Fat type in phytosterol products influence their cholesterol-lowering potential: A systematic review and meta-analysis of RCTs

Progress in Lipid Research

Volumn 64, Issue , 2016, Pages 16-29

  Ferguson, Jessica J A ^a   Stojanovski, Elizabeth ^a   MacDonald Wicks, Lesley ^a   Garg, Manohar L ^a  

^a UNIVERSITY OF NEWCASTLE   (Australia)

Author keywords

Canola; Cholesterol; Dairy; Phytosterols; Rapeseed; Sunflower

Indexed keywords

CHOLESTEROL; LOW DENSITY LIPOPROTEIN CHOLESTEROL; MONOUNSATURATED FATTY ACID; OMEGA 3 FATTY ACID; PHYTOSTEROL; ANTILIPEMIC AGENT; FAT INTAKE; VEGETABLE OIL;

BODY MASS; CHOLESTEROL BLOOD LEVEL; CLINICAL EFFECTIVENESS; DATA EXTRACTION; FAT INTAKE; HUMAN; INTERVENTION STUDY; META ANALYSIS; NUTRITIONAL HEALTH; OXIDATION KINETICS; PRIORITY JOURNAL; QUALITY CONTROL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SYSTEMATIC REVIEW; TREATMENT DURATION; ANIMAL; BLOOD; CARDIOVASCULAR DISEASES; CHEMISTRY; CLINICAL TRIAL (TOPIC); FACTUAL DATABASE; METABOLISM; PATHOLOGY; THERAPEUTIC USE;

ANIMALS; CARDIOVASCULAR DISEASES; CHOLESTEROL; CLINICAL TRIALS AS TOPIC; DATABASES, FACTUAL; DIETARY FATS; HUMANS; HYPOLIPIDEMIC AGENTS; PHYTOSTEROLS; PLANT OILS;

EID: 84981216447     PISSN: 01637827     EISSN: 18732194     Source Type: Journal    
DOI: 10.1016/j.plipres.2016.08.002     Document Type: Review

References (112)

1. [1] Organisation WH, Cardiovascular diseases (CVDs) [internet]., 2015 [updated January 2015; cited 2015 19 August]. Available from: http://www.who.int/mediacentre/factsheets/fs317/en/.
2. [2] Bloom, D.E., Cafiero, E.T., Jané-Llopis, E., Abrahams-Gessel, S., Bloom, L.R., Fathima, S., et al. The Global Economic Burden of Noncommunicable Diseases. 2011, World Economic Forum, Geneva September. Report No.: 080911.
3. [3] Australian Institute of Health and Welfare, High Blood Cholesterol. Cat. No. AUS 156. Ed. 2012–2013, Australian Institute of Health and Welfare, Canberra.
4. [4] De Smet, E., Mensink, R.P., Plat, J., Effects of plant sterols and stanols on intestinal cholesterol metabolism: suggested mechanisms from past to present. Mol. Nutr. Food Res. 56:7 (2012), 1058–1072.
5. [5] Joyce, T., Stanols and Sterols. 2015, The British Dietetic Association.
6. [6] Demonty, I., Ras, R.T., van der Knaap, H.C., Duchateau, G.S., Meijer, L., Zock, P.L., et al. Continuous dose-response relationship of the LDL-cholesterol-lowering effect of phytosterol intake. J. Nutr. 139:2 (2009), 271–284.
7. [7] Gylling, H., Plat, J., Turley, S., Grinsberg, H.N., Ellegard, L., Jessup, W., et al. Plant sterols and plant stanols in the management of dyslipidaemia and prevention of cardiovascular disease. Atherosclerosis, 232, 2014.
8. [8] Patel, M.D., Thompson, P.D., Phytosterols and vascular disease. Atherosclerosis 186 (2006), 12–19.
9. [9] Micallef, M.A., Garg, M.L., Beyond blood lipids: phytosterols, statins and omega-3 polyunsaturated fatty acid therapy for hyperlipidemia. J. Nutr. Biochem. 20:12 (2009), 927–939.
10. [10] Jones, P.J., Raeini-Sarjaz, M., Ntanios, F.Y., Vanstone, C.A., Feng, J.Y., Parsons, W.E., Modulation of plasma lipid levels and cholesterol kinetics by phytosterol versus phytostanol esters. J. Lipid Res., 41(5), 2000 (Internet, 697–705 pp.).
11. [11] Garti, N., Avrahami, M., Aserin, A., Improved solubilization of celecoxib in U-type nonionic microemulsions and their structural transitions with progressive aqueous dilution. J. Colloid Interface Sci. 299:1 (2006), 352–365.
12. [12] Ling, W.H., Jones, P.J., Dietary phytosterols: a review of metabolism, benefits and side effects. Life Sci. 57:3 (1995), 195–206.
13. [13] Plat, J., Mensink, R.P., Plant stanol and sterol esters in the control of blood cholesterol levels: mechanism and safety aspects. Am. J. Cardiol. 96:1 SUPPL. (2005), 15D–22D.
14. [14] Peterson, D.W., Effect of soybean sterols in the diet on plasma and liver cholesterol in chicks. Proc. Soc. Exp. Biol. Med. 78 (1951), 671–677.
15. [15] National Heart Foundation of Australia, Phytosterol/Stanol enriched foods. 2007–2009, National Australian Heart Foundation December. Report No.: PRO-095.
16. [16] Ras, R.T., Geleijnse, J.M., Trautwein, E.A., LDL-cholesterol-lowering effect of plant sterols and stanols across different dose ranges: a meta-analysis of randomised controlled studies. Br. J. Nutr. 112:2 (2014), 214–219.
17. [17] LaRosa, J.C., Low-density lipoprotein cholesterol reduction: the end is more important than the means. Am. J. Cardiol. 100:2 (2007), 240–242.
18. [18] Blair, S.N., Capuzzi, D.M., Gottlieb, S.O., Nguyen, T., Morgan, J.M., Cater, N.B., 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 (2000), 46–52.
19. [19] Neil, H.A., Meijer, G.W., Roe, L.S., Randomised controlled trial of use by hypercholesterolaemic patients of a vegetable oil sterol-enriched fat spread. Atherosclerosis 156:2 (2001), 329–337.
20. [20] Castro Cabezas, M., de Vries, J.H., Van Oostrom, A.J., Iestra, J., van Staveren, W.A., Effects of a stanol-enriched diet on plasma cholesterol and triglycerides in patients treated with statins. J. Am. Diet. Assoc. 106:10 (2006), 1564–1569.
21. [21] Nicholls, S.J., Brandrup-Wognsen, G., Palmer, M., Barter, P.J., Meta-analysis of comparative efficacy of increasing dose of Atorvastatin versus Rosuvastatin versus Simvastatin on lowering levels of atherogenic lipids (from VOYAGER). Am. J. Cardiol. 105:1 (2010), 69–76.
22. [22] 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. 75:1 (2002), 79–86.
23. [23] Fernandez, M.L., West, K.L., Mechanisms by which dietary fatty acids modulate plasma lipids. J. Nutr. 135 (2005), 2075–2078.
24. [24] Dias, C.B., Garg, R., Wood, L.G., Garg, M.L., Saturated fat consumption may not be the main cause of increased blood lipid levels. Med. Hypotheses 82:2 (2014), 187–195.
25. [25] Hayes, K.C., Saturated fats and blood lipids: new slant on an old story. Can. J. Cardiol. 11:Suppl. G (1995), 39G–46G.
26. [26] Hu, F.B., Stampfer, M.J., Manson, J.E., Ascherio, A., Colditz, G.A., Speizer, F.E., et al. Dietary saturated fats and their food sources in relation to the risk of coronary heart disease in women. Am. J. Clin. Nutr. 70 (1999), 1001–1008.
27. [27] Mensink, R.P., Zock, P.L., Kester, A.D., Katan, M.B., Effects of dietary fatty acids and carbohydrates on the serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials. Am. J. Clin. Nutr. 77 (2003), 1146–1155.
28. [28] Hegsted, D.M., Mcgandy, R.B., Myers, L., Stare, F.J., Quantitative effects of dietary fat on serum cholesterol in man. Am. J. Clin. Nutr. 17 (1965), 281–295.
29. [29] Hunter, J.E., Zhang, J., Kris-Etherton, P.M., Cardiovascular disease risk of dietary stearic acid compared with trans, other saturated, and unsaturated fatty acids: a systematic review. Am. J. Clin. Nutr. 91:1 (2010), 46–63.
30. [30] Gillingham, L.G., Gustafson, J.A., Han, S.Y., Jassal, D.S., Jones, P.J., High-oleic rapeseed (canola) and flaxseed oils modulate serum lipids and inflammatory biomarkers in hypercholesterolaemic subjects. Br. J. Nutr. 105:3 (2011), 417–427.
31. [31] Negele, L., Schneider, B., Ristl, R., Stulnig, T.M., Willfort-Ehringer, A., Helk, O., et al. Effect of a low-fat diet enriched either with rapeseed oil or sunflower oil on plasma lipoproteins in children and adolescents with familial hypercholesterolaemia. Results of a pilot study. Eur. J. Clin. Nutr. 69:3 (2015), 337–343.
32. [32] Lin, L., Allemekinders, H., Dansby, A., Campbell, L., Durance-Tod, S., Berger, A., et al. Evidence of health benefits of canola oil. Nutr. Rev. 71:6 (2013), 370–385.
33. [33] Gustafson, I., Vessby, B., Ohrvall, M., Nydahl, M., A diet rich in monounsaturated rapeseed oil reduces the lipoprotein cholesterol concentration and increases the relative content of n-3 fatty acids in serum in hyperlipidemic subjects. Am. J. Clin. Nutr. 59 (1994), 667–674.
34. [34] Valsta, L.M., Jauhiainen, M., Aro, A., Katan, M.B., Mutanen, M., Effects of a monounsaturated rapeseed oil and a polyunsaturated sunflower oil diet on lipoprotein levels in humans. Arterioscler. Thromb. 12 (1992), 50–57.
35. [35] Dietschy, J.M., Dietary fatty acids and the regulation of plasma low density lipoprotein cholesterol concentrations. J. Nutr. 128:2 Suppl. (1998), 444S–448S.
36. [36] Siri-Tarino, P.W., Sun, Q., Hu, F.B., Krauss, R.M., Saturated fatty acids and risk of coronary heart disease: modulation by replacement nutrients. Curr. Atheroscler. Rep. 12:6 (2010), 384–390.
37. [37] Hayes, K.C., Khosla, P., Hajri, T., Pronczuk, A., Saturated fatty acids and LDL receptor modualtion in humans and monkeys. Prostaglandins Leukot. Essent. Fatty Acids 57:4 & 5 (1997), 411–418.
38. [38] Daumerie, C.M., Woollett, L.A., Dietschy, J.M., Fatty acids regulate hepatic low density lipoprotein receptor activity through redistribution of intracellular cholesterol pools. Proc. Natl. Acad. Sci. 89:22 (1992), 10797–10801.
39. [39] Spady, D.K., Woollett, L.A., Dietschy, J.M., Regulation of plasma LDL-cholesterol levels by dietary cholesterol and fatty acids. Annu. Rev. Nutr. 13 (1993), 355–381.
40. [40] Rumsey, S.C., Galeano, N.F., Lipschitz, B., Deckelbaum, R.J., Oleate and other long chain fatty acids stimulate low density lipoprotein receptor activity by enhancing acyl coenzyme A:cholesterol acyltransferase activity and altering intracellular regulatory cholesterol pools in cultured cells. J. Biol. Chem. 270 (1995), 10008–10016.
41. [41] Degirolamo, C., Shelness, G.S., Rudel, L.L., LDL cholesteryl oleate as a predictor for atherosclerosis: evidence from human and animal studies on dietary fat. J. Lipid Res.(50(Suppl.)), 2009, S434–S439.
42. [42] Mattson, F.H., Grundy, S.M., Comparison of effects of dietary saturated, monounsaturated, and polyunsaturated fatty acids on plasma lipids and lipoproteins in man. J. Lipid Res. 26 (1985), 194–202.
43. [43] Kris-Etherton, P., Monounsaturated fatty acids and risk of cardiovascular disease. Circulation 100 (1999), 1253–1258.
44. [44] Hargrove, R.L., Etherton, T.D., Pearson, T.A., Harrison, E.H., Kris-Etherton, P., Low fat and high monounsaturated fat diets decrease human low density lipoprotein oxidative susceptibility in vitro. J. Nutr. 131 (2001), 1758–1763.
45. [45] Mustad, V.A., Ellsworth, J.L., Cooper, A.D., Kris-Etherton, P.M., Etherton, T.D., Dietary linoleic acid increases and palmitic acid decreases hepatic LDL receptor protein and mRNA abundance in young pigs. J. Lipid Res. 37 (1996), 2310–2323.
46. [46] Tobin, K.A., Steineger, H.H., Alberti, S., Spydevold, O., Auwerx, J., Gustafsson, J.A., et al. Cross-talk between fatty acid and cholesterol metabolism mediated by liver X receptor-alpha. Mol. Endocrinol. 14:5 (2000), 741–752.
47. [47] Illingworth, D.R., Schmidt, E.B., The influence of dietary n-3 fatty acids on plasma lipids and lipoproteins. Ann. N. Y. Acad. Sci. 676 (1993), 60–69.
48. [48] Dubios, V., Breton, S., Linder, M., Fanni, J., Parmentier, M., Fatty acid profiles of 80 vegetable oils with regard to their nutritional potential. Eur. J. Lipid Sci. Technol. 109 (2007), 710–732.
49. [49] Rifai, N., Warnick, G.R., Dominiczak, M.H., Handbook of Lipoprotein Testing. second ed., March 1, 2001, AACC Press (819 pp.).
50. [50] Development RaSB, (eds.) Dietetics. AoNa. Evidence Analysis Manual: Steps in the Academy Evidence Analaysis Process, 2012, 1–111.
51. [51] DerSimonioan, R., Laird, N., Meta-analysis in clinical trials. Control. Clin. Trials 7:3 (1986), 177–188.
52. [52] Higgins, J.P.T., Thompson, S.G., Deeks, J.J., Altman, D.G., Measuring inconsistency in meta-analyses. Br. Med. J. 327:7414 (2003), 557–560.
53. [53] Begg, C.B., Mazumdar, M., Operating characteristics of a rank correlation test for publication bias. Biometrics 50:4 (1994), 1088–1101.
54. [54] Genser, B., Silbernagel, G., De Backer, G., Bruckert, E., Carmena, R., Chapman, M.J., et al. Plant sterols and cardiovascular disease: a systematic review and meta-analysis. Eur. Heart J. 33:4 (2012), 444–451.
55. [55] Threapleton, D.E., Greenwood, D.C., Evans, C.E., Cleghorn, C.L., Nykjaer, C., Woodhead, C., et al. Dietary fibre intake and risk of cardiovascular disease: systematic review and meta-analysis. BMJ, 347, 2013, f6879.
56. [56] Wang, F., Zheng, J., Yang, B., Jiang, J., Fu, Y., Li, D., Effects of vegetarian diets on blood lipids: a systematic review and meta-analysis of randomized controlled trials. J. Am. Heart Assoc., 4(10), 2015, e002408.
57. [57] Wu, L., Wang, Z., Zhu, J., Murad, A.L., Prokop, L.J., Murad, M.H., Nut consumption and risk of cancer and type 2 diabetes: a systematic review and meta-analysis. Nutr. Rev. 73:7 (2015), 409–425.
58. [58] Zhou, D., Yu, H., He, F., Reilly, K.H., Zhang, J., Li, S., et al. Nut consumption in relation to cardiovascular disease risk and type 2 diabetes: a systematic review and meta-analysis of prospective studies. Am. J. Clin. Nutr. 100:1 (2014), 270–277.
59. [59] Liu, Z.M., Chen, Y.M., Ho, S.C., Effects of soy intake on glycemic control: a meta-analysis of randomized controlled trials. Am. J. Clin. Nutr. 93:5 (2011), 1092–1101.
60. [60] Mohammadifard, N., Salehi-Abargouei, A., Salas-Salvado, J., Guasch-Ferre, M., Humphries, K., Sarrafzadegan, N., The effect of tree nut, peanut, and soy nut consumption on blood pressure: a systematic review and meta-analysis of randomized controlled clinical trials. Am. J. Clin. Nutr. 101:5 (2015), 966–982.
61. [61] The Stata Journal: StataCorp LP, 2001-2016 Available from: http://www.stata-journal.com.
62. [62] Curtin, F., Elbourne, D., Altman, D.G., Meta-analysis combining parallel and cross-over clinical trials. III: the issue of carry-over. Stat. Med. 21 (2002), 2161–2173.
63. [63] Geelen, A., Zock, P.L., de Vries, J.H., Katan, M.B., Apolipoprotein E polymorphism and serum lipid response to plant sterols in humans. Eur. J. Clin. Investig. 32:10 (2002), 738–742.
64. [64] Cleeman, J.I., Grundy, S.M., Becker, D., Clark, L.T., Cooper, R.S., Denke, M.A., et al. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA 285 (2001), 2486–2497.
65. [65] Clifton, P.M., Noakes, M., Sullivan, D., Erichsen, N., Ross, D., Annison, G., et al. Cholesterol-lowering effects of plant sterol esters differ in milk, yoghurt, bread and cereal. Eur. J. Clin. Nutr. 58:3 (2004), 503–509.
66. [66] Katan, M.B., Grundy, S.M., Jones, P., Law, M., Miettinen, T., Paoletti, R., et al. Efficacy and safety of plant stanols and sterols in the management of blood cholesterol levels. Mayo Clin. Proc. 78:8 (2003), 965–978.
67. [67] Law, M., Plant sterol and stanol margarines and health. BMJ 320 (2000), 861–864.
68. [68] Musa-Veloso, K., Poon, T.H., Elliot, J.A., Chung, C., A comparison of the LDL-cholesterol lowering efficacy of plant stanols and plant sterols over a continuous dose range: results of a meta-analysis of randomized, placebo-controlled trials. Prostaglandins Leukot. Essent. Fatty Acids, 85(1), 2011 (Internet, 9–28 pp.).
69. [69] Cholesterol: Better Health Channel, [updated February 2014; cited 2015 9 Dec]. Available from: https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/cholesterol.
70. [70] Grundy, S.M., What is the desirable ratio of saturated, polyunsaturated, and monounsaturated fatty acids in the diet?. Am. J. Clin. Nutr. 66:Suppl. (1997), 988S–990S.
71. [71] Gardner, C.D., Kraemer, H.C., Monounsaturated versus polyunsaturated dietary fat and serum lipids: a meta-analysis. Arterioscler. Thromb. Vasc. Biol. 15 (1995), 1917–1927.
72. [72] Ruiu, G., Pinach, S., Veglia, F., Gambino, R., Marena, S., Uberti, B., et al. Phytosterol-enriched yogurt increases LDL affinity and reduces CD36 expression in polygenic hypercholesterolemia. Lipids 44:2 (2009), 153–160.
73. [73] Jesch, E.D., Seo, J.M., Carr, T.P., Lee, J.Y., Sitosterol reduces messenger RNA and protein expression levels of Niemann-Pick C1-like 1 in FHs 74 Int cells. Nutr. Res. 29:12 (2009), 859–866.
74. [74] Moghadasian, M.H., Nguyen, L.B., Shefer, S., Salen, G., Batta, A.K., Frohlich, J.J., Hepatic cholesterol and bile acid synthesis, low-density lipoprotein receptor function, and plasma and fecal sterol levels in mice: effects of apolipoprotein E deficiency and probucol or phytosterol treatment. Metabolism 50:6 (2001), 708–714.
75. [75] Corby, J., Fatty acid composition and the oxidation of low-density lipoproteins. Biochem. Med. Metab. Biol. 49 (1993), 25–35.
76. [76] Turpeinen, A.M., Alfthan, G., Valsta, L., Hietanen, E., Salonen, J.T., Schunk, H., et al. Plasma and lipoprotein lipid peroxidation in humans on sunflower and rapeseed oil diets. Lipids 30:6 (1995), 485–492.
77. [77] Palomaki, A., Pohjantahti-Maaroos, H., Wallenius, M., Kankkunen, P., Aro, H., Husgafvel, S., et al. Effects of dietary cold-pressed turnip rapeseed oil and butter on serum lipids, oxidized LDL and arterial elasticity in men with metabolic syndrome. Lipids Health Dis., 9, 2010, 137.
78. [78] Nielsen, N.S., Pedersen, A., Sandström, B., Marckmann, P., Høy, C.-E., Different effects of diets rich in olive oil, rapeseed oil and sunflower-seed oil on postprandial lipid and lipoprotein concentrations and on lipoprotein oxidation susceptibility. Br. J. Nutr. 87:05 (2002), 489–499.
79. [79] Egert, S., Kratz, M., Kannenberg, F., Fobker, M., Wahrburg, U., Effects of high-fat and low-fat diets rich in monounsaturated fatty acids on serum lipids, LDL size and indices of lipid peroxidation in healthy non-obese men and women when consumed under controlled conditions. Eur. J. Nutr. 50:1 (2011), 71–79.
80. [80] Alhassan, S., Reese, K.A., Mahurin, J., Plaisance, E.P., Hilson, B.D., Garner, J.C., et al. Blood lipid responses to plant stanol ester supplementation and aerobic exercise training. Metab. Clin. Exp., 55(4), 2006 (Internet, 541–9 pp.).
81. [81] Baumgartner, S., Mensink, R.P., Husche, C., Lutjohann, D., Plat, J., Effects of plant sterol- or stanol-enriched margarine on fasting plasma oxyphytosterol concentrations in healthy subjects. Atherosclerosis 227:2 (2013), 414–419.
82. [82] Blomqvist, S.M., Jauhiainen, M., van Tol, A., Hyvonen, M., Torstila, I., Vanhanen, H., et al. Effect of sitostanol ester on composition and size distribution of low- and high-density lipoprotein. Nutr. Metab. Cardiovasc. Dis. 3 (1993), 158–164.
83. [83] Buyuktuncer, Z., Fisunoglu, M., Guven, G.S., Unal, S., Besler, H.T., The cholesterol lowering efficacy of plant stanol ester yoghurt in a Turkish population: a double-blind, placebo-controlled trial. Lipids Health Dis., 12(1), 2013 (Internet).
84. [84] Charest, A., Vanstone, C., St-Onge, M.P., Parson, W., Jones, P.J., Lamarche, B., Phytosterols in nonfat and low-fat beverages have no impact on the LDL size phenotype. Eur. J. Clin. Nutr. 59:6 (2005), 801–804.
85. [85] Christiansen, L.I., Lahteenmaki, P.L., Mannelin, M.R., Seppanen-Laakso, T.E., Hiltunen, R.V., Yliruusi, J.K., Cholesterol-lowering effect of spreads enriched with microcrystalline plant sterols in hypercholesterolemic subjects. Eur. J. Clin. Nutr. 40:2 (2001), 66–73.
86. [86] Gagliardi, A.C., Maranhao, R.C., de Sousa, H.P., Schaefer, E.J., Santos, R.D., Effects of margarines and butter consumption on lipid profiles, inflammation markers and lipid transfer to HDL particles in free-living subjects with the metabolic syndrome. Eur. J. Clin. Nutr. 64:10 (2010), 1141–1149.
87. [87] Gylling, H., Radhakrishnan, R., Miettinen, T.A., 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 96:12 (1997), 4226–4231.
88. [88] Gylling, H., Halonen, J., Lindholm, H., Konttinen, J., Simonen, P., Nissinen, M.J., et al. The effects of plant stanol ester consumption on arterial stiffness and endothelial function in adults: a randomised controlled clinical trial. BMC Cardiovasc. Disord., 13, 2013.
89. [89] Hallikainen, M.A., Uusitupa, M.I., 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. 69:3 (1999), 403–410.
90. [90] Hallikainen, M.A., Sarkkinen, E.S., Gylling, H., Erkkila, A.T., Uusitupa, M.I., Comparison of the effects of plant sterol ester and plant stanol ester-enriched margarines in lowering serum cholesterol concentrations in hypercholesterolaemic subjects on a low-fat diet. Eur. J. Clin. Nutr. 54:9 (2000), 715–725.
91. [91] Hallikainen, M.A., Sarkkinen, E.S., Uusitupa, M.I., Plant stanol esters affect serum cholesterol concentrations of hypercholesterolemic men and women in a dose-dependent manner. J. Nutr. 130:4 (2000), 767–776.
92. [92] Hallikainen, M., Lyyra-Laitinen, T., Laitinen, T., Agren, J.J., Pihlajamaki, J., Rauramaa, R., et al. Endothelial function in hypercholesterolemic subjects: effects of plant stanol and sterol esters. Atherosclerosis 188:2 (2006), 425–432.
93. [93] Hallikainen, M., Lyyra-Laitinen, T., Laitinen, T., Moilanen, L., Miettinen, T.A., Gylling, H., Effects of plant stanol esters on serum cholesterol concentrations, relative markers of cholesterol metabolism and endothelial function in type 1 diabetes. Atherosclerosis 199:2 (2008), 432–439.
94. [94] Hendriks, H.F., Weststrate, J.A., van Vliet, T., Meijer, G.W., 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. 53:4 (1999), 319–327.
95. [95] Hyun, Y.J., Oh, Y.K., Joo, B.K., Lee, J.H., Jang, Y., Liponkoski, L., et al. Plant stanol esters in low-fat yogurt reduces total and low-density lipoprotein cholesterol and low-density lipoprotein oxidation in normocholesterolemic and mildly hypercholesterolemic subjects. Nutr. Res. 25:8 (2005), 743–753.
96. [96] Jauhiainen, T., Salo, P., Niittynen, L., Poussa, T., Korpela, R., Effects of low-fat hard cheese enriched with plant stanol esters on serum lipids and apolipoprotein B in mildly hypercholesterolaemic subjects. Eur. J. Clin. Nutr. 60:11 (2006), 1253–1257.
97. [97] Korpela, R., Tuomilehto, J., Hogstrom, P., Seppo, L., Piironen, V., Salo-Vaananen, P., et al. Safety aspects and cholesterol-lowering efficacy of low fat dairy products containing plant sterols. Eur. J. Clin. Nutr. 60:5 (2006), 633–642.
98. [98] Lottenberg, A.M., Nunes, V.S., Nakandakare, E.R., Neves, M., Bernik, M., Lagrost, L., et al. The human cholesteryl ester transfer protein I405V polymorphism is associated with plasma cholesterol concentration and its reduction by dietary phytosterol esters. J. Nutr. 133:6 (2003), 1800–1805.
99. [99] Miettinen, T.A., 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. 333:20 (1995), 1308–1312.
100. [100] Nigon, F., Serfaty-Lacrosniere, C., Beucler, I., Chauvois, D., Neveu, C., Giral, P., et al. Plant sterol-enriched margarine lowers plasma LDL in hyperlipidemic subjects with low cholesterol intake: effect of fibrate treatment. Clin. Chem. Lab. Med. 39:7 (2001), 634–640.
101. [101] Plat, J., Mensink, R.P., Vegetable oil based versus wood based stanol ester mixtures: effects on serum lipids and hemostatic factors in non-hypercholesterolemic subjects. Atherosclerosis 148:1 (2000), 101–112.
102. [102] Ras, R.T., Demonty, I., Zebregs, Y.E., Quadt, J.F., Olsson, J., Trautwein, E.A., Low doses of eicosapentaenoic acid and docosahexaenoic acid from fish oil dose-dependently decrease serum triglyceride concentrations in the presence of plant sterols in hypercholesterolemic men and women. J. Nutr. 144:10 (2014), 1564–1570.
103. [103] Ras, R.T., Fuchs, D., Koppenol, W.P., Garczarek, U., Greyling, A., Keicher, C., et al. The effect of a low -fat spread with added plant sterols on vascular function markers: results of the Investigating Vascular Function Effects of Plant Sterols (INVEST) study. Am. J. Clin. Nutr. 101:4 (2015), 733–741.
104. [104] Simons, L.A., Additive effect of plant sterol-ester margarine and cerivastatin in lowering low-density lipoprotein cholesterol in primary hypercholesterolemia. Am. J. Cardiol. 90:7 (2002), 737–740.
105. [105] Theuwissen, E., Plat, J., Van Der Kallen, C.J., Van Greevenbroek, M.M., Mensink, R.P., Plant stanol supplementation decreases serum triacylglycerols in subjects with overt hypertriglyceridemia. Lipids 44:12 (2009), 1131–1140.
106. [106] Turpeinen, A.M., Ikonen, M., Kivimäki, A.S., Kautiainen, H., Vapaatalo, H., Korpela, R., A spread containing bioactive milk peptides Ile-Pro-Pro and Val-Pro-Pro, and plant sterols has antihypertensive and cholesterol-lowering effects. Food Funct., 3(6), 2012 (Internet, 621–7 pp.).
107. [107] Vanstone, C.A., Raeini-Sarjaz, M., Parsons, W.E., Jones, P.J., Unesterified plant sterols and stanols lower LDL-cholesterol concentrations equivalently in hypercholesterolemic persons. Am. J. Clin. Nutr. 76:6 (2002), 1272–1278.
108. [108] Vasquez-Trespalacios, E.M., Romero-Palacio, J., Efficacy of yogurt drink with added plant stanol esters (Benecol, Colanta) in reducing total and LDL cholesterol in subjects with moderate hypercholesterolemia: a randomized placebo-controlled crossover trial NCT01461798. Lipids Health Dis., 13(1), 2014 (Internet).
109. [109] Vissers, M.N., Zock, P.L., Meijer, G.W., Katan, M.B., Effect of plant sterols from rice bran oil and triterpene alcohols from sheanut oil on serum lipoprotein concentrations in humans. Am. J. Clin. Nutr. 72:6 (2000), 1510–1515.
110. [110] Gylling, H., Hallikainen, M., Raitakari, O.T., Laakso, M., Vartiainen, E., Salo, P., et al. Long-term consumption of plant stanol and sterol esters, vascular function and genetic regulation. Br. J. Nutr. 101:11 (2009), 1688–1695.
111. [111] Hendriks, H.F., Brink, E.J., Meijer, G.W., Princen, H.M., Ntanios, F.Y., Safety of long-term consumption of plant sterol esters-enriched spread. Eur. J. Clin. Nutr. 57:5 (2003), 681–692.
112. [112] Charest, A., Desroches, S., Vanstone, C.A., Jones, P.J., Lamarche, B., Unesterified plant sterols and stanols do not affect LDL electrophoretic characteristics in hypercholesterolemic subjects. J. Nutr. 134:3 (2004), 592–595.