Plant sterols and cardiovascular disease: A systematic review and meta-analysis

European Heart Journal

Volumn 33, Issue 4, 2012, Pages

  Genser, Bernd ^a,b   Silbernagel, Gnther ^c   De Backer, Guy ^d   Bruckert, Eric ^e   Carmena, Rafael ^f   Chapman, M John ^e,g   Deanfield, John ^h   Descamps, Olivier S ⁱ   Rietzschel, Ernst R ^d   Dias, Karen C ^b   Mrz, Winfried ^a,j,k  

^a UNIVERSITY OF HEIDELBERG   (Germany)

^b FEDERAL UNIVERSITY OF BAHIA   (Brazil)

^c UNIVERSITY OF TÜBINGEN   (Germany)

^d GHENT UNIVERSITY   (Belgium)

^e PITIÉ SALPÊTRIÈRE HOSPITAL   (France)

^f University Hospital   (Spain)

^g INSERM   (France)

^h UNIVERSITY COLLEGE LONDON   (United Kingdom)

ⁱ Center of Medical Research   (Belgium)

^j SYNLAB ACADEMY   (Germany)

^k MEDICAL UNIVERSITY OF GRAZ   (Austria)

more..

Author keywords

Cardiovascular disease; Coronary heart disease; LDL C; Phytosterols; Plant sterols

Indexed keywords

CAMPESTEROL; CHOLESTEROL; PHYTOSTEROL; SITOSTEROL;

BLOOD LEVEL; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CHOLESTEROL BLOOD LEVEL; CONCENTRATION (PARAMETERS); DIET; HUMAN; MEDICAL LITERATURE; PRIORITY JOURNAL; PUBLISHING; REVIEW; SYSTEMATIC REVIEW;

CARDIOVASCULAR DISEASES; CHOLESTEROL; DIET; EPIDEMIOLOGIC METHODS; HUMANS; PHYTOSTEROLS; PUBLICATION BIAS; RISK FACTORS; SITOSTEROLS;

EID: 84857155669     PISSN: 0195668X     EISSN: 15229645     Source Type: Journal    
DOI: 10.1093/eurheartj/ehr441     Document Type: Review

References (67)

1. World Health Organisation. The Global Burden of Disease: 2004 Update. World Health Organisation, Geneva, 2008.
2. Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation 1998;97:1837-1847. (Pubitemid 28213628)
3. Sacks FM, Pasternak RC, Gibson CM, Rosner B, Stone PH. Effect on coronary atherosclerosis of decrease in plasma cholesterol concentrations in normocholesterolaemic patients. Harvard Atherosclerosis Reversibility Project (HARP) Group. Lancet 1994;344:1182-1186. (Pubitemid 24323706)
4. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994;344: 1383-1389.
5. Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, McKillop JH, Packard CJ. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med 1995;333:1301-1307.
6. Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG, Brown L, Warnica JW, Arnold JM, Wun CC, Davis BR, Braunwald E. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med 1996;335:1001-1009. (Pubitemid 26338729)
7. Farquhar JW, Sokolow M. Response of serum lipids and lipoproteins o man to beta-sitosterol and safflower oil; a longterm study. Circulation 1958;17:890-899.
8. Bronte-Stewart B, Antonis A, Eales L, Brock JF. Effects of feeding different fats on serum-cholesterol level. Lancet 1956;270:521-526.
9. Ahrens EH Jr, Insull W Jr, Blomstrand R, Hirsch J, Tsaltas TT, Peterson ML. The influence of dietary fats on serum-lipid levels in man. Lancet 1957;272:943-953.
10. Ostlund RE Jr. Phytosterols in human nutrition. Annu Rev Nutr 2002;22:533-549. (Pubitemid 35221472)
11. Silbernagel G, März W. Plant sterols: cardiovascular risk factors. J Lab Med 2008; 32:209-218.
12. Chan YM, Varady KA, Lin Y, Trautwein E, Mensink RP, Plat J, Jones PA. Plasma concentrations of plant sterols: physiology and relationship with coronary heart disease. Nutr Rev 2006;64:385-402. (Pubitemid 44525198)
13. 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.
14. Brendsel J, Green SJ. Regarding the potential perils of phytosterols. Atherosclerosis 2007;192:227-229; author reply 30. (Pubitemid 46602311)
15. Weingärtner O, Böhm M, Laufs U. Controversial role of plant sterol esters in the management of hypercholesterolaemia. Eur Heart J 2009;30:404-409.
16. Schonfeld G. Plant sterols in atherosclerosis prevention. Am J Clin Nutr 2010;92: 3-4.
17. Salen G, Horak I, Rothkopf M, Cohen JL, Speck J, Tint GS, Shore V, Dayal B, Chen T, Shefer S. Lethal atherosclerosis associated with abnormal plasma and tissue sterol composition in sitosterolemia with xanthomatosis. J Lipid Res 1985; 26:1126-1133. (Pubitemid 16258297)
18. Payne MY. Too young to be having a heart attack. Lancet 2001;358(suppl):S64.
19. Bhattacharyya AK, Connor WE. Beta-sitosterolemia and xanthomatosis. A newly described lipid storage disease in two sisters. J Clin Invest 1974;53:1033-1043.
20. Berge KE, Tian H, Graf GA, Yu L, Grishin NV, Schultz J, Kwiterovich P, Shan B, Barnes R, Hobbs HH. Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science 2000;290:1771-1775. (Pubitemid 32004809)
21. Lee MH, Lu K, Hazard S, Yu H, Shulenin S, Hidaka H, Kojima H, Allikmets R, Sakuma N, Pegoraro R, Srivastava AK, Salen G, Dean M, Patel SB. Identification of a gene, ABCG5, important in the regulation of dietary cholesterol absorption. Nat Genet 2001;27:79-83. (Pubitemid 32044523)
22. Assmann G, Cullen P, Erbey J, Ramey DR, Kannenberg F, Schulte H. Plasma sitosterol elevations are associated with an increased incidence of coronary events in men: results of a nested case-control analysis of the Prospective Cardiovascular Munster (PROCAM) study. Nutr Metab Cardiovasc Dis 2006;16: 13-21.
23. 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;35:1185-1191. (Pubitemid 30206893)
24. Matthan NR, Pencina M, Larocque JM, Jacques PF, D'Agostino RB, Schaefer EJ, Lichtenstein AH. Alterations in cholesterol absorption and synthesis characterize Framingham offspring study participants with coronary heart disease. J Lipid Res 2009;50:1927-1935.
25. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009;67: e1000097.
26. Danesh J, Collins R, Appleby P, Peto R. Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies. JAMA 1998;279:1477-1482. (Pubitemid 28228207)
27. Teupser D, Baber R, Ceglarek U, Scholz M, Illig T, Gieger C, Holdt LM, Leichtle A, Greiser KH, Huster D, Linsel-Nitschke P, Schafer A, Braund PS, Tiret L, Stark K, Raaz-Schrauder D, Fiedler GM, Wilfert W, Beutner F, Gielen S, Grosshennig A, Konig IR, Lichtner P, Heid IM, Kluttig A, El Mokhtari NE, Rubin D, Ekici AB, Reis A, Garlichs CD, Hall AS, Matthes G, Wittekind C, Hengstenberg C, Cambien F, Schreiber S, Werdan K, Meitinger T, Loeffler M, Samani NJ, Erdmann J, Wichmann HE, Schunkert H, Thiery J. Genetic regulation of serum phytosterol levels and risk of coronary artery disease. Circ Cardiovasc Genet 2010;3:331-339.
28. Dickersin K, Berlin JA. Meta-analysis: state-of-the-science. Epidemiol Rev 1992;14: 154-176. (Pubitemid 23024558)
29. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7: 177-188. (Pubitemid 17189972)
30. Glueck CJ, Speirs J, Tracy T, Streicher P, Illig E, Vandegrift J. Relationships of serum plant sterols (phytosterols) and cholesterol in 595 hypercholesterolemic subjects, and familial aggregation of phytosterols, cholesterol, and premature coronary heart disease in hyperphytosterolemic probands and their first-degree relatives. Metabolism 1991;40:842-848.
31. Sudhop T, Gottwald BM, von Bergmann K. Serum plant sterols as a potential risk factor for coronary heart disease. Metabolism 2002;51:1519-1521. (Pubitemid 36018822)
32. Weingartner O, Lutjohann D, Ji S, Weisshoff N, List F, Sudhop T, von Bergmann K, Gertz K, Koenig J, Schafers HJ, Endres M, Bohm M, Laufs U. Vascular effects of diet supplementation with plant sterols. J Am Coll Cardiol 2008;51: 1553-1561. (Pubitemid 351512314)
33. Helske S, Miettinen T, Gylling H, Mayranpaa 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;49:1511-1518.
34. Miettinen TA, Nissinen M, Lepantalo M, Alback A, Railo M, Vikatmaa P, Kaste M, Mustanoja S, Gylling H. Non-cholesterol sterols in serum and endarterectomized carotid arteries after a short-term plant stanol and sterol ester challenge. Nutr Metab Cardiovasc Dis 2010; [Epub ahead of print].
35. Miettinen TA, Railo M, Lepantalo M, Gylling H. Plant sterols in serum and in atherosclerotic plaques of patients undergoing carotid endarterectomy. J Am Coll Cardiol. 2005;45:1794-1801. (Pubitemid 40779859)
36. 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.
37. Sutherland WHF, Williams MJA, Nye ER, Restiaux NJ, de Jong SA, Walker HL. Associations of plasma noncholesterol sterol levels with severity of coronary disease. Nutr Metab Cardiovasc Dis 1998;8:386-391. (Pubitemid 128584538)
38. Thiery J, Ceglarek U, Fiedler GM, Leichtle A, Baumann S, Deupser D, Lang O, Baumert J, Meisinger C, Loewel H, Doering A. Elevated campesterol serum levels: a significant predictor of incident myocardial infarction: results of the Population-based MONICA/KORA Follow-up Study 1994 to 2005. Circulation 2006;114:II884.
39. Escurriol V, Cofan M, Moreno-Iribas C, Larranaga N, Martinez C, Navarro C, Rodriguez L, Gonzalez CA, Corella D, Ros E. Phytosterol plasma concentrations and coronary heart disease in the prospective Spanish EPIC cohort. J Lipid Res 2010;51:618-624.
40. Fassbender K, Lutjohann D, Dik MG, Bremmer M, Konig J, Walter S, Liu Y, Letiembre M, von Bergmann K, Jonker C. Moderately elevated plant sterol levels are associated with reduced cardiovascular risk-the LASA study. Atherosclerosis 2008;196:283-288.
41. Gylling H, Hallikainen M, Rajaratnam RA, Simonen P, Pihlajamaki J, Laakso M, Miettinen TA. The metabolism of plant sterols is disturbed in postmenopausal women with coronary artery disease. Metabolism 2009;58:401-407.
42. Matthan NR, Resteghini N, Robertson M, Ford I, Shepherd J, Packard C, Buckley BM, Jukema JW, Lichtenstein AH, Schaefer EJ. Cholesterol absorption and synthesis markers in individuals with and without a CHD event during pravastatin therapy: insights from the PROSPER trial. J Lipid Res 2010;51:202-209.
43. Pinedo S, Vissers MN, von Bergmann K, Elharchaoui K, Lutjohann D, Luben R, Wareham NJ, Kastelein JJ, Khaw KT, Boekholdt SM. Plasma levels of plant sterols and the risk of coronary artery disease: the prospective EPIC-Norfolk Population Study. J Lipid Res 2007;48:139-144. (Pubitemid 46052905)
44. Rajaratnam RA, Gylling H, Miettinen TA. Cholesterol absorption, synthesis, and fecal output in postmenopausal women with and without coronary artery disease. Arterioscler Thromb Vasc Biol 2001;21:1650-1655. (Pubitemid 34215586)
45. Shay CM, Evans RW, Orchard TJ. Do plant sterol concentrations correlate with coronary artery disease in type 1 diabetes? A report from the Pittsburgh Epidemiology of Diabetes Complications Study. J Diabetes 2009;1:112-117.
46. Silbernagel G, Fauler G, Hoffmann MM, Lutjohann D, Winkelmann BR, Boehm BO, Maerz W. The associations of cholesterol metabolism and plasma plant sterols with all-cause-and cardiovascular mortality. J Lipid Res 2010;51: 2384-2393.
47. Silbernagel G, Fauler G, Renner W, Landl EM, Hoffmann MM, Winkelmann BR, Boehm BO, Maerz W. The relationships of cholesterol metabolism and plasma plant sterols with the severity of coronary artery disease. J LipidRes 2009;50:334-341.
48. Strandberg TE, Gylling H, Tilvis RS, Miettinen TA. Serum plant and other noncholesterol sterols, cholesterol metabolism and 22-year mortality among middle-aged men. Atherosclerosis 2010;210:282-287.
49. Strandberg TE, Tilvis RS, Pitkala KH, Miettinen TA. Cholesterol and glucose metabolism and recurrent cardiovascular events among the elderly: a prospective study. J Am Coll Cardiol 2006;48:708-714. (Pubitemid 44175730)
50. Weingartner O, Weingartner N, Scheller B, Lutjohann D, Graber S, Schafers HJ, Böhm M, Laufs U. Alterations in cholesterol homeostasis are associated with coronary heart disease in patients with aortic stenosis. Coron Artery Dis 2009;20: 376-382.
51. 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;24:2326-2332. (Pubitemid 39658037)
52. 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;203:284-290.
53. Miettinen TA, Tilvis RS, Kesämiemi YA. Serum plant sterols and cholesterol precursors reflect cholesterol absorption and synthesis in volunteers of a randomly selected male population. Am J Epidemiol 1990;13:20-31. (Pubitemid 20014696)
54. Greenberg ME, Smith JD, Sehayek E. Moderately decreased cholesterol absorption rates are associated with a large atheroprotective effect. Arterioscler Thromb Vasc Biol 2009;29:1745-1750.
55. Simonen P, Gylling H, Howard AN, Miettinen TA. Introducing a new component of the metabolic syndrome: low cholesterol absorption. Am J Clin Nutr 2000;72: 82-88. (Pubitemid 30441661)
56. Gylling H, Hallikainen M, Kolehmainen M, Toppinen L, Pihlajamäki J, Mykkänen H, Agren JJ, Rauramaa R, Laakso M, Miettinen TA. Cholesterol synthesis prevails over absorption in metabolic syndrome. Transl Res 2007;149:310-316. (Pubitemid 46818162)
57. Pihlajamaki J, Gylling H, Miettinen TA, Laakso M. Insulin resistance is associated with increased cholesterol synthesis and decreased cholesterol absorption in normoglycemic men. J Lipid Res 2004;45:507-512. (Pubitemid 38337997)
58. Simonen PP, Gylling HK, Miettinen TA. Diabetes contributes to cholesterol metabolism regardless of obesity. Diabetes Care 2002;25:1511-1515. (Pubitemid 41071103)
59. Hallikainen M, Kolehmainen M, Schwab U, Laaksonen DE, Niskanen L, Rauramaa R, Pihlajamaki J, Uusitupa M, Miettinen TA, Gylling H. Serum adipokines are associated with cholesterol metabolism in the metabolic syndrome. Clin Chim Acta 2007;383:126-132. (Pubitemid 47016459)
60. Gylling H, Tuominen JA, Koivisto VA, Miettinen TA. Cholesterol metabolism in type 1 diabetes. Diabetes 2004;53:2217-2222. (Pubitemid 39145574)
61. Kesaniemi YA, Ehnholm C, Miettinen TA. Intestinal cholesterol absorption efficiency in man is related to apoprotein E phenotype. J Clin Invest 1987;80:578-581.
62. Cohen JC, Pertsemlidis A, Fahmi S, Esmail S, Vega GL, Grundy SM, Hobbs HH. Multiple rare variants in NPC1L1 associated with reduced sterol absorption and plasma low-density lipoprotein levels. Proc Natl Acad Sci USA 2006;103: 1810-1815. (Pubitemid 43228775)
63. Gylling H, Hallikainen M, Pihlajamaki J, Agren J, Laakso M, Rajaratnam RA, Rauramaa R, Miettinen TA. Polymorphisms in the ABCG5 and ABCG8 genes associate with cholesterol absorption and insulin sensitivity. J Lipid Res 2004;45: 1660-1665. (Pubitemid 39296205)
64. Gami AS, Witt BJ, Howard DE, Erwin PJ, Gami LA, Somers VK, Montori VM. Metabolic syndrome and risk of incident cardiovascular events and death: a systematic review and meta-analysis of longitudinal studies. J Am Coll Cardiol 2007; 49:403-414. (Pubitemid 46135879)
65. Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 1998;339:229-234. (Pubitemid 28350165)
66. Strandberg TE, Pitkala KH. Frailty in elderly people. Lancet 2007;369:1328-1329. (Pubitemid 46590373)
67. Weingartner O, Lutjohann D, Ji S, Weisshoff N, List F, Sudhop T, von Bergmann K, Gertz K, Konig J, Schafers HJ, Endres M, Bohm M, Laufs U. Vascular effects of diet supplementation with plant sterols. J Am Coll Cardiol 2008;51: 1553-1561. (Pubitemid 351512314)