutr Diet. 2004 Dec; 17(6): 561-569.
Davidson MH, Maki KC, Umporowicz DM, Ingram KA, Dicklin MR, Schaefer E, Lane RW, McNamara JR, Ribaya-Mercado JD, Perrone G, Robins SJ, Franke WC. Safety and tolerability of esterified phytosterols administered in reduced-fat spread and salad dressing to healthy men and women. J Am Coll Nutr. 2001 Aug; 20(4): 307-319.
De Jong A, Plat J, Bast A, Godschalk RW, Basu S, Mensink RP. Effects of plant sterol and stanol ester consumption on lipid metabolism, antioxidant status and markers of oxidative stress, endothelial function and low-grade inflammation in patients on current statin treatment. Eur J Clin Nutr. 2008 Feb; 62(2): 263-273. Epub 2007 May 9.
Fassbender K, Lütjohann D, Dik MG, Bremmer M, König J, Walter S, Liu Y, Letièmbre M, von Bergmann K, Jonker C.Moderately elevated plant sterol levels are associated with reduced cardiovascular risk: The LASA study. Atherosclerosis. 2008 Jan; 196 (1): 283-288.
Gylling H, Hallikainen M, Raitakari OT, Laakso M, Vartiainen E, Salo P, Korpelainen V, Sundvall J, Miettinen TA. Long-term consumption of plant stanol and sterol esters, vascular function and genetic regulation. Br J Nutr. 2009 Jun; 101 (11): 1,688-1,695.
Helske S, Miettinen T, Gylling H, Mäyränpää M, Lommi J, Turto H, Werkkala K, Kupari M, Kovanen PT. Accumulation of cholesterol precursors and plant sterols in human stenotic aortic valves. J Lipid Res. 2008 Jul; 49 (7): 1,511-1,518.
Hendriks HFJ, Brink EJ, Meijer GW, Princen HMG, Ntanios FY. Safety of long-term consumption of plant sterol esters-enriched spread. Eur J Clin Nutr. 2003 May; 57(5): 681-692.
Homma Y, Ikeda I, Ishikawa T, Tateno M, Sugano M, Nakamura H. Decrease in plasma low-density lipoprotein cholesterol, apolipoprotein B, cholesteryl ester transfer protein, and oxidized low-density lipoprotein by plant stanol ester-containing spread: A randomized, placebo-controlled trial. Nutrition. 2003 Apr; 19 (4): 369-374.
Korpela R, Tuomilehto J, Högström P, Seppo L, Piironen V, Salo-Väänänen P, Toivo J, Lamberg-Allardt C, Kärkkäinen M, Outila T, Sundvall J, Vilkkilä S, Tikkanen MJ. Safety aspects and cholesterol-lowering efficacy of low-fat dairy products containing plant sterols. Eur J Clin Nutr. 2006 May; 60 (5): 633-642.
Lea LJ, Hepburn PA. Safety evaluation of phytosterol-esters. Part 9: Results of a European post-launch monitoring programme. Food Chem Toxicol. 2006 Aug;44 (8):1,213-1,222.
Maki KC, Davidson MH, Umporowicz DM, Schaefer EJ, Dicklin MR, Ingram KA, Chen S, McNamara JR, Gebhart BW, Ribaya-Mercado JD, Perrone G, Robins SJ, Franke WC. Lipid reponses to plant-sterol-enriched reduced-fat spreads incorporated into a National Cholesterol Education Program Step I diet. Am J Clin Nutr 2001 Jul; 74 (1): 33-43.
Mensink RP, Ebbing S, Lindhout M, Plat J, van Heugten MMA. Effects of plant stanol esters supplied in low-fat yoghurt on serum lipids and lipoproteins, non-cholesterol sterols and fat soluble antioxidant concentrations. Atherosclerosis 2002 Jan; 160(1):205-213.
Nestel P, Cehun M, Pomeroy S, Abbey M, Weldon G. Cholesterol-lowering effects of plant sterol esters and non-esterified stanols in margarine, butter and low-fat foods. European Journal of Clinical Nutrition. 2001 Dec; 55 (12): 1,084-1,090.
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.
Ntanios FY, Homma Y, Ushiro S. A spread enriched with plant sterol-esters lowers blood cholesterol and lipoproteins without affecting vitamins A and E in normal and hypercholesterolemic Japanese men and women. J Nutr. 2002; 132 (12): 3,650-3,655.
O'Neill FH, Sanders TA, Thompson GR. Comparison of efficacy of plant stanol ester and sterol ester: Short-term and longer-term studies. Am J Cardiol. 2005 Jul 4; 96 (1A): 29D-36D.
Quilez J, Rafecas M, Brufau G, Garcia-Lorda P, Megias I, Bullo M, Ruiz JA, Salas-Salvado J. Bakery products enriched with phytosterol esters, a-tocopherol and ß-carotene decrease plasma LDL-cholesterol and maintain plasma ß-carotene concentrations in normocholesterolemic men and women. J Nutr 2003 Oct; 133(10):3103-3109.
Raitakari OT, Salo P, Gylling H, Miettinen TA Plant stanol ester consumption and arterial elasticity and endothelial function. Br J Nutr. 2008; 100: 603-608.
Rajaratnam RA, Gylling H, Miettinen TA. Independent association of serum squalene and noncholesterol sterols with coronary artery disease in postmenopausal women. J Am Coll Cardiol. 2000 Apr; 35(5): 1,185-1,191.
Schiepers OJ, de Groot RH, van Boxtel MP, Jolles J, de Jong A, Lütjohann D, Plat J, Mensink RP. Consuming functional foods enriched with plant sterol or stanol esters for 85 weeks does not affect neurocognitive functioning or mood in hypercholesterolemic individuals. J Nutr. 2009 Jul; 139 (7): 1,368-1,373.
Silbernagel G, Fauler G, Renner W, Landl EM, Hoffmann MM, Winkelmann BR, Boehm BO, März W. The relationships of cholesterol metabolism and plasma plant sterols with the severity of coronary artery disease. J Lipid Res. 2009 Feb; 50 (2): 334-341.
Tuomilehto J, Tikkanen MJ, Högström P, Keinänen-Kiukaanniemi S, Piironen V, Toivo J, Salonen JT, Nyyssönen K, Stenman UH, Alfthan H, Karppanen H. Safety assessment of common foods enriched with natural non-esterified plant sterols. Eur J Clin Nutr. 2009 May; 63 (5): 684-691.
Volpe R, Niittynen L, Korpela R, Sirtori C, Bucci A, Fraone N, Pazzucconi F. Effects of yoghurt enriched with plant sterols on serum lipids in patients with moderate hypercholesterolaemia. British Journal of Nutrition 2001 Aug; 86(2):233-239.
Weingärtner O, Lütjohann D, Ji S, Weisshoff N, List F, Sudhop T, von Bergmann K, Gertz K, König J, Schäfers HJ, Endres M, Böhm M, Laufs U. Vascular effects of diet supplementation with plant sterols. J Am Coll Cardiol. 2008 Apr 22; 51 (16): 1,553-1,561.
Wilund KR, Yu L, Xu F, Vega GL, Grundy SM, Cohen JC, Hobbs HH. No association between plasma levels of plant sterols and atherosclerosis in mice and men. Arterioscler Thromb Vasc Biol. 2004 Dec; 24 (12): 2,326-2,332.
Windler E, Zyriax BC, Kuipers F, Linseisen J, Boeing H. Association of plasma phytosterol concentrations with incident coronary heart disease Data from the CORA study, a case-control study of coronary artery disease in women. Atherosclerosis. 2009 Mar; 203(1): 284-290.
Devaraj S, Jialal I, Vega-Lopez S. Plant sterol-fortified orange juice effectively lowers cholesterol levels in mildly hypercholesterolemic healthy individuals. Arterioscler Thromb Vasc Biol 2004; 24:e25-e28.
Gylling H, Radhakrishnan R, Miettinin 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
Hallikainen MA, Sarkkinen ES, Uusitupa MI. Plant stanol esters affect serum cholesterol concentrations of hypercholesterolemic men and women in a dose-dependent manner. J Nutrition. 2000;130:767-776.
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: 1,308-1,312.
Tikkanen MJ, Hogstrom P, Tuomilehto J, Keinanen-Kiukaanniemi S, Sundvall J, and Karppanen H. Effect of a diet based on low-fat foods enriched with nonesterified plant sterols and mineral nutrients on serum cholesterol. Am J Cardiol 2001; 88:1157-1162.
Vanstone CA, Raeini-Sarjaz M, Parsons WE, Jones PJH. Unesterified plant sterols and stanols lower LDL-cholesterol concentrations equivalently in hypercholesterolemic persons. Am J Clin Nutr 2002; 76:1272-1278.
Blair SN, Capuzzi DM, Gottlieb SO, Nguyen T, Morgan JM, Cater NB. Incremental reduction of serum total cholesterol with the addition of plant stanol ester-containing spread to statin therapy. Am J Cardiol 2000; 86: 46-52.
Lichtenstein AH, Deckelbaum RJ. AHA Science Advisory. Stanol/sterol ester-containing foods and blood cholesterol levels. A statement for healthcare professionals from the Nutrition Committee of the Council on Nutrition, Physical Activity, and Metabolism of the American Heart Association.. Circulation. 2001;103:1177-1179.
References not graded in Academy of Nutrition and Dietetics Evidence Analysis Process
Hu FB, Willett WC. Optimal diets for prevention of coronary heart disease. JAMA. 2002 Nov 27; 288 (20): 2, 569-2, 578. Review. PMID: 12444864.
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 Aug; 78 (8): 965-978. Review. PMID: 12911045.
Patel SB. Plant Sterols and Stanols: Their Role in Health and Disease. J Clin Lipidol. 2008 Apr; 2 (2): S11-S19. PMID: 19343077; PMCID: PMC2390824.